AJP - Heart Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 287: H896-H904, 2004. First published March 18, 2004; doi:10.1152/ajpheart.00041.2004
0363-6135/04 $5.00
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/2/H896    most recent
00041.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Barra, J. G.
Right arrow Articles by Pichel, R. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Barra, J. G.
Right arrow Articles by Pichel, R. H.

Contribution of myocardium hydraulic skeleton to left ventricular wall interaction and synergy in dogs

Juan Gabriel Barra, Alberto José Crottogini, Peter Willshaw, Elena Catalina Lascano, and Ricardo Horacio Pichel

Department of Physiological, Pharmacological, and Biochemical Sciences, Favaloro University, C1078AAI Buenos Aires, Argentina

Submitted 21 January 2004 ; accepted in final form 12 March 2004


   ABSTRACT
TOP
 ABSTRACT
MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
The most premature motion change after coronary occlusion is early diastolic thinning of the ischemic left ventricular (LV) wall, with concomitant thickening of the normoperfused wall. We aimed 1) to demonstrate that these early changes are the result of the absence of fluid within the ischemic myocardium (hydraulic skeleton) rather than to cell anoxia and 2) to quantitate the contribution of the lack of hydraulic skeleton to left ventricular asynergy of contraction in seven anesthetized dogs submitted to acute, short-lasting circumflex artery (Cx) occlusion (ischemia) and to perfusion of the Cx with an oxygen-free solution (anoxia). We analyzed the time course of regional work index (WI, area of the LV pressure-wall thickness loop) and regional efficiency (defined as the ratio of WI to the maximum possible work). Interwall asynergy was defined as the difference between the regional efficiency of the anterior and posterior walls. After 9–10 s, posterior wall efficiency decreased 37 ± 6% with anoxia and 72 ± 3% with ischemia (P < 0.025), and interwall asynergy was 0 ± 6% with anoxia and 32 ± 5% with ischemia (P < 0.05). The contribution of absent hydraulic skeleton to interwall asynergy (calculated as the difference between %asynergy in anoxia and %asynergy in ischemia) was 30 ± 8% (P < 0.05). In conclusion, the earliest wall motion change observed after acute coronary occlusion, namely ischemic wall thinning concomitant with normoperfused wall thickening during isovolumic relaxation, is the result of the absence of intracoronary fluid. The lack of hydraulic skeleton within the myocardium contributes ~30% to interwall asynergy.

regional myocardial function; pressure-wall thickness loops; isovolumic relaxation; myocardial ischemia; left ventricular asynergy

THE NORMAL PATTERN OF left ventricle contraction, or synergy, has been defined as a uniform, almost concentric inward motion of all points along the ventricular inner surface during systolic ejection to produce maximal effective work at minimal energy cost (14). The synergistic motility of the ventricular walls is altered after acute coronary occlusion. In this condition, the ischemic wall displays progressive systolic hypokinesia and, after ~30 s of ischemia, it shows a diskynetic pattern, with systolic thinning and postejective thickening (6, 10, 36, 41, 42, 45). The earliest change after sudden coronary occlusion consists of thinning of the ischemic wall during the initial phase of isovolumic relaxation. On the other hand, the normoperfused wall displays the opposite variation, i.e., it thickens while relaxing (7, 18, 19, 26, 34, 43). This phenomenon occurs after only one or two beats after occlusion, making it unlikely that they are caused by the well-known metabolic alterations induced by tissue hypoxia (11, 20–24). Considering that most of the myocardial perfusion, particularly at the subendocardial level, starts during early diastole, namely during isovolumic relaxation, we hypothesized that this motility change is because of the absence of blood within the vascular bed of the ischemic wall and that the lack of a hydraulic skeleton within the ischemic myocardium would not only affect diastole but also the normal synergy of left ventricular contraction.

In the present study, we tested these hypotheses by comparing the effects of a short-lasting acute coronary occlusion vs. infusion of an oxygen-free solution on the area of left ventricular (LV) pressure-wall thickness loops of the ischemic and normoperfused LV walls in anesthetized, open-chest dogs.


   MATERIALS AND METHODS
TOP
 ABSTRACT
 MATERIALS AND METHODS
RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 
Surgical preparation.

Seven mongrel dogs weighing 18.8–26.5 kg (24.4 ± 3.3, mean ± SD) were operated on. Anesthesia was induced with intravenous thiopental sodium (20 mg/kg) and was maintained with 1.5% enflurane. A thoracotomy was performed at the left fifth intercostal space, and the heart was suspended in a pericardial cradle. A left ventricular pressure transducer (model P7; Konigsberg, Pasadena, CA) and a fluid-filled catheter for later calibration of the pressure transducer were introduced through a stab wound near the apex. Two pairs of ultrasonic microcrystals (5 MHz) for continuous wall thickness measurements were implanted at the anterior and posterior walls of the left ventricle following the technique described by Sasayama et al. (36). The left circumflex artery and the left subclavian artery were dissected free at their origins, and the dog was anticoagulated with heparin (5,000 IU). With the use of a catheter made from silicone rubber (2 mm ID), the left subclavian artery was connected to the proximal part of the left circumflex artery, which had been ligated at its origin immediately before connection so that the blood supplying the left circumflex bed came from the subclavian artery. The time elapsed between circumflex ligation and restoration of circulation through the left circumflex artery ranged from 35 to 120 s. In all dogs, functional recovery of the posterior wall after reperfusion was complete. Additionally, by means of a three-way stopcock inserted in the silicon tube, a perfusion line from a bottle containing dextran 40 at 37°C was connected. In each case, the bottle was positioned at a height that would allow a perfusion pressure equal to the dog's systolic blood pressure (Fig. 1).



View larger version (29K):
[in this window]
[in a new window]
  		Fig. 1. Surgical instrumentation. A three-way stopcock interposed in the silicone tube connecting the left subclavian artery with the left circumflex coronary artery allowed alternative perfusion of the posterior wall of the left ventricle (LV) with blood and with dextran 40. Instrumentation was completed with 2 pairs of ultrasonic dimension gauges to measure LV anterior and posterior wall thickness and a solid-state microtransducer to measure LV pressure. RV, right ventricle; Ao, aorta; LA, left artery.

 
After the instrumentation was completed, the pericardial cradle was loosened so that the heart could return to its anatomic position, the thoracotomy borders were approximated, and the preparation was allowed to stabilize during 20–30 min. During the experiment, the temperature of the animal was maintained between 37 and 38°C. All procedures agreed with the Guide for the Care and Use of Laboratory Animals published by the United States National Research Council (National Academy Press, Washington, DC, 1996).

Experimental protocol.

The fluid-filled catheter was connected to a Statham P23 DB pressure transducer previously calibrated with a mercury column, and the pressure signal provided by the microtransducer was adjusted to match that of the Statham transducer. Thereafter, the fluid-filled catheter was disconnected and closed. The wall thickness signals were calibrated in millimeters using the 1-mm step calibration facility of the sonomicrometer (Triton Technology, San Diego, CA). The left ventricular pressure (LVP) signal and both wall thickness signals (Th) were digitized on-line every 4 ms (Keithley MetraByte DAS16 Board) and displayed on the screen of a computer in the form of LVP-Th loops.

After signal stabilization, 10 consecutive beats were recorded during the control state (preocclusion control), and immediately afterward acute left circumflex occlusion was produced by clamping the silicone tube interposed between the subclavian and coronary arteries (coronary occlusion). All signals were digitized on-line during 15 s of occlusion, and then the clamp was opened to allow for reperfusion. When all signals had returned to control preocclusion values, a new series of control beats was recorded (predextran control) and then the three-way stopcock was turned to allow dextran to perfuse the left circumflex bed for 15 s, during which all signals were digitized on-line (intracoronary perfusion with dextran).

Next, blood perfusion was reestablished, and, after all signals had returned to control levels, a final recording of control beats was performed. The sequence of these two experimental situations was randomized. At the end of the experiments, the animals were killed with an overdose of inhaled enflurane followed by a bolus injection of potassium chloride. Correct positioning of the microcrystal pairs was verified at necropsy.

Data analysis.

Onset of isovolumic contraction was defined at the start of the rapid upstroke of time derivative of LVP (dP/dt), and onset of isovolumic relaxation was set at 20 ms before peak negative dP/dt (10, 31). Because we studied phenomena occurring within the wall rather than in the LV cavity, we prioritized the wall motion waveform and/or the LVP/Th loop morphology rather than opening and/or closure of the mitral and aortic valves. Thus, by observation of the control LVP-Th loops in each dog, end of isovolumic contraction was defined at the instant before the loss of verticality of the isovolumic contraction tracing, i.e., the instant before the onset of systolic thickening. This point happened to occur at or very close to 20 ms after peak positive dP/dt. Similarly, by analyzing the control LVP/Th loops of each dog, we determined end of isovolumic relaxation as the ultimate point before the onset of wall thinning. This occurred at or very close to 70 ms after peak negative dP/dt. When applying the 70-ms criterion to the LVP/Th loops occurring under occlusion, we verified that, in all cases, this instant coincided with the point where the isometric relaxation tracing "touched" the diastolic exponential function. This guaranteed (as in the case of isovolumic contraction) not to neglect any area (regional work) of the phenomenon under study.

Regional myocardial work was estimated as a work index (WI) derived from the regional LVP-Th relationship (15, 39). In this way, the apparent regional myocardial work index (WIapparent) was calculated in each beat from the area of the LVP-Th loop, according to the equation:

where oic is onset of isovolumic contraction, ed is end diastole, and i is a given instant of the cardiac beat comprised between oic and ed.

We then calculated the work index corresponding to the isovolumic contraction (WIIC) and the isovolumic relaxation (WIIR) as follows:


where oe is onset of ejection, ee end of ejection, and eir end of isovolumic relaxation.

The data points comprised between eir and oic were fitted to the exponential function LVP = eTh·a+b and used for those cases in which extrapolated values of wall thickness were needed to calculate the isovolumic areas.

The maximum possible regional work index (WImax possible) was defined as the sum of WIapparent and the absolute values for work index during the isovolumic phases.

In turn, the regional work index effectively used to eject in the circulation (WIejective) was calculated by subtracting from WIapparent the absolute values for work index during the isovolumic phases.

The ratio between WIejective and WImax possible was considered to indicate regional wall efficiency:

We assumed that 100% efficiency in developing work index occurs if the isovolumic phases of the LVP-Th loop have zero surface. Any nonzero value in one or both isovolumic areas decreases that efficiency. For this reason, WIejective was calculated by subtracting from the apparent work index the absolute values of the isovolumic work indexes. Because we computed the absolute values to be subtracted in the calculation of the numerator of wall efficiency, any negative or positive value in one or both isovolumic areas, in turn, must decrease that efficiency.

The difference between posterior and anterior wall efficiencies was considered to be an indication of the interwall asynergy.

Finally, to assess the net effect of the lack of hydraulic skeleton on left ventricular asynergy, we calculated the difference between the asynergy seen during intracoronary perfusion with dextran and that observed during coronary occlusion.

Statistical analysis.

Values for both control conditions are reported as the average of the beats recorded. During transient states (coronary occlusion and intracoronary perfusion with dextran), the hemodynamic values reported are those observed at the end of these situations; for wall thickness, we also report the final value except when the maximal effect occurred before the end of the maneuver. To construct the beat-to-beat mean temporal curves, we interpolated the data every 500 ms.

Values obtained during both control conditions, coronary occlusion, and intracoronary perfusion with dextran were compared using ANOVA for repeated measures followed by Tukey's test for multiple comparisons. Statistical significance was set at P < 0.05.


   RESULTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
DISCUSSION
 GRANTS
 REFERENCES
 
Hemodynamic variables are shown in Table 1. Both maneuvers decreased the maximum rate of pressure development and decay but did not affect peak systolic pressure.


View this table:
[in this window]
[in a new window]
  		Table 1. Hemodynamic effects of 15 s of coronary occlusion or selective perfusion with dextran in the left circumflex artery

 
As can be seen, no differences were found between both control states, indicating complete recovery of the basal condition after the first intervention. The same occurred with wall thickening, where the values for the first control state in the anterior and posterior walls (16.9 ± 3.1 and 18.6 ± 2.8%, respectively) did not differ (P = not significant) from their corresponding values at the second control condition (17.1 ± 3.3 and 18.5 ± 2.6%).

Figure 2 shows LVP and Th signals during coronary occlusion (A) and dextran perfusion (B). During coronary occlusion, early diastolic thinning of the ischemic wall occurred already after three beats and progressed on a beat-to-beat basis. In other words, the ischemic wall started to thin at the very onset of relaxation when, normally, it should show an approximately isometric pattern. This pattern of abnormal motility (the key phenomenon under study) and its rapid progression were highly repeatable among dogs. Concomitantly, the normoperfused wall displayed postejective thickening. During dextran perfusion, the posterior wall progressively thinned but, unlike coronary occlusion, it preserved its motility pattern, which, in turn, resulted in preservation of the normal function pattern of the normoperfused wall. In effect, the signals for the initial and final beats of that wall were almost superimposable.



View larger version (29K):
[in this window]
[in a new window]
  		Fig. 2. Left ventricular pressure and wall thickness tracings of normoperfused (anterior) and altered perfused (posterior) walls during 15 s of left circumflex artery occlusion (A) and left circumflex artery perfusion with dextran (B). These waveform patterns were highly repeatable in all animals. Thin solid line, first beat (control); thick solid line, last beat; dashed line, intermediate beats; open circles, onset of isovolumic contraction, onset of ejection, end of ejection, and end of isovolumic relaxation.

 
Figure 3 shows the LVP-Th loops of the normoperfused (A and B, top) and ischemic (A and B, bottom) walls during coronary occlusion (A) and dextran perfusion (B). It can be seen that the beat-to-beat loss of loop area in the ischemic wall during coronary occlusion resulted in a concomitant gain of area of the normal wall. However, this extra area occurred during isovolumic relaxation, thus not contributing to ejective work. During dextran perfusion, an overall thinning of the ischemic wall occurred. However, the general morphology of the loop was preserved and, as a result, the LVP-Th loop of the normoperfused wall did not undergo significant changes in either its area or its morphology.



View larger version (43K):
[in this window]
[in a new window]
  		Fig. 3. Left ventricular pressure-wall thickness loops of normoperfused (anterior) and altered perfused (posterior) walls during 15 s of left circumflex artery occlusion (A) and left circumflex artery perfusion with dextran (B). Thin solid line, first beat (control); thick solid line, last beat; dashed line, intermediate beats; open circles, onset of isovolumic contraction, onset of ejection, end of ejection, and end of isovolumic relaxation.

 
Figure 4 shows the time course of regional work index during isovolumic relaxation in the normoperfused and ischemic walls. Coronary occlusion resulted in progressively increasing negative values for WIIR in the ischemic wall. The normoperfused wall showed progressive increases in WIIR. During dextran perfusion, the values for WIIR remained close to zero in both walls. Only in the last two seconds did WIIR values in both walls diverge symmetrically, although not significantly.



View larger version (21K):
[in this window]
[in a new window]
  		Fig. 4. Time course of work index developed during isovolumic relaxation (IR WI) during 15 s of coronary occlusion (open symbols) or selective intracoronary perfusion with dextran (filled symbols) of the left circumflex artery. Circles, anterior wall; triangles, posterior wall. *P < 0.05 and {dagger}P < 0.01 between occlusion and dextran. Values are means ± SE; n = 7 experiments. Arrow, onset of maneuver.

 
Figure 5 depicts the time course of regional efficiency for both ventricular walls. At the onset of each maneuver, regional efficiency was close to 100%. After 9–10 s, posterior wall efficiency fell from 96.5 ± 0.5 to 24.6 ± 2.8% (net drop of 72 ± 3%) after occlusion, whereas with dextran perfusion it fell from 98.3 ± 0.6 to 61.2 ± 6.4% (net drop of 37 ± 6%, P < 0.025 with regard to occlusion). In addition, the rate of efficiency loss was faster with occlusion. Anterior wall efficiency decreased to 59.4 ± 4.4% with occlusion and decreased to 67.4 ± 5.3% with dextran perfusion, starting from 93.0 ± 0.8 and 93.9 ± 1.9%, respectively. The normoperfused anterior wall tended to be less efficient under occlusion, but the differences were not significant.



View larger version (20K):
[in this window]
[in a new window]
  		Fig. 5. Time course of regional wall efficiency during 15 s of coronary occlusion (open symbols) or selective perfusion with dextran (filled symbols) of the left circumflex artery. Circles, anterior wall; triangles, posterior wall. *P < 0.05 and {dagger}P < 0.01 between occlusion and dextran. Values are means ± SE; n = 7 experiments. Arrow, onset of maneuver.

 
Interwall asynergy is shown in Fig. 6. It is seen that, under occlusion, asynergy increased steadily from the ideal zero value (perfect synergy), reaching ~40% by the end of the maneuver. On the other hand, the loss of synergy under dextran perfusion was slower and significantly less than with coronary occlusion, reaching ~10% by the end of the experiment. After 9–10 s, interwall asynergy was 0 ± 6% with anoxia and 32 ± 5% with ischemia (P < 0.05).



View larger version (15K):
[in this window]
[in a new window]
  		Fig. 6. Interwall asynergy calculated as the difference (posterior wall – anterior wall) of regional wall efficiency during 15 s of coronary occlusion (open symbols) or selective perfusion with dextran (filled symbols) of the left circumflex artery. *P < 0.05 and {dagger}P < 0.01 between occlusion and dextran. Values are means ± SE; n = 7 experiments. Arrow, onset of maneuver.

 
Finally, Fig. 7 shows the net contribution of the absence of hydraulic skeleton in the ischemic wall to interwall asynergy. After a steady increase over the first few seconds, the net contribution of absent fluid within the ischemic wall reached a plateau of 30 ± 8% (P < 0.05 respect to the initial 0 value). In other words, the presence of a hydraulic skeleton in the ischemic myocardium contributes 30% to the LV synergy of contraction needed to perform ejective work.



View larger version (14K):
[in this window]
[in a new window]
  		Fig. 7. Time course of the net mechanical contribution of the hydraulic skeleton to interwall asynergy, as assess by the difference between the values for asynergy during 15 s of coronary occlusion and selective perfusion with dextran of the left circumflex artery. *P < 0.05 and {dagger}P < 0.01 vs. initial control value. Values are means ± SE; n = 7 experiments. Arrow, onset of maneuver.

 

   DISCUSSION
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
GRANTS
 REFERENCES
 
Most of the studies on left ventricular wall thickness and impaired regional coronary blood flow have analyzed the effects of tissue hypoxia on ischemic and normoperfused zones of the left ventricle (10, 31, 36), or the interaction between the different layers of the left ventricular wall in the presence of a coronary flow restriction (5, 12, 17, 32, 37, 38, 44, 46). In contrast, few studies have addressed this subject from the point of view of the presence or absence of a mass of fluid within the left ventricular wall (30). Moreover, in the report by Miller et al. (30), the subject under investigation is the effect of hyper- rather than hypoperfusion on LV function.

The relevance of coronary blood as a hydraulic media within the myocardial wall has long been acknowledged (27, 28).

That the presence of intramyocardial coronary fluid volume plays a role in wall dynamics is evident when looking at wall dimension changes during sudden coronary occlusion. Experimental (7, 34, 43) and clinical (18, 26) studies have shown that the earliest change in wall motion following coronary occlusion has two characteristics: first, it occurs during isovolumic relaxation, namely when myocardial perfusion (especially at the subendocardium) starts, and second, it is much too premature to be attributed to cell hypoxia. The metabolic consequences of acute closure of a major coronary artery (cessation of aerobic metabolism, depletion of creatine phosphate, onset of anaerobic glycolysis, and accumulation of metabolites in the ischemic tissue) begin 10 s after occlusion (20), and the earliest wall motion change (wall thinning or segment lengthening during isovolumic relaxation) starts no later than 1 s after occlusion. The interacting normoperfused wall, in turn, displays a change that is the mirror image of the former, namely thickening (or segment shortening) during isovolumic relaxation.

Our aims were 1) to test the hypothesis that the above-mentioned phenomenon results from absent hydraulic skeleton within the ischemic myocardium and not from cell hypoxia and 2) to quantify the contribution of the hydraulic skeleton to left ventricular synergy.

To satisfy the first aim, we compared the area of the LV pressure wall thickness loops during isovolumic relaxation under regional coronary occlusion and under regional perfusion with an oxygen-free solution. To avoid the confounding effects of metabolic anoxia, we restricted the analysis to the first 15 s after the onset of each experimental maneuver. Our results showed that the presence of fluid volume within the intramyocardial coronary bed allowed the isovolumic relaxation areas to stay close to zero in both walls, thus confirming that the significant symmetrical changes in isovolumic relaxation area observed in the ischemic and normoperfused walls (see Fig. 4) are the consequence of absent hydraulic skeleton rather than cell hypoxia.

To quantify the mechanical relevance of the hydraulic skeleton on interwall synergy, we adopted the regional work index, derived from the area of the LV pressure-wall thickness loop (15, 39), as a reliable indicator of regional external work (9, 25, 31). We considered the real regional ejective work (i.e., the work effectively used to pump blood in the aorta) as the difference between the measured loop area and the absolute values for the areas occurring during the isovolumic phases of the cardiac cycle (which ideally should be 0). In turn, we defined maximum possible regional work as the sum of the measured loop area and the isovolumic areas. Under normal conditions, ejective work should be equal or close to maximum possible work; therefore, the ratio between both (regional efficiency) should approach one. Under regional ischemia, one ventricular wall will decrease its efficiency while the other preserves it. Therefore, the difference between these regional efficiencies should provide an estimation of the LV interwall asynergy.

A comment should be made about the instants used to define isovolumic areas. It must be noticed that our aim was to analyze phenomena occurring within the wall rather than in the LV cavity. Consequently, to define points of onset and end of isovolumic (in fact, isometric) phases, we prioritized the wall motion waveform and/or the LVP/Th loop morphology rather than opening and/or closure of the mitral and aortic valves. The criteria selected for onset of both isovolumic phases are widely used in the literature and do not merit further discussion. The other two (end of both isovolumic phases) were the matter of very careful observation, because the criteria of selection should guarantee the following two crucial requisites for a study based on isovolumic work: 1) no area belonging to an isovolumic phase could be disregarded and 2) any area outside an isovolumic area must be neglected. Rigorously speaking, throughout this paper the term "isometric" should have been used instead of "isovolumic." However, we preferred to respect the usual terminology employed to describe the cardiac cycle.

Our results showed that interwall asynergy was significantly greater when, in addition to oxygen deprivation, fluid volume was absent from the intramyocardial coronary bed. In this condition, interwall synergy fell >40% from its basal value, whereas preservation of the hydraulic skeleton resulted in only a 10% loss of synergy. Hence, >30% of the observed asynergy is accounted for by the absence of intracoronary fluid volume.

In isolated rat hearts, Kanaide et al. (21, 22) demonstrated that the typical early dyskinesis of the ischemic region occurred when the oxygen supply appeared still sufficient for the normal mitochondrial oxidative function and when the ATP and creatine phosphate content remained at aerobic levels. In contrast, the amplitude of systolic wall thickening decreased much more gradually and without systolic bulging when anoxic perfusion, or global ischemia, was performed (21, 22). They concluded that, during acute coronary occlusion, the early dyskinesis was the result of passive extension or thinning of the ischemic wall induced by the contraction of the remaining normoperfused myocardium. Our results extend those of Kanaide et al. by showing that the predominance of the normoperfused myocardium on the ischemic wall is not the result of an imbalance in intrinsic fiber contractility between both regions but the result of the absence of intravascular fluid within the ischemic wall. From the observation of Figs. 2 and 3, it is reasonable to assume that the lack of this hydraulic skeleton prevents the ischemic wall from opposing to the force imposed by the normoperfused myocardium, and interwall asynergy occurs.

The erectile effect of coronary perfusion pressure has been reported by several authors (1, 2, 3, 35). Doyle et al. (7) showed that the pattern of ischemic dysfunction, as indicated by the analysis of pressure-segment length loops, differed between abrupt (<30 s) and gradual coronary occlusions. They claimed that the dysfunction produced by abrupt occlusion most likely represented a mechanical effect of sudden myocardial ischemia coupled with loss of the erectile effect normally produced by the flow of blood in the coronary arteries. Our results, using the pressure-wall thickness framework, support this observation and, in addition, quantitates the contribution of intracoronary fluid to interwall synergy. Another study reporting the effect of incomplete coronary occlusion on wall dynamics is that by Skulstad et al. (40), in which the left anterior descending (LAD) flow of dogs was reduced in ~50%. As shown in Fig. 1 of their paper, at this degree of LAD flow reduction, the anterior wall waveform resembles very much that of our dogs, suggesting that this motion pattern appears even if one-half the normal amount of intravascular fluid is present. However, these recordings are taken 1–2 min after flow reduction; therefore, the abnormal wall behavior may be due at least in part to cell hypoxia. On the other hand, if this degree of flow reduction were not enough to induce cell hypoxia, then the abnormal wall motion would be entirely attributed to the lack of the remaining 50% intravascular fluid, thus supporting the relevance of the hydraulic skeleton. In any case, given the differences in timing of signal recording between Skulstad's dogs and ours, these speculations should be taken with caution.

In a study of regional dysfunction of normally perfused myocardium adjacent to an ischemic myocardium (the so-called functional border zone), Mazhary et al. (29) showed that, when comparing LAD vs. circumflex occlusions, the width of the dysfunctional myocardium was primarily dependent on hemodynamic factors, such as systolic ventricular pressure, rather than on anatomic differences between LAD and circumflex ischemias. In their dogs, increasing LV systolic pressure widened the border zone, whereas changing blood flow did not. Although this may appear to disagree with our results, it must be taken into account that, in Mazhary's dogs, the change imposed on blood flow was equal to the difference in relative flows resulting from LAD and circumflex occlusions, and that was only 13%. This subtle change was probably not enough to evidence any effect of the hydraulic skeleton on wall dynamics as it was in our dogs where the changes in flow were equal or close to 100%. In agreement with our observations and those of others, they report hyperfunction of the remote, nonischemic LAD territory during circumflex occlusion.

Limitations of the study.

The use of an anesthetized, open-chest, mechanically ventilated preparation is a limitation of our study. The effects of these conditions on hemodynamics and myocardial contractility may be the reasons for the relatively low peak systolic pressure values, as well as the values for wall thickening and maximum rate of left ventricular pressure development and decay, which are lower than those observed in conscious, chronically instrumented animals. However, in experimental conditions comparable to ours, other authors have reported values similar to those obtained in the present study (3, 40).

An additional flaw of this study is the lack of flow measurement in the subclavian-coronary anastomosis, which would have allowed dextran perfusion to be set on the basis of control flow rather than on control systolic pressure. As can be seen in Fig. 3, during dextran perfusion, a subtle thickening of the posterior wall during isovolumic relaxation occurred, suggesting a certain degree of overperfusion that probably would not have occurred should this experimental condition be carried out under flow rather than pressure control.

Clinical implications.

The clinical implications of our study are not straightforward. Postejective shortening after ischemia or infarct has been claimed as a marker of late recovery of wall motion after reperfusion, both in animals (4, 40) and, recently, in humans (8, 16). Recent works emphasizes the importance of the analysis of regional function, mainly during isovolumic relaxation (13, 19, 33). However, the role played by the loss of hydraulic skeleton in this context is not known. Coronary spasm and coronary angioplasty are examples of acute coronary occlusion (18, 26). In these settings, it should be taken into account that a significant amount of the observed ventricular dysfunction is because of the lack of fluid within the intramyocardial vessels rather than because of cardiomyocyte anoxia. In any case, the clinical relevance of our results remains to be determined.

In conclusion, our results show that the earliest wall motion change observed after acute coronary occlusion, namely ischemic wall thinning concomitant with normoperfused wall thickening during isovolumic relaxation, is the result of the absence of intracoronary fluid rather than because of cell anoxia and that this lack of hydraulic skeleton within the myocardial vessels contributes up to 30% to the interwall asynergy of left ventricular contraction.


   GRANTS
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
REFERENCES
 
This work was supported by grants from the René G. Favaloro University Foundation, Buenos Aires, Argentina.


   ACKNOWLEDGMENTS
 
Present address for P. Willshaw: School of Health Sciences, University of Wales Swansea, SA28PP, United Kingdom.


   FOOTNOTES
 

Address for reprint requests and other correspondence: J. G. Barra, Dept. of Physiological, Pharmacological, and Biochemical Sciences, Favaloro Univ., Solís 453, C1078AAI Buenos Aires, Argentina (E-mail: jgbarra{at}favaloro.edu.ar).

The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.


   REFERENCES
TOP
 ABSTRACT
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 GRANTS
 REFERENCES
 

  1. Arnold G, Kosche F, Miessner E, Neitzert A, and Lochner W. The importance of the perfusion pressure in the coronary arteries for the contractility and the oxygen consumption of the heart. Pflügers Arch Gesamte Physiol Menschen Tiere 299: 339–356, 1968.[CrossRef][Medline]
  2. Arnold G, Morgenstern C, and Lochner W. The autoregulation of the heart work by the coronary perfusion pressure. Pflügers Arch 321: 34–55, 1970.[CrossRef][ISI][Medline]
  3. Aversano T and Marino PN. Effect of ischemic zone size on nonischemic zone function. Am J Physiol Heart Circ Physiol 258: H1786–H1795, 1990.[Abstract/Free Full Text]
  4. Brown MA, Norris RM, Takayama M, and White HD. Post-systolic shortening: a marker of potential for early recovery of acutely ischaemic myocardium in the dog. Cardiovasc Res 21: 703–716, 1987.[ISI][Medline]
  5. Crottogini AJ, Guth BD, Barra JG, Willshaw P, Lascano EC, and Pichel RH. Interventricular coronary steal induced by stenosis of left anterior descending coronary artery in exercising pigs. Circulation 83: 1361–1370, 1991.[Abstract/Free Full Text]
  6. Crottogini AJ, Willshaw P, Barra JG, Lascano EC, and Pichel RH. Differential effects of left anterior descending coronary occlusion on left and right ventricular anterior wall thickening in the conscious pig. Cardiovasc Res 26: 221–225, 1992.[Abstract/Free Full Text]
  7. Doyle RL, Foex P, Ryder WA, and Jones LA. Differences in ischaemic dysfunction after gradual and abrupt coronary occlusion: effects on isovolumic relaxation. Cardiovasc Res 21: 507–514, 1987.[ISI][Medline]
  8. Edvardsen T, Urheim S, Skulstad H, Steine K, Ihlen H, and Smiseth OA. Quantification of left ventricular systolic function by tissue Doppler echocardiography. Added value of measuring pre- and postejection velocities in ischemic myocardium. Circulation 105: 2071–2077, 2002.[Abstract/Free Full Text]
  9. Fan D, Soei LK, Stubenitsky R, Boersma E, Duncker DJ, Verdouw PD, and Krams R. Contribution of asynchrony and nonuniformity to mechanical interaction in normal and stunned myocardium. Am J Physiol Heart Circ Physiol 273: H2146–H2154, 1997.[Abstract/Free Full Text]
  10. Gallagher KP, Kumada T, Koziol JA, McKown MD, Kemper WS, and Ross J Jr. Significance of regional wall thickening abnormalities relative to transmural myocardial perfusion in anesthetized dogs. Circulation 62: 1266–1274, 1980.[Abstract/Free Full Text]
  11. Gayheart PA, Vinten-Johansen J, Johnston WE, Hester TO, and Cordell AR. Oxygen requirements of the dyskinetic myocardial segment. Am J Physiol Heart Circ Physiol 257: H1184–H1191, 1989.[Abstract/Free Full Text]
  12. Glagov S, Zarins C, Giddens DP, and Ku DN. Hemodynamics and atherosclerosis. Insights and perspectives gained from studies of human arteries. Arch Pathol Lab Med 112: 1018–1031, 1988.[ISI][Medline]
  13. Hatle L and Sutherland GR. Regional myocardial function: a new approach. Eur Heart J 21: 1337–57, 2000.[Free Full Text]
  14. Herman MV and Gorlin R. Implications of left ventricular asynergy. Am J Cardiol 23: 538–547, 1969.[CrossRef][ISI][Medline]
  15. Heusch G, Rose J, Skyschally A, Post H, and Schulz R. Calcium responsiveness in regional myocardial short-term hibernation and stunning in the in situ porcine heart. Inotropic responses to postextrasystolic potentiation and intracoronary calcium. Circulation 93: 1556–1566, 1996.[Abstract/Free Full Text]
  16. Hosokawa H, Sheehan FH, and Suzuki T. Measurement of postsystolic shortening to assess viability and predict recovery of left ventricular function after acute myocardial infarction. J Am Coll Cardiol 35: 1842–1849, 2000.[Abstract/Free Full Text]
  17. Indolfi C, Guth BD, Miyazaki S, Miura T, Schulz R, and Ross J Jr. Heart rate reduction improves myocardial ischemia in swine: role of interventricular blood flow redistribution. Am J Physiol Heart Circ Physiol 261: H910–H917, 1991.[Abstract/Free Full Text]
  18. Jamal F, Kukulski T, D'hooge J, De Scheerder I, and Sutherland G. Abnormal postsystolic thickening in acutely ischemic myocardium during coronary angioplasty: a velocity, strain, and strain rate Doppler myocardial imaging study. J Am Soc Echocardiogr 12: 994–996, 1999.[CrossRef][ISI][Medline]
  19. Jamal F, Szilard M, Kukulski T, Liu XS, D'hooge J, Bijnens B, Rademakers F, Hatle L, Descheerder I, and Sutherland GR. Changes in systolic and postsystolic wall thickening during acute coronary occlusion and reperfusion in closed-chest pigs: implications for the assessment of regional myocardial function. J Am Soc Echocardiogr 14: 691–697, 2001.[CrossRef][ISI][Medline]
  20. Jennings RB, Murry CE, Steenbergen C Jr, and Reimer KA. Development of cell injury in sustained acute ischemia. Circulation 82: II2–II12, 1990.
  21. Kanaide H, Taira Y, and Nakamura M. Transmural anoxic wave front and regional dysfunction during early ischemia. Am J Physiol Heart Circ Physiol 253: H240–H247, 1987.[Abstract/Free Full Text]
  22. Kanaide H, Yoshimura R, Makino N, and Nakamura M. Regional myocardial function and metabolism during acute coronary artery occlusion. Am J Physiol Heart Circ Physiol 242: H980–H989, 1982.[Abstract/Free Full Text]
  23. Kloner RA and Jennings RB. Consequences of brief ischemia: stunning, preconditioning, and their clinical implications: part 1. Circulation 104: 2981–2989, 2001.[Abstract/Free Full Text]
  24. Kloner RA, Przyklenk K, and Whittaker P. Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues. Circulation 80: 1115–1127, 1989.[Abstract/Free Full Text]
  25. Koh TW, Pepper JR, and Gibson DG. Early changes in left ventricular anterior wall dynamics and coordination after coronary artery surgery. Heart 78: 291–297, 1997.[Abstract/Free Full Text]
  26. Kukulski T, Jamal F, D'Hooge J, Bijnens B, De Scheerder I, and Sutherland GR. Acute changes in systolic and diastolic events during clinical coronary angioplasty: a comparison of regional velocity, strain rate, and strain measurement. J Am Soc Echocardiogr 15: 1–12, 2002.[CrossRef][ISI][Medline]
  27. Lunkenheimer PP and Ising H. The hydraulic skeleton of the heart. A working hypothesis on the mechanism of ventricle unfolding. Zentralbl Veterinarmed A 21: 365–378, 1974.[ISI][Medline]
  28. Lunkenheimer PP. The hydraulic function of intramyocardial fluids subject to the erectile properties of the ventricular wall of mammalian hearts. Zentralbl Veterinarmed A 22: 632–644, 1975.[ISI][Medline]
  29. Mazhari R, Omens JH, Covell JW, and McCulloch AD. Structural basis of regional dysfunction in acutely ischemic myocardium. Cardiovasc Res 47: 284–293, 2000.[Abstract/Free Full Text]
  30. Miller WP, Nellis SH, Liedtke AJ, Whitesell L, and Effron BA. Coronary hyperperfusion and ventricular function in intact and isovolumic pig hearts. Am J Physiol Heart Circ Physiol 258: H500–H507, 1990.[Abstract/Free Full Text]
  31. Miyazaki S, Goto Y, Guth BD, Miura T, Indolfi C, and Ross J Jr. Changes in regional myocardial function and external work in exercising dogs with ischemia. Am J Physiol Heart Circ Physiol 264: H110–H116, 1993.[Abstract/Free Full Text]
  32. Perrone-Filardi P, Bacharach SL, Dilsizian V, Maurea S, Frank JA, and Bonow RO. Regional left ventricular wall thickening. Relation to regional uptake of 18fluorodeoxyglucose and 201Tl in patients with chronic coronary artery disease and left ventricular dysfunction. Circulation 86: 1125–1137, 1992.[Abstract/Free Full Text]
  33. Pislaru C, Anagnostopoulos PC, Seward JB, Greenleaf JF, and Belohlavek M. Higher myocardial strain rates during isovolumic relaxation phase than during ejection characterize acutely ischemic myocardium. J Am Coll Cardiol 40: 1487–1494, 2002.[Abstract/Free Full Text]
  34. Sabbah HN and Stein PD. Early segmental thinning of the left ventricular wall following regional ischemia. Cathet Cardiovasc Diagn 9: 473–482, 1983.[ISI][Medline]
  35. Salisbury PF, Cross CE, and Rieben PA. Influence of coronary artery pressure upon myocardial elasticity. Circ Res 8: 794–800, 1960.[Abstract/Free Full Text]
  36. Sasayama S, Franklin D, Ross J Jr, Kemper WS, and McKown D. Dynamic changes in left ventricular wall thickness and their use in analyzing cardiac function in the conscious dog. Am J Cardiol 38: 870–879, 1976.[CrossRef][ISI][Medline]
  37. Schamhardt HC, Verdouw PD, and Saxena PR. Improvement of perfusion and function of ischaemic porcine myocardium after reduction of heart rate by alinidine. J Cardiovasc Pharmacol 3: 728–738, 1981.[ISI][Medline]
  38. Schaper W and Pasyk S. Influence of collateral flow on the ischemic tolerance of the heart following acute and subacute coronary occlusion. Circulation 53: I57–I62, 1976.
  39. Schulz R, Miyazaki S, Miller M, Thaulow E, Heusch G, Ross J Jr, and Guth BD. Consequences of regional inotropic stimulation of ischemic myocardium on regional myocardial blood flow and function in anesthetized swine. Circ Res 64: 1116–1126, 1989.[Abstract/Free Full Text]
  40. Skulstad H, Edvardsen T, Urheim S, Rabben SI, Stugaard M, Lyseggen E, Ihlen H, and Smiseth OA. Postsystolic shortening in ischemic myocardium: active contraction or passive recoil? Circulation 106: 718–724, 2002.[Abstract/Free Full Text]
  41. Smalling RW, Ekas RD, Felli PR, Binion L, and Desmond J. Reciprocal functional interaction of adjacent myocardial segments during regional ischemia: an intraventricular loading phenomenon affecting apparent regional contractile function in the intact heart. J Am Coll Cardiol 7: 1335–1346, 1986.[Abstract]
  42. Theroux P, Franklin D, Ross J Jr, and Kemper WS. Regional myocardial function during acute coronary artery occlusion and its modification by pharmacologic agents in the dog. Circ Res 35: 896–908, 1974.[Abstract/Free Full Text]
  43. Theroux P, Ross J Jr, Franklin D, Kemper WS, and Sasayama S. Regional myocardial function in the conscious dog during acute coronary occlusion and responses to morphine, propranolol, nitroglycerin, and lidocaine. Circulation 53: 302–314, 1976.[Abstract/Free Full Text]
  44. Weihs H, Mutschler E, and Walland A. Alinidine prevents hypoperfusion-induced transmural flow redistribution in isolated paced rat hearts. Clin Exp Pharmacol Physiol 21: 471–476, 1994.[ISI][Medline]
  45. Willshaw P, Lascano EC, Crottogini AJ, Negroni J, and Pichel R. Tri-axial graphics as an aid to understanding left ventricular function in conscious dogs. J Biomed Eng 6: 107–112, 1984.[ISI][Medline]
  46. Zelis R, Flaim SF, Liedtke AJ, and Nellis SH. Cardiocirculatory dynamics in the normal and failing heart. Annu Rev Physiol 43: 455–476, 1981.[CrossRef][ISI][Medline]




This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/2/H896    most recent
00041.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Barra, J. G.
Right arrow Articles by Pichel, R. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Barra, J. G.
Right arrow Articles by Pichel, R. H.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.