AJP - Heart and Circulatory Physiology, Vol 271, Issue 2 660-H667, Copyright © 1996 by American Physiological Society

ARTICLES

Hydroxyl radical production during myocardial ischemia and reperfusion in cats

C. A. O'Neill, L. W. Fu, B. Halliwell and J. C. Longhurst
Department of Internal Medicine, University of California, Davis 95616, USA.

We previously showed that generation of reactive oxygen species during myocardial ischemia and reperfusion stimulates cardiac sympathetic afferent nerve endings. We hypothesized that, in this feline model of brief ischemia and reperfusion, HO. is produced during ischemia and the rate and concentration of production of HO.during reperfusion is dependent on the duration of myocardial ischemia. Therefore, we evaluated the time dependency of production of HO. during reperfusion after 2, 5, and 10 min of reversible occlusion of the left anterior descending (LAD) coronary artery to induce ischemia in cats (n = 10). Blood samples collected from the coronary vein at 0.25, 1, 2, and 4 min after 2 min of ischemia revealed net cumulative rate of production of p-, m-, and o-tyrosine of 99 +/- 31, 10 +/- 5.1, and 0.8 +/- 0.2 nmol.min-1.g-1, respectively. After 5 min of ischemia, net cumulative rates of production of p-, m-, and o-tyrosine during reperfusion were 177 +/- 63, 74 +/- 26, and 1.6 +/- 0.8 nmol.min-1.g-1, respectively, whereas after 10 min of ischemia production rates were 153 +/- 42, 78 +/- 29, and 2.1 +/- 0.5 nmol.min-1.g-1, respectively. The highest rate of production of tyrosines was observed immediately after ischemia, perhaps indicating a washout of HO.-derived products that had accumulated in the myocardium during ischemia. To evaluate production of HO. during ischemia, deoxygenated saline (PO2 10 +/- 0.9 mmHg) containing phenylalanine was perfused into the ischemic coronary vascular bed through a cannula placed in the LAD (n = 16). Perfusate was collected from the coronary vein during the 10 min of ischemia. Net production of HO. during ischemia, measured by the production of p-, m-, and o-tyrosine, was 82 +/- 11, 6.6 +/- 0.4, and 1.7 +/- 0.3 nmol.min-1.g-1, respectively. Pretreatment with deferoxamine (10 mg/kg, n = 7) or dimethylthiourea (10 mg/kg, n = 6) decreased net production of HO. during ischemia and reperfusion. These results demonstrate that HO. is produced during brief ischemia and reperfusion, with the greatest amount being produced immediately after ischemia. Additionally, we show that the duration of brief ischemia determines the rate of production of HO. during reperfusion.

This article has been cited by other articles:

				L. G. Kevin, E. Novalija, M. L. Riess, A. K. S. Camara, S. S. Rhodes, and D. F. Stowe Sevoflurane Exposure Generates Superoxide but Leads to Decreased Superoxide During Ischemia and Reperfusion in Isolated Hearts Anesth. Analg., April 1, 2003; 96(4): 949 - 955. [Abstract] [Full Text] [PDF]

				L. G. Kevin, A. K. S. Camara, M. L. Riess, E. Novalija, and D. F. Stowe Ischemic preconditioning alters real-time measure of O2 radicals in intact hearts with ischemia and reperfusion Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H566 - H574. [Abstract] [Full Text] [PDF]

				A. Skyschally, R. Schulz, P. Gres, H.-G. Korth, and G. Heusch Attenuation of ischemic preconditioning in pigs by scavenging of free oxyradicals with ascorbic acid Am J Physiol Heart Circ Physiol, February 1, 2003; 284(2): H698 - H703. [Abstract] [Full Text] [PDF]

				C. Li, R. L. Kao, T. Ha, J. Kelley, I. W. Browder, and D. L. Williams Early activation of IKK{beta} during in vivo myocardial ischemia Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1264 - H1271. [Abstract] [Full Text] [PDF]

				E. Carmeliet Cardiac Ionic Currents and Acute Ischemia: From Channels to Arrhythmias Physiol Rev, July 1, 1999; 79(3): 917 - 1017. [Abstract] [Full Text] [PDF]

				C. Li, W. Browder, and R. L. Kao Early activation of transcription factor NF-kappa B during ischemia in perfused rat heart Am J Physiol Heart Circ Physiol, February 1, 1999; 276(2): H543 - H552. [Abstract] [Full Text] [PDF]