HYDROXYL RADICAL PRODUCTION DURING MYOCARDIAL-ISCHEMIA AND REPERFUSION IN CATS

We previously showed that generation of reactive oxygen species during myocardial ischemia and reperfusion stimulates cardiac sympathetic af ferent nerve endings. We hypothesized that, in this feline model of br ief ischemia and reperfusion, HO . is produced during ischemia and the rate and concentration of production of HO . during reperfusion is de pendent on the duration of myocardial ischemia. Therefore, we evaluate d the time dependency of production of HO . during reperfusion after 2 , 5, and 10 min of reversible occlusion of the left anterior descendin g (LAD) coronary artery to induce ischemia in cats (n = 10). Blood sam ples 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 high est rate of production of tyrosines was observed immediately after isc hemia, 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) con taining phenylalanine was perfused into the ischemic coronary vascular bed through a cannula placed in the LAD (n = 16). Perfusate was colle cted from the coronary vein during the 10 min of ischemia. Net product ion 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 H O . during ischemia and reperfusion. These results demonstrate that HO . is produced during brief ischemia and reperfusion, with the greates t amount being produced immediately after ischemia. Additionally, we s how that the duration of brief ischemia determines the rate of product ion of HO . during reperfusion.