Myocardial protection in the occlusion/reperfusion dog model: the role of ischemic necrosis vs reperfusion injury

RESUMO

The present study was designed to assess the possbility of maximizing the effects of reperfusion by the association of the calcium channel blocker, verapamil and the iron chelator deferoxamine, to delay necrosis and avoid reperfusion injury. Sixty-four mongrel dogs (15 ñ 1.1 (SD)Kg) were successfully subjected to 24 h of reperfusion following 90-min occlusion of the left anterior coronary artery. ECG and arterial presure were monitored. The risk area (RA; percent left ventricle (LV)) was determined by the infusion of Evans blue into the aortic root and the area of necrosis (AN; per cent RA) by triphenyltetrazolium chloride staining. Myocardial presevation was defined as per cent RA not necrosed calculated as (RA - AN)/RA x 100.RA was similar in all dogs, i.e., 33 ñ 2 per cent LV (SD). There were no differences in arterial pressure, heart rate or double product among groups. Myocardial preservation was 60 ñ 13 per cent RA in 9 control dogs submitted to reperfusion only (group C), and 58 ñ 18 per cent RA in 17 dogs treated with deferoxamine (500 mg, iv), 30 min before reperfusion (group DF). Verapamil (0.2 mg/Kg, iv) was given alone 15 min after occlusion to 15 dogs (group VP), followed by prereperfusion deferoxamine to 16 dogs (goup VP + DF) and in two doses after occlusion and 15 min before reperfusion in 7 dogs (group VP + VP). Myocardial preservation was greater in the latter groups when compared to controls, namely 76 ñ 13 per cent RA in group VP, 74 ñ 11 per cent in group VP + DF and 73 ñ 9 per cent in group VP + VP (P = 0.04 vs group C., ANOVA). The data suggest that mechanism underlying this beneficial effect is mainly related to the retardation of nectosis progression. O2 free radicals or Ca2+-induced reperfusion injury do not play a major role