Myocardial protection in the occlusion/reperfusion dog model: the role of ischemic necrosis vs reperfusion injury.
The present study was designed to assess the possibility 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 +/- 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 pressure were monitored. The risk area (RA; % left ventricle (LV)) was determined by the infusion of Evans blue into the aortic root and the area of necrosis (AN; %RA) by triphenyltetrazolium chloride staining. Myocardial preservation was defined as %RA not necrosed calculated as (RA-AN)/RA x 100. RA was similar in all dogs, i.e., 33 +/- 2% LV (SD). There were no differences in arterial pressure, heart rate or double product among groups. Myocardial preservation was 60 +/- 13% RA in 9 control dogs submitted to reperfusion only (group C), and 58 +/- 18% 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 (group 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 +/- 13% RA in group VP, 74 +/- 11% in group VP+DF and 73 +/- 9% in group VP+VP (P = 0.04 vs group C, ANOVA). The data suggest that the mechanism underlying this beneficial effect is mainly related to the retardation of necrosis progression. O2 free radicals or Ca(2+)-induced reperfusion injury do not play a major role.
Chagas
A C
AC
Divisão de Experimentação, Faculdade de Medicina, Universidade de São Paulo, Brasil.
Pileggi
F
F
Lopes
E A
EA
Da-Luz
P L
PL
D000818:Animals; D003331:Coronary Vessels / Q000473:pathology; D003676:Deferoxamine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D005609:Free Radicals; D007501:Iron / Q000097:blood; D015425:Myocardial Reperfusion / Q000534:rehabilitation*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D014665:Vasodilator Agents / Q000627:therapeutic use*; D014700:Verapamil / Q000627:therapeutic use*
D005609:Free Radicals; D014665:Vasodilator Agents; D014700:Verapamil; D007501:Iron; D003676:Deferoxamine