Coronary venous retroinfusion of felodipine reduces myocardial necrosis after coronary occlusion and reperfusion.
The effect of the vasoselective calcium antagonist felodipine on myocardial necrosis was studied in 14 anesthetized pigs subjected to 45-min occlusion of the left anterior descending coronary artery (LAD) followed by 24-h reperfusion. Felodipine (7 nmol/kg, n = 7), or the corresponding amount of vehicle diluted in 300 ml saline (n = 7) was infused in the great cardiac vein for 30 min beginning 5 min before onset of reperfusion. Regional myocardial function was measured as percentage of systolic segment shortening (%SS) by sonomicrometry. The recovery in ischemic myocardium was significantly already better among felodipine-treated animals after 30-min reperfusion (mean +/- SD = 9.1 +/- 6.1 vs. 0.1 +/- 3.2%, p < 0.05). The improved recovery in the felodipine group persisted throughout the observation period; %SS was 8.5 +/- 5.9% after 24-h reperfusion. No significant improvement was observed in the vehicle group after 24 h (%SS = 2.7 +/- 2.0%, p < 0.05). The area of the infarct was measured by triphenyl tetrazolium chloride staining. When expressed as percentage of the left ventricle, the infarct was smaller in the felodipine group (8.2 +/- 4.0%) than in the vehicle group (14.6 +/- 3.5%; p < 0.01). The corresponding values for infarct size expressed as percentage of the area at risk was 38.6 +/- 18.9% in the felodipine group and 69.8 +/- 6.7% in the vehicle group (p < 0.01). Peak plasma felodipine concentration was reached 30 min after onset of reperfusion (4.9 +/- 1.2 nM).(ABSTRACT TRUNCATED AT 250 WORDS)
Hatori
N
N
Department of Cardiology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
Haga
Y
Y
Sjöquist
P O
PO
Nordlander
M
M
Rydén
L
L
D000818:Animals; D003331:Coronary Vessels; D015736:Felodipine / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D009336:Necrosis; D011897:Random Allocation; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects
D015736:Felodipine