Myocardioprotective effects of felodipine in an antihypertensive dosage: an experimental study in pigs.
The objective of this study was to test the hypothesis that treatment with the calcium antagonist felodipine in normal clinical dosages may have a myocardio-protective effect in the event of ischemia followed by reperfusion. Comparing the cardioprotective effects of felodipine and an agent of another class allowed the influence of blood pressure reduction per se to be evaluated. Twenty open-chest pigs were exposed to 45 minutes of myocardial ischemia via occlusion of the left anterior descending coronary artery (LAD) followed by 240 minutes of reperfusion. Either felodipine (felo group; n = 7) or sodium nitroprusside (SNP group; n = 7) was administered intravenously starting at 180 minutes before the LAD occlusion in a dose that was intended to reduce the mean arterial blood pressure (MAP) by 30%. Six pigs (vehicle group) serving as controls received a mixture of polyethylene glycol (PEG) and 5% glucose, the vehicles for felodipine and SNP, intravenously. MAP in the felo and SNP groups was reduced to 65% and 72% of the preinfusion levels, respectively. Infarct size as a percentage of the area at risk was 49% in the felo, 73% (P < 0.05) in SNP, and 79% (P < 0.01) in the vehicle groups, respectively. Felodipine, given in a dose resulting in plasma levels corresponding to the therapeutic range in patients on antihypertensive treatment, reduced infarct size following myocardial ischemia/reperfusion. Afterload reduction induced by nitroprusside did not influence infarct size. Thus, felodipine exerted a myocardioprotective effect unrelated to the mechanism of afterload reduction in clinically relevant antihypertensive dosages.
Shimizu
M
M
Department of Cardiology, Karolinksa Hospital, Stockholm, Sweden.
Wang
Q D
QD
Sjöquist
P O
PO
Nordlander
R
R
Rydén
L
L
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D015736:Felodipine / Q000627:therapeutic use*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009599:Nitroprusside / Q000627:therapeutic use; D013552:Swine
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D009599:Nitroprusside; D015736:Felodipine