Failure of iloprost to protect the regionally ischemic, reperfused porcine heart.
The effect of iloprost (Schering AG, Berlin), a stable prostacyclin analogue, was investigated in ischemic, reperfused porcine hearts. The left anterior descending coronary artery (LAD) was distally occluded in 18 pigs for 45 min followed by 3-d of reperfusion. Nine pigs were continuously treated with iloprost at a dose of 25 ng/kg per min. Treatment was started as intracoronary infusion into the proximal LAD 10 min before occlusion. The intercoronary infusion was replaced by an intravenous infusion after 45 min of reperfusion, which was continued until the end of the experiment. Infarct size was determined as the ratio of infarcted (tetrazolium stain) to ischemic myocardium (dye technique). Regional systolic shortening was assessed by sonomicrometry. Myocardial concentrations of adenosine triphosphate were evaluated at the end of the experiment. Generation of free radicals by stimulated polymorphonuclear neutrophils was determined by luminol-enhanced chemiluminescence. Histologic and immunohistologic techniques were applied to characterize the myocardial inflammatory response. Global hemodynamics did not differ between the two groups. Neither infarct size (control group 68 +/- 18%, treated group 74 +/- 14%), recovery of systolic shortening (control group 3 +/- 6%, treated group 6 +/- 6%), nor myocardial adenosine triphosphate concentrations were improved by iloprost treatment. Myocardial inflammatory response remained unaffected by this treatment. The capacity of coronary venous, stimulated polymorphonuclear neutrophils to generate free radicals was slightly suppressed in the treated group before ischemia, at the end of ischemia and during early reperfusion. In this preparation, iloprost did not exhibit any beneficial effect on infarct size, recovery of systolic shortening and myocardial adenosine triphosphate concentrations.
Klein
H H
HH
Department of Cardiology, University of Marburg, Germany.
Pich
S
S
Bohle
R M
RM
Schuff-Werner
P
P
Schörling
M
M
Nebendahl
K
K
D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D005260:Female; D005609:Free Radicals; D006439:Hemodynamics / Q000187:drug effects; D016285:Iloprost / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D013552:Swine; D014693:Ventricular Fibrillation / Q000503:physiopathology
D005609:Free Radicals; D000255:Adenosine Triphosphate; D016285:Iloprost