Intracoronary SIN-1C during reperfusion reduces infarct size in dog.
Reperfusion of ischemic myocardium may aggravate the ischemic state of injury and thus augment infarct size (reperfusion injury). The aim of this study was to reduce infarct size by an intervention at the time of reperfusion that acts only on a reperfusion-specific pathomechanism. It was investigated whether SIN-1C, a metabolite of molsidomine, can protect against reperfusion injury in canine hearts in vivo. Ten anesthetized open chest dogs underwent 1 h of left anterior descendent artery (LAD) occlusion and were randomly assigned to receive either intracoronary SIN-1C or vehicle infusion as a placebo during the first hour of reperfusion. The infusion was adjusted to LAD flow to achieve a regional blood concentration of 5 x 10(-3) M. Infarct size was assessed by triphenyltetrazolium staining after 6 h of reperfusion. Left ventricular pressure (LVP) was similar in both groups (SIN-1C: 101 +/- 6, placebo: 89 +/- 6 mm Hg, mean +/- SEM, n = 5) at the beginning of the experiment and did not change significantly thereafter from baseline values in both groups. During SIN-1C infusion, the LAD flow was increased (SIN-1C: 195 +/- 38, control: 86 +/- 17 ml/min/100 g at 30 min of reperfusion, p < 0.05), while systemic hemodynamics remained unaltered. A reduction in infarct size (percent of area at risk) was seen in the SIN-1C group (11.4 +/- 2.8%) compared with the placebo group (24.4 +/- 3.9%, p < 0.05). Infusion of papaverin (5 x 10(-5) M) following an identical protocol caused a similar vasodilation as SIN-IC, but did not reduce infarct size in five additional dox experiments.(ABSTRACT TRUNCATED AT 250 WORDS)
Schlack
W
W
Abteilung für Herz- und Kreislaufphysiologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
Uebing
A
A
Schäfer
M
M
Bier
F
F
Grunert
S
S
Ebel
D
D
Piper
H M
HM
Thämer
V
V
D000097:Acetonitriles / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D007262:Infusions, Intravenous; D008297:Male; D009025:Morpholines / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000473:pathology; D009336:Necrosis / Q000473:pathology; D010208:Papaverine / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D000097:Acetonitriles; D009025:Morpholines; C093946:SIN 1C; D010208:Papaverine