Acetaminophen and myocardial infarction in dogs

Abstract

The hypothesis that acetaminophen can reduce necrosis during myocardial infarction was tested in male dogs. Two groups were studied: vehicle- (n=10) and acetaminophen-treated (n=10) dogs. All dogs were obtained from the same vendor, and there were no significant differences in their ages (18 +/- 2 mo), weights (24 +/- 1 kg), or housing conditions. Selected physiological data, e.g., coronary blood flow, nonspecific collateral flow, epicardial temperature, heart rate, systemic mean arterial pressure, left ventricular developed pressure, the maximal first derivative of left ventricular developed pressure, blood gases, and pH, were collected at baseline and during regional myocardial ischemia and reperfusion. There were no significant differences in coronary blood flow, nonspecific collateral flow, epicardial temperature, heart rate, systemic mean arterial pressure, or blood gases and pH between the two groups at any of the three time intervals, even though there was a trend toward improved function in the presence of acetaminophen. Infarct size, the main objective of the investigation, was markedly and significantly reduced by acetaminophen. For example, when expressed as a percentage of ventricular wet weight, infarct size was 8 +/- 1 versus 3 +/- 1%(P <0.05) in vehicle- and acetaminophen-treated hearts, respectively. When infarct size was expressed as percentage of the area at risk, it was 35 +/- 3 versus 13 +/- 2% (P <0.05) in vehicle- and acetaminophen-treated groups, respectively. When area at risk was expressed as percentage of total ventricular mass, there were no differences in the two groups. Results reveal that the recently reported cardioprotective properties of acetaminophen in vitro can now be extended to the in vivo arena. They suggest that it is necessary to add acetaminophen to the growing list of pharmaceuticals that possess cardioprotective efficacy in mammals.

Acetaminophen-mediated cardioprotection via inhibition of the mitochondrial permeability transition pore-induced apoptotic pathway

“…Previous studies show that, in an in vivo canine preparation of myocardial infarction, acetaminophen treatment results in a significant reduction of necrotic tissue (33). In the present study, we proposed that acetaminophen might also have an effect on the mitochondrial pathway of apoptosis following ischemia/reperfusion.…”

“…Additional studies from our laboratory have demonstrated that acute acetaminophen treatment also confers protection in a canine model of myocardial infarction (18,33). However, while structural, functional, and biochemical evidence of acetaminophen-mediated cardioprotection exists, mechanistic data are noticeably absent.…”

Cardioprotective effects of nitroparacetamol and paracetamol in acute phase of myocardial infarction in experimental rats

“…The present study is the first report that NO-paracetamol and paracetamol could significantly reduce infarct size in rats after permanent MI. However, Merrill et al (22) showed that paracetamol reduced infarct size in dogs and in rats after ischemia-reperfusion (8). Some of the theories put forward included the hypothesis that paracetamol diminishes hydrogen peroxide-induced ventricular dysfunction (21).…”

Retrospective Determination of the Area at Risk for Reperfused Acute Myocardial Infarction With T2-Weighted Cardiac Magnetic Resonance Imaging

“…To evaluate therapeutic procedures and drugs aimed at modulating infarct size, it is important not only to measure the size of an infarct but also to know how much myocardium was at risk. 4,5 Thus, the percentage of infarcted myocardium within the area at risk provides an index that controls for factors that modulate infarct size other than the intervention or treatment. 6 -8 Measuring the area at risk is difficult in patients with acute myocardial infarction (MI).…”