Acetaminophen shows positive in vivo cardioprotective effects in heart attack, arrhythmia
Infarct size reduced 60%+ by three different measures
BETHESDA, Md. (Nov. 11, 2004) – Long an under-studied yet widely-used over-the-counter medication, acetaminophen over the last few years is becoming recognized for a range of potential therapeutic uses beyond headache and pain.
One promising area is cardiology, where researchers decided to test the "common wisdom" that acetaminophen had no potential in treating heart disease. This position has been popular in the medical community despite that fact that "there are no in vivo reports on acetaminophen efficacy during myocardial infarction," a team from Rutgers University notes in the November issue of the American Journal of Physiology-Heart and Circulatory Physiology.
The researchers tested the "gold standard" in the cardiovascular area: "what kind of cardioprotection a medical agent provides, specifically by measuring the infarct size" in a simulated heart attack, according to Gary F. Merrill, the lead author. The team found that acetaminophen significantly reduced the infarct size by 60% or more by three different key measurements in treated dogs, compared with a physiologically identical but untreated control group.
While the heart areas at risk were similar in the two groups, the actual infarct size of untreated animals was 22 grams plus or minus 3g versus 9g ± 2g in treated animals, or about a 60% reduction. Similarly, infarct size expressed as a percentage of the area at risk in untreated hearts was 35% ± 3% versus acetaminophen-treated dogs where it was 13% ± 2%, about a 63% reduction. And when the infarct size was expressed as a percentage of the entire myocardium, the difference in infarct size was equally significant: 8% ± 1% for untreated dogs versus 3% ± 1% for acetaminophen-treated dogs – a 62.5% decrease.
Other variables stable; acetaminophen anti-arrhythmic action observed
The researchers noted that the "absence of differences in ventricular function and in the general respiratory-metabolic status of the dogs suggests that statistically significant variability in myocardial infarction cannot be explain on the basis of ventricular mechanics, metabolism or respiration."
They said the results of the current study "extend our recent work in vitro to the in vivo arena and reveal salutary effects of acetaminophen in the neurohumorally intact, blood-perfused tissue environment of the canine myocardium. Results suggest that acetaminophen is among the most efficacious of the cardioprotective agents discovered to date."
The study, "Acetaminophen and myocardial infarction in dogs," was written by Gary F. Merrill, Tyler H. Rork, and Norell M. Spiler at the Department of Cell Biology and Neurosciences, Division of Life Sciences, Rutgers University, Piscataway, New Jersey, and Roseli Golfetti of the State University of Sao Paulo at Campinas, Brazil, who was at Rutgers during the research experiments.
Although studying arrhythmia wasn't part of the protocol and thus wasn't monitored rigorously, the authors note that "during both ischemia and reperfusion, acetaminophen-treated hearts appeared much more stable, electrically, than (control) hearts. For example, nonsustained ventricular tachycardia occurred regularly in (control) dogs during reperfusion but was less evident in the presence of acetaminophen." Specifically in four of the 10 control dogs "nonsustained tachycardia occurred regularly" during reperfusion, but was observed in only one of the treated dogs.
Caveats and next steps
Given the significance of their findings, the authors put forth this caution: "Metabolism of acetaminophen by dogs is different than in humans. Therefore, the results obtained at the doses used (30 mg/kg) might be only applicable to dogs and not to humans. More work is needed to reveal the potential salutary effects of this agent in other tissues and organ systems under other physiological and/or pathophysiological conditions."
For instance, Merrill said that "one of the disappointing findings in the current study was a follow up to earlier studies on guinea pig hearts where one of the most pronounced effects was mechanical; acetaminophen aided the left ventricle during reperfusion. But in dogs, acetaminophen only affected the necrotic part of the heart. In other words, acetaminophen had no net beneficial mechanical effects on a dog heart."
Merrill noted that study of acetaminophen continues to grow. For instance "as-yet-unpublished investigations are exploring the effects of acetaminophen on diet and vascular atherogenesis, spread of necrosis and apoptosis postmyocardial infarction, and procedurally induced myocardial infarction." And certainly "an investigation of the potential antiarrythmic qualities of acetaminophen, in an in vivo setting, should be conducted," they added.
Finally, the researchers pointed out that the current experiment directly administered acetaminophen at two intervals during the induced heart attack and that studying chronic, small-dose ingestion might yield useful findings.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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