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Potassium channel activators cromakalim and celikalim (WAY-120,491) fail to decrease myocardial infarct size in the
J M Kitzen1, J D McCallum, C Harvey
1Department of Cardiovascular-Metabolic, Wyeth-Ayerst Research Laboratories, Princeton, N.J.
Pharmacology
|January 1, 1992
Summary
K channel activator drugs like cromakalim and celikalim worsened myocardial infarction injury when given directly into the coronary artery. Intravenous administration did not show these harmful effects, suggesting they are not suitable for acute heart attack treatment.
Area of Science:
- Cardiovascular Pharmacology
- Ischemic Heart Disease Research
Background:
- Potassium (K) channel activators are investigated for potential cardioprotective effects.
- Myocardial infarction (MI) involves ischemia and reperfusion injury, necessitating effective acute treatments.
Purpose of the Study:
- To evaluate the cardioprotective efficacy of K channel activators, cromakalim and celikalim, in a canine model of myocardial infarction.
- To determine the impact of drug administration route (intracoronary vs. intravenous) on infarct size.
Main Methods:
- A canine model of myocardial infarction was induced (90 min ischemia, 5 h reperfusion).
- Cromakalim and celikalim were administered via intracoronary or intravenous routes.
- Infarct size, area at risk, and rate-pressure product were assessed.
Main Results:
- Intracoronary administration of cromakalim and celikalim significantly increased infarct size compared to vehicle control.
- Intravenous administration of these drugs did not alter infarct size.
- Diltiazem administered intravenously showed a trend towards reducing infarct size, though not statistically significant.
Conclusions:
- K channel activators, cromakalim and celikalim, may exacerbate ischemic injury when administered intracoronarily.
- These drugs are unlikely to be effective for acute therapeutic management of myocardial ischemic injury.
- The route of administration is critical when considering K channel activators for cardiovascular conditions.