Additive beneficial effects of two inhibitors of vasoconstrictor mediators in acute myocardial ischemia.

Abstract

A specific inhibitor of thromboxane A2 (TxA2) synthesis, CGS-12970, a new angiotensin-converting enzyme (ACE) inhibitor, CGS-16617, and a combination of both agents were evaluated for their ability to reduce the extension of myocardial infarct size in rats. Myocardial creatine kinase (CK) loss from the left ventricular free wall (LVFW) 48 hr after left coronary artery ligation was used as an index of ischemic damage. Treatment with either CGS-12970 (4 mg/kg) or CGS-16617 (1 microgram/kg) alone did not attenuate the loss of CK from LVFW significantly, compared with animals receiving only the vehicles for these drugs. However, the combined use of both agents significantly reduced CK depletion from LFVW (P less than 0.01). These findings support the interrelated role of TxA2 and angiotensin II as mediators of myocardial ischemia and suggest that combined inhibition of their formation may be useful in the treatment of acute myocardial infarction.

• Authors: H Bitterman, D J Lefer, A M Lefer
• Journal: Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) (Proc Soc Exp Biol Med) Vol. 185 Issue 3 Pg. 262-6 (Jul 1987) ISSN: 0037-9727 [Print] United States
• PMID: 3037554 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Benzazepines
• Pyridines
• 3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid
• Creatine Kinase
• Thromboxane-A Synthase
• libenzapril

Topics

• Acute Disease
• Angiotensin-Converting Enzyme Inhibitors
• Animals
• Benzazepines (therapeutic use)
• Blood Pressure (drug effects)
• Coronary Disease (drug therapy, enzymology, physiopathology)
• Creatine Kinase (metabolism)
• Drug Therapy, Combination
• Heart Rate (drug effects)
• Male
• Myocardial Infarction (prevention & control)
• Myocardium (enzymology)
• Pyridines (therapeutic use)
• Rats
• Rats, Inbred Strains
• Thromboxane-A Synthase (antagonists & inhibitors)
• Vasoconstriction (drug effects)