Effect of Lisinopril and Isosorbide-5-Mononitrate on Hemodynamics and Mortality in Rats with Permanent Coronary Artery Occlusion

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Abstract
Summary: We studied the hemodynamic effects of lisinopril and isosorbide-5-mononitrate in rats with permanent coronary occlusion. Rats (n = 35) underwent left coronary occlusion, and ECGs were recorded before and after occlusion. Ventricular arrhythmias were observed in 57% (20 of 35) of animals. Treatment was given immediately after coronary occlusion and for 2 subsequent days. The control group received 100 mg/kg lactose (i.e., 80% vehicle for isosorbide-5-mononitrate). Lisinopril (100 mg/kg body weight) and isosorbide-5-mononitrate (400 mg/kg body weight) reduced systolic blood pressure (SBP) from 134 ± 9 to 115 ± 9 mm Hg (p < 0.05) and from 137 ± 9 to 126 ± 9 mm Hg, respectively; the hypotensive effect lasted 2–3 days. No effect on BP was noted in the control group. Overall mortality was 23%; 8 of 35 animals died within 10–15 min of coronary occlusion. Survival after 4 weeks was similar in each group (∼80%). Left ventricular pressure (LVP) was measured 4 weeks after coronary artery occlusion and was similar in each group. However, dP/dt was lower in hearts with infarction than in hearts with none (12,608 ± 906 vs. 8,992 ± 1,242 mm Hg/s). The extent of the infarction was the same in groups with coronary artery occlusion. Lisinopril is more effective than isosorbide-5-mononitrate in reducing BP after acute myo-cardial infarction (AMI). Medium-term survival (4 weeks) is not jeopardized by effective treatment with angiotensin-converting enzyme (ACE) inhibitors or long-acting nitrates.

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