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Effects of pre-, peri-, and postmyocardial infarction treatment with omapatrilat in rats: survival, arrhythmias, ventricular function, and remodeling

¹Division of Cardiology, University Health Network, Toronto General Hospital, Toronto, Ontario M5G 2C4; ²Department of Cardiology, Jewish General Hospital, Montreal, Quebec H3T 1E2; ⁴Department of Medicine, Montréal Heart Institut, Montreal, Quebec H1T 1C8; and ³Division of Cardiology, Saint Michael's Hospital, Toronto, Ontario, Canada M5B 1W8

Submitted 30 December 2002 ; accepted in final form 19 March 2003

We showed previously that the vasopeptidase inhibitor (VPI) omapatrilat improves peri-myocardial infarction (MI) survival, but the mechanisms involved and whether these effects are sustained remained to be determined, and are the subject of this study. Rats (n = 272) received omapatrilat (20 mg · kg^-1 · day^-1) starting 7 days before MI and continued peri- and post-MI, or no treatment (control). One group of rats had continuous ambulatory ECG and blood pressure recordings started 6 h before MI and continued until 24 h after MI, when survival was evaluated, and the rats were killed, and MI size was evaluated. A second group had left ventricular (LV) remodeling evaluated by echocardiography at 30 days and, at 38 days, had cardiac hemodynamics and morphology done and survival evaluated. Survival 24 h after MI (n = 255) improved with omapatrilat (60% vs. 46% for control; P = 0.0378). Over the next 37 days, there was no further improvement with omapatrilat but the early benefit was sustained. Omapatrilat reduced MI size 24 h after MI (36 ± 2 vs. 42 ± 2 mm² for controls; P = 0.034). Omapatrilat reduced ventricular arrhythmia score 1–12 h after MI. Omapatrilat decreased blood pressure, but not during the first 24 h after MI. Omapatrilat reduced LV diastolic and systolic dimensions and LV and right ventricular weights compared with control large MI, indicating a decrease in reactive hypertrophy. Improvement in cardiac remodeling was accompanied by improved cardiac hemodynamics. Thus this study indicates that pre-, peri-, and post-MI treatment with the VPI omapatrilat is beneficial in survival, ventricular arrhythmias, LV remodeling, and cardiac function.

vasopeptidase inhibitor

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