BACKGROUND: Late reperfusion during acute myocardial infarction results in delayed recovery of ventricular function and less remodeling, whereas ventricular unloading with nitrates improves function and attenuates remodeling. Whether late reperfusion combined with prolonged unloading with isosorbide-5-mononitrate (ISMN) might produce greater functional recovery and less remodeling than late reperfusion alone is not known. METHODS AND RESULTS: In vivo left ventricular function and topography (echocardiograms), postmortem topography (planimetry), and collagen (hydroxyproline) were measured in dogs that were randomized to reperfusion 2 hours after left anterior descending coronary artery ligation, and ISMN (n = 12) or placebo (n = 12) was given as 25 mg IV over 4 hours followed by 50 mg PO QID for 6 weeks. Compared with placebo, the ISMN group had similar heart rate but lower left atrial pressure, mean arterial pressure, and rate-pressure products. Although in vivo baseline remodeling and functional parameters were similar in the two groups, by 6 weeks the ISMN group had smaller (P < or = .05) infarct and noninfarct segment lengths, ventricular volumes, and mass; less (P < .001) asynergy; and greater (P < .001) ejection fraction. More important, by 2 days, ejection fraction was 18% greater (P < .025) and asynergy 26% less (P < .05) with ISMN. At 6 weeks, ISMN showed less (P < or = .05) scar size, scar collagen, cavity dilation, noninfarct wall thickness, and apical bulging than placebo. In another 4 dogs, acute ISMN produced less improvement in function and remodeling than prolonged ISMN. CONCLUSIONS: Late reperfusion of acute anterior myocardial infarction combined with prolonged ISMN unloading results in greater and earlier recovery of ventricular function and less remodeling than late reperfusion alone.
BACKGROUND: Late reperfusion during acute myocardial infarction results in delayed recovery of ventricular function and less remodeling, whereas ventricular unloading with nitrates improves function and attenuates remodeling. Whether late reperfusion combined with prolonged unloading with isosorbide-5-mononitrate (ISMN) might produce greater functional recovery and less remodeling than late reperfusion alone is not known. METHODS AND RESULTS: In vivo left ventricular function and topography (echocardiograms), postmortem topography (planimetry), and collagen (hydroxyproline) were measured in dogs that were randomized to reperfusion 2 hours after left anterior descending coronary artery ligation, and ISMN (n = 12) or placebo (n = 12) was given as 25 mg IV over 4 hours followed by 50 mg PO QID for 6 weeks. Compared with placebo, the ISMN group had similar heart rate but lower left atrial pressure, mean arterial pressure, and rate-pressure products. Although in vivo baseline remodeling and functional parameters were similar in the two groups, by 6 weeks the ISMN group had smaller (P < or = .05) infarct and noninfarct segment lengths, ventricular volumes, and mass; less (P < .001) asynergy; and greater (P < .001) ejection fraction. More important, by 2 days, ejection fraction was 18% greater (P < .025) and asynergy 26% less (P < .05) with ISMN. At 6 weeks, ISMN showed less (P < or = .05) scar size, scar collagen, cavity dilation, noninfarct wall thickness, and apical bulging than placebo. In another 4 dogs, acute ISMN produced less improvement in function and remodeling than prolonged ISMN. CONCLUSIONS: Late reperfusion of acute anterior myocardial infarction combined with prolonged ISMN unloading results in greater and earlier recovery of ventricular function and less remodeling than late reperfusion alone.