Infarct size reduction and attenuation of global left ventricular remodeling with the CorCap cardiac support device following acute myocardial infarction in sheep.

backgroundWhether mechanical restraint of the left ventricle (LV) can influence remodeling following myocardial infarction (MI) remains poorly understood. The following discussion details three studies examining the effects of surgically placing a cardiac support device (CSD) over the entire epicardial surface, on infarct expansion, global cardiac function and myocyte geometry and function post-MI.

methodsThe effects of passive constraint on infarct expansion and global cardiac function/myocardial energetics were investigated in 10 sheep (5 MI only; 5 MI + CSD) using pressure-volume analysis and magnetic resonance imaging (MRI). Additionally, 11 sheep (5 MI only; 6 MI + CSD) were used to study the effects of passive restraint on myocyte geometry and function post-MI, with 10 additional uninstrumented sheep serving as controls. Baseline data was collected followed by the creation of an anterior infarct. 1 week post-infarct the animals underwent a second set of data collection studies followed by placement of the CSD in the experimental groups. Additional data was collected at 2 and 3 months post-MI. The animals in the myocyte function group underwent additional studies immediately following the 3 month time point.

resultsInfarct expansion was diminished as a result of the CSD. At 1 week post-MI the akinetic area was similar in both groups. At the terminal time-point, the akinetic area in the control group was similar to the 1-week time-point whereas, in the CSD group, the area of akinesis decreased (P = 0.001). A comparison of the two groups at the terminal time-point demonstrates a significantly diminished area of akinesis in the CSD group (P = 0.004). The relative area of akinesis followed a similar pattern. The CSD group also exhibited a decrease in end-diastolic volume (control 110.3 +/- 19.8 mL vs. CSD 67.6 +/- 4.7 mL, P = .006) and an improved ejection fraction (control 15.5% +/- 5.7% vs. CSD 29.46% +/- 4.42%, P = .008) relative to the control group. Myocardial energetics were also enhanced in the CSD group as evidenced by significant improvements in potential energy (control 2,015 +/- 503 mL x mm Hg/beat vs. CSD 885 +/- 220 mL x Hg/beat, P = .006), efficiency (control 39.4% +/- 13.6% vs. CSD 59.8% +/- 8.5%, P = .044), and oxygen consumption (control 0.072 +/- 0.013 mL O(2)/beat vs. CSD 0.052 +/- 0.007 mL O(2)/beat, P = .034). Isolated LV myocyte shortening velocity was reduced by 35% from control values (P < 0.05) in both MI groups. LV myocyte beta-adrenergic response was reduced with MI, but normalized in the MI + CSD group. Relative collagen content was increased and matrix metalloproteinase-9 was decreased within the MI border region of the CSD group.

conclusionsThe CorCap cardiac support device retarded infarct expansion, improved global and regional cardiac function and beneficially modified LV and myocyte remodeling post-MI. These findings provide evidence that non-pharmacological strategies can interrupt adverse LV remodeling post-MI.