Background. It has been suggested that left ventricular unloading at the time of reperfusion provides superior infarct salvage over reperfusion alone. The purpose of this study was to show that the Hemopump transvalvular axial-flow left ventricular assist device provides superior left ventricular unloading, ischemic zone collateral blood flow, and infarct size reduction compared with intra-aortic balloon counterpulsation and reperfusion alone.Methods and Results. Eighteen dogs were instrumented with regional myocardial function sonomicrometers in the ischemic and control zones. The left anterior descending coronary artery just distal to the first diagonal branch was instrumented with a silk snare and Doppler flow probe. Additionally, pressure catheters were placed in the left atrial appendage, left ventricular apex, and ascending aorta for hemodynamic measurements. Regional myocardial blood flow was determined by using 15 -gm radioactive microspheres. Measurements were made in the control state, immediately after coronary occlusion, at 1 and 2 hours after coronary occlusion, with reperfusion, and 1 hour after reperfusion. In treated animals, left ventricular assistance was maintained during the entire period of occlusion and reperfusion. The Hemopump was associated with a significant decrease in left ventricular systolic and diastolic pressure, whereas mean arterial pressure was maintained. Intra-aortic balloon counterpulsation resulted in no significant changes in left ventricular systolic pressure and a modest decrease in left ventricular diastolic pressure. Regional unloading as assessed by sonomicrometers was significant in the Hemopump animals and absent in the balloon pump animals. Absolute regional myocardial blood flow in the ischemic zone increased slightly (p=0.002) in the Hemopump animals and did not change in the balloon pump animals. Infarct size expressed as percentage of the zone at risk was 62.6% in the control animals, 27.22% in the balloon pump animals, and 21.7% in the Hemopump animals.Conclusions. Mechanical unloading of the ventricle during ischemia and reperfusion appears to result in significant infarct salvage compared with reperfusion alone. The Hemopump appears to provide superior left ventricular systolic and diastolic unloading compared with intra-aortic counterpulsation in

We tested the hypothesis that unloading the left ventricle just prior to reperfusion provides infarct size reduction compared with left ventricular (LV) unloading postreperfusion and reperfusion alone. Twenty-four mongrel dogs were subjected to 2 hr of left anterior descending artery occlusion and 4 hr of reperfusion. A transvalvular (TV) left ventricular assist device (LVAD) was inserted just prior to reperfusion and maintained during the rest of the experiment (LV Assist Pre group). In the LV Assist Post group, the TV LVAD was inserted and activated just after reperfusion. A control group was subjected to reperfusion alone with a sham-TV LVAD. At baseline, the hemodynamic data were similar in the three groups. Myocardial infarct size expressed as percentage of area at risk was significantly reduced in the LV Assist Pre group compared to the control group (P = 0.011) and to the LV Assist Post group (P < 0.05). At 4 hr of reperfusion, transmural myocardial blood flow in the ischemic zone was slightly higher in the animals unloaded prior to reperfusion compared to controls and significantly higher than in the LV Assist Post group (P = 0.04). Postreperfusion end-diastolic wall thickness returned to baseline level in the TV LV Assist Pre group compared to both controls and TV LV Assist Post group. In these latter two groups, a significant increase in postreperfusion end-diastolic wall thickness and contraction band necrosis in the central ischemic zone correlated well with the degree of reperfusion injury. LV unloading prior to, but not after, reperfusion reduces the extent of myocardial necrosis in canine hearts subjected to 2 hr of left anterior descending artery occlusion and 4 hr of reperfusion compared to either reperfusion alone or LV unloading after reperfusion.

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Our findings suggest that endothelin-1 release and calcium overload are important mediators of reperfusion injury and that they can be significantly reduced by left ventricular unloading before coronary artery reperfusion during myocardial infarction.

Purpose: In acute myocardial infarction, left ventricular (LV) unloading reduces endothelin-1 (ET-1) release. We tested that endogenous ET-1 released during acute myocardial infarction might mediate ischemia/reperfusion (I/R) injury by stimulating increased intracellular calcium concentration, [Ca²⁺]_i, and apoptosis. Methods: Rabbits were subjected to 1 h of coronary artery occlusion followed by 3 h of reperfusion. Unloading was initiated 15 min prior to reperfusion and was maintained during reperfusion. The control group was subjected to reperfusion. Animals were treated with ET-1 receptor antagonist BQ123. In parallel, isolated rabbit cardiomyocytes subjected to simulated I/R with or without ET-1 or BQ123, intracellular Ca²⁺ and cell death were assessed with flow cytometry. Results: LV unloading prior to reperfusion reduced myocardial ET-1 release at 2 h of reperfusion. Infarct size was reduced in unloaded and BQ123 groups versus controls. LV unloading and BQ123 treatment reduced the percentage of apoptotic cells associated with increases in Bcl-2 protein levels in ischemic regions. BQ123 reduced both ET-1-induced [Ca²⁺]_i increase and cell death for myocytes subjected to stimulated I/R. Conclusion: We propose that components of reperfusion injury involve ET-1 release which stimulates calcium overload and apoptosis. Intravenous ET-1 receptor blockade prior to reperfusion may be a protective adjunct to reperfusion therapy in acute myocardial infarction patients.