Total unloading of the Left Ventricle by circulatory Assist Device (LVAD) strikingly reduces the infract size in ischemia-reperfusion injury

Abstract

Purpose: The pressure-volume area (PVA) of the left ventricle (LV) is tightly coupled with myocardial oxygen consumption/demand (MVO2). Theoretical analysis indicates that, the partial LVAD support (PARTIAL) where LV remains ejecting, reduces LV preload while increases afterload, and thus does not decrease much the PVA or MVO2. In contrast, the total LVAD support (TOTAL) where LV no longer ejects, markedly decreases LV volume, thereby MVO2. We hypothesized PARTIAL and TOTAL unloading would have major differences in the infract size in ischemia-reperfusion injury. Methods: We created ischemia by occluding major branches of the left anterior descending coronary artery for 90 min, reperfused for the following 300 min and assessed the infract size (normalized by the risk area). We allocated 12 anesthetized dogs into 3 groups, no support (CONT), PARTIAL (LV output=LVAD flow) and TOTAL (no LV output). Results: Mean arterial pressure (MAP) did not differ among 3 groups (CONT: 97±11, PARTIAL: 96±2.6 and TOTAL: 101±7.1 mmHg). In TOTAL, LV peak-systolic pressure (42±11 mmHg) was much lower than that of MAP confirming no LV ejection. LVAD significantly reduced the infarct size (CONT: 40±3.2, PARTIAL: 27.6±5.8, and TOTAL: 5.0±1.6%, p<0.0005). However, the reduction was by far lager in TOTAL than in PARTIAL (p<0.05). The reduction in infarct size relative to CONT is 31% for PARTIAL and 88% for TOTAL (Fig. 1). Changes in the serum level of creatine kinase MB (300 min after reperfusion) resembled that in the infarct size (p=0.0375) (Fig. 2). ![Figure][1] Conclusions: The fact that the infarct size is strikingly reduced by TOTAL whereas moderately reduced by PARTIAL indicates that total unloading and minimization of metabolic demand are essential in order to maximize the beneficial impact of LVAD on the infarct size. [1]: pending:yes