From bedside to bench and back again: translational studies of mechanical unloading of the left ventricle to promote recovery after acute myocardial infarction.
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ABSTRACT:
SUBMITTER: Kapur NK
PROVIDER: S-EPMC6259487 | biostudies-literature | 2018
REPOSITORIES: biostudies-literature
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Project description:BackgroundLeft ventricular assist device (LVAD) mechanically unloads the left ventricle (LV). Theoretical analysis indicates that partial LVAD support (p-LVAD), where LV remains ejecting, reduces LV preload while increases afterload resulting from the elevation of total cardiac output and mean aortic pressure, and consequently does not markedly decrease myocardial oxygen consumption (MVO2). In contrast, total LVAD support (t-LVAD), where LV no longer ejects, markedly decreases LV preload volume and afterload pressure, thereby strikingly reduces MVO2. Since an imbalance in oxygen supply and demand is the fundamental pathophysiology of myocardial infarction (MI), we hypothesized that t-LVAD minimizes MVO2 and reduces infarct size in MI. The purpose of this study was to evaluate the differential impact of the support level of LVAD on MVO2 and infarct size in a canine model of ischemia-reperfusion.MethodsIn 5 normal mongrel dogs, we examined the impact of LVAD on MVO2 at 3 support levels: Control (no LVAD support), p-LVAD and t-LVAD. In another 16 dogs, ischemia was induced by occluding major branches of the left anterior descending coronary artery (90 min) followed by reperfusion (300 min). We activated LVAD from the beginning of ischemia until 300 min of reperfusion, and compared the infarct size among 3 different levels of LVAD support.Resultst-LVAD markedly reduced MVO2 (% reduction againstControl-56 ± 9%, p<0.01) whereas p-LVAD did less (-21 ± 14%, p<0.05). t-LVAD markedly reduced infarct size compared to p-LVAD (infarct area/area at risk: CONTROL; 41.8 ± 6.4, p-LVAD; 29.1 ± 5.6 and t-LVAD; 5.0 ± 3.1%, p<0.01). Changes in creatine kinase-MB paralleled those in infarct size.ConclusionsTotal LVAD support that minimizes metabolic demand maximizes the benefit of LVAD in the treatment of acute myocardial infarction.
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Project description:Aimto compare a conventional primary reperfusion strategy with a primary unloading approach before reperfusion in preclinical studies.Methodswe performed a meta-analysis of preclinical studies. The primary endpoint was infarct size (IS). Secondary endpoints were left ventricle end-diastolic pressure (LVEDP), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO). We calculated mean differences (MDs) and associated 95% confidence intervals (CIs). Sensitivity and subgroup analyses on the primary and secondary endpoints, as well as a meta-regression on the primary endpoint using the year of publication as a covariate, were also conducted.Results11 studies (n = 142) were selected and entered in the meta-analysis. Primary unloading reduced IS (MD -28.82, 95% CI -35.78 to -21.86, I2 96%, p < 0.01) and LVEDP (MD -3.88, 95% CI -5.33 to -2.44, I2 56%, p = 0.02) and increased MAP (MD 7.26, 95% CI 1.40 to 13.12, I2 43%, p < 0.01) and HR (MD 5.26, 95% CI 1.97 to 8.55, I2 1%, p < 0.01), while being neutral on CO (MD -0.11, 95% CI -0.95 to 0.72, I2 88%, p = 0.79). Sensitivity and subgroup analyses showed, overall, consistent results. The meta-regression on the primary endpoint demonstrated a significant influence of the year of publication on effect estimate.Conclusionsin animal models of myocardial infarction, a primary unloading significantly reduces IS and exerts beneficial hemodynamic effects compared to a primary reperfusion.
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