Left ventricular unloading before reperfusion reduces endothelin-1 release and calcium overload in porcine myocardial infarction
ABSTRACT The aim of this study was to test the hypothesis that after an acute myocardial infarction, endothelin-1 release with subsequent calcium overload is a mediator of myocardial reperfusion injury, which can be inhibited, in part, by left ventricular unloading immediately before reperfusion. We recently have reported that left ventricular unloading before reperfusion reduces infarct size after acute myocardial infarction. However, the biologic mechanisms of infarct salvage in unloaded hearts subjected to ischemia/reperfusion remain undefined.
Twelve pigs were subjected to 1 hour of left anterior descending coronary artery occlusion followed by 4 hours of reperfusion. A left ventricular assist device was initiated 15 minutes before reperfusion and maintained during reperfusion (assist device group, n = 6). A control group (n = 6) was subjected to reperfusion alone. Infarct size, endothelin-1 plasma levels, intracellular calcium levels, and apoptosis were analyzed in both groups.
At reperfusion, left ventricular unloading significantly decreased left ventricular end-diastolic and end-systolic pressures. Infarct size, expressed as a percentage of zone at risk, was also significantly reduced by 54% in the group with the left ventricular assist device compared with controls. Support with a left ventricular assist device reduced endothelin-1 release from the heart at 15 minutes, 30 minutes, and 1 hour of reperfusion. Myocardial release of endothelin-1 was significantly correlated with infarct size at 15 minutes of reperfusion (r = 0.79; P = .008). Left ventricular unloading caused a significant reduction of calcium overload and of the percentage of apoptotic cells in the ischemic region.
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.
- The Journal of thoracic and cardiovascular surgery 08/2009; 138(1):262. DOI:10.1016/j.jtcvs.2008.09.084 · 3.99 Impact Factor
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ABSTRACT: No-reflow after primary percutaneous coronary intervention (PCI) in ST-elevation myocardial infarction (STEMI) is associated with poor prognosis. Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor that might aggravate reperfusion injury. The aim of our study was to assess the relationship between systemic ET-1 levels and the occurrence of no-reflow as well as to evaluate the prognostic value of ET-1 in a high-risk STEMI population. We examined 128 consecutive patients undergoing primary PCI in acute STEMI <12 hours after symptom onset. Endothelin-1 was assessed before and immediately after primary PCI. Patients were categorized into 2 groups defined by the median ET-1 level on admission. No-reflow was assessed by 3 different methods after PCI: angiographic Thrombolysis in Myocardial Infarction (TIMI) flow and myocardial blush grade, electrocardiographic ST-resolution, and microvascular obstruction (MO) measured by cardiac magnetic resonance imaging (MRI). The primary clinical end points were mortality and major adverse cardiovascular events. Clinical follow-up was conducted after a median of 19 months. Patients with angiographically (TIMI flow < or =2 or TIMI flow 3 with final myocardial bush grade < or =2 after PCI), electrocardiographically (ST-resolution <30%), and MRI- (presence of MO) detected no-reflow had significantly higher ET-1 levels on admission. At multivariable logistic regression analysis, ET-1 levels on admission were the only significant predictor of MRI-detected no-reflow (P = .03) together with left ventricular ejection fraction (P = .002). An elevated ET-1 level > or = the median on admission was a significant predictor of long-term mortality. Endothelin-1 on admission is associated with no-reflow and increased long-term mortality in a high-risk STEMI population reperfused by primary PCI.American heart journal 05/2010; 159(5):882-90. DOI:10.1016/j.ahj.2010.02.019 · 4.56 Impact Factor
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ABSTRACT: Myocardial tissue engineering ambitions to regenerate, repair or replace damaged cardiac muscle by combining cellular and engineering technologies. Several issues must be addressed before this approach may one day find clinical applications for cardiac disorders such as congenital diseases or ventricular dysfunction following myocardial infarction for example. The chance of the myocardial tissue engineering approach is nevertheless real. Indeed, on the one hand, several clinical studies have recently confirmed the positive effect of stem cell therapy in patients with heart failure. On the other hand, research from several laboratories have demonstrated over the past decade that engineered muscle tissues can be created and successfully applied in models of myocardial injury. Engineering a functional myocardial graft faces with many challenges, and various approaches have been investigated. In the current chapter, we focus our review on hydrogel-based engineered tissues for myocardial application. The literature on injectable and implantable hydrogel constructs is discussed and an overview of our own experience is presented. We emphasize important aspects on development of hydrogel constructs in particular the mechanical and electrical conditioning of the construct as well as smart hydrogels.12/2010: pages 165-185;