The Journal of surgical research
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In many clinical scenarios, a relatively untrained right ventricle may be subjected to acute elevations in pulmonary artery and right ventricular pressures. The right and left heart are distinctly different in this regard and there is currently no in vivo model to study right ventricular ischemia in the setting of acute pressure overload. In acute injury, cardiomyocytes produce tumor necrosis factor, which mediates a proinflammatory pathway, eventually leading to myocardial dysfunction. Stem cells have been shown to reduce the production of proinflammatory mediators by the ischemic myocardium and protect the myocardium. Pretreatment with stem cells has been shown to protect the left ventricle. The effect of acute pressure overload to the untrained right ventricle is still not well understood. Furthermore, it is unclear whether pretreatment with stem cells would protect the right ventricle when it is subjected to acute pressure overload and concomitant ischemia reperfusion injury. The purpose of this study was (1) to create a simple model of acute pressure overload for the study of concomitant right ventricular ischemia and reperfusion, and (2) to evaluate the effect of pretreatment with stem cells prior to ischemia reperfusion injury. ⋯ This compounded injury model allowed the study of right ventricular dysfunction in the setting of acute pressure overload and ischemia. Additionally, we have also demonstrated that pretreatment with stem cells of an acutely pressure overloaded right ventricle prior to ischemia reperfusion injury improves functional recovery. This is the first report of a modified Langendorff technique to study right ventricular function in the setting of acute pressure overload and ischemia and the effect of pretreatment with stem cells.
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Neutrophil infiltration is a major determinant of ischemia-reperfusion injury (IRI). Statins improve endothelial function by elevating nitric oxide synthase activity and inhibiting adhesion molecule expression and may, therefore, inhibit IRI-induced neutrophil extravasation. Although statins are protective against myocardial IRI and stroke, a role for statins in ameliorating skeletal muscle IRI has not yet been confirmed. This study, therefore, addressed the hypothesis that simvastatin would attenuate the severity of tissue damage during skeletal muscle IRI. ⋯ The inhibition by simvastatin of IRI-induced neutrophil infiltration in skeletal muscle suggests that statins may be a useful therapy to attenuate the severity of IRI but their precise mechanisms of action remains to be determined. Nitric oxide also plays a cytotoxic, rather than protective, role in mediating IRI in this model.