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Objective: Myocardial injury after ischemia and reperfusion may be mediated, in part, by oxygen-derived free radicals. In this study the protective effects of extracellular superoxide dismutase overexpression were directly assessed in the hearts of transgenic mice, after ischemia and reperfusion injury, using an isolated work-performing murine heart preparation and computerized analysis of functional data., Methods: A blinded study was performed to compare cardiac function in the hearts of both transgenic mice with a 3.5-fold overexpression of myocardial extracellular superoxide dismutase (n = 6, 22 to 26 gm) and littermate controls (n = 8, 22 to 26 gm). Preload-dependent cardiac output, contractility, heart rate, stroke work, and stroke volume were evaluated in the two groups before and after a 6-minute period of normothermic ischemia., Results: No differences were found between extracellular superoxide dismutase hearts and control hearts in any parameter of myocardial function before ischemia. After ischemia, decreases in cardiac output occurred in both groups; however, this decrease was larger in control mice compared with extracellular superoxide dismutase mice. A higher percentage of recovery was also observed in the contractility, heart rate, stroke work, and stroke volume of extracellular superoxide dismutase hearts compared with control hearts., Conclusion: After global normothermic ischemia and subsequent reperfusion, decreases in cardiac function occurred in both extracellular superoxide dismutase and control mice; however, a higher percentage of recovery was observed in the extracellular superoxide dismutase overexpressed hearts. These data suggest that extracellular superoxide dismutase transgene overexpression significantly improves preservation of myocardial function after ischemia and reperfusion injury.

Objective: Chronic pulmonary hypertension is difficult to treat and despite the introduction of several therapeutic options, no single therapy is universally recommended. Nitric oxide has had some role clinically in improving pulmonary hemodynamics in this setting; however, basic investigation has not been performed in an appropriate large animal model of stable pulmonary hypertension. This study was designed to examine the effects of inhaled nitric oxide on pulmonary hemodynamics in the setting of a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension and used Fourier analysis for assessment of pulmonary vascular impedance., Methods: Sixteen mongrel dogs (22 to 25 kg) were used. Animals underwent percutaneous pulmonary artery catheterization to measure-right-sided hemodynamics before and 6 weeks after a right atrial injection of either monocrotaline pyrrole (n = 8) or placebo (n = 8). Six weeks after the injection all hearts were instrumented with an ultrasonic flow probe, sonomicrometric dimension transducers, and micromanometers. Data were collected at baseline and after nitric oxide administration. Harmonic derivation of functional data was achieved with Fourier analysis., Results: Six weeks after the injection, significant increases in pulmonary artery pressure and pulmonary vascular resistance were observed in the monocrotaline pyrrole group. Nitric oxide led to significant decreases in pulmonary vascular impedance. Significant improvements in pulmonary blood flow, transpulmonary efficiency, and left ventricular filling were also observed., Conclusions: This investigation demonstrates the well-known clinical effects of nitric oxide in improving pulmonary hypertension, which were also associated with an increase in pulmonary blood flow, transpulmonary efficiency, and left ventricular filling in the setting of monocrotaline pyrrole-induced pulmonary hypertension.