Endomyocardial nitric oxide synthase and the hemodynamic phenotypes of human dilated cardiomyopathy and of athlete's heart

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Abstract
Objective: In dilated cardiomyopathy and in athlete's heart, progressive LV dilatation is accompanied by rightward displacement of the diastolic LV pressure–volume relation. In dilated cardiomyopathy, an increase in diastolic LV stiffness can limit this rightward displacement thereby decreasing LV systolic performance. Because nitric oxide (NO) reduces diastolic LV stiffness, the present study relates diastolic LV stiffness and LV systolic performance to intensity of endomyocardial NO synthase (NOS) gene expression in dilated cardiomyopathy and in athlete's heart. Methods: Microtip LV pressures, conductance-catheter or angiographic LV volumes, echocardiographic LV wall thicknesses and snap-frozen LV endomyocardial biopsies were obtained in 33 patients with dilated cardiomyopathy and in three professional cyclists referred for sustained ventricular tachycardia. Intensity of LV endomyocardial inducible NOS (NOS2) and constitutive NOS (NOS3) gene expression was determined using quantitative reverse transcription–polymerase chain reaction (RT–PCR). Results: Dilated cardiomyopathy patients with higher diastolic LV stiffness-modulus and lower LV stroke work had lower NOS2 and NOS3 gene expression at any given level of LV end-diastolic wall stress. The intensity of NOS2 and NOS3 gene expression observed in athlete's heart was similar to dilated cardiomyopathy with low LV diastolic stiffness-modulus and preserved LV stroke work. Conclusions: High LV endomyocardial NOS gene expression is observed in athlete's heart and in dilated cardiomyopathy with low diastolic LV stiffness and preserved LV stroke work. Favourable effects on the hemodynamic phenotype of high LV endomyocardial NOS gene expression could result from a NO-mediated decrease in diastolic LV stiffness and a concomitant rise in LV preload reserve.

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