A prospective study of plasma nitrates following human heart transplantation - Relevance to myocardial function

Background: Nitric oxide (NO) has been shown to affect myocardial function in positive and negative inotropic ways. Expression of inducible nitric oxide synthase and release of nitric oxide into the circulation has been associated with acute rejection in animal studies. The role of NO and the associated myocardial dysfunction seen during acute rejection in humans has not been adequately defined. In a prospective sequential study, we have studied the relationship between plasma nitrate and biopsy-proven acute rejection, and systolic and diastolic function after heart transplantation. Methods: Biopsies were performed weekly and then fortnightly up to 12 weeks after transplantation and on clinical indication of rejection in 37 patients. Plasma nitrates were obtained on the morning of each biopsy (total 341). An echocardiogram was performed immediately prior to each biopsy in which the systolic parameters, ejection fraction (EF) and fractional shortening (fs), and the diastolic parameters, isovolumetric relaxation time (IVRT), mitral valve pressure half-time (MVPHT), mitral valve deceleration time (MVDT), e:a ratio, and a wave duration, were measured. Results: Plasma-nitrate level showed no significant correlation with the systolic parameters, EF or fs, or with changes in EF or fs. No significant correlation was found between plasma-nitrate level and the diastolic parameters IVRT, MVPHT, MVDT, mitral valve a wave duration, or e:a ratio. Conclusions: This study has shown no correlation between plasma nitrate and impaired systolic or diastolic function after heart transplantation. Instead there was a weak trend for elevated nitrate to be associated with better systolic function.