Inducible Nitric Oxide Synthase Gene Expression and Diastolic Function in Heart Transplant Recipients

Purpose A pulmonary wedge pressure >18 mmHg following volume load has been proposed as a partition value for the detection of HFpEF. In both experimental and clinical settings, the hemodynamic changes in filling pressures have been attributed to a nitric oxide(NO)-mediated rightward shift of the pressure-volume relationship. The present study investigates the hemodynamic response to a volume challenge upon diastolic function in heart transplant(HTx) recipients and examines the role of inducible nitric oxide synthase(iNOS) gene expression on diastolic function changes. Methods 36 HTx recipients with normal left ventricular function (ejection fraction[EF]: 61 ± 12%) and without rejection and graft vasculopathy underwent right heart catheterization for the measurement of the degree of hemodynamic response to volume loading after saline infusion of 7 mL/kg over 10 min. Pulmonary capillary wedge pressure(PCWP), right atrial pressure(RAP), and mean pulmonary artery pressure(PA) were measured, following which the PCWP and stroke volume index(SVI) were used for Starling(SVI/PCWP) curve construction. Pts were categorized into the normal (group A, n=20) and abnormal hemodynamics (group B, n=16, PCWP >15 mmHg at rest or >18 mmHg following volume load) groups. For the establishment of the potential role of NO as a mediator of hemodynamic response, the iNOS endomyocardial gene expression level was measured . Results No differences were observed in terms of donor and recipient age, baseline hemodynamic parameters, and EF between both groups. Volume load significantly increased PCWP and PA in both groups, without any significant change in blood pressure or heart rate. Saline infusion was associated with a significant increase in SVI in group A but not group B. Moreover, in group A, the Starling curves revealed a higher SVI at any given PCWP. Group A exhibited significantly higher iNOS gene expression levels than Group B. Conclusion In HTx, rapid saline infusion increases the filling pressure and unmasks the presence of left ventricular diastolic dysfunction. Interestingly, pts with an abnormal hemodynamic response show a blunted Frank-Starling response, as evidenced by the higher PCWP and lack of SVi increase at any given PCWP. The higher iNOS gene expression level in our control group suggests the potential role of NO as a mediator of diastolic function in heart Tx patients.