Primary allograft aortic valve replacement can give acceptable results for up to 25 years. The late results can be improved by the use of a viable allograft, by matching patient and donor age, and by more liberal use of free root replacement with re-implantation of the coronary arteries rather than tailoring the root to accommodate a subcoronary implantation.

Endogenous ET-1 has a tonic positive inotropic effect in normal subjects, independent of effects on the peripheral vasculature and unmasked by inhibition of ET(A) receptors. However, the effect of short-term ET(A) blockade in DCM patients was opposite to that in normal subjects, which suggests that ET-1 may cause negative inotropic effects in the failing heart.

Nitric oxide (NO) modulates myocardial contractile behavior in several isolated preparations, e.g., cardiac myocytes and papillary muscles, via elevation of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). We have recently reported that the exogenous NO donor, sodium nitroprusside, selectively modulates left ventricular (LV) relaxation in the isolated ejecting guinea pig heart, independent of coronary flow. We now report the effects of endogenously released NO on LV performance in this preparation (constant heart rate and loading). Both bradykinin (1 nM, n = 6) and substance P (100 nM, n = 6) accelerated early LV relaxation (maximum change in time constant, tE, -10.5 +/- 1.6 and -13.4 +/- 2.1%, respectively; both P < 0.05), without significantly altering early systolic parameters (e.g., rate of LV pressure development). These effects were inhibited by hemoglobin (P < 0.05; n > or = 6), which inactivates NO. Bradykinin (100 nM, n = 10) had an additional negative inotropic effect, which was not inhibited by hemoglobin. Neither agonist altered relaxation in isolated papillary muscles. These data suggest that endogenous NO, probably released from coronary microvascular endothelial cells, modulates LV relaxation in the intact heart.

Background-Nitric oxide (NO) exerts autocrine/paracrine effects on cardiac function, including alterations of the inotropic state. In vitro studies suggest that NO modulates the myocardial force-frequency relationship. Basal left ventricular (LV) contractility is depressed and the force-frequency relationship is blunted in human heart failure, and it is speculated that an increase in NO production is involved. Methods and Results-We compared the effects of intracoronary NO synthase inhibition with N G -monomethyl-L-arginine (L-NMMA; 25 mol/min) on basal LV function and the response to incremental atrial pacing in patients with dilated cardiomyopathy (nϭ11; mean age, 51 years) and in control subjects with atypical chest pain and normal cardiac function (nϭ7; mean age, 54 years). In controls, L-NMMA significantly reduced basal LV dP/dt max (from 1826 to 1578 mm Hg/s; PϽ0.002), but had no effect on heart rate, mean aortic pressure, or right atrial pressure. Pacing-induced increases in LV dP/dt max were unaltered by L-NMMA. In patients with dilated cardiomyopathy, L-NMMA had no effect on baseline LV dP/dt max (from 1313 to 1337 mm Hg/s; PϭNS). The blunted pacing-induced rise in LV dP/dt max in these patients was unaltered by L-NMMA. Conclusion-Endogenous NO has a small baseline positive inotropic effect in the normal human heart, which is lost in heart failure patients. NO does not significantly influence the force-frequency relationship in either the normal or failing human heart in vivo. Because this study was performed in patients with moderate heart failure, whether the findings apply to subjects with more severe heart failure requires further investigation.