. Indexes of diastolic RV function: load dependence and changes after chronic RV pressure overload in lambs. Am J Physiol Heart Circ Physiol 282: H1350-H1358, 2002. First published December 13, 2001; 10.1152/ajpheart.00782.2001.-Diastolic function is a major determinant of ventricular performance, especially when loading conditions are altered. We evaluated biventricular diastolic function in lambs and studied possible load dependence of diastolic parameters [minimum first derivative of pressure vs. time (dP/dt min) and time constant of isovolumic relaxation ()] in normal (n ϭ 5) and chronic right ventricular (RV) pressure-overloaded (n ϭ 5) hearts by using an adjustable band on the pulmonary artery (PAB). Pressure-volume relations were measured during preload reduction to obtain the end-diastolic pressure-volume relationship (EDPVR). In normal lambs, absolute dP/dt min and were lower in the RV than in the left ventricle whereas the chamber stiffness constant (b) was roughly the same. After PAB, RV and dP/dt min were significantly higher compared with control. The RV EDPVR indicated impaired diastolic function. During acute pressure reduction, both dP/dt min and showed a relationship with end-systolic pressure. These relationships could explain the increased dP/dt min but not the increased -value after banding. Therefore, the increased after banding reflects intrinsic myocardial changes. We conclude that after chronic RV pressure overload, RV early relaxation is prolonged and diastolic stiffness is increased, both indicative of impaired diastolic function.hemodynamics; hypertrophy; pressure-volume relation; ventricular function, diastole THE IMPORTANCE of diastolic function as a major determinant of ventricular performance has long been recognized. Impaired diastolic function may precede systolic ventricular dysfunction (13,14), and it influences the performance of the contralateral ventricle via ventricular interdependence (23,34,39). The gold standard for determination of right ventricular (RV) [and left ventricular (LV)] diastolic function is still considered to be cardiac catheterization with simultaneous high-fidelity pressure and volume measurements (32).Because RV cineangiography is only sporadically performed during routine diagnostic catheterization and because complex RV geometry hampers adequate RV volume determination, few data are available about RV diastolic function. With the combined pressureconductance catheter it has recently become possible to determine ventricular pressure and volume simultaneously and independently of ventricular geometry in the LV as well as in the RV (3,11).Using this method, we are able to determine parameters of diastolic function such as the end-diastolic pressure-volume relationship (EDPVR) and chamber stiffness constant (b) that are well accepted for LV diastolic analysis. Furthermore, some of the LV relaxation parameters have shown a relationship with load (systolic pressure) that may render them less reliable to characterize intrinsic diastolic properties (26, 33)...

In various clinical situations of congenital heart disease, the right ventricle (RV) is subject to a chronic systemic pressure overload which affects biventricular function and may progress to the development of RV failure. Young lambs (2-3 wk old) underwent adjustable pulmonary artery banding (PAB) at systemic (aortic) level for 8 wk. Biventricular function was determined by using load-independent indexes of global ventricular contractile performance by the end-systolic pressure-volume relationship (ESPVR) using the conductance catheter at baseline and during dobutamine infusion. PAB resulted in a significant fivefold increase in RV end-systolic pressure (12-64 mmHg) and a doubling of the RV-to-left ventricular (LV) wall thickness ratio (P < 0.01). RV global contractile performance increased significantly, as indicated by an increased slope of the ESPVR. Compared with age-matched control lambs, cardiac output decreased from 2.6 to 1.6 l/min (P < 0.05) whereas heart rates were equal. In contrast with RV volume, LV volume decreased significantly after PAB (P < 0.01), whereas the LV-ESPVR slope was unchanged. In the PAB group, the RV, but not the LV, showed a reduced response to dobutamine. We concluded that chronic RV pressure overload for 8 wk results in diminished pump function despite compensatory increased RV global contractile performance.

Myocardial hyperplasia is generally considered to occur only during fetal development. However, recent evidence suggests that this type of response may also be triggered by cardiac overload after birth. In congenital heart disease, loading conditions are frequently abnormal, thereby affecting ventricular function. We hypothesized that chronic right ventricular pressure overload imposed on neonatal hearts initiates a hyperplastic response in the right ventricular myocardium. To test this, young lambs (aged 2-3 weeks) underwent adjustable pulmonary artery banding to obtain peak right ventricular pressures equal to left ventricular pressures for 8 weeks. Transmural cardiac tissue samples from the right and left ventricles of five banded and five age-matched control animals were studied. We found that chronic right ventricular pressure overload resulted in a twofold increase in right-to-left ventricle wall thickness ratio. Morphometric right ventricular myocardial tissue analysis revealed no changes in tissue composition between the two groups; nor were right ventricular myocyte dimensions, relative number of binucleated myocytes, or myocardial DNA concentration significantly different from control values. In chronic pressure overloaded right ventricular myocardium, significantly ( P < 0.01) more myocyte nuclei were positive for the proliferation marker proliferating cellular nuclear antigen than in control right ventricular myocardium. Chronic right ventricular pressure overload applied in neonatal sheep hearts results in a significant increase in right ventricular free wall thickness which is primarily the result of a hyperplastic myocardial response.

LAD embolisation not only results in a significantly diminished LV systolic function but also causes RV systolic function to decline significantly. Regional dysfunction by necessity entails global dysfunction as well. Analysis of ventricular geometry reveals that both the septum and the RV free wall increase their length, which plays an important role in the pathophysiology of diminished RV systolic function concomitant with reduced LV function.