Chronic right ventricular pressure overload results in a hyperplastic rather than a hypertrophic myocardial response

Abstract

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.

Functional and haemodynamic assessment of mild-to-moderate pulmonary valve stenosis at rest and during exercise

“…The onset, haemodynamic profile and compensatory mechanisms in pulmonary hypertension are very different compared with patients with PV stenosis. In the studied patients, the pressure load is already present to some extent at birth, it is a purely systolic pressure load and neurohormonal or gene and protein synthesis alterations are thought to play a role in the better preservation of right ventricular morphology 19 20 21. To what extent each contributes to this favourable remodelling of the RV has still to be investigated.…”

Turning crocodilian hearts into bird hearts: growth rates are similar for alligators with and without right-to-left cardiac shunt

“…Occlusion of the LAo likely causes pathological, pressure overload hypertrophy of the right ventricle (Eme et al, 2009a) [see Faber et al (Faber et al, 2006) and Leeuwenburgh et al (Leeuwenburgh, 2008) for mammalian examples], whereas chronic exercise can increase alligator heart mass (Eme et al, 2009b), possibly leading to a greater stroke volume (e.g. Rowell, 1974;Scheuer and Tipton, 1977).…”

Surgical removal of right-to-left cardiac shunt in the American alligator(Alligator mississippiensis) causes ventricular enlargement but does not alter apnoea or metabolism during diving

“…Pulmonary artery banding increases outflow resistance and is a treatment for correction of specific congenital heart defects in humans (Muller and Damman, 1952;Oppido et al, 2004;Locker et al, 2008). Numerous studies have demonstrated that PA banding results in pressure overload hypertrophy of the RV (Faber et al, 2006;Leeuwenburgh et al, 2008). Distinct histological changes are associated with ventricular hypertrophy resulting from different causal mechanisms.…”

“…For example, in rats ventricular cellular hypertrophy is associated with a decrease in DNA concentration (Vliegen et al, 1990). By contrast, concomitant increases in both DNA content and ventricular size are indicative of hyperplastic cellular and subcellular 'growth' (Grimm et al, 1970;Linzbach, 1976;Herget et al, 1997;Leeuwenburgh et al, 2008). Hyperplastic growth of the myocardium occurs during normal embryonic and fetal vertebrate development and continues for a short, but indefinite period after hatching or parturition (Li et al, J. Eme and others Mean number of apnoeas Sham Table 2.…”