Mechanism of Pressure-Overload Right Ventricular Hypertrophy in Infant Rabbits

Abstract

SummaryAlthough pressure-overload right ventricular hypertrophy is a long-term risk in some congenital heart diseases such as tetralogy of Fallot, how it develops is unclear. The aim of this study was to investigate the mechanism of development of this right ventricular heart failure.Pulmonary artery banding in 10-day-old rabbits induced pressure-overload right ventricular hypertrophy as they grew. Comparisons were made with age-matched sham controls (n = 24 per group). In weekly serial echocardiography, the right ventricular contraction and diastolic function decreased from 3 weeks after surgery (P < 0.01), and the right ventricle became hypertrophic from 4 weeks after (P < 0.05). Pressure-overload increased cardiomyocyte apoptosis from 4 weeks postoperatively (TUNEL staining and Western blotting analysis, P < 0.05); and fibrosis occurred in the right ventricular cardiomyocytes at 8 weeks after operation (Masson's trichrome stain, P < 0.01).In our model, pressure-overload to the right ventricle caused the right ventricular disorder, hypertrophy, and fibrosis. Apoptosis of right ventricular cardiomyocytes was involved in progression. We have shown for the first time the mechanism whereby pressure-overload right ventricular hypertrophy develops in an infant rabbit model. (Int Heart J 2011; 52: 56-60)

Transmural dispersion of repolarization and cardiac remodeling in ventricles of rabbit with right ventricular hypertrophy

“…The decrease in both myocardial contraction and relaxation after pulmonary banding suggested that the RVH rabbits possess systolic and diastolic dysfunctions. These results are in accordance with previous study in infant rabbits in which the cardiac function impaired beginning at 3 weeks after surgery (Minegishi, Kitahori, Murakami, & Ono, 2011).…”

“…These results are consistent with previous studies in infant rabbits and adult rats which demonstrated that pulmonary artery banding induced pressure-overload, right ventricular hypertrophy, and apoptosis of the myocytes beginning at 4 weeks after banding and suggested that the apoptosis may lead to myocardial dysfunction (Braun, Szalai, Strasser, & Borst, 2003;Ikeda, Hamada, & Hiwada, 1999;Minegishi et al, 2011;Teiger et al, 1996).…”

Tauroursodeoxycholic acid inhibits apoptosis associated with ventilator-induced lung injury in rabbits

“…These possibilities will require further investigation but are plausible contributory mechanisms for our observation given the recent reports showing that: (i) the increased right ventricular afterload including that associated with excessive lung inflation can result in cardiomyocyte apoptosis 35,36 ; and (ii) TUDCA appears to also have a beneficial role in pulmonary hypertension 18 . Regardless of the mechanism, we found that UDCA has the potential to preserve CO and mitigate the development of high pulmonary vascular resistance as lung injury develops.…”

Obstruction-Induced Pulmonary Vascular Remodeling

“…The peak right systolic pressure gradient was calculated from the highest peak velocity using the modified Bernoulli equation [22]. Right ventricular systolic pressure was calculated as the sum of the peak right systolic pressure gradient and the estimated right atrial pressure, which was assumed to be 10 mm Hg based on values from healthy infant rabbits [23,24]. …”