Right ventricular preload and afterload challenge induces contractile dysfunction and arrhythmia in isolated hearts of dystrophin-deficient male mice.

Duchenne muscular dystrophy (DMD) is an X-linked recessive myopathy due to mutations in the dystrophin gene. Diaphragmatic weakness in DMD causes hypoventilation and elevated afterload on the right ventricle (RV). Thus, RV dysfunction in DMD develops early in disease progression. Herein, we deliver a 30-min sustained RV preload/afterload challenge to isolated hearts of wild-type (Wt) and dystrophic (Dmdmdx-4Cv) mice at both young (2-6 month) and middle-age (8-12 month) to test the hypothesis that the dystrophic RV is susceptible to dysfunction with elevated load. Young dystrophic hearts exhibited greater pressure development than wild type under baseline (Langendorff) conditions, but following RV challenge exhibited similar contractile function as wild type. Following the RV challenge, young dystrophic hearts had an increased incidence of premature ventricular contractions (PVCs) compared to wild type. Hearts of middle-aged wild-type and dystrophic mice had similar contractile function during baseline conditions. After RV challenge, hearts of middle-aged dystrophic mice had severe RV dysfunction and arrhythmias, including ventricular tachycardia. Following the RV load challenge, dystrophic hearts had greater lactate dehydrogenase (LDH) release than wild-type mice indicative of damage. Our data indicate age-dependent changes in RV function with load in dystrophin deficiency, highlighting the need to avoid sustained RV load to forestall dysfunction and arrhythmia.

Tricuspid annulus cinching force under pulmonary hypertensive right ventricle conditions: An ex vivo study.

This study investigates the force required to reduce or "cinch" the tricuspid annulus under elevated right ventricular pressures, commonly seen in patients with pulmonary hypertension. Tricuspid regurgitation affects 1.6 million Americans. Approximately 43% of patients who undergo tricuspid valve repair to correct tricuspid regurgitation will develop residual pulmonary hypertension, putting them at risk for developing increased right ventricle pressures. Previous studies have quantified the forces required to cinch the tricuspid annulus by only pressurizing the right ventricle, leaving out forces from the pressurized left ventricle and septal wall unaccounted for. This study pressurized both left and right ventricles of 10 porcine hearts to their normal physiological pressures of 110 mmHg and 30 mmHg respectively, then increased right ventricular pressures to mimic moderate and severe pulmonary hypertension. A suture was anchored around the free wall of the tricuspid annulus with the free end attached to a force transducer. The force transducer was mounted on a slider system which pulled the suture at regular intervals. The cinching force on the tricuspid annulus was quantified with each annular reduction by simulating peak systole condition in both ventricles. The data was compared with only the right ventricle pressurized as previous studies did. There were significant differences in required cinching forces with each increase in right ventricular pressure and between trials that pressurized both ventricles versus only the right ventricle, suggesting adoption of this physiologically improved protocol. We also found with increased cinching of the tricuspid annulus, notable changes occur in the mitral annulus.