LAUSR

Duchenne muscular dystrophy (DMD) is an X-linked recessive myopathy caused by mutations in the gene encoding dystrophin. Dystrophin is present in striated muscle cells and stabilizes the sarcolemma to mitigate contraction-induced damage. The main cause of death in DMD is cardiopulmonary failure by age 30. Diaphragmatic weakness in DMD causes restrictive lung disease and excessive afterload on the right ventricle (RV). Thus, RV dysfunction in DMD patients is typically observed early in disease progression. The objective of this study was to investigate ex vivo RV function in a mouse model of muscular dystrophy and test the hypothesis that RV function is impaired following a sustained increase in ventricular preload and afterload. Right-ventricular pressure development (Pdev) and rate of pressure decay (dP/dtMin) were monitored in isolated perfused hearts of 2-6 month normal (C57BL/6, n=5) and dystrophic (mdx4CV, n=5) male mice. Measurements were obtained under unloaded conditions and during right-ventricular load challenge (10 mmHg preload; 20 mmHg afterload). Coronary effluent lactate dehydrogenase (LDH) levels were measured following 30 minutes of sustained load challenge to assess cardiac damage. Our results show dystrophic hearts exhibited greater RV Pdev than normal hearts under unloaded conditions (24±2 mmHg mdx4CV vs 15±2 mmHg C57BL/6, P=0.015). In response to load challenge, Pdev increased (P<0.05) in both groups, but it was similar between dystrophic and normal hearts (32±1 mmHg mdx4CV vs 33±3 mmHg C57BL/6). Rate of pressure decay was similar between dystrophic and normal hearts under both conditions. Levels of LDH following load challenge were higher (P<0.05) in dystrophic versus normal hearts. In conclusion, in the absence of ventricular load RV contractile function was enhanced in dystrophic hearts. With RV load both dystrophic and normal hearts exhibited similar contractile function, yet sustained load challenge increased cellular damage in dystrophic versus normal hearts. National Institutes of Health, University of Missouri School of Medicine, University of Missouri System This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.