Functional, metabolic and ultrastructural alterations as a result of cardiac hypertrophy

Michael Eugene Dunn, University of Rhode Island

Abstract

Effects of gene manipulation on mouse heart function generally require aortic banding or other additional molecular modification in order to achieve full expressions of cardiac responses. The neurohormonal independent characterization of myocardial functional and metabolic changes concurrent with skeletal muscle pathology resulting from aortic banding in the mouse have not been investigated. The objective of this study was to characterize the effects of thoracic aortic banding alone on mouse left ventricular function, skeletal muscle pathological changes and glycolytic flux three and six weeks post-banding. Working hearts were perfused (KH solution containing 3% albumin and 0.4 mM palmitate) at identical volume and pressure loads, 3 and 6 weeks after partial ligation of the thoracic aorta or sham surgery. Pressure-volume loops were obtained with an intraventricular 1.4F Millar catheter. Glycolytic flux was quantified as the rate of 3H2O produced from 5-3H-glucose. Skeletal muscle biopsies were morphologically analyzed with a transmission electron microscope. Compared to hearts from sham controls, hearts from banded mice at three and six weeks: 1) Were markedly hypertrophic; 2) Exhibited pronounced reductions in systolic pressure, ejection fraction and other measurements of left ventricular function; 3) Demonstrated a degree of hypertrophy dependent elevation in end diastolic pressure; 4) Displayed robust decrease in glycolytic flux; 5) Presented with evidence of hypertrophy-length dependent fiber specific mitochondrial alterations. Overt hypertrophic heart failure with associated pathological skeletal muscle alterations and reactive declines in cardiac glycolytic flux are evident as early as three weeks, and persist for at least six weeks, after aortic banding in the mouse. ^

Subject Area

Biology, Physiology

Recommended Citation

Michael Eugene Dunn, "Functional, metabolic and ultrastructural alterations as a result of cardiac hypertrophy" (2010). Dissertations and Master's Theses (Campus Access). Paper AAI3415515.
http://digitalcommons.uri.edu/dissertations/AAI3415515

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