Morphological and molecular development in python model of pathological cardiac hypertrophy

Abstract

The Burmese python (Python molurus) experiences rapid physiological hypertrophy of the heart with feeding. Within days after consuming a meal equaling in mass to 25% of snake's body mass, heart mass will have increased by as much as 30%. Given the python's capacity for physiological hypertrophy, we are exploring whether a pathological model of cardiac hypertrophy can be generated by chronic pressure overload. To induce pressures overload, we ligated the python's left systemic artery, thereby diverting all left ventricular output through the right systemic artery. Ligation alone generated a 20% increase in ventricular mass. The combination of ligation and feeding resulted in a 32% increase in ventricular mass. Characteristic of pathological hypertrophy for mammals is an increase in cardiac fibrosis. We observed a 32% increase (P = 0.05) in the amount of fibrotic tissue for hearts from ligated pythons compared to hearts from fed non‐ligated snakes. Molecular markers for the pathological phenotype of mammalian cardiac hypertrophy include upregulation of gene expression for α‐isoform of skeletal muscle actin (α‐SA) and β‐MHC, and a decrease in expression for α‐MHC and SERCA2. Ligation generated the pathological response of an increase in α‐SA and β‐MHC expression, while at the same time non‐pathological responses of increased α‐MHC and SERCA2 expression. The python heart responds to pressure overload with a combination of physiological and pathological traits that may collectively deter the loss of cardiac performance. Support for this research has been provided by the National Science Foundation (IOS‐0466139 to SS) and Hiberna Corp.