Submitted to: American Journal of Physiology - Heart and Circulatory Physiology
Publication Type: Peer reviewed journal
Publication Acceptance Date: 2/20/2007
Publication Date: 9/1/2007
Citation: Chandler, M.P., Morgan, E.E., Mcelfresh, T.A., Kung, T.A., Rennison, J.H., Hoit, B.D., Young, M.E. 2007. Heart failure progression is accelerated following myocardial infarction in type II diabetic rats. American Journal of Physiology - Heart and Circulatory Physiology. 293(3):H1609-H1616. Interpretive Summary: The strongest risk factor for the development of heart disease is diabetes, of which type II diabetes is the most common form in humans. Furthermore, patients with type II diabetes have a worse prognosis when heart disease develops. The purpose of the present study was therefore to determine whether type 2 diabetes accelerates heart disease after a heart attack (myocardial infarction). The results show that type 2 diabetes accelerates heart disease after a heart attack (myocardial infarction), in rodents.
Technical Abstract: Clinical studies have shown a greater incidence of myocardial infarction in diabetic patients and following an infarction, diabetes is associated with an increased risk for the development of left ventricular dysfunction and heart failure. The goal of this study was to determine if the progression of heart failure following myocardial infarction in type II diabetic (T2D) rats is accelerated compared to non-diabetic rats. Male non-diabetic WKY and T2D Goto-Kakizaki (GK) rats underwent coronary artery ligation or sham surgery to induce heart failure. Eight and twenty weeks post-ligation, 2-D echocardiography and left ventricular pressure measurements were made. Heart failure progression, as assessed by enhanced left ventricular remodeling and contractile dysfunction and was accelerated eight weeks post-ligation in the T2D animals. Left ventricular remodeling was evident from increased end-diastolic and end-systolic diameters and areas in the GK compared to the WKY ligated group. Furthermore, enhanced left ventricular contractile dysfunction was evident from a greater deterioration in fractional shortening and enhanced myocardial performance index (an index of global LV dysfunction) in the GK ligated group. This accelerated progression was accompanied by greater increases in atrial natriuretic factor and skeletal α-actin (gene markers of heart failure and hypertrophy) mRNA levels in GK ligated hearts. Despite similar decreases in metabolic gene expression (i.e., PPAR regulated genes associated with fatty acid oxidation) between infarcted WKY and GK rat hearts, myocardial triglyceride levels were elevated in the GK hearts only. These results, demonstrating enhanced remodeling and left ventricular dysfunction eight weeks post-ligation provide evidence of an accelerated progression of heart failure in type II diabetic rats