Heart failure progression is accelerated following myocardial infarction in type 2 diabetic rats.
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 (LV) dysfunction and heart failure. The goal of this study was to determine if the progression of heart failure following myocardial infarction in type 2 diabetic (T2D) rats is accelerated compared with nondiabetic rats. Male nondiabetic Wistar-Kyoto (WKY) and T2D Goto-Kakizaki (GK) rats underwent coronary artery ligation or sham surgery to induce heart failure. Postligation (8 and 20 wk), two-dimensional echocardiography and LV pressure measurements were made. Heart failure progression, as assessed by enhanced LV remodeling and contractile dysfunction, was accelerated 8 wk postligation in the T2D animals. LV remodeling was evident from increased end-diastolic and end-systolic diameters and areas in the GK compared with the WKY infarcted group. Furthermore, enhanced LV 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 infarcted group. This accelerated progression was accompanied by greater increases in atrial natriuretic factor and skeletal alpha-actin (gene markers of heart failure and hypertrophy) mRNA levels in GK infarcted hearts. Despite similar decreases in metabolic gene expression (i.e., peroxisome proliferator-activated receptor-alpha-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 LV dysfunction 8 wk postligation provide evidence of an accelerated progression of heart failure in T2D rats.
Chandler
Margaret P
MP
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106-4970, USA. mpc10@case.edu
Morgan
Eric E
EE
McElfresh
Tracy A
TA
Kung
Theodore A
TA
Rennison
Julie H
JH
Hoit
Brian D
BD
Young
Martin E
ME
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D002303:Cardiac Output, Low / Q000378:metabolism / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006339:Heart Rate / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D018487:Ventricular Dysfunction, Left; D020257:Ventricular Remodeling
D000199:Actins; D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger; D009320:Atrial Natriuretic Factor