Short-term diabetes attenuates left ventricular dysfunction and mortality rates after myocardial infarction in rodents

Abstract

OBJECTIVES:To investigate the effects of hyperglycemia on left ventricular dysfunction, morphometry, myocardial infarction area, hemodynamic parameters, oxidative stress profile, and mortality rate in rats that had undergone seven days of myocardial infarction.INTRODUCTION:Previous research has demonstrated that hyperglycemia may protect the heart against ischemic injury.METHODS:Male Wistar rats were divided into four groups: control-sham, diabetes-sham, myocardial infarction, and diabetes + myocardial infarction. Myocardial infarction was induced 14 days after diabetes induction. Ventricular function and morphometry, as well as oxidative stress and hemodynamic parameters, were evaluated after seven days of myocardial infarction.RESULTS:The myocardial infarction area, which was similar in the infarcted groups at the initial evaluation, was reduced in the diabetes + myocardial infarction animals (23±3%) when compared with the myocardial infarction (42±7%, p<0.001) animals at the final evaluation. The ejection fraction (22%, p = 0.003), velocity of circumferential fiber shortening (30%, p = 0.001), and left ventricular isovolumetric relaxation time (26%, p = 0.002) were increased in the diabetes + myocardial infarction group compared with the myocardial infarction group. The diabetes-sham and diabetes + myocardial infarction groups displayed increased catalase concentrations compared to the control-sham and myocardial infarction groups (diabetes-sham: 32±3; diabetes + myocardial infarction: 35±0.7; control-sham: 12±2; myocardial infarction: 16±0.1 pmol min-1 mg-1 protein). The levels of thiobarbituric acid-reactive substances were reduced in the diabetes-sham rats compared to the control-sham rats. These positive adaptations were reflected in a reduced mortality rate in the diabetes + myocardial infarction animals (18.5%) compared with the myocardial infarction animals (40.7%, p = 0.001).CONCLUSIONS:These data suggest that short-term hyperglycemia initiates compensatory mechanisms, as demonstrated by increased catalase levels, which culminate in improvements in the ventricular response, infarcted area, and mortality rate in diabetic rats exposed to ischemic injury.

VEGF165 Gene Therapy Improves Left Ventricular Function and Exercise Capacity in Diabetic Rats after Myocardial Infarction: Impact on Mortality Rate

“…underwent surgical occlusion of the left coronary artery or sham, which resulted in myocardial infarction, as previously described elsewhere [5,7,14]. Briefly, a left intercostal thoracotomy was performed, the third intercostal space dissected, and the heart exposed.…”

“…Echocardiography was performed by a double-blinded observer, under the guidelines of the American Society of Echocardiography, 1 day (initial evaluation) after MI and 30 days (final evaluation) after pHuVEGF 165 Echocardiographic parameters were measured as described in detail elsewhere [5,7,14].…”

“…Regions with systolic thickness under normal, as well as portions with paradoxal movement, were considered as infarcted. The infarcted area (%) was thus determined by the ratio of these regions by the total area of LV walls [5,7,14]. To confirm the echocardiography, the MI area was also analyzed after all other evaluations (30 days after pHuVEGF 165 or saline injections) by dissecting the fibrous scar from the remaining LV muscle.…”

“…In the experimental setting, our group has evidenced that diabetic rats have an imbalance in the oxidative stress profile [5], changes in the cellular survival pathway [6], reduced expression of the cardiac calcium handling proteins and ventricular function [7] at different times after MI.…”

Cardiovascular research in CLINICS

“…Rodrigues et al (11) investigated the effects of hyperglycemia on left ventricular dysfunction, morphometry, myocardial infarction area, hemodynamic parameters, oxidative stress profile, and mortality rate in diabetic and nondiabetic rats that had undergone seven days of myocardial infarction. The authors observed that the myocardial infarction area and mortality were reduced, whereas the ejection fraction, velocity of circumferential fiber shortening, and left ventricular isovolumetric relaxation time were increased in the diabetic animals compared with the myocardial infarction group.…”