Hyperglycemia can delay left ventricular dysfunction but not autonomic damage after myocardial infarction in rodents

Abstract

BackgroundAlthough clinical diabetes mellitus is obviously a high risk factor for myocardial infarction (MI), in experimental studies disagreement exists about the sensitivity to ischemic injury of an infarcted myocardium. Recently, our group demonstrated that diabetic animals presented better cardiac function recovery and cellular resistance to ischemic injury than nondiabetics. In the present study, we evaluated the chronic effects of MI on left ventricular (LV) and autonomic functions in streptozotocin (STZ) diabetic rats.MethodsMale Wistar rats were divided into 4 groups: control (C, n = 15), diabetes (D, n = 16), MI (I, n = 21), and diabetes + MI (DI, n = 30). MI was induced 15 days after diabetes (STZ) induction. Ninety days after MI, LV and autonomic functions were evaluated (8 animals each group). Left ventricular homogenates were analyzed by Western blotting to evaluate the expression of calcium handling proteins.ResultsMI area was similar in infarcted groups (~43%). Ejection fraction and +dP/dt were reduced in I compared with DI. End-diastolic pressure was additionally increased in I compared with DI. Compared with DI, I had increased Na+-Ca2+ exchange and phospholamban expression (164%) and decreased phosphorylated phospholamban at serine16 (65%) and threonine17 (70%) expression. Nevertheless, diabetic groups had greater autonomic dysfunction, observed by baroreflex sensitivity and pulse interval variability reductions. Consequently, the mortality rate was increased in DI compared with I, D, and C groups.ConclusionsLV dysfunction in diabetic animals was attenuated after 90 days of myocardial infarction and was associated with a better profile of calcium handling proteins. However, this positive adaptation was not able to reduce the mortality rate of DI animals, suggesting that autonomic dysfunction is associated with increased mortality in this group. Therefore, it is possible that the better cardiac function has been transitory, and the autonomic dysfunction, more prominent in diabetic group, may lead, in the future, to the cardiovascular damage.

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

“…Control rats were injected with buffer only (10 mM citrate buffer, pH 4.5). Forty-eight hours after STZ injection, diabetes was confirmed by blood glucose levels above 200 mg/dL [7].…”

“…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.…”