High glucose induces ventricular instability and increases vasomotor tone in rats

Abstract

Cardiovascular complications of diabetes commonly lead to considerable morbidity and mortality [1]. Recent prospective studies indicate that glycaemic control of diabetes is an important predictor not only of microvascular disease [2] but also of macrovascular complications, including coronary heart disease [3]. Among the many potential mechanisms proposed to explain why poor glycaemic control of diabetes might predict coronary events and worsen the prognosis both in diabetic and non-diabetic patients after myocardial infarction [ Abstract Aims/hypothesis. To investigate cardiac repolarization time in streptozotocin-induced diabetic rats and isolated hearts perfused with high glucose concentration.Methods. We studied the effects of streptozotocin-induced diabetes on the cardiac repolarisation time (Q-T interval) in Sprague-Dawley rats during a 4-day period of hyperglycaemia and a subsequent 4-day period of normoglycaemia. The Q-T interval was also evaluated in isolated hearts of non-diabetic rats, in condition of high glucose concentration.Results. Hyperglycaemia in streptozotocin rats increased mean blood pressure and led to a significant (p < 0.001) prolongation of Q-T values, which normalized after 4 days of normoglycaemia with intravenous insulin infusion. Perfusion of isolated hearts in condition of high glucose concentration caused a significant prolongation of Q-T values and increased coronary perfusion pressure (p < 0.001). The effects of high glucose were completely prevented by glutathione and almost completely by l-arginine, the natural precursor of nitric oxide. In a condition of normal glucose, l-NAME, an inhibitor of endogenous nitric oxide synthesis, increased both Q-T and CPP values to levels similar to those induced by high glucose (p < 0.001). Verapamil completely prevented Q-T lengthening and reduced by about two-thirds CPP values (p < 0.001). Conclusion/Interpretation. Streptozotocin-diabetes in rats produces significant haemodynamic and electric perturbations that are reversed by normoglycaemia. Moreover, high glucose increases Q-T and CPP values in the isolated hearts of non-diabetic rats. The latter effects are reversed by glutathione and l-arginine, partially reversed by verapamil and mimicked by l-NAME. By increasing the production of free radicals, high glucose could reduce nitric oxide availability to target cells inducing a state of increased vasomotor tone and ventricular instability. [Diabetologia (2001) 44: 464±470]

Relationship between QT interval and cardiovascular risk factors in healthy young subjects

“…Acute hyperglycaemia increases QTc duration in experimental animals 25 and in healthy subjects 26 by increasing sympathetic activity 27 and cytosolic calcium content. 28 In diabetic patients, the association between glycaemia and QTc may be also QT interval in young subjects G Leotta et al mediated by insulin-resistance and chronic hyperinsulinaemia, since insulin increases sympathetic activity and hyperpolarizes plasma membrane of cardiac myocytes.…”

Resveratrol alleviates cardiac dysfunction in streptozotocin-induced diabetes: Role of nitric oxide, thioredoxin, and heme oxygenase

“…Most of the protective biological actions associated with resveratrol was found to be associated with its intrinsic radical scavenging properties. Hyperglycemia in diabetes leads to cardiovascular complications induced by oxidative stress (15). It is, therefore, anticipated that modulation of redox signaling may be causally related to cardioprotection mediated by resveratrol.…”

“…Concomitant with this hypothesis, in our previous study resveratroltreated myocardium after MI significantly induced thioredoxin (Trx-1), heme oxygenase (HO-1) and VEGF expression along with increased capillary density. This resveratrolmediated cardioprotection and angiogenic response via upregulation of VEGF was blocked by SnPP (HO-1 inhibitor) (9,15).…”

Impact of ventricular arrhythmias on survival in patients after myocardial infarction

“…Furthermore, it was proved that the increased concentration of creatinine in blood serum is connected with 40% increase in the risk of cardiovascular incident or death in case of such patients [15] . It has also been confirmed by D'Amico M. et al, who proved that the lowering of GFR value < 60 ml/min/1.73m² is connected with the greater risk of SCD, furthermore this risk increase proportionally to the further decrease of GFR value [14] . Irrespectively of the current studies, the results achieved in the present analysis indicate that in patients with increased creatinine value who suffered from myocardial infarction, additional ventricular excitement is observed significantly more frequently, what might worsening the prognosis in long-term observation.…”

“…The outcomes achieved from present analysis clearly indicate that the increased glucose level at admission significantly increases the frequency of numerous ventricular extrasystoles in those patients. It has been proved by earlier researches, that hyperglycaemia was not only triggering adverse hemodynamic effects such as increasing heart rate, systolic and diastolic arterial pressure or catecholamines concentration in blood serum, but also leads to electrophysiological disorders, including the extending QT interval [14] . What is more, in the case of the patients with history of diabetes and coronary disease the risk of death grows significantly.…”