The sensitivity of the myocardium to ischemia and the level of protection achieved by ischemic preconditioning is shaped by the joint influence of several mechanisms in diabetes mellitus. In vivo studies were made in alloxan diabetic and non-diabetic control rabbits to assess if the effects of preconditioning and sulfonylurea pretreatment with either glibenclamide or glimepiride (0.05-0.2-0.6 micromol kg (-1)) influence the extent of the infarcted area caused by one hour ligature of the left coronary artery. For our study, we defined preconditioning as 2 minutes of ischemia followed by 2 minutes of reperfusion, which was repeated 3 times. The interrelationship of the diabetic pathophysiological state, and sulfonylurea treatment during ischemic preconditioning were studied by comparing the infarcted areas and the rate of infarction to risk areas in left ventricular slices using computer planimetry. In healthy control rabbits preconditioning reduced infarcted area (29.6 +/- 3.0% vs. 48.8 +/- 2.8% p < 0.0005), while in diabetic rabbits this protection did not occur (53.3 +/- 7.3% vs. 56.6 +/- 4.4% NS). Glibenclamide in all of applied doses prevented the protective effect in control animals (infarction/ risk area: HP: 0.47 +/- 0.04 vs. HP Glib-0.05 : 0.69+/-0.06 p< 0.004 vs. HP Glib-0.2 : 0.72+/-0.09 p< 0.002 vs. HP Glib-0.6 : 0.75 +/- 0.04 p< 0.001). In contrast, in diabetic rabbits low dose of glibenclamide contributed to the same development of preconditioning. However the highest dose of glibenclamide (infarction/risk area: DP Glib-0.6 : 0.77 +/- 0.17 vs. DP Glib-0.05 : 0.55 < 0.03 p < 0.047) and the consequences of the diabetic state blocked the salutary effect. Glimepiride had no considerable influence on the protective effect, either in control nor in diabetic animals. Glibenclamide and glimepiride, presumably due to their different sulfonylurea receptor affinity in the heart, resulted in different influence on preconditioning in healthy control animals. Glibenclamide treatment seemed to be more harmful when less K (+)ATP channels were activated. The accomplishment of myocardial preconditioning in diabetes mellitus is claimed to be determined by the interaction of both metabolically influenced K (+)ATP channel activity and the dose of sulfonylurea.

It has been shown that simultaneous administration of norepinephrine (10mug/kg/min) and drotaverine (200 mug/kg/min) does induce interstitial myocardial edema which tends to increase left ventricular diastolic stiffness. These results suggest that in myocardial ischaemia temporary increase of left ventricular diastolic stiffness may be caused by interstitial edema.

QT interval alterations were measured in 41 non-insulin-dependent (type 2) diabetic patients and 14 age- and sex-matched control subjects. Cardiac autonomic neuropathy (CAN) was assessed by noninvasive tests (deep breathing, Valsalva maneuver and lying-to-standing) and diabetics were divided into three groups according to the results of these tests: diabetics with definitive (n = 14), early (n = 13) and without (n = 14) CAN. The corrected values of QT intervals (QTc) at rest were significantly longer in diabetics with definitive (447 +/- 5 ms; p less than 0.001), early (426 +/- 5 ms; p less than 0.05) and without (424 +/- 5 ms; p less than 0.05) CAN than in controls (407 +/- 5 ms). Moreover, QTc intervals at rest were significantly (p less than 0.01) longer in diabetics with definitive CAN than in diabetics with early and without CAN. QTc intervals at maximum tachycardia, induced by Valsalva maneuver, were considerably longer in diabetics with definitive CAN (451 +/- 6 ms) than in controls (407 +/- 6 ms; p less than 0.001) and in diabetics with early (434 +/- 6 ms; p less than 0.05) or without (422 +/- 6 ms; p less than 0.01) CAN. Furthermore, QTc intervals at maximum tachycardia were significantly (p less than 0.01) longer in diabetics with early CAN than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of chronic antidiabetic treatment were examined in a clinically manifest, but non-ketotic diabetic animal model in which increased stabilization of steric structure in the cardiac connective tissue and left ventricular diastolic stiffness have been demonstrated. These changes accounted for decreased left ventricular performance during left ventricular afterload. Each of 8 diabetic dogs was given daily 8-16 IU of insulin, 250-750 mg carbutamide or 2-10 mg glibenclamide, respectively; doses were always adjusted to the actual metabolic requirements and findings were compared to those of 11 untreated diabetic and 6 healthy dogs. After three months, the hemodynamic and metabolic studies showed that the metabolically controlled diabetic dogs had less marked alterations in the connective cardiac tissue, left ventricular diastolic stiffness and performance. Apart from a considerable rise of arterial blood pressure during carbutamide treatment, no other difference was found in the cardiac actions of the three hypoglycemic agents tested.