In aware of the well-known altered vascular responsiveness in the diabetic vasculature, this study aimed to compare the haemodynamic and PGI2 releasing effects of angiotensin in metabolically healthy (12) and alloxan-(560 umol/kg) diabetic (12) dogs as well as to analyze the role of vascular adrenoceptors in this. In vivo the effect of intracoronarially administered angiotensin (63-125-250-500-1000 pmol/kg/min) on coronary blood flow, mean arterial blood pressure, myocardial contractile force and heart rate was investigated without and with pretreatment of 2 umol/kg phentolamine. In vitro PGI2 release by isolated coronary rings was induced by 50 nmol/l angiotensin before and after pretreatment with 5 umol/l phentolamine and measured by radioimmunoassay. Angiotensin enhances dose-dependently both the mean arterial blood pressure and coronary blood flow, while it provokes a considerable (p < 0.05) increase of PGI2 formation by isolated coronary arterial rings. These alterations could be prevented by phentolamine administration both in vivo and in vitro, while this drug did not affect the angiotensin-induced enhancement of diabetic coronary blood flow. On the other hand the increase of blood pressure by angiotensin was found to be more (p < 0.05) expressed in diabetes and it could be further potentiated by phentolamine. PGI2 synthesis by isolated diabetic coronary rings could not be modified either by angiotensin alone or in combination with phentolamine. On the basis of above data, the lack of stimulated vascular PGI2 formation mediated by alpha-adrenergic mechanisms is supposed to causatively contribute to the diminished sensitivity of diabetic coronary arteries to vasodilation.

Angiotensin II↗

PubMedDate not supplied

The role of myocardial edema in the left ventricular diastolic stiffness.

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.

Animals↗

PubMedDate not supplied

Effects of enhanced coronary flow during cardiopulmonary bypass: development of myocardial edema.

Coronary blood flow, left ventricular diastolic stiffness, ventricular water content and ventricular thiocyanate space were investigated in empty fibrillating and empty beating dog hearts during cardiopulmonary bypass. In empty fibrillating hearts coronary blood flow was considerably enhanced even at levels of normal perfusion pressure. A close correlation was demonstrated between enhanced coronary flow, left ventricular diastolic stiffness, tissue water content and thiocyanate space.

Animals↗

PubMedDate not supplied

Effect of acute hypoxia on cardiac function in alloxan-diabetic dogs.

The aim of the present study was to examine the left ventricular and haemodynamic parameters during acute hypoxia induced by carbon monoxide intoxication and/or after norepinephrine administration in metabolically healthy and alloxan-diabetic dogs. In metabolically healthy animals after carbon monoxide intoxication followed by norepinephrine administration myocardial oedema occurred with a concomitant elevation of diastolic stiffness in the left ventricular wall, resulting in impaired cardiac performance. In the alloxan-diabetic animals no myocardial oedema developed and therefore no further increase of the originally elevated left ventricular diastolic stiffness could be observed. Close correlations were demonstrable between the enhanced water content and diastolic stiffness of the left ventricular wall in metabolically healthy animals as well as between the myocardial contractile force and cardiac output index in both control and diabetic dogs. In contrast to the controls, following norepinephrine administration per se decrease of cardiac performance could be observed in the alloxan-diabetic animals. Based on these results, it can be concluded that an increase of left ventricular diastolic stiffness impairs the cardiac performance in acute hypoxia following norepinephrine administration both in control and in diabetic animals, even if different reasons are responsible for it.

Animals↗

PubMedDate not supplied

Effects of coronary occlusion and norepinephrine on the myocardium of alloxan-diabetic dogs.

The aim of this study was to clarify the role of altered diabetic vascular reactivity in ischaemic heart disease. In diabetic condition, the necrotic area of myocardial infarction was significantly extended and myocardial oedema failed to develop after administration of norepinephrine 2 or 48 hours after ligation of the left anterior descending coronary artery. In metabolically healthy dogs the necrotic area of myocardial infarction was considerably smaller and an increase in myocardial water content, in myocardial thiocyanate space, in microscopically demonstrable permeability and in diastolic stiffness of left ventricular wall occurred when norepinephrine was administered 2 or 48 hours after coronary infarction. A close correlation was demonstrable between enhanced water content, thiocyanate space and diastolic stiffness in metabolically healthy animals, whereas in diabetic condition diastolic stiffness was primarily increased, and decreased when norepinephrine was infused after coronary ligation. Therefore, the altered vascular reactivity in diabetes is supposed to be responsible for the lack of oedema in the nonischaemic part of myocardium after norepinephrine infusion as well as for the size and severity of myocardial infarction.

Animals↗

PubMedDate not supplied

Is malondialdehyde a marker of the effect of oxygen free radicals in rat heart tissue?

We tested the effect of exogenous purine derived free radicals and H2O2 vs ischemia and reperfusion on the thiobarbituric-acid (TBA)-reactive material and malondialdehyde (MDA) formation in isolated rat hearts using the thiobarbituric acid test and high performance lipid chromatography (HPLC). We could not detect increased thiobarbituric-acid-reactive material or MDA production during 6 mM H2O2 infusion, during free radical generation by purine-derived free radicals, or using ischemia and reperfusion. Increased thiobarbituric-acid-reactive material and MDA tissue levels were detected only during infusion of 12 mM H2O2 (p less than 0.001). We conclude that the generally used thiobarbituric acid assay for MDA is susceptible to artifacts and unsuited as an indirect measure for low-to-medium-levels of oxygen free radicals. Using HPLC assay, which accurately measures MDA, no evidence was found that MDA is a primary and direct lipid peroxidation product of exogenous or endogenous reactive oxygen species.

Animals↗

PubMedDate not supplied

QT interval prolongation in type 2 (non-insulin-dependent) diabetic patients with cardiac autonomic neuropathy.

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)

Adult↗

PubMedDate not supplied

Effect of diabetes therapy on the myocardium in experimental diabetes.

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.

Animals↗

PubMedDate not supplied

Preclinical abnormality of left ventricular performance in patients with insulin-dependent diabetes mellitus.

The left ventricular systolic function of 32 patients with insulin-dependent diabetes mellitus was investigated by measurement of systolic time intervals. Patients with clinical signs of sclerosis in the coronary arteries were excluded. Twenty-nine sex- and age-matched healthy people served as controls. Resting values of PEP/LVET ratio and of the corrected pre-ejection period were significantly higher in diabetics than in controls. The alterations of systolic time intervals during volume-loading induced by passive leg-raising as well as by isometric handgrip test indicated an increase in left ventricular performance in healthy people. The unchanged systolic time intervals observed in diabetics during the same loadings indicated a decrease in the functional reserve of the diabetic left ventricle. The systolic time intervals observed in patients with type-1 diabetes could be evaluated as a preclinical abnormality of left ventricular performance and as early signs of diabetic cardiomyopathy.

Adult↗

PubMedDate not supplied

Effects of hypoxia and adrenergic stimulation induced alterations in PGI2 synthesis by diabetic coronary arteries.

Before the onset of histologically detectable alterations in diabetic arteries, a considerable decrease in vasodilatory potential is seen. While analyzing this phenomenon, the role of altered PGI2 synthesis in rings of coronary arteries from metabolically healthy and alloxan-diabetic dogs was measured by radioimmunoassay during baseline, under the influence of phenylephrine (100 mumol/L), and during hypoxia with or without the presence of the alpha adrenergic blocker phentolamine (5 mumol/L). Basal levels of PGI2 synthetized by healthy and diabetic coronaries were no different (7.9 +/- 2.1 and 6.4 +/- 1.4 pg/mg vessel). Phenylephrine potentiated PGI2 synthesis in controls (150 +/- 22%), while it proved to be ineffective in the diabetic animals (98 +/- 6%). Under hypoxic conditions, PGI2 production of healthy coronaries (152 +/- 24%) increased, while that in the diabetic ones (82 +/- 7%) decreased (p less than 0.01). In the presence of phentolamine no difference could be detected between the two groups. Given all these data, the decreased ability of the diabetic coronaries to vasodilate develops due to diminished PGI2 production, presumably controlled by adrenergic mechanisms. Furthermore, the more severe outcome of ischaemic heart disease in diabetes mellitus might be explained by the lack of an enhanced coronary PGI2 synthesis under hypoxic conditions.

Adrenergic alpha-Antagonists↗