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1.
Exp Clin Endocrinol Diabetes ; 110(5): 212-8, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12148084

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/physiopathology , Diabetic Angiopathies/pathology , Glyburide/therapeutic use , Hypoglycemic Agents/therapeutic use , Ischemic Preconditioning , Myocardial Infarction/pathology , Sulfonylurea Compounds/therapeutic use , Animals , Male , Myocardial Infarction/prevention & control , Rabbits , Reference Values
2.
Acta Physiol Scand ; 169(3): 183-7, 2000 Jul.
Article in English | MEDLINE | ID: mdl-10886032

ABSTRACT

The aim of the present study was to investigate the effects of experimental diabetes and hyperglycaemia per se on the endothelium-dependent relaxation of isolated canine coronary arteries and to analyse the possible involvement of the cyclooxygenase pathway in the alterations induced by hyperglycaemia. Rings from the left anterior descending coronary arteries of 18 metabolically healthy, six alloxan-diabetic and six insulin-treated alloxan diabetic dogs were set up for isometric tension recording. Diabetic coronaries as well as healthy vessels subjected to in vitro hyperglycaemia (25.5 mmol L-1 glucose) showed impaired (P < 0.05) relaxation to acetylcholine (3 nmol L-1-10 micromol L-1) compared with normoglycaemic, i.e. metabolically healthy and insulin-treated diabetic controls, either before or after indomethacin (3 micromol L-1) administration. The maximal dilation elicited by acetylcholine was further decreased (P < 0.05) by the cyclooxygenase inhibitor in the diabetic coronaries only. Relaxation to sodium nitroprusside did not differ among groups. These results suggest that hyperglycaemia may result in impaired endothelium-dependent dilation of coronary arteries. Diminished relaxation of diabetic coronaries is worsened by the inhibition of the synthesis of vasodilator cyclooxygenase products.


Subject(s)
Coronary Vessels/physiopathology , Diabetes Mellitus, Experimental/physiopathology , Endothelium, Vascular/metabolism , Hyperglycemia/metabolism , Vasodilation , Acetylcholine/pharmacology , Animals , Blood Glucose , Coronary Vessels/metabolism , Cyclooxygenase Inhibitors/pharmacology , Diabetes Mellitus, Experimental/metabolism , Dinoprost/pharmacology , Dogs , Enzyme Inhibitors/pharmacology , Female , In Vitro Techniques , Indomethacin/pharmacology , Male , Nitroarginine/pharmacology , Nitroprusside/pharmacology , Osmolar Concentration , Vasoconstriction/drug effects , Vasodilation/drug effects , Vasodilator Agents/pharmacology
3.
Cardiovasc Res ; 34(1): 157-63, 1997 Apr.
Article in English | MEDLINE | ID: mdl-9217885

ABSTRACT

OBJECTIVE: To study the influence of diabetes on the endothelium-dependent vasodilation in the coronary arterial bed. METHODS: The effects of acetylcholine (ACh 2-36 pmol.kg-1; 18 nmol.1(-1)-9.8 mumol.1(-1); 0.1-10 mumol.1(-1), L-arginine (1 mmol.1(-1) and sodium nitroprusside (1 nmol.1(-1)-100 mumol.1(-1)) were measured on coronary conductivity, vascular tone and cGMP release (RIA) in healthy and diabetic dogs. RESULTS: ACh-mediated (in cumulative intra-arterial infusion) increase in coronary conductivity was reduced (P < 0.01) in the diabetic dogs in vivo, whereas no increase in cGMP release was observed in isolated diabetic coronaries (P < 0.05) which could not be enhanced by L-arginine (P < 0.05). Inhibition of cyclo-oxygenase after 20 min further impaired (P < 0.01) responsiveness to ACh in vivo and diminished the ACh response in isolated coronary strips of the diabetic dogs, but not in those of the controls. Relaxation in response to sodium nitroprusside was not altered by diabetes. CONCLUSIONS: Diminished vasodilation in diabetes is due to a defect in endothelial nitric oxide production and action. Vasodilating prostanoids do not sufficiently compensate this defect.


Subject(s)
Acetylcholine/pharmacology , Arginine/pharmacology , Coronary Vessels/metabolism , Diabetes Mellitus, Experimental/metabolism , Endothelium, Vascular/physiopathology , Nitric Oxide/physiology , Vasodilation/drug effects , Animals , Coronary Circulation/drug effects , Coronary Vessels/drug effects , Cyclic GMP/metabolism , Cyclooxygenase Inhibitors/pharmacology , Diabetes Mellitus, Experimental/physiopathology , Dogs , Dose-Response Relationship, Drug , Endothelium, Vascular/drug effects , Female , Ibuprofen/pharmacology , In Vitro Techniques , Indomethacin/pharmacology , Male , Nitric Oxide/biosynthesis , Nitroprusside/pharmacology , Vasodilator Agents/pharmacology
4.
Mol Cell Biochem ; 163-164: 151-7, 1996.
Article in English | MEDLINE | ID: mdl-8974051

ABSTRACT

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.


Subject(s)
Angiotensin II/pharmacology , Coronary Vessels/drug effects , Diabetes Mellitus, Experimental/physiopathology , Epoprostenol/metabolism , Animals , Blood Glucose/metabolism , Body Weight , Coronary Circulation/drug effects , Coronary Vessels/metabolism , Dogs , Dose-Response Relationship, Drug , Female , Heart Rate/drug effects , Hemodynamics/drug effects , Male , Phentolamine/pharmacology
5.
Diabetes Res Clin Pract ; 31 Suppl: S15-20, 1996 Jul.
Article in English | MEDLINE | ID: mdl-8864636

ABSTRACT

The effects of different ATP-sensitive potassium channel blocker sulphonylurea drugs (0.01-1000 mumol/l, or kg) were investigated in vitro on the electrical threshold, conduction time, effective refractory period and automaticity of left atrium, right ventricle and Purkinje fibers as well as in vivo on strophanthidin-, ischaemia- and reperfusion-induced arrhythmias and on vagal nerve stimulation in rabbits, rats and dogs. They proved to exert different actions not only quantitatively but also qualitatively. In vitro, glibenclamide diminished the electrical activity of the heart muscle preparations, while chlorpropamide stimulated it, whereas glimepiride does not seem to affect it markedly. In vivo, glibenclamide and glimepiride decrease, while gliclazide and tolbutamide increase, the amount of strophanthidin- and ischaemia-induced ventricular ectopic beats and the duration of ventricular fibrillation. In the case of glimepiride the effect was dependent on the metabolic state. The different actions of sulphonylureas on the electrophysiological properties of the heart cannot be explained solely by their ATP-dependent potassium channel blocking potencies.


Subject(s)
Cardiovascular Diseases/etiology , Diabetes Mellitus/drug therapy , Heart/drug effects , Hypoglycemic Agents/pharmacology , Sulfonylurea Compounds/pharmacology , Action Potentials/drug effects , Adenosine Triphosphate/physiology , Animals , Cardiovascular Diseases/physiopathology , Diabetes Complications , Diabetes Mellitus/physiopathology , Heart/physiology , Humans , Hypoglycemic Agents/adverse effects , Potassium Channels/drug effects , Potassium Channels/physiology , Sulfonylurea Compounds/adverse effects
6.
Acta Physiol Hung ; 84(1): 9-18, 1996.
Article in English | MEDLINE | ID: mdl-8993670

ABSTRACT

This study was undertaken to investigate the role of nitric oxide (NO), cyclooxygenase products and bradykinin (Bk) receptors in the Bk evoked responses of canine renal arteries and perfused kidneys. Rings of isolated canine renal arteries were mounted in organ chambers for measurement of isometric force. The isolated canine kidneys were perfused with Krebs-solution (constant flow) and the perfusion pressure was continuously recorded. The influence of the cyclooxygenase inhibitor indomethacin and the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginin (L-NOARG) on the vasocontractile responses to phenylephrine (PE) were examined in both preparations. Furthermore, the effects of Bk on the tone of canine isolated renal arteries and on the vasopressor responses of isolated buffer-perfused kidneys of dogs were tested in the absence and presence of enzyme inhibitors and the B2 kinin receptor antagonist HOE-140. It was found that indomethacin enhanced the contractile responses of large renal arteries to PE by 77 +/- 10%. In intact artery rings L-NOARG (0.1 mM) caused an additional potentiation of the PE-induced contractions in the presence of indomethacin (from 11.5 +/- 1.2 mN to 21.6 +/- 1.7 mN). However, L-NOARG failed to affect contractile responses to PE in endothelium-denuded rings. Bk produced a concentration-dependent relaxation of the precontracted endothelium-intact renal arteries. The IC50 value for Bk was 11.2 +/- 3.7 nM. The relaxant activity of the peptide in renal artery rings was not affected by indomethacin (3 microM). However, in the presence of L-NOARG a significantly higher concentration (IC50 = 860 +/- 300 nM) of Bk was required to relax renal arteries. The Bk receptor antagonist HOE-140 (10 nM for 40 min) attenuated the relaxant effect of Bk in renal artery rings (from an IC50 of 14.2 +/- 2.5 nM to 216 +/- 37 nM). Indomethacin (3 microM for 20 min) did not significantly alter the arteriolar vasoconstriction (from 45 +/- 4 mm Hg to 48 +/- 5 mm Hg, n = 5) evoked by PE. By contrast, L-NOARG (0.1 mM) potentiated (from 56 +/- 7 mm Hg to 94 +/- 11 mm Hg) the PE-induced vasopressor responses in perfused kidneys. Bk reduced the size of the pressor responses at relatively low concentrations (2-60 nM) but the dose-response curve was flat and the maximum inhibitory effect hardly exceeded 50 percent. Indomethacin (3 microM) did not modify the inhibitory effect of Bk in perfused kidney. In the presence of L-NOARG, Bk depressed the PE induced vasopressor effects with a maximum of 18 +/- 20%. Preincubation of the kidney preparations with the Bk antagonist HOE 140 (10 nM for 40 min) almost completely abolished the inhibitory effect of Bk on the PE induced vasopressor responses. The results suggest that the endothelial NO plays a fundamental role in the relaxant effect of Bk and considerably modulates vascular reactivity to PE in canine renal vasculature. Furthermore, significant difference exists between conduit and resistance vessels of dog's kidney in the effect of indomethacin on the adrenergic contractions.


Subject(s)
Bradykinin/pharmacology , Muscle, Smooth, Vascular/drug effects , Renal Artery/drug effects , Renal Circulation/drug effects , Vasodilator Agents/pharmacology , Adrenergic beta-Antagonists/pharmacology , Animals , Bradykinin/analogs & derivatives , Bradykinin/antagonists & inhibitors , Buffers , Cyclooxygenase Inhibitors/pharmacology , Dogs , Enzyme Inhibitors/pharmacology , Female , In Vitro Techniques , Indomethacin/pharmacology , Male , Muscle Tonus/drug effects , Nitric Oxide Synthase/antagonists & inhibitors , Nitroarginine/pharmacology , Perfusion , Phenylephrine/antagonists & inhibitors , Phenylephrine/pharmacology , Vasoconstrictor Agents/antagonists & inhibitors , Vasoconstrictor Agents/pharmacology , Vasodilator Agents/antagonists & inhibitors
7.
Arch Int Pharmacodyn Ther ; 330(1): 39-52, 1995.
Article in English | MEDLINE | ID: mdl-8849309

ABSTRACT

The effects of the angiotensin-converting enzyme inhibitors, captopril, lisinopril and enalapril-maleate (the latter being a prodrug that has to be converted into enalaprilat), and bradykinin were investigated in the presence or absence of indomethacin and bradykinin receptor antagonists in dog renal arterial rings precontracted with either prostaglandin F2 alpha or phenylephrine. At a high precontraction level (10 microM of prostaglandin F2 alpha), captopril did not relax the arteries. However, when the tension was low (0.5 microM), both captopril and lisinopril produced endothelium-dependent relaxations. The maximum relaxations for captopril and lisinopril were 57 +/- 6% and 64 +/- 15%, respectively. Enalapril-maleate failed to relax the renal arteries even when the vascular tone was low. In endothelium-intact arteries precontracted with phenylephrine (0.2 microM), captopril and lisinopril produced a maximum relaxation of 60 +/- 9% and 29 +/- 5%, respectively, in arteries with intact endothelium, whilst responses to enalapril-maleate were inconsistent. Renal artery rings with rubbed endothelium failed to relax in response to bradykinin or captopril. We observed significant variations in both captopril- and lisinopril-induced endothelium-dependent relaxations in one tenth of the preparations. The relaxations to bradykinin and captopril were not affected by indomethacin (3 microM), whereas they were markedly attenuated by NG-nitro-L-arginine (0.1 mM). The bradykinin-antagonist, N alpha-adamantane-acetyl-D-Arg-(Hyp3, Thi5,8, D-Phe7)BK, or the specific bradykinin2 receptor antagonist, HOE140, completely abolished the relaxation responses to captopril and reduced the potency of bradykinin, but failed to affect the acetylcholine-induced responses. The results suggest that the relaxant effect of captopril is mediated by endogenous bradykinin or by activation of bradykinin receptors. The proposed mechanisms by which captopril relaxes the renal arteries are: (1) inhibition of tissue kininase II, which leads to accumulation of endogenous bradykinin; (2) shift in angiotensin I metabolism towards (a) relaxant angiotensin derivative(s); and (3) interaction with bradykinin receptors.


Subject(s)
Bradykinin/pharmacology , Captopril/pharmacology , Muscle Relaxation/drug effects , Renal Artery/drug effects , Animals , Dogs , Dose-Response Relationship, Drug , Endothelium/drug effects , Female , Indomethacin/pharmacology , Male , Phenylephrine/pharmacology
8.
Orv Hetil ; 134(34): 1861-4, 1993 Aug 22.
Article in Hungarian | MEDLINE | ID: mdl-8355976

ABSTRACT

The authors investigate the advantage of the intensified insulin therapy and the use of pen-type devices in the practice of the Diabetic Outpatient Clinic of National Institute of Cardiology. The metabolic control improved markedly during intensified insulin therapy already after a short time as three months without any change in the applied dosage. Furthermore pen-type devices have been recognized to let the patients better accept the daily more than two injections, to improve the life-style, and last but not least to decrease the waste quantity of insulin. Authors want to draw attention to the fact that more than 33% of diabetic patients with intensified insulin therapy have a higher demand for insulin, then it could be injected by the pen devices used at this time and by cartridges available in Hungary at this moment. Therefore, availabilities of both cartridges of 3 ml volume would become necessary without any delay.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Insulin Infusion Systems , Insulin/administration & dosage , Adult , Female , Humans , Hungary , Male , Middle Aged
9.
Mol Cell Biochem ; 109(2): 189-96, 1992 Feb 12.
Article in English | MEDLINE | ID: mdl-1320734

ABSTRACT

The aim of this study was to clarify whether or not arachidonic acid metabolic disorders are caused by a substrate inavailability and whether such disorders might contribute to circulatory disturbances in the diabetic myocardium. Norepinephrine induced a decrease in the conductivity of both coronary arterial bed and myocardial microcirculation in alloxan-diabetic dogs. It was markedly (p less than 0.05) attenuated both by indomethacin and acetylsalicylic acid pretreatments indicating an imbalance among the vasoactive prostanoids in diabetes. TXA2 release from the diabetic coronary rings was found to be elevated and could be normalized after the blockade of vascular adrenoceptors by phentolamine (p less than 0.05). PGI2 synthesis was also enhanced by adrenergic blockade in the diabetic arterial rings. After pretreatment with 14C arachidonic acid, in order to measure substrate availability, the arachidonic acid metabolic rate was less in the diabetic coronary arteries than in healty vessels (p less than 0.05). Ten mumol/l norepinephrine decreased arachidonic acid metabolism in the presence of prelabelled substrate in the diabetic animals, compared to an increase observed in metabolically healthy dogs. Therefore diabetes appears to diminish arachidonic acid metabolism and uptake independent of adrenoceptors and to induce an imbalance between vasoconstrictor and vasodilator cyclooxygenase products, resulting in elevated TXA2 release controlled by adrenergic mechanisms which may contribute to an impairment in myocardial microcirculation.


Subject(s)
Arachidonic Acids/metabolism , Coronary Vessels/metabolism , Diabetes Mellitus, Experimental/metabolism , Alloxan , Animals , Aspirin/pharmacology , Coronary Circulation/drug effects , Dogs , Epoprostenol/metabolism , Female , Indomethacin/pharmacology , Male , Microcirculation/drug effects , Myocardium/metabolism , Norepinephrine/pharmacology , Phentolamine/pharmacology , Prazosin/pharmacology , Prostaglandin-Endoperoxide Synthases/metabolism , Receptors, Adrenergic, alpha/drug effects , Thromboxane A2/metabolism , Vasoconstriction/drug effects
10.
Arzneimittelforschung ; 42(2): 111-3, 1992 Feb.
Article in English | MEDLINE | ID: mdl-1610416

ABSTRACT

The effect of glimepiride (CAS 93479-97-1) on the electrical threshold, conduction time, effective refractory period and automaticity of left atrium and right ventricle in the isolated rabbit heart was investigated and compared with those of chlorpropamide and glibenclamide. From the sulphonylureas investigated only glibenclamide diminished the electrical activity of rabbit heart muscle preparations. Chlorpropamide and glimepiride have a mild effect to change the basic parameters on the opposite direction. It seems that glimepiride does not have a significant effect on cardiac muscle in vitro.


Subject(s)
Heart/drug effects , Hypoglycemic Agents/pharmacology , Sulfonylurea Compounds/pharmacology , Animals , Chlorpropamide/pharmacology , Electric Stimulation , Electrophysiology , Female , Heart Conduction System/drug effects , In Vitro Techniques , Male , Rabbits , Refractory Period, Electrophysiological/drug effects
11.
Acta Med Hung ; 49(1-2): 39-51, 1992.
Article in English | MEDLINE | ID: mdl-1296186

ABSTRACT

A retrospective study was performed on 1040 diabetic patients. The survival time of those treated with first generation sulphonylureas (n = 227) was considerably (P < 0.001) shorter after the first attack of angina pectoris (5 +/- 1 years, mean +/- S.E.) or acute myocardial infarction (6 +/- 1 years) than of those (9 +/- 1 years) on glibenclamide treatment (n = 144), with regime alone (n = 282) or treated with insulin (n = 387). The systolic blood pressure of patients with first generation sulphonylureas (166 +/- 1/91 +/- 1 mmHg) proved to be higher (P < 0.01) than those treated with glibenclamide (159 +/- 1/91 +/- 1 mmHg) or being on regime alone (155 +/- 1/89 +/- 1 mmHg) or on insulin (156 +/- 1/89 +/- 1 mmHg) treatments. Serum sodium level was found to be lower (P < 0.05) in patients treated with any kind of sulphonylureas (138 +/- 1 mmol/l) than in the other patients (143 +/- 1 mmol/l). During an observation period, 576 of patients died, 412 of them due to cardiovascular or renal failures. Among the diabetic subjects suffering from coronary heart disease no difference could be detected in risk factors except for higher systolic blood pressure. The shorter survival time of patients treated with first-generation sulphonylureas might be explained by the arrhythmogenic activity of first-generation sulphonylureas. Improvement in therapy, metabolic and cardiovascular alterations during the survey can not be responsible for the shorter survival time of patients treated with first generation-sulphonylureas.


Subject(s)
Coronary Disease/physiopathology , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Sulfonylurea Compounds/therapeutic use , Angina Pectoris/physiopathology , Blood Pressure , Coronary Disease/complications , Coronary Disease/epidemiology , Diabetes Mellitus, Type 2/complications , Female , Humans , Male , Middle Aged , Myocardial Infarction/physiopathology , Retrospective Studies , Risk Factors , Treatment Outcome
12.
Diabetes Res ; 16(4): 193-7, 1991 Apr.
Article in English | MEDLINE | ID: mdl-1802487

ABSTRACT

The vagal function was assessed by oesophageal scintigraphy and cardiovascular autonomic function tests in 65 diabetic patients without gastrointestinal symptoms of autonomic neuropathy and in 20 control subjects. Oesophageal radioisotope transit time was abnormal in 32% of diabetics. Values of cardiovascular function tests were normal in 34% of diabetics while definitive and early signs of cardiac autonomic neuropathy were found in 34% and 32% of diabetics, respectively. The results of oesophageal scintigraphy and cardiovascular function tests were concordant only in 54% of diabetics. Simultaneous impairment of oesophageal motility and cardiovascular (vagal) reflexes could be frequently but not uniformly observed in diabetics. Thus, vagal innervation of different organs (oesophagus and heart) might be affected to different degrees in diabetic patients.


Subject(s)
Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Diabetic Neuropathies/physiopathology , Esophagus/physiopathology , Gastrointestinal Transit , Heart Rate , Muscle, Smooth/physiopathology , Valsalva Maneuver , Diabetes Mellitus, Type 1/diagnostic imaging , Diabetes Mellitus, Type 2/diagnostic imaging , Diabetic Neuropathies/diagnostic imaging , Esophagus/diagnostic imaging , Esophagus/physiology , Female , Humans , Male , Middle Aged , Muscle, Smooth/diagnostic imaging , Muscle, Smooth/physiology , Radionuclide Imaging , Reference Values , Technetium Tc 99m Pentetate
13.
Acta Cardiol ; 46(2): 189-200, 1991.
Article in English | MEDLINE | ID: mdl-2048366

ABSTRACT

For evaluating the clinical significance of QT interval prolongation in diabetics with cardiac autonomic neuropathy (CAN), 53 diabetic patients were followed-up for 5 years or to death and the results of cardiovascular function tests as well as the values of QT intervals were repeatedly determined. At baseline investigation, the QTc intervals were significantly longer in diabetics with definitive (456 +/- 5 ms, mean +/- SEM, n = 17) than those with early (435 +/- 5 ms, n = 13, p less than 0.01) and without (413 +/- 4 ms, n = 23, p less than 0.001) signs of CAN or in controls (414 +/- 5 ms, n = 15, p less than 0.001). Thirteen patients died during the follow-up period (1 without, 2 with early and 10 with definitive signs of CAN) but QTc intervals did not differ significantly between patients with cardiac (456 +/- 9 ms, n = 8) and non-cardiac (459 +/- 15 ms, n = 5) causes of death. At reinvestigation of 40 patients, the severity of CAN worsened in 22 patients, remained unchanged in 15 patients and improved in 3 patients. Accordingly, the mean values of autonomic function tests decreased (beat-to-beat variation from 15 +/- 2 to 9 +/- 1 beats/min, p less than 0.01; 30:15 ratio from 1.19 +/- 0.03 to 1.09 +/- 0.02, p less than 0.01) while QTc interval increased (from 424 +/- 3 to 431 +/- 4 ms, p less than 0.01). It was concluded that CAN carries a poor prognosis in diabetic patients. Nevertheless, QTc interval prolongation could be evaluated as rather an additional sign of CAN than the only explanation for mechanism in the pathogenesis of sudden cardiac death in diabetic patients.


Subject(s)
Autonomic Nervous System Diseases/etiology , Diabetes Complications , Diabetic Neuropathies/etiology , Long QT Syndrome/etiology , Adult , Autonomic Nervous System Diseases/physiopathology , Diabetes Mellitus/mortality , Diabetes Mellitus/physiopathology , Diabetic Neuropathies/mortality , Diabetic Neuropathies/physiopathology , Female , Follow-Up Studies , Heart Function Tests , Humans , Long QT Syndrome/physiopathology , Male , Middle Aged , Prognosis , Reference Values
14.
Diabetes Res Clin Pract ; 11(1): 47-52, 1991 Jan.
Article in English | MEDLINE | ID: mdl-2019235

ABSTRACT

The effects of first generation sulphonylurea compounds carbutamide, gliclazide and tolbutamide as well as second generation compounds glibenclamide and glipizide on the cardiovascular system were investigated in dogs. Six dogs received each compound intravenously at cumulative dose levels of 74, 296, 1184 mumol/kg of carbutamide and tolbutamide, 0.4, 2.0, 10.0 mumol/kg of glibenclamide and glipizide, and 16, 48 and 144 mumol/kg of gliclazide. Mean arterial blood pressure, myocardial contractile force, cardiac output and heart rate were measured. The rate of change of myocardial contractile force development (positive dF/dt), as well as of myocardial relaxation (negative dF/dt) were measured. The first generation sulphonylureas were found, in dogs, to exert a positive inotropic effect in contrast to second generation compounds. The clinical importance of our findings may be in the potential for the malfunction of the cardiovascular system (based on cardiopathy, neuropathy, atherosclerosis, and obesity), developing in diabetes, to be further impaired by the first generation sulphonylureas. Therefore, second generation sulphonylureas should be preferred in the therapy of type 2 diabetics, if satisfactory metabolic control cannot be achieved by dietary management alone and sulphonylurea treatment becomes necessary.


Subject(s)
Blood Glucose/metabolism , Cardiovascular System/drug effects , Hemodynamics/drug effects , Hypoglycemic Agents/pharmacology , Potassium/blood , Sulfonylurea Compounds/pharmacology , Animals , Blood Pressure/drug effects , Body Weight/drug effects , Cardiac Output/drug effects , Dogs , Dose-Response Relationship, Drug , Female , Heart Rate/drug effects , Male , Myocardial Contraction/drug effects , Reference Values , Regression Analysis
15.
Acta Diabetol Lat ; 27(4): 295-301, 1990.
Article in English | MEDLINE | ID: mdl-2087930

ABSTRACT

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)


Subject(s)
Autonomic Nervous System Diseases/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Diabetic Neuropathies/physiopathology , Electrocardiography , Heart Diseases/physiopathology , Adult , Aged , Female , Heart Rate , Humans , Male , Middle Aged , Regression Analysis , Statistics as Topic , Valsalva Maneuver
17.
Cardiovasc Res ; 24(9): 707-10, 1990 Sep.
Article in English | MEDLINE | ID: mdl-2121358

ABSTRACT

STUDY OBJECTIVE: The aim was to determine the role of cyclo-oxygenase products in the vasoconstrictor response of femoral arterial bed to noradrenaline and to analyse the role of vascular adrenoceptors in the synthesis of cyclo-oxygenase products. DESIGN: The influence of intra-arterially injected cyclo-oxygenase inhibitors indomethacin and acetylsalicylic acid on alterations in conductance of femoral arterial bed induced by noradrenaline was compared in metabolically healthy and alloxan diabetic dogs. PGI2 and TXA2 synthesising ability of isolated femoral arterial rings was measured with and without inhibition of alpha adrenoceptors by phentolamine. SUBJECTS: 18 metabolically healthy and 18 alloxan (560 mumol.kg-1) diabetic dogs of either sex, weight 16-28 kg, were studied. MEASUREMENTS AND MAIN RESULTS: Noradrenaline produced greater (p less than 0.01) pressor effects in the femoral arterial bed of alloxan diabetic dogs than in the hind limb of control animals. Blockade of cyclo-oxygenase either by indomethacin 10 mumol.kg-1 or by acetylsalicylic acid 140 mumol.kg-1 markedly reduced the response to noradrenaline in alloxan treated animals, but not in controls, thereby eliminating the different responsiveness of the two groups. Femoral arterial rings from diabetic animals synthesised similar amounts of PGI2 as control rings but formed more TXA2 (p less than 0.05). Phentolamine pretreatment (5 mumol.litre-1) markedly reduced the production of TXA2, but not of PGI2, in diabetic vessels. CONCLUSIONS: The results show an increased release of TXA2 by isolated diabetic femoral arteries. It is therefore suggested that an alpha adrenoceptor mediated increase in TXA2 biosynthesis may play a part in the vascular hyperreactivity of the diabetic femoral arterial bed.


Subject(s)
Diabetes Mellitus, Experimental/physiopathology , Femoral Vein/drug effects , Norepinephrine/pharmacology , Thromboxane A2/biosynthesis , Vasoconstriction/drug effects , Animals , Aspirin/pharmacology , Cyclooxygenase Inhibitors , Diabetes Mellitus, Experimental/metabolism , Dogs , Dose-Response Relationship, Drug , Epoprostenol/biosynthesis , Female , Femoral Vein/metabolism , Femoral Vein/physiopathology , Indomethacin/pharmacology , Male , Organ Culture Techniques , Phentolamine/pharmacology
19.
Cardiology ; 77(1): 9-16, 1990.
Article in English | MEDLINE | ID: mdl-2354481

ABSTRACT

The left ventricular diastolic and systolic functions were assessed in 27 strictly selected type 1 diabetic patients without overt heart disease and 50 age- and sex-matched control subjects. For evaluating left ventricular performance, complex mechanocardiography including digitized apexcardiography was used at rest and after symptom-limited, graded dynamic exercise. The values of diastolic/systolic time intervals and amplitude parameters did not differ significantly between the diabetic and control groups at rest. A longer value of corrected early apexcardiographic relaxation time (diabetics: 38.7 +/- 2.6 ms, controls: 17.3 +/- 2.1 ms, p less than 0.001) and a smaller normalized amplitude of relaxation (diabetics: 0.014 +/- 0.004 ms-1, controls: 0.056 +/- 0.006 ms-1, p less than 0.001) were observed after dynamic exercise suggesting disturbances of the early diastole in diabetic patients. No correlations could be found between the diastolic abnormalities and the diabetic control. Significant correlation was observed between the diastolic disorders and the duration of diabetes mellitus. Testing left ventricular performance by complex mechanocardiography including digitized apexcardiography after dynamic exercise in patients with type 1 diabetes might be useful for recognizing diastolic abnormalities even when no alterations could be identified at rest. Diastolic disorders could appear in diabetic patients without overt heart disease and clinical symptoms. Left ventricular systolic function might be normal, although exercise-induced alterations of diastolic function might already be present in type 1 diabetic patients.


Subject(s)
Diabetes Mellitus, Type 1/physiopathology , Diastole , Exercise Test , Heart/physiopathology , Myocardial Contraction , Adolescent , Adult , Blood Glucose/analysis , Diabetes Mellitus, Type 1/blood , Female , Heart Rate , Humans , Kinetocardiography , Male
20.
Orv Hetil ; 131(3): 119-26, 1990 Jan 21.
Article in Hungarian | MEDLINE | ID: mdl-2405334

ABSTRACT

In a retrospective study of 962 diabetic (male: 441, female: 521) patients in the Diabetic Outpatient Clinic of the National Institute of Cardiology between 1st November 1967 and 31st October 1988 the survival time of diabetics treated with first generation sulphonylureas was considerably less after the first attack of angina pectoris or acute myocardial infarction compared with that of individuals controlled with regime alone or being on glibenclamide or insulin treatments. The systolic blood pressure proved to be higher in diabetics treated with first generation sulphonylureas. During the observation, among the 183 patients on insulin- as well as in the 262 individuals on first and 230 on second generation sulphonylurea treatments, and in the 287 diabetics controlled with regime alone, 547 (male: 241, female: 306) patients died, 403 of them due to cardiovascular and renal failures. Between the diabetics suffering from ischaemic heart diseases no difference could be detected relating the risk factors except the higher systolic blood pressure. The alterations in the cardiovascular states during the survey, the improvement of therapeutical interventions, the alterations in the carbohydrate and lipid metabolism are not supposed to be involved in the shorter survival time of diabetics treated with first generation sulphonylureas. The shorter survival time might be explained by the arrhythmogenic activity of first generation sulphonylureas described in earlier studies. On this basis we are tempted to draw the conclusion that second generation sulphonylureas must be selected in the diabetes care, if the metabolic state could not be normalized by diet and regime only.


Subject(s)
Coronary Disease/chemically induced , Diabetes Mellitus/drug therapy , Hypoglycemic Agents/adverse effects , Sulfonylurea Compounds/adverse effects , Blood Pressure/drug effects , Female , Heart/drug effects , Humans , Male , Middle Aged
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