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  • 1
    ISSN: 1432-0428
    Keywords: Alloxan-diabetes ; coronary artery ; α-adrenergic receptors ; prostacyclin ; thromboxane ; phenylephrine ; phentolamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Before the onset of histologically detectable alterations of diabetic arteries, a considerable decrease of vasodilation ability develops. The role of an altered prostaglandin biosynthesis in this phenomenon was investigated in connection to the altered vascular adrenergic mechanisms. The effect of phenylephrine on prostacyclin production of isolated coronary arterial rings (100 μmol/l) as well as on conductivity of the coronary arterial bed (7.5-15-30-60 pmol·kg−1·min−1) were compared in 12 metabolically healthy and 12 alloxan-diabetic (560 μmol/kg) dogs. Furthermore, the effect of phentolamine (5 μmol/l) on the prostacyclin and thromboxane productions of the isolated vessels (coronary, femoral and basilar arteries) was investigated by radioimmunoassay. Although the basal prostacyclin amounts synthesized by healthy and diabetic coronary vessels were not different (5.1±1.6 and 4.9±1.4pg/mg vessel/30 min), similarly to femoral and basilar arteries, the diabetic arterial rings produced significantly (p〈0.05) more thromboxane than the control rings. The α-adrenergic blockade by phentolamine did not influence the prostacyclin production in the healthy arteries, but considerably (p〈0.05) increased it in the diabetic coronary arteries. Phentolamine normalised the thromboxane synthesis in the diabetic group (p〈0.01) and enhanced (p〈0.05) it in the metabolically healthy group. Phenylephrine was ineffective (98±6%) on the prostacyclin production in vitro versus the stimulated (150±22%) prostacyclin synthesis detected in the metabolically healthy group; and in vivo induced a more significant (p〈0.05) decrease in the coronary conductivity in diabetic than in control groups. These results refer to the supposition that altered adrenergic mechanisms are involved in the imbalamce of the vasoactive prostaglandins contributing to the high incidence of ischaemic heart disease in diabetes mellitus.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Key words Diabetes mellitus ; myocardium ; streptozotocin diabetes ; vitamin E ; endothelium ; coronary vessels ; autonomic neuropathy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Increased oxidative stress has been suggested to contribute to disturbances in the regulation of coronary flow and the increased cardiac risk in diabetes mellitus. Using the isolated perfused heart of streptozotocin-diabetic rats our study shows that basal and maximal coronary flow (tested by infusion of sodium nitroprusside) are not altered in diabetes, but that 5-hydroxytryptamine (5-HT) stimulated endothelium-dependent increase in coronary flow becomes progressively impaired. This defect of the endothelium-dependent vasodilatation was prevented by perfusion of the hearts with superoxide dismutase and pretreatment of the diabetic rats with tocopherol-acetate. Morphological studies also revealed that pretreatment with tocopherol-acetate was cardioprotective, and largely prevented severe alterations of myocardial structure typically observed after a diabetes duration of 3 months; deterioration and fragmentation of myofilament bundles were seen less, and the numbers of areas of focal necrosis and of contraction bands were clearly reduced. In contrast to untreated diabetic hearts the autonomic nerve fibers detected by catecholamine fluorescence were running in parallel in hearts of tocopherol-treated diabetic rats, and the amount of catecholamines was not different from that of healthy control rats. Trichrome staining and immunohistochemical staining of collagen I and III showed a dramatic increase in the number and the size of deposits of collagen fibers at precapillary locations in the diabetic hearts which were significantly reduced by anti-oxidative treatment. These findings demonstrate that oxidative stress may not only play a major role in the impairment of endothelium-dependent regulation of coronary flow, but also in the development of perivascular fibrosis and severe changes of the autonomic nerves and contractile system in myocardium. [Diabetologia (1995) 38: 1157–1168]
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; myocardium ; streptozotocin diabetes ; vitamin E ; endothelium ; coronary vessels ; autonomic neuropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Increased oxidative stress has been suggested to contribute to disturbances in the regulation of coronary flow and the increased cardiac risk in diabetes mellitus. Using the isolated perfused heart of streptozotocin-diabetic rats our study shows that basal and maximal coronary flow (tested by infusion of sodium nitroprusside) are not altered in diabetes, but that 5-hydroxytryptamine (5-HT) stimulated endothelium-dependent increase in coronary flow becomes progressively impaired. This defect of the endothelium-dependent vasodilatation was prevented by perfusion of the hearts with Superoxide dismutase and pretreatment of the diabetic rats with tocopherol-acetate. Morphological studies also revealed that pretreatment with tocopherol-acetate was cardioprotective, and largely prevented severe alterations of myocardial structure typically observed after a diabetes duration of 3 months; deterioration and fragmentation of myofilament bundles were seen less, and the numbers of areas of focal necrosis and of contraction bands were clearly reduced. In contrast to untreated diabetic hearts the autonomic nerve fibers detected by catecholamine fluorescence were running in parallel in hearts of tocopherol-treated diabetic rats, and the amount of catecholamines was not different from that of healthy control rats. Trichrome staining and immunohistochemical staining of collagen I and III showed a dramatic increase in the number and the size of deposits of collagen fibers at precapillary locations in the diabetic hearts which were significantly reduced by anti-oxidative treatment. These findings demonstrate that oxidative stress may not only play a major role in the impairment of endothelium-dependent regulation of coronary flow, but also in the development of perivascular fibrosis and severe changes of the autonomic nerves and contractile system in myocardium.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 38 (1995), S. 509-517 
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; cardiopathy ; ACE-inhibition ; captopril ; BB rats ; regional perfusion ; myocardial function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of this study was to examine the influence of inhibition on angiotensin converting enzyme (ACE) of myocardial function and perfusion of the rat impaired by diabetes. Spontaneously diabetic rats were treated with the ACE-inhibitor captopril for 4 months. Cardiac performance was analysed in the isolated heart perfused at constant volume. Epicardial perfusion was determined by measuring changes in epicardial fluorescence after injection of a bolus of fluoresceinisothiocyanate-dextrane (3 kDa) as described previously. As compared to untreated diabetic controls, captopril prevented the increase of end diastolic pressure, coronary perfusion pressure and vascular resistance. The intravascular volume was enlarged and the epicardial perfusion rate increased in hearts of diabetic rats treated with captopril as compared to diabetic controls. Treatment of diabetic rats with the ACE-inhibitor captopril (1) increases the number of perfused capillaries, and (2) can partly prevent the development of cardiac dysfunction in diabetes. Together with morphological data demonstrating an inhibition of interstitial and perivascular fibrosis in hearts of diabetic rats treated with captopril, our data suggest that ACE-inhibition is cardioprotective in diabetes. These observations are also compatible with the assumption that an accelerated generation of angiotensin II may be involved in the pathophysiological chain of events leading to diabetic cardiopathy.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 38 (1995), S. 509-517 
    ISSN: 1432-0428
    Keywords: Key words Diabetes mellitus ; cardiopathy ; ACE-inhibition ; captopril ; BB rats ; regional perfusion ; myocardial function.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The aim of this study was to examine the influence of inhibition on angiotensin converting enzyme (ACE) of myocardial function and perfusion of the rat impaired by diabetes. Spontaneously diabetic rats were treated with the ACE-inhibitor captopril for 4 months. Cardiac performance was analysed in the isolated heart perfused at constant volume. Epicardial perfusion was determined by measuring changes in epicardial fluorescence after injection of a bolus of fluoresceinisothiocyanate-dextrane (3 kDa) as described previously. As compared to untreated diabetic controls, captopril prevented the increase of end diastolic pressure, coronary perfusion pressure and vascular resistance. The intravascular volume was enlarged and the epicardial perfusion rate increased in hearts of diabetic rats treated with captopril as compared to diabetic controls. Treatment of diabetic rats with the ACE-inhibitor captopril (1) increases the number of perfused capillaries, and (2) can partly prevent the development of cardiac dysfunction in diabetes. Together with morphological data demonstrating an inhibition of interstitial and perivascular fibrosis in hearts of diabetic rats treated with captopril, our data suggest that ACE-inhibition is cardioprotective in diabetes. These observations are also compatible with the assumption that an accelerated generation of angiotensin II may be involved in the pathophysiological chain of events leading to diabetic cardiopathy. [Diabetologia (1995) 38: 509–517]
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Keywords Apoptosis ; proinsulin ; umbilical vein ; endothelial cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary There is much evidence that diabetes and hyperglycaemia contribute to the impairment of endothelial function and induce severe changes in the proliferation, the adhesive and synthetic properties of endothelial cells. Induction of apoptosis could represent one mechanism to prevent the new accumulation of those vascular defects and to allow generation of vascular endothelium. In this study, we demonstrate that high concentrations of glucose or proinsulin induce apoptosis in human umbilical endothelial cells by three independent methods (DNA fragmentation, fluorescence activated cell sorting analysis, and morphology). The number of apoptotic cells was increased by glucose (30 mmol/l or proinsulin (100 nmol/l) from less than 10 % to about 30 %. Activation of protein kinase C (PKC) largely prevented the induction of apoptosis, whereas inhibition of PKC further increased the number of apoptotic cells. Similar changes as induced by glucose were also observed after incubation of the cells with the non-metabolisable 3-0-methylglucose. These findings indicate that hyperglycaemic conditions stimulate the induction of apoptosis in endothelial cells by a mechanism which is independent from the formation of diacylglycerol and the activation of PKC. The induction of apoptosis by the non-metabolisable glucose suggests that formation of oxygen derived radicals by autoxidative processes is involved and may lead to an activation of transcription factors such as nuclear transcription factor-ϰB (NF-ϰB) transferring the activation signal into the nucleus and leading to changes in gene expression necessary for induction of apoptosis. [Diabetologia (1998) 41: 249–256]
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 18 (1980), S. 391-394 
    ISSN: 1432-0428
    Keywords: Prostaglandins ; prostacyclin ; PGE2 ; perfused rat heart ; prostaglandin endoperoxides ; coronary flow ; platelet aggregation ; streptozotocin diabetes ; bioassay
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The release of prostacyclin and PGE2 from the isolated perfused hearts of acutely diabetic (streptozotocin 100 mg/kg) rats was studied and compared with hearts from control animals. Prostacyclin and PGE2 were measured by a differential bioassay technique. No basal release of either prostaglandin was detected. However, after addition of arachidonic acid, a dose dependent release of prostacyclin and PGE2 was noted. Prostacyclin was identified as the major prostaglandin. Release of prostacyclin and PGE2 from acutely diabetic rat hearts was increased 2–3 times compared to control hearts. No release of prostaglandin endoperoxides was observed in either group of hearts.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 67 (1989), S. 253-259 
    ISSN: 1432-1440
    Keywords: Platelet volume ; Thrombopoiesis ; Megakaryocytes ; Glycoprotein IB ; Flow-Cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Increased functional properties of diabetic platelets might be already conditionated during thrombopoiesis in the stem cell system. This hypothesis was studied by recording the distribution characteristics of the peripheral platelet pool in 218 diabetic patients versus 51 controls. Furthermore, platelet membrane coating with the stem cell marker glycoprotein IB was analyzed in 41 diabetic subjects and compared to 23 healthy volunteers. A consistant, significant shift of the volume distribution to larger platelets was found in diabetics: Mean platelet volume (MPV) — 7.9±0.9 versus 7.2±0.8 [fl]; Megathrombocyte index (MTI) — 20.4±2.8 versus 18.1±2.5 [fl]. These deviations were present in all patient subsets, however did not correlate to parameters of glucose metabolism. Whole blood platelet count was increased in the patient group: 195.0±59.5 versus 184.0±37.5×103 plts/ul. Coating with glycoprotein IB receptors correlated significantly to platelet size in platelets of both controls and diabetics (r normal=0.52±0.07;r diabetic=0.46±0.1). The quantitativ expression of glycoprotein IB was significantly enhanced in the diabetic group: 54500×1.28±1 versus 39100×1.3±1 molecules per platelet. In conclusion, these findings strongly support the assumption of diabetic stem cell dysfunction of the megakaryocytic series and progenitor cells resulting in platelets with primarily increased potency to adhere and aggregate in diabetes mellitus.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Zeitschrift für Kardiologie 88 (1999), S. 215-224 
    ISSN: 1435-1285
    Keywords: Schlüsselwörter Koronare Herzerkrankung – diabetische Kardiopathie – endotheliale Dysfunktion – korpuskuläre Hyperreaktivität – Diabetes mellitus ; Key words Coronary artery disease – diabetic cardiopathy – endothelial dysfunction – corpuscular hyperreactivity – metabolic syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Most people with the Metabolic Syndrome die from thrombotic complications superimposed to degenerative arterial vascular lesions, mostly myocardial infarction. Type-2-Diabetes is a risk factor per se for such complications, but often clusters with dyslipoproteinemia, hypertension and obesity. This is referred to as “Metabolic Syndrome” and often operates on a genetically programmed susceptibility which accelerates the pathogenesis of coronary artery disease in front of a much wider diabetes specific cardiopathy. From a pathophysiological point of view none of these associated risk factors explains the pathogenetic series of events leading to the precipitation of an occlusive thrombus at sites of complicated coronary plaques. In patients with the Metabolic Syndrome the coagulation system is switched towards a prethrombotic state, involving increased plasmatic coagulation, diminished fibrinolysis, decreased endothelial thromboresistance and predominantly platelet hyperreactivity (“diabetic thrombocytopathy”). Some of these factors are associated with an increased coronary risk (e.g. fibrinogen, PAI-1, platelets), but are also directly linked to the pathogenesis of “atherothrombosis”. Altered cardiac remodelling together with adhesion and coagulation mechanisms appears suitable to explain decreased functional performance of infarcted organs, decreased success of acute (reduced fibrinolytic response, no reflow phenomenon) and longterm intervention strategies for vessel patency (PTCA, CABG) in Diabetes. Glucose adjustment alone will not adequately neutralize these complex mechanisms, but in the situation of myocardial infarction eumetabolization with parenteral glucose-insulin-potassium infusion appears mandatory similar to non-diabetics. On the longterm a multidimensional interventional repertoire is required particularly in patients with the Metabolic Syndrome including antihypertensive, antidyslipoproteinemic and antithrombotic drugs, customized according to the individual patients needs as assessed by early diagnostic measures (“early secondary prevention”).
    Notes: Zusammenfassung Über 75% der Patienten mit Diabetes mellitus sterben an ischämischen Gefäßereignissen, mehrheitlich dem Herzinfarkt. Der überwiegende Teil der Fälle von Typ-2-Diabetes tritt regelhaft im Rahmen eines Risikofaktorenclusters aus Dyslipoproteinämie, Hypertonie und Adipositas (“metabolisches Syndrom”) auf. Dies ereignet sich häufig vor einem genetisch determinierten Hintergrund, der die pathogenetische Bedeutung dieser Risikofaktoren, insbesondere für das Herz, erhöht. Diese epidemiologischen Risikofaktoren allein können jedoch die pathogenetische Sequenz der okklusiven koronaren Herzkrankheit bis zum Infarkt nicht hinreichend erklären. Das Gerinnungssystem spielt dabei eine entscheidende Rolle. Es befindet sich in einem labilen Gleichgewicht (“präthrombotischer Zustand”): erhöhte Verfügbarkeit plasmatischer Koagulatoren, verminderte Fibrinolyse, verminderte endotheliale Thromboresistenz sowie korpuskuläre Hyperreaktivität des Blutes. Einige Faktoren dieses Gerinnungsnetzwerkes sind direkt bei der Entstehung des ischämischen Endpunktes, d. h. der Thrombusbildung, involviert (z. B. Thrombozyten, PAI-1 oder Fibrinogen). Die Kombination struktureller Veränderungen des Arbeitsmyokards zusammen mit der Hyperkoagulabilität des Blutes können die schlechte funktionelle Reserve infarzierter Diabetikerherzen erklären und sind für den deutlich reduzierten Erfolg von akuten (Fibrinolyse) und längerfristigen Interventionen zur Erlangung von Gefäßoffenheit (PTCA, CABG) verantwortlich. Eine metabolische Kontrolle alleine kann diese komplexe Interdependenz zwischen Risikofaktoren und ihren mittelbaren Konsequenzen nicht neutralisieren, ist aber eine zwingende Voraussetzung zur Verbesserung der Prognose akuter Koronarsyndrome. Gerade bei Diabetikern ist eine mehrdimensionale Intervention erforderlich, die eine Beratung zu gesunder Lebensführung (z. B. Nikotinkarenz) einschließt und sich neben genereller Normalisierung von Blutdruck, Blutfetten sowie der Hyperkoagulabilität an den individuellen Erfordernissen der Patienten orientiert.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-1238
    Keywords: ARDS ; Extracorporeal circulation ; Extracorporeal CO2-removal ; Extracorporeal membrane oxygenation ; Gas exchange
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Extracorporeal circulation can cause lung damage, which would be especially counterproductive during extracorporeal gas exchange for the treatment of acute respiratory failure. To test the hypothesis that partial venovenous bypass with extracorporeal CO2-removal combined with low-frequency positive pressure ventilation (ECCO2R-LFPPV) can adversely affect lung fluid balance, extravascular thermal lung volume (ETV) and hemodynamics were assessed before, during and after ECCO2R-LFPPV in normal closed ehest dogs. In series I dogs (n=6) subjected to 10 h of ECCO2R-LFPPV, ETV did not change significantly from control (7.1 ml/kg±0.99 SE) during or after bypass. Gravimetric extravascular lung water and lung histology after bypass were found to be normal. In series II dogs (n=5), subjected to shorter periods of ECCO2R-LFPPV, ETV also remained unchanged. In contrast to previous reports using sheep, pulmonary arterial hypertension during bypass was not observed. Thus, ECCO2R-LFPPV was not associated with increased lung water, pulmonary hypertension or morphological lung changes under the conditions studied and does not seem to cause lung damage in normal lungs.
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