Biochemical and functional changes in hearts from rabbits with diabetes

Bhimji, Shabir; Godin, David V.; McNeill, John H.

doi:10.1007/bf00280890

Cited by 41 publications

(12 citation statements)

References 32 publications

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“…Most rabbits given alloxan developed diabetes. However, in agreement with a previous study (2), a smaller group of rabbits had no evidence of diabetes despite administration of a standard dose of alloxan. Myocytes from this group were studied to examine whether effects of alloxan on the Na ϩ -K ϩ pump may be independent of the development of diabetes.…”

Section: Resultssupporting

confidence: 90%

Alloxan-induced diabetes reduces sarcolemmal Na⁺-K⁺ pump function in rabbit ventricular myocytes

Hansen¹,

Clarke²,

Buhagiar³

et al. 2007

American Journal of Physiology-Cell Physiology

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The effect of diabetes on sarcolemmal Na(+)-K(+) pump function is important for our understanding of heart disease associated with diabetes and design of its treatment. We induced diabetes characterized by hyperglycemia but no other major metabolic disturbances in rabbits. Ventricular myocytes isolated from diabetic rabbits and controls were voltage clamped and internally perfused with the whole cell patch-clamp technique. Electrogenic Na(+)-K(+) pump current (I(p), arising from the 3:2 Na(+)-to-K(+) exchange ratio) was identified as the shift in holding current induced by Na(+)-K(+) pump blockade with 100 micromol/l ouabain in most experiments. There was no effect of diabetes on I(p) recorded when myocytes were perfused with pipette solutions containing 80 mmol/l Na(+) to nearly saturate intracellular Na(+)-K(+) pump sites. However, diabetes was associated with a significant decrease in I(p) measured when pipette solutions contained 10 mmol/l Na(+). The decrease was independent of membrane voltage but dependent on the intracellular concentration of K(+). There was no effect of diabetes on the sensitivity of I(p) to extracellular K(+). Pump inhibition was abolished by restoration of euglycemia or by in vivo angiotensin II receptor blockade with losartan. We conclude that diabetes induces sarcolemmal Na(+)-K(+) pump inhibition that can be reversed with pharmacological intervention.

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Section: Resultssupporting

confidence: 90%

Alloxan-induced diabetes reduces sarcolemmal Na⁺-K⁺ pump function in rabbit ventricular myocytes

Hansen¹,

Clarke²,

Buhagiar³

et al. 2007

American Journal of Physiology-Cell Physiology

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“…These abnormalities are characteristic of those described for diabetic rats 20 -28 " 30 and rabbits. 31 " 33 The increase of left ventricular chamber volume relative to heart mass in diabetic rabbit hearts confirms a similar observation in rat hearts 28 and is suggestive of a dilated diabetic cardiomyopathy. Despite these abnormalities of cardiac function, diabetes did not increase the severity of ischemic injury in the isolated heart or coronary ligation preparations.…”

Section: Discussionsupporting

confidence: 77%

Effects of alloxan-induced diabetes on ischemia-reperfusion injury in rabbit hearts.

Vogel

Apstein

1988

Circulation Research

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Hearts from rabbits with 8-16 weeks of alloxan-diabetes were compared with hearts from normal rabbits to determine whether diabetic myocardium is more sensitive to ischemic injury. In isolated buffer-perfused hearts, left ventricular developed pressure, diastolic pressure, time to peak pressure (TTPP), time to half-maximal relaxation (RT^), and positive and negative dP/dt were measured during generation of left ventricular filling curves before and after 90 minutes of low-flow ischemia. Hearts from diabetic rabbits (blood glucose, 384 ±28 mg/dl, mean ±95% confidence limits) had left ventricular developed and diastolic pressures similar to normal hearts but exhibited significant increases in TTPP and RT^ with decreased positive and negative dP/dt. Left ventricular chamber volume relative to heart mass was greater in diabetic than in normal hearts. Recovery of developed pressure after ischemia was similar in normal (41 ± 16%) and diabetic hearts (47 ± 13%). In diabetic hearts during recovery from ischemia, TTPP and R m remained increased compared with normal hearts, with positive and negative dP/dt decreased compared with normal hearts, in proportion to the preischemic differences. After ischemia, high-energy phosphates were depleted to the same extent in normal and diabetic rabbits. In coronary ligation experiments, histochemically determined infarct size in diabetic rabbits after 30 minutes occlusion and 24 hours reperfusion was similar to that in normal rabbits when adjusted for a significantly smaller heart weight and a correspondingly smaller anatomic risk region in the diabetic animals. Thus, despite characteristic abnormalities of mechanical function in diabetic hearts, the severity of injury after ischemia with reperfusion was normal for diabetic hearts.

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“…This conclusion is also supported by experimental studies using animal models in which diabetes was induced chemically or developed spontaneously as in BB rats [4][5][6][7]. It has been postulated that wall thickening and luminal narrowing of the intramural coronary microvasculature [3,8] reduce the coronary flow reserve [3,8] and limit the adaptation of coronary flow to the metabolic demand.…”

mentioning

confidence: 85%

Endothelial relaxation is disturbed by oxidative stress in the diabetic rat heart: influence of tocopherol as antioxidant

Rösen

Ballhausen

Bloch³

et al. 1995

Diabetologia

147

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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[Diabetologia ( ) 38: 1157[Diabetologia ( -1168

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Biochemical and functional changes in hearts from rabbits with diabetes

Cited by 41 publications

References 32 publications

Alloxan-induced diabetes reduces sarcolemmal Na⁺-K⁺ pump function in rabbit ventricular myocytes

Alloxan-induced diabetes reduces sarcolemmal Na⁺-K⁺ pump function in rabbit ventricular myocytes

Effects of alloxan-induced diabetes on ischemia-reperfusion injury in rabbit hearts.

Endothelial relaxation is disturbed by oxidative stress in the diabetic rat heart: influence of tocopherol as antioxidant

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Biochemical and functional changes in hearts from rabbits with diabetes

Cited by 41 publications

References 32 publications

Alloxan-induced diabetes reduces sarcolemmal Na+-K+ pump function in rabbit ventricular myocytes

Alloxan-induced diabetes reduces sarcolemmal Na+-K+ pump function in rabbit ventricular myocytes

Effects of alloxan-induced diabetes on ischemia-reperfusion injury in rabbit hearts.

Endothelial relaxation is disturbed by oxidative stress in the diabetic rat heart: influence of tocopherol as antioxidant

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Alloxan-induced diabetes reduces sarcolemmal Na⁺-K⁺ pump function in rabbit ventricular myocytes

Alloxan-induced diabetes reduces sarcolemmal Na⁺-K⁺ pump function in rabbit ventricular myocytes