Cardiac dysfunction in isolated perfused hearts from spontaneously diabetic BB rats

1990 ◽  
Vol 68 (4) ◽  
pp. 514-518 ◽  
Author(s):  
Brian Rodrigues ◽  
John H. McNeill
Keyword(s):  
Cardiac Function ◽  
Heart Function ◽  
Insulin Dose ◽  
Cardiac Contractility ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Myosin Atpase ◽  
Bb Rat ◽  
Relaxation Rates ◽  
Bb Rats

The purpose of this investigation was to examine cardiac function and biochemistry in spontaneously diabetic BB rats, a strain in which diabetes occurs spontaneously and closely resembles insulin-dependent diabetes in humans. The study involved two groups: nondiabetic littermates of BB rats and BB diabetic rats treated daily with a very low insulin dose such that the rats were severely hyperglycemic and hyperlipidemic. The hearts from these two groups were isolated and heart function (using isolated perfused working hearts) and biochemistry were examined 6 weeks after the onset of diabetes. BB diabetic rats exhibited a lower calcium-stimulated myosin ATPase activity and depressed left ventricular developed pressure, cardiac contractility, and ventricular relaxation rates compared with BB nondiabetic littermates. These results suggest that the chronically diabetic state in the BB rat produces cardiac changes similar to those demonstrable after chemical diabetes induced by alloxan or STZ, or that seen during human diabetes mellitus.Key words: diabetes, cardiac function, Wistar BB rat, myosin ATPase, cardiomyopathy.

Cardiac function in spontaneously diabetic BB rats treated with low and high dose insulin

1989 ◽  
Vol 67 (6) ◽  
pp. 629-636 ◽  
Author(s):  
Brian Rodrigues ◽  
Gail M. McGrath ◽  
John H. McNeill
Keyword(s):  
Cardiac Function ◽  
Calcium Transport ◽  
Heart Function ◽  
Insulin Dose ◽  
Diabetic Rats ◽  
Diabetic Group ◽  
Bb Rat ◽  
High Dose ◽  
Drug Induced ◽  
Bb Rats

Cardiac abnormalities observed in animals with drug-induced diabetes may be due to the direct cardiotoxic effect of the drugs or factors not related to the diabetic state. The purpose of this investigation was to examine cardiac sarcoplasmic reticular (SR) calcium transport and heart function in the BB rat, a strain in which diabetes occurs spontaneously and clearly resembles insulin-dependent diabetes in humans. Complete insulin withdrawal for 2 or 4 days from BB diabetic rats leads to a spectrum of metabolic derangements including a loss of body weight, hyperglycemia, and elevated triglyceride levels confirming the insulin dependence of this model. The present study involved treating BB diabetic rats with a low (hyperglycemic) and high (normoglycemic) insulin dose for 12 weeks after the detection of glycosuria. The hearts from these animals were then isolated, and SR Ca2+ transport and heart function (using isolated perfused working hearts) were examined and compared with BB nondiabetic littermates or Wistar controls. Strain-related differences were found in ATP-dependent SR Ca2+ transport between the Wistar and BB rats. There were, however, no significant diabetes-related differences in SR Ca2+ transport between the low dose insulin treated diabetic group (LD) and the high dose insulin treated diabetic group (HD) or the nondiabetic littermates. Plasma lipid concentrations of the LD and HD BB rats and nondiabetic littermates were also generally higher than those of control Wistar rats indicating strain-related but not diabetes-related differences. In addition, there were no differences in cardiac function between the LD and BB nondiabetic littermates or Wistar controls. These studies suggest that since persistent hyperglycemia in the LD BB rat produced no significant physiological abnormalities in the heart, other factors must be contributing to the depression of heart function noted during diabetes.Key words: diabetes, BB rat, sarcoplasmic reticular calcium transport, heart function.

Cardiac function in spontaneously hypertensive diabetic rats

1986 ◽  
Vol 251 (3) ◽  
pp. H571-H580 ◽  
Author(s):  
B. Rodrigues ◽  
J. H. McNeill
Keyword(s):  
Cardiac Function ◽  
Heart Function ◽  
Myocardial Dysfunction ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Developed Pressure ◽  
Working Heart ◽  
Diabetes Induction

The isolated perfused working heart was used to study hypertensive diabetes-induced alterations in cardiac function at 6 and 12 wk after diabetes was induced. At 6 wk after diabetes induction, cardiac performance was depressed in the diabetic animals. However, there was no difference in cardiac function between normotensive Wistar and spontaneously hypertensive (SHR) diabetic rats. Wistar-Kyoto (WKY) rats were also included as normotensive controls in our 12-wk study. Hearts from 12-wk SHR and Wistar diabetic animals exhibited a depressed left ventricular developed pressure and positive and negative dP/dt when compared with control animals. However, this depression was not seen in the WKY diabetic animals. In addition, quantitation of various parameters of heart function revealed highly significant differences between SHR diabetic animals and all other groups associated with an increased mortality. Serum lipids were elevated in SHR and Wistar and were unaffected in WKY diabetic rats. Furthermore, thyroid hormone levels were not depressed in WKY diabetic rats as seen in the other two diabetic groups. This normal lipid metabolism and thyroid status could, in part, explain the lack of cardiac dysfunction in these animals. The data provide further evidence that the combination of hypertension and diabetes mellitus produces greater myocardial dysfunction than with either disease alone and is associated with a significant mortality.

Alterations of heart function and Na+-K+-ATPase activity by etomoxir in diabetic rats

1999 ◽  
Vol 86 (3) ◽  
pp. 812-818 ◽  
Author(s):  
Kiminori Kato ◽  
Donald C. Chapman ◽  
Heinz Rupp ◽  
Anton Lukas ◽  
Naranjan S. Dhalla
Keyword(s):  
Heart Rate ◽  
Cardiac Function ◽  
Atpase Activity ◽  
Binding Sites ◽  
Heart Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Carnitine Palmitoyltransferase ◽  
Heart Weight ◽  
High Affinity

To examine the role of changes in myocardial metabolism in cardiac dysfunction in diabetes mellitus, rats were injected with streptozotocin (65 mg/kg body wt) to induce diabetes and were treated 2 wk later with the carnitine palmitoyltransferase inhibitor (carnitine palmitoyltransferase I) etomoxir (8 mg/kg body wt) for 4 wk. Untreated diabetic rats exhibited a reduction in heart rate, left ventricular systolic pressure, and positive and negative rate of pressure development and an increase in end-diastolic pressure. The sarcolemmal Na+-K+-ATPase activity was depressed and was associated with a decrease in maximal density of binding sites (Bmax) value for high-affinity sites for [3H]ouabain, whereas Bmax for low-affinity sites was unaffected. Treatment of diabetic animals with etomoxir partially reversed the depressed cardiac function with the exception of heart rate. The high serum triglyceride and free fatty acid levels were reduced, whereas the levels of glucose, insulin, and 3,3′,-5-triiodo-l-thyronine were not affected by etomoxir in diabetic animals. The activity of Na+-K+-ATPase expressed per gram heart weight, but not per milligram sarcolemmal protein, was increased by etomoxir in diabetic animals. Furthermore, Bmax (per g heart wt) for both low-affinity and high-affinity binding sites in control and diabetic animals was increased by etomoxir treatment. Etomoxir treatment also increased the depressed left ventricular weight of diabetic rats and appeared to increase the density of the sarcolemma and transverse tubular system to normalize Na+-K+-ATPase activity. Therefore, a shift in myocardial substrate utilization may represent an important signal for improving the depressed cardiac function and Na+-K+-ATPase activity in diabetic rat hearts with impaired glucose utilization.

Hypertriglyceridemia in experimental diabetes: relationship to cardiac dysfunction

1994 ◽  
Vol 72 (5) ◽  
pp. 447-455 ◽  
Author(s):  
Brian Rodrigues ◽  
Paul F. Grassby ◽  
Mary L. Battell ◽  
Stephanie Y. N. Lee ◽  
John H. McNeill
Keyword(s):  
Cardiac Function ◽  
Cardiac Dysfunction ◽  
Heart Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Plasma Triglyceride ◽  
Diabetic Rat ◽  
Diabetic Patients ◽  
Beneficial Effects ◽  
Rate Of Increase

The incidence of mortality from cardiovascular disease is higher in diabetic patients. The objective of the present investigation was to test die hypothesis that the diabetes-induced depression in cardiac function may be due to hypertriglyceridemia. Hyperlipidemia and a depressed left ventricular developed pressure and rate of increase and decrease of ventricular pressure (±dP/dt) were produced in isolated hearts from rats made diabetic with streptozotocin compared with hearts from control animals. This depressed cardiac performance was successfully prevented by hydralazine treatment (for 3 weeks), which also lowered plasma triglyceride levels and suggested that hyperlipidemia may be important in altering cardiac function in experimental diabetic rats. The beneficial effects of clofibrate, verapamil, prazosin, enalapril, and benazepril administration were then studied in diabetic rats. The treatments (with die exception of enalapril) significantly reduced plasma triglyceride levels but did not prevent die onset of heart dysfunction in chronically diabetic rats. These studies suggest that in the chronically diabetic rat, hypertriglyceridemia may not be as important as previously suggested, in the development of cardiac dysfunction. Since acute dichloroacetate perfusion improves cardiac function in 6 week (but not 24 week) diabetic rats, it appears more likely that improving myocardial glycose utilization is more critical than triglyceride lowering, in preventing cardiac dysfunction in die diabetic rat at this time point.Key words: diabetes, triglycerides, heart function, glucose oxidation.

Cardiac function and myosin ATPase in diabetic rats treated with insulin, T3, and T4

1983 ◽  
Vol 244 (4) ◽  
pp. H592-H598 ◽  
Author(s):  
D. W. Garber ◽  
A. W. Everett ◽  
J. R. Neely
Keyword(s):  
Heart Rate ◽  
Cardiac Function ◽  
Atpase Activity ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Myosin Atpase ◽  
Myosin Atpase Activity ◽  
Pressure Development ◽  
Serum T3 ◽  
Myosin Isozyme

The effects of insulin, T4, and T3 treatment on cardiac function, myosin ATPase activity, and myosin isozyme distribution were studied in alloxan diabetic rats. Diabetes resulted in depressed peak ventricular pressure development, heart rate, and left ventricular +dP/dt. Myocardial Ca2+-activated myosin ATPase activity was reduced in association with lower serum levels of T3 and T4. The V1 isozyme of myosin decreased, and both V2 and V3 isozymes increased. Insulin treatment totally reversed the changes in function, serum thyroid hormones, and myosin ATPase activity. Treatment of diabetic animals with T4 (5 or 10 micrograms/day) prevented the decrease in myosin ATPase but did not prevent the changes in cardiac function, myosin isozymes, or serum T3 levels. Pharmacological doses of T3 (3 micrograms/day) that were adequate to maintain higher than normal serum T3 corrected the decrease in Ca2+-activated myosin ATPase and heart rate but only partially corrected the changes in pressure development and myosin isozyme distribution. Only when serum T3 was increased to four times normal was cardiac function corrected.

Working heart function in diabetes is not improved by spironolactone treatment

2003 ◽  
Vol 81 (5) ◽  
pp. 493-496 ◽  
Author(s):  
Subodh Verma ◽  
Violet G Yuen ◽  
Mitesh Badiwala ◽  
Todd J Anderson ◽  
John H McNeill
Keyword(s):  
Cardiac Function ◽  
Heart Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Cardiac Complications ◽  
Potential Contribution ◽  
Receptor Blockade ◽  
Beneficial Effects ◽  
Aldosterone Receptor ◽  
Working Heart

Aldosterone antagonism has emerged as an important strategy for end-stage congestive heart failure. To evaluate the potential contribution of aldosterone towards the cardiac complications of diabetes, this study examined the effects of chronic aldosterone receptor blockade (with spironolactone) on isolated working heart function in streptozotocin (STZ) - induced diabetic rats. Wistar rats were divided into four groups: control, control spironolactone-treated, diabetic, and diabetic spironolactone-treated. Following chronic spironolactone treatment (8 weeks), cardiac function was assessed in terms of the rate of contraction (+dP/dT), rate of relaxation (–dP/dT), and left ventricular developed pressure (LVDP). Untreated diabetic rats exhibited marked cardiac dysfunction when compared with age matched controls (p < 0.001). Long-term spironolactone treatment did not improve these parameters. These data demonstrate the lack of beneficial effects of aldosterone receptor blockade on isolated working heart function in diabetes.Key words: aldosterone, streptozotocin-induced diabetes, aldosterone receptor blocker, spironolactone, cardiac function.

scholarly journals Sodium–glucose co‐transporter 2 inhibition with empagliflozin improves cardiac function in non‐diabetic rats with left ventricular dysfunction after myocardial infarction

2019 ◽  
Vol 21 (7) ◽  
pp. 862-873 ◽  
Author(s):  
Salva R. Yurista ◽  
Herman H.W. Silljé ◽  
Silke U. Oberdorf‐Maass ◽  
Elisabeth‐Maria Schouten ◽  
Mario G. Pavez Giani ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Function ◽  
Left Ventricular Dysfunction ◽  
Ventricular Dysfunction ◽  
Diabetic Rats ◽  
Left Ventricular

Muscle metabolism and cardiac function of the myopathic hamster following training

1977 ◽  
Vol 43 (6) ◽  
pp. 936-941 ◽  
Author(s):  
W. L. Sembrowich ◽  
M. B. Knudson ◽  
P. D. Gollnick
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Function ◽  
Myocardial Function ◽  
Cardiac Contractility ◽  
Muscle Metabolism ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Treadmill Running ◽  
Succinate Dehydrogenase Activity ◽  
Positive Effect

The effect of 18 wk of treadmill running on skeletal muscle metabolism and myocardial function of normal and myopathic hamsters was examined. BIO 14.6 hamsters could tolerate an exercise intensity of about 18 m/min for 40 min, 5 days/wk. Further increases in speed or number of bouts per day resulted in a falloff in performance. Normal hamsters could tolerate higher speeds and longer exercise bouts. Exercise did not change the severity of lesions of either the heart or skeletal muscle of the myopathic hamsters. A training effect was evidenced by increased succinate dehydrogenase activity in the soleus muscle. Cardiac function was evaluated as contractility measured from left ventricular pressure curves and expressed as (dP/dt)/kP. The results suggested that cardiac contractility was not as severely depressed in the trained BIO 14.6 strain of hamsters as in nontrained controls. However, (dP/dt)/kP was lower in the trained myopathic animals than in normal hamsters. ATP, CP, and glycogen levels were lower in myopathic hamsters with the lowest values occurring in the trained group. These data demonstrate that the BIO 14.6 strain of hamster can tolerate exercise training and that such training may have a positive effect on cardiac function.

Improvement in cardiac dysfunction in streptozotocin-induced diabetic rats following chronic oral administration of bis(maltolato)oxovanadium(IV)

1993 ◽  
Vol 71 (3-4) ◽  
pp. 270-276 ◽  
Author(s):  
Violet G. Yuen ◽  
Chris Orvig ◽  
Katherine H. Thompson ◽  
John H. McNeill
Keyword(s):  
Blood Glucose ◽  
Heart Function ◽  
Myocardial Dysfunction ◽  
Plasma Lipid ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Patients ◽  
Vanadium Complex ◽  
Significant Correction ◽  
Streptozotocin Diabetic Rats

Decreased cardiac function in streptozotocin-diabetic rats has been used as a model of diabetes-induced cardiomyopathy, which is a secondary complication in diabetic patients. The present study was designed to evaluate the therapeutic effect of a new organic vanadium complex, bis(maltolato)oxovanadium(IV), (BMOV), in improving heart function in streptozotocin-diabetic rats. There were four groups of male, Wistar rats: control (C), control treated (CT), diabetic (D), and diabetic treated (DT). Treatment consisted of BMOV, 0.5 mg/mL (1.8 mM) for the first 3 weeks and 0.75 mg/mL (2.4 mM) for the next 22 weeks, in the drinking water of rats allowed ad libitum access to food and water. BMOV lowered blood glucose to < 9 mM in 70% of DT animals without any increase in plasma insulin levels, and mean blood glucose and plasma lipid levels were significantly lower in DT vs. D rats. Tissue vanadium levels were measured in plasma, bone, kidney, liver, muscle, and fat of BMOV-treated rats. Plasma vanadium levels averaged 0.84 ± 0.07 μg/mL (16.8 μM) in CT rats and 0.76 ± 0.05 μg/mL (15.2 μM) in DT animals. The highest vanadium levels at termination of this chronic feeding study were in bone, 18.3 ± 3.0 μg/g (0.37 μmol/g) in CT and 26.4 ± 2.6 μg/g (0.53 μmol/g) in DT rats, with intermediate levels in kidney and liver, and low, but detectable levels in muscle and fat. There were no deaths in either the CT or DT group, and no overt signs of vanadium toxicity were present. Tissue vanadium levels were not correlated with the glucose-lowering effect. Isolated working heart parameters of left ventricular developed pressure (LVDP) and rate of pressure development (+dP/dT, and −dP/dT) indicated that BMOV treatment resulted in significant correction of the heart dysfunction associated with streptozotocin-induced diabetes in rat.Key words: bis(maltolato)oxovanadium(IV), vanadium, diabetes, streptozotocin, myocardial dysfunction.

Impaired nitric oxide production in coronary endothelial cells of the spontaneously diabetic BB rat is due to tetrahydrobiopterin deficiency

2000 ◽  
Vol 349 (1) ◽  
pp. 353-356 ◽  
Author(s):  
Cynthia J. MEININGER ◽  
Rebecca S. MARINOS ◽  
Kazuyuki HATAKEYAMA ◽  
Raul MARTINEZ-ZAGUILAN ◽  
Jose D. ROJAS ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
De Novo ◽  
Diabetic Rats ◽  
Bb Rat ◽  
No Production ◽  
Gtp Cyclohydrolase I ◽  
Gtp Cyclohydrolase ◽  
Bb Rats ◽  
Metabolic Basis ◽  
Rate Limiting

Endothelial cells (EC) from diabetic BioBreeding (BB) rats have an impaired ability to produce NO. This deficiency is not due to a defect in the constitutive isoform of NO synthase in EC (ecNOS) or alterations in intracellular calcium, calmodulin, NADPH or arginine levels. Instead, ecNOS cannot produce sufficient NO because of a deficiency in tetrahydrobiopterin (BH4), a cofactor necessary for enzyme activity. EC from diabetic rats exhibited only 12% of the BH4 levels found in EC from normal animals or diabetes-prone animals which did not develop disease. As a result, NO synthesis by EC of diabetic rats was only 18% of that for normal animals. Increasing BH4 levels with sepiapterin increased NO production, suggesting that BH4 deficiency is a metabolic basis for impaired endothelial NO synthesis in diabetic BB rats. This deficiency is due to decreased activity of GTP-cyclohydrolase I, the first and rate-limiting enzyme in the de novo biosynthesis of BH4. GTP-cyclohydrolase activity was low because of a decreased expression of the protein in the diabetic cells.

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