Effects of triiodothyronine and carnitine therapy on myocardial dysfunction in diabetic rats

1986 ◽  
Vol 64 (6) ◽  
pp. 669-672 ◽  
Author(s):  
Arun G. Tahiliani ◽  
John H. McNeill
Keyword(s):  
Left Atrial ◽  
Calcium Uptake ◽  
Myocardial Dysfunction ◽  
Diabetic Rats ◽  
Myosin Atpase ◽  
Myocardial Performance ◽  
Cardiac Myosin ◽  
Heart Preparation ◽  
Streptozotocin Diabetic Rats ◽  
Working Heart

Streptozotocin-diabetic rats were treated with a combination of triiodothyronine and carnitine for 6 weeks. These compounds were used as they are known to correct the diabetes-induced depression of cardiac myosin ATPase and sarcoplasmic reticular (SR) calcium uptake, respectively. Myocardial performance, which was assessed using the working heart preparation, revealed a depression of function in untreated diabetics when compared with controls at most left atrial filling pressures. Hearts from diabetic rats treated with the combination exhibited depression at only the higher filling pressures as compared with untreated or treated controls. The results suggest that functional alterations occurring as a result of diabetes cannot be accounted for by the depression of cardiac myosin ATPase and SR calcium uptake alone.

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.

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.

Improvement in cardiac function in streptozotocin-diabetic rats by salt loading

1994 ◽  
Vol 72 (11) ◽  
pp. 1288-1293 ◽  
Author(s):  
Soter Dai ◽  
Heather Fraser ◽  
Violet G. Yuen ◽  
John H. McNeill
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Cardiac Function ◽  
Body Weight Gain ◽  
Myocardial Dysfunction ◽  
Streptozotocin Diabetes ◽  
Diabetic Rats ◽  
Salt Loading ◽  
Glucose Levels ◽  
Streptozotocin Diabetic Rats

Effects of salt loading by drinking 0.9% NaCl solution on the myocardial performance in nondiabetic and diabetic Wistar rats were studied using the isolated working heart apparatus. Body weight and fluid and food intakes of these animals were monitored. Blood pressure and plasma levels of glucose, insulin, cholesterol, and triglycerides were also measured. Diabetes was induced by intravenous injection of streptozotocin (60 mg/kg). Diabetic rats were found to develop myocardial dysfunction at 8 weeks after STZ injection, accompanied by significant increases in food and fluid intakes, slowed body weight gain, hyperglycemia, hypoinsulinemia, and hyperlipidemia but without significant changes in blood pressure. Salt loading did not cause significant changes in any of the parameters studied in nondiabetic rats. However, in streptozotocin-diabetic rats given saline to drink, the impaired myocardial function was significantly improved and was associated with a significant reduction in hyperphagia and hyperlipidemia. Plasma glucose levels significantly decreased at weeks 1–3 but increased to the levels of untreated diabetic animals at weeks 4–7. There was an increase in fluid intake, but neither blood pressure nor plasma insulin levels were significantly affected. It is suggested that the improvements in cardiac function and hyperlipidemia in diabetic rats by salt loading may be related to each other; however, the mechanisms for these effects are not clear but are unlikely to be due to changes in glycemic control.Key words: streptozotocin diabetes, salt loading, cardiac dysfunction.

scholarly journals Myocardial performance in conscious streptozotocin diabetic rats

2006 ◽  
Vol 5 (1) ◽  
Author(s):  
Giulianna R Borges ◽  
Mauro de Oliveira ◽  
Helio C Salgado ◽  
Rubens Fazan
Keyword(s):  
Diabetic Rats ◽  
Myocardial Performance ◽  
Streptozotocin Diabetic Rats

T3 treatment does not prevent myocardial dysfunction in chronically diabetic rats

1988 ◽  
Vol 254 (2) ◽  
pp. H265-H273
Author(s):  
R. W. Barbee ◽  
R. E. Shepherd ◽  
A. H. Burns
Keyword(s):  
Heart Rate ◽  
Cardiac Function ◽  
Myocardial Dysfunction ◽  
Systolic Pressure ◽  
Cardiac Pacing ◽  
Diabetic Rats ◽  
Heart Weight ◽  
Citrate Buffer ◽  
Heart Preparation

The isolated working heart preparation was used to investigate the effect of continuous triiodothyronine (T3) administration on cardiac function and metabolism of rats rendered diabetic for a period of 4 wk with streptozocin (STZ). T3 controlled-release pellets were implanted 1 wk after STZ (70 mg/kg) injection. Rats injected with citrate buffer without STZ received T3 pellets 1 and/or 2 wk later. A comparable number of rats received placebo pellets. Untreated diabetic rats exhibited a decrease in spontaneous heart rate and myocardial cytochrome c concentrations concurrent with depressed plasma T3 values compared with untreated controls. T3 treatment did not improve in vitro cardiac performance (assessed as cardiac output times peak systolic pressure per gram dry heart weight) in hearts from diabetic rats perfused with glucose alone. Addition of octanoate reversed this depression and improved cardiac function to a greater extent in treated than in untreated diabetic animals. However, these differences between treated and untreated diabetic animals disappeared when heart rate was controlled by cardiac pacing. Furthermore, T3 treatment of controls and diabetics did not alter the oxidation of octanoate or the cardiac responsiveness to isoproterenol. These results suggest that experimental diabetic cardiomyopathy is partly attributable to a substrate deficiency and is not due entirely to hypothyroidism.

Myocardial performance of STZ-diabetic DOCA-hypertensive rats

1992 ◽  
Vol 263 (6) ◽  
pp. H1798-H1805 ◽  
Author(s):  
S. Dai ◽  
J. H. McNeill
Keyword(s):  
Plasma Cholesterol ◽  
Myocardial Dysfunction ◽  
Weight Ratio ◽  
Insulin Level ◽  
Diabetic Rats ◽  
Dependent Manner ◽  
Myocardial Performance ◽  
Ventricular Enlargement ◽  
Hypertensive Rats ◽  
Heart Apparatus

Myocardial performance of streptozotocin (STZ)-diabetic deoxycorticosterone acetate (DOCA)-hypertensive rats was examined using the isolated working heart apparatus at various time periods after induction of the experimental diseases. Blood pressure, pulse rate, and plasma levels of glucose, insulin, cholesterol, and triglycerides, as well as ventricular weight-to-body weight ratio, were also determined. In nondiabetic rats it was found that DOCA hypertension was associated with an increase in plasma cholesterol, a decrease in circulating insulin level, lower weight gain, and ventricular enlargement compared with control rats. Diabetic rats developed myocardial dysfunction in a time-dependent manner and exhibited hyperglycemia, hypoinsulinemia, bradycardia, and ventricular enlargement. Compared with the normotensive diabetic animals, STZ-diabetic DOCA-hypertensive rats showed a similar magnitude of myocardial dysfunction and a greater degree of ventricular enlargement, but significantly less severe hyperglycemia. It is concluded that DOCA-induced hypertension does not aggravate the severity of myocardial dysfunction developed in STZ-diabetic rats. It is also suggested that DOCA may have an action on glucose metabolism either directly or via an effect on insulin secretion.

Prevention and reversal of altered myocardial function in diabetic rats by insulin treatment

1983 ◽  
Vol 61 (5) ◽  
pp. 516-523 ◽  
Author(s):  
Arun G. Tahiliani ◽  
Rao V. S. V. Vadlamudi ◽  
John H. McNeill
Keyword(s):  
Insulin Treatment ◽  
Myocardial Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Myocardial Performance ◽  
Perfused Heart ◽  
Rat Hearts ◽  
Heart Preparation ◽  
Developed Pressure

Isolated perfused hearts from diabetic rats exhibit a decreased responsiveness to increasing work loads. However, the precise time point at which functional alterations occur is not clearly established. Previous observations in our laboratory have suggested that the alterations in myocardial function are not apparent at 30 days whereas they are clearly seen 100 days after streptozotocin-induced diabetes. We studied the cardiac function of 6-week diabetic rats using the isolated perfused heart preparation. The 6-week time period was found to be sufficient to cause depression of myocardial function in these animals. We also studied the effect of insulin treatment on myocardial performance of diabetic rats. Insulin treatment was initiated 3 days and 6 weeks after injection of streptozotocin (STZ). The treatment was continued for 6 and 4 weeks in the respective groups. Hearts from 6-week diabetic animals exhibited a depressed left ventricular developed pressure (LVDP) and positive and negative dP/dt at higher filling pressures when compared with 6-week control animals. However, the depression was not seen in the 6-week insulin-treated diabetic animals. Ten-week diabetic rat hearts also showed a depression of LVDP and positive and negative dP/dt when compared with 10-week controls. The group of animals that had been diabetic for 6 weeks and then treated for 4 weeks with insulin exhibited a reversal of the depressed myocardial function. These results demonstrate that depression of myocardial performance, which is evident 6 weeks after diabetes is induced, can be prevented if insulin treatment is initiated as the disease is induced. Further, insulin treatment is capable of reversing the abnormalities after they have occurred.

scholarly journals Effects of exercise training on autonomic and myocardial dysfunction in streptozotocin-diabetic rats

2000 ◽  
Vol 33 (6) ◽  
pp. 635-641 ◽  
Author(s):  
K.L.D. De Angelis ◽  
A.R. Oliveira ◽  
P. Dall'Ago ◽  
L.R.A. Peixoto ◽  
G. Gadonski ◽  
...  
Keyword(s):  
Exercise Training ◽  
Myocardial Dysfunction ◽  
Diabetic Rats ◽  
Streptozotocin Diabetic Rats

Lack of effect of thyroid hormone on diabetic rat heart function and biochemistry

1984 ◽  
Vol 62 (6) ◽  
pp. 617-621 ◽  
Author(s):  
Arun G. Tahiliani ◽  
John H. McNeill
Keyword(s):  
Heart Function ◽  
Myocardial Dysfunction ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Diabetic Rat ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Chain Acyl ◽  
Uptake Activity ◽  
Streptozotocin Diabetic Rats ◽  
Developed Pressure

Cardiac functional abnormalities are frequently seen in diabetics and diabetes is also known to produce a state of mild hypothyroidism. To study the degree of involvement of diabetes-induced hypothyroidism on altered myocardial function, thyroid replacement therapy was carried out in streptozotocin-diabetic rats. Triiodothyronine (T3) treatment was initiated 3 days after the rats were made diabetic and was carried out for 6 weeks thereafter. Isolated perfused hearts from diabetic rats exhibited a depression in left ventricular developed pressure and positive and negative dP/dt at higher filling pressures as compared with controls. The depression could not be prevented by thyroid treatment. Calcium uptake activity in the cardiac sarcoplasmic reticulum (SR) was also depressed as a result of diabetes and this depression also was not prevented by thyroid treatment. Long chain acyl carnitine levels were found to be elevated in diabetic cardiac SR and could not be lowered by T3 treatment. The results indicate that the myocardial dysfunction observed in diabetic rats is due to factors other than the induced hypothyroidism.

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