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T F Schaible

Publications and source records attributed to T F Schaible.

45 records · Page 3Linked to original sources
PubMed1983

Left ventricular function after chronic insulin treatment in diabetic and normal rats.

Previous reports have documented a cardiomyopathy in rats resulting from streptozotocin-induced diabetes. In order to determine the reversibility of streptozotocin-induced cardiomyopathy to insulin therapy, hearts from rats made diabetic by streptozotocin for 6 weeks and then treated with insulin for 3 weeks were compared with untreated diabetic rats and control rats not injected with streptozotocin. When perfused in an isolated working heart apparatus with 5.5 mM glucose as substrate, hearts from untreated diabetic rats when compared to hearts from either streptozotocin-injected rats treated with insulin or control rats showed significant depressions in peak left ventricular pressure, maximal positive and negative dP/dt, oxygen extraction, lactate production and effluent lactate; pyruvate ratio. Ca2+-actomyosin ATPase was also depressed in untreated diabetics. As left atrial pressure was raised in untreated diabetic rats, a decline in cardiac output was observed, whereas in insulin-treated or control groups there was no such negative response. Indices of cardiac performance were significantly greater in insulin-treated rats when compared to control rats suggesting overcorrection with insulin therapy. To explore whether insulin treatment may have a beneficial effect on the myocardium control rats were made hyperinsulinemic for 6 to 7 weeks. Shorter isovolumic relaxation times and elevated values for Ca2+-actomyosin ATPase were observed in hearts from hyperinsulinemic animals when compared to hearts from control animals. These results demonstrate complete reversibility of streptozotocin-induced cardiomyopathy and confirm that this condition is due to insulin deficiency and not to a primary cardiotoxic effect of streptozotocin.

Animals↗
PubMed1983

Impaired coronary flow and ventricular function in hearts of hypertensive rats.

Hearts of rats made hypertensive (BP greater than 150 mmHg) by left renal artery clipping and sham operated controls were studied in two series of experiments. In series I, cardiac function was studied in an isolated working heart apparatus at weeks 4, 9 to 10 and 16 to 17 post-surgery. In series II, coronary flow was studied during normoxic and anoxic retrograde perfusions at days 6 to 9 and at weeks 4 and 10 post-surgery. In series I, when compared with controls, hypertensives had lower body weights at weeks 4 and 9 to 10, and higher left ventricular weights at each period. Heart function was depressed for hypertensives when compared with controls as measured by lower stroke volume, peak left ventricular systolic pressure, stroke work, ejection fraction, positive dP/dt, peak aortic flow, and maximal flow acceleration. Relaxation rate as measured by negative dP/dt was also depressed. Hearts from hypertensives had significantly lower coronary flows and MVO2, and increased percent oxygen extraction and effluent lactate/pyruvate ratios. LVEDP was significantly elevated for hypertensives, when LVEDV (ml) was similar for hypertensives and controls. Myocardial actomyosin ATPase activity was depressed for hypertensives at weeks 9 to 10 and 16 to 17 post-surgery. In series II, when hearts were perfused retrogradely, coronary flow was lower for hypertensives than for controls during normoxia at days 6 to 9 and at week 4, and during anoxia at all time periods. The findings demonstrate that impaired coronary vascular reserve develops within days of the development of hypertension in rats, and this can be associated with impaired ventricular function.

Animals↗
PubMed1983

Effects of experimental diabetes on adrenergic and cholinergic receptors of rat myocardium.

To more fully characterize the alterations in myocardial adrenergic and cholinergic receptors induced by the diabetic state, we investigated the binding characteristics of (--) [3H] dihydroalprenolol to beta adrenergic receptors (bAR), [3H] prazosin to alpha adrenergic receptors (aAR), and [3H] quinuclidinyl-benzilate to muscarinic cholinergic receptors (MCR) in myocardial membranes derived from rats 8 wk after treatment with streptozotocin. We also studied an equal number of animals from three control groups: free-eating nondiabetics, pair-weighted nondiabetics, and streptozotocin-treated animals treated daily with insulin. Diabetic hearts demonstrated 27% fewer bAR (P less than 0.01) and 31% fewer aAR (P less than 0.01) than free-eating controls, without changes in MCR, and without changes in antagonist affinity, agonist affinity, or agonist slope factor (pseudo-Hill coefficient) for any class of receptors. Food restriction had no effect on receptor characteristics, and treatment of diabetic rats with insulin prevented any downregulation of cardiac bAR or aAR. The parallel decrease in both bAR and aAR suggests that streptozotocin-induced hypothyroidism is not the primary causative factor of bAR downregulation in this model, since hypothyroidism produces upregulation of aAR. Furthermore, the lack of change in cardiac MCR suggests that the adrenergic receptor alterations are not the result of nonspecific abnormalities of protein synthesis in the diabetic heart. Further studies are required to establish the physiologic significance of these receptor alterations, but these data support the hypothesis that altered adrenergic receptor properties may underlie, at least in part, the chronotropic and inotropic abnormalities of cardiac performance that are associated with the diabetic state.

Animals↗
PubMed1982

Physiologic cardiac hypertrophy corrects contractile protein abnormalities associated with pathologic hypertrophy in rats.

To evaluate the combined effects of cardiac overload imposed by hypertension and by chronic exercise, male and female rats were made hypertensive by unilateral renal artery stenoses and made to exercise in an 8-10-wk swimming program. Sedentary normotensive animals, sedentary hypertensive animals and normotensive animals exposed to the swimming program were also studied. Hypertension was associated with the development of cardiac hypertrophy, and this was exaggerated in hypertensive swimmers. Actomyosin, Ca2+-myosin, and actin-activated Mg2+-myosin ATPase activities were enhanced in normotensive swimmers, depressed in hypertensives and were normal or increased in hypertensive swimmers. Myosin isoenzyme analysis showed a predominant V1 pattern in normals; an increase in percent V1 isoenzyme is swimmers; a predominant V3 pattern in hypertensives; and a return to the predominant V1 pattern in hypertensive swimmers. These findings suggest that the hypertrophy imposed by hypertension and hypertrophy imposed by physical training using a chronic swimming program are distinctly different biological phenomena. Physical training by swimming prevents the changes in cardiac myosin induced by hypertension despite the exaggeration of hypertrophy.

Actomyosin↗
PubMed1981

Cardiac responses to exercise training in male and female rats.

The purpose of the present study was to determine if contractile function adapts to physical training in the same way in hearts of male and female rats. Male and female rats were trained with a running program sufficient to cause equal increases in cytochrome oxidase activity in gastrocnemius muscles in both groups. Hearts were then studied in an isolated perfused working rat heart apparatus with varying preloads and fixed afterloads. Five groups were studied: 1) free-eating sedentary males (MS-FE); 2) running males (MR); 3) sedentary females (FS); 4) running females (FR); and 5) food-restricted sedentary; males (MS-FR). Heart weights were similar in MS-FE and MR and in FS, FR, and MS-Fr. Stroke work, stroke volume, coronary flow, and myocardial oxygen consumption were significantly higher in MR than in MS-FE but were almost identical in FR and FS. MS-FR showed stroke work, stroke volume, and ejection fractions that were similar to MR but higher than MS-FE and both female groups. Thus when hearts of equal weights were compared, a training effect was only seen in males. These results suggest that despite similar skeletal muscle adaptations, hearts of male rats adapt to physical training by running with improved intrinsic performance, whereas hearts of female rats do not.

Animals↗
PubMed1981

Cardiac function in hypertrophied hearts from chronically exercised female rats.

Physiological cardiac hypertrophy was produced in female rats by subjecting them to a swimming program for 8 wk. Conditioned rats (C) had body weights similar to sedentary control rats (S), but hearts from C weighed 33% more than hearts from S. Heart function was assessed in an isolated working-heart apparatus at similar heart rates and aortic diastolic pressures and over a range of 5-20 cmH2O left atrial filling pressure (LAP). At any given LAP, absolute values for cardiac output and coronary flow were greater (p less than 0.001) in C than S, but when these values were normalized for dry left ventricular (LV) weight, no differences were observed. Peak LV systolic pressure and ejection fraction were greater (p less than 0.01) in C than S at all LAP. Derived measures of contractility calculated at the midwall demonstrated greater (p less than 0.01) velocity and extent of circumferential fiber shortening in C compared with S. Therefore, chronic swimming in female rats leads to enhanced contractile performance of the left ventricle despite a marked degree of hypertrophy. These results contrast with our earlier observations in female rats trained by running where neither hypertrophy nor enhanced function were observed.

Animals↗
PubMedDate not supplied

Comparison of heart function in male and female rats.

The objective of this investigation was to compare intrinsic cardiac function in male and female rats. The first series of experiments (Series I) compared hearts from age-matched males and females at 18 weeks of age. Since body and heart weight were 65 and 51 per cent greater respectively in male rats in this study, a second series of experiments was performed (Series II) where heart mass was matched in males and females by studying males at 10 weeks of age and females at 18 weeks of age. Cardiac function was studied in an isolated working heart apparatus at similar heart rates and at controlled levels of end-diastolic pressure and aortic diastolic pressure (ADP). In Series I coronary flow and end-diastolic volume (both per g LV) were the same in male and female hearts, while stroke work (per g LV), ejection fraction and fractional shortening were significantly greater in male hearts but only as the ADP was increased. In Series II all of these measurements were significantly greater in male hearts at all loading conditions. The magnitude of the differences between male and female hearts was greater in Series II than in Series I which may have been due to a Frank-Starling effect in male hearts from Series II. The results indicate that intrinsic cardiac function is moderately greater in male rats compared to female rats. Studies employing similar size male and female hearts suggest that differences in heart mass may have accounted for the differential response to ADP in Series I.

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