Pseudosinusoidal fetal heart rate pattern and fetal anaemia: case report and review.

The association of a pseudosinusoidal fetal heart rate pattern with fetal anaemia is reported. A system of classifying this cardiotocographic feature as minor, intermediate or major is discussed. The clinical correlates of each of these gradings and the differentiation from a true sinusoidal fetal heart rate pattern are presented.

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

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronotropic function in spontaneously diabetic BB rats.

In the present study, isolated atrial function in spontaneously diabetic BB Wistar rats maintained for 12 weeks on a low (BB-LI) and a high (BB-HI) dosage of insulin was examined. Basal atrial rates were unchanged in the diabetic animals, relative to nondiabetic littermates (ND-BB) or Wistar controls. The BB-HI animals were euglycemic and responded to isoproterenol in a similar manner to the ND-BB and Wistar control animals. In contrast, BB-LI animals remained hyperglycemic and exhibited lower responses to the maximum chronotropic effects of isoproterenol. Plasma thyroid hormone levels were unaltered in the BB-diabetic animals. These results therefore reveal an absence of bradycardia and hypothyroidism in spontaneously diabetic BB rats, in contrast to previous observations in streptozotocin diabetic rats. However, a decrease in chronotropic response to isoproterenol was still noted in the BB-LI animals. These findings suggest that decreased positive chronotropic effect of isoproterenol in diabetes may not be a direct consequence of altered thyroid status.

Ultrastructural study of the effect of insulin dosage on the myocardium of spontaneously diabetic BB rats.

Cardiac ultrastructure was studied in spontaneously diabetic BB rats maintained on two different regimens of insulin daily. For 3 months from the onset of overt diabetes, one diabetic group was well controlled with daily subcutaneous administration of sufficient insulin to prevent glycosuria (9.0-13.0 U/kg). Approximately half of this dose (4.5 U/kg) of insulin was given daily to a second group of diabetic rats. Normal Wistar rats and nondiabetic BB rats were used as controls. Blood glucose values were three- to four-fold higher with respect to these controls in the diabetic BB rats receiving the smaller dose of insulin but were significantly lower than controls in diabetic animals receiving the higher insulin dose. A 30% difference in body weight with respect to the Wistar controls, obvious hyperliposis, and some nerve degeneration were seen in the low dose insulin group of diabetics. Such changes did not occur in the well-controlled insulin-treated group. Electron microscopic examination of the left ventricular tissue revealed mild damage in both groups of diabetics consisting of small focal lesions and mild edema along the sarcoplasmic reticulum and sometimes adjacent to the sarcolemma. Thus, insulin treatment, which prevented glycosuria, resulted in normal tissue lipid levels and prevented nerve damage but had little effect on the other diabetes-induced ultrastructural alterations in the myocardium of these rats.

Adriamycin cardiomyopathy: pathological and membrane functional changes in a canine model with mild impairment of left ventricular function.

Mild impairment of left ventricular function determined echocardiographically was produced in dogs by serial intravenous administration of adriamycin (1 mg/kg/week for 10 weeks). Mild histological changes were observed including vacuolar degeneration but there was a minimal disruption of myocardial architecture (mean severity score 1.4). Ultrastructure of the heart was relatively intact but focal changes included a slight disarray of cellular structure with mitochondrial swelling and distortion, myocytolysis, sarcoplasmic reticular vacuolization, increased glycogen and lipid levels and rounding of nuclei with large condensed nucleoli. Despite involvement of the sarcoplasmic reticulum in damaged myocytes, the transverse-tubules appeared to be normal. It was felt that these changes represent an early stage of adriamycin cardiomyopathy. Ouabain binding was carried out as a test of sarcolemmal integrity. A significant increase in the total number of ouabain binding sites without a change in the dissociation constant was seen. A correlation was observed between the degree of impairment of left ventricular function and the observed increase in ouabain binding. These results support the concept of sarcolemmal membrane alteration as an early mechanism of adriamycin-induced myocardial functional impairment.

Cardiac ultrastructural changes in streptozotocin-induced diabetic rats: effects of insulin treatment.

The effect of insulin treatment on myocardial ultrastructure was studied in experimentally induced diabetic male rats. Rats received an intravenous injection of 60 mg/kg streptozotocin and were tested for glycosuria 3 days later. Half of these animals were then given 3.0 U of protamine zinc insulin daily subcutaneously and again tested for glycosuria. The significant loss in weight observed in the untreated diabetics was prevented in the insulin-treated diabetics. Electron microscopic observation of the left ventricular myocardium from 3 month untreated diabetics revealed mild edema adjacent to the sarcoplasmic reticulum. A more severe form of edema, focal in nature, was also observed. Some distended mitochondria and disrupted banding were associated with these focal areas of edema. Increased lipid levels and intramitochondrial dense staining particles were found in the untreated diabetics. On the other hand, hearts from insulin-treated diabetics did not exhibit these alterations. They did, however, exhibit mitochondrial clumping which was also seen in the untreated diabetics and the same capillary changes. The latter involved a thickening of the lamina densa, loss of the lamina lucida and an increased number of micropinocytotic vesicles in the capillary walls. These results suggest that insulin treatment is capable of preventing only some of the ultrastructural changes induced by streptozotocin-diabetes in rat hearts.

Alterations in alpha 1-adrenoceptor stimulation of isolated atria from experimental diabetic rats.

This purpose of this investigation was to determine the influence of experimental diabetes (3 months) on the responsiveness of rat isolated atria to alpha 1-adrenoceptor stimulation by phenylephrine. Diabetes was chemically induced with streptozotocin (65 mg/kg i.v.) in 42- to 43-day-old, nonfasted male Sprague-Dawley derived rats. Chronotropic (right atria) and inotropic (left atria) indices were recorded in response to alpha 1-adrenoceptor stimulation by phenylephrine. These experiments were performed in the presence of beta-adrenoceptor antagonism (timolol). Isolated right atria from diabetic rats demonstrated a greater increase in heart rate in response to phenylephrine than did corresponding control atria. Left atria were supersensitive (decrease in EC50 values) and hyperresponsive to alpha 1-adrenoceptor stimulation by phenylephrine when compared with stimulation of control left atria. Diabetic left atria in response to phenylephrine were observed to exchange more radioactive calcium (45Ca2+) than control left atria, whereas both diabetic and control left atria exchanged the same amount of 45Ca2+ during basal contractile conditions. Phenylephrine had no effect on 45Ca2+ efflux from either diabetic or control atria. These results indicate that 3 months of uncontrolled experimental diabetes in the rat produces an enhancement of alpha 1-adrenoceptor activation of isolated atria, and that there is an alteration in Ca2+ mobilization which may contribute to the enhanced receptor activation.

A functional and ultrastructural analysis of experimental diabetic rat myocardium. Manifestation of a cardiomyopathy.

The effects of experimental diabetes on cardiac function and ultrastructure were studied in rats that had been diabetic for 6-24 wk. Experimental diabetes was produced by the intravenous (i.v.) injection of 65 mg/kg streptozocin (STZ) into rats 42-43 days old. Diabetic rat hearts perfused at 15 cm H2O on the working heart apparatus demonstrated depressed cardiac function (i.e., lower left ventricular pressure and +/- dP/dt) at 6, 12, and 24 wk of diabetes. Electron microscopic analysis of ventricular myocardium revealed increased lipid deposition from 6 to 24 wk of diabetes and progressive deterioration of the myocardial cell integrity at 12 and 24 wk of diabetes. This deterioration was characterized by loss of contractile protein, vacuolization (swollen sarcoplasmic reticulum), myelin formations, myocytolysis, and contracture bands. These alterations paralleled the depression of cardiac function at 12 and 24 wk of diabetes. There was, however, depressed function at 6 wk of diabetes but no observable alterations in myocardial ultrastructure. Therefore, experimental diabetes produced ultrastructural alterations in the rat heart that manifested themselves only after a demonstrable depression in cardiac function.