Quantification of coronary artery calcification (CAC) determined by electron-beam computed tomography (EBCT), known as the CAC score (CACS), correlates with total plaque amount and coronary risk factors and strongly associates with maximal stenosis in the epicardial arteries. However, data are limited concerning the CACS in chronic dialysis patients, although atherosclerotic vascular disease is the most frequent complication. We examined the relation between coronary risk factors, metabolic factors of calcium and other minerals, and CACS progression in 24 dialysis patients. The mean patient age was 53 +/- 14 (SD) years, and mean duration of dialysis was 64 +/- 69 months. In each patient, the CACS was measured twice, with a mean interscan period of 17 +/- 3 months. The mean CACS progressed from 449 +/- 605 to 669 +/- 894 overall, and the mean change in CACS (DeltaCACS) was 220 +/- 78. Patients were divided into two groups: slow progressors, with DeltaCACS of 7.5 +/- 31 (n = 12), and rapid progressors, with DeltaCACS of 432 +/- 458 (n = 12). Triglyceride concentrations (198 +/- 65 versus 103 +/- 50 mg/dL; P < 0.001) were high, and high-density lipoprotein cholesterol (HDL-C) concentrations (46 +/- 11 versus 60 +/- 18 mg/dL; P < 0.05) were low in rapid progressors. Rapid progression of CAC was associated with high triglyceride and low HDL-C concentrations. The clinical significance of these observations remains to be determined.

To determine whether thyroid hormones, triiodothyronine (T3) and thyroxine (T4), have any direct, nongenomic effects on vascular smooth muscle cells, we evaluated the effects of these hormones on rat coronary arteries. Bolus injection of T3 or T4 elicited a transient, dose-dependent decrease in coronary perfusion pressure (CPP), as well as an increase in arterial vasodilation. Vasodilation occurred immediately after injection, peaked at 15 seconds, and lasted 80 seconds. Reverse T3 had no effect on CPP or vasodilation. The rapidity of these effects suggests that they are not mediated by the T3-nuclear receptor, but are direct, nongenomic effects of thyroid hormones. Our results also suggest that thyroid hormones may play a role in preventing myocardial ischemia by inducing coronary artery vasodilation.

1. The cardiac functional response to extracellular Ca2+ in isolated working hearts was evaluated in streptozotocin-induced diabetic rats treated or not treated with gliclazide. 2. Gliclazide treatment of diabetic rats allowed a partial recovery of the body weight decrease, but not of the hyperglycemia nor insulinopenia. 3. The cardiac mechanical response of diabetic rats was altered, especially at high Ca2+ concentration, and 6-week gliclazide treatment restored the dysfunction close to the control values. 4. The results suggest that gliclazide treatment restores the cardiac function of chronic diabetic rats partly through modulating the Ca2+ metabolism.

We report on an unusual patient with a threatened occlusive dissection, in whom prolonged (48-hr) inflation of a balloon catheter with localized heparin infusion proved successful. This intracoronary infusion catheter maintained distal coronary flow on a unique spiral coil design, and may provide an alternative or a bridge to emergency operation or stent implantation.

Troglitazone, a new oral antidiabetic agent, shows hypoglycemic effects in insulin resistant animal models and humans. This study was conducted to evaluate the effects of troglitazone on the heart of diabetic animals. Streptozotocin (STZ)-induced diabetic rats and age-matched controls were treated with troglitazone as a 0.2% food admixture for 6 weeks. Basal and postischemic cardiac functions at 14 weeks of age were then examined in isolated working heart. Troglitazone treatment did not attenuate the insulinopenia and hyperglycemia of diabetic rats, but it partially improved the hypertriglyceridemia. Troglitazone treatment partially restored the basal heart rate and cardiac work of diabetic rats to nearly control values. Troglitazone also improved the postischemic functional deficits of diabetic rats: heart rate (untreated 61% of baseline at 30-minute reperfusion v treated 92%, P <.001), left ventricular (LV) developed pressure (54% v 94%, P <.001), peak positive ([LV +dP/dt] 54% v 93%, P <.001) and negative ([LV -dP/dt] 53% v 94%, P <.001) first derivative of LV, and cardiac work (44% v 98%, P <.001). Diabetic animals showed ultrastructural damage including disarray of sarcomere, disorganization of mitochondrial matrix, cytoplasmic vacuolization, and invagination of nuclear membrane; these were partially normalized by troglitazone treatment. Our results suggest that troglitazone treatment has a cardioprotective effect on the basal and postischemic cardiac function of STZ-induced diabetic rats. Copyright (C) 1996 hy W.B. Saunders Company

The effects of Ca2+ concentration on postischemic myocardial stunning were studied in isolated working hearts of rats with streptozotocininduced diabetes and of age-matched control rats. During reperfusion after 10 min of ischemia, hearts from control rats showed complete recovery of cardiac function at Ca2+ concentrations of 1.25, 1.88, and 2.50 mmol/L, while the recovery of diabetic rats was decreased only at a Ca2+ concentration of 2.50 mmol/L. Although myocardial Na+ and Ca2+ concentrations were comparable between control and diabetic rats, only diabetic rats showed increases in myocardial concentration of Na+ during ischemia and Ca2+ during reperfusion at a Ca2+ concentration of 2.50 mmol/L. Results suggest that diabetic rat hearts are vulnerable to postischemic stunning via an overload of calcium.

1. Streptozotocin-induced diabetic rats showed poor post-ischemic recovery in isolated working rat hearts.2. Diabetic rats showed myocardial Na+ accumulation after ischemia, and Ca2+ level and water content elevation after reperfusion.3. A 6-wk nifedipine treatment improved post-ischemic recovery of cardiac parameters and prevented myocardial Na+ accumulation after ischemia and myocardial Ca2+ level and water content elevation after reperfusion of diabetic rats.4. Results suggest that nifedipine treatment improves cardiac dysfunction in the reperfused ischemic hearts of diabetic rats through normalization of the Na+-Ca2+ imbalance and water content.

Streptozotocin-induced diabetic and age-matched control rats were treated with 0.03% nifedipine-containing chow for 6 weeks, and mechanical response to Ca(2+) was studied using isolated working hearts. At 14 weeks of age, 7 weeks after a streptozotocin injection, diabetic rats had a lower body weight and heart weight than controls, and an increase in heart weight-to-body weight ratio. Nifedipine treatment did not alter these parameters of controls, but decreased the heart weight and heart weight-to-body weight ratio of diabetic rats without affecting the body weight. In diabetic rats, systolic blood pressure was decreased compared to controls (124 +/- 5 vs. 137 +/- 6 mm Hg, p < 0.01), and reduced more by nifedipine treatment (111 +/- 4 mm Hg, p < 0.01). In control rats, LV developed pressure, LV +/- dP/dt, and cardiac work were unchanged regardless of the increment in preload at 1.25, 1.88, and 2.50 mM Ca(2+). However, the responses of diabetic rats were decreased with an increment in preload at 2.5 mM Ca(2+). Nifedipine treatment produced a partial recovery of all four parameters at 2.5 mM Ca(2+) in diabetic rats. The myocardial Ca(2+) content and sarcolemmal lipid peroxidation were similar in hearts from control and diabetic rats at all Ca(2+) concentrations and nifedipine treatment did not affect these values. Results suggest that chronic nifedipine treatment improve the contractility of diabetic rat hearts under high Ca(2+) conditions.

Troglitazone, a newly developed oral antidiabetic agent, improves hyperglycemia, and has been reported to improve insulin resistance and to decrease hepatic glucose production in diabetic animals. However, the exact mechanism of Troglitazone on the improvement of insulin resistance is not known. Chronic administration of fructose to normal rats leads to hyperglycemia, and hyperinsulinemia; it induces insulin resistance. To reveal the mechanism of Troglitazone, we studied the effect of Troglitazone on serum glucose and insulin in the fructose-induced, insulin-resistant rats. Male Sprague-Dawley (SD) rats were fed either on standard chow or one containing fructose. Troglitazone was administrated as a food admixture (150 mg/kg/day) for 8 weeks. The rats were fed on (1) standard chow, (2) standard chow and Troglitazone, (3) fructose-enriched chow, or (4) fructose-enriched chow and Troglitazone. Blood samples were obtained every two weeks, and the levels of serum glucose and insulin were measured. Fructose-enriched chow increased serum glucose and insulin levels and insulin-to-glucose ratios. Troglitazone improved the fructose-induced increases in serum glucose, insulin levels, and insulin/glucose ratios. In conclusion, Troglitazone improved the fructose-induced insulin resistance.

Objectives. This study investigated whether insulin response to an oral glucose load correlates to acetylcholine-induced coronary vasoconstriction in subjects with vasospastic angina.Background. It has been suggested that coronary vasospasm is caused by augmented vascular responsiveness possibly exerted by atherosclerosis. Recently, insulin resistance syndrome has been proposed as a major promotor of atherosclerotic disease, potentially enhancing vascular smooth muscular tone.Methods. Among subjects with angiographically smooth coronary arteries, we selected 14 subjects with vasospastic angina and 14 age- and gender-matched subjects with atypical chest pain. We compared coronary vasomotor response to acetylcholine infusion, glucose and insulin responses to an oral glucose load (75 g), serum lipid concentrations, obesity, heart rate, blood pressure and smoking habits in both groups.Results. Fasting serum insulin concentrations and insulin response were higher in subjects with vasospastic angina than in those with atypical chest pain; however, glucose tolerance, obesity, heart rate, blood pressure and smoking habits did not differ between groups. In subjects with vasospastic angina, nearly all coronary segments, except distal segments of the left circuraflex coronary artery, were constricted at peak acetylcholine infusion (20 to 100 μg), whereas all segments were dilated in subjects with atypical chest pain. Regression analysis for both groups demonstrated a correlation between coronary vasoconstriction and fasting serum insulin concentrations (r = 0.52, p < 0.01), insulin response (r = 0.71, p < 0.001), serum triglyceride concentrations (r = 0.51, p < 0.05) and atherogenic index (r = 0.44, p < 0.05).Conclusions. Results show that acetylcholine-induced coronary vasoconstriction in subjects with vasospastic angina correlates with hyperinsulinemia and enhanced insulin response, suggesting insulin resistance syndrome as a feature of vasospastic angina.

FK506, a agent extracted from a streptomyces, has more potent immunosuppressive properties compared with cyclosporin in vitro. We compared the preventive effect of FK506 on the development of diabetes mellitus with that of cyclosporin in BB rats, which are regarded as a useful model of insulin-dependent diabetes mellitus. BB rats aged 30 days were treated intramuscularly with FK506 (0.1 mg/kg/day and 0.32 mg/kg/day) or with cyclosporin (10 mg/kg, alternate days) until 150 days of age. Diabetes developed in 2 (10.5%) of 19 rats treated with the lower dose of FK506 and none of 20 rats with the higher dose of FK506; on the other hand, 1 (5.3%) of 19 rats treated with cyclosporin developed diabetes. In contrast, 9 (36.0%) of 25 control rats became diabetic. The cumulative incidence of diabetes mellitus in the group treated with FK506 (0.32 mg/kg) showed a decrease similar to or more than that of the cyclosporin-treated group. Histological examination showed that FK506 and cyclosporin prevented the reduction in the average size of islets and in the area of beta cells. The analysis of lymphocyte subsets proved the decrease of W3/25: OX8 ratio in both FK506- and cyclosporin-treated groups. These data suggest that the administration of FK506 might be a more useful tool for preventing the development of insulin-dependent diabetes mellitus.