Fumio Nagamine

Cardioprotective effects of troglitazone in streptozotocin-induced diabetic rats.

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 cardiprotective effect on the basal and postischemic cardiac function of STZ-induced diabetic rats.

Increased QT dispersion and cardiac adrenergic dysinnervation in diabetic patients with autonomic neuropathy

Diabetic patients with autonomic neuropathy showed an increase in QTc dispersion correlated with cardiac adrenergic dysinnervation. A larger prospective study in a diabetic population is needed to assess whether QT dispersion increases the risk of arrhythmogenicity through autonomic dysfunction.

Enhanced insulin response relates to acetylcholine-induced vasoconstriction in vasospastic angina

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 circumflex coronary artery, were constricted at peak acetylcholine infusion (20 to 100 micrograms), 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.

Chronic gliclazide treatment affects basal and post-ischemic cardiac function in diabetic rats

1. A 6-week gliclazide treatment improved left ventricular developed pressure and left ventricular end-diastolic pressure, left ventricular pressure-rate products in isolated working hearts from streptozotocin-induced diabetic rats. 2. Post-ischemic recovery in heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure, left ventricular pressure-rate products and cardiac work were also shown in gliclazide-treated diabetic rats. 3. Gliclazide treatment did not modify the degree of insulinopenia and hyperglycemia, nor the myocardial energy metabolism during ischemia-reperfusion. 4. The results suggest that the gliclazide treatment has a cardioprotective effect on basal and post-ischemic cardiac functions of chronic diabetes.

Effect of intracoronary captopril on coronary blood flow and regional myocardial function in dogs.

To evaluate the cardiac effect of an inhibitor of angiotensin-converting enzyme, the effect of intracoronary (i.c.) captopril on coronary blood flow and regional myocardial function was examined in the anesthetized open-chest dog. Blood flow of the left circumflex coronary artery (LCX), left ventricular pressure (LVP), aortic pressure (AoP) and regional myocardial segment length were measured continuously. Captopril i.v. (0.3 mg/kg) produced an immediate reduction in AoP and an increase in percent shortening of myocardial segments followed by a decrease in coronary vascular resistance and increases in heart rate and LVdP/dt. Reductions in LCX flow induced by i.c. angiotensin were attenuated and i.c. bradykinin-induced increases in LCX flow were augmented after captopril. On the contrary, i.c. infusion of captopril (0.01 mg/min) into the LCX caused no change in hemodynamic variables and myocardial shortening although responses to angiotensin I and bradykinin were markedly modified. These results suggest that captopril may have no direct cardiac effect.

Late Complications in Traumatic Coronary Artery Fistula: Report of a Case Requiring Surgical Repair after 8 Years

We report the unusual case of a patient with traumatic coronary artery fistula who had been free of symptoms for more than 4 years, but who ultimately required surgical repair 8 years after the trauma due to late complications including angina pectoris, atrial flutter and fibrillation, congestive heart failure, and tricuspid regurgitation. Our findings suggest that early surgical repair should be undertaken in cases of traumatic coronary artery fistula, even if the shunt is minimal and early symptoms are mild. The persistence of, or a slow increase in, shunt flow over the years greatly increases the risk of the ultimate development of life-threatening complications.

Impaired mechanical response to calcium of diabetic rat hearts : reversal by nifedipine treatment

Summary: Streptozotocin-induced diabetic and age-matched control rats were treated with 0.03% nifedipine-containing chow for 6 weeks, and mechanical response to Ca2+ 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 Ca2+. However, the responses of diabetic rats were decreased with an increment in preload at 2.5 mM Ca2+. Nifedipine treatment produced a partial recovery of all four parameters at 2.5 mM Ca2+ in diabetic rats. The myocardial Ca2+ content and sarcolemmal lipid peroxidation were similar in hearts from control and diabetic rats at all Ca2+ concentrations and nifedipine treatment did not affect these values. Results suggest that chronic nifedipine treatment improve the contractility of diabetic rat hearts under high Ca2+ conditions.

Long-term nifedipine treatment reduces calcium overload in isolated reperfused hearts of diabetic rats

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.

Effect of gliclazide on the functional response to calcium in diabetic rat heart

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.

Enhancement of postischemic myocardial stunning by calcium overload in hearts of diabetic rats.

The effects of Ca2+ concentration on postischemic myocardial stunning were studied in isolated working hearts of rats with streptozotocin-induced diabetes and of age-matched control rats. During reperfusion after 10 min of ischemia, hearts from control rats showed complete recovery of cardiac function of 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.