Influence of oral verapamil on glucoregulatory hormones in man.

We evaluated the effect of treatment with placebo or verapamil (320 mg/day) for 2 weeks on glucose-induced insulin secretion and hypoglycemia-stimulated counterregulatory hormone secretion in hypertensive patients. Verapamil treatment was associated with a significant reduction in diastolic blood pressure (P = 0.02 vs. placebo). During a hyperglycemic clamp (plasma glucose raised 125 mg/dl above basal level) maintained for 90 min, plasma insulin increased 4- to 5-fold (early) and then to values 8- to 10-fold above baseline (late). These increments were identical during placebo or verapamil treatment. The rates of glucose metabolized during each study also were similar, suggesting that no significant change in insulin action occurred during drug treatment. When plasma glucose was allowed to decline precipitously from hyperglycemic levels (220 mg/dl) to nadirs ranging from 42-77 mg/dl, plasma concentrations of glucagon, cortisol, epinephrine, and norepinephrine all increased; however, no consistent differences in the counter-regulatory hormone responses could be attributed to verapamil therapy. We conclude that physiologically effective drug concentrations of verapamil capable of influencing blood pressure do not have a significant effect on secretion of glucoregulatory hormones in man.

Impaired wound healing in streptozotocin diabetes. Prevention by supplemental vitamin A.

Goodson and Hunt showed that wound healing is impaired in streptozotocin (Sz) diabetic rats; we speculated that this impairment results from defective early inflammatory responses to wounding. Because we had shown that supplemental vitamin A stimulates the early inflammatory response to wounding in nondiabetic rats, we studied the effect of supplemental vitamin A on wound healing in rats with Sz-induced diabetes. Male Sprague-Dawley rats were fed a commercial rat chow containing twice the amount of vitamin A recommended by the NRC for healthy rats. The rats ate and drank (tap water) ad libitum. Two-thirds of the rats were injected (intravenously) with Sz 60 mg/kg body weight. All of these rats became diabetic (hyperglycemia greater than 350 mg/dl, hyperphagic, polydipsic, polyuric, glycosuric greater than 2%). Seven days later, half of the Sz-injected rats were continued on the chow (Group 2) while the other half (Group 3) were switched to the chow supplemented with 150,000 units of vitamin A/kg chow. The next day, all were wounded (7 cm skin incisions and s.c. polyvinyl alcohol sponge implants). Similarly wounded saline injected nondiabetic rats ingesting the unsupplemented chow served as controls (Group 1). The wounds of Group 2 rats healed poorly compared to Group 1 (breaking strength of skin incisions, 308 +/- 19 g vs 584 +/- 23 g, p less than 0.001; hydroxyproline of the sponge reparative tissue, 0.87 mg vs 2.40 mg/100 mg sponge p less than 0.001). Supplemental vitamin A (Group 3) did not affect the hyperglycemia, hyperphagia, polydipsia or glycosuria, but increased the breaking strengths of the incisions of the diabetic rats (468 +/- 40 g, p less than 0.001), and the sponge hydroxyproline (2.38 mg/100 mg sponge, p less than 0.001). In another experiment, in which the wounding and start of supplemental vitamin A were delayed until 28 days after streptozotocin administration (50 mg/kg body weight), similar results were obtained. Streptozotocin diabetes also caused a decrease in the cross-linking of reparative collagen as judged by the ratio of breaking strengths of skin incisions before and after formalin fixation. Supplemental vitamin A did not influence this defect. Sz also caused peripheral lymphocytopenia, adrenal hypertrophy and thymic involution which responded to the supplemental vitamin A. Based upon experimental data and theoretical considerations we conclude Sz diabetes causes two defects in wound healing: a) quantitatively (reduction in reparative collagen accumulation) and b) qualitative reduction in the degree of cross-linking of reparative wound collagen. The action of supplemental vitamin A in correcting the impaired wound healing, adrenal enlargement, thymic involution and lymphocytopenia of Sz-diabetic rats is independent of an effect on their disturbed carbohydrate metabolism.

Effects of DC electric countershock on ventricular function, cation balance and endogenous norepinephrine in the dog heart.

Effects of DC electric countershock on cardiac function in thoracotomized dogs were evaluated from recordings of ECG, aortic pressure, left ventircular pressure and its first derivative, and coronary sinus flow. Samples of arterial and coronary venous plasma and left ventricular myocardium obtained before and after countershock at times corresponding to post-shock arrhythmias and recovery were analyzed for Mg++, K+ and Ca++, and norepinephrine. At 1 min after countershock, ECG changes included transient cardiac arrhythmias and ST segment alterations, accompanied by depressed ventricular function and decreased myocardial Ca++ concentration. At 5 min postshock, coronary venous Mg++ and K+ concentrations had risen and ventricular function was still depressed. Function recovered within 10-20 min. There was no evidence of consistent loss of endogenous myocardial norepinephrine.