Role of epinephrine during insulin-induced hypoglycemia in fasted rats.

Responses to insulin-induced hypoglycemia in fasted sham-operated (SHAM), adrenodemedullated (ADM), and epinephrine-infused ADM (ADM + E) rats were studied to ascertain the specific role of epinephrine in increasing resting skeletal muscle content of adenosine 3',5'-cyclic monophosphate (cAMP) and fructose 2,6-bisphosphate (F-2,6-P2), which are involved in stimulation of muscle glycogenolysis and lactate production. Rats from each group were fasted for 24 h and then infused intravenously with insulin (30, 60, or 90 min) to produce plasma insulin values of approximately 92 microU/ml. One-half of the insulin-infused ADM rats were also infused with epinephrine (ADM + E). Muscle and blood lactate, muscle cAMP, and muscle F-2,6-P2 increased and muscle glycogen decreased in SHAM rats. Each of these changes was prevented or attenuated in ADM rats and restored in ADM + E rats. Liver cAMP, glycogen, and F-2,6-P2 responses to hypoglycemia were similar in SHAM, ADM, and ADM + E rats. Blood glucose decreased to 0.74 +/- 0.05 mM in ADM rats compared with 1.54 +/- 0.11 mM in SHAM and 1.34 +/- 0.15 mM in ADM + E rats after 90 min of insulin infusion. The increase in plasma epinephrine is therefore essential in the counterregulatory response to insulin-induced hypoglycemia in fasted rats. Resting skeletal muscle glycogenolysis and lactate production for hepatic gluconeogenic substrate appear to be important components of the counterregulatory response in fasted rats.

Clinical determinants of mortality in chronic congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy.

To determine which of the many clinical parameters routinely collected influence mortality in patients with congestive heart failure (CHF), 201 patients with idiopathic or ischemic dilated cardiomyopathy were prospectively followed for a 28-month study period. Mean age of the study group was 62 +/- 10 years, 60% had ischemic cardiomyopathy, and two-thirds were in New York Heart Association functional class II or III. Fifteen clinical variables were analyzed using a Cox proportional hazards model, while individual variables also were calculated for independent prognostic significance. There were 85 deaths, 26 (31%) of which were sudden cardiac deaths. Three characteristics at the study entry independently predicted an increased mortality risk: left ventricular ejection fraction, maximal oxygen uptake and ischemic cardiomyopathy. A Cox proportional hazards model showed that the combination of VO2max, S3 and the diagnosis of ischemic cardiomyopathy provided the best estimates of risk for an early death. Mortality for the low-risk group was only 5% at 6 months and 10% at 1 year. In contrast, in patients with an S3, ischemic cardiomyopathy and low maximal oxygen uptake, 6-month mortality was 24% and 36% at 1 year (p less than 0.001). Thus, these patients at high risk with left ventricular dysfunction associated with ischemic heart disease, a decreasing exercise tolerance and the development of an S3 should be strongly considered for an interventional trial with the aim of decreasing mortality.