Elevated skeletal muscle glucose transporter levels in exercise-trained middle-aged men.

Exercise training has been proposed to improve whole body insulin sensitivity through a postreceptor adaptation in skeletal muscle. This study examined if levels of the insulin-responsive muscle glucose transporter protein (GLUT-4) were associated with improved insulin sensitivity in trained vs. sedentary middle-aged individuals. Muscle GLUT-4 levels and oral glucose tolerance test (OGTT) responses were obtained in age-matched trained and sedentary men (n = 11). Plasma insulin levels during the OGTT were significantly lower (P less than 0.01) in the trained men, whereas no differences were seen in plasma glucose responses. GLUT-4 protein content was approximately twofold higher in the trained men (2.41 +/- 0.17 vs. 1.36 +/- 0.11 micrograms standard, P less than 0.001). OGTT responses and GLUT-4 levels were not altered 15-18 h after a standard exercise bout in six representative sedentary subjects. These data suggest that GLUT-4 levels are increased in conjunction with insulin sensitivity in chronically exercise-trained middle-aged men. This finding suggests a possible mechanism for the improved insulin sensitivity observed with exercise training in humans.

Peak running velocity, submaximal energy expenditure, VO2max, and 8 km distance running performance.

The purposes of this study were to examine (1) if the peak running velocity achieved during maximal treadmill testing is related to 8 km distance running performance (DRP) and (2) if the relationship between selected physiological determinants are consistant for two 8 km races within a competitive season. Seven members of a University cross-country team (mean +/- SE) (age, 19.4 +/- 0.5 years, VO2max 67.0 +/- 1.0 ml/kg/min were tested 2-3 days following a mid-season race (Race M) and the season-ending conference championship (Race C). Despite similar weather and terrain, Race C (29:22 +/- 1:22 min:sec) was significantly (p less than 0.05) slower than Race M (28:31 +/- 0:58 min:sec). However, no significant differences (p greater than 0.05) were observed between testing sessions for calculated energy expenditure heart rate oxygen consumption and RER during submaximal running (248 and 268 m/min), postsubmaximal run lactate, peak running velocity, and VO2max. A significant correlation (p less than 0.05) was observed for Race M with with calculated energy expenditure during submaximal running at both speeds (r = 0.85) and with peak running velocity (r = -0.76). Regression analysis revealed that 92% of the total variance for Race M was accounted for by calculated energy expenditure during submaximal running and VO2max. No significant correlation or regression relationship was observed for any variables with Race C. These results suggest that peak running velocity, calculated energy expenditure during submaximal running, and VO2max can be associated with 8 km running performance. However, the relationship between 8 km DRP and the variables measured can differ for two races over a competitive season.

Effects of fitness level and the regional distribution of fat on carbohydrate metabolism and plasma lipids in middle- to older-aged men.

Many cross-sectional studies have demonstrated the influences of fitness level or the regional distribution of fat on lipid and carbohydrate metabolism; however, the relative contribution of these two variables in the same subjects has not been extensively examined. The purpose of this study was to determine the impact of regional adiposity on plasma lipids and carbohydrate metabolism in middle- to older-aged men with a wide range of fitness levels. Forty-six sedentary and exercise-trained men (age [mean +/- SE], 52.8 +/- 0.88 years) were included in this study. Fitness level was assessed by (a) time to exhaustion, and (2) maximal oxygen uptake achieved during an incremental treadmill test. Plasma lipid levels were determined in the basal, fasting state. Carbohydrate metabolism was evaluated by the glucose and insulin responses (total glucose and insulin areas under the curve, insulin sensitivity index [ISI]) to a 75-g, 2-hour oral glucose tolerance test (OGTT). Abdomen to hip ratio (AHR) was used as the index of regional adiposity. Multiple regression analysis indicated that fitness level and the percentage of body fat were significant predictors (approximately 56% of total variance) for total insulin area under the curve and the ISI. A comparison between the sedentary and trained subjects showed that training resulted in an improved ISI at an equal AHR. Fitness level was also the only significant multiple regression predictor for high-density lipoprotein (HDL)-cholesterol (25% of total variance) and accounted for the greatest amount of variance in triglyceride levels (34%), although AHR was also a significant predictor (6%).(ABSTRACT TRUNCATED AT 250 WORDS)

The golden hours of the myocardial infarction: nonthrombolytic interventions.

Emergency care of patients with acute myocardial infarction requires active decision making to use agents that may improve morbidity and mortality. Thrombolysis remains the primary tool to accomplish this goal. Other pharmacologic agents, including lidocaine, nitrates, calcium channel blockers, beta-blockers, and aspirin, have been used acutely in myocardial infarction in the hopes of preventing death and salvaging myocardium. The decision to select one or all of these agents requires a knowledge of the clinical evidence of their efficacy and risk-to-benefit ratios. The clinical studies of the use of these agents acutely in the management of myocardial infarction are reviewed.

An evaluation of waist to hip ratio measurement methods in relation to lipid and carbohydrate metabolism in men.

The purpose of this study was to determine which method of measuring waist to hip ratio (WHR) was the most effective in assessing decrements associated with an abdominal fat distribution in 46 non-obese, middle to older aged men (mean +/- s.e., age 52.8 +/- 0.88 years; body fat 19.7 +/- 0.72 percent). Circumferences were obtained at the following sites and WHR calculated (waist circumference/hip circumference): (1) minimal waist/maximal hip; (2) level of umbilicus/maximal hip; (3) level of umbilicus/level of greater trochanters; (4) level of umbilicus/level of superior iliac spine; and (5) level of 1/3 of the distance between the xiphiod process and umbilicus/level 4 cm below the superior iliac spine. Significant (P less than 0.05) associations were observed for measurement methods 1, 2 and 3 with indices of lipid and carbohydrate metabolism, body composition, and fitness level. Measurement method 5 was not related to any metabolic or physiological variables, while measurement method 4 was intermediate in terms of the strength of the associations. These findings suggest that the predictive strength of WHR can vary depending upon the measurement method used.

Feasibility of intraoperative aortic root angiography in the identification of critical coronary lesions.

Early revascularization is critical for the treatment of acute myocardial infarction (AMI) because the ischemic myocardium begins to suffer irreversible damage after 4 h from the onset of symptoms. However, to make a diagnosis, perform coronary angiography, and prepare for operative revascularization usually takes longer than 4 h. Also, once a patient develops severe cardiogenic shock, coronary angiography is often impossible. Without angiography, the patient is no longer a candidate for surgical repair. To circumvent this problem, we designed this experiment to determine whether intraoperative aortic root angiography after cardiopulmonary bypass and cardioplegic arrest could satisfactorily substitute for angiographic examination in the identification of critical coronary lesions. The feasibility of this approach was tested in dog hearts in which one or tow of the major coronary arteries were ligated. The ascending aorta was then clamped, contrast material was injected, and continuous real-time fluoroscopic images were obtained and recorded on videotape. The videotape was then analyzed by three physicians independently, each without prior knowledge of the lesion locations. Lesions of the left anterior descending artery, the circumflex coronary artery, and the right coronary artery were identified with 94, 91, and 94% accuracy, respectively, for an overall identification rate of 92%. We conclude that aortic root angiography reliably demonstrates coronary artery lesions, and refinements in this technique may allow certain patients to undergo coronary operations without preoperative catheterization.

Thyroxine metabolism in the low thyroxine state of critical nonthyroidal illnesses.

This study reports in vitro and in vivo parameters of T4 metabolism in patients with critical nonthyroidal illnesses who were selected because of serum total T4 values less than 3 micrograms/dl and normal TSH levels. Despite the depressed total T4 concentrations, the normal serum free T4 values (7 of 9 patients), T4 production rates (8 of 9), and TSH responses to TRH (8 of 8) provided evidence for normal free T4 availability to peripheral tissues. Elevated rT3 values in 10 of 14 patients were consistent with this view. However, serum free T4 index determinations markedly underestimated free T4 (20 of 20). This resulted from failure of the T3 uptake measurement to reflect the defective state of serum T4 binding. Defective serum T4 binding to carrier proteins was evidenced by the 2- to 3-fold increase in both the free fraction and the MCR values for T4. The normal early distribution phase, despite defective serum T4 binding, suggested an additional abnormality of deficient extravascular T4 binding. The blunted TSH response to TRH and the low normal values for both T4 production rates and free T4 levels measured by equilibrium dialysis indicated mild pituitary suppression, possibly related to elevated serum cortisol levels. Since an overt deficiency of free T4 availability does not appear to exist in the low T4 state of critical nonthyroidal illness, T4 therapy cannot currently be recommended.

The influence of long-term low dose thyrotropin-releasing hormone infusions on serum thyrotropin and prolactin concentrations in man.

The purpose of the present study was to evaluate in man the relative thyrotroph and lactotroph response to a 48-h low dose constant TRH infusion. Before, during, and after the 75 ng/min TRH constant infusion, serum samples were obtained every 4 h in six euthyroid ambulating male subjects for measurements of TSH, PRL, T4, and T3. The TSH response, employing a specific and sensitive human TSH RIA, demonstrated a significant rise from the mean basal pre-TRH value of 2.35 +/- 0.64 microU/ml (+/- SEM) to 3.68 +/- 0.80 (P < 0.005) during the TRH infusion; this value fell below the basal level to 1.79 +/- 0.47 (P < 0.05) post infusion. Serum T4 values were increased above basal both during (P < 0.025) and after (P < 0.025) TRH infusion, whereas serum T3 values were not significantly changed throughout the entire study period. The daily TSH nocturnal surge was augmented in both absolute and relative terms during the first 24 h or the TRH infusion, unchanged during the second 24 h of infusion, and inhibited during the first postinfusion day. Other than a minimal increase in serum PRL during the first few hours of the infusion, no significant alteration in the mean basal concentration or circadian pattern of PRL secretion was evident during or after the low dose TRH infusion. These findings would indicate that 1) near-physiological stimulation of the pituitary with TRH produces a greater stimulation of TSH release than of PRL release and 2) the factor or factors producing the circadian TSH surge may not be mediated through fluctuations in endogenous TRH.

Effect of hypophosphatemia on myocardial performance in man.

Severe hypophosphatemia is associated in man with low intracellular stores of ATP and a set of specific cellular dysfunctions. To investigate whether hypophosphatemia affects myocardial performance, we measured cardiac output by thermodilution and calculated stroke work in seven patients with severe hypophosphatemia before, during and after repletion with an intravenous potassium phosphate solution. Mean left ventricular stroke work for these patients increased from 49.57 to 71.71 g-m per beat (P less than 0.01) at the same or higher afterload whereas pulmonary-artery wedge pressure fell from a mean value of 10.1 to 6.7 torr (P less than 0.02). Return of serum phosphate to normal, therefore, improved myocardial stroke work independently of the Starling effect. The mechanism of this improvement in contractile force is unknown but may be related to intracellular availability of ATP.