Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes.

Total GLUT4 content in skeletal muscle from individuals with type 2 diabetes is normal; however, recent studies have demonstrated that translocation of GLUT4 to the plasma membrane is decreased in response to insulin stimulation. It is not known whether physical exercise stimulates GLUT4 translocation in skeletal muscle of individuals with type 2 diabetes. Five subjects (two men, three women) with type 2 diabetes and five normal control subjects (5 men), as determined by a standard 75-g oral glucose tolerance test, were recruited to determine whether an acute bout of cycle exercise activates the translocation of GLUT4 to the plasma membrane in skeletal muscle. Each subject had two open biopsies of vastus lateralis muscle; one at rest and one 3-6 weeks later from the opposite leg after 45-60 min of cycle exercise at 60-70% of VO2max. Skeletal muscle plasma membranes were prepared by subcellular fractionation, and GLUT4 content was determined by Western blotting. Plasma membrane GLUT4 increased in each subject in response to exercise. The mean increase in plasma membrane GLUT4 for the subjects with type 2 diabetes was 74 +/-20% above resting values, and for the normal subjects the increase was 71+/-18% above resting values. Although plasma membrane GLUT4 content was approximately 32% lower at rest and after exercise in the muscle of the subjects with type 2 diabetes, the differences were not statistically significant. We conclude that in contrast to the previously reported defect in insulin-stimulated GLUT4 translocation in skeletal muscle of individuals with type 2 diabetes, a single bout of exercise results in the translocation of GLUT4 to the plasma membrane in skeletal muscle of individuals with type 2 diabetes. These data provide the first direct evidence that GLUT4 translocation is an important cellular mechanism through which exercise enhances skeletal muscle glucose uptake in individuals with type 2 diabetes.

Myocardial perfusion scintigraphy: effect on diagnostic and clinical management algorithms.

UNLABELLED: Research has demonstrated that myocardial perfusion imaging increases the sensitivity and specificity of stress electrocardiography. However, the additional effect of the perfusion component of a stress study on clinical management algorithms remains poorly defined. METHODS: We prospectively assessed the decision-making process in 518 patients, from 191 clinicians, undergoing stress myocardial perfusion imaging in our departments. Each clinician was asked, by telephone interview, to define the probability of reversible myocardial ischemia and their management plan (i.e., no antianginal treatment, medical therapy or an invasive intervention) in three stages: pretest, after the stress data was made available and after completion of the perfusion study. RESULTS: The results of the stress data alone influenced the estimate of the probability of reversible ischemia in 149 of 518 patients, and management strategy in 50 of 518 patients. The data from the perfusion component in isolation changed probability of reversible disease in 219 of 518 patients and altered clinical management in 77 of 518 patients. Of 103 patients in whom an invasive procedure was planned after the stress data, the availability of the perfusion data led to deferral of catheterization in 48 cases (46.6%). Conversely, of the 415 patients triaged to a noninvasive plan after stress data, only 29 (7.0%) were changed to an invasive strategy. Of note, only 2.3% of women changed from a conservative strategy as a consequence of the perfusion data, compared to 9.1% of men. CONCLUSION: The perfusion component of a stress study has a significant effect on both estimation of clinical probability and the definition of patient management strategy. Myocardial perfusion imaging reduced the number of catheterizations in patients initially triaged to an invasive management strategy. Conversely, the effect of stress and perfusion data in patients triaged to conservative management on clinical grounds, especially women, remains less well defined.

Extrarenal potassium homeostasis with maximal exercise in end-stage renal disease.

Serum potassium levels rise substantially during vigorous exercise as a result of the release of potassium from contracting muscle cells. Widespread use of erythropoietin has allowed for increased exercise capacity in patients with ESRD, raising the concern for severe exertional hyperkalemia. The aim of this study was to determine whether ESRD is associated with alterations in potassium and the neurohumoral mediators of extrarenal potassium disposal with maximal exercise. Eight stable hemodialysis patients (aged 37 +/- 16 yr, mean +/- SE) and eight healthy control subjects (aged 44 +/- 13 yr) exercised to exhaustion, using a graded cycle ergometer. There were no significant differences in exercise performance between groups as assessed by peak work rate, maximal oxygen consumption, and rate pressure product. Although the baseline potassium level was higher in the dialysis group (5.0 +/- 0.2 mEq/L) than in control subjects (4.5 +/- 0.1 mEq/L), both groups had a similar pattern of increase during exercise (with an increment of approximately 1 mEq/L) and a similar return to baseline after exercise. However, the dialysis patients had higher basal norepinephrine levels (820 +/- 104 versus 441 +/- 56 pg/mL, P < 0.01) and a greater response to exercise (3122 +/- 429 versus 1696 +/- 424 pg/mL, P < 0.01), higher basal insulin levels (11 +/- 1 versus 7 +/- 1 microU/mL, P < 0.05), higher insulin post-exercise levels (19 +/- 3 versus 11 +/- 1 microU/mL, P < 0.05), and higher basal aldosterone levels (621 +/- 250 versus 109 +/- 13 pg/mL, P < 0.05) with an increase response to exercise (1100 +/- 350 versus 350 +/- 17 pg/mL, P < 0.05). In summary, despite higher basal potassium, dialysis patients have normal potassium responses to maximal exercise. More vigorous insulin, catecholamine, and aldosterone levels may contribute to the maintenance of extrarenal potassium homeostasis in ESRD.

Psychological predictors of subsequent medical care among patients hospitalized with cardiac disease.

BACKGROUND: There have been numerous reports indicating a relation between psychological distress and coronary artery disease. The authors tried to determine whether psychological distress in patients hospitalized for coronary artery disease is associated with the amount of medical care required after discharge. METHODS: Using a prospective clinical cohort, 210 patients who had been admitted for myocardial infarction (n = 67), percutaneous transluminal coronary angioplasty (n = 75), or coronary artery bypass grafting (n = 68) were followed for 6 months. Index psychological status was determined from questionnaires measuring depression and anxiety. Disease severity was assessed by the index hospitalization medical record of left ventricular ejection fraction, number of stenotic vessels, and number of noncardiac comorbidities. The amount of subsequent medical care delivered was based on the number of days of rehospitalization for cardiac-related illness and for any reason within 6 months after discharge. This was determined from a combination of computer medical record and patient self-report. RESULTS: The authors first determined that both psychological depression and disease severity each predicted days of rehospitalization. (Anxiety was not predictive of rehospitalization.) Next, disease severity was controlled for using partial correlation, and depression was still predictive of rehospitalization. Finally, the authors combined the predictor variables using a regression model to predict rehospitalization. Depression was a significant main effect in all models predicting rehospitalization. CONCLUSIONS: Psychological depression appears to be an important predictor of rehospitalization among persons who have been admitted with coronary artery disease.

The impact of clinical data on interpretation of thallium scintigrams.

BACKGROUND: The availability of clinical information often influences the interpretation of diagnostic imaging information. METHODS AND RESULTS: In this study we examined the impact of such data on interpretation of exercise thallium scans and the differences in analysis of such information between radiologists and clinicians. Two hundred thirty-seven exercise tolerance test-thallium scans (122 in patients with suspected coronary disease and 115 in patients with documented coronary disease) were read prospectively, first without and then with the knowledge of clinical information. Test scores, the readers' and clinicians' interpretations of historic data, and any changes in readings or interpretation of scintigraphic data were recorded. We found that the addition of clinical information resulted in changes in interpretation of 63 test results (27%), 20 (8%) of them major. Furthermore, clinical data significantly affected final test scores in 26 patients (11%), potentially affecting clinical management in this group. The changes in test scores were triggered predominantly by differences in interpretation of perfusion abnormalities rather than thallium lung uptake or left ventricular dilation with exercise. The impact of clinical data on overall test scores was greater in patients with suspected than documented coronary disease (p < 0.05). There was good agreement in assessment of clinical information between scan readers and a clinician in tests done in patients with suspected coronary artery disease but not in patients with known coronary disease. CONCLUSIONS: We conclude that clinical information has major influences on the interpretation of thallium scans, and interpretation of data can vary significantly between cardiologists and radiologists depending on the nature of the clinical data.

Comparison of two transfusion strategies after elective operations for myocardial revascularization.

We performed a prospective, randomized trial of two different strategies for postoperative packed red blood cell replacement in 39 autologous blood donors undergoing elective myocardial revascularization. The "liberal" group received blood to achieve a hematocrit value of 32%, and the "conservative" group received transfusions for a hematocrit value less than 25%. Although the groups had significantly different mean hematocrit values from the fourth postoperative hour (28.7% versus 31.2%) through the fifth postoperative day (28.4% versus 31.3%), there were no significant differences in fluid requirement, hemodynamic parameters, or hospital complications. Significantly fewer units of packed cells were required in the conservatively transfused group (20 units/20 patients) compared with the liberally transfused group (37 units/18 patients) (p = 0.012). Exercise tests were performed on the fifth and sixth postoperative days, with a transfusion being given to the conservative group between tests. Although a significant improvement in exercise endurance occurred in the conservative group receiving a transfusion (p = 0.008), no significant difference in duration or degree of exercise was demonstrated between the two groups on either day. In comparing these two groups of profoundly anemic patients, we identified no adverse consequence associated with the greater degree of hemodilution and could identify no correlation between hematocrit value and exercise capacity. We conclude that although the limits of hemodilution are still poorly defined, postoperative blood transfusion in revascularized patients should be guided by clinical indications and not by specific hematocrit values.

Enhanced left ventricular diastolic filling associated with long-term endurance training.

Normal aging is associated with an impairment in early left ventricular diastolic filling. To test the hypothesis that long-term endurance exercise training is associated with enhanced ventricular diastolic filling indices, we compared transmitral pulsed Doppler inflow spectra in healthy young adults; healthy elderly, sedentary subjects (sedentary old); and healthy elderly, endurance athletes (master athletes). Our data demonstrate that, despite an increase in left ventricular mass, early diastolic filling was enhanced in master athletes compared to the sedentary old. Blood pressure of both master athletes and the sedentary olds was greater than the young adults, but the higher blood pressure did not correlate to changes in filling parameters. Resting systolic function and heart rate were not significantly different in all three different groups. Early left ventricular filling indices in master athletes more closely resemble transmitral inflow patterns of healthy young adults. Long-term endurance exercise is associated with physiologic hypertrophy and ventricular filling dynamics more characteristic of the young than the old.

The effect of caffeine on exercise tolerance and left ventricular function in patients with coronary artery disease.

STUDY OBJECTIVE: To determine whether acute oral caffeine ingestion by patients with coronary artery disease results in decreased treadmill exercise performance or deterioration of echocardiographic measures of systolic or diastolic left ventricular function. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Referral-based cardiovascular exercise laboratory at an urban teaching hospital. PATIENTS: Thirteen volunteers with clinically stable coronary artery disease who had exercise tests after a 2-week caffeine-free washout period. Patients continued treatment with standard antianginal medications during the study period. INTERVENTIONS: Maximal exercise treadmill testing and exercise echocardiography were done at baseline, after acute ingestion of a placebo beverage (97% caffeine-free coffee), or after drinking an identical beverage containing 250 mg of caffeine sodium benzoate. MEASUREMENTS AND MAIN RESULTS: Acute ingestion of caffeine produced a serum level of 4.50 +/- 0.16 micrograms/mL, but had no effect on resting supine heart rate, blood pressure, left ventricular fractional shortening, posterior left ventricular wall thinning or peak rates of increase in left ventricular diastolic dimension. Despite a small increase in peak systolic blood pressure during exercise (baseline, 153 +/- 8; placebo, 154 +/- 8; caffeine, 161 +/- 7 mm Hg; P less than 0.05), exercise duration, time to onset of angina, and time to 0.1 mV ST depression did not differ after ingestion of placebo or caffeine. Rate-pressure product at onset of angina and onset of 0.1 mV of ST depression were also unchanged. In response to exercise, echocardiographic measures of left ventricular systolic and diastolic function were unchanged after caffeine compared with placebo ingestion. CONCLUSIONS: These data suggest that patients with exercise-induced ischemia who are receiving appropriate antianginal therapy tolerate the caffeine-equivalent of three cups of coffee without detrimental effect on intensity of ischemia, myocardial function, or exercise duration.

Hemodynamic responses to noninvasive external cardiac pacing.

Although improvements in noninvasive external cardiac pacing have led to a technique with reliable electrical capture and reduced patient discomfort, hemodynamic responses to this pacing mode have not been described previously. Accordingly, this technique was applied to 16 patients with a clinical diagnosis of angina pectoris undergoing cardiac catheterization. Three patients had normal coronary arteries, whereas the remaining 13 had significant coronary artery disease. All patients had noninvasive pacing at increasing heart rates to 85 percent of age-predicted maximal heart rate. At maximal pacing, all patients demonstrated a rise in atrial, pulmonary artery, and mean aortic pressures. Cardiac index remained unchanged, reflecting parallel increases in arteriovenous oxygen difference and oxygen consumption. One minute after cessation of pacing, pulmonary artery pressure and oxygen consumption remained elevated, whereas arteriovenous oxygen difference returned to baseline with a subsequent rise in cardiac index. Angina occurred in eight patients with coronary artery disease at peak pacing and was accompanied by a rise in left ventricular end-diastolic pressure after pacing. In eight patients without pacing-induced angina, including the three patients with normal coronary arteries, there was no significant change in left ventricular end-diastolic pressure after pacing. It is concluded that noninvasive external cardiac pacing produces a rise in both right and left heart filling pressures and in oxygen consumption that persist after pacing, and may provoke angina and hemodynamic abnormalities consistent with myocardial ischemia. This mode of pacing appears hemodynamically safe with maintenance of cardiac index and aortic pressure at 85 percent of maximal age-predicted heart rate.

Noninvasive external cardiac pacing for thallium-201 scintigraphy.

Improvements in noninvasive external cardiac pacing have led to a technique with reliable electrical capture and tolerable patient discomfort. To assess the use of this modality of pacing in combination with thallium scintigraphy as a noninvasive pacing stress test, we applied simultaneous noninvasive cardiac pacing, hemodynamic monitoring, and thallium-201 scintigraphy in 14 patients undergoing cardiac catheterization for chest pain syndromes. Two patients had normal coronary arteries, while the remaining 12 had significant coronary artery disease. Thallium scintigraphic responses to pacing were compared to routine exercise thallium stress testing in nine of these 14 patients. All patients were noninvasively paced to more than 85% of the age-predicted maximum heart rate. Twelve patients demonstrated reversible thallium defects, which corresponded in 11 cases to significant lesions seen on coronary angiography. Of nine patients who underwent both pacing and exercise thallium stress tests, comparable maximal rate-pressure products were achieved. Moreover, thallium imaging at peak pacing and during delayed views did not differ significantly from exercise thallium scintigraphy. A limiting factor associated with the technique was local patient discomfort, which occurred to some degree in all patients. We conclude that noninvasive external cardiac pacing together with thallium scintigraphy is capable of detecting significant coronary artery disease and may be comparable to routine exercise thallium stress testing. This new modality of stress testing could be useful in patients unable to undergo the exercise required for standard exercise tolerance testing, particularly if improvements in the technology can be found to reduce further the local discomfort.

Supine versus upright anterior images: comparison in T1-201 myocardial scintigraphy.

In patients undergoing exercise thallium-201 myocardial scintigraphy, activity in the inferior wall on anterior images may appear diminished when the standard supine view is used, but normal when the view is acquired with the patient upright. To determine the clinical significance of this observation, the distribution of thallium-201 activity was semiquantitatively assessed in supine and upright anterior images obtained immediately after exercise in 93 patients (65 men, 28 women). The presence of inferior wall and coronary artery disease was established with coronary angiography or from documentation of previous myocardial infarction. Supine and upright images were compared with use of receiver operating characteristic curves. In male patients diagnostic accuracy for identification of both inferior wall and coronary artery disease was improved through the use of the upright anterior image. In women, there was no significant difference in reader performance with upright and supine images. Upright anterior images should be routinely obtained in men in order to reduce the frequency of false-positive identification of inferior wall defects.

Assessment of long-term therapy with milrinone and the effects of milrinone withdrawal.

To assess the long-term efficacy of milrinone in patients with severe congestive heart failure, we obtained hemodynamic measurements (systemic arterial and right heart catheterization) in 13 patients at baseline and after intravenous administration of milrinone. After continuous oral milrinone therapy of 8 +/- 4 months duration, repeat hemodynamic study was performed in patients on oral milrinone therapy, after withdrawal of milrinone, and after readministration of milrinone intravenously. Comparison of initial baseline and withdrawal hemodynamic measurements for the group as a whole showed no interval progression of heart failure, as reflected by the pulmonary capillary wedge pressure (27 +/- 8 to 24 +/- 12 mm Hg, NS) or the cardiac index (2.0 +/- 0.4 to 2.1 +/- 0.8 liters/min/m2, NS). Individual comparisons of milrinone-free hemodynamics revealed that five patients had improved hemodynamically, three patients were unchanged, and five patients had deteriorated, four of whom manifested dependence on milrinone with a progressive hemodynamic decline after milrinone withdrawal which required readministration of milrinone on an emergency basis. Continued efficacy of milrinone was observed on readmission after withdrawal: pulmonary capillary wedge pressure fell from 27 +/- 8 to 16 +/- 10 mm Hg (p = .001) initially and from 24 +/- 12 to 13 +/- 11 mm Hg (p = .001) at readministration, while cardiac index rose from 2.0 +/- 0.4 to 2.8 +/- 0.5 liters/min/m2 (p = .001) initially and from 2.1 +/- 0.8 to 2.7 +/- 0.5 liters/min/m2 (p = .005) upon readministration.(ABSTRACT TRUNCATED AT 250 WORDS)

Catecholamine modulation of rapid potassium shifts during exercise.

Plasma potassium rises during muscular exercise and falls rapidly when exercise is stopped. Since the sympathoadrenal system is stimulated with exertion and both alpha- and beta-adrenergic agonists affect internal potassium homeostasis, we studied the influence of catecholamines on potassium shifts during and after exercise. Six healthy subjects were given maximal exercise stress tests under three conditions: with no medication (control), during beta-blockade with propranolol, and during alpha-blockade with phentolamine. Compared with a peak rise in plasma potassium of 1.23 +/- 0.27 mmol per liter (mean +/- S.E.M.) during the control study, propranolol caused a rise of 1.89 +/- 0.35 (P less than 0.01) and a sustained elevation during recovery. Phentolamine diminished the rise of potassium (0.70 +/- 0.21 mmol per liter; P less than 0.01) and lowered the potassium level throughout recovery. These effects of catecholamines were independent of the venous pH, the plasma bicarbonate and serum glucose levels, and urinary potassium excretion, and they did not appear to be due to insulin. High norepinephrine and epinephrine levels confirmed the release of catecholamines capable of stimulating alpha- and beta-receptors. Exercise work did not differ among the groups. beta-Adrenergic receptors appear to moderate the acute hyperkalemia of exercise, whereas alpha-adrenergic receptors act to enhance hyperkalemia and may protect against hypokalemia when exertion ceases.

Endurance training effects on plasma hormonal responsiveness and sex hormone excretion.

A prospective study of the hormonal effects of a moderate exercise training program (4-wk control, 8-wk training) was conducted in seven young women. Sixty-minutes continuous bicycle ergometer tests of fixed relative intensity were performed at the beginning, middle, and end of the training period. The capacity of these acute bouts of exercise to affect circulating levels of stress markers, reproductive hormones, and hormones with possible antireproductive potential was measured. In addition, the urinary excretion of reproductive hormones was monitored continuously via serial overnight urine collections. Within testing sessions, plasma concentrations of all stress markers and antireproductive hormones rose significantly. Across testing sessions, only beta-endorphin + beta-lipotropin and cortisol exhibited an increment in peak responses as training progressed. Plasma reproductive hormone levels showed insignificant acute changes, and cyclic menstruation and preovulatory gonadotropin surges continued in all subjects. However, ovarian function was disturbed in four subjects as evidenced by a decreased excretion of estriol, free progesterone, or both. Transient infertility is a known clinical accompaniment of hormonal changes of comparable subtlety.