Mechanisms of impaired exercise capacity in short duration experimental hyperthyroidism.

To investigate the mechanism of reduced exercise tolerance in hyperthyroidism, we characterized cardiovascular function and determinants of skeletal muscle metabolism in 18 healthy subjects aged 26 +/- 1 yr (mean +/- SE) before and after 2 wk of daily ingestion of 100 micrograms of triiodothyronine (T3). Resting oxygen uptake, heart rate, and cardiac output increased and heart rate and cardiac output at the same submaximal exercise intensity were higher in the hyperthyroid state (P less than 0.05). However, maximal oxygen uptake decreased after T3 administration (3.08 +/- 0.17 vs. 2.94 +/- 0.19 l/min; P less than 0.001) despite increased heart rate and cardiac output at maximal exercise (P less than 0.05). Plasma lactic acid concentration at an equivalent submaximal exercise intensity was elevated 25% (P less than 0.01) and the arteriovenous oxygen difference at maximal effort was reduced (P less than 0.05) in the hyperthyroid state. These effects were associated with a 21-37% decline in activities of oxidative (P less than 0.001) and glycolytic (P less than 0.05) enzymes in skeletal muscle and a 15% decrease in type IIA muscle fiber cross-sectional area (P less than 0.05). Lean body mass was reduced (P less than 0.001) and the rates of whole body leucine oxidation and protein breakdown were enhanced (P less than 0.05). Thus, exercise tolerance is impaired in short duration hyperthyroidism because of decreased skeletal muscle mass and oxidative capacity related to accelerated protein catabolism but cardiac pump function is not reduced.     

高压氧辅助治疗青年人心肌缺血398例

Background: Main causes of youth myocardial ischemia are smoking and hypercholesterolemia, which leads to disorder of collateral circulation, increase of cardiac accidence and coronary atherosclerosis. Hypoxia is easy to happen because thick of sclerotic vessels wall nearly reaches the maximal diffuse distance in this tissue. CO in cigarettes can lead to hypoxia and myocardial ischemia. After use of hyperbaric oxygen, blood fat decrease, incidence of coronary atherosclerosis decreases apparently. And it promotes myocardial hypoxia and metabolism, increases myocardial contraction and promotes heart function, thereby decrease incidence of angina, myocardial infarction and sudden death.     

Lung function and exercise performance in hyperthyroidism before and after treatment

In order to investigate the mechanism of dyspnoea in hyperthyroidism measurements of spirometry, lung volume, transfer factor for carbon monoxide and its subdivisions, maximal respiratory pressures, methacholine challenge, arterial blood gases were made and exercise studies performed on 16 patients before treatment for hyperthyroidism. Methacholine challenge showed that only three of 14 patients increased airway reactivity, which was mild. Maximal pressures which could be generated by the respiratory muscles were reduced in some patients, as was functional residual capacity. Exercise ventilation and breathing frequency were increased and the respiratory exchange ratio was abnormally high. Anaerobic threshold was measured in nine of 15 subjects and was below normal in each case. All but two subjects stopped exercise because of dyspnoea, and the maximum oxygen uptake achieved by the group was 53 per cent (n = 15, range 26-66 per cent) of predicted maximum oxygen consumption. The maximum ventilation averaged only 43 per cent (n = 15, range 16-96 per cent) of the maximal breathing capacity predicted from spirometric tests. Nine patients were studied shortly after being rendered euthyroid by treatment. At rest, only maximal respiratory pressures increased significantly. On exercise, the maximal workload attained and the ventilation achieved increased significantly. Breathing patterns, maximal oxygen consumption, ventilation, anaerobic threshold and cardiac frequency remained unchanged. We conclude that: patients with hyperthyroidism do not generally have increased airway reactivity; when hyperthyroid, respiratory muscles are weak, and improve following treatment; exercise capacity is impaired in hyperthyroid patients probably because of a combination of an inefficiently rapid and shallow breathing pattern, an increase of anaerobic metabolism and discomfort associated with the act of breathing. Although exercise capacity increases and the sensation of dyspnoea may decrease after treatment the pattern of breathing does not immediately return to normal.     

Acute regional vascular effects of intravenous captopril in a rat model of myocardial infarction and failure

The effects of i.v. captopril on regional blood flow (radioactive microspheres, 15 +/- 5 micron), hemodynamics and maximal oxygen consumption were evaluated in conscious rats with congestive heart failure due to large myocardial infarction (n = 9, infarct size 39.5 +/- 2% of left ventricle) and compared to data obtained from rats subjected to sham surgical procedures (n = 8). In both groups data were obtained at rest and during submaximal treadmill exercise during alternate infusion of captopril and saline. In the congestive heart failure group captopril reduced systemic vascular resistance, mean arterial pressure and left ventricular systolic pressure (P less than .05 each). Blood flow to the renal, gastrointestinal and coronary circulations was reduced in the heart failure group treated with saline vehicle. Flow to the renal and gastrointestinal beds of heart failure animals was enhanced to values similar to those observed in sham animals during captopril treatment. Left ventricular coronary flow was also increased significantly by captopril in both sham and heart failure animals. The most prominent effects of captopril occurred in the renal circulation of the heart failure group in which blood flow increased by 55%. Blood flow to skeletal muscle and skin was unchanged by captopril both in sham and heart failure animals at rest and during exercise. Maximal oxygen consumption was not affected by captopril treatment. Thus, captopril induced a differential pattern of vasodilation with the greatest effect in the renal bed and a less intensive effect in the gastrointestinal and coronary beds. The unchanged flow to skeletal muscle may explain the failure of captopril to improve exercise capacity after short-term administration.     

Exercise physiology and cardiovascular fitness

Endurance exercise training produces numerous metabolic and cardiovascular effects. Metabolic adaptations include an increase in oxidative capacity of skeletal muscle (greater number and size of mitochondria); an increase in skeletal muscle myoglobin concentration; a greater ability to oxidize fatty acids for energy; and an increase in stored glycogen. Cardiovascular effects of training include a decrease in resting heart rate and heart rate response to submaximal exercise; an increase in resting and exercise stroke volume; an increase in maximal cardiac output; an increase in VO2max; and an increase in arteriovenous oxygen difference. Aerobic exercise training contributes to cardiovascular fitness, because it beneficially alters the coronary artery disease risk profile. An inverse relationship exists between physical fitness and resting heart rate, body weight, percent body fat, serum cholesterol, triglycerides, glucose, and systolic blood pressure. In addition, exercise training increases the high-density lipoprotein fraction of total cholesterol. Endurance exercise is any activity that uses large muscle groups, can be performed continuously, and is rhythmic and aerobic in nature. To develop and maintain cardiovascular fitness, this exercise should be performed at a frequency of 3 to 5 days per week, an intensity of 60% to 90% HRmax or 50% to 85% HRmax reserve, and a duration of 20 to 60 minutes.     

Respiratory and circulatory adaptation to isometric and dynamic exercise in chronic lung disease

Summary. Changes at the beginning of isometric and dynamic low level exercise were studied in 23 patients with chronic lung disease. Ventilation, oxygen consumption and vascular pressures in systemic and pulmonary circulation were continuously monitored, and cardiac output was measured by thermodilution every minute. Circulatory changes took place suddenly at the beginning of isometric exercise and gradually during dynamic exercise. Ventilatory changes followed almost the same progressive pattern in both types of exercise. Ventilation increase in relation to oxygen uptake was slightly smaller during isometric exercise. Pulmonary artery pressure showed no further increase after the initial change, although ventilation was still rising.     

Oxidative stress in cardiac and skeletal muscle dysfunction associated with diabetes mellitus

Diabetes mellitus increases the risk of heart failure independently of underlying coronary artery disease. It also causes skeletal muscle dysfunction, which is responsible for reduced exercise capacity commonly seen in heart failure. The underlying pathogenesis is partially understood. Several factors may contribute to the development of cardiac and skeletal muscle dysfunction in heart failure and diabetes mellitus. Based on the findings in animal models, this review discusses the role of oxidative stress that may be involved in the development and progression of cardiac and skeletal dysfunction associated with diabetes.     

A clinical course of coronary heart disease after pacemaker implantation and optimization of the pacing regime

AIM: To study effects of pacemaker implantation on the course of coronary heart disease (CHD) with stable angina pectoris and choice of optimal regimen of pacing. MATERIAL AND METHODS: A total of 154 CHD patients with a pacemaker were examined. All the patients had angina of effort of functional class II-IV. RESULTS: The symptoms of the disease improved in 72 (46.8%) patients (group 1): the number of anginal attacks decreased, exercise tolerance increased, the dose of antianginal medicines went down. Pain attacks became more frequent, response to nitroglycerin changed in 30 (19.5%) patients of group 2. This was explained by 1.5-2-fold enhancement of heart rate by pacemaker raising myocardial oxygen consumption and psychocardial syndrome. In 52 (33.8%) patients of group 3 anginal attacks characteristics did not change. CONCLUSION: To optimize coronary reserve, frequency of electroimpulses must be reprogrammed to adjust to a functional class of angina and chronic cardiac failure as well as pacing regime. In particular, low coronary reserve demands optimal frequency of 55-65 imp/min while congenital cardiac failure--75-85 imp/min.     

Deficiency of skeletal muscle succinate dehydrogenase and aconitase. Pathophysiology of exercise in a novel human muscle oxidative defect.

We evaluated a 22-yr-old Swedish man with lifelong exercise intolerance marked by premature exertional muscle fatigue, dyspnea, and cardiac palpitations with superimposed episodes lasting days to weeks of increased muscle fatigability and weakness associated with painful muscle swelling and pigmenturia. Cycle exercise testing revealed low maximal oxygen uptake (12 ml/min per kg; healthy sedentary men = 39 +/- 5) with exaggerated increases in venous lactate and pyruvate in relation to oxygen uptake (VO2) but low lactate/pyruvate ratios in maximal exercise. The severe oxidative limitation was characterized by impaired muscle oxygen extraction indicated by subnormal systemic arteriovenous oxygen difference (a-v O2 diff) in maximal exercise (patient = 4.0 ml/dl, normal men = 16.7 +/- 2.1) despite normal oxygen carrying capacity and Hgb-O2 P50. In contrast maximal oxygen delivery (cardiac output, Q) was high compared to sedentary healthy men (Qmax, patient = 303 ml/min per kg, normal men 238 +/- 36) and the slope of increase in Q relative to VO2 (i.e., delta Q/delta VO2) from rest to exercise was exaggerated (delta Q/delta VO2, patient = 29, normal men = 4.7 +/- 0.6) indicating uncoupling of the normal approximately 1:1 relationship between oxygen delivery and utilization in dynamic exercise. Studies of isolated skeletal muscle mitochondria in our patient revealed markedly impaired succinate oxidation with normal glutamate oxidation implying a metabolic defect at the level of complex II of the mitochondrial respiratory chain. A defect in Complex II in skeletal muscle was confirmed by the finding of deficiency of succinate dehydrogenase as determined histochemically and biochemically. Immunoblot analysis showed low amounts of the 30-kD (iron-sulfur) and 13.5-kD proteins with near normal levels of the 70-kD protein of complex II. Deficiency of succinate dehydrogenase was associated with decreased levels of mitochondrial aconitase assessed enzymatically and immunologically whereas activities of other tricarboxylic acid cycle enzymes were increased compared to normal subjects. The exercise findings are consistent with the hypothesis that this defect impairs muscle oxidative metabolism by limiting the rate of NADH production by the tricarboxylic acid cycle.     

Investigation of the Physiological Basis for Increased Exercise Threshold for Angina Pectoris after Physical Conditioning

Eight patients with coronary heart disease and exertional angina pectoris successfully completed an 11-15 wk program of endurance exercise conditioning. Angina threshold was determined by upright bicycle ergometer exercise and by atrial pacing. The product of heart rate and arterial systolic blood pressure at the exercise angina threshold was higher after conditioning. suggesting that conditioning increased the maximum myocardial O(2) supply during exercise. However, when angina was induced by atrial pacing, heart rate, arterial blood pressure, coronary blood flow, and myocardial O(2) consumption at the angina threshold were the same before and after conditioning. Myocardial lactate extraction during atrial pacing was abnormal in the same five patients before and after conditioning. Conditioning caused no detectable changes in coronary collaterals as judged by coronary arteriograms.The increase in exercise angina threshold appeared to be due to a functional adaptation in either myocardial O(2) supply or the relationship between hemodynamic work and myocardial O(2) consumption. The adaptation was limited to exercise, and did not occur during a different stress to myocardial O(2) supply, atrial pacing.     

Exercise intolerance, lactic acidosis, and abnormal cardiopulmonary regulation in exercise associated with adult skeletal muscle cytochrome c oxidase deficiency.

A 27-yr-old woman with lifelong severe exercise intolerance manifested by muscle fatigue, lactic acidosis, and prominent symptoms of dyspnea and tachycardia induced by trivial exercise was found to have a skeletal muscle respiratory chain defect characterized by low levels of reducible cytochromes a + a3 and b in muscle mitochondria and marked deficiency of cytochrome c oxidase (complex IV) as assessed biochemically and immunologically. Investigation of the pathophysiology of the exercise response in the patient revealed low maximal oxygen uptake (1/3 that of normal sedentary women) in cycle exercise and impaired muscle oxygen extraction as indicated by profoundly low maximal systemic arteriovenous oxygen difference (5.8 ml/dl; controls = 15.4 +/- 1.4, mean +/- SD). The increases in cardiac output and ventilation during exercise, normally closely coupled to muscle metabolic rate, were markedly exaggerated (more than two- to threefold normal) relative to oxygen uptake and carbon dioxide production accounting for prominent tachycardia and dyspnea at low workloads. Symptoms in our patient are similar to those reported in other human skeletal muscle respiratory chain defects involving complexes I and III, and the exaggerated circulatory response resembles that seen during experimental inhibition of the mitochondrial respiratory chain. These results suggest that impaired oxidative phosphorylation in working muscle disrupts the normal regulation of cardiac output and ventilation relative to muscle metabolic rate in exercise.     

Metabolic Control of the Circulation: EFFECTS OF ACETATE AND PYRUVATE

Chloralose-anesthetized dogs were infused intravenously with either Tris-acetate or Tris-pyruvate at 0.0375, 0.075, and 0.15 mmol/kg per min successively, each for 20 min. Acetate infusion increased cardiac output, left ventricular dP/dt and dP/dt/P, and coronary blood flow, while pyruvate infusion did not. Infusions of either substance increased arterial blood and skeletal muscle concentrations of citrate and malate, but only acetate infusion increased the tissue AMP content and decreased the ATP:AMP ratio. The increase in cardiac output produced by acetate was accompanied by an increase in total body oxygen consumption and a decrease in the difference between arterial and mixed venous blood oxygen.Myocardial oxygen consumption increased during acetate infusion, but the decrease in myocardial oxygen extraction and the increase in coronary sinus blood oxygen saturation suggest that an active coronary vasodilation which was not a result of the increased cardiac work, occurred. The concentration of hypoxanthine in the coronary sinus and the content of myocardial adenosine increased, which suggests that the increase in coronary blood flow was caused by the vasodilator action of adenosine released from the myocardium, and that adenosine production is not necessarily tied to PO(2).These systemic and coronary hemodynamic changes also occurred when acetate (0.075 mmol/kg per min) was infused into conscious dogs. Acetate infusion also increased blood flow to the gastrointestinal tract, kidneys, intercostal muscle, and diaphragm. These changes were not affected by propranolol pretreatment, but were abolished by pretreatment with fluoroacetate which reduced acetate oxidation.These results suggest that the circulatory stimulation produced by acetate was not caused by increases in tricarboxylic acid cycle intermediates. Instead, it was probably related to the increased cleavage of ATP to AMP that accompanies activation of acetate to acetyl CoA, and was not mediated via beta-adrenergic receptors. It is speculated that hemodynamic changes may occur in patients who undergo hemodialysis with acetate-containing dialysate. Hemodynamic changes of ethanol may also be brought about by acetate, which is one of the intermediates that accumulates during ethanol metabolism.     

Trans-sodium crocetinate does not affect oxygen uptake in rats during treadmill running

Trans-sodium crocetinate (TSC), the isomer of the carotenoid compound crocetin, is found markedly to increase survival in hemorrhagic shock subsequent to 50-60% blood loss, mainly via restored resting oxygen consumption (VO(2)), blood pressure and heart rate. The proposed mechanism is that TSC increases oxygen diffusivity, and thus availability, in plasma. If this were found to be a prominent feature in the oxygen transfer from blood to skeletal muscle fiber mitochondria, increased VO(2) during exercise would be expected because of reduced partial pressure of venous oxygen (increased utilization), which we aimed to elucidate in this study. Male Sprague-Dawley rats were intravenously injected with 0.3 mL kg(-1) TSC (40 microg mL(-1)) or placebo and immediately thereafter tested on a ramped treadmill test protocol. Rats were introduced to the experimental protocols beforehand. Administration of TSC had a neutral effect on submaximal and maximal VO(2) (VO(2max)) as well as running performance measured as maximal running time and maximal aerobic running velocity. Thus, in this study we cannot report any effects of TSC on steady-state submaximal VO(2) or VO(2max) at exhaustive exercise.     

Skeletal muscle and the control of ventilation on exercise: evidence for metabolic receptors

Abstract. Patients with chronic heart failure have an increased ventilatory response to exercise, and have metabolically abnormal skeletal muscle. It has been proposed that a neural signal to ventilation arising from exercising muscle may be heightened in chronic heart failure. Our objective was to detect evidence for such a signal in normal subjects by studying ventilatory behaviour during exercise with muscles in different metabolic states. Fifteen normal subjects undertook treadmill exercise both with and without cuffs inflated around each thigh to suprasystolic pressure. In a second experiment, a group of 11 normal subjects undertook cycle exercise using arms or legs at the same absolute work load. Metabolic gas exchange was measured using mass spectrometry with indicator gas dilution. The ventilatory response was greater at a given workload when subjects exercised with inflated cuffs. Oxygen consumption was reduced in keeping with the isolation of the exercising muscle bulk from the circulation. The ventilation/carbon dioxide output relationship was described by a linear regression function, but the slope of the relationship was increased by 25% from 20.9 (0.46) to 25.43 (0.73) P< 0.001). Arm exercise at the same load as leg exercise resulted in unchanged oxygen consumption indicating that the same external work was being performed. There was an increase in ventilation at a given workload. The ventilation/carbon dioxide output slope was increased by 25% (from 21.9 (0.9) to 26.3 (0.8))(P<0.001).There is a signal to ventilation arising from exercising skeletal muscle which is enhanced by the ischaemia induced by cuff inflation during exercise. This signal appears to be neural. Second, the signal to ventilation is a function of work per unit muscle rather than total external work. These finding may have possible implications for the understanding of the increased ventilatory response to exercise in patients with heart failure, in whom there are both metabolic muscle abnormalities and a reduction in skeletal muscle bulk.     

Inhibition of free fatty acids metabolism as a therapeutic target in patients with heart failure

Recent studies have evidenced that alterations of cardiac metabolism can be present in several cardiac syndromes. In heart failure, wasting of subcutaneous fat and skeletal muscle is relatively common and suggests an increased utilisation of non-carbohydrate substrates for energy production. In fact, fasting blood ketone bodies as well as fat oxidation during exercise have been shown to be increased in patients with heart failure. This metabolic shift determines a reduction of myocardial oxygen consumption efficiency. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilisation by the heart. To date, the most effective metabolic treatments include several pharmacological agents that directly inhibit fatty acid oxidation. Clinical studies have shown that these agents can substantially increase the ischaemic threshold in patients with effort angina. However, the results of current research is also supporting the concept that shifting the energy substrate preference away from fatty acid metabolism and towards glucose metabolism could be an effective adjunctive treatment in patients with heart failure, in terms of left ventricular function and glucose metabolism improvement. In fact, these agents have also been shown to improve overall glucose metabolism in diabetic patients with left ventricular dysfunction. In this paper, the recent literature on the beneficial therapeutic effects of modulation of cardiac metabolic substrates utilisation in patients with heart failure is reviewed and discussed.     

Is the beneficial effect of prior exercise on postprandial lipaemia partly due to redistribution of blood flow?

Preprandial aerobic exercise lowers postprandial lipaemia (a risk factor for coronary heart disease); however, the mechanisms responsible are still not clear. The present study investigated whether blood flow to skeletal muscle and/or the liver was increased in the postprandial period after exercise, relative to a control trial, and whether this resulted from increased cardiac output or redistribution of flow. Eight overweight inactive males, aged 49.4±10.5?years (mean±S.D.), acted as their own controls in a counterbalanced design, either walking briskly for 90?min at 60% V?O2max (maximal oxygen uptake), or resting in the lab, on the evening of day 1. The following morning, a fasting blood sample was collected, participants consumed a high-fat breakfast, and further venous blood samples were drawn hourly for 6?h. Immediately after blood sampling, Doppler ultrasound was used to measure cardiac output and blood flow through both the femoral artery of one leg and the hepatic portal vein, with the ultrasonographer blinded to trial order. The total postprandial triacylglycerol response was 22% lower after exercise (P=0.001). Blood flow through the femoral artery and the hepatic portal vein was increased by 19% (P<0.001) and 16% (P=0.033), respectively, during the 6-h postprandial period following exercise; however, postprandial cardiac output did not differ between trials (P=0.065). Redistribution of blood flow, to both exercised skeletal muscle and the liver, may therefore play a role in reducing the plasma triacylglycerol response to a high-fat meal on the day after an exercise bout.     

Principles of Exercise Physiology: Responses to Acute Exercise and Long-term Adaptations to Training

Physical activity and fitness are associated with a lower prevalence of chronic diseases, such as heart disease, cancer, high blood pressure, and diabetes. This review discusses the body's response to an acute bout of exercise and long-term physiological adaptations to exercise training with an emphasis on endurance exercise. An overview is provided of skeletal muscle actions, muscle fiber types, and the major metabolic pathways involved in energy production. The importance of adequate fluid intake during exercise sessions to prevent impairments induced by dehydration on endurance exercise, muscular power, and strength is discussed. Physiological adaptations that result from regular exercise training such as increases in cardiorespiratory capacity and strength are mentioned. The review emphasizes the cardiovascular and metabolic adaptations that lead to improvements in maximal oxygen capacity.     

Coronary Occlusion and Coronary Insufficiency

Acute coronary attacks may be divided clinically, electrocardiographically, pathologically and therapeutically into (i) classical angina pectoris, (2) acute coronary insufficiency and (3) acute coronary occlusion. In 1000 consecutive cardiac consultations, 450 of 618 cases with organic heart disease had coronary artery disease. Of these 450 cases, 38 per cent had chronic coronary insufficiency (angina pectoris or congestive failure), 26 per cent had acute coronary insufficiency, and 36 per cent had acute coronary occlusion. The differentiation between coronary occlusion and insufficiency which can be made electrocardiographically in 95 per cent of cases is discussed in this paper.     

Effects of chronic dobutamine administration on the response to acute exercise in dogs

Summary. The effects of chronic dobutamine administration on haemodynamic and metabolic responses to submaximal and maximal exercise were studied in dogs. Dobutamine was infused at a rate of 40 μg/kg min^-1, 2 h day^-1, 5 days week^-1 for a period of 6 weeks. Acute infusion of dobutamine for 1 h increased heart rate by 73 ± 30 beats min^-1 and cardiac output by 143 ± 141 ml/min kg^-1, reduced mean arterial blood pressure by 12 ± 10 mmHg and arterial-venous O₂ difference by 1.5 ± 1 vol%. Maximal oxygen consumption, heart rate, stroke volume, cardiac output and arterial-venous O₂ difference were unchanged after 6 weeks of treatment. Reductions in heart rate at rest and during submaximal exercise following chronic dobutamine treatment were small and significant only at the lowest exercise level studied. Mixed venous lactate concentrations measured at rest, during submaximal and maximal exercise and at 2 min of recovery were not different after dobutamine treatment. Chronic dobutamine infusion did not change the citrate synthase activity in the lateral gastrocnemius muscle. These results suggest that chronic dobutamine therapy in healthy dogs does not produce aerobic training responses.     

Arterial hypoxemia in awake dogs. Role of the sympathetic nervous system in mediating the systemic hemodynamic and regional blood flow responses

The role of the sympathetic nervous system in the systemic hemodynamic and regional blood flow responses to hypoxia was studied in awake dogs by pre-exposing the animals to phentolamine alone (alpha block) or to phentolamine plus propranolol (alpha + beta block). Hypoxia was produced by switching from room air to either an 8% or 5% oxygen-nitrogen mixture. During 8% oxygen breathing, cardiac output, heart rate, left ventricular dP/dt, dP/dt/P, myocardial oxygen consumption, and myocardial blood flow increased, and both total peripheral and coronary vascular resistance fell. These changes were similar in all groups with and without adrenergic blockade. However, during 5% oxygen breathing, the rises in cardiac output, heart rate, left ventricular dP/dt, myocardial oxygen consumption, and myocardial blood flow and the decrease in coronary vascular resistance were less marked in the group given alpha + beta block than the intact animals or group given alpha block. Coronary blood flow correlated with myocardial metabolic demands. Adrenal and skeletal muscle blood flows increased during hypoxia. Breathing 5% oxygen also increased flow to the brain, but renal and splanchnic flows showed only minor changes. These changes in organ vascular resistance were unaffected by the adrenergic blockade. Our results indicate that although the sympathetic nervous system plays an important role in the systemic hemodynamic responses to hypoxia, the dominant local metabolic factors probably are primarily responsible for hypoxic vasodilation in the awake dog.