Adaptation of cardiac morphology and function to endurance and strength training. A comparative study using MR imaging and echocardiography in males and females.

Left ventricular (LV) dimensions and function and maximal oxygen uptake (VO(2)max) were measured in endurance-trained (10 male, m, 10 female, f), strength-trained athletes (8 m, 10 f) and untrained subjects (9 m, 10 f). LV dimensions were measured using magnetic resonance imaging (MRI) and echocardiography and the results were equal irrespective of method. Endurance-trained m and f had significantly higher LV volumes and mass than both strength-trained and controls. No VO(2)max or dimensional differences were seen between strength-trained and untrained subjects. In endurance-trained males, LV volumes and mass/kg bw were higher than in endurance-trained females. There was no significant gender difference for strength-trained or untrained subjects regarding body weight-related heart dimensions. It is concluded that LV dimensions and volumes are strongly dependent on oxygen transport capacity in normal subjects practising different modes of training, and that the gender differences, if LV dimensions are related to aerobic work capacity, are smaller than previously reported.

Maximal muscle activation is not limited by pulmonary ventilation in chronic hypoxia.

This study was conducted to test the hypothesis that inhibitory reflexes from respiratory centres in the brain or respiratory muscles limit the central motor drive to limb muscles during exhaustive exercise in chronic hypoxia. Experiments were performed on five members of an expedition to the Himalayas, following 56-81 days at altitudes of 5200-7500 m. During the last minute of exhaustive maximal two-legged cycling with and without 4% CO2 inhalation performed on different days, repeated maximal voluntary handgrip contractions (MVC) over 60 s (5 s contraction, 5 s rest; x 6) were performed at rest and exhaustive exercise MVC or rate of decay of MVC was unaffected by simultaneous engagement of a major fraction of the muscle mass (leg muscles) and a very high pulmonary ventilation. With 4% CO2, peak pulmonary ventilation during the exhaustive exercise increased further by 41 L min-1 (140-181 L min-1; P < 0.05) without affecting the handgrip strength. These findings suggest that during exhaustive exercise of large muscle groups in chronic hypoxia, both maximal voluntary contraction force and dynamic muscle contractile force are not limited by extreme activation of respiratory centres or muscles.

Cardiovascular response to exercise in humans following acclimatization to extreme altitude.

The purpose of this study was to assess the effects of acclimatization to extreme altitude on the cardiovascular system, using vagal and adrenergic blockade and acute restoration of normoxia during exercise to maximum with one and two legs. Fourteen climbers on an expedition to the Himalayas were studied at a lower base camp (5250 m) following 56-81 days at altitudes between 5250 and 8700 m. After acclimatization, peak heart rate (HRpeak), oxygen uptake (VO2peak) and noradrenaline (NA) were similar during maximal one- and two-legged cycling, whereas peak plasma lactate was higher during the one-legged protocol. HRpeak (range 113-168 beats min-1) was lowest when subjects returned from the higher camps. The degree of partial restoration of HRpeak to more normal values within seconds of 60% O2 inhalation (range 5-35 beats min-1 HRpeak increase) was greatest in subjects with low HRpeak. HR responses to beta-1 blockade increased as a function of HRpeak and the HR responses to atropine were the least in subjects with high HRpeak. These findings suggest that (a) the reduction in HRpeak is linked to the duration and severity of the hypoxaemia, (b) the degree of restoration of HRpeak with acute normoxia is dependent on the level of attenuation or down-regulation of cardiac sympathetic activation (SNA), (c) cardiac vagal drive is masked to a lesser extent in chronic hypoxia because of attenuated SNA and lower HRpeak values, and (d) the lower blood lactate levels at altitude is a function of muscle mass involvement rather than adrenergic activation, as normal peak values were reached during exercise with a small muscle mass.

The diagnostic and prognostic importance of ambulatory ST recording compared to a predischarge exercise test after an episode of unstable angina or non-Q wave myocardial infarction.

The diagnostic and prognostic value of ambulatory ST recordings after admission to the CCU and before discharge was compared to a symptom-limited predischarge exercise test in 170 men with unstable angina pectoris or non-Q wave myocardial infarction. ST depression in recordings before discharge identified a small group of patients (18%) out of whom 23% had a myocardial infarction within 3 months compared to 7% in those without this finding. The exercise test gave more diagnostic information, with ST depression found in 52% including 70% of those with ST depression at Holter monitoring. After 3 months, 13% of patients with ST depression at exercise test had a myocardial infarction compared to 5% in the other patients. ST depression at exercise also indicated an increased risk of myocardial and future severe angina over a longer time period. Thus ST recordings are recommended before discharge in all patients after an episode of unstable coronary artery disease as it identifies the patients with the most severe prognosis who might benefit from early revascularization. In those without ST depression at Holter a predischarge exercise test will give further information regarding the long-term risk for angina and coronary events.

Very early risk stratification by electrocardiogram at rest in men with suspected unstable coronary heart disease. The RISC Study Group.

OBJECTIVES: To determine the possibility of very early prognostic stratification based on electrocardiograms (ECGs) at rest and/or cardiac enzyme levels after an episode of suspected unstable coronary heart disease. DESIGN AND SETTING: Men with suspected unstable angina or non-Q-wave myocardial infarction were studied in the coronary care units of eight hospitals. The ECGs at rest and creatinine kinase were followed. SUBJECTS: In total 911 men were followed for 12 months. Of 8136 consecutively admitted, 3365 fulfilled the inclusion criteria. Excluded were 2454 patients, mainly because of a larger myocardial damage, signs of myocardial dysfunction, other serious cardiac or non-cardiac disease or an ECG not possible to interpret regarding ST-T-segment changes in the precordial leads. MAIN OUTCOME MEASURES: End-points at follow-up were cardiac death, myocardial infarction and severe (class III or IV) angina. RESULTS: Compared to patients with normal a ECG who had an 8% 1-year risk of myocardial infarction or death, the risk with isolated negative T waves was 14% (P < 0.05), ST elevation 16% (P < 0.05), ST depression 18% (P < 0.01) and the combination of ST elevation and ST depression 26% (P < 0.001). The only finding related to future severe angina was ST depression. The risk of cardiac events was comparably elevated in patients with anterior or inferior site of ECG changes. Cardiac enzyme levels had no predictive value regarding future events. CONCLUSIONS: Electrocardiograms at rest obtained during the initial days of hospitalization provide very early and valuable prognostic information in men admitted with suspected unstable coronary heart disease.

Risk stratification by early exercise testing after an episode of unstable coronary artery disease. The RISC Study Group.

After stabilization of symptoms by medication a predischarge exercise test was performed in 855 men admitted with suspected unstable angina (54%) or non-Q-wave myocardial infarction (46%). Multiple logistic regression analysis demonstrated that the number of leads with ST-depression at exercise, low maximal work load, increasing age and ST-elevation in electrocardiogram at rest had independent prognostic value concerning the risk of myocardial infarction or death during the following year. Therefore a combination of extension of ST-depression and peak work load was used to define 'high and low risk response' at the exercise test. After 1 year the mortality in patients with 'high risk' compared to 'low risk' exercise response was 3.6% and 0% (P < 0.001) and the risk of either myocardial infarction or death was 15.4% and 3.9% (P < 0.0001), respectively. ST-depression, occurrence of angina and low peak load at exercise were independent predictors of future severe angina. After 1 year 29.5% of patients with any of these indicators at exercise had incapacitating symptoms that necessitated referral for coronary angiography compared to 4.8% in the group without these findings (P < 0.0001). The predictive value of the exercise test remained high in subgroups based on inclusion diagnosis, age or findings in electrocardiogram at rest and independently of treatment with beta-blockade, other antianginal medication or aspirin at the time of the exercise test.

The new medical education at the Faculty of Health Sciences, Linköping University--a challenge for both students and teachers.

The medical faculty at the Linköping University was established in 1970. Until 1986 the medical students spent their first two preclinical years in Uppsala and the last three and a half years in Linköping following a conventional medical curriculum. In the fall of 1986 the Health University (Faculty of Health Sciences) was established with a common organization and educational aims i.e. problem-based learning and multiprofessional education for six health educations, physicians, nurses, physioterapists, occupational therapists, laboratory technologists and community care managers. The medical education in Linköping then became complete with a thorough innovation of the curriculum. The first students following the new curriculum will have their final examinations in January 1992. The experiences of teachers and students are overwhelmingly positive as shown in an evaluation from the other five health curricula of shorter duration. Since no medical students have so far completed their studies according to the new curriculum no corresponding evaluation for the medical education is yet available. However, the author here describes his experiences in the new role as tutor and examiner.

The predictive value of silent ischemia at an exercise test before discharge after an episode of unstable coronary artery disease. RISC Study Group.

The prognostic value of silent ischemia during a symptom-limited predischarge exercise test (ET) was evaluated in 740 men after an episode of unstable angina or non-Q wave myocardial infarction. The 51% of patients with ST depression at the ET had a higher rate of myocardial infarction or death after 1 year (18%) compared with those without ST depression (9%; p less than 0.01). This increased risk was not influenced by the presence or absence of pain at the ET: 18.3% in patients with painful ischemia compared with 18.1% in patients with silent ischemia. However, ST depression combined with pain at the ET predicted a higher incidence of class III or IV angina at follow-up (43.9% compared with 16.7% in the group with asymptomatic ST depression; p less than 0.001). Because revascularization in addition to alleviating symptoms also enhances the prognosis in certain groups of patients, selections for coronary angiography and possible revascularization should not be made only on the basis of symptoms but also on the presence of myocardial ischemia, whether symptomatic or not.

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.

Should the exercise test (ET) be performed at discharge or one month later after an episode of unstable angina or non-Q-wave myocardial infarction?

The diagnostic and prognostic value of symptom limited exercise tests (ET) performed before discharge and after one month were compared in men admitted to hospital after an episode of unstable angina or a non-Q-wave myocardial infarction (MI). A 'Positive ET' was defined as either a maximal work load below 100 W or ST-depression greater than or equal to 0.1 mV in 1-2 leads below 130 W or ST-depression greater than or equal to 0.1 mV in more than 2 leads at any load at the ET. During follow-up, severe angina was the only indication for coronary angiography and revascularization. There were no significant differences in diagnostic findings between the tests--Positive ET in 47% and Negative ET in 25% at both ETs. The occurrence of MI or death and the need of revascularization were related to signs of ischemia at both ETs. There were no differences in prognostic value between the early and late tests regarding MI or death or future severe angina during the 11 months' follow-up after the one month ET. However, half (10%) of the overall event rate (20%) during the one year follow-up occurred during the first months. The risk of these events could be identified by the predischarge but, for obvious reasons, not by the one month ET. Therefore, the present study suggests that a symptom limited ET should be performed before discharge in men stabilized after an episode of unstable angina or non-Q-wave MI.

Cardiac rehabilitation after coronary artery bypass grafting: effects on exercise performance and risk factors.

After coronary artery bypass grafting (CABG), 49 nonselected patients followed a cardiac rehabilitation program that included medical follow-up and physical training, both in outpatient groups and on an individual basis at home. The effect of the program on exercise test variables, coronary risk factors, and medication one year after surgery was compared to a nonexercised control group (n = 98). The study group showed less increase in the rate-pressure product, indicating a favorable effect on myocardial oxygen consumption (0.7 +/- 5.4 vs 2.8 +/- 5.6, p less than .05); a lower frequency of angina at exercise testing (6% vs 18%, p less than .01); a reduction in resting systolic and diastolic blood pressure (9/4mmHg, p less than .01); fewer smokers (6% vs 17%, p less than .05); and fewer patients taking long-acting nitrates (0% vs 10.2%, p less than .05). It is suggested, therefore, that an organized cardiac rehabilitation program may be advantageous after CABG.

Impaired oxidative metabolism increases adenine nucleotide breakdown in McArdle's disease.

Two patients with muscle phosphorylase deficiency [McArdle's disease (McA)] were studied during bicycle exercise at 40 (n = 2) and 60 W (n = 1). Peak heart rate was 170 and 162 beats/min, corresponding to approximately 90% of estimated maximal heart rate. Muscle samples were taken at rest and immediately after exercise from the quadriceps femoris. Lactate content remained low in both muscle and blood. Acetylcarnitine, which constitutes a readily available form of acetyl units and thus a substrate for the tricarboxylic acid cycle, was very low in McA patients both at rest and during exercise, corresponding to approximately 17 and 11%, respectively, of that in healthy subjects. Muscle NADH was unchanged during exercise in McA patients in contrast to healthy subjects, in whom NADH increases markedly at high exercise intensities. Despite low lactate levels, arterial plasma NH3 and muscle inosine 5'-monophosphate increased more steeply relative to work load in McA patients than in healthy subjects. The low postexercise levels of lactate, acetylcarnitine, and NADH in McA patients support the idea that exercise performance is limited by the availability of oxidative fuels. Increases in muscle inosine 5'-monophosphate and plasma NH3 indicate that lack of glycogen as an oxidative fuel is associated with adenine nucleotide breakdown and increased deamination of AMP. It is suggested that the early onset of fatigue in McA patients is caused by an insufficient rate of ADP phosphorylation, resulting in transient increases in ADP.

Experimental studies on the mechanism of glyceryl trinitrate-tolerance and dependence.

Tolerance to glyceryl-trinitrate (GTN) in arteries and veins was studied in different in vitro and in vivo models. The development of GTN tolerance was associated with a down-regulation of the cGMP system, i.e. an impairment of the nitrocompound-dependent activation of guanylate cyclase and an increase of the cGMP-phosphodiesterase activity. We suggest that a decreased function of the cGMP system might cause an impairment of the negative feedback loop involving cGMP in blood vessels, and a concomitant supersensitivity to contractile stimuli.

Effects and adverse effects of autonomic blockade in physical exercise.

Training bradycardia during autonomic blockade has been studied in rats and humans. The heart rate after autonomic blockade (intrinsic heart rate) is also lowered as a part of the adaptation to training. However, this nonautonomic component of the cardiac adaptation requires a long duration of intense endurance training to appear. This is in contrast to the autonomic component of the training bradycardia. From animal studies we have concluded that even if the training bradycardia is due to an adaptation within the heart itself, the adrenergic nerves are important for the development of a slow intrinsic heart rate. Neither the beta-receptor stimulation nor the degree of the heart rate increase during exercise is the main stimulus for the development of a training-induced bradycardia. Well-trained bicyclists had an intrinsic heart rate 20 beats lower than untrained normal control subjects. The heart rate at rest and the maximal heart rate were also on an average 20 beats lower for the bicyclists. There was no significant difference between propranolol and the beta 1 selective metoprolol in this study regarding their effects on heart rate and on deterioration of the maximal oxygen consumption after blockade. This deterioration was more marked in the well-trained than in the sedentary group. Based upon studies both in normal subjects and patients a careful rating of symptoms including physical exertion, fatigue or pain in the legs, dyspnea and chest pain using a Borg scale is recommended during exercise testing with beta blockade.(ABSTRACT TRUNCATED AT 250 WORDS)