Cancer risk of patients with ischaemic syndromes.

INTRODUCTION: Angiogenesis constitutes the regulation of collateral formation in subjects with ischaemic syndromes and is also a prerequisite for cancer progression. Patients with severe symptomatic ischaemic syndromes may have a reduced ability for angiogenesis and thus a lower risk to develop cancer. SUBJECTS AND METHODS: Patients below 80 years and treated for acute myocardial infarction (AMI), angina pectoris (AP), intermittent claudication (IC) or undergoing revascularization during 1972-1991 in Stockholm county (n=63 921) were followed regarding cancer incidence 1972-2000. Cancer incidence was compared with that of the general population of Stockholm County by standardized incidence ratios (SIR). RESULTS: An increased incidence of cancer overall compared with the general population was seen in patients treated for AMI [SIR men 1.08 (95% Confidence Interval 1.04-1.11) and women 1.15 (1.09-1.21)], AP [men 1.16 (1.11-1.21) and women 1.06 (1.00-1.12)] and IC [men 1.48 (1.31-1.64) and women 1.43 (1.17-1.68)]. This increase was mainly due to an increased incidence of tobacco-related cancer. In patients undergoing revascularization no increase in incidence was seen [SIR men 0.97 (0.91-1.03) and women 1.06 (0.91-1.20)]. CONCLUSION: Patients with mild to moderate symptomatic ischaemic syndromes are, as expected, at increased risk of subsequently develop tobacco-related cancer. A lack of increased cancer risk in patients undergoing revascularization could be due to a reduced ability for angiogenesis in patients with severe atherosclerotic disease but may also be related to lifestyle changes.

Determination of cardiac involvement in sarcoidosis by magnetic resonance imaging and Doppler echocardiography.

OBJECTIVES: To elucidate whether cardiac magnetic resonance imaging (MRI) could be useful in disclosing structural changes in the myocardium in sarcoidosis patients and to relate echo-Doppler derived indices of left ventricular function to electrocardiogram (ECG) findings. DESIGN: The MRI was performed in 18 consecutive patients with sarcoidosis. Left ventricular ejection fraction (LVEF), i.e. systolic function, was estimated echocardiographically by Simpson's two-dimensional method (n = 16). Diastolic function was estimated by age-corrected Doppler-derived indices: isovolumetric relaxation time (IVRT), deceleration time (DT) and early filling/atrial contraction ratio (E/A ratio). RESULTS: Eleven patients had conduction defects or dysrhythmias (ECG+) whilst seven patients had a normal ECG (ECG-). In two patients, high signalling, contrast-enhanced, isolated regions, suggestive of deposits, were seen in the left ventricular myocardium on MRI. Both these patients had abnormal ECGs and signs of systolic and/or diastolic dysfunction on echocardiography. LVEF was subnormal in seven of 10 of the ECG+ patients and in two of six of the ECG-. Signs of diastolic dysfunction were found in 59% and 56% of the measurements in the ECG+ and ECG- patients, respectively. CONCLUSION: We conclude (i) that myocardial deposits on MRI in sarcoidosis patients have a high specificity for cardiac involvement but a rather low sensitivity; (ii) that a substantial proportion of sarcoidosis patients with abnormal ECGs have echocardiographic signs of systolic and/or diastolic dysfunction.

ECG-abnormalities in Japanese and Swedish patients with sarcoidosis. A comparison.

BACKGROUND AND AIM OF THE WORK: ECG abnormalities are more common in patients with sarcoidosis than in controls. The incidence of cardiac sarcoid granulomas in the Japanese population has been found to be higher than that seen in Caucasians. We compared the prevalence of ECG abnormalities in Japanese and Swedish patients with sarcoidosis. METHODS: Twelve-lead routine ECG's were compared between consecutive patients (134 Japanese and 149 Swedish) of similar age with histologically verified sarcoidosis or a high clinical probability of the disease and a history of no more than 12 months before the ECG. RESULTS: There was no statistically significant difference in the prevalence of first degree AV block, ST-T-segment abnormalities, right bundle branch block (RBBB) and left anterior block (LAH) in Japanese and Swedish patients. Among the Swedes, the results were compared with those of a smaller group (n = 29) of older patients with a longer disease course. In these few patients LAH and RBBB occurred more frequently than in patients with a recent diagnosis. CONCLUSIONS: ECG abnormalities in patients with sarcoidosis seem to be of similar frequency in Japan and Sweden. ST-T changes and first degree AV block would appear early in the course of the disease, whereas more pronounced conduction defects may appear later.

Chronic cobalt exposure affects antioxidants and ATP production in rat myocardium.

Chronic cobalt exposure is characterized by severe cardiac insufficiency. Since the mechanisms of cobalt toxicity are not yet clear, we analysed the effects of chronic cobalt exposure on antioxidant enzyme activities and myocardial mitochondrial ATP production rate in a rat model. One group of rats was fed a conventional diet and another a cobalt supplemented diet for 24 weeks. The manganese-superoxide dismutase activity was markedly reduced in the cobalt rats (18+/-4.7 U/mg protein) compared to the control rats (100+/-22 U/mg protein; p <0.001). Activity in the respiratory chain enzymes succinate-cytochrome c reductase, NADH-cytochrome c reductase and cytochrome c oxidase was also reduced in the cobalt rats (p<0.01). Glutamate dehydrogenase activity, located in the mitochondrial matrix, was unchanged. The mitochondrial ATP production rate in relation to myocardial mass was lower in the cobalt rats for all substrates tested except palmitoyl-l-carnitine + malate. In conclusion, 24 weeks of chronic cobalt exposure induces a marked decrease in manganese-superoxide dismutase activity, a moderate decrease in mitochondrial ATP production rate and a general reduction in the capacity of the respiratory chain. The impairment in mitochondrial ATP production might be secondary to the decreased manganese-superoxide dismutase activity, causing inactivation of mitochondrial factors susceptible to superoxide radicals.

Monotherapy with amlodipine or atenolol versus their combination in stable angina pectoris.

BACKGROUND: The basic cause of angina pectoris is imbalance between the metabolic needs of the myocardium and the capacity of the coronary circulation to deliver sufficient oxygenated blood to satisfy these needs. HYPOTHESIS: The study was undertaken to evaluate whether the effect of combined amlodipine and atenolol therapy on patients with stable angina pectoris and with ST-depression during exercise testing and 48-h ambulatory electrocardiographic monitoring is superior to that of either agent given alone. METHODS: Patients with stable angina pectoris and ST depression during exercise and ambulatory monitoring were randomized to receive amlodipine (n = 116) or atenolol (n = 116), or both (n = 119). All patients were also treated with short- and long-acting nitrates. The design was a double-blind, randomized, triple-arm parallel group study with 10 weeks of administration of the test medication. RESULTS: In terms of time to onset of ST depression > 1 mm, time to onset of angina, total exercise time, maximum achieved workload, and peak intensity of angina, amlodipine and atenolol alone were as effective as their combination. During ambulatory monitoring, atenolol was more effective than amlodipine regarding total time and number of ST-depression episodes, and as effective as the combined drugs. CONCLUSION: For individual patients with stable angina pectoris, combination of a beta blocker with a calcium antagonist is not necessarily more effective than either drug given alone.

Myocardial morphology and cardiac function in rats with renal failure.

The effects of chronic renal failure on cardiac performance and myocardial morphology were studied in rats: 17 with 5/6 nephrectomy (CRF rats) and 12 with sham operation (controls). Cardiac function was assessed 8 weeks postoperatively, using the Langendorff technique for an isolated working heart model. After the hemodynamic study the hearts were fixed for electron and light microscopy. In the CRF rats left ventricular systolic pressure was significantly higher at all preloads (10-20 cmH2O) and afterloads (70-90 cmH2O), and left ventricular stroke work was significantly increased at preload 20 cmH2O with afterloads 70 or 90 cmH2O. Light microscopy revealed fibronecrotic lesions consisting of fibroblastic proliferation with newly formed collagen interposed between or entrapping degenerative myocytes. The changes were focally distributed, with perivascular accentuation and were most frequent in the basal half of the ventricular wall. Electron microscopy of non-necrotic myocytes showed intact myocytes, with mitochondria morphometrically similar in the 2 groups, but a significantly lower incidence of mitochondrial granules in the CRF rats. Thus 8 weeks of CRF showed no cardiac dysfunction associated with the focally distributed fibronecrotic myocardial lesions and decrease in mitochondrial granules. The precise mechanism of the discrepancy between the morphological change and the cardiac function is unclear. One possible explanation may be that because the pathological changes in the myocardium were focal or mild to moderate, some compensation mechanism may be involved or it may be the turning point of functional change from acute renal failure to the chronic state.

In vitro flow dynamics of a new mechanical cardiac valve prosthesis--"tricusp".

The hydrodynamic performance of a newly developed JCL-trileaflet mechanical heart valve prostheses (Tricusp) was measured and compared with some of the currently most used heart valve prostheses types. All experiments were performed in an electrohydraulic, computer-controlled pulse duplicator simulating the left side of the human circulatory system. Testing conditions were set according to a Food and Drugs Administration interlaboratory comparison protocol, with cardiac outputs 3.0, 4.5, 6.5 or 8.0 l/min and a constant heart rate of 70 beats/min. Mean systolic pressure differences, volume and energy losses, dimensionless pressure losses and energy loss coefficients were calculated from the recorded pressure, volume and flow tracings. The results with the Tricusp valve were found to be as good, or even better than those with the currently most used commercially available bileaflet valves.

Progressive decline in renal function induces a gradual decrease in total hemoglobin and exercise capacity.

We examined 58 patients (38 men, 20 women; mean age: 45 +/- 12 years; body mass index: 24 +/- 4 kg/m2) with a glomerular filtration rate (GFR) ranging from 3 to 32 ml/min, in order to determine the effects of a progressive decline in renal function on total hemoglobin (THb) and exercise capacity. The THb ranged from 185 to 759 g and the hemoglobin concentration ranged from 66 to 151 g/l. Maximal exercise capacity ranged from 50 to 260 W (40-143% of the expected norm). Nearly all the patients interrupted their exercise tests due to general fatigue, leg tiredness or a combination of these factors. There was a significant partial correlation between THb and GFR after sex and age had been accounted for (r = 0.39; p < 0.005). Maximal exercise capacity and THb showed a significant partial correlation after sex, age and GFR had been accounted for (r = 0.27; p < 0.05). Maximal exercise capacity showed a significant partial correlation with GFR after sex, age and THb had been accounted for (r = 0.30; P < 0.05). In conclusion, there is a gradual decline in THb and maximal exercise capacity as uremia progresses. Anemia appears to be a contributory cause responsible for the decrease in maximal exercise capacity along with other factors pertinent to uremia per se.

Acute cobalt exposure and oxygen radical scavengers in the rat myocardium.

Excessive amounts of cobalt are cardiotoxic, although the mechanism for this toxicity remains unclear. We studied the effects of acute cobalt exposure on the activities of free radical scavengers in the myocardium in 5 groups of rats. Six rats served as a control group and were given a daily subcutaneous injection of 1 ml saline for 8 days. The other 4 groups of rats received a daily injection subcutaneously of cobalt chloride in doses of 1 mg/kg bw, 5 mg/kg bw, 20 mg/kg bw and 50 mg/kg bw, respectively for 8 days. There was a marked and dose-dependent accumulation of cobalt in the myocardium of the cobalt exposed rats. Creatine kinase, copper-zinc superoxide dismutase (CuZn-SOD) and alpha-tocopherol content did not differ between the control and the cobalt exposed groups. The activity of glutathione peroxidase increased, while the activity of manganese-superoxide dismutase (Mn-SOD) was significantly reduced in the cobalt exposed groups. There was an inverse relationship (r = 0.60, P < 0.0001) between the cobalt content and Mn-SOD activity in the myocardium. These results suggest that acute cobalt cardiotoxicity may involve a reduction of intrinsic scavengers resulting in an increased vulnerability to oxygen free radical toxicity.

Effects of renal failure on skeletal muscle.

In this cross-sectional study, we examined biopsies from the vastus lateralis muscle of 13 predialytic uremic men (mean age 46 +/- 8 years). Their average glomerular filtration rate was 14 +/- 7 ml/min x 1.73 m2 and their maximal exercise capacity, measured by standardized exercise test on a bicycle ergometer, was 184 +/- 45 W (94% of the expected norm). The proportion of type I fibers (type I%) in the uremic group was similar to that of the reference group (42 +/- 11 vs. 41 +/- 8% NS). The proportion of type IIA fibers (type IIA%) in the uremic group was higher than in the reference group (44 +/- 10 compared to 35 +/- 9%, p < 0.05). The proportion of type IIB fibers (type IIB%) was lower than in the reference group (13 +/- 8 vs. 21 +/- 8%, p < 0.05). Type I fiber area was similar to that of the reference group (4,768 +/- 1,033 vs. 4,627 +/- 1,112 microns 2, NS). Type IIA and type IIB fiber areas tended to be smaller than those of the reference group (type IIA fiber area: 4,515 +/- 929 vs. 5,213 +/- 1,288 microns 2, NS; type IIB fiber area: 3,953 +/- 1,066 vs. 4,406 +/- 1,582 microns 2, NS) with a type IIA area/type I area ratio which was significantly lower than in the reference group. Citrate synthase activity was 0.48 +/- 0.08 mu kat/g in the uremic group and 0.50 +/- 0.08 mu kat/g in the reference group, NS.(ABSTRACT TRUNCATED AT 250 WORDS)

The hemodynamic importance of atrial systole: a function of the kinetic energy of blood flow?

The relative importance of atrial systole on left ventricular filling was investigated at rest and during exercise in 25 patients with dual chamber pacemakers. The mean blood flow velocity over the mitral valve, the velocities of the rapid filling phase (E), the active filling phase (A), and the E/A ratio were determined by pulsed Doppler-echocardiography. The patients were first examined at rest during AV sequential pacing (DVI) at 70 and 104 beats/min. The investigation was subsequently repeated during atrial synchronous pacing (VDD) at rest and during supine submaximal exercise at workloads adjusted to achieve heart rates corresponding to those during DVI pacing. The mean blood flow velocity at rest did not differ between DVI and VDD pacing at 70 beats/min (0.46 vs 0.49 m/sec). When the resting heart rate was increased to 104 beats/min (DVI) the mean blood flow velocity increased to 0.56 msec (P < 0.001). At a corresponding heart rate during exercise (VDD) the velocity increased to 0.70 msec (P < 0.001). At a resting heart rate of 70 beats/min the E/A ratio (n = 14) did not differ significantly between DVI and VDD pacing. With an increased resting heart rate (DVI) the E/A ratio decreased from 0.94 +/- 0.45 to 0.78 +/- 0.18; NS. When the heart rate increased during exercise (VDD) the E/A ratio increased from 0.75 +/- 0.14 to 0.97 +/- 0.16; P < 0.001. There was a positive correlation between the increase of the mean blood flow velocity and the increase of the E/A ratio during exercise (r = 0.69, P < 0.01). No such correlation was found when the heart rate was changed at rest. Thus, the importance of atrial systole on ventricular filling diminishes during exercise in accordance with increasing blood flow velocity, which by physical principles is related to the kinetic energy. The relative importance of atrial systole is hence inversely correlated to the kinetic energy of the blood flow.

The effects of beta blockade with (epanolol) and without (atenolol) intrinsic sympathomimetic activity in stable angina pectoris. The Visacor Study Group.

Beta blockade constitutes efficient therapy for stable angina pectoris. The effects of lowering blood pressure and heart rate with such treatment are not always desired. Epanolol is a beta 1-selective partial agonist with minor effects on blood pressure and heart rate at rest. Atenolol is a pure beta 1-selective antagonist with more pronounced effects on blood pressure and heart rate at rest. The effects of epanolol, 200 mg o.d., and atenolol, 100 mg o.d., were compared in 173 middle-aged patients with stable angina pectoris in a randomized, double-blind, parallel group-controlled study for one year. No significant differences were shown in angina attack rate, nitrate consumption, or exercise performance. Resting heart rate and blood pressure were significantly lower on atenolol. Epanolol tended to be better tolerated than atenolol, as shown by visual analogue scales of well-being, activity, energy, and warm extremities, further supported by fewer reports on possible adverse reactions. In conclusion, epanolol appears to be as effective as atenolol and better tolerated in patients with stable angina pectoris.

A double-blind study of submaximal exercise tolerance and variation in paced rate in atrial synchronous compared to activity sensor modulated ventricular pacing.

To assess the variation in paced rate during everyday activity and the importance of atrioventricular synchronization (AV synchrony) for submaximal exercise tolerance, atrial synchronous (DDD) and activity rate modulated ventricular (VVI,R) pacing were compared in 17 patients with high degree AV block. The patients were randomly assigned to either mode and evaluated by treadmill exercise to moderate exertion and by 24-hour Holter monitoring after 2 months in the DDD and VVI,R modes, respectively. At the end of the study, the patients were programmed to the pacing mode corresponding to the preferred study period. During the treadmill test, the mean exercise time to submaximal exertion (Borg 5/10), exertion ratings and respiratory rate did not differ between pacing modes despite a significantly lower ventricular rate in the VVI,R mode. The atrial rate during VVI,R pacing was significantly higher than the ventricular rate, but did not differ from the ventricular rate during DDD pacing. There was a diurnal variation in paced rate in both pacing modes. Paced ventricular rate was, however, higher and variation in paced rate greater in DDD compared to VVI,R pacing. Nine patients preferred the DDD mode, three patients preferred the VVI,R mode, while five subjects did not express any preference. The results from this study indicate that the variation in paced rate during activity sensor-driven VVI,R pacing does not match that during DDD pacing neither during everyday activities nor during submaximal treadmill exercise. Nevertheless, no differences in exercise time, Borg ratings, and respiratory rate during submaximal exercise were found. Thus, for most patients with high degree AV block, DDD and VVI,R pacing seem equally satisfactory for submaximal exercise.

Binding of dietary cobalt to sarcoplasmic reticulum proteins.

It has previously been shown that cobalt accumulates in the myocardium of rats, mainly the sarcoplasmic reticulum (SR) and the mitochondrial inner membrane. In order to investigate the mode of accumulation of cobalt in the SR, rats were given a dietary cobalt supplementation of 40 mg of CoSO4 x 7H2O kg-1 body wt, after which the rats were sacrificed and the sarcoplasmic reticulum was isolated. The SR proteins were subjected to analysis by polyacrylamide gel electrophoresis followed by protein staining and determination of the content of cobalt in each protein band. The major cobalt-binding protein was found to have a molecular weight of about 100,000; a 200,000 molecular weight protein was also found to bind cobalt, although less extensively. These results suggest that cobalt is bound to the monomeric and dimeric forms of Ca(2+)-ATPase in the SR of the myocardium.

Is DDD pacing superior to VVI,R? A study on cardiac sympathetic nerve activity and myocardial oxygen consumption at rest and during exercise.

Rate responsive ventricular pacing (VVI,R) has been demonstrated to equal atrial synchronous ventricular pacing (DDD) with regard to hemodynamics and exercise tolerance. Whether the two modes are also comparable, with regard to cardiac metabolic effects, is not yet clear. We assessed central hemodynamics, cardiac sympathetic nerve activity (cardiac norepinephrine overflow), and myocardial oxygen consumption in 16 patients treated with rate responsive atrial synchronous ventricular pacemakers (DDD,R) due to high degree AV block. The study was performed at rest and during supine exercise at two workloads (30 +/- 12 and 68 +/- 24 watts, respectively) during VDD and rate matched VVI pacing (VVIm). Ventricular rates at rest and during both workloads were almost identical. Cardiac output at rest tended to be higher in the VDD mode, due to a slightly higher stroke volume. Central pressures including right atrial pressure and pulmonary capillary wedge pressure were similar in the pacing modes. The coronary sinus blood flow, the coronary sinus arteriovenous oxygen difference, and the myocardial oxygen consumption did not differ between the two pacing modes. Cardiac norepinephrine overflow was similar in the two pacing modes, at rest or during exercise. Thus, we found no significant differences between VDD and VVIm pacing with regard to central hemodynamics, cardiac sympathetic nerve activity (cardiac norepinephrine overflow), or myocardial oxygen consumption either at rest or during moderate exercise.

Longevity in patients with high degree atrioventricular block paced in the atrial synchronous or the fixed rate ventricular inhibited mode.

Survival in patients paced for high degree AV block has been demonstrated to be influenced by underlying cardiac disease in particular congestive heart failure. One previous study has suggested that dual chamber pacing may improve the vital prognosis for such patients. To investigate this, 74 patients treated with rate adaptive atrial synchronous (VDD) and 74 patients treated with VVI pacemakers for high degree AV block, were retrospectively studied for a mean of 5.4 years by life-table analysis. The two groups had an equal distribution of age, sex, date of pacemaker implantation, and concomitant cardiovascular diseases. Total mortality and estimated survival did not differ between the two groups. The estimated survival in the VDD group at 1, 3, and 5 years for patients without and with congestive heart failure was 94%, 86% and 78%, and 92%, 83% and 72%, respectively. In the VVI group the corresponding values were 95%, 90%, and 83% for patients without congestive heart failure and 82%, 64%, and 47% for those with congestive heart failure (P = 0.008). Compared to the expected survival rate of the general Swedish population, only the VVI group with congestive heart failure, had an excess mortality (P = 0.007). Patients with high degree AV block have a fairly normal vital prognosis irrespective of pacing mode. The prognosis for patients with congestive heart failure was negatively affected by VVI pacing. Thus, for patients with congestive heart failure the choice of pacing mode is of vital importance, whereas for patients without congestive heart failure, other factors such as feeling of well-being and exercise capacity should decide the final choice of pacing mode.

Effects of recombinant human extracellular-superoxide dismutase type C on myocardial reperfusion injury in isolated cold-arrested rat hearts.

The efficacy of recombinant human extracellular-superoxide dismutase type C (EC-SOD C) on myocardial reperfusion injury was explored in hypothermically arrested rat hearts, as was its site of action. Forty isolated working rat hearts were subjected to 30 min of global ischemia followed by 30 min of reperfusion. The hearts were arrested by the administration of 10 mL of cold perfusate at the onset of ischemia. At the same time, they were randomly assigned to one of five groups; A: cold perfusate only; B: cold perfusate + EC-SOD C 10.4 mg/L (30,000 U/L); C: cold perfusate+bovine CuZn-SOD 7.5 mg/L (30,000 U/L); D: cold perfusate + EC-SOD C 10.4 mg/L + heparin 50,000U/L; E: cold perfusate + heparin 50,000 U/L. Heparin was given to prevent binding of EC-SOD C to endothelial cell surfaces. Left ventricular function was studied before ischemia and at the end of reperfusion. Percent recovery of maximal left ventricular dP/dt after reperfusion was more pronounced in group B (109 +/- 24%; p less than .05) than in groups A (42 +/- 40%), C (47 +/- 36%), D (44 +/- 33%) and E (58 +/- 25%). Likewise, percent recovery of the double product (heart rate x systolic left ventricular pressure) was better in group B (104 +/- 18%; p less than .05) than in the other groups (A: 47 +/- 37%, C: 49 +/- 36%, D: 50 +/- 35%, E: 69 +/- 31%). Compared to the preischemic level, creatine kinase increased significantly in the coronary effluent after reperfusion in groups A, C, D, and E, but not in group B. The results suggest that EC-SOD C, which attaches to the endothelial cell surfaces, might be particularly effective as protection against myocardial reperfusion injury when given together with cardioplegic solution.

Clinical experience of pacemaker treatment in children.

Pacemaker treatment is more complicated in children than in adults, mainly because of electrode problems. A pacemaker system was implanted in 23 children aged 2 days-14 years (mean 4.8 years, with 11 less than or equal to 3 years) at the Karolinska Hospital since 1983. The indications for pacing were peroperative atrioventricular block (AVB) in 13 cases, congenital AVB in five, sinoatrial disorder in four and slow ventricular arrhythmia in one case. The initially implanted electrode was epicardial in ten children (in the first 2 years of the study) and endocardial in the other 13. Eight of the ten epicardial electrodes had to be replaced by endocardial within a mean of 2.5 years. There were 18 reoperations, the reasons being increased threshold/exit block--all epicardial leads (8 cases), electrode failure (1), 'stretching' of the electrode secondary to body growth (4), local infection (3) and generator replacement (2). The reoperation rate was unacceptably high in children with epicardial electrodes. Endocardial pacing is the method of choice even for small infants.

Effects of exercise training in predialytic uremic patients.

We examined the effects of physical training in 10 predialytic uremic patients (7 men, 3 women, mean age 47 +/- 8 years) with an average glomerular filtration (GFR) of 15 +/- 7 ml/min x 1.73 m2. All 10 patients participated in an exercise programme 3 times/week for 3 months and were compared to a control group of 9 patients with comparable baseline variables. The exercise group increased its maximal exercise capacity measured by standardized exercise test on a bicycle ergometer, from an average 159 +/- 49 to 174 +/- 57 W (p less than 0.01). They also showed a decrease in heart rate at equal load (138 +/- 29-123 +/- 18 beats/min, p less than 0.05). The control group did not change its exercise capacity (171 +/- 60 and 171 +/- 65 W, respectively, NS), nor its heart rate at equal load (124 +/- 24 and 123 +/- 24 beats/min, respectively, NS). Thigh muscular function assessed by static endurance increased from a median 77 s (range 27-197) to 113 s (range 66-201), p less than 0.002. Dynamic muscular endurance increased from a median number of 41 movements (range 28-105) to 93 movements (range 45-139), p less than 0.001. The corresponding figures for the controls were: static endurance 60 (range 20-209) and 47 s (range 9-203), respectively, NS; dynamic endurance 53 (range 19-190) and 43 movements (range 10-126), respectively, NS. Total hemoglobin, blood volume, GFR, blood pressure and echocardiographic variables remained unchanged during the observation period. We conclude that in predialytic uremic patients, physical training improves exercise capacity mainly due to an improved muscular function.