Physical training in Syndrome X: physical training counteracts deconditioning and pain in Syndrome X.

OBJECTIVES: The aim of this study was to evaluate the effects of exercise training and body-awareness training in female patients with Syndrome X. BACKGROUND: Patients with Syndrome X, defined as effort-induced angina pectoris, a positive exercise test and a normal coronary angiogram, suffer from a chronic pain disorder. We hypothesized that this disorder results in physical deconditioning with decreased exertional pain threshold. METHODS: Twenty-six patients were randomly assigned to two training groups (A, B) and a control group (C). Group A (n = 8) started, after baseline measurements, with eight weeks of body-awareness training followed by eight weeks of exercise training on a bicycle ergometer three times a week for 30 min at an intensity of 50% of peak work rate. Group B (n = 8) performed only eight weeks of exercise training. Group C (n = 10) acted as controls without any intervention whatsoever. The effects on exercise performance, hormonal secretion, vascular function, adenosine sensitivity and quality of life were evaluated. RESULTS: Body-awareness training did not change the pain response. The two training groups did not differ in effects of exercise training. Exercise capacity before training was below the gender- and age-matched reference range and improved by 34% with training to a level not different from the reference range. Onset of pain was delayed by 100% from 3 +/- 2 to 6 +/- 3 min (p < 0.05) while maximum pain did not change. Thus the pain-response-to-exercise curve was shifted to the right. Syndrome X patients showed a hypersensitivity to low-dose adenosine infusion compared to healthy age- and gender-matched controls (p < 0.0001) that did not change with exercise training. Endothelium-dependent blood flow increase was at baseline within reference range and tended to increase (p < 0.06) following training. In Group A the concentration of cortisol in urine decreased by 53% after body-awareness training (p < 0.05), and this change from baseline remained after physical exercise training (p < 0.05). A similar decrease occurred with only exercise training (Group B). CONCLUSIONS: Physical deconditioning with lower exertional threshold for pain is a prominent feature in Syndrome X. Physical training in Syndrome X results in an increased exercise capacity with lesser anginal pain. We suggest physical training as an effective treatment in Syndrome X.

Increase in skeletal muscle lipoprotein lipase following endurance training in man.

The effect of regular physical training on skeletal muscle lipoprotein lipase activity (LPLA) was investigated in 16 healthy men of normal body weight. They trained on cycle ergometers for 8 weeks. During the training period half the group were given the beta-adrenergic receptor blocker propanolol (160 mg/day) and the other half placebo tablets. Muscle tissue samples were taken before the training period and 4 days after the last training session and drug intake to ensure that there were no acute effects of either training or drug treatment. The maximal oxygen uptake (Vo2max, 1/min) increased by 8% with training. LPLA increased by 47% and 31% in the placebo and beta-blockade group, respectively. Capillary density increased by 19% and 17%. The statistical analysis revealed a significant effect of training but not of beta-blockade on these changes. The present longitudinal training study in healthy men confirms the results of cross-sectional studies showing higher muscle LPLA in well-trained than in sedentary men.

Effect of epinephrine infusion on chest pain in syndrome X in the absence of signs of myocardial ischemia.

Eight female patients (aged 51 to 65 years) with New York Heart Association class II angina pectoris, normal coronary angiograms, normal hyperventilation, and abnormal exercise stress tests (chest pain and ST depression), and 5 sex- and age-matched controls participated in this study. Epinephrine was given intravenously to both patients and controls at 5-minute intervals in doses of 0.1, 0.2, 0.3, 0.4, and 0.6 nmol/kg/min. After rest (15 minutes), the alpha-adrenoceptor antagonist phentolamine or placebo was administered intravenously to patients in a double-blind, crossover study on 2 separate occasions in doses of 250 micrograms/min for 5 minutes and 500 micrograms/min for the next 10 minutes; the epinephrine infusion was repeated. Blood pressure, heart rate, and electrocardiogram were monitored continuously and pain was estimated on the Borg CR-10 scale. On a third occasion, chest pain was induced in patients using the same epinephrine protocol during echocardiographic monitoring. In the control group, all patients received the maximal epinephrine dose. No chest discomfort or pain developed. In the patient group, the maximal tolerable epinephrine dose (0.39 +/- 0.19 nmol/kg/min) decreased diastolic pressure (-14 +/- 9 mm Hg, p < 0.01) and increased heart rate (+24 +/- 10 beats/min, p < 0.01), not statistically different from the control group. Pulse pressure increased in the patient group (27 +/- 17 mm Hg, p < 0.01) but not in the controls. Left ventricular ejection fraction at baseline was within reference limits (58% to 75%) and did not change during epinephrine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Beat-to-beat QRS amplitude variability after acute myocardial infarction and coronary artery bypass grafting.

Ischemic myocardial injury has been demonstrated to be associated with increased beat-to-beat electrical variability of the depolarization phase. This can be quantified by electrocardiographic (ECG) signal variance analysis, a technique that has proven its diagnostic value in the detection of coronary artery disease (CAD). This study evaluates QRS amplitude variability during a 6-month follow-up period in 73 patients with acute myocardial infarction (AMI) and in 56 patients subjected to coronary artery bypass grafting (CABG). The beat-to-beat QRS amplitude variability was quantified with variance electrocardiography. The equipment allows computerized time domain analysis of high-fidelity ECG signals from 24 leads, and the detected electrical heterogeneity is then expressed as a nondimensional index ranging from 0 to 150, with values >90 being indicative of ischemic myocardial involvement. One week after AMI 55% of the patients presented with an abnormal QRS variability index >90. A significant (p <0.01) increase in the index values occurred during the follow-up period, but only in the patients with an initial index <70. In the CABG group 44% of the patients had a preoperative QRS variability index >90. The values increased (p <0.05) in all patients after surgery; the increase was transient in patients with an initial index <70 (p <0.01). The results demonstrate that the myocardial injury in patients with CAD is often associated with increased electrical variability of myocardial depolarization. The QRS amplitude variability index can be used as a marker of such an injury, and analysis of its changes in the course of ischemic cardiac events may provide new insights into the dynamics of ischemic heart disease and the myocardial healing process.

Altered cardiovascular responsiveness to adrenoceptor agonists in endurance-trained men.

The influence of physical training on responses to intravenous infusions of phenylephrine (Phe) and isoproterenol (Iso) were investigated in 10 well-trained runners (WT) and 10 age-matched untrained controls (UT). The latter were reinvestigated after a 4-mo training period. The venous plasma Iso and Phe concentrations attained during infusions were lower in WT than in UT. Responses were related to the corresponding plasma concentrations. Phe-induced decreases and Iso-induced increases in heart rate were less pronounced (P less than 0.01) in WT than in UT. At venous plasma concentrations of 100 nM Phe and 0.8 nM Iso, the responses were -9 +/- 1 and 30 +/- 2, and -17 +/- 2 and 44 +/- 4 beats/min, respectively. Increases in blood pressures during Phe infusions were greater in WT than in UT (100 nM Phe: systolic 36 +/- 3 vs. 25 +/- 3 mmHg, P less than 0.05). The Iso-induced decrease in diastolic blood pressure was also more pronounced in WT (0.8 nM Iso: -29 +/- 3 vs. -15 +/- 2 mmHg, P less than 0.01). Iso-induced changes in systolic time intervals showed no consistent differences between training states. Increases in plasma adenosine 3',5'-cyclic monophosphate during Iso infusions were smaller (P less than 0.05) in WT than in UT, whereas increases in plasma glycerol were larger (P less than 0.05). Lymphocyte beta 2-adrenoceptor function and binding characteristics did not differ between training states. In summary, the present results indicate that beta-adrenergic vasodilator and alpha-adrenergic vasopressor responses are enhanced in endurance-trained subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Applied physiology of marathon running.

Performance in marathon running is influenced by a variety of factors, most of which are of a physiological nature. Accordingly, the marathon runner must rely to a large extent on a high aerobic capacity. But great variations in maximal oxygen uptake (VO2 max) have been observed among runners with a similar performance capacity, indicating complementary factors are of importance for performance. The oxygen cost of running or the running economy (expressed, e.g. as VO2 15 at 15 km/h) as well as the fractional utilisation of VO2 max at marathon race pace (%VO2 Ma X VO2 max-1) [where Ma = mean marathon velocity] are additional factors which are known to affect the performance capacity. Together VO2 max, VO2 15 and %VO2 Ma X VO2 max-1 can almost entirely explain the variation in marathon performance. To a similar degree, these variables have also been found to explain the variations in the 'anaerobic threshold'. This factor, which is closely related to the metabolic response to increasing exercise intensities, is the single variable that has the highest predictive power for marathon performance. But a major limiting factor to marathon performance is probably the choice of fuels for the exercising muscles, which factor is related to the %VO2 Ma X VO2 max-1. Present indications are that marathon runners, compared with normal individuals, have a higher turnover rate in fat metabolism at given high exercise intensities expressed both in absolute (m/sec) and relative (%VO2 max) terms. The selection of fat for oxidation by the muscles is important since the stores of the most efficient fuel, the carbohydrates, are limited. The large amount of endurance training done by marathon runners is probably responsible for similar metabolic adaptations, which contribute to a delayed onset of fatigue and raise the VO2 Ma X VO2max-1. There is probably an upper limit in training kilometrage above which there are no improvements in the fractional utilisation of VO2 max at the marathon race pace. The influence of training on VO2 max and, to some extent, on the running economy appears, however, to be limited by genetic factors.

Running on land and in water: comparative exercise physiology.

The effect of water immersion on cardiorespiratory and blood lactate responses during running was investigated. Wearing a buoyant vest, 10 trained runners (mean age 26 yr) ran in water at four different and specified submaximal loads (target heart rates 115, 130, 145, and 155-160 beats.min-1) and at maximal exercise intensity. Oxygen uptakes (VO2), heart rates, perceived exertion, and blood lactate concentrations were measured. Values were compared with levels obtained during treadmill running. For a given VO2, heart rate was 8-11 beats.min-1 lower during water running than during treadmill running, irrespective of exercise intensity. Both the maximal oxygen uptake (4.03 vs 4.60 1 x min-1) and heart rate (172 vs 188 beats.min-1) were lower during water running. Perceived exertion (legs and breathing) and the respiratory exchange ratio (RER) were higher during submaximal water running than during treadmill running, while ventilation (1 x min-1) was similar. The blood lactate concentrations were consistently higher in water than on the treadmill, both when related to VO2 and to %VO2max. Partly in conformity with earlier cycle ergometer studies, these data suggest that immersion induces acute cardiac adjustments that extend up to the maximal exercise level. Furthermore, both the external hydrostatic load and an altered running technique may add to an increased anaerobic metabolism during supported water running.

The relationship between body mass and oxygen uptake during running in humans.

Oxygen uptake during treadmill running was measured at submaximal and maximal intensities in six different groups of endurance athletes (N = 134) and in seven endurance-trained men. The relationship between body mass (M) and oxygen uptake (VO2) was evaluated by deriving the exponent b in the equation VO2 = a.Mb. Thus, if b = 1, the oxygen uptake increases in proportion to body mass and oxygen uptake per kg is independent of body mass; if b less than 1, than the oxygen uptake per kg is inversely related to body mass. The exponent b was found to be less than unity for all groups for both submaximal (b = 0.76, s = 0.06) and maximal oxygen uptake (b = 0.71, s = 0.05). These results indicate that neither submaximal nor maximal oxygen uptake increases in proportion to body mass during running. The relationship between submaximal oxygen uptake and body mass observed in this study may explain why the oxygen uptake per kg of body mass has been found to be higher for children than for adults.

[A new surgical technique in atrial fibrillation. The maze procedure restores sinus rhythm]. / Ny hjärtkirurgisk metod vid förmaksflimmer. Maze-operation återställer sinusrytm.

Atrial fibrillation (AF) is a common arrhythmia associated with significant morbidity and increased mortality, partly due to the increased risk of stroke. The maze procedure, introduced by James Cox of the USA, is an internationally established surgical alternative in cases of unsuccessful medical or catheterised treatment of paroxysmal or chronic AF. It is an open heart procedure, involving multiple transmural incisions and continuous suture lines in both atria. By creating a maze of atrial tissue, the re-entrant circuits causing the AF are interrupted, hence re-establishing regular sinus rhythm and atrioventricular synchronization. The article reviews the initial 3-year experience of the procedure in 10 patients with AF, either paroxysmal (n = 5) or chronic (n = 5). The indications for surgery were disabling symptoms in all 10 cases, medical treatment failure in nine cases, previous AF-associated stroke in three cases, and a significant atrial septal defect in one case. All patients underwent extensive investigation both pre- and post-operatively. Postoperatively, nine of the 10 patients manifested regular sinus or atrial rhythm and freedom from or amelioration of preoperative symptoms associated with AF. There were no deaths, neurological complications or long-term recurrence of arrhythmia. One patient had an early recurrence of AF that was not amenable to medical treatment, and was subsequently treated with His' bundle ablation. Of the remaining nine patients, seven manifested signs of some postoperative atrial contraction at echocardiography, the occurrence of which needs to be borne in mind with a view to reducing the risk of future thromboembolic events. We recommend the maze procedure as an attractive surgical option in cases of unsuccessful medical treatment of paroxysmal or chronic AF.

Lung function, arterial saturation and oxygen uptake in elite cross country skiers: influence of exercise mode.

Arterial desaturation during exercise is common in endurance-trained athletes, a phenomenon often more pronounced when the muscle mass engaged in the exercise is large. With this background, the present study monitored seven international-level cross country skiers performing on a treadmill while running (RUN), double poling (DP; upper body exercise) and diagonal skiing (DIA; arm and leg exercise). Static and dynamic lung function tests were performed and oxygen uptake was measured during submaximal and maximal exercise. Lung function variables (including the diffusion capacity) were only 5-20% higher than reported in sedentary men. Vital capacity was considerably lower than expected from the skiers' maximal oxygen uptake (VO(2max)), but the maximal ventilation followed a linear relationship with VO(2max). None or only a mild desaturation was observed in DP, RUN and DIA. Blood lactate concentration was slightly higher in DIA than in DP but not different from RUN. In DIA, VO(2max) was 6.23 +/- 0.47 L/min (mean +/- SD), which was 3.8% and 13.9% higher than in RUN and DP, respectively, with similar peak heart rates for the three exercise modes. No relationships were present either between the degree of desaturation and pulmonary functions tests, or with peak oxygen uptakes. The low blood lactate accumulation during the exhaustive efforts contributed to the arterial oxygen saturation being mild in spite of the very high oxygen uptake observed in these skiers.

Maximal and submaximal oxygen uptake during running: how should body mass be accounted for?

Oxygen uptake during running, i.e., the running economy, is an important factor in determining running performance in endurance events. The relation to performance is particularly strong when the aerobic running capacity is calculated, i.e., when running economy is related to the maximal oxygen uptake. There is considerable interindividual variation in running economy, and the reason for this is only partly understood. To some extent, this may be due to the way in which the oxygen uptake during running is usually expressed. This may especially be true when subjects with different or changing body masses are compared. Several lines of evidence, including earlier animal studies as well as more recent human studies, favor the expression of submaximal and maximal oxygen uptake during running in terms of ml.kg-0.75.min-1 rather than as ml.kg-1.min-1.

Maximal and submaximal oxygen uptakes and blood lactate levels in elite male middle- and long-distance runners.

Physiological characteristics of elite runners from different racing events were studied. Twenty-seven middle- and long-distance runners and two 400-m runners belonging to the Swedish national team in track and field were divided, according to their distance preferences, into six groups from 400 m up to the marathon. The maximal oxygen uptake (VO2 max, ml X kg-1 X min-1) on the treadmill was higher the longer the main distance except for the marathon runners (e.g., 800-1500-m group, 72.1; 5000-10,000-m group, 78.7 ml X kg-1 X min-1). Running economy evaluated from oxygen uptake measurements at 15 km/h (VO2 15) and 20 km/h (VO2 20) did not differ significantly between the groups even though VO2 15 tended to be lower in the long-distance runners. The running velocity corresponding to a blood lactate concentration of 4 mmol/l (vHla 4.0) differed markedly between the groups with the highest value (5.61 m/s) in the 5000-10,000-m group. The oxygen uptake (VO2) at vHla 4.0 in percentage of VO2 max did not differ significantly between the groups. The blood lactate concentration after exhaustion (VO2 max test) was lower in the long-distance runners. In summary, the present study demonstrates differences in physiological characteristics of elite runners specializing in different racing events. The two single (but certainly inter-related) variables in which this was most clearly seen were the maximal oxygen uptake (ml X kg-1 X min-1) and the running velocity corresponding to a blood lactate concentration of 4 mmol/l.

Physiological characteristics of elite male runners in and off-season.

The seasonal variation in physiological characteristics of elite male runners was studied. Five middle distance (mean age 21 yrs) and 5 long distance runners (23 yrs), all members of the Swedish national track and field team, participated in treadmill tests on 4 occasions over a period of one year: in January, in May, during the highly competitive summer period and the following January. The maximal oxygen uptake (VO2 max, ml X kg-1 X min-1) increased successively during the season and was significantly (p less than 0.01) higher during the summer than in the winter (74.2 to 77.4 ml X kg-1 X min-1). From the competitive summer period to the second winter the VO2 max (ml X kg-1 X min-1) showed a significant decrease. The absolute value of VO2 max (1/min) was not significantly changed during this one-year period, however. Running economy was evaluated from oxygen uptake determinations at 15 km/h (VO2 15) and 20 km/h (VO2 20). Slightly lower values of VO2 15 and VO2 20 were noted during the season, and after one year VO2 20 was significantly decreased. Such an improvement in running economy with time was also found in a larger group of elite runners (n = 16) when determined from an average of 7 treadmill tests. The running velocity corresponding to a blood lactate concentration of 4 mmol/l increased from January to the summer season. The blood lactate concentration after exhaustion (VO2 max test) increased significantly from January to May.

Oxygen uptake during running as related to body mass in circumpubertal boys: a longitudinal study.

To investigate the effect of endurance training on physiological characteristics during circumpubertal growth, eight young runners (mean starting age 12 years) were studied every 6 months for 8 years. Four other boys served as untrained controls. Oxygen uptake (VO2) and blood lactate concentrations were measured during submaximal and maximal treadmill running. The data were aligned with each individual's age of peak height velocity. The maximal oxygen uptake (VO2max; ml.kg-1.min-1) decreased with growth in the untrained group but remained almost constant in the training group. The oxygen cost of running at 15 km.h-1 (VO2 15, ml.kg-1.min-1) was persistently lower in the trained group but decreased similarly with age in both groups. The development of VO2max and VO2 15 (l.min-1) was related to each individual's increase in body mass so that power functions were obtained. The mean body mass scaling factor was 0.78 (SEM 0.07) and 1.01 (SEM 0.04) for VO2max and 0.75 (SEM 0.09) and 0.75 (SEM 0.02) for VO2 15 in the untrained and trained groups, respectively. Therefore, expressed as ml.kg-0.75.min-1, VO2 15 was unchanged in both groups and VO2max increased only in the trained group. The running velocity corresponding to 4 mmol.l-1 of blood lactate (nu la4) increased only in the trained group. Blood lactate concentration at exhaustion remained constant in both groups over the years studied. In conclusion, recent and the present findings would suggest that changes in the oxygen cost of running and VO2max (ml.kg-1.min-1) during growth may mainly be due to an overestimation of the body mass dependency of VO2 during running.(ABSTRACT TRUNCATED AT 250 WORDS)

Body-mass-modified running economy and step length in elite male middle- and long-distance runners.

To minimize the influence of body mass on oxygen uptake (VO2) during running, submaximal and maximal VO2 should preferentially be expressed as ml.kg-0.75.min-1. In this study, the levels of such body-mass-modified running economy were investigated at different velocities in elite runners and related to step lengths and anthropometric measures. Twenty-six Swedish National Team middle- and long-distance runners performed submaximal (4 velocities) and maximal treadmill tests. In 17 runners repeated (2-4) tests were performed within 6 months. The maximal oxygen uptake (VO2max; 214 vs 202 ml.kg-0.75.min-1) and running velocity at 4 mmol.l-1 blood lactate were higher in the long- (n = 12) than in the middle-distance group (n = 14). The oxygen uptake at 15 km.h-1 (VO2 15) was lower (129 vs 138 ml.kg-0.75.min-1, p < 0.01) and the VO2/velocity slope higher in the long-distance runners, with similar VO2 18 in the two groups. Step lengths at 18 (168 vs 173 cm) and 15 km.h-1 did not differ significantly between the groups, but the increase in step length per km.h-1 velocity raise was greater in the middle-distance runners. Step lengths at these velocities were positively related to body mass and stature, negatively to relative leg length. Stature and leg length were greater in runners displaying low VO2 15, whereas no corresponding difference was seen for VO2 18. The figures for running economy at 15 and 18 km.h-1 were poorly related to the concomitantly determined step lengths at the respective velocities.(ABSTRACT TRUNCATED AT 250 WORDS)

The validity of isokinetic knee extensor endurance measurements with reference to treadmill running capacities.

The validity of isokinetic knee extensor endurance measurements with reference to treadmill running capacities was investigated. Nine male elite middle-distance runners completed a test consisting of 100 repetitive maximal eccentric and 100 concentric knee extensor actions where peak torque (Nm) and work (J) were measured. On a different day, submaximal and maximal treadmill tests were performed. Stepwise regression analysis was applied to determine the isokinetic variables with the greatest influence on the selected treadmill running capacities, including submaximal oxygen uptake (VO(2)) and maximal blood lactate. Eccentric total work was significantly and negatively related to submaximal VO(2) at all three running velocities investigated (12, 14, and 15 km.h(-1)). The R(2) values ranged from 0.48-0.59 for V0(2) ml.kg(-0.75).min(-1), indicating that 48-59 % of the variability in VO(2) ml.kg(-0.75).min(-1) could be accounted for by eccentric total work. The corresponding R(2) values for VO in ml.kg(-1).min(-1) were 0.50-0.58. Concentric relative endurance was significantly and negatively related to maximal blood lactate (R(2) = 0.73). This study has shown that isokinetic knee extensor endurance measurements of eccentric total work and concentric relative endurance are substantially related to measures of treadmill running capacity, as expressed by submaximal V02 and maximal blood lactate. It is suggested that these isokinetic measures may be used to evaluate specified running capacities in male elite middle-distance runners.

A case of Brucella melitensis endocarditis successfully treated by a combination of surgical resection and antibiotics.

Endocarditis is a rare complication of brucellosis, often fatal, and the treatment is controversial. We present a case of Brucella melitensis endocarditis successfully treated by a combination of surgical resection and antibiotics.

Changes in onset of blood lactate accumulation (OBLA) and muscle enzymes after training at OBLA.

Eight well-trained middle and long distance male runners added to their regular training program a weekly 20-min treadmill run at a velocity calculated to elicit a blood lactate concentration of 4 mmol X 1-1. VO2 max, the running velocity eliciting 4 mmol X 1-1 blood lactate (VOBLA), and the activities of citrate synthase (CS), phosphofructokinase (PFK), lactate dehydrogenase (LDH) and LDH isozymes in the M. vastus lateralis were determined before and after 14 weeks of this training. Significant increases were observed in VOBLA and the relative fraction of heart-specific LDH, while the activity of PFK and the ratio of PFK/CS decreased after training. The change in VOBLA was negatively correlated to the mean rate of blood lactate accumulation during the last 15 min of the treadmill training runs, and positively correlated to the percentage of slow twitch fibers in the M. vastus lateralis. The data support the hypothesis that a steady state training intensity which approximates VOBLA will increase VOBLA, and will result in measureable local metabolic adaptations in the active skeletal muscles of well-trained runners without a significant change in maximal aerobic power. Muscle fiber type composition may be an indicator of the "trainability" of the musculature.

Dissociation of training effects on skeletal muscle mitochondrial enzymes and myoglobin in man.

The effect of endurance training on skeletal muscle myoglobin concentration in man was investigated. 8 healthy sedentary males (20-31 yrs) trained on cycle ergometers 40 min/day, 4 days a week for 8 weeks. The work consisted of continuous exercise at a work load that during the last 5 weeks corresponded to 75% of the pretraining maximal oxygen uptake (VO2 max). The training program resulted in a 7% increase in VO2 max (p less than 0.01). The activities of the mitochondrial enzymes citrate synthase (CS), succinate dehydrogenase (SDH) and cytochrome c oxidase (Cyt-c-ox) in the quadriceps femoris muscle, as indicators of muscle respiratory capacity, increased by 62-82% (p less than 0.01). The metabolic adaptation of skeletal muscle was further indicated by a 17% increase in the work load corresponding to a blood lactate concentration of 4 mmol/l, as determined by a progressive exercise test (p less than 0.05). There was, however, no change in the myoglobin concentration of the thigh muscle with training (-1%, NS). It is suggested that endurance exercise in man at 75% of the maximal oxygen uptake does not severely tax the functions of myoglobin in skeletal muscle.

Analgesic effects of adenosine in syndrome X are counteracted by theophylline: a double-blind placebo-controlled study.

It has been proposed that adenosine mediates ischaemic pain in humans. Patients with cardiac Syndrome X are hypersensitive to potential pain stimuli, including adenosine. On the other hand, recent findings suggest that low-dose adenosine infusion may have analgesic effects. Our aim was to test two hypotheses: (1) that the analgesic effect of adenosine is peripheral in origin, and (2) that part of the hypersensitivity to pain of patients with cardiac Syndrome X results from a disturbed mechanism of adenosine analgesia. A total of 12 female Syndrome X patients and eight healthy age-matched female controls were studied in a randomized, double-blind and placebo-controlled study. Adenosine (70 microg/min) or placebo was infused into the forearm via an intra-arterial catheter. After 15 min of infusion, a tourniquet on the upper arm was inflated to 225 mmHg to ensure arterial occlusion. The patient then carried out dynamic handgrip work at 60 Hz. Pain or discomfort in the forearm was estimated continuously according to the Borg CR-10 scale. After the first test, theophylline was infused for 10 min intravenously at a dose of 5 mg/kg body weight. The ischaemic forearm test was then repeated. On a second occasion, the procedure was repeated with the opposite treatment (adenosine/placebo). Only six of 12 Syndrome X patients completed the protocol because of pain during the catheterization procedure or an inability to establish an intra-arterial line. The time to onset of pain in the working, ischaemic forearm was greater for subjects treated with adenosine than for those treated with placebo, both in those Syndrome X patients who tolerated catheterization (49+/-27 s compared with 32+/-18 s; P<0.03) and in healthy controls (40+/-19 s compared with 16+/-8 s; P<0.02). The time to maximum pain, limiting ischaemic work, was also greater with adenosine pretreatment both in Syndrome X patients (137+/-28 s compared with 106+/-28 s; P<0.03) and in healthy controls (109+/-31 compared with 82+/-18 s; P<0.01). After infusion of theophylline there was no difference between adenosine and placebo in either group. Intra-arterially infused adenosine had similar peripheral analgesic effects on experimentally induced muscular ischaemia in those female Syndrome X patients who tolerated intra-arterial catheterization and in healthy controls. Thus adenosine analgesia is counteracted by theophylline, suggesting that the effect is mediated by membrane-bound peripheral adenosine receptors.