Cerebral blood flow velocity during and after sustained isometric skeletal muscle contractions in man.

1. Twenty-seven young subjects used their right hand to perform sustained, isometric contractions at 40% of maximum for 2 min while lying supine. 2. During the last 30 s of exercise, mean arterial blood pressure increased by 38 +/- 4 mmHg (mean +/- S.E.M.) and heart rate by 27 +/- 2 beats/min. 3. Nineteen of the subjects respired eucapnically during exercise, increasing ventilation by 4.1 +/- 0.5 litres/min. Eight subjects hyperventilated (7.1-19.6 litres/min) and decreased end-tidal PCO2 by 8.2 to 15.1 mmHg during the last minute of exercise. 4. In the eucapnic subjects mean flow velocity in the right (i.e. contralateral to the activated cortex) middle cerebral artery increased by 11.4 +/- 1.0 cm/s, a change of 17%, during the contraction. This represents an increase in volume flow to the territory of this vessel, but an increase in global flow to the brain cannot be inferred. 5. In the eight subjects who hyperventilated during exercise, there was no rise of flow velocity in the middle cerebral artery, and in some subjects there was a fall during the first 2 min of recovery. These findings suggest that if subjects hyperventilate during handgrip exercise there could be a fall in volume flow to many regions of the brain during and after the exercise.

Nitric oxide-mediated vasodilation in human pregnancy.

The maternal circulation vasodilates during pregnancy. We investigated the contribution of nitric oxide to this vasodilatation. Using venous occlusion plethysmography, we measured the effect of nitric oxide synthase inhibition on hand blood flow during human pregnancy. We compared the response to a brachial artery infusion of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) with the response to norepinephrine in three groups of women: nonpregnant, early pregnant (9-15 wk), and late pregnant (36-41 wk). Basal hand blood flow increased significantly during late pregnancy compared with nonpregnant and early pregnant subjects (P = 0.007). L-NMMA produced a greater reduction in hand blood flow in both pregnant groups compared with nonpregnant controls (P = 0.0003). Norepinephrine produced an attenuated response in late pregnancy compared with nonpregnant and early pregnant women (P = 0.0029). If other vascular beds respond in the same way as the hand, the gestational increase in vasoconstrictor response to L-NMMA that we observed implicates increased generation of nitric oxide in the fall of peripheral vascular resistance during healthy human pregnancy.

Cardiac output and oxygen uptake in patients with renal failure.

1. Cardiac index, oxygen uptake and haemoglobin concentration have been measured in eight patients with end-stage renal failure, and the values compared with those in eight healthy control subjects. Assuming the arterial blood to be 97% saturated, the oxygen saturation of mixed venous blood has been calculated. 2. Cardiac index was lower in the patients (2.45 +/- 0.42 litres min-1 m-2) compared with the control subjects (3.74 +/- 0.17 litres min-1 m-2). Oxygen uptake was reduced from 147 +/- 16 ml STP min-1 m-2 in the control subjects to 112 +/- 9 ml STP min-1 m-2 in the patients. 3. Oxygen saturation of mixed venous blood was 53 +/- 8% in the patients compared with 79 +/- 2% in the control subjects, suggesting some degree of tissue hypoxia. If oxygen uptake were not reduced in renal failure, then the mixed venous blood oxygen saturation would be as low as 40%. 4. The oxygen saturation of blood sampled from the superior vena cava of patients with renal failure was 57 +/- 6%. 5. The data on oxygen uptake and venous oxygen saturation suggest that in the patients with end-stage renal failure, the low values of cardiac index, previously measured by impedance cardiography, are accurate.

Respiratory responses to sustained isometric muscle contractions in man: the effect of muscle mass.

1. Respiratory responses to sustained isometric contractions of a small mass of muscle (the finger flexors) during handgripping, and of a larger mass of muscle (the quadriceps) during extension of the leg at the knee, have been studied in man. 2. For both masses of muscle the increases of ventilation and of oxygen consumption were greater for contractions at 40% maximum voluntary contraction (MVC) than for contractions at 20% MVC. 3. The increase of ventilation was not related to the mass of muscle involved. 4. At 20% MVC oxygen consumption during contraction of the quadriceps was greater than that during handgripping. At 40% MVC the oxygen consumptions were similar. The oxygen debts following both handgrip and knee extensor contractions at 20% MVC were negligible. Following 40% MVC contractions of the quadriceps a significant oxygen debt was recorded but no debt was apparent following 40% MVC contractions of the finger flexors. 5. The increases of ventilation during isometric exercise were generally inappropriately high for the increases of gas exchange. This led to reductions of the end-tidal carbon dioxide pressure (PET,CO2), especially towards the end of exercise. 6. Following 40% MVC handgripping hyperventilation continued despite the reduced alveolar PCO2. By contrast, following 40% MVC knee extension PET,CO2 transiently rose above the resting level, but did not stimulate ventilation. 7. It appears that following fatiguing isometric contractions hyperventilation continues and appears to be independent of alveolar PCO2. It is suggested that stimuli which increase ventilation during exercise may continue to act during the early phase of recovery.

Reactive hyperaemia in the human forearm.

Reactive hyperaemia in the human forearm has been studied following 5, 10 and 15 min occlusion of the circulation using mercury-in-rubber strain gauges. Following 5 min occlusion the initial high blood flows declined exponentially with a half-life ranging from 14 to 45 s. After 10 and 15 min occlusion the flow pattern is represented by a plateau followed by an exponential of similar time course to the above. Flows did not decay totally along this exponential but deviated onto a second, slower exponential with half-lives ranging from 50 to 560 s. The hyperaemia represented by the area under the second exponential makes a greater contribution to the total flows in non-muscular tissues. It is suggested that this phase of the hyperaemia may be the result of tissue warming during the initial period of high flows.

The effect of exercise on the production and clearance of testosterone in well trained young men.

Tritium-labelled testosterone was infused into four well-trained subjects at rest and during one hour of exercise at about 60% of their maximum aerobic power. This exercise regime led to a mean increase of 27% (range 10-51%) in plasma testosterone concentration. At the same time there were significant decreases in the estimated hepatic plasma flow (EHPF) (45%; range 28-67%), metabolic clearance rate of testosterone (MCRT) (29%; range 18-37%) and plasma volume (8.2%; range 3-10%). The production rate of testosterone decreased by 10% (range 9-22%) but this was not statistically significant. The ratio MCRT:EHPF increased in 3 out of 4 subjects in response to exercise but there was considerable inter-subject variation both at rest and during exercise. These findings suggest that the exercise-induced elevation of testosterone level is due solely to the reduction in the rate at which testosterone is cleared from the plasma. The principal cause of the reduction in MCRT is probably the reduction in EHPF but the variation in the ratio MCRT:EHPF suggests that changes in the extrahepatic clearance of testosterone may also be involved.

Resting blood flow in the paretic and nonparetic lower legs of hemiplegic persons: relation to local skin temperature.

It is commonly observed in patients with established hemiplegia following cerebrovascular accidents (CVA), that the skin temperature (Ts) of the leg and foot is notably cooler on the affected side of the body; the relationship to cutaneous blood flow, however, has not previously been investigated. In the present study, observations of foot and calf blood flow via venous occlusion plethysmography in water were made in six patients with hemiplegia of 5-13 months duration, both at observed Ts and at standard temperature (ST). Similar measurements were obtained on six age-matched control subjects. The patients' mean Ts values for the foot and calf were significantly lower on the affected side, while those for the nonaffected side were not significantly different from control group values. At non-equivalent water temperatures (Tw) blood flows in the patients' affected feet were lower than those on the nonaffected side, but at the ST they were similar. Further, under these conditions, the flows in both feet were lower than in control subjects. Flows in the patients' affected calves were not significantly reduced at non-equivalent TW; at the ST they did not differ significantly from those of the controls. These observations suggest that, in patients who have suffered a stroke, the reduction of TS of the affected limb is associated with reduced limb blood flow, which cannot be attributed to changes in limb tissue composition. Since the reduced limb blood flow on the affected side is more marked in the foot, it is likely to be due to reduction of blood flow in the skin. In addition, the reduction of flow in the foot of the nonaffected leg suggests a more generalized change of skin circulation in these patients.

Quantitative assessments of gait and mobility in Parkinson's disease.

Gait and mobility of 50 Parkinsonian patients were studied using an instrumented walkway and by analysis of video tape. Whilst walking velocities did not differ from those of subjects with other conditions affecting gait, worsening of the patients' clinical condition was related to deterioration of scores in these objective tests.

Studies of gait and mobility in the elderly.

The gait and mobility of 71 subjects aged 60--99 years were studied by completion of a questionnaire, by measurement of time and distance factors using a metal walkway, and by examination of the subject's performance on a simple "obstacle' course. Sway was measured with an ataxiameter. The subjects spanned a wide range of activity levels from those whose outdoor activity was unlimited to those who were housebound. The velocity of walking decreased slightly with age, but depended more on pathology affecting the motor system and on the subject's habitual activity. The mean velocity of walking for the subjects was lower than previously reported for elderly persons. Since the latter were obtained on "elite' subjects with no pathology of the central nervous or locomotor systems, it is proposed that data obtained on subjects in this study, who claimed unlimited activity, might constitute more realistic controls for studies of the effects of disease or for evaluation of rehabilitation. Other factors contributing to mobility, such as rising from a chair, ascending and descending stairs and turning around, were also more dependent on the presence of pathology than on age. The importance of balance was demonstrated by associations between ataxia scores and the velocity of walking and performance on the obstacle course. Subjects who used walking aids walked more slowly, had poor performances on the obstacle course and higher ataxia scores.

The influence of the infusion of noradrenaline on plasma cortisol levels in man.

1. Noradrenaline was infused into normal resting male subjects for consecutive 20 min periods at 3, 7.5 and 15 microgram min-1. At the end of the 1 hr of noradrenaline infusion, total catecholamine levels were in the range 4-6 microgram l.-1, comparable with those observed in severe exercise. 2. At all rates of infusion there were marked elevations of arterial blood pressure leading to reflex reductions of heart rate. Blood flow in the foot was reduced but blood flow in the calf was unaffected. Following the infusion, blood pressure rapidly returned to normal but the heart rate was raised by some 15 beat min-1 higher than the preinfusion control for at least 90 min. 3. Plasma cortisol tended to decrease slightly during the noradrenaline infusion but in twelve out of seventeen experiments it began to rise 30-75 min after termination of the infusion, reaching values 5-15 microgram 100 ml.-1 higher than those at the end of the noradrenaline infusion. Simultaneous rises in plasma aldosterone level were observed in those experiments in which it was measured. 4. Because of the long delay in the onset of hypercortisolaemia it is suggested that this is initiated not by the noradrenaline levels per se but by some physiological readjustments to the rapid fall in plasma noradrenaline level when the infusion was discontinued. The nature of these changes was not determined. 5. It is concluded that the elevated levels of plasma noradrenaline observed during exercise are not responsible for the synchronous increases in cortisol secretion.

The decline of aerobic capacity and muscle strength following fractures of the lower limb.

Aerobic capacities and muscle strengths of the uninjured limbs have been measured in patients who had suffered fractures of the lower limb. In patients treated in plaster-of-Paris aerobic capacity and strength fell rapidly following injury, to an extent greater than might be expected as a result of resting in bed. Before removal of the plaster-of-Paris, both aerobic capacity and strength had improved. Further improvement occurred in the injured limb after resuming use of the injured limb. In patients treated by traction and thus subjected to long periods in bed, the reductions of aerobic capacity and strength, measured shortly after resuming movements, were more profound than in patients treated with plaster-of-Paris.

The subdivision of beta-adrenoceptors in the cardiovascular system of the rat.

1 The antagonism by the beta-adrenoceptor blocking drugs, propranolol (non-selective) and practolol (beta-selective), of the cardiovascular actions of isoprenaline has been investigated in the rat. 2 All doses of practolol (0.1, 1 and 3 mg/kg) blocked the cardio-accelerator action of isoprenaline but only the largest dose blocked the vasodilator effect. 3 All doses of propranolol (0.01, 0.03 and 0.1 mg/kg) blocked the vasodilator effect of isoprenaline but only the largest dose diminished the tachycardia. 4 It is concluded that in the rat, as in other species, beta-adrenoceptors may be subdivided into beta 1 (cardiac) and beta 2 (peripheral vascular) types.

Abnormalities of the gait occurring during recovery from fractures of the lower limb and their improvement during rehabilitation.

The gait patterns of 19 patients recovering from fractures of the lower limb were analysed using a metal track on which patients walked in shoes fitted with metal contacts. The technique demonstrated marked abnormalities of the gait when patients were admitted to a rehabilitation unit, with an overall reduction of the extent of these abnormalities during treatment. Marked improvements of gait occurred whilst the patients were walking with the aid of crutches. However, little improvement occurred whilst the patients walked with sticks, but when sticks were discarded further marked improvements occurred.

Voluntary isometric muscle strength of patients undergoing rehabilitation following fractures of the lower limb.

Isometric muscle strength was measured in 32 servicemen recovering from fractures of the lower limb. At the time when patients were admitted for rehabilitation there were marked reductions of strength in the injured limb of muscles acting at the hip, knee and ankle joints. Marked improvement of strength occurred during rehabilitation, but there were still significant differences between the limbs at the time of discharge from the rehabilitation unit.