Plasma lactate concentration and muscle blood flow during dynamic exercise with negative-pressure breathing.

This study assessed the hypothesis that increasing cardiac filling pressure (CFP) would enhance contracting muscle blood flow (MBF) by stretching cardiopulmonary baroreceptors and attenuate the increase in plasma lactate concentration ([Lac(-)](p)) during dynamic exercise. Continuous negative-pressure breathing (CNPB) (-15 cmH(2)O) was used to increase the CFP by accelerating the venous return to the heart. In the first series of experiments, 10 men performed a graded exercise seated on a cycle ergometer with (N1) and without CNPB (C1). The increase in [Lac(-)](p) for N1 was attenuated at 60%, 90%, and 100% of maximal exercise intensity compared with that in C1 (P < 0.001). Also, the increases in mean arterial pressure (MAP) and plasma catecholamine concentrations were attenuated in N1 compared with those in C1 throughout the graded exercise (P < 0.05). However, heart rate and pulse pressure were not significantly influenced by CNPB. Second, we studied the impact of CNPB on forearm MBF during a rhythmic handgrip exercise in 5 of the 10 subjects. Forearm MBF was measured immediately after cessation of the exercise by venous occlusion plethysmography at rest, 30%, 50%, and 70% of maximal work load (WL(max)) with (N2) and without CNPB (C2). Forearm MBF and vascular conductance for both trials increased with the increase in intensity, but forearm skin blood flow measured by laser-Doppler flowmetry remained unchanged. MBF and vascular conductance in N2, however, increased more than in C2 at every intensity (P < 0.01) except for MBF at 70% WL(max), whereas the increase in MAP for N2 was attenuated compared with that in C2 (P < 0.05). Thus augmented active muscle vasodilation occurred in N2 with a lower increase in MAP compared with that in C2. These findings suggest that the stretch of intrathoracic baroreceptors, such as cardiopulmonary mechanoreceptors, by CNPB increased MBF by suppressing sympathetic nerve activity. The attenuation of the increase in [Lac(-)](p) might be caused, at least partially, by the increased MBF.

The cGMP pathway is not responsible for the blunted hypoxic vasoconstriction in rat lungs after altitude exposure.

To examine the contribution of the cyclic guanosine monophosphate (cGMP) pathway in changes in pulmonary vasoconstriction during the initial days of altitude exposure, we tested the effects of LY83583 (an inhibitor of guanylate cyclase activation) and those of N(G)-monomethyl-L-arginine (an inhibitor of nitric oxide synthesis) on airway hypoxia- (3% O2) and angiotensin II- (AII, 0.2 microg) induced vasoconstrictions in lungs from the rats exposed to either moderate altitude (MA, 570 torr) or high altitude (HA, 430 torr) At 2 days' exposure, hypoxic response was significantly blunted compared with the response in low-altitude (LA, 710 torr) lungs in an altitude-dependent manner. At 7 days' exposure, the response was recovered fully in MA lungs but partially in HA lungs. AII response was not significantly blunted at 2 days' exposure, but was significantly augmented in an altitude-dependent manner at 7 days' exposure. LY83583 (10 micromol L(-1)) potentiated both responses in LA lungs but did not significantly potentiate either response in any altitude-exposed lungs. N(G)-monomethyl-L-arginine (10 micromol L(-1)) potentiated both responses in LA lungs but did not significantly potentiate either response in HA lungs at 2 days' and 7 days' exposure. Thus the cGMP pathway is not responsible for either the change in hypoxic vasoconstriction or the change in AII vasoconstriction in rat lungs during the initial 7 days of altitude exposure.

Electromyographic (EMG) study of cold shivering in the chronic spinal dog.

Cold shivering in six chronic spinal dogs (T9-10), which became capable of weight-bearing standing and/or walking with their hindlimbs, was studied by electromyography (EMG). In the forequarters, EMG activities in the form of grouping discharges (GD) accompanied by visible tremor (VT) were induced at an ambient temperature of 15 degrees C in all the dogs. In the hindquarters, GD with VT were induced at 3 degrees C in one dog. Although GD with VT were not induced in in the remaining dogs, GD without VT were produced by additional cutaneous stimuli to the hindquarters at 3 degrees C. These stimuli never produced GD in the hindquarters at room temperature. Though the mean frequency of GD in the hindquarters was lower than that in the forequarters, the range of the frequency in the hindquarters was much the same as that in the forequarters. During the experiment, the drop in rectal temperature was less than 0.6 degrees C in all of the dogs. These findings suggest that the chronically isolated spinal cord is responsible for cold shivering, while its excitability to cold exposure is less than that of the spinal cord governed by the supraspinal center.

Effects of exercise-training on hypoxia and angiotensin II-induced pulmonary vasoconstrictions.

The present study was undertaken to determine whether exercise-training for 6 weeks would inhibit pulmonary vasoconstriction induced by hypoxia in isolated, blood-perfused rat lungs. Hypoxic pulmonary vasoconstriction (HPV) and angiotensin II (AII)-induced pulmonary vasoconstriction were significantly less in the exercise-trained (ET) group than in the control (cont) group with all challenges. Normoxic pulmonary arterial and capillary pressures in the ET group were significantly lower than those in the cont group and capillary pressor response to hypoxia was less in the ET group than in the cont group. In conclusion, it appears that HPV and AII-induced vasoconstrictions can be reduced by exercise-training, because it would seem that exercise-training repeated responses to increased shear-stress resulting from elevated blood flow in pulmonary vessels.

Cardiopulmonary function in bicycle racing over mountainous terrain at moderate altitude.

To examine cardiopulmonary function during exercise in a mountainous region at moderate altitude, we measured cardiac frequency, oxygen consumption (VO2), and percentage arterial hemoglobin oxygen saturation (%SaO2) before and after a bicycle race with a starting point at 638 m and finishing point at 1980 m. The time required to ascend an elevation of 10 m was prolonged with increasing altitude, and heart rate also increased with altitude. The %SaO2 at the starting point and at the finishing point differed significantly (P < 0.01). Faster cyclists exhibited higher %SaO2 and lower VO2, while slower cyclists exhibited a reduction in %SaO2 and an increase in VO2 immediately after the race. The %SaO2 recovery time was significantly correlated with the racing time (r = 0.54, P < 0.001). Therefore, the faster cyclists' oxygen debt upon completion of the race may be small and recovery of cardiopulmonary function may be fast, while the slower cyclists' oxygen debt may be large and recovery of cardiopulmonary function may be slow.

Cardio-pulmonary function of cyclists competing on an ascending mountain course between altitudes of 1400 m and 2800 m.

Physiological changes were investigated in the cardio-respiratory function of competitors in a bicycle race which involved not a flat course but ascending a mountain, from 1400 m to 2800 m. Heart rate throughout the race, arterial oxygen saturation and pulmonary function before and after the race of well trained competitors were measured. The individual's maximal heart rate during the race was designated as HRmax for the calculations. (1) There were significant correlations between the age and the mean %HRmax during the race, between mean %HRmax and time, and between age and time (n = 15); the mean %HRmax had a 3.90 times greater effect on time than did age. (2) The individuals who performed best had lower values of oxygen saturation just after finishing the race (n = 51). (3) At 1 min after reaching the finishing line, oxygen saturation levels had recovered to the value of 20 min after finishing the race, whereas the heart rate was still in the process of recovery (n = 18). (4) Maximum expiratory flow at 50% vital capacity measured 30 min after reaching the finishing line was significantly higher than at the starting point. The intensity of the load on the cardiac system produced by completion of this course was estimated to be almost the same as that of a full marathon on a flat course. The time depended on both the youth of the cyclist and on his ability to maintain a high value of %HRmax during the race.

Effects of exercise training at 1,500 m on arterial oxygen saturation and pulse rate.

We compared the effects of exercise training at a low (610 m) altitude with those at moderate (1,500 m) altitude on arterial oxygen saturation (SaO2) and pulse rate (PR) between two groups of men: five subjects in the low altitude group (LG), and five other subjects in the moderate-altitude group (MG), after giving them a series of bicycle training in a hypobaric chamber. Training intensity was 75% HRmax for 60 min/day, 3 times per week for 5 weeks. Before and after the training, Sao2 and PR were measured with a pulse oximeter during step-tests under various air pressures, corresponding to 610 m, 2,000 m, and 4,000 m, respectively, in the chamber. We found that: 1) Sao2 during the step-test carried out at 2,000 m and 4,000 m in the hypobaric chamber was significantly increased in MG compared with that in LG; and 2) PR during the step-tests at 610 m, 2,000 m, and 4,000 m was significantly decreased in MG compared with that in LG. Thus, we conclude that exercise training at a moderate altitude is a useful method for increasing Sao2 and decreasing PR and may prevent mountain sickness.

Effects of high altitudes on finger cooling test in Japanese and Tibetans at Qinghai Plateau.

The influences of both hypobaric hypoxia and cold on peripheral circulation were studied using the finger cooling test (measurement of the decrease in finger temperature, measured at the dorsal surface of the finger, during immersion of the hand in 0 degrees C water for 20 min) at Qinghai Plateau. The same test was carried out at simulated altitudes in a 25 degrees C climatic chamber to separate the hypobaric hypoxia influence from that of cold. In Japanese subjects at Qinghai Plateau there was a significant difference between finger skin temperatures (FSTs) during 20 min of 0 degrees C water immersion at altitudes of 2260 m and 4860 m by ANOVA. Mean finger skin temperature during the 20-min immersion (5-20 min, MST) measured at 4860 m was significantly lower than that at 2260 m. In Tibetan subjects, there was also a significant difference between FSTs at 2260 m and at 4860 m by ANOVA. MST at 4860 m tended to be lower than that at 2260 m. In the 25 degrees C climatic chamber, there was a significant difference between FSTs of Japanese expedition members at 2000 m and at 4000 m by ANOVA. MST was higher at 4000 m than at 2000 m, contrary to the data obtained in Qinghai. In conclusion, the higher skin temperature in response to local cold immersion, which would have been caused by stronger hypobaric hypoxia, must have been masked by the lower ambient temperature.

Thermogenesis induced by inhibition of shivering during cold exposure in exercise-trained rats.

The present investigation was conducted to examine the role of nonshivering and shivering thermogenesis caused by cold exposure in exercise-trained rats. Wistar rats were divided into warm-acclimated (WA), exercise-trained (ET) and cold-acclimated (CA) groups. The trachea was cannulated and a ventilator was connected under light anesthesia and in the supine position. Shivering, oxygen consumption, colonic temperature, blood glucose, and free-fatty acids were measured at 25 degrees C and then at 0 degrees C room temperatures. D-tubocurarine chloride (curare, 0.04 mg/100 g body weight, ip) was given to inhibit muscular activity. Cold-induced oxygen consumption in the ET and WA groups did not decrease when shivering was inhibited, whereas it increased in the CA. The magnitude just after shivering onset for the ET and CA groups as significantly greater than for the WA group. Colonic temperature at the onset of shivering was significantly higher in the WA group than in the ET and the CA groups. The blood glucose concentration during cold exposure and curarization was elevated in the ET group, and did not change in the CA or WA groups. The present results suggest that endurance training at a thermoneutral environment increases cold-induced thermogenic capacity in rats, which may be attributed to preferential carbohydrate utilization.

Purification and characterization of a protein associated with genetically-determined longevity difference in Drosophila melanogaster.

Earlier studies have shown a correlation between the presence of a 77 kDa protein in the proteins extracted from young adult Drosophila melanogaster (D.m.) and the autosomal longevity allele. A2 at the JmA locus. In this study, a 77 kDa protein has been isolated from pupae of D.m. of a long-lived strain of genotype A2A2, and was purified by DEAE chromatography, ConA column chromatography, and two cycles of gel filtration. The purified protein has a molecular weight of 76,600 (by SDS-PAGE), an isoelectric point of pH 6.5, and molar extinction coefficient A(280(1%) = 18.3. It is a glycoprotein containing 3.3% hexose. Supplementing the food of D.m. with the purified protein at 5 x 10(-4) micrograms/ml, beginning at day 5 after emergence, resulted in an increase in the survival rate and maximal life span of both short-lived and long-lived strains of D.m.

Pulmonary circulation during exercise in rats.

Pulmonary arterial pressure of treadmill-running rats became significantly higher than the sedentary control level, while systemic arterial pressure did not rise. The rise of pulmonary arterial pressure seemed to be accompanied with the increase of cardiac output.

Climatic adaptation in thermogenesis and thermal insulation in wood mice (Apodemus argenteus).

Wood mice (Apodemus argenteus) were trapped live at three different altitudes (below 1,000, 1,900, and 2,400 m) during a 1-year period (Feb. 1984-Jan. 1985). After remaining at the trapped locations for 10-14 days, they were transferred into a climatic chamber at an altitude of 610 m. Oxygen consumption (VO2) and colonic temperature (Tco) were measured at chamber temperatures (Ta) of five steps (30, 20, 10, 0, and -10 degrees C) in freely moving conditions. In response to Ta of 0 degrees C for the mice trapped in winter when their mean local habitat temperature (Te) were lower than 0 degrees C, there was a significant inverse correlation between VO2 and Te (r = -0.70, p less than 0.001) whereas no significant correlation (r = 0.23) was observed in the mice trapped in other seasons when Te was higher than 0 degrees C. The correlation between Tco and Te was significant (r = -0.66, p less than 0.001) over the entire range of Te. The pelt weight of the mice trapped at Te higher than 0 degrees C had a significant inverse correlation with Te (r = -0.65, p less than 0.001), but not in the mice trapped at Te lower than 0 degrees C. After measurement of VO2 and Tco at Ta of 0 degrees C, the mice who had lived in colder habitats (below 0 degrees C) showed 0% mortality, whereas the mortality of the populations which had lived in warmer habitats was 13%. These results suggest that, in wood mice, adaptation to severe cold is established by an enhanced thermogenesis and by an increased insulation of the pelt in moderate cold.

Morphological differences in hearts of rats well adapted and poorly adapted to chronic hypoxia.

We carried out an experiment to analyze morphological differences in hearts of rats well adapted and poorly adapted to chronic hypoxia. Male and female Wistar rats, 1 week, 4 weeks and 9 weeks old, were employed on the assumption that adaptive ability was dependent on age and sex. These rats were raised at an altitude of 2,400 m and were kept for 7 to 9 weeks. Control groups were maintained at an altitude of 600 m during the same period of time. Each group consisted of 4 to 6 rats. At the end of the experiment, body weight, heart weight, ratio of heart weight to body weight and hematocrit were measured, and ventricular wall thickness, myocardial fiber diameter, capillary supply and mitochondria were morphometrically studied. Of the 6 experimental groups, the 4-week-old male rats (M2) had the highest body weight, as compared with the other experimental groups. In addition, relative to these other experimental groups, the following features were found for M2. Heart weight was intermediate, heart weight/body weight ratio was low and hematocrit was also low. Ventricular wall thickness was intermediate in the right ventricle (RV) and interventricular septum (IVS) but was thin in the left ventricle (LV). Myocardial fiber diameter was intermediate in the RV, large in the IVS and small in the LV. Capillary supply was intermediate in the RV and dense in the IVS and LV. Mitochondria were small but cristal density and percentage area, estimated from electron micrographs, were found to be high.(ABSTRACT TRUNCATED AT 250 WORDS)

[Thermogenic responses of high-altitude adapted rats on low temperatures and low pressures].

The male rats were raised in two groups, one at Mt. Yatsugatake (2,100 m above sea level, the average ambient temperature 12.5 degrees C) for 30 days, and the other at a laboratory of Matsumoto (610 m above sea level, the average temperature 20 degrees C). The steady-state oxygen consumptions (VO2) and the rectal temperatures (TR) were measured under exposure conditions of various temperatures combined with different simulated altitudes. The values of VO2 and TR for a control group at 610 m-20 degrees C were regarded as 100% and the relative changes to the control values were obtained at various temperatures in the respective low-pressure condition. When measured at a simulated altitude of 2,000 m on the 2nd day after the rats raised at Mt. Yatsugatake were translocated to Matsumoto, the values at 0 degrees C and 10 degrees C room temperatures, VO2 and TR, were still significantly increased as compared with those of rats raised at Matsumoto. On the 40th day after the translocation from Mt. Yatsugatake, however, the values turned out to exhibit no significant difference in both groups. These results indicated that the greater thermogenesis of high-altitude adapted rats had been established by combined stimuli of low temperatures and low pressures as compared with those of Matsumoto-level adapted rats, but the responses returned to the control level by deadaptation process at 40 days after the translocation.