Effects of Sixty-Minute Race-Pace Running on Cardiac Stress Biomarkers in Recreational Distance Runners.

Sudden cardiac death (SCD) in athletes is generally rare, but a serious complication of cardiovascular events during exercise. Although regular intensive physical exercise is thought to be a key to a healthy life, unsuspected pathologies might lead to SCD during or after physical activity. Cardiac dysfunction and elevated cardiac markers have been reported after prolonged exercise. We sought to clarify the cardiac marker levels and hydration status in healthy, middle-aged male subjects for 24 hours after running sixty-minute at race-pace. The participants were 47.4±1.7 years old, had peak oxygen consumption of 47.1±1.2ml/kg/min, and regularly running 70.5±6.4km/week. Blood biomarkers were performed before, immediately after, at the fourth and twenty-fourth hours after running. Compared to initial values, creatine kinase (before:161.2±22.5U/L, 24 hours after:411.9±139.7U/L, p<0.001) and CK-MB (before:4.3±0.7ng/ml, 24 hours after:10.1±3.0ng/ml, p<0.001) were significantly elevated immediately after running and remained significantly high for 24 hours. In addition, Troponin-I (before:5.0±1.1ng/l, 4 hours after:81.5±29.9ng/l, p<0.001) and NT-proBNP (before: 31.2±5.3pg/ml, immediately after: 64.4±8.5pg/ml, p<0.01) were significantly elevated immediately after running and returned to baseline levels in 24 hours. The sixty-minute running caused significant dehydration, but athletes were rehydrated at the 4th hour in their voluntary hydration behavior. As the individual data were analyzed, it was interesting to see that some of the athletes had critical biomarker levels without any cardiac symptom. Our findings indicate that race-pace sixty-minute running may induce a possible transient silent myocardial injury in apparently healthy master runners. Detailed pre-participation screening of these athletes may be necessary to reduce the risk of SCD.

Effect of Regular Aerobic Training on Serum C-Reactive Protein and IL-6 Levels in Obese Women.

OBJECTIVE: This study's objective was to evaluate interleukin-6 (IL-6) and C-reactive protein (CRP) responses and performance changes in obese women after 8 weeks of aerobic training with an intensity of 50 to 60% of their individual maximum oxygen uptake (VO2). METHODS: A total of 18 sedentary women with an average age of 44.3 (± 1.9) years volunteered for this study. Over a period of 8 weeks, in 4 40-minute sessions per week, the participants walked at an exercise intensity that caused their heart rates to increase to levels corresponding to 50 to 60% of their VO2 peaks. Blood samples were collected from the participants, both when they were at rest and a couple of minutes after the end of the 1st exercise session. Sampling was repeated in the 4th and 8th weeks, before and after the last training sessions. RESULTS: The participants' body mass indices and weights decreased significantly by the end of the 8th week, while their maximum running speeds and VO2 peaks increased significantly. There were no differences in CRP or IL- 6 concentrations between the pre- and post-training sessions, but most of the participants' IL-6 levels dropped below 10 pg/ml after 8 weeks of training. CONCLUSION: Although no significant changes were observed in CRP or IL-6 concentrations, it is important to note that in response to aerobic training, the IL-6 levels of most of the participants fell to what is generally considered acceptable.

Changes in substrate utilization rates during 40 min of walking within the Fatmax range.

BACKGROUND AND AIMS: The aim of this study was to evaluate changes in fat oxidation rate during 40 min of continuous exercise and identify the intensity at the highest fat oxidation rate (Fatmax). METHODS: A total of 14 sedentary males with age, body height, weight, and BMI averages of 29.3 ± 0.7 years, 178.3 ± 1.7 cm, 81.1 ± 3.9 kg, and 25.4 ± 0.9 kg/m2, respectively, were included in the study. Fatmax was determined using an indirect calorimeter with an incremental treadmill walking test at least after 12 h of fasting. On a separate day, at least after 12 h of fasting, the participants walked for 40 min within their predetermined individual Fatmax heart rate and speed ranges. RESULTS: The initial fat oxidation rate was not sustained within the first 16 min of exercise and was reduced; however, carbohydrate oxidation reached a stable level after nearly 10 min. CONCLUSIONS: In sedentary individuals, during low-intensity physical activity, fat oxidation rates may not be sustainable as expected from Fatmax testing. Therefore, when exercise is prescribed, one should consider that the fat oxidation rate might decrease in sedentary overweight individuals.

Living, training and playing in the heat: challenges to the football player and strategies for coping with environmental extremes.

Dehydration and hyperthermia both, if sufficiently severe, will impair exercise performance. Dehydration can also impair performance of tasks requiring cognition and skill. Body temperature may exceed 40 °C in competitive games played in hot weather, but limited data are available. Football played in the heat, therefore, poses a challenge, and effects on some aspects of performance become apparent as environmental temperature increases above about 12-15 °C. Prior acclimatization will reduce the impact of high environmental temperatures but provides limited protection when humidity is also high. Ingestion of fluids is effective in limiting the detrimental effects on performance: drinks with added carbohydrate and electrolytes are generally more effective than plain water and drinks may be more effective if taken cold than if taken at ambient temperature. Pre-exercise lowering of body temperature may aid some aspects of performance, but the efficacy has not been demonstrated in football.

Hydration and sweating responses to hot-weather football competition.

During a football match played in warm (34.3 ± 0.6 °C), humid (64 ± 2% rh) conditions, 22 male players had their pre-match hydration status, body mass change, sweat loss and drinking behavior assessed. Pre-match urine specific gravity (1.012 ± 0.006) suggested that all but three players commenced the match euhydrated. Players lost 3.1 ± 0.6 L of sweat and 45 ± 9 mmol of sodium during the 90-min match and replaced 55 ± 19% of their sweat losses and hence by the end of the game were 2.2 ± 0.9% lighter. The water volume consumed during the game was highly variable (1653 ± 487 mL; 741-2387 mL) but there was a stronger relationship between the estimated pre-game hydration status and water volume consumed, than between sweat rate and water volume consumed. In a second match, with the same players 2 weeks later in 34.4 ± 0.6 °C, 65 ± 3% rh, 11 players had a sports drink available to them before and during the match in addition to water. Total drink volume consumed during the match was the same, but approximately half the volume was consumed as sports drink. The results indicate that substantial sweat water and electrolyte losses can occur during match play in hot conditions and a substantial water and sodium deficit can occur in many players even when water or sports drink is freely available.

The effects of exercise, heat, cooling and rehydration strategies on cognitive function in football players.

We investigated the cognitive effects of exercising in the heat on the field players of two football teams in a series of three matches. Different rehydration and cooling strategies were used for one of the teams during the last two games. Cognitive functions were measured before, during and immediately after each football match, as well as core temperature, body mass, plasma osmolality and glucose levels, allowing an estimate of their differential impacts on cognition. The pattern of results suggests that mild-moderate dehydration during exercise in the heat (up to 2.5%) has no clear effect on cognitive function. Instead, plasma glucose and core temperature changes appear to be the main determinants: higher glucose was related to faster and less accurate performance, whereas core temperature rises had the opposite effect. The 50% correlation between plasma glucose and core temperatures observed during exercise in the heat may help to stabilize cognitive performance via their opposing effects. The glucose-like effects of sports drinks appear to be mediated by increased plasma glucose levels, because drinks effects became non-significant when plasma glucose levels were added to the models. The cooling intervention had only a beneficial effect on complex visuo-motor speed.

Effect of hot environmental conditions on physical activity patterns and temperature response of football players.

Heat stress may contribute to decreased match performance when football is played in extreme heat. This study evaluated activity patterns and thermal responses of players during soccer matches played in different environmental conditions. Non-acclimatized soccer players (n=11, 20±2 years) played two matches in conditions of moderate heat (MH) and high heat (HH) index. Core temperature (T(c) ) and physical performance were measured using a telemetric sensor and a global positioning system, respectively. The average ambient temperature and relative humidity were MH 34±1 °C and 38±2%; HH 36±0 °C and 61±1%. Peak T(c) in the MH match was 39.1±0.4 °C and in the HH match it was 39.6±0.3 °C. The total distance covered in the first and second halves was 4386±367 and 4227±292 m for the MH match and 4301±487 and 3761±358 m for the HH match. Players covered more distance (P<0.001) in the first half of the HH match than in the second half. In football matches played at high environmental temperature and humidity, the physical performance of the players may decrease due to high thermal stress.

The effect of L-(+)-lactate on tension development and excitability in in vitro rat diaphragm muscle.

BACKGROUND: The aim of this study was to determine the effect of lactate anion, independent of H+, on in vitro rat diaphragm muscle tension development, and to evaluate the changes in excitability by measuring resting membrane potential (RMP) and the amplitude of the sarcolemma action potential (AP). METHODS: Diaphragm muscle strips taken from 5 Wistar strain albino rats were placed in a tissue bath aerated with 95% O2 and 5% CO2 continuously at 30 degrees C. The muscle was attached to an isometric force transducer and stimulated indirectly by the phrenic nerve (0.2 msec, 0.5 Hz, and supramaximally). Two groups were studied, each subjected to a different sequence of 20 min exposures to a high level of lactate (high [La]), (20 mM) or control periods (C) without lactate. The first group was subjected to (C, high [La], C), and the second was subjected to (high [La], C, high [La]). Following the preparation of high [La] solution, pH was adjusted by adding saturated NaOH. In the second part of this experiment conventional microelectrode technique was used to determine the RMP and amplitude of sarcolemma AP of the rat diaphragm muscle. Thirteen muscles were used and 20-30 measurements were performed in both C and high [La] groups. RESULTS: Addition of lactate reduced the mean tension development significantly (p<0.05) at isopH (pH was 7.34+/-0.001 for C vs 7.33+/-0.001 for high [La]). Mean values of RMP (84.29+/-0.29 mV for C, -84.82+/-0.28 mV for high[La]) and amplitude of sarcolemma AP (118.86+/-0.72 mV for C, 119.19+/-0.71 mV for high[La]) did not differ significantly. CONCLUSIONS: We conclude that lactate reduces tension development at iso-pH without altering the amplitude of sarcolemma AP and RMP.

Contraction duration affects metabolic energy cost and fatigue in skeletal muscle.

It has been suggested that during a skeletal muscle contraction the metabolic energy cost at the onset may be greater than the energy cost related to holding steady-state force. The purpose of the present study was to investigate the effect of contraction duration on the metabolic energy cost and fatigue process in fully perfused contracting muscle in situ. Canine gastrocnemius muscle (n = 6) was isolated, and two contractile periods (3 min of isometric, tetanic contractions with 45-min rest between) were conducted by each muscle in a balanced order design. The two contractile periods had stimulation patterns that resulted in a 1:3 contraction-to-rest ratio, with the difference in the two contractile periods being in the duration of each contraction: short duration 0.25-s stimulation/0.75-s rest vs. long duration 1-s stimulation/3-s rest. These stimulation patterns resulted in the same total time of stimulation, number of stimulation pulses, and total time in contraction for each 3-min period. Muscle O2 uptake, the fall in developed force (fatigue), the O2 cost of developed force, and the estimated total energy cost (ATP utilization) of developed force were significantly greater (P < 0.05) with contractions of short duration. Lactate efflux from the working muscle and muscle lactate concentration were significantly greater with contractions of short duration, such that the calculated energy derived from glycolysis was three times greater in this condition. These results demonstrate that contraction duration can significantly affect both the aerobic and anaerobic metabolic energy cost and fatigue in contracting muscle. In addition, it is likely that the greater rate of fatigue with more rapid contractions was a result of elevated glycolytic production of lactic acid.

Pulmonary hemodynamic response to exercise in subjects with prior high-altitude pulmonary edema.

Individuals with a prior history of (susceptible to high altitude pulmonary edema (HAPE-S) have high resting pulmonary arterial pressures, but little data are available on their vascular response to exercise. We studied the pulmonary vascular response to exercise in seven HAPE-S and nine control subjects at sea level and at 3,810 m altitude. At each location, both normoxic (inspired PO2 = 148 Torr) and hypoxic (inspired PO2 = 91 Torr) studies were conducted. Pulmonary hemodynamic measurements included pulmonary arterial and pulmonary arterial occlusion pressures. A multiple regression analysis demonstrated that the pulmonary arterial pressure reactivity to exercise was significantly greater in the HAPE-S group. This reactivity was not influenced by altitude or oxygenation, implying that the response was intrinsic to the pulmonary circulation. Pulmonary arterial occlusion pressure reactivity to exercise was also greater in the HAPE-S group, increasing with altitude but independent of oxygenation. These findings suggest an augmented flow-dependent pulmonary vasoconstriction and/or a reduced vascular cross-sectional area in HAPE-S subjects.

Exercise-induced VA/Q inequality in subjects with prior high-altitude pulmonary edema.

Ventilation-perfusion (VA/Q) mismatch has been shown to increase during exercise, especially in hypoxia. A possible explanation is subclinical interstitial edema due to high pulmonary capillary pressures. We hypothesized that this may be pathogenetically similar to high-altitude pulmonary edema (HAPE) so that HAPE-susceptible people with higher vascular pressures would develop more exercise-induced VA/Q mismatch. To examine this, seven healthy people with a history of HAPE and nine with similar altitude exposure but no HAPE history (control) were studied at rest and during exercise at 35, 65, and 85% of maximum 1) at sea level and then 2) after 2 days at altitude (3,810 m) breathing both normoxic (inspired Po2 = 148 Torr) and hypoxic (inspired Po2 = 91 Torr) gas at both locations. We measured cardiac output and respiratory and inert gas exchange. In both groups, VA/Q mismatch (assessed by log standard deviation of the perfusion distribution) increased with exercise. At sea level, log standard deviation of the perfusion distribution was slightly higher in the HAPE-susceptible group than in the control group during heavy exercise. At altitude, these differences disappeared. Because a history of HAPE was associated with greater exercise-induced VA/Q mismatch and higher pulmonary capillary pressures, our findings are consistent with the hypothesis that exercise-induced mismatch is due to a temporary extravascular fluid accumulation.

Blood flow distribution in working in situ canine muscle during blood flow reduction.

The purpose of this study was to determine whether reduction in apparent muscle O2 diffusing capacity (Dmo2) calculated during reduced blood flow conditions in maximally working muscle is a reflection of alterations in blood flow distribution. Isolated dog gastrocnemius muscle (n = 6) was stimulated for 3 min to achieve peak O2 uptake (VO2) at two levels of blood flow (controlled by pump perfusion): control (C) conditions at normal perfusion pressure (blood flow = 111 +/- 10 ml.100 g-1.min-1) and reduced blood flow treatment [ischemia (I); 52 +/- 6 ml.100 g-1.min-1]. In addition, maximal vasodilation was achieved by adenosine (A) infusion (10(-2)M) at both levels of blood flow, so that each muscle was subjected randomly to a total of four conditions (C, CA, I, and IA; each separated by 45 min of rest). Muscle blood flow distribution was measured with 15-microns-diameter colored microspheres. A numerical integration technique was used to calculate Dmo2 for each treatment with use of a model that calculates O2 loss along a capillary on the basis of Fick's law of diffusion. Peak VO2 was reduced significantly (P < 0.01) with ischemia and was unchanged by adenosine infusion at either flow rate (10.6 +/- 0.9, 9.7 +/- 1.0, 6.7 +/- 0.2, and 5.9 +/- 0.8 ml.100 g-1.min-1 for C, CA, I, and IA, respectively). Dmo2 was significantly lower by 30-35% (P < 0.01) when flow was reduced (except for CA vs. I; 0.23 +/- 0.03, 0.20 +/- 0.02, 0.16 +/- 0.01, and 0.13 +/- 0.01 ml.100 g-1.min-1.Torr-1 for C, CA, I, and IA, respectively). As expressed by the coefficient of variation (0.45 +/- 0.04, 0.47 +/- 0.04, 0.55 +/- 0.03, and 0.53 +/- 0.04 for C, CA, I, and IA, respectively), blood flow heterogeneity per se was not significantly different among the four conditions when examined by analysis of variance. However, there was a strong negative correlation (r = 0.89, P < 0.05) between Dmo2 and blood flow heterogeneity among the four conditions, suggesting that blood flow redistribution (likely a result of a decrease in the number of perfused capillaries) becomes an increasingly important factor in the determination of Dmo2 as blood flow is diminished.

Effect of gradual reduction in O2 delivery on intracellular homeostasis in contracting skeletal muscle.

This study was designed to investigate 1) whether a protocol employing a gradual reduction in O2 availability to submaximally contracting muscle results in relatively minor disturbances in intracellular homeostasis and 2) the interaction between tissue oxygenation and the proposed regulators of muscle respiration, metabolism, and force production. O2 delivery to isolated submaximally contracting [isometric contractions at 3 Hz; approximately 50% of peak O2 uptake (VO2)] in situ canine gastrocnemius (n = 6) was manipulated by decreasing arterial PO2 (hypoxemia; H) or muscle blood flow (ischemia; I) during three separate periods in each muscle [control (C), H, or I; each separated by 45 min of rest]. O2 delivery was reduced gradually in small steps every 3 min by H or I during two of the contraction periods (6 steps for a total of 21 min; O2 delivery reduced by 67% by the end of 21 min), whereas C was at normal O2 delivery for a 15-min period. Muscle VO2 was maintained at control levels for the first two O2 delivery reduction steps for the H and I conditions and then fell proportionally with O2 delivery to approximately 35% of the initial value by the end of the 21-min contraction period. Muscle force development generally fell in parallel with VO2. There was no significant changes from the values obtained during C contractions in intracellular concentrations of ATP, phosphocreatine, NH3, calculated free ADP, lactate, and redox state ratios as the O2 delivery was reduced, even with the severe decline in VO2 and developed force. These results demonstrated that when O2 availability was reduced gradually to contracting skeletal muscle, 1) developed force (ATP utilization) was reduced through a tight coupling with aerobic ATP supply, such that there was little additional disruption of intracellular homeostasis, and 2) there was an apparent dissociation of some of the proposed regulators of cell respiration and force development from the control of these processes.

Effect of reducing alveolar surface tension on stress failure in pulmonary capillaries.

We previously showed that when pulmonary capillaries are exposed to high transmural pressures, stress failure of the blood-gas barrier occurs. It has been suggested that the surface tension of the alveolar lining layer may protect against stress failure because at high transmural pressures the capillaries bulge into the alveolar spaces. To test this hypothesis, we abolished the gas-liquid surface tension of the alveoli by filling rabbit lungs with normal saline. The lungs were then perfused at capillary transmural pressures of 32.5 or 52.5 cmH2O for 1 min with autologous blood, the blood was washed out with a saline-dextran mixture (3 min), and the lungs were fixed for electron microscopy with buffered glutaraldehyde; all perfusions were done at the same pressure. The frequency of breaks was measured in the capillary endothelial layer, alveolar epithelial layer, and basement membranes, and the data were compared with those in air-filled lungs at the same capillary transmural pressure and lung volume. We found that the frequency of breaks in the endothelium was not significantly different between air and saline filling and that there were fewer breaks in the outer boundary of the epithelial cells. By contrast, after saline filling, a larger number of breaks were seen in the inner boundary of the epithelium. The frequency of disruptions of the inner boundary of the epithelium was closely correlated with the volume of edema fluid collected at the trachea during the perfusion. These breaks in the inner boundary of the epithelium had not previously been seen in air-filled lungs exposed to the same pressures. The results suggest that abolishing the surface tension of the alveolar lining layer removes support from parts of the blood-gas barrier when the capillaries are subjected to a high transmural pressure but that not all portions of the barrier are subjected to the same forces.

Effect of [Hb] on blood flow distribution and O2 transport in maximally working skeletal muscle.

We investigated whether the reduction in calculated muscle diffusion capacity for O2 (DmO2) previously shown to occur with lowered hemoglobin concentration ([Hb]) perfusion of maximally working muscle is related to changes in the blood flow distribution. If blood flow distribution is altered during low [Hb] conditions, the reduction in the calculated DmO2 may in fact be due to increasing heterogeneity and not to some other hemoglobin-related factor. Color-stained (15-microns-diam) microspheres were injected into the artery supplying maximally working isolated in situ dog gastrocnemius muscle (n = 6) while it was being perfused (flow controlled by pump perfusion) with whole blood at three different levels of [Hb] (14.1 +/- 0.5, 8.9 +/- 0.4, and 5.7 +/- 0.4 (SE) g/100 ml] in a blocked-order design. Muscle blood flow and arterial PO2 were not changed as [Hb] was altered. Maximal O2 uptake (11.8 +/- 1.3, 8.2 +/- 0.8, and 6.0 +/- 0.9 ml.100 g-1 min-1 for those [Hb] values, respectively) and the associated estimate of DmO2 (0.25 +/- 0.03, 0.18 +/- 0.03, and 0.15 +/- 0.03 ml.100 g-1.min-1.Torr-1) declined significantly (P < 0.05) with [Hb]. However, the dispersion of the blood flow distribution did not change significantly and, if anything, indicated less heterogeneity at lower [Hb] (coefficient of variation - 0.52 +/- 0.06, 0.46 +/- 0.05, and 0.43 +/- 0.03). These results suggest that in maximally working canine muscle in situ, when O2 delivery is reduced by lowering [Hb] (at constant blood flow), changes in blood flow distribution play no significant role in the reduction of maximal O2 uptake and calculated DmO2. The apparent increase in the resistance to O2 diffusion (i.e., reduction in the DmO2) during anemia may therefore be a result of increased red blood cell spacing in the capillary, slow chemical off-loading kinetics of O2 from Hb, or some other effect that remains to be determined.

Effect of increased duration of high perfusion pressure on stress failure of pulmonary capillaries.

We have previously shown that raising the capillary transmural pressure (Ptm) in rabbit lung causes disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers of the wall. In those studies the lungs were perfused with autologous blood (1 min), then saline/dextran (3 min), followed by glutaraldehyde fixative (10 min), all at the same pressure. The present study was designed to determine whether increasing the time of exposure of the capillaries to the increased pressure altered the frequency of stress failure. The procedure was identical to that of the previous study except that the duration of the blood perfusion was extended from 1 to 10 and 100 min. We chose a Ptm of 32.5 cm H2O because our previous studies showed that this caused only a few disruptions per millimeter endothelial and epithelial boundary length (0.7 +/- 0.4 and 0.9 +/- 0.6 (SE), respectively). Ten New Zealand white rabbit lungs were perfused with autologous blood plus homologous blood from additional rabbits for 10 and 100 min. After 100 min of blood perfusion the number of disruptions per millimeter endothelial and epithelial boundary length (0.66 +/- 0.4 and 0.52 +/- 0.33 (SE), respectively) was not significantly different from the earlier study. Thus, increasing the duration of the increased Ptm during blood perfusion by 100-fold did not alter the incidence of stress failure. These results indicated that any viscoelastic behavior resulting in further strain and ultimately failure of the capillary walls is insignificant over a wide range of exposure times to increased pressure under the conditions of this study.

Determinants of maximal exercise VO2 during single leg knee-extensor exercise in humans.

Previously, a reduction in fractional inspired O2 (FIO2) during dynamic exercise of the human quadriceps muscles of one leg resulted in increased muscle blood flow (Q) and a fall in femoral venous O2 tension (PO2) but no change in peak O2 uptake (VO2). These data can be interpreted as reflecting an increase in muscle O2 diffusive capacity (DO2) in hypoxia or, alternatively, that maximum O2 uptake (VO2max) was not reached for these muscles when air was breathed, in which case the theory of diffusion limitation to VO2max is not applicable to these data. Therefore, the primary goal of this study was to test the hypothesis that VO2max would be reduced in hypoxia as a result of the decreased O2 supply and a constant diffusional conductance from blood to exercising muscle. To resolve this, five trained men were studied performing single leg incremental knee-extensor exercise to VO2max while breathing air (N) and again while breathing 12% O2 (H). The maximum work rate (WRmax) was 30-50 W greater and produced even greater associated maximum leg Q (N = 9.1 +/- 0.61 and H = 8.2 +/- 0.65 l/min, P < 0.05) and leg O2 than in previous studies. Hypoxia reduced quadriceps muscle VO2max (N = 1.4 +/- 0.1 and H = 1.1 +/- 0.1 l/min, P < 0.05). In the two conditions the relationships between 1) measured femoral venous PO2 (N = 18 +/- 0.5 and H = 13 +/- 0.5 Torr) and VO2max and 2) calculated mean capillary PO2 (N = 37 +/- 0.4 and H = 28 +/- 0.8 Torr) and VO2max were each one of proportionality.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathogenesis of high-altitude pulmonary oedema: direct evidence of stress failure of pulmonary capillaries.

The pathogenesis of high-altitude pulmonary oedema (HAPE) is disputed. Recent reports show a strong correlation between the occurrence of HAPE and pulmonary artery pressure, and it is known that the oedema is of the high-permeability type. We have, therefore, proposed that HAPE is caused by ultrastructural damage to pulmonary capillaries as a result of stress failure of their walls. However, no satisfactory electron microscopy studies are available in patients with HAPE, and animal models are difficult to find. Madison strain Sprague-Dawley rats show a brisk pulmonary pressure response to acute hypoxia and are susceptible to HAPE. We exposed 13 Madison rats to a pressure of 294 torr for up to 12.5 h, or 4 rats to 236 torr for up to 8 h. Pulmonary arterial or right ventricular systolic pressures measured with a catheter increased from 30.5 +/- 0.5 (SEM) in controls (n = 4) to 48 +/- 2 torr (n = 11). The lungs were fixed for electron microscopy with intravascular glutaraldehyde. Frothy bloodstained fluid was seen in the trachea of three animals. Ultrastructural examination showed evidence of stress failure of pulmonary capillaries, including disruption of the capillary endothelial layer, or all layers of the wall, swelling of the alveolar epithelial layer, red blood cells (RBCs) and oedematous fluid in the alveolar wall interstitium, proteinaceous fluid and RBCs in the alveolar spaces, and fluid-filled protrusions of the endothelium into the capillary lumen.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased [lactate] in working dog muscle reduces tension development independent of pH.

The purpose of this work was to examine the effect of the lactate ion on the fatigue process in working muscle independent of muscle [H+]. L-(+)-lactate was infused, at a pH that did not change arterial pH, into the blood perfusing an isolated, in situ dog gastrocnemius (N = 5) working at a submaximal intensity (isometric contractions at 2 Hz) and compared with control (C) conditions without lactate infusion. Each muscle was stimulated to work for two 60-min periods (separated by 45 min rest), consisting of three 20-min time periods with either the high arterial lactate condition (high [La]) or C condition sequentially ordered within each 60-min work period. Blood flow and O2 delivery were held constant between the C and high [La] conditions. Arterial and venous blood measurements and muscle biopsies were taken (7 biopsies from each condition) during each condition. Lactate infusion significantly increased arterial [La] (C = 4.2 +/- 0.2 mM vs high [La] = 14.4 +/- 0.2; mean +/- SE) and muscle [La] (C = 8.1 +/- 0.8 mM w.w. vs high [La] = 12.0 +/- 1.4) while arterial and muscle pH were unchanged between conditions. Muscle tension development was significantly reduced (C = 94 +/- 2 N.100 g-1 vs high [La] = 80 +/- 3) during lactate infusion and muscle O2 uptake changed proportionally with tension. These findings support an effect of the lactate anion on tension development which is independent of pH.

Initial fall in skeletal muscle force development during ischemia is related to oxygen availability.

We examined the hypothesis that the initial decline (first 1-2 min) in force development that occurs in working muscle when blood flow is halted is caused by O2 availability and not another factor related to blood flow. This was tested by reducing O2 delivery (muscle blood flow X arterial O2 content) to working muscle by either stopping blood flow [ischemia (I)] or maintaining blood flow with low arterial O2 content [hypoxemia (H)]. If initial decline in force development were similar between these two methods of reducing O2 delivery, it would suggest O2 availability as the common pathway. Isolated dog gastrocnemius muscle was stimulated at approximately 60-70% of maximal O2 uptake (1 isometric tetanic contraction every 2 s) until steady-state conditions of muscle blood flow and developed force were attained (approximately 3 min). Two conditions were then sequentially imposed on the working muscle: I, induced by shutting off pump controlling arterial perfusion of the muscle and clamping venous outflow, and H, induced by perfusing the muscle with deoxygenated blood (collected before testing while animal breathed N2) at steady-state blood flow level. Rates of the fall in force production in 17 matched conditions of H and I (approximately 40 s for each condition) were compared in 6 muscles tested. The blood perfusing the muscle during H had arterial PO2 = 8 +/- 1 (SE) Torr, arterial PCO2 = 37 +/- 1 Torr, and arterial pH = 7.39 +/- 0.03. The rate of decline in developed force was not significantly different (P = 0.46) between the 17 matched conditions of H (0.66 +/- 0.10 g force.g mass-1.s-1) and I (0.79 +/- 0.15 g force.g mass-1.s-1). These findings suggest that the initial fall in developed force in working skeletal muscle that occurs with ischemia is related to O2 availability.