Changes in gastrointestinal cell integrity after marathon running and exercise-associated collapse.

PURPOSE: Endurance exercise and hyperthermia are associated with compromised intestinal permeability and endotoxaemia. The presence of intestinal fatty acid-binding protein (I-FABP) in the systemic circulation suggests intestinal wall damage, but this marker has not previously been used to investigate intestinal integrity after marathon running. METHODS: Twenty-four runners were recruited as controls prior to completing a standard marathon and had sequential I-FABP measurements before and on completion of the marathon, then at four and 24 h later. Eight runners incapacitated with exercise-associated collapse (EAC) with hyperthermia had I-FABP measured at the time of collapse and 1 hour later. RESULTS: I-FABP was increased immediately on completing the marathon (T0; 2593 ± 1373 ng·l-1) compared with baseline (1129 ± 493 ng·l-1; p < 0.01) in the controls, but there was no significant difference between baseline and the levels at four hours (1419 ± 1124 ng·l-1; p = 0.7), or at 24 h (1086 ± 302 ng·l-1; p = 0.5). At T0, EAC cases had a significantly higher I-FABP concentration (15,389 ± 8547 ng.l-1) compared with controls at T0 (p < 0.01), and remained higher at 1 hour after collapse (13,951 ± 10,476 ng.l-1) than the pre-race control baseline (p < 0.05). CONCLUSION: I-FABP is a recently described biomarker whose presence in the circulation is associated with intestinal wall damage. I-FABP levels increase after marathon running and increase further if the endurance exercise is associated with EAC and hyperthermia. After EAC, I-FABP remains high in the circulation for an extended period, suggesting ongoing intestinal wall stress.

Effects of caffeine on endurance capacity and psychological state in young females and males exercising in the heat.

Acute caffeine ingestion is considered effective in improving endurance capacity and psychological state. However, current knowledge is based on the findings of studies that have been conducted on male subjects mainly in temperate environmental conditions, but some physiological and psychological effects of caffeine differ between the sexes. The purpose of this study was to compare the physical performance and psychological effects of caffeine in young women and men exercising in the heat. Thirteen male and 10 female students completed 2 constant-load walks (60% of thermoneutral peak oxygen consumption on a treadmill until volitional exhaustion) in a hot-dry environment (air temperature, 42 °C; relative humidity, 20%) after caffeine (6 mg·kg-1) and placebo (wheat flour) ingestion in a double-blind, randomly assigned, crossover manner. Caffeine, compared with placebo, induced greater increases (p < 0.05) in heart rate (HR) and blood lactate concentrations in both males and females but had no impact on rectal or skin temperatures or on walking time to exhaustion in subjects of either gender. Caffeine decreased (p < 0.05) ratings of perceived exertion and fatigue in males, but not in females. In females, but not in males, a stronger belief that they had been administered caffeine was associated with a shorter time to exhaustion. In conclusion, acute caffeine ingestion increases HR and blood lactate levels during exercise in the heat, but it has no impact on thermoregulation or endurance capacity in either gender. Under exercise-heat stress, caffeine reduces ratings of perceived exertion and fatigue in males but not in females.

Circulatory endotoxin concentration and cytokine profile in response to exertional-heat stress during a multi-stage ultra-marathon competition.

Exertional-heat stress has the potential to disturb intestinal integrity, leading to enhanced permeability of enteric pathogenic micro-organisms and associated clinical manifestations. The study aimed to determine the circulatory endotoxin concentration and cytokine profile of ultra-endurance runners (UER, n=19) and a control group (CON, n=12) during a five stage 230km ultra-marathon (mean ± SD: 27h38min ± 3h55min) conducted in hot and dry environmental conditions (30ºC to 40ºC and 31% to 40% relative humidity). Body mass and tympanic temperature were measured, and venous blood samples were taken before (pre-stage) and immediately after (post-stage) each stage of the ultra-marathon for the analysis of gram-negative bacterial endotoxin, C-reactive protein, cytokine profile (IL-6, IL-1ß, TNF-α, IFN-γ, IL-10, and IL- 1ra), and plasma osmolality. Gastrointestinal symptoms and perceptive thermal tolerance rating were also monitored throughout competition. Mean exercise-induced body mass loss over the five stages ranged 1.0% to 2.5%. Pre- and poststage plasma osmolality in UER ranged277 to 282mOsmol/kg and 286 to 297 mOsmol/kg, respectively. Pre-stage concentrations of endotoxin (peak: 21% at Stage 5), C-reactive protein (889% at Stage 3), IL-6 (152% at Stage 2), IL-1ß (95% at Stage 5), TNF-α (168% at Stage 5), IFN-γ (102% at Stage 5),IL-10 (1271% at Stage 3), and IL-1ra (106% at Stage 5) increased as the ultra-marathon progressed in UER; while no changes in CON were observed (except for IL-1ß, 71% at Stage 5). Pre- to post-stage increases were observed for endotoxin (peak: 22% at Stage 3), C-reactive protein (25% at Stage 1), IL-6 (238% at Stage 1), IL-1ß (64% at Stage 1), TNF-α (101% at Stage 1), IFN-γ (39% at Stage 1), IL-10 (1100% at Stage 1), and IL-1ra(207% at Stage 1) concentrations in UER. Multi-stage ultra-marathon competition in the heat resulted in a modest circulatory endotoxaemia accompanied by a pronounced pro-inflammatory cytokinaemia by post-Stage 1, both of which were sustained throughout competition at rest (pre-stage) and after stage completion. Compensatory anti-inflammatory responses and other external factors (i.e., training status, cooling strategies, heat acclimatization, nutrition and hydration) may have contributed towards limiting the extent of pro-inflammatory responses in the current scenario.

A randomized controlled trial of aspirin and exertional heat stress activation of platelets in firefighters during exertion in thermal protective clothing.

PURPOSE: Platelet aggregation is enhanced in firefighters following short bouts of work in thermal protective clothing (TPC). We sought to determine if aspirin therapy before and/or following exertion in TPC prevents platelet activation. METHODS: In a double-blind, placebo-controlled study, 102 firefighters were randomized to receive daily therapy (81 mg aspirin or placebo) for 14 days before and a single dose (325 mg aspirin or placebo) following exercise in TPC resulting in four potential assignments: aspirin before and after exercise (AA), placebo before and after exercise (PP), aspirin before and placebo after exercise (AP), and placebo before and aspirin after exercise (PA). Platelet closure time (PCT) was measured with a platelet function analyzer before the 2-week treatment, after the 2 week treatment period, immediately after exercise, and 30, 60, and 90 minutes later. RESULTS: Baseline PCT did not differ between groups. PCT changed over time in all four groups (p < 0.001) rising to a median of >300 seconds [IQR 99, 300] in AA and >300 [92, 300] in AP prior to exercise. Following exercise, median PCT decreased to in all groups. Median PCT returned to >300 seconds 30 minutes later in AA and AP and rose to 300 seconds in PA 60 minutes after exercise. CONCLUSIONS: Daily aspirin therapy blunts platelet activation during exertional heat stress and single-dose aspirin therapy following exertional heat stress reduces platelet activation within 60 minutes.

Alteration in circulating metabolites during and after heat stress in the conscious rat: potential biomarkers of exposure and organ-specific injury.

BACKGROUND: Heat illness is a debilitating and potentially life-threatening condition. Limited data are available to identify individuals with heat illness at greatest risk for organ damage. We recently described the transcriptomic and proteomic responses to heat injury and recovery in multiple organs in an in vivo model of conscious rats heated to a maximum core temperature of 41.8°C (Tc,Max). In this study, we examined changes in plasma metabolic networks at Tc,Max, 24, or 48 hours after the heat stress stimulus. RESULTS: Circulating metabolites were identified by gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry. Bioinformatics analysis of the metabolomic data corroborated proteomics and transcriptomics data in the tissue at the pathway level, supporting modulations in metabolic networks including cell death or catabolism (pyrimidine and purine degradation, acetylation, sulfation, redox alterations and glutathione metabolism, and the urea cycle/creatinine metabolism), energetics (stasis in glycolysis and tricarboxylic acid cycle, ß-oxidation), cholesterol and nitric oxide metabolism, and bile acids. Hierarchical clustering identified 15 biochemicals that differentiated animals with histopathological evidence of cardiac injury at 48 hours from uninjured animals. The metabolic networks perturbed in the plasma corroborated the tissue proteomics and transcriptomics pathway data, supporting a model of irreversible cell death and decrements in energetics as key indicators of cardiac damage in response to heat stress. CONCLUSIONS: Integrating plasma metabolomics with tissue proteomics and transcriptomics supports a diagnostic approach to assessing individual susceptibility to organ injury and predicting recovery after heat stress.

Sickle cell trait.

Sickle cell trait can pose a grave risk for some athletes. In the past few years, exertional sickling has killed nine athletes, including five college football players in training. Exercise-physiology research shows how and why sickle red cells can accumulate in the bloodstream during intense exercise bouts. Sickle cells can "logjam" blood vessels and lead to collapse from ischemic rhabdomyolysis. Diverse clinical and metabolic problems from explosive rhabdomyolysis can threaten life. Sickling can begin in 2-3 minutes of any all-out exertion, or during sustained intense exertion--and can reach grave levels very soon thereafter if the athlete struggles on or is urged on by coaches despite warning signs. Heat, dehydration, altitude, and asthma can increase the risk for and worsen sickling. This exertional sickling syndrome, however, is unique and in the field can be distinguished from heat illnesses. Sickling collapse is a medical emergency. Fortunately, screening and precautions can prevent sickling collapse and enable sickle-trait athletes to thrive in their sports.

Acute BDNF and cortisol response to low intensity exercise and following ramp incremental exercise to exhaustion in humans.

The effect of short-term aerobic exercise and a following ramp incremental cycle ergometry to exhaustion on the acute response of the serum concentrations of brain derived neurotrophic factor (BDNF) and cortisol (COR) was examined in 8 healthy male athletes. Venous and capillary blood samples were drawn at rest, immediately after a 10 min warm-up period with aerobic exercise and after a ramp test to exhaustion, as well as 3, 6, 10 and 15 min post exercise. Capillary blood lactate (LA) concentration and blood gases as well as serum BDNF and COR concentrations did not change during the warm-up period. LA was increased (p<0.05) at the end of the ramp test and during recovery period while bicarbonate concentration, carbon dioxide pressure, pH and base excess were decreased (p<0.05) during this period. Serum BDNF was increased at the point of exhaustion (p<0.05) while no significant differences were found between values at rest and those during recovery period. At 10 and 15 min post incremental exercise, COR concentrations were increased (p<0.05) compared to rest. The present study is the first to demonstrate in humans that in contrast to short duration aerobic exercise immediately after a following short duration high-intensity exercise to exhaustion, there is a transient augmentation of serum BDNF concentration. Short-term response of serum BDNF and COR concentrations differs as BDNF returns to baseline level faster than COR.

Distribution and mitogen response of peripheral blood lymphocytes after exertional heat injury.

To determine whether immune disturbances during exertional heat injury (EHI) could be distinguished from those due to exercise (E), peripheral lymphocyte subset distributions and phytohemagglutinin-stimulated CD69 mitogen responses as discriminated by flow cytometry were studied in military recruits [18.7 +/- 0.3 (SE) yr old] training in warm weather. An E group (3 men and 3 women) ran 1.75-2 miles. During similar E, 11 recruits (10 men and 1 woman) presented with suspected EHI. EHI (40.4 +/- 0.3 degrees C) vs. E (38.6 +/- 0.2 degrees C) body temperature was significantly elevated (P < 0.05). Heat illness was largely classified as EHI, not heatstroke, because central nervous system manifestations were generally mild. Blood was collected at E completion or EHI onset (0 h) and 2 and 24 h later. At 0 h (EHI vs. E), suppressor, natural killer, and total lymphocyte counts were significantly elevated, helper and B lymphocyte counts remained similar, and the helper-to-suppressor ratio was significantly depressed. By 2 h, immune cell dynamics between groups were similar. From 0 to 24 h, T lymphocyte subsets revealed significantly reduced phytohemagglutinin responses (percent CD69 and mean CD69 fluorescent intensity) in EHI vs. E. Thus immune cell dynamics with EHI were distinguishable from E. Because heat stress as reported in exercise or heatstroke is associated with similar immune cell disturbances, these findings in EHI contributed to the suggestion that heat stress of varying severity shares a common pathophysiological process influencing the immune system.

Plasma testosterone and cortisol responses to training-intensity exercise in mild and hot environments.

Seven endurance-trained and heat-nonacclimated men (Mean+/-SEM: 20+/-1 yr; VO2max = 67+/-2 ml x kg(-1) x min(-1)) ran in two environments (M: 23 degrees C, H: 38 degrees C; 7 days apart) at two absolute training-intensity velocities (S1: 240 m x min(-1); followed by S2: 270 m x min(-1); 10 min each) during the winter months. Blood samples were taken via cannula before (pre) S1 and after S1 and S2. Plasma testosterone (TEST) concentrations increased (p<0.05) above pre levels after S1 in M (19+/-3 versus 24+/-3 nmol x L(-1)) and H (18+/-2 versus 23+/-3 nmol x L(-1)), and after S2 in H (18+/-2 versus 24+/-1 nmol x L(-1)). Plasma cortisol (CORT) and the molar ratio of TEST/CORT were unchanged from pre levels after S1 and S2 during M and H. No differences were found in plasma TEST, CORT, or the molar ratio of TEST/CORT between M and H. These results indicated that circulating levels of TEST and CORT were not changed in endurance-trained, heat-nonacclimated athletes in response to short-duration running performed at the same absolute intensity in the heat, compared to mild environmental conditions. The lack of significant differences in the molar ratio of TEST/CORT, between the 23 degrees C and 38 degrees C trials, suggested that this short-duration exercise challenge performed in the heat was no more of an anabolic or catabolic stimulus for these athletes.

Concentrations of soluble tumor necrosis factor and interleukin-6 receptors in heatstroke and heatstress.

OBJECTIVE: Increased proinflammatory cytokine concentrations have been implicated in the pathogenesis of heatstroke. Soluble cytokine receptors can modulate circulating cytokine activities. We examined the possible role of soluble tumor necrosis factor receptors (sTNFR 60, sTNFR 80) and interleukin-6 receptor (sIL-6R) in heatstroke by determining their concentrations before and after cooling, as well as in heatstressed controls. DESIGN: Prospective controlled study. SETTING: Heatstroke Center, Makkah, Saudi Arabia (1993 pilgrimage). PATIENTS: Twenty-five consecutive heatstroke patients before and after cooling, 14 heatstressed controls (HSC), and 13 normal controls (NC). MEASUREMENTS AND MAIN RESULTS: Concentrations of sTNFR 60, sTNFR 80, and sIL-6R, as well as their ligands, were measured using commercially available enzyme-linked immunosorbent assay kits. Mean sTNFR 60 concentration was increased in heatstroke (p <.0001, vs. NC; p < .0001, vs. HSC) and in HSC (p = .004, vs. NC). Mean sTNFR 80 concentration was increased in heatstroke and decreased in HSC (p = .01, heatstroke vs. HSC). Mean sIL-6R concentration was decreased in heatstroke and increased in HSC (p = .04, heatstroke vs. NC; p = .001, heatstroke vs. HSC). IL-6 was undetectable in NC and mean IL-6 concentration was more increased in heatstroke than in HSC (p = .001). Rectal temperature and creatinine concentrations correlated significantly with sTNFR 60, sTNFR 80, sIL-6R, and IL-6 concentrations. After cooling, mean concentrations of sIL-6R and sTNFR 80 increased significantly, whereas the mean sTNFR 60 concentration did not change. Residual neurologic deficits were associated with higher precooling IL-6 (p = .002) and postcooling sTNFRs (p < .0001) concentrations. CONCLUSIONS: Significant changes in cytokine receptor concentrations are associated with heatstress. In heatstroke, the changes are more pronounced, and for some cytokine receptors, the changes are in the opposite direction (compared with changes in heatstress). Concentrations of IL-6 and sTNFRs correlate with hyperthermia and outcome. Cooling did not normalize sTNFR concentrations, suggesting failure to control the inflammatory response.

Exercise-associated collapse in cyclists is unrelated to endotoxemia.

Endotoxemia occurs when intestinal ischemia allows bacterial lipopolysaccharide to translocate from colonic flora into the bloodstream, which triggers release of cytokines that can cause hypotension, rigors, fever, shock, and even death. Recently, blood endotoxin levels were shown to be higher in athletes needing medical attention (330 pg.ml-1) than in their competitors with similar performances (81 pg.ml-1). Though there were no data showing that these athletes had elevated core temperatures or severe illness, speculation followed that endotoxin may play a causal role in heat stroke. We examined the relationship between endotoxemia and mild post-exertional illness in 39 cyclists after a 100-mile ride. Thirteen cyclists had at least one of the following: orthostatic hypotension, rigors, nausea, vomiting, diarrhea, or syncope. Only 2/26 case-controls had any of these symptoms. Data were collected on vital signs, hemoglobin, sodium, creatine kinase, creatinine, and uric acid. Endotoxin titer was determined by chromogenic assay; tumor necrosis factor alpha (TNF-alpha) titer was determined by ELISA. One ill cyclist had an endotoxin level of 330 pg.ml-1, one control had an endotoxin level of 150 pg.ml-1, but endotoxin level was < or = 64 pg.ml-1 in all others. Comparison of pre- and post-ride data showed that controls increased creatine kinase activity (154 +/- 34 vs 561 +/- 191 IU.dl, P < 0.05), creatinine concentration (1.5 +/- 0.0 vs 1.6 +/- 0.0 mg.dl-1, P < 0.05), and uric acid concentration (5.4 +/- 0.3 vs 6.3 +/- 0.3 mg.dl-1, P < 0.05). Ill cyclists had lower serum sodium than post-ride controls (138 +/- 2 vs 142 +/- 0.6 mEq.l-1, P < 0.05), but there were no differences between groups in CK, creatinine, or uric acid. These findings suggest that endotoxemia may complicate, but does not cause mild post-exertional illness in cyclists.

The coagulopathy of heat stroke: alterations in coagulation and fibrinolysis in heat stroke patients during the pilgrimage (Haj) to Makkah.

Haemostatic measurements were undertaken in 132 patients diagnosed with heat stroke during the pilgrimage to Makkah, in two successive summers of 1989-90. The control group comprised 49 patients, all pilgrims, with a wide range of clinical conditions, but without hyperpyrexia or deranged haemostasis. Heat stroke patients showed (i) significant prolongation of the prothrombin (PT), activated partial thromboplastin (aPTT) and thrombin times (TT) but normal reptilase time (RT); (ii) significant reduction in plasma levels of antithrombin III (AT-III), factor V, proteins C and S, plasminogen activator inhibitor (PAI) and platelet count; (iii) increase in plasma factor VIII, tissue plasminogen activator (t-PA) and serum FDP; (iv) no significant changes in plasma fibrinogen, plasminogen, alpha 2-antiplasmin and factors VII and X. Heat stroke patients were then grouped into those with and those without bleeding symptoms. Bleeders showed greater prolongation of the PT, aPTT and TT and significant reductions in fibrinogen, AT-III, factors V, VIII and X, plasminogen, alpha 2-antiplasmin and platelet count. Logistic regression and discriminant analysis showed that AT-III was the parameter associated most with heat stroke and reliable enough to predict its occurrence, whether or not bleeding occurred. The results indicate that activation of the haemostatic mechanism, consumptive in nature, regularly accompanies heat stroke and highlights the physiological role of AT-III in checking this activation process.

Interleukin-1 beta production during the onset of heat stroke in rabbits.

During the onset of heat stroke, rabbits displayed hyperthermia (42.8 degrees C), decreased arterial blood pressure, increased intracranial pressure, decreased cerebral perfusion pressure and increased interleukin-1 beta production (in both the hypothalamus and plasma), compared to those of normothermic, control rabbits. In addition, the heat-stroke animals which received an i.v. injection of interleukin 1-receptor antagonist (200 micrograms/kg) had a survival time (interval between onset of heat stroke and death) longer than that of the heat-stroke animals which received control-vehicle solution. The data indicate that interleukin-1 production plays a role in pathogenesis of heat stroke in rabbits.

Elevated pyrogenic cytokines in heatstroke.

STUDY OBJECTIVES: Heatstroke, characterized by hyperthermia and neurologic abnormalities, can cause shock, adult respiratory distress syndrome, and multiorgan failure culminating in death. The mediation of metabolic changes and tissue damage is not fully understood. Recent evidence suggests the involvement of endotoxin, tumor necrosis factor alpha (TNF-alpha), and interleukin 1 alpha (IL-1 alpha) and we hypothesized that other pyrogenic cytokines may be implicated. DESIGN: Prospective analysis. SETTING: Heatstroke Center in Makkah (Mecca), Saudi Arabia. MEASUREMENTS AND RESULTS: We measured plasma IL-1 beta, IL-6, and interferon gamma (INF-gamma) concentrations by enzyme-linked immunosorbent assay in 28 heatstroke patients at the time of hospital admission (precooling) and after complete cooling (postcooling), and in 10 normal control subjects. We measured C-reactive protein (CRP) as a marker of acute phase response and calculated severity of illness using the simplified acute physiology score. Twenty-five male and 3 female subjects had mean (+/- SEM) rectal temperature of 41.2 +/- 0.2 degrees C. IL-6, IL-1 beta, and INF-gamma concentrations were elevated in 100 percent, 39 percent, and 50 percent of patients to (mean +/- SEM) 220 +/- 44 pg/ml, 42 +/- 14 pg/ml, and 1,180 +/- 879 pg/ml, respectively (normal control values: < 3.5 pg/ml, < 4.5 pg/ml, < 20 pg/ml). The CRP value was elevated in 72 percent of patients to 152 +/- 40 mg/L (control value: 0 to 17 mg/L). The IL-6 concentrations correlated with severity of illness (r = 0.516, p = 0.03); two patients with the highest concentrations died. There was no significant correlation between circulating levels of IL-6, IL-1 beta, INF-gamma, and temperature, or between IL-6, IL-1 beta, and CRP. Postcooling, IL-6, and IL-1 beta were still above normal control values; INF-gamma could be detected in one patient only. CONCLUSION: Our findings of elevated circulating IL-6, IL-1 beta, and INF-gamma in the presence of acute phase response, and correlation with severity of illness, suggest that these cytokines have a role in the pathogenesis of heatstroke, which could lead to new therapeutic strategies.

Electrocardiographic abnormalities in patients with heat stroke.

Serial electrocardiograms were taken in 46 Hajj Pilgrims suffering from heat stroke immediately after cooling 12 and 24 h later. The collected data were analyzed and revealed that a statistically significant number of patients with heat stroke had sinus tachycardia (43 percent, p < 0.05), conduction defect (22 percent, p < 0.046), prolonged Q-T interval (61 percent, p < 0.007), diffuse nonspecific ST-T changes (26 percent, p < 0.036), and ST-T changes (localized to the ECG leads confirming to a territory of coronary artery) consistent with myocardial ischemia (21 percent, p < 0.02). Although adverse effects of heat stroke on the heart are multifactorial, the above data indicate that heat stroke predisposes to certain risk of myocardial ischemia and conduction disturbances. This may reflect the true cardiovascular status of these heat stroke victims.

Alteration of taurine homeostasis in acute heatstroke.

OBJECTIVE: To investigate the potential role of taurine as a hypothermic modulator during heatstroke. DESIGN: Prospective analyses. SETTING: Heatstroke Center in makkah, Saudi Arabia. PATIENTS: Twenty-nine adult patients with heatstroke. INTERVENTIONS: High-performance liquid chromatography was used to measure plasma and urine taurine concentrations in heatstroke patients on admission (precooling) and 24 hrs after complete cooling (postcooling). MEASUREMENTS AND MAIN RESULTS: There were 18 males and 11 females with a mean rectal temperature of 42.2 +/- 0.14 degrees C. At the precooling time period, the taurine concentrations were increased (plasma 180 +/- 14 mumol/L; urine 4142 +/- 720 mumol/L [normal ranges 45.5 to 138.2 and 168 to 1890 mumol/L, respectively]). At the postcooling time period, taurine concentrations were significantly (p < .0001) decreased (54 +/- 6 and 802 +/- 160 mumol/L for plasma and urine, respectively). No correlation was found between taurine and creatine kinase activity, or between precooling temperature and taurinemia or taurinuria. CONCLUSIONS: The source and clinical significance of the increased taurine concentrations are to be determined. The involvement of taurine in the regulation of core body temperature suggests that it may have an adaptive role in heatstroke.

Invasive evaluation of patients with heat stroke.

Right-heart catheterization was performed in ten patients who suffered heat stroke on their pilgrimage to Mecca, Saudi Arabia. The group included seven men and three women who had mean rectal temperatures of 42.4 degrees C. Other findings included the following: heart rate (mean, 120 beats/min); cardiac output (mean, 8.2 ml/min/m2); arterial pressure (mean, 65 mm Hg); cardiac indices (mean, 4.4 ml/min/m2); right atrial pressure (mean, 6 mm Hg); pulmonary capillary wedge pressure (mean, 10 mm Hg); systemic vascular resistance (mean, 684 dyne.s.cm-5); pulmonary vascular resistance (mean, 86 dyne.s.cm-5); oxygen delivery (mean 837 ml/min/m2); oxygen consumption (mean 160 ml/min/m2); mixed venous oxygen tension (mean, 56 mm Hg); and shunt fraction (mean, 20 percent). Nine patients survived. One, who had a cardiopulmonary arrest before any treatment could be administered, died.