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Effects of three curvilinear inspiratory resistances (R1, R2, R3) on the cardiorespiratory responses of seven well-trained men during incremental cycling tests to exhaustion were studied by comparison to the low resistance R0 (at 1 l/s, R0 = 0.2; R3 = 6.5 cmH2O-s/l). Submaximal VO2 and the gas exchange anaerobic threshold (AT) were not affected by increasing resistance. Although maximal work rates were not significantly changed, highly significant reductions were observed for VE (R0 = 166.3; R3 = 99.7 l/min BTPS), VO2 max (R0 = 4,26; R3 = 3.74 l/min), HR (R0 = 185; R3 = 176 beats/min), and endurance (R0 = 17.3; R3 = 15.5 min) suggesting that aerobic work tolerance was dependent on ventilatory capacity. In additional tests removal of R3 at exhaustion abruptly increased VE and VO2, and permitted work to continue. Ventilation and work tolerance were therefore limited by R3 before the legs fatigued. Breathing 35% O2 against R3 produced significant, although small, increases in AT, VO2 max, peak HR, and endurance while decreasing the hyperventilatory response to work above AT. Thus, aerobic work tolerance reduced with high inspiratory resistance was partly restored by moderate hyperoxia, apparently because the ventilatory limit was delayed.

In brief Sports nutritionists generally think an athlete's increased mineral requirements can be satisfied by a greater but well-balanced caloric intake. This study supports that concept, demonstrating that 12 male runners who consumed an unrestricted, isocaloric diet maintained normal plasma mineral levels without using mineral supplements during a 500-km (312-mile) road race. None of the nine minerals tested (calcium, phosphorus, sodium, potassium, chloride, magnesium, iron, copper, and zinc) showed tendencies to become persistently reduced over the 20-day period.

The influence of early graft surface thromboreactivity on long-term arterial polyester (Dacron) graft patency was investigated with separate ex vivo and in vivo animal models. First, parallel, flow-regulated external aortocaval fistulae were created in five pigs with use of paired 8 mm X 35 cm crimped, warp-knitted, low-profile filamentous velour Dacron tubes: one tube preclotted with autologous blood, the other autoclaved after being soaked in human albumin. Autologous radiolabeled platelets, red cells, and radiolabeled human fibrinogen were injected at initiation of graft flow, with timed graft samples submitted for isotope gamma well-counting. Flow surface accumulation of radiolabeled blood elements was greater on the preclotted graft limb at-all time intervals studied, greatest after 5 minutes of flow initiation with RBC accumulation on the preclotted limb 5.19 +/- 0.84 (x +/- S.E.), platelet accumulation 5.57 +/- 1.00, and fibrinogen accumulation 1.82 +/- 0.14 times greater than that on the albumin-treated limb. Second, bilateral iliofemoral artery bypass grafts were placed in 12 mongrel dogs using 6 mm X 10 cm externally supported, noncrimped, warp-knitted, low-profile filamentous Dacron tubes. Before implant in each dog, one graft limb was clotted with autologous blood and the other was autoclaved after being soaked in 25% human albumin. Fresh autologous radiolabeled platelets were injected after wound closure in seven of these dogs. Postimplant graft imaging at 24 and 72 hours showed radiolabeled platelet accumulation to be 1.43 +/- 0.21 and 2.05 +/- 0.18 times greater on the preclotted graft limb. Six of 12 preclotted graft limbs and 7 of 12 albumin-treated graft limbs were patent when animals were killed 5 to 6 months after implant (not significant). Heat-denatured albumin-coated Dacron surfaces have a reduced early thromboreactivity but do not appear to greatly potentiate long-term arterial graft patency.

The effect of the opioid antagonist naloxone on drinking and the subsequent suppression of plasma vasopressin were evaluated in seven dogs following 24 hr of water deprivation. Each animal underwent an intravenous injection of vehicle as a control and a low (0.05 mg/kg) and high (1 mg/kg) dose of naloxone. Plasma vasopressin was significantly (p less than 0.05) increased from a control value of 4.6 +/- 1.9 microU/ml to 9.9 +/- 3.1 microU/ml after the high dose of naloxone. Fluid intake was not altered by naloxone; 42 +/- 6 ml/kg for the control, 45 +/- 8 ml/kg at the low dose, and 49 +/- 7 ml/kg for the high dose. Six minutes after the onset of drinking vasopressin was reduced by 48% for the control, 41% for the low dose and 45% for the high dose, with no significant difference among treatments. Thus, in dehydrated dogs naloxone presumably blocks endogenous opioids, elevates vasopressin following dehydration, but does not affect drinking behavior or the subsequent suppression of vasopressin after drinking.

Arterial blood lactate concentration at the end of fixed volume hemorrhage was evaluated as a predictor of survival in unmedicated chronically instrumented immature swine. Compared to basal values, 8.4 +/- 4.5 mg/dl (means +/- SD, n = 52), hemorrhaged animals (n = 71) with a lactate of 43.9 +/- 37.1 mg/dl lived while animals (n = 65) with a lactate of 106.5 +/- 40.4 mg/dl died. Lactate concentration at the end of hemorrhage successfully predicted survival (81.0%). Prospective evaluation, using a blood lactate concentration of 125 mg/dl (n = 27), showed a predictive success of 81.0%. Arterial plasma lactate concentration at the end of hemorrhage thus may be used to predict survival in the conscious swine.

Urinary excretion rate of antidiuretic hormone (UADHV) was studied in male volunteers in response to hypobaric hypoxia. The first series consisted of three groups. The chamber was decompressed to 465, 495, and 438 Torr during high-altitude (HA) exposure for groups I (n = 5), II (n = 5), and III (n = 4), respectively. In group I, the chamber air contained 3.77% CO2 to prevent alkalosis. The level of hypoxemia was similar in groups I and II. Mean 24-h UADHV was unchanged in group I, but increased 96% (P less than 0.05) and 180% (P less than 0.05) in groups II and III, respectively, on day 1 at HA and was normal during subsequent days at HA regardless of symptoms of acute mountain sickness. Shorter sampling intervals employed in a second series of experiments conducted at 495 Torr revealed a twofold increase in UADHV (P less than 0.05) 8-12 h after ascent in eight asymptomatic subjects; UADHV returned to base line within 9 h and remained low. The symptomatic subjects both had increased UADHV (3- and 8-fold from base line) between 2 and 4 h after ascent. Increased UADHV in asymptomatic subjects may be a result of the concomitant decrease in plasma volume, both of which appeared to be eliminated by CO2 supplementation.

Dextran metabolism was investigated in ten hemorrhaged and seven euvolemic conscious swine. Chronically instrumented, splenectomized swine were subjected to a progressive fixed-volume hemorrhage (27 ml/kg over 45 min). Resuscitation with 4 ml/kg of a 7.5% NaCl/6% dextran 70 (HSD) solution was begun 5 min later. Blood and urine samples were drawn before and during hemorrhage, and at 15, 60, and 120 min following intravenous HSD infusion. Hemorrhage significantly reduced cardiac output (CO) and mean arterial pressure (MAP) and eliminated urinary flow. HSD administration to hemorrhaged pigs returned CO and MAP to control values and improved urinary flow. Creatinine clearance returned to prehemorrhage values. These parameters were not affected by HSD in nonhemorrhaged animals. Plasma dextran concentrations were 20-30% higher in hemorrhaged pigs compared with euvolemic swine. In additional studies, plasma t1/2 for dextran was 9.4 hr in hemorrhaged pigs (n = 3) compared to 10.8 hr in euvolemic animals (n = 2). These data show that HSD ameliorates the effects of hemorrhage on cardiovascular and renal function and suggest that plasma clearance of dextran may be affected by hemorrhage.

The role of angiotensin II in the hormonal and renal responses to maximal exercise was investigated by using the angiotensin-converting enzyme inhibitor captopril. Nine male subjects performed a standardized maximal treadmill test with and without acute captopril treatment (25 mg orally). At rest, captopril elevated plasma renin activity and lowered aldosterone levels. With maximal exercise, captopril treatment reduced the increase in mean arterial blood pressure by 8 mmHg and the increase in plasma renin activity by 3.0 ng ANG I.ml-1.h-1. The responses of adrenocorticotropin (ACTH), cortisol, and vasopressin to maximal exercise were not altered by captopril treatment. Although aldosterone levels were reduced at rest with captopril, during maximal exercise no difference was noted between treatments. Captopril treatment had no effects on the renal handling of salts or water during exercise. In conclusion, angiotensin II plays a role in the increase in mean blood pressure during maximal exercise in normal subjects but has no effect on the exercise responses of ACTH, vasopressin, and aldosterone or on the renal handling of salts and water.

To assess the role of endogenous opioids in the secretion of pituitary and adrenal hormones, we injected intravenously the antagonist naloxone (1 mg/kg) into six dogs, euhydrated or dehydrated. Plasma renin activity (PRA), osmolality, and concentrations of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, vasopressin, Na+, and K+ were measured. Dehydration elevated (P less than 0.05) PRA, vasopressin, osmolality, and Na+. Thirty minutes after injection of naloxone, osmolality, Na+, K+, hematocrit, and plasma protein were not altered. Naloxone-induced elevations of ACTH (25 +/- 10 and 22 +/- 4 pg/ml) and cortisol (4.8 +/- 1.0 and 5.1 +/- 1.0 micrograms/dl) were similar during euhydration and dehydration, respectively. The increase in aldosterone due to naloxone was greater after euhydration (7.7 +/- 3 ng/dl) than during dehydration (2.3 +/- 0.8 ng/dl). Naloxone increased vasopressin by (5.3 +/- 2.8 microU/ml) during dehydration but not during euhydration. Intravenous hypertonic saline infusions showed that naloxone potentiates the osmotic release of vasopressin. Our results indicated that dehydration did not alter the inhibitory role of opioids in regulation of ACTH and cortisol but suppressed the inhibition of aldosterone secretion. Our findings also showed that opioids inhibit secretion of vasopressin during dehydration by decreased responsiveness to osmotic stimulation.

To evaluate the effects that repeated long-distance running has on plasma aldosterone concentration and urinary excretion of solutes, fifteen male runners were studied during a 20-day, 500-km road race. Venous blood samples were taken on day 1 prior to running, on day 11 after 10 days of running, on day 13 after a 70-h rest, and on day 18 after an additional five days of running. Overnight urine samples were obtained on day 10 before and after running and on days 11, 12, and 13 during the 70-h rest period. Plasma sodium concentrations on days 13 and 18 and plasma potassium concentrations on days 11 and 13 were decreased (P less than 0.05). Plasma aldosterone levels were increased on days 11 and 18 after running and returned to pre-race levels on day 13 after 70 h of rest. Plasma cortisol concentrations were not altered. The urinary excretion rates of sodium were elevated and of aldosterone were decreased after 70 h of rest. Increase in excretion rate of urinary sodium correlated with decrease in concentration of plasma aldosterone. These findings show that plasma aldosterone levels are chronically elevated with repeated long-distance running, resulting in a decrease in urinary excretion rate of sodium.

This study examined the plasma aldosterone and corticosteroid responses to a 60-min infusion of adrenocorticotropin (ACTH) or angiotensin (ANG) II started immediately after an acute isotonic saline volume expansion (0.5 ml . kg-1 . min-1 for 30 min). Five conscious dogs of either sex with exteriorized carotid loops were used in this repeated-design study. Volume expansion per se caused a 10% decrease in hematocrit, a 12.5% decrease in plasma protein, and a 2.7-mmHg increase in central venous pressure with no change in mean arterial pressure, heart rate, or plasma sodium. Volume expansion per se also resulted in significant reductions in vasopressin, plasma renin activity, ACTH, aldosterone, and corticosteroid levels. The aldosterone responses to ACTH and ANG II were significantly inhibited (46-71%) by acute volume expansion. The corticosteroid response to ACTH was 19-29% inhibited by volume expansion. We conclude that acute volume expansion significantly inhibits the adrenocortical sensitivity to its tropic hormones probably via alterations of synergistic factors.

Plasma concentrations of vasopressin (antidiuretic hormone), a powerful pressor agent and primary regulator of body fluid homeostasis, are elevated in a dose-related fashion to increases in exercise intensity. The response of plasma vasopressin levels to exercise is not modified by gender, but is reduced with training at absolute submaximal exercise intensities. However, the duration of the exercise and hydration status of the subject alters the observed increase. The increase in plasma vasopressin concentrations during exercise may be mediated by a variety of factors: plasma osmolality, blood pressure, blood volume, plasma concentrations of angiotensin II, psychological variables, and peripheral nerve stimulation. Furthermore, decreases in the metabolism of vasopressin, due to alterations in renal and hepatic blood flow during exercise, may contribute to the increase in plasma concentrations. Although plasma vasopressin concentrations are elevated during exercise, there is no definitive effect during exercise, as the excretion rate of free water is increased, sweat rate and composition are not changed, and a role in plasma volume regulation is dubious. Thus, the function of the elevation in plasma vasopressin levels during exercise is unclear at the present time.

The presence of pericardial adhesions may increase morbidity and mortality during reoperation for cardiac disease. Pericardial substitutes (patches) are commercially available, and reportedly they reduce or prevent adhesions. We implanted five (1984 to 1985) newer pericardial substitutes in dogs. A new polytetrafluoroethylene surgical membrane, two types of glutaraldehyde-stabilized bovine pericardium, formaldehyde-preserved bovine pericardium, and glutaraldehyde-stabilized equine pericardial patches were each implanted in six adult dogs (total 30 dogs) with two dogs from each of the five groups killed at 3, 9, and 18 months. At autopsy the condition of each patch was recorded photographically, and specimens were substituted for histologic examination. Adhesions and epicardial reactions were graded as none, minimal, moderate, or severe. None of the materials produced severe pericardial adhesions, and no adhesions were detected in nine dogs. Eleven dogs had no epicardial reaction and only one showed a severe reaction. Adhesions to portions of the suture line required sharp dissection in 11 dogs. If there is concern over the possibility of calcification in heterologous tissue, polytetrafluoroethylene may be chosen. Patch type did not significantly alter patch behavior.

Renal and endocrine responses were studied in 10 male runners during a 20-day 500-km race. Overnight urine and prerun blood samples were taken prior to running on days 1, 2, 5, 8, 14, 17, and 20. Day 13 followed 70 h of rest. Urine flow rate, osmotic clearance, tubular free water reabsorption, urinary vasopressin excretion rate, and body weight were not significantly changed. Creatinine clearance was constant except for an elevation on day 5. Plasma osmolality was elevated on days 2, 14, and 17. Plasma sodium was increased (P less than 0.05) on days 2 and 13 but reduced on day 20. The percentage of filtered sodium excreted was significantly reduced on all nights following running and elevated on recovery day 13. Urinary aldosterone excretion rate was significantly elevated 162, 117, and 97% on days 5, 8, and 20 and returned to control levels on day 13 after 70 h of rest. These data suggest that in response to repeated long-distance running normal fluid balance is regained within 12 h. However, it is necessary to conserve sodium for at least 24 h after exercise as evidenced by the decrease in the percent filtered sodium excreted and continued elevation of aldosterone excretion.

The chronic toxicity and oncogenic potential of ingested vinylidene chloride (VDC) was evaluated in a 2-year study on Sprague-Dawley rats and the subchronic toxicity was evaluated in beagle dogs in a 97-day study. The vinylidene chloride was incorporated in the drinking water of the rats at nominal concentrations of 50, 100 or 200 ppm. The time weighted average mg/kg body weight/day dosages of vinylidene chloride administered to the male and female rats over the 2-year period at the various mean analyzed concentrations were 7, 10 or 20 for the males and 9, 14 or 30 for the females. Dogs were administered vinylidene chloride in peanut oil incorporated in a gelatin capsule at concentrations which provided 6.25, 12.5 or 25 mg vinylidene chloride/kg body weight/day. There were no significant differences between the groups of rats or dogs ingesting vinylidene chloride and their corresponding control groups in the following parameters: appearance and demeanor, mortality, body weight, food consumption, hematology, urinalysis, clinical chemistry determinations, organ weights and organ to body weight ratios. There were no significant differences in water consumption of the groups of rats ingesting vinylidene chloride and the controls. The sole treatment-related observation in the rats, evident only upon microscopic examination, was in the liver. The observation was characterized by a minimal amount of hepatocellular swelling with midzonal fatty change which occurred in the females at all dose levels and in the males only at the 200 ppm level. No exposure-related neoplastic changes occurred in the rats in any of the test groups. No exposure-related gross or histopathological changes were present in the tissues taken from the dogs at the termination of the 97-day study.

Plasma vasopressin concentrations (pAVP) are elevated during dehydration due to alterations in extracellular fluid (ECF) volume and tonicity. The contributions of the reduction in volume and increase in plasma osmolality to the rise in pAVP were assessed in 6 dogs with bilateral carotid loops following 24 h of fluid, but not food, deprivation. Dehydration significantly (p less than 0.05) increased plasma osmolality from 297 +/- 1 to 315 +/- 2 mosm/kg), decreased body weight from 20.8 +/- 1.2 to 20.3 +/- 1.2 kg, and elevated pAVP from 1.4 +/- 0.2 to 5.3 +/- 0.6 pg/ml. The effect of extracellular fluid volume reduction was tested by reexpanding this compartment in dehydrated dogs with 0.15 M NaCl. Plasma vasopressin concentration was significantly reduced by 1.3 +/- 0.2 pg/ml (33 +/- 4%) and plasma osmolality unchanged following volume replacement. The contribution of the increase in plasma osmolality was assessed by bilateral intracarotid infusions of water at 0.6 ml/min/artery which lowered jugular venous plasma osmolality to euhydrated values (296 +/- 4 mosm/kg), but did not significantly reduce systemic plasma osmolality. Plasma vasopressin levels were significantly reduced 3.2 +/- 1.1 pg/ml (70 +/- 5%). Thus, following 24 h of fluid deprivation in dogs, the rise in pAVP is due to changes in both ECF volume and tonicity. The increase in tonicity plays a greater role in the elevation of pAVP, than the reduction in volume.

The purpose was to test the hypothesis that twice daily, short-term, variable intensity isotonic and intermittent high-intensity isokinetic leg exercise would maintain peak O2 uptake (VO2) and muscular strength and endurance, respectively, at or near ambulatory control levels during 30 days of -6 degrees head-down bed rest (BR) deconditioning. Nineteen men (aged 32-42 yr) were divided into no exercise control (peak VO2 once/wk, n = 5), isokinetic (Lido ergometer, n = 7), and isotonic (Quinton ergometer, n = 7) groups. Exercise training was conducted in the supine position for two 30-min periods/day for 5 days/wk. Isotonic training was at 60-90% of peak VO2, and isokinetic training (knee flexion-extension) was at 100 degrees/s. Mean (+/- SE) changes (P less than 0.05) in peak VO2 (ml.m-1.kg-1) from ambulatory control to BR day 28 were 44 +/- 4 to 36 +/- 3, -18.2% (3.27-2.60 l/m) for no exercise, 39 +/- 4 to 40 +/- 3, +2.6% (3.13-3.14 l/min) for isotonic, and 44 +/- 3 to 40 +/- 2, -9.1% (3.24-2.90 l/min) for isokinetic. There were no significant changes in any groups in leg peak torque (right knee flexion or extension), leg mean total work, arm total peak torque, or arm mean total work. Mean energy costs for the isotonic and isokinetic exercise training were 446 kcal/h (18.8 +/- 1.6 ml.min-1.kg-1) and 214 kcal/h (8.9 +/- 0.5 ml.m-1.kg-1), respectively. Thus near-peak, variable intensity, isotonic leg exercise maintains peak VO2 during 30 days of BR, while this peak, intermittent, isokinetic leg exercise protocol does not.

Five male subjects having a wide range of relative body fat, 9.2-20.2%, were studied during total body immersion in water at 25.2 degrees C. The regional surface area of each subject was calculated from anthropometric data utilizing a segmental geometric model. Skin temperatures (Tsk) and regional skin heat loss were measured prior to and during 30 min immersion at 13 sites. During immersion, mean Tsk was 25.9 degrees C and remained significantly higher than the water temperature. A measurable temperature gradient for heat flow was observed from all body segments. Segimental temperature in water ranged from 26.7-25.4 degrees C, being warmest at the neck and coolest at the foot. Heat the flow per regional area was highest in the neck, 187 W/m2, and least at the foot, 12 W/m2. Heat flow from each body region was dependent on regional Tsk. Skinfold thickness was a minor factor in altering regional heat flow in the foot, hand, lower arm, upper arm, thigh, and calf; in the torso, neck, and head regions it was of major importance in detering heat loss.

Groups of male and female Fischer 344 rats were administered acrylamide in their drinking water at 0, 0.05, 0.2, 1, 5, or 20 mg/kg/day for up to 93 days. Following the administration of acrylamide in the drinking water, male rats from each dose level were held for up to 144 days of recovery. The 20 mg/kg/day groups had definite treatment-related effects after 92 (males) and 93 (females) days. They were dragging the rear limbs, body weights were decreased, serum cholinesterase activity was decreased in top dose females, and packed cell volume, red blood cell, and hemoglobin values were slightly decreased in males and females. In the 20 mg/kg/day groups, the primary target tissue was the peripheral nerve with lesions consisting of severe degeneration characterized by demyelinization and axonal loss. Slight spinal cord degeneration was observed. Other effects included atrophy of skeletal muscle, testicular atrophy, and distended urinary bladders; these were probably secondary to the nerve degeneration. After 144 days of recovery, the lesions had partially or completely reversed. Parameters affected at the 5 mg/kg/day dose level after 92 (males) and 93 (females) days consisted of peripheral nerve degeneration which were of a lesser degree of severity than those seen in the 20 mg/kg/day groups and appeared to have completely reversed after 111 days of recovery. In rats given 1 mg/kg/day, a minimal treatment-related effect was observed in males after 92 days, and this was limited to very slight nerve degeneration using electron microscopy (females were not examined by electron microscopy). This observed effect appeared to have reversed after 25 days of recovery. No treatment-related effects were seen in any of the parameters monitored in the rats given 0.05 or 0.2 mg/kg/day of acrylamide.

Blood pressure, pulse rate (PR), serum osmolality and electrolytes, as well as plasma vasopressin (PVP) and plasma renin activity (PRA), were measured in five men and two women [mean age 38.6 +/- 3.9 (SE) yr] before, during, and after inflation of an antigravity suit that covered the legs and abdomen. After 24 h of fluid deprivation the subjects stood quietly for 3 h: the 1st h without inflation, the 2nd with inflation to 60 Torr, and the 3rd without inflation. A similar control noninflation experiment was conducted 10 mo after the inflation experiment using five of the seven subjects except that the suit was not inflated during the 3-h period. Mean arterial pressure increased by 14 +/- 4 (SE) Torr (P less than 0.05) with inflation and decreased by 15 +/- 5 Torr (P less than 0.05) after deflation. Pulse pressure (PP) increased by 7 +/- 2 Torr (P less than 0.05) with inflation and PR decreased by 11 +/- 5 beats/min (P less than 0.05); PP and PR returned to preinflation levels after deflation. Plasma volume decreased by 6.1 +/- 1.5% and 5.3 +/- 1.6% (P less than 0.05) during hours 1 and 3, respectively, and returned to base line during inflation. Inflation decreased PVP from 6.8 +/- 1.1 to 5.6 +/- 1.4 pg/ml (P less than 0.05) and abolished the significant rise in PRA during hour 1. Both PVP and PRA increased significantly after deflation: delta = 18.0 +/- 5.1 pg/ml and 4.34 +/- 1.71 ng angiotensin I X ml-1 X h-1, respectively. Serum osmolality and Na+ and K+ concentrations were unchanged during the 3 h of standing.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial natriuretic factor is reported to be elevated during and immediately following exercise and is thought to play a role in fluid homeostasis and cardiovascular regulation. The predominant stimuli for atrial natriuretic factor release during exercise appear to be increases in atrial pressures or atrial distension, both of which are reported to increase with exercise. The intensity and perhaps duration of exercise also influence the magnitude of the atrial natriuretic factor response. It is not clear if the rise in plasma atrial natriuretic factor during exercise plays any role in altering renal function since high intensity exercise is typically associated with an antidiuresis. However, elevations in plasma atrial natriuretic factor may in part be responsible for the increase in urine flow reported when exercise is performed at low or moderate intensities. Atrial natriuretic factor also has vascular effects which may be important in buffering or moderating the blood pressure response to exercise. The atrial natriuretic factor response to exercise and basal levels of the hormone are greatly elevated in patients who suffer from a variety of cardiovascular and pulmonary disease conditions. These elevated plasma atrial natriuretic factor values are associated with increases in atrial pressure and appear to be related to the severity of disease. Although much controversy exists regarding the renal and vascular effects of atrial natriuretic factor, the measurement of this hormone, particularly during exercise, may be of clinical value by providing an additional tool to evaluate patients and determine the effectiveness of various treatment regimens.

Lifetime ingestion by rats of 0.2 mg/kg/day of hexachlorobutadiene caused no discernible ill effects. Slight degrees of primarily renal toxicity occurred with 2 mg/kg/day; 20 mg/kg/day caused multiple toxic effects, including renal tubular neoplasms.

Efficacy of small-volume resuscitation (4 ml/kg) with 7.5% NaCl in 6% Dextran 70 (HSD), 7.5% NaCl (HS), dextran (D), and 0.9% NaCl (NS) was evaluated in conscious swine bled 37.5 ml/kg over 60 min. Hemorrhage reduced cardiac index (CI), stroke volume (SV), and mean arterial pressure (MAP). Four-hour survival after HSD (67%) was significantly (P less than 0.05) greater than after HS (25%), D (17%), or NS (0%). The superior performance of HSD, and to a lesser extent HS, was associated with rapid plasma volume expansion, improved CI and SV, and decreased heart rate. The acute increases in cardiac index and stroke volume were greater following treatment with HSD and the improvement persisted for 4 hr. HSD also produced a transient increase in MAP. Plasma Na+ concentration and osmolality were increased to a similar extent with HSD and HS, while plasma K+ levels were initially decreased, returning to control levels within 60 min. HSD appears to be a superior small-volume resuscitation solution compared to the other treatments with no detrimental effects.

Adrenal function was studied in 2 groups of intensive care unit (ICU) patients with varying degrees of illness, as determined by Acute Physiological and Chronic Health Evaluation (APACHE). The 15 seriously ill patients with high APACHE scores (greater than or equal to 25) had elevated Therapeutic Intervention Scores and increased mortality compared to the 15 ill patients (APACHE, less than or equal to 10; 67% vs. 27%). Plasma cortisol, aldosterone, and androstenedione concentrations were increased in the ICU patients compared to those in normal subjects (n = 23), being greater in the seriously ill patients. Plasma dehydroepiandrosterone sulfate (DHEAS) concentrations were low in both groups of ICU patients. The ratios of aldosterone or androstenedione to cortisol were not altered, whereas the DHEAS to cortisol ratios were reduced in the ICU patients. ACTH injection elicited increases in plasma cortisol, aldosterone, and androstenedione concentrations in both groups of ICU patients, and the ratios of aldosterone and androstenedione to cortisol did not change. In the seriously ill patients, plasma DHEAS increased, so that the DHEAS to cortisol ratio did not change, whereas in less ill patients plasma DHEAS did not increase, so that the DHEAS to cortisol ratio was reduced. In this study of patients admitted to an ICU, impairment of adrenal steroid secretion appears to be specific for DHEAS. Although plasma cortisol was elevated in ill patients proportional to the degree of illness, the contribution of the concomitant decrease in DHEAS to this increase is not clear.

Hexachlorobutadiene (HCBD), while not produced commercially in the United States, may be encountered as an unwanted by-product of certain processes associated with the chlorination of hydrocarbons. Studies were conducted to assess the potential long-term toxicity of HCBD. In a reproduction study conducted in rats, dose levels of 20 or 2.0 mg/kg-day of HCBD induced slight maternal toxicity (primarily of the kidney) but caused no adverse effects on reproductive parameters-percent pregnancy and neonatal survival/development. A decreased neonatal body weight was noted at the highest dose level of 20 mg/kg-day of HCBD. No toxicologic effects were observed among the adults at a dose level of 0.2 mg/kg-day or among the neonates at dose levels of 0.2 or 2.0 mg/kg-day of HCBD. In a chronic toxicity study in rats, ingestion of 20 mg/kg-day for up to 2 years caused multiple toxicologic effects, primarily of the kidney, including the development of renal tubular adenomas and adenocarcinomas. Ingestion of the intermediate dose level of 2 mg/kg-day caused lesser degrees of toxicity, but no evidence of neoplasia. Ingestion of the lowest dose level of 0.2 mg/kg-day of HCBD caused no effects that could be attributed to treatment. These data indicate a dose-response relationship for HCBD-induced toxicity affecting primarily the kidney. HCBD-induced neoplasms occurred only at a dose level higher than that causing discernible renal injury.

A retrospective study showed that variability in the responses of heart rate and mean arterial pressure to hemorrhage in conscious swine can be induced by handling procedures, hyperthermia, and splenectomy. All animals were hemorrhaged 38.5 ml/kg over 1 hour. Physical restraint caused tachycardia prior to hemorrhage, an effect that was enhanced during hemorrhage; hemorrhage had no effect on the heart rate of unrestrained animals. Animals restrained in a sling also had an attenuated fall in mean arterial pressures throughout the experiment compared to normothermic swine. Splenectomized swine had elevated heart rates compared to sham-operated animals, with the difference persisting throughout hemorrhage. No difference in mean arterial pressure was noted due to splenectomy. These sources (handling, hyperthermia, and splenectomy) of experimental variability should be considered in the design and interpretation of experiments using conscious swine.

Regional differences in skin temperature (Ts) were determined by infrared radiography in four competitive swimmers of varying body compositions, prior to, after 5 min of immersion in water (Tw) at 23.5 degrees C, and after a 500-m freestyle swim at a training pace. Decreases in skin temperature that correlated with skinfold thickness were seen post-immersion (r = 0.56, p less than 0.05). After swimming, skin temperatures were highest in regions overlying active muscle masses and were independent of skinfold thickness. These regions were the deltoids, trapezius, triceps and biceps brachi, and pectorals. Swimming increased the extent of warmer skin surface areas and gradient Ts-Tw, over which heat loss could occur.

Dacron fabrics with a wide range of porosities were autoclaved for 3 minutes after being soaked in serum, 5% albumin, or 25% albumin. Porosity of compound Dacron grafts made with 25% albumin was less than 1 ml/min/cm2 regardless of the fabric base, whereas porosity of grafts made with serum or 5% albumin was proportional to the porosity of the base fabric. Porosity of the compound grafts remained stable for more than 48 hours and to pressure greater than 450 mm Hg, if the grafts were kept moist. Tubes of Marlex mesh coated with heat-denatured albumin, implanted as infrarenal aortic replacements in dogs, showed complete albumin absorption by 3 weeks. However, perigraft tissue reaction and graft incorporation were minimal and extensive false aneurysm formation resulted. Knitted filamentous Dacron 6 mm tubes coated with heat-denatured albumin were implanted as iliofemoral bypass grafts in 12 dogs, with blood-preclotted knitted filamentous Dacron grafts implanted as contralateral control grafts. Comparison of the albumin-coated grafts with the blood-preclotted control grafts showed no differences in healing or patency at 4 to 6 months. Heat-denatured 25% albumin forms a strong and hemostatic coating regardless of fabric base. Albumin-Dacron compound grafts are easily and rapidly made in the operating room, handle well, and are suitable for large and medium-sized arterial replacements without changes in healing or patency. Because of slow tissue incorporation, however, albumin-coated knitted Dacron grafts should be avoided in patients who require long-term anticoagulation therapy.

We measured RBC count, blood hemoglobin concentration, and related hematologic factors in 12 male marathon runners during a 20-day, 312-mile road race. The RBC and hemoglobin levels decreased significantly, from 5.17 million per cubic millimeter and 16.0 g/dL, respectively, to 4.36 million per cubic millimeter and 13.4 g/dL. Although the runners became marginally anemic during the race, their running speeds were not significantly changed. There were no abnormal clinical signs other than rare instances of hematuria. This study indicates that a sudden increase in long-distance running mileage above the regular training level may cause "sports anemia," a functional pseudoanemia that, in mild cases, does not impair endurance performance.

Plasma high-density lipoprotein (HDL)-cholesterol and lipid levels were measured in 12 male marathon runners (mean age, 40 years) who ran an average of 28 km/day for ten days, rested 70 hours, then continued to run for eight more days, covering a total distance for both running periods of 500 km. Blood samples were obtained on eight mornings. After one week of running, HDL-cholesterol levels increased 18% and triglyceride levels decreased 22%. However, the three-day rest period reversed these changes. As running resumed, HDL-cholesterol levels again increased and triglyceride levels decreased. There were no significant changes in total cholesterol, body weight, or skinfold thickness despite an average caloric intake of 4,800 kcal/day. Heavy beer drinking had no discernible effect on HDL-cholesterol levels, but may have caused mild hepatic injury as suggested by significantly increased serum alanine transferase and gamma-glutamyl transferase values. This study demonstrates that HDL-cholesterol levels increase with higher running mileage and decrease within days of stopping exercise when caloric and alcohol intake remain elevated.

This study was conducted to determine the hemodynamic response to uncontrolled hemorrhage following aortotomy in anesthetized swine. Eight Yorkshire swine underwent splenectomy and stainless steel wire placement in the anterior infrarenal aorta and were instrumented with Swan-Ganz and carotid artery catheters. Following an equilibration period, the wire was pulled. This produced a 5 mm aortotomy and spontaneous intraperitoneal hemorrhage. Serial measurements of mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), and cardiac output (CO) were obtained. From baseline to 5 min after aortotomy, there was a profound decrease in MAP in conjunction with a significant decrease in CO and MPAP. After the initial 5 min period, there was a progressive elevation in MAP, CO, and MPAP. Peripheral vascular resistance (PVR) was significantly decreased after aortotomy and returned to baseline after 60 min. From these data, we conclude that aortotomy produces a rapid depression and spontaneous recovery in MAP, CO, and MPAP. Aortotomy also produces a significant decrease in PVR, which is not generally associated with hemorrhagic hypotension.

Six patients with spontaneously occurring arrhythmias were studied to assess the antiarrhythmic properties of helium. The patients were divided into two subgroups breathing air, helium-oxygen (heliox), and nitrogen-oxygen (nitrox) in an alternating sequence during successive 20-min periods under continuous ECG surveillance at rest. There were no significant reductions in spontaneously occurring premature ventricular beats while breathing heliox, compared to breathing air of nitrox. Alternating the breathing gases in this manner caused no change in plasma concentration of electrolytes or in activity of serum glutamic-oxaloacetic transaminase or lactic acid dehydrogenase. We conclude that helium does not affect spontaneously occurring chronic premature ventricular beats in conscious resting man when it is breathed for a period of up to 20 min.

The regulation of sodium metabolism and the renin-angiotensin-aldosterone system was evaluated during 24 h of water, but not food, deprivation and during rehydration in the dog. Dehydration caused increases in plasma concentrations of sodium (6.0 +/- 0.7 meq/l), protein (0.8 +/- 0.1 g/dl), vasopressin (5.3 +/- 0.9 pg/ml), and renin activity (3.5 +/- 1.1 ng AI X ml-1 X 3 h-1). Plasma aldosterone was unchanged and plasma potassium fell slightly (0.2 +/- 0.1 meq/l). During dehydration, food, and thus sodium intake fell by more than 10% in 12 of 19 dogs, but urinary sodium excretion increased significantly, leading to a negative sodium balance (1.9 +/- 0.2 meq/kg). Sodium retention was observed after rehydration and sodium balance; plasma electrolytes, vasopressin, and plasma renin activity (PRA) returned turned to control levels after the 1st day of recovery. However, plasma aldosterone was slightly elevated at this time, returning to control after the 2nd day of recovery. The dehydration-induced natriuresis could not be accounted for by a fall in plasma aldosterone. However, sodium retention following rehydration could be aldosterone dependent, because additional studies showed a threefold rise in plasma levels of the hormone 1 h after drinking. The acute rise in aldosterone correlated closely (r = 0.82) with the fall in plasma sodium after drinking but not with changes in adrenocorticotrophic hormone, PRA, or plasma potassium. It is concluded that natriuresis is a homeostatic response to dehydration as a means of ameliorating the rise in body fluid osmolality.(ABSTRACT TRUNCATED AT 250 WORDS)

Dogs administered 500 or 250 mg of salol/kg/day showed transient toxicity of a reversible nature. Doses of 125 mg salol/kg/day caused no discernible ill effects in spite of urinary phenol levels elevated as high as 6144 ppm. It appears as if exposure to a compound other than benzene can cause an elevation of urinary phenol.

The effect of short-term bilateral intracarotid infusions of hypertonic saline on plasma vasopressin concentration (pAVP) was evaluated in five dogs. Intracarotid infusion of saline at 90 mumol . kg-1 . min-1 . artery-1 significantly (P less than 0.05) increased jugular vein osmolality (pOsm) and sodium concentration (pNa+) within 2 min. Saphenous vein pOsm was not altered during the 6 min of infusion, whereas pNa+ was increased (P less than 0.05) from 0.8 +/- 0.1 to 2.3 +/- 0.3 pg/ml. Subsequent experiments using hypertonic saline infusions of 90 and 180 mumol . kg-1 . min-1 administered intracarotidly and intravenously for 6 min were performed. Intracarotid isotonic infusions and intravenous hypertonic infusions did not significantly alter pAVP. Hypertonic intracarotid saline increased jugular vein pOsm and pNa+ in a dose-related fashion, whereas saphenous vein pOsm and pNa+ were not significantly changed after 6 min of infusion. Plasma vasopressin, compared with the isotonic intracarotid infusion (1.5 +/- 0.3 pg/ml), was increased (P less than 0.05) after hypertonic saline to 3.2 +/- 0.6 and 4.8 +/- 0.2 pg/ml for the 90 and 180 mumol . kg-1 . min-1 infusions, respectively. The cerebral osmolality indicated by jugular vein pOsm was therefore increased in the absence of changes in systemic pOsm during intracarotid hypertonic infusions. The increase in pAVP in response to these changes in pOsm supports the presence of central osmoreceptors regulating vasopressin release in the area of distribution of the common carotid arteries.

The role of the brain renin-angiotensin system in the ACTH response to ether stress in rats was investigated by injecting the angiotensin II receptor blocking drug saralasin, the angiotensin II converting enzyme inhibitors enalaprilat and captopril, and the renin inhibitor L 363714 intraventricularly and measuring the ACTH and corticosterone concentration in plasma 10 min after ether stress. ACTH and corticosterone were elevated to at least the same level in rats treated with the inhibitors as they were in rats treated with the corresponding vehicles; indeed, ACTH values were somewhat greater in stressed rats treated with the converting enzyme inhibitors and the renin inhibitor. ACTH values in the absence of ether were not affected by saralasin, enalaprilat, and captopril and were increased by L 363714. The data do not support the hypothesis that the brain renin-angiotensin system is involved in the maintenance of ACTH secretion or that it mediates the increase produced by ether stress.

A conscious porcine model was used to investigate the adequacy of O2 delivery relative to O2 demand, initially during a fixed-volume hemorrhage (37.5 ml/kg over 1 hr) and subsequently after resuscitation with 7.5% NaCl/6% Dextran 70 (4 ml/kg). Hemorrhage produced a small increase in O2 consumption, severe lactacidemia, and a doubling of apparent O2 demand. These effects were attributable to a behavioral compensation (periodic bouts of muscle activity) which presumably served to improve venous return. Despite enhanced ventilatory function, arterial O2 delivery was markedly reduced by hemorrhage, an effect that was due entirely to decrements in cardiac output and hemoglobin level. The disparity between O2 delivery and O2 demand was lessened following resuscitation with 7.5% NaCl/6% Dextran 70, primarily by suppression of demand and secondarily by an augmentation of delivery.

A technique is described for the intermittent collection of blood from the rat tail. By using commonly available equipment, blood samples can easily be obtained from rats without the need for anaesthesia. The development of this technique makes the rat more readily available as an animal model for repeated withdrawals of small blood samples for pharmacokinetic or bioavailability evaluations.

To study the effects of nonosmotic and nonvolumetric factors that may influence secretion of vasopressin, serum Na+, K+, and osmolality (Osm), hemoglobin, hematocrit, plasma arginine vasopressin (AVP), aldosterone (PA), and renin activity (PRA) were measured in five men and three women (26-50 yr, 73 +/- 4 kg) before and after 24 h of mild dehydration (food but no fluid) and seven times during the 1st h after rehydration with 10 ml/kg of tap water (17.5 +/- 0.5 degrees C) consumed in 105 s (range 35-240 s). Dehydration increased mean serum Na+ 3.7 +/- 0.7 meq/l (P less than 0.05), osmolality 9.1 +/- 1.1 mosmol/kg (P less than 0.05), and AVP from a hydrated level of 1.7 +/- 0.2 to 3.3 +/- 0.5 pg/ml (delta = 1.6 pg/ml, P less than 0.05). After rehydration AVP fell to 2.4 +/- 0.3 pg/ml (P less than 0.05) within 3 min and reached the water-replete level of 1.8 +/- 0.3 pg/ml 9 min after drinking started. Serum Na+ and Osm did not change until 30-60 min after drinking. No significant changes occurred in PRA, hemogloblin, hematocrit, or calculated delta in plasma volume, but PA increased from 11.1 +/- 1.5 ng/dl after dehydration to 15.6 +/- 2.6 ng/dl (P less than 0.05) between 30 and 60 min after drinking. The rapid fall in plasma AVP after rehydration took place in the absence of the expected changes in the primary regulators of plasma AVP (i.e., osmolality and plasma volume), with no change in blood pressure. The results suggest that oropharyngeal factors, alone or combined with gastric stimuli, are implicated.