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Showing papers in "American Journal of Physiology in 1968"





Journal ArticleDOI
TL;DR: It is concluded that the EDV, ESV, and stroke volumes of mammals are linear functions of body weight and not of body surface or metabolic rate; and that cardiac output is alinear function of metabolic rate'and not a linear function ofBody surface area.
Abstract: Holt, J. P., E. A. Rhode, and H. Kines. Ventricular volumes and body weight in mammals. Am. J. Physiol. 215(3): 704-715. 1968.—Left and right ventricular end-diastolic (EDV), endsystolic (ESV), and stroke volumes, heart rates, cardiac output, total peripheral resistance (TPR), and other cardiovascular variables have been measured in the control state in nine species of mammals varying 1,790-fold (rat to horse) in body weight. The log-log relationships between these variables and bodyweight (BW), body surface, metabolic rate, heart weight, and ventricular weight have been determined and are described bypower law equations. On the basis of these results relationships for each ventricle are described by equations in which ventricu lar volumes are related to BW1-0, heart rate to BW °-20, cardiac output to BW075, and TPR to BW"0-75. Evidence is presented that in the control state the heart rate of mammals is a function of metabolic rate per unit body weight, and left ventricular stroke work per unit body weight is constant. It is concluded that the EDV, ESV, and stroke volumes of mammals are linear functions of body weight and not of body surface or metabolic rate; and that cardiac output is a linear function of metabolic rate'and not a linear function of body surface area. It is sug gested that ventricular volumes be reported as volume per unit body weight-

245 citations


Journal ArticleDOI
TL;DR: The concept of the role of the cerebral arterial blood in homeothermy of the brain in the primate is applicable as a general approach to the study of brain temperature and temperature regulation in other mammals.
Abstract: HAYWARD,JAMESN., AND MARY ANN BAKER. Role of cmdral arterial blood in the rqphtion of brain temperature in the monkey. Am. J. Physiol. 215(Z): 389-403. 1.968.-The major determinant of cerebral temperatures in the monkey is the temperature of the arterial blood perfusing the brain. We measured arterial blood temperatures in the aortic arch simultaneously with those at extracranial and intracranial sites in 16 chronic monkeys. Sequential thermal changes occurred in the central arterial blood, cerebral. arterial blood, and in the brain during feeding, sleeping, arousal, and saline injections. Information about the thermal state of the body core is carried rapidly by the arterial blood to the thermodetector neural elements in the preoptic-anterior hypothalamic region of the brain. Maneuvers which after ventilation and the levels of carbon dioxide in the blood c.ln change the tone of the cerebral vessels and cause a shift in cerebral blood flow. In our monkeys such shifts in the rate of AO~V of the cooler arterial blood through the j(varmer brain altered the convective heat transfer in the brain and predictably changed the brain-blood temperature gradients. Our concept of the role of the cerebral arterial blood in homeothermy of the brain in the primate is applicable as a general approach to the study of brain temperature and temperature regulation in other mammals.

244 citations


Journal ArticleDOI
TL;DR: This technic, when coupled with a determination of the percentage of cells which stain for peroxidase, provides a fairly rapid and simple means of determining total marrow neutrophils.
Abstract: CHERVENICK, P. A., D. R. BOGGS, J. C. MARSH, G. E. CARTWRIGHT, AND M. M. WINTROBE. Quantitatize studz’iz of blood and bone marrw neutrophils in normal mice. Am. J. Physiol. 215(2) : 353-360. 1968.-A method for determining the total number of nucleated cells in the marrow cavity of the humerus of a motise is described. This technic proved to be reasonably accurate. The humerus contained an average of 7.15 X 106 nucleated cells which constituted 2.8 y0 of the total cells in the entire marrow as judged by distribution of radioactive iron in the skeleton. This technic, when coupled with a determination of the percentage of cells which stain for peroxidase, provides a fairly rapid and simple means of determining total marrow neutrophils. No difference was observed in leukocyte concentration in venous blood samples obtained from the orbital sinus, vena cava, or tail when properly controlled comparisons were made. However, leukocyte concentration in bIood samples from the aorta was less than one-half that in venous samples. AII of the following factors were found to influence the leukocyte concentration in venous blood samples: repeated sampling, ether or pentobarbital anesthesia, heparin administration, time of day, and heating the tail.

241 citations


Journal ArticleDOI
TL;DR: Renal clearances of creatinine, lithium, sodium, and potassium were determined in six healthy human subjects and may form the basis of a procedure for active treatment of lithium poisoning.
Abstract: THOMSEN, KLAUS, AND MOGENS SCHOU. Renal lithium excretion k man. Am. J. Physiol. 215(4): 823-827. 1968.--Renal clearances of creatinine, lithium, sodium, and potassium were determined in six healthy human subjects. Lithium excretion was not significantly affected by water diuresis or the administration of furosemide, bendroflumethiazide, ethacrynic acid, ammonium chloride, spironolactone, or potassium chloride. Sodium-poor diet led to decrease and extra dietary sodium chloride to increase of lithium excretion; the changes took place relatively slowly. Osmotic diuresis (urea) and the administration of sodium bicarbonate, acetazolamide, and aminophylline all produced significant increase of lithium excretion. Lithium ions seem to be reabsorbed mainly in the proximal tubules. The observations may form the basis of a procedure for active treatment of lithium poisoning.

232 citations



Journal ArticleDOI
TL;DR: Although a circadian rhythm was not detected for dopamine and norepinephrine in the whole brain, the data did suggest that these two catecholamines are characterized by reproducible higher frequency, andradian rhythms.
Abstract: SCHEVING, L. E., W. H. HARRISON, P. GORDON, AND J. E. PAULY. Daily @ctuation (circadian and ultra&h) in biogenic amines of the rat brain. Am. J. Physiol. 2 14( 1) : 166-l 73. 1968.-Fluorometric measurements were made of serotonin, dopamine, and norepinephrine extracted from brains which were obtained from different subgroups of adult male rats killed at hourly intervals over three separate 24-hr periods. With a method involving sampling at hourly intervals, a synchronized circadian rhythm in serotonin with a crest extending from 1130 to 1730, followed by a trough between 2030 and 2130 wasdemonstrated in rats maintained on a 12-hr photoperiod (0600 to 1800 CST) followed by 12 hr of darkness. Although a circadian rhythm was not detected for dopamine and norepinephrine in the whole brain, the data did suggest that these two catecholamines are characterized by reproducible higher frequency, &radian rhythms. ‘The importance of these studies involving the biogenic amines, their specific relationship to the physiology of sleep, and their pertinence to neurochemical studies are discussed.

208 citations


Journal ArticleDOI
TL;DR: All parts of the nephron were relatively impermeable to mannitol but were permeable to urea, which is consistent with what would be predicted if the driving force of the countercurrent system were a sodium pump in the ascending limb of the loop of Henle, although such a pump was not demonstrated.
Abstract: MORGAN, TREFOR, AND ROBERT MT. BERLINER. Permeability of the loop of Henle, uasu recta, and collecting duct to water, urea, and sodium. Am. J. Physiol. 215(l): 108-115. 1968.-The permeability of the loops of Henle, collecting ducts, and vasa recta have been studied by free-flow perfusion. When ADH was absent the diffusional permeability coefficient for THO in the descending limb (DL) was I 19 ZII 14 (SE) cm se0 X lo-“, ascending limb (AL) 50 =t 4.5 collecting duct (CD) 45 =t 3.1, and vasa recta (VR) at least 192 & 20. ADH increased the value for collecting ducts to 87 + 7 without changing the other values. The diffusional permeability coefficients for urea were DL 13 =t 3.0; AL 14 =t 2.0; CD 20 + 1.3; and VR 47 + 3.3. ADH increased the permeability of the CD (30 + 2.4) without affecting the other structures. The permeability of the descending limb changed before the hairpin bend. Net water flux was DL 58 + 6.2 nliters cmm2 milliosmoF min-I, AL 4.4 + 1.1; CD (no ADH) 4.2 zk 2.2; CD (ADH) 30 + 2.6. All parts of the nephron were relatively impermeable to mannitol but were permeable to urea. NaCl did not enter the collecting duct or ascending limb but entered the descending limb of Henle’s loop. These observations are consistent with what would be predicted if the driving force of the countercurrent system were a sodium pump in the ascending limb of the loop of Henle, although such a pump was not demonstrated in this preparation.

204 citations



Journal ArticleDOI
TL;DR: Calcium ion itself will not produce a release of insulin, but it is necessary for normal insulin secretion in response to glucose or tolbutamide, and was studied in the isolated perfused rat pancreas.
Abstract: CURRY, DONALD L., LESLIE L. BENNETT, AND GEROLD M. GR~DSKY. Requirement for calcium ion in insulin secretiorz by the perfused rut p ancreas. Am. J. Physiol. 214(l): 174-178. 1968.The effect of calcium ion on insulin release was studied in the isolated perfused rat pancreas. Following a standard glucose stimulus, insulin secretion (determined by immunochemical assay of the total portal vein effluent) was directly dependent on perfusate calcium ion concentrations up to 4 mEq/liter, At calcium levels greater than this, the total insulin release exhibited a plateau which was independent of calcium ion concentration. Following a standard 2-min tolbutamide stimulus, insulin release was directly dependent on the perfusate calcium concentration throughout the whole spectrum of calcium COP centrations studied (0.59-10.9 mEq/liter). At high calcium levels, insulin secretion was prolonged throughout a 6-min period of tolbutamide stimulation. Preparations which were perfused with solutions containing glucose, but to which no calcium had been added, failed to have a significant release of insulin. When calcium was added to the perfusates of these preparations, a marked increase in insulin secretion was observed (provided that the calcium deprivation lasted no longer than 20 min). Calcium ion itself will not produce a release of insulin, but it is necessary for normal insulin secretion in response to glucose or tolbutamide.


Journal ArticleDOI
TL;DR: While canalicular flow is linearly related to bile acid secretion rate, there appears to be an independent basal rate of canalicular bile production, which is concentrated as much as threefold by ductal or ductular fluid reabsorption in the dog.
Abstract: WHEELERJENRY ~.,ELIZABETH D.Ross, AND STANLEY E. BRADLEY. Canalicular bile production in dogs. Am. J. Physiol. 2 14(4) : 866-874. 1968.-Biliary clearances of 14C-labeled creatinine, erythritol, inulin, mannitol, sucrose, and urea were measured in three unanesthetized cholecystectomized dogs equipped with Thomas duodenal cannulas. Sodium taurocholate was infused intravenously at varying rates to produce changes in bile flow. Clearance of mannitol varied linearly with bile acid secretion rate and in most cases was higher than bile flow. Clearances of creatinine, erythritol, and urea were similar to mannitol clearance except that erythritol clearance was slightly higher than mannitol clearance in one of the three dogs. Bile-to-plasma concentration ratios were usually greater than one and were highest at low rates of bile acid secretion. Inulin and sucrose clearances were very low. Secretin choleresis had no effect on mannitol clearance. These data suggest that clearances of compounds such as mannitol and erythritol provide an estimate of canalicular bile flow in the dog. While canalicular flow is linearly related to bile acid secretion rate, there appears to be an independent basal rate of canalicular bile production. Canalicular bile is concentrated as much as threefold by ductal or ductular fluid reabsorption in the dog.

Journal ArticleDOI
TL;DR: The data suggest the existence of an active transport system for H ion movement into the tubular lumen and confirm the importance of carbonic anhydrase at the luminal membrane for rapid carbonic acid dehydration.
Abstract: VIEIRA, FRANCISCO LACAZ, AND GERHARD MALNIC Hydrogen ion secretion by rat renal cortical tubules as studied by an antimony microelectrode. Am. J. Physiol. 214(4) : 710-718. 1968.-The pH of proximal and distal tubular fluid of rats on a control diet and of similar rats submitted to 5Cr, NaHC03 or acetazolamide infusions was measured in situ by an antimony microelectrode. The preparation and standardization of this simple electrode system is described. Mean in situ pH in proximal tubules of control rats was 6.71, in distal tubules 6.33. In this group hydrogen ion transport was shown to proceed against an electrochemical potential gradient. The same occurred in proximal tubules of acetazolamide-infused rats. It was not apparent in distal tubules of the latter group nor in proximal and distal tubules of NaHC03-loaded rats. In addition, measurements of disequilibrium pH were made by comparisonof in situ pH values with those obtained after equilibrating tubular fluid collected from the same nephron site with mineral oil of known PcoZs Significant disequilibrium pH values were observed in proximal tubular fluid only from the acetazolamide-treated rats. In distal tubular fluid, on the other hand, significant values were found in all experimental groups. The data suggest the existence of an active transport system for H ion movement into the tubular lumen. They confirm the importance of carbonic anhydrase at the luminal membrane for rapid carbonic acid dehydration.

Journal ArticleDOI
TL;DR: Single-comb White Leghorn chickens hatched and living in a high-altitude environment of 12,500-ft elevation, had pulmonary arterial blood pressures approximately twice as great as found in chickens at sea level and the proportionality coefficients of this relationship in chickens were double those reported by others in cattle.
Abstract: BURTON, R. R., E. L. BESCH, AND A. H. SMITH. Efect of chronic hypoxia on the pulmonary arterial blood pressure of the chicken. Am. J. Physiol. 214(6): 1438-1442. 1968.-Single-comb White Leghorn chickens hatched and living in a high-altitude environment of 12,500-ft elevation, had pulmonary arterial blood pressures approximately twice as great as found in chickens at sea level. The pulmonary arterial blood pressures were highly correlated with the relative right ventricular masses of the individual birds at all altitudes. The proportionality coefficients of this relationship in chickens were double those reported by others in cattle. In the female chicken it appears that each 1 mm Hg increase in the mean pulmonary arterial blood pressure above sea level control values results in a 41-mg increase in the right ventricular mass (hypertrophy). Inhalation of 95y0 oxygen and 57; carbon dioxide for 10 min had no apparent effect on this pulmonary arterial hypertension at high altitude, although acute hypoxia (asphyxia, by tracheal occlusion) produced a pulmonary arterial hypertension in sea-level birds. The occlusion of one major pulmonary artery produced a 6791, increase in the pulmonary arterial blood pressure in the unobstructed lung. Chronic hypoxia ( 12,500-ft elevation) produced a 47y0 reduction in the arterial oxygen tension and no significant changes in the arterial carbon dioxide tension and pH. Anesthesia at the surgical level in chickens results in an acute hypoxia and an acidosis. This hypoxic effect from the anesthesia was much less marked at high altitude. Pulmonary arterial blood pressures reached control values within 2 days after the high altitude-adapted animals were returned to sea level.

Journal ArticleDOI
TL;DR: It was shown that at any instant during ejection, the performance of the ventricle was dependent on the interrelations between myocardial fiber length, tension, velocity, and the impedance to ejection.
Abstract: URSCHEL, CHARLES W., JAMES W. COVELL, EDMUND H. SONNENBLICK, JOHN Ross, JR., AND EUGENE BRAUNWALD. Effects of decreased aortic compliance on performance of the left ventricle. Am. J. Physiol. 214(2): 298-304. 1968.-The effects of decreased aortic compliance on the performance of the left ventricle were studied in eight dogs by diverting their aortic blood flow through a rigid bypass. Despite unchanged myocardial contractility, judged by the force-velocity relation during isovolumic systole, direction of blood into the rigid byDass 1. caused increases in peak systolic pressure, duration of ejection, and left ventricular end-diastolic pressure. Stroke volume was unchanged and the ejection fraction therefore declined. Peak and integrated myocardial fiber tension rose as a result of the increases in left ventricular pressure and size and because of the increase in tension, circumferential fiber and contractile element velocities decreased. Further, it was shown that at any instant during ejection, the performance of the ventricle was dependent on the interrelations between myocardial fiber length, tension, velocity, and the impedance to ejection. In other experiments, aortic blood flow was diverted through the rigid bypass while preload was held constant. Under these circumstances, stroke volume fell and left ventricular tension rose to a smaller extent than when preload was allowed to rise. These experiments illustrate that the mechanical performance of the left ventricle is altered by the physical characteristics of the arterial tree. Decreased aortic compliance, as occurs during aging in man, therefore increases the impedance to ejection and the tension load on the myocardium.


Journal ArticleDOI
TL;DR: The data indicate that during starvation the weight loss of the small intestine is out of proportion to body weight loss, the total intestinal cell population is diminished, and there is a decrease in the RNA, protein, and water content of the individual cells.
Abstract: STEINER, MANFRED, HECTOR R. BOURGES, LEWIS S. FREEDMAN, AND SEYMOUR J. GRAY, Effect uf starvation on the tissue composition of the small intestine in the rat. Am. J. Physiol. 2 15( I > : 75-77. 1968.-The effects of a 6-day period of complete starvation on the major tissue constituents of the small intestine were studied in male albino rats. The DNA, RNA, protein, and total tissue water contents of the entire small intestine were determined. The weight loss of the small intestine (53 c/,) after starvation was greater than that of the whole body (32”/;). The decrease in RNA, protein, and total tissue jvater (49-52 70) was commensurate with the weight loss of the small intestine. In sharp contrast, DNA fell by only 36 G;?c. Expressed per milligram DNA, the RNA, protein, and water were reduced by 2 l26’5,. The changes in the cell constituents of the mucosal scrapings paralleled those observed in the full thickness. The data indicate that during starvation the weight loss of the small intestine is out of proportion to body weight loss, the total intestinal cell population is diminished, and there is a decrease in the RNA, protein, and water content of the individual cells. A reduction in cell size is postulated on the basis of the loss of cell water.


Journal ArticleDOI
TL;DR: A rate-limiting metabolic device, which is rapidly reversible at Paz between 5 and 100 mm Hg, could serve as a control for the production of high-energy intermediates necessary for vascular smooth muscle contraction and provide a means whereby PO:! could account for local autoregulation of blood flow in situ.
Abstract: DETAR, REED, AND DAVID F. BOHR. Oxygen and vascular smooth muscle contraction. Am. J. Physiol. 214(Z): 241-244. 1968.-Oxygen tension is an important determinant of the contractile tension developed by isolated helical strips of rabbit aorta. A decrease in PO:! below 100 mm Hg causes the contractile response to epinephrine (l-3 pg/liter) to diminish linearly to near zero levels at < 1 mm Hg. If oxygen tension is rapidly decreased from 100 mm Hg to a lower steady-state value during a sustained contraction produced by epinephrine, the time constant of decreased contractile tension is less than 4 min. If the smooth muscle is stimulated with epinephrine near the end of a 15-min hypoxic period, and contractile tension is allowed to reach a steady state, an increase in PO? to 100 mm Hg causes recovery of contractile tension, with a time constant of less than 2.5 min providing the PO:! during hypoxia is >5 mm Hg. The time constant is approximately 3.5 min after 60 min of hypoxia (> 5 mm Hg). At 5 mm Hg or less, however, the time constant is 5.5 min after 15 min hypoxia, and is greater than 15 min after 60 min hypoxiaThe immediate dependence of contractile tension on PO? is explained on the assumption that oxygen plays a metabolic role within the mitochondria of the smooth muscle cells, as the final electron acceptor in the respiratory chain. Such a rate-limiting metabolic device, which is rapidly reversible at Paz between 5 and 100 mm Hg, could serve as a control for the production of high-energy intermediates necessary for vascular smooth muscle contraction and provide a means whereby PO:! could account for local autoregulation of blood flow in situ.






Journal ArticleDOI
TL;DR: Ingestion of a high-protein diet apparently results in a series of homeostatic responses as protein intake is elevated and activities of enzymes of amino acid catabolism increase; subsequently plasma amino acid concentrations decrease and food intake returns to normal.
Abstract: ANDERSON, H. L., N. J. BENEVENGA, AND A. E. HARPER. Associations among food and protein intake, serine dehydratase, and plasma amino acids. Am. J. Physiol. 214(5): 1008-1013. 1968.Relationships among liver serine-threonine dehydratase activity, plasma amino acid concentrations, and food and protein intake were studied in growing rats undergoing adaptation to high-protein diets. Serine-threonine dehydratase activity was low initially but increased as protein intake rose above the amount required for rapid growth. Plasma amino acid concentrations were greatly elevated 1 day after animals were fed high-protein diets but, with the exceptions of leucine, isoleucine, and valine, decreased thereafter as serine-threonine dehydratase activity increased. Food intake of rats fed high-protein diets was depressed initially when serine-threonine dehydratase activity was low and plasma amino acid concentrations were high. Food intake rose subsequently as enzyme activity increased and plasma amino acid concentrations decreased. Ingestion of a high-protein diet apparently results in a series of homeostatic responses. l initially plasma amino acid concentrations rise and food intake falls; despite this, protein intake is elevated and activities of enzymes of amino acid catabolism increase; subsequently plasma amino acid concentrations decrease and food intake returns to normal.


Journal ArticleDOI
TL;DR: The dynamic response of the hindlimb resistance vessels to sympathetic stimulation was studied in 16 dogs, using step and sinusoidally modulated stimuli, and the significance of these findings in local and general circulatory control is discussed.
Abstract: ROSENBAUM, ‘MAURICE, AND DAVID RACE. Frequency-response characteristics of nascdar resistance vessek Am. J. Physiol. 215(6) : 1397-1402. 1968.-The dynamic response of the hindlimb resistance vessels to sympathetic stimulation was studied in 16 dogs, using step and sinusoidally modulated stimuli. The system is nonlinear and the form of the rise in resistance differs from that of the fall. A step input is followed by a delay of approximately 0.5 set before any detectable change occurs, and then by an approximately exponential rise in resistance with an average time constant of 9 sec. Cessation of stimulation is followed by a period of approximately 2.5 set during which the resistance does not change, then by a fall in resistance, which is slightly slower than the rise, and variable overshoot depending on the stimulus duration. The overshoot suggests a resonant frequency of approximately 0.034 cycle/set. Sinusoidally modulated stimulation indicates a limited frequency response corresponding with the slow response of the system, and resonance around the average corner frequency of 0.017 cycle/ set is suggested in some experiments. The significance of these findings in local and general circulatory control is discussed.

Journal ArticleDOI
TL;DR: The respiration of resting and panting birds was studied in nine species representing a wide range of size, morphology, and habits and suggest that the respiratory system of birds is a more effective gas exchange system than that of mammals and also that the mesobronchial bypass route cannot prevent alkalosis during panting.
Abstract: CALDER, W+ A., AND KNUT SCHMIDT-NELSEN. Punting and blood carbon dioxide in birds. Am. J* Physiol, 215(2): 4771482. 1968.-The respiration of resting and panting birds was studied in nine species representing a wide range of size, morphology, and habits. All these birds had similar values for arterial blood PCU~ and pH during normal resting respiration (28 mm C02, pH = 7.5). These values are much lower than those for mammals, which suggests a more thorough ventiXatory air renewal in the avian lungs. Panting during heat stress resulted in hypocapnia and alkalosis in aI1 species, even in the pelican which makes extensive use of the nonrespiratory gular pouch for evaporative cooling. The findings suggest that the respiratory system of birds is a more effective gas exchange system than that of mammals, and also that the mesobronchial bypass route cannot prevent alkalosis during panting. the respiratory system which exceed the needs for gas exchange, Panting and gular movements and their thermoregulatory effects have been studied in several birds (e.g., 3, 7, 11, 16, 21-23) but information on the simultaneous gas exchange is available only for the pigeon (6) and the ostrich (26). Within the avian lung, the large mesobronchi and the smaller parabronchi are parallel routes for air passing to and/or from the air sacs. The mesobronchial route could serve as a bypass route or shunt, so that evaporative cooling could be augmented without hyperventilating the parabronchial gas exchange surfaces (30). However, considerable hypocapnia and alkalosis occur in pigeons that pant vigorously (6) which indicates that shunting, if it exists at all, is insufficient to prevent acid-base shifts. In contrast, the large, flightless ostrich does not become hypocapnic and alkalotic during panting (26). Are these phenomena, low Pcoz at rest and thermoregulatory hypocapnia, generally characteristic of the respiratory systems of birds capable of flight or peculiar to the pigeon? This paper reports a comparative study in which we sought to answer this question. hypocapnia; hyperventilation; alkalosis; temperature regulation; respiration; gular flutter