Nielsen. Influence of body temperature on the development of fatigue during prolonged exercise in the heat. J. Appl. Physiol. 86(3): 1032-1039, 1999.-We investigated whether fatigue during prolonged exercise in uncompensable hot environments occurred at the same critical level of hyperthermia when the initial value and the rate of increase in body temperature are altered. To examine the effect of initial body temperature [esophageal temperature (T es ) ϭ 35.9 Ϯ 0.2, 37.4 Ϯ 0.1, or 38.2 Ϯ 0.1 (SE)°C induced by 30 min of water immersion], seven cyclists (maximal O 2 uptake ϭ 5.1 Ϯ 0.1 l/min) performed three randomly assigned bouts of cycle ergometer exercise (60% maximal O 2 uptake) in the heat (40°C) until volitional exhaustion. To determine the influence of rate of heat storage (0.10 vs. 0.05°C/min induced by a water-perfused jacket), four cyclists performed two additional exercise bouts, starting with T es of 37.0°C. Despite different initial temperatures, all subjects fatigued at an identical level of hyperthermia (T es ϭ 40.1-40.2°C, muscle temperature ϭ 40.7-40.9°C, skin temperature ϭ 37.0-37.2°C) and cardiovascular strain (heart rate ϭ 196-198 beats/min, cardiac output ϭ 19.9-20.8 l/min). Time to exhaustion was inversely related to the initial body temperature: 63 Ϯ 3, 46 Ϯ 3, and 28 Ϯ 2 min with initial T es of ϳ36, 37, and 38°C, respectively (all P Ͻ 0.05). Similarly, with different rates of heat storage, all subjects reached exhaustion at similar T es and muscle temperature (40.1-40.3 and 40.7-40.9°C, respectively), but with significantly different skin temperature (38.4 Ϯ 0.4 vs. 35.6 Ϯ 0.2°C during high vs. low rate of heat storage, respectively, P Ͻ 0.05). Time to exhaustion was significantly shorter at the high than at the lower rate of heat storage (31 Ϯ 4 vs. 56 Ϯ 11 min, respectively, P Ͻ 0.05). Increases in heart rate and reductions in stroke volume paralleled the rise in core temperature (36-40°C), with skin blood flow plateauing at T es of ϳ38°C. These results demonstrate that high internal body temperature per se causes fatigue in trained subjects during prolonged exercise in uncompensable hot environments. Furthermore, time to exhaustion in hot environments is inversely related to the initial temperature and directly related to the rate of heat storage. hyperthermia; skin blood flow; heart rate; stroke volume IT IS WELL DOCUMENTED that endurance can be impaired in hot compared with temperate climates (10,12,28) and that time to exhaustion is influenced by alterations of the initial body temperature (1,22,32,39). The attainment of a critically high level of body temperature has been proposed as the main factor limiting endurance performance in hot environments (7,28). The observation that trained subjects working at 60% of peak O 2 uptake (V O 2 peak ) in the heat [40°C, 10% relative humidity (RH)] for 9-12 consecutive days improved exercise performance from 48 to 80 min but fatigued at a core temperature of 39.7°C appears to support this notion (28). This large improvement in exercise time t...

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The discovery of the S-shaped O2 equilibrium curve and the Bohr effect in 1904 stimulated a fertile and continued research into respiratory functions of blood and allosteric mechanisms in haemoglobin (Hb). The Bohr effect (influence of pH/CO2 on Hb O2 affinity) and the reciprocal Haldane effect (influence of HbO2 saturation on H+/CO2 binding) originate in the Hb oxy-deoxy conformational change and allosteric interactions between O2 and H+/CO2 binding sites. In steady state, H+ is passively distributed across the vertebrate red blood cell (RBC) membrane, and intracellular pH (pHi) changes are related to changes in extracellular pH, Hb-O2 saturation and RBC organic phosphate content. As the Hb molecule shifts between the oxy and deoxy conformation in arterial-venous gas transport, it delivers O2 and takes up CO2 and H+ in tissue capillaries (elegantly aided by the Bohr effect). Concomitantly, the RBC may sense local O2 demand via the degree of Hb deoxygenation and release vasodilatory agents to match local blood flow with requirements. Three recent hypotheses suggest (1) release of NO from S-nitroso-Hb upon deoxygenation, (2) reduction of nitrite to vasoactive NO by deoxy haems, and (3) release of ATP. Inside RBCs, carbonic anhydrase (CA) provides fast hydration of metabolic CO2 and ensures that the Bohr shift occurs during capillary transit. The formed H+ is bound to Hb (Haldane effect) while HCO3- is shifted to plasma via the anion exchanger (AE1). The magnitude of the oxylabile H+ binding shows characteristic differences among vertebrates. Alternative strategies for CO2 transport include direct HCO3- binding to deoxyHb in crocodilians, and high intracellular free [HCO3-] (due to high pHi) in lampreys. At the RBC membrane, CA, AE1 and other proteins may associate into what appears to be an integrated gas exchange metabolon. Oxygenation-linked binding of Hb to the membrane may regulate glycolysis in mammals and perhaps also oxygen-sensitive ion transport involved in RBC volume and pHi regulation. Blood O2 transport shows several adaptive changes during exposure to environmental hypoxia. The Bohr effect is involved via the respiratory alkalosis induced by hyperventilation, and also via the pHi change that results from modulation of RBC organic phosphate content. In teleost fish, beta-adrenergic activation of Na+/H+ exchange rapidly elevates pHi and O2 affinity, particularly under low O2 conditions.

In catalyzing the reversible hydration of CO2 to bicarbonate and protons, the ubiquitous enzyme carbonic anhydrase (CA) plays a crucial role in CO2 transport, in acid-base balance, and in linking local acidosis to O2 unloading from hemoglobin. Considering the structural similarity between bicarbonate and nitrite, we hypothesized that CA uses nitrite as a substrate to produce the potent vasodilator nitric oxide (NO) to increase local blood flow to metabolically active tissues. Here we show that CA readily reacts with nitrite to generate NO, particularly at low pH, and that the NO produced in the reaction induces vasodilation in aortic rings. This reaction occurs under normoxic and hypoxic conditions and in various tissues at physiological levels of CA and nitrite. Furthermore, two specific inhibitors of the CO2 hydration, dorzolamide and acetazolamide, increase the CA-catalyzed production of vasoactive NO from nitrite. This enhancing effect may explain the known vasodilating effects of these drugs and indicates that CO2 and nitrite bind differently to the enzyme active site. Kinetic analyses show a higher reaction rate at high pH, suggesting that anionic nitrite participates more effectively in catalysis. Taken together, our results reveal a novel nitrous anhydrase enzymatic activity of CA that would function to link the in vivo main end products of energy metabolism (CO2/H+) to the generation of vasoactive NO. The CA-mediated NO production may be important to the correlation between blood flow and metabolic activity in tissues, as occurring for instance in active areas of the brain.

Abstract. In this article we introduce new bounds on the effective condition number of deflated and preconditioned-deflated symmetric positive definite linear systems. For the case of a subdomain deflation such as that of Nicolaides [SIAM J. Numer. Anal., 24 (1987), pp. 355-365], these theorems can provide direction in choosing a proper decomposition into subdomains. If grid refinement is performed, keeping the subdomain grid resolution fixed, the condition number is insensitive to the grid size. Subdomain deflation is very easy to implement and has been parallelized on a distributed memory system with only a small amount of additional communication. Numerical experiments for a steady-state convection-diffusion problem are included.

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In many applications. such as atmospheric chemistry. large systems of ordinary differential equations (ODEs) with both stiff and nonstiff parts have to be solved numerically. A popular approach in such cases is to integrate the stiff parts implicitly and the nonstiff parts explicitly. In this paper we study a class of implicit-explicit (!MEX) linear multistep methods intended for such applications. The paper focuses on the linear stability of popular second order methods like extrapolated BDE Crank-Nicolson leap-frog and a particular class of Adams methods. We present results for problems with decoupled eigenvalues and comment on some specific CFL restrictions associated with advection terms. © I 997 Elsevier Science B. Y.

Experiments performed on isolated intestinal segments from the marine teleost fish, the European flounder (Platichthys flesus), revealed that the intestinal epithelium is capable of secondary active HCO3(-) secretion in the order of 0.2-0.3 micromol x cm(-2) x h(-1) against apparent electrochemical gradient. The HCO3(-) secretion occurs via anion exchange, is dependent on mucosal Cl(-), results in very high mucosal HCO3(-) concentrations, and contributes significantly to Cl(-) and fluid absorption. This present study was conducted under in vivo-like conditions, with mucosal saline resembling intestinal fluids in vivo. These conditions result in a transepithelial potential of -16.2 mV (serosal side negative), which is very different from the -2.2 mV observed under symmetrical conditions. Under these conditions, we found a significant part of the HCO3(-) secretion is fueled by endogenous epithelial CO2 hydration mediated by carbonic anhydrase because acetazolamide (10(-4) M) was found to inhibit HCO3(-) secretion and removal of serosal CO(2) was found not to influence HCO3(-) secretion. Reversal of the epithelial electrochemical gradient for Cl(-) (removal of serosal Cl(-)) and elevation of serosal HCO3(-) resulted in enhanced HCO3(-) secretion and enhanced Cl(-) and fluid absorption. Cl(-) absorption via an anion exchange system appears to partly drive fluid absorption across the intestine in the absence of net Na(+) absorption.