Jack A. Loeppky

Body Temperature, Autonomic Responses, and Acute Mountain Sickness

A few studies have reported increased body temperature (T(o)) associated with acute mountain sickness (AMS), but these usually include exercise, varying environmental conditions over days, and pulmonary edema. We wished to determine whether T(o) would increase with AMS during early exposure to simulated altitude at rest. Ninety-four exposures of 51 men and women to reduced P(B) (423 mmHg = 16,000 ft = 4850 m) were carried out for 8 to 12 h. AMS was evaluated by LL and AMS-C scores near end of exposure, and T(o) was measured by oral digital thermometer before altitude and after 1 (A1), 6 (A6), and last (A12) h at simulated altitude. Other measurements included ventilation, O(2) consumption and autonomic indicators of plasma catecholamines, HR, and HR variability. Average T(o) increased by 0.5 degrees F from A1 to A12 in all subjects (p < 0.001). Comparison between 16 subjects with lowest AMS scores (mean LL = 1.0, range = 0 to 2.5) and 16 other subjects with highest AMS scores (mean LL = 7.4, range = 5 to 11) demonstrated a transient decline in T(o) from A1 to A6 in AMS, in contrast to a rise in non-AMS (p = 0.001). Catecholamines, HR, and HR variability (increased low F/high F ratio) indicated significant elevation of sympathetic activity in AMS, where T(o) fell, but no change in metabolic rate. The apparently greater heat loss during early AMS suggests increased hypoxic vasodilation in spite of enhanced sympathetic drive. Greater hypoxic vasodilation and elevated HR in AMS in the absence of other changes suggest that augmentation of beta-adrenergic tone may be involved in early AMS pathophysiology.

Quantitative description of whole blood CO2 dissociation curve and Haldane effect

A simple procedure is presented to describe accurately the whole blood CO2 dissociation curve on linear content (CCO2) and pressure (PCO2) coordinates with an exponential equation (CCO2 = K . PCO2b). A single coordinate and the hemoglobin concentration, Hb, are required. Whole blood CCO2 can be calculated from values for pH, PCO2, Hb and O2 saturation by empirically accurate equations. The mathematical description of the CO2 curve was employed to quantitate the in vivo Haldane factor (fH) from simultaneous arterial and mixed venous blood samples in 20 healthy exercising subjects. The mean +/- SE was 0.28 +/- 0.03 (vol. % delta CCO2/vol. % delta HbO2). In 20 patients with severe obstructive lung disease fH was 0.29 +/- 0.08 when calculated from arterial samples while breathing air and 100% O2. Values for fH were not related significantly to acid-base status or Hb as suggested by previous workers. By assuming these or other values for fH, the in vivo change in blood PCO2 resulting from a given change in oxygenation can be predicted.

Effect of a Marathon Run on Serum Lipoproteins, Creatine Kinase, and Lactate Dehydrogenase in Recreational Runners

Abstract The objective of this study was to determine the effect of a marathon run on serum lipid and lipoprotein concentrations and serum muscle enzyme activities and follow their recovery after the run. These blood concentrations were measured before, immediately after, and serially after a marathon run in 15 male recreational runners. The triglyceride level was significantly elevated postrace, then fell 30% below baseline 1 day after the run, and returned to baseline after 1 week. Total cholesterol responded less dramatically but with a similar pattern. High-density lipoprotein cholesterol remained significantly elevated and low-density lipoprotein cholesterol was transiently reduced for 3 days after the run. The total cholesterol/high-density cholesterol ratio was significantly lowered for 3 days. Serum lactate dehydrogenase activity significantly doubled postrace and then declined but remained elevated for 2 weeks. Serum creatine kinase activity peaked 24 hr after the run, with a 15-fold rise, and returned to baseline after 1 week. The rise of these enzymes reflects mechanically damaged muscle cells leaking contents into the interstitial fluid. It is concluded that a prolonged strenuous exercise bout in recreational runners, such as a marathon, produces beneficial changes in lipid blood profiles that are significant for only 3 days. However, muscle damage is also evident for 1 week or more from the dramatic and longlasting effect on enzyme levels. Laboratory values for these runners were outside normal ranges for some days after the race.

Comments on Point: Counterpoint: Hypobaric hypoxia induces/does not induce different responses from normobaric hypoxia.

112:1788-1794, 2012. ; J Appl Physiol Joshua C. Weavil, Peter Bartsch and Charles F. Nelatury Samuel Verges, Patrick Levy, Eric M. Snyder, Bruce D. Johnson, Jonathon L. Stickford, Y. Millet, Benjamin D. Levine, James H. Wessel III, Bernard Wuyam, Renaud Tamisier, MacInnis, Michael S. Koehle, Thomas Rupp, Marc Jubeau, Stephane Perrey, Guillaume Laymon, Jack A. Loeppky, Matiram Pun, Kai Schommer, Mary C. Vagula, Martin J. S. Chapman, Johnny Conkin, Hugo Nespoulet, Darren P. Casey, Bryan J. Taylor, Abigail Olivier Girard, Michael S. Koehle, Jordan A. Guenette, Samuel Verges, Robert F. normobaric hypoxia induces/does not induce different responses from Comments on Point:Counterpoint: Hypobaric hypoxia

Hypoxemia and acute mountain sickness: which comes first?

Hypoxemia is usually associated with acute mountain sickness (AMS), but most studies have varied in time and magnitude of altitude exposure, exercise, diet, environmental conditions, and severity of pulmonary edema. We wished to determine whether hypoxemia occurred early in subjects who developed subsequent AMS while resting at a simulated altitude of 426 mmHg (approximately 16,000 ft or 4880 m). Exposures of 51 men and women were carried out for 8 to 12 h. AMS was determined by Lake Louise (LL) and AMS-C scores near the end of exposure, with spirometry and gas exchange measured the day before (C) and after 1 (A1), 6 (A6), and last (A12) h at simulated altitude and arterial blood at C, A1, and A12. Responses of 16 subjects having the lowest AMS scores (nonAMS: mean LL=1.0, range=0-2.5) were compared with the 16 having the highest scores (+AMS: mean LL=7.4, range=5-11). Total and alveolar ventilation responses to altitude were not different between groups. +AMS had significantly lower PaO2 (4.6 mmHg) and SaO2 (4.8%) at A1 and 3.3 mmHg and 3.1% at A12. Spirometry changes were similar at A1, but at A6 and A12 reduced vital capacity (VC) and increased breathing frequency suggested interstitial pulmonary edema in +AMS. The early hypoxemia in +AMS appears to be the result of diffusion impairment or venous admixture, perhaps due to a unique autonomic response affecting pulmonary perfusion. Early hypoxemia may be useful to predict AMS susceptibility.

Contribution of the Haldane effect to the rise of arterial Pco2 in hypoxic patients breathing oxygen.

Arterial (Paco2), alveolar (Paco2), mixed expired (Peco2) CO2 pressures, CO2 production (Vco2) as well as arterial O2 saturation (Sao2) were measured on 20 severely hypoxic and hypercapnic patients breathing air (A) and 100% O2 (HO). On HO, mean Paco2 increased to 56.6 torr from 50.8 torr on A, whereas there was no significant change in Paco2 (38.3 on A, 38.6 on HO), so that the arterial-alveolar gradient (aADCO2) increased from 12.5 to 18.0 torr. Peco2 remained essentially the same. There was a statistically significant correlation between the increase in Paco2 on HO and the arterial unsaturation (100 - Sao2) on A and also between Paco2 on A and its increment on HO. When the rise in Paco2 and aADCO2 were estimated which resulted from the shift in the Co2 dissociation curve due to complete oxygen-ation of hemoglobin on HO (Haldane effect), 78% of the observed change in Paco2 could be accounted for. The deadspace/tidal volume ratio (Vd/Vt) increased from 0.59 on A to 0.64 on HO and 87% of this difference could be attributed to the Haldane effect. The results emphasize the importance of considering this effect when interpreting alterations in Paco2, aADCO2 and Vd/Vt on transition from air to hyper-oxia, particularly in patients with severe hypoxemia and hypercapnia.

Validation of a two-compartment model of ventilation/perfusion distribution

Ventilation (V (A)) to perfusion (Q ) heterogeneity (V (A)/Q ) analyses by a two-compartment lung model (2C), utilizing routine gas exchange measurements and a computer solution to account for O(2) and CO(2) measurements, were compared with multiple inert gas elimination technique (MIGET) analyses and a multi-compartment (MC) model. The 2C and MC estimates of V (A)/Q mismatch were obtained in 10 healthy subjects, 43 patients having chronic obstructive pulmonary disease (COPD) and in 14 dog experiments where hemodynamics and acid-base status were manipulated with gas mixtures, fluid loading and tilt-table stressors. MIGET comparisons with 2C were made on 6 patients and 32 measurements in healthy subjects before and after exercise at normoxia and altitude hypoxia. Statistically significant correlations for logarithmic standard deviations of V (A)/Q distributions (SD(V (A)/Q )) were obtained for all 2C comparisons, with similar values between 2C and both other methods in the 1.1-1.5 range, compatible with mild to moderate COPD. 2C tended to overestimate MC and MIGET values at low and underestimate them at high SD(V (A)/Q ) values. SD(V (A)/Q ) weighted by Q agreed better with MC and MIGET estimates in the normal range, whereas SD(V (A)/Q ) weighted by V (A) was closer to MC at higher values because the V (A)-weighted SD(V (A)/Q ) is related to blood-to-gas PCO(2) differences that are elevated in disease, thereby allowing better discrimination. The 2C model accurately described functional V (A)/Q characteristics in 26 normal and bronchoconstricted dogs during non-steady state rebreathing and could be used to quantify the effect of reduced O(2) diffusing capacity in diseased lungs. These comparisons indicate that 2C adequately describes V (A)/Q mismatch and can be useful in clinical or experimental situations where other techniques are not feasible.

Effect of head-down tilt on brain water distribution.

Abstract Vascular and tissue fluid dynamics in the microgravity of space environments is commonly simulated by head-down tilt (HDT). Previous reports have indicated that intracranial pressure and extracranial vascular pressures increase during acute HDT and may cause cerebral edema. Tissue water changes within the cranium are detectable by T2 magnetic resonance imaging. We obtained T2 images of sagittal slices from five subjects while they were supine and during −13° HDT using a 1.5-Tesla whole-body magnet. The analysis of difference images demonstrated that HDT leads to a 21% reduction of T2 in the subarachnoid cerebrospinal fluid (CSF) compartment and a 11% reduction in the eyes, which implies a reduction of water content; no increase in T2 was observed in other brain regions that have been associated with cerebral edema. These findings suggest that water leaves the CSF and ocular compartments by exudation as a result of increased transmural pressure causing water to leave the cranium via the spinal CSF compartment or the venous circulation.

Effects of ischemic training on leg exercise endurance

This study tested whether ischemic exercise training (Tr(IS+EX)) would increase endurance of ischemic (Ex(IS)) and ramp exercise (Ex(RA)) knee-extension tests more than exercise training (Tr(EX)) alone. Ten healthy subjects performed pre- and posttraining tests with each leg. For Ex(RA), after subjects warmed up, a weight was added each minute until they were exhausted. Ex(IS) was similar, but after warm-up, we inflated a thigh cuff to 150 mmHg instead of adding weights. One leg was chosen for Tr(IS+EX) (cuff inflated to 150 mmHg during exercise) and the other for Tr(EX), both with a small weight on each leg, four to six times per daily session for 3 to 5 min each, 5 days per week for 6 weeks. Ex(IS) duration increased 120% more (p = 0.002) in the Tr(IS+EX) leg than in the contralateral Tr(EX) leg, whereas Ex(RA) duration increased only 16% (nonsignificant). Tr(IS+EX )and Tr(EX) significantly attenuated the ventilation increase (ergoreflex) during Ex(IS). TheO(2) debt for Ex(IS )was significantly lower and systolic blood pressure recovery was faster after Tr(IS+EX) than after Tr(EX). Heart rate recovery after Ex(RA )andEx(IS )was faster after Tr(IS+EX). Apparently, Tr(IS+EX) with low-intensity resistance increases exercise endurance and attenuates the ergoreflex and therefore may be a useful tool to increase regional muscle endurance to improve systemic exercise capacity in patients.

Acute effects of head-down tilt and hypoxia on modulators of fluid homeostasis

In an effort to understand the interaction between acute postural fluid shifts and hypoxia on hormonal regulation of fluid homeostasis, the authors measured the responses to head‐down tilt with and without acute exposure to normobaric hypoxia. Plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP), plasma aldosterone (ALD), and plasma renin activity (PRA) were measured in six healthy male volunteers who were exposed to a head‐down tilt protocol during normoxia and hypoxia. The tilt protocol consisted of a 17° head‐up phase (30 minutes), a 28° head‐down phase (1 hour), and a 17° head‐up recovery period (2 hours, with the last hour normoxic in both experiments). Altitude equivalent to 14,828 ft was simulated by having the subjects breathe an inspired gas mixture with 13.9% oxygen. The results indicate that the postural fluid redistribution associated with a 60‐minute head‐down tilt induces the release of ANP and cGMP during both hypoxia and normoxia. Hypoxia increased cGMP, cAMP, ALD, and PRA throughout the protocol and significantly potentiated the increase in cGMP during head‐down tilt. Hypoxia had no overall effect on the release of ANP, but appeared to attenuate the increase with head‐down tilt. This study describes the acute effects of hypoxia on the endocrine response during fluid redistribution and suggests that the magnitude, but not the direction, of these changes with posture is affected by hypoxia.