H. L. Olesen

MAXIMAL OXYGEN DEFICIT OF SPRINT AND MIDDLE DISTANCE RUNNERS

Anaerobic energy capacity was evaluated by maximal oxygen deficit (MOD) as well as by blood gas and muscle biopsy variables during short exhausting running in six recreational (RR) and eight competitive sprint and middle distance runners (SMDR). On 3 days runs to exhaustion were executed. Two runs were performed at a treadmill gradient of 15% at speeds which resulted in exhaustion after approximately 1 (R15%, 1min) and 2–3 min (R15%, 2–3min), respectively. On the 3rd day, the subjects ran with the treadmill at a gradient of 1% at a speed which caused exhaustion after 2–3 min (R1%, 2–3min). The runner performance was assessed from 400 m [RR, median 64.8 (range 62.2–69.6) s; SMDR, median 49.4 (range 48.5–52.0) s] and 800 m [RR, median 158.8 (range 153.3–170.2) s; SMDR, median 115.2 (range 113.3–123.3) s] track times. Muscle biopsies from gastrocnemius muscle were obtained before and immediately after R15%, 2–3min, from which muscle lactate and creatine phosphate (CP) concentrations, fibre type distribution, capillaries per fibre, total lactate dehydrogenase (LDH) activity and the LDH isoenzyme pattern were determined. The MOD increased with the treadmill gradient and duration. During both treadmill and track runs, SMDR performance was superior to that of RR, but no significant differences were observed with respect to MOD, muscle fibre type distribution, total LDH activity, its iso-enzyme pattern, changes in muscle lactate or CP concentrations. However, after treadmill runs, peak venous lactate concentration and partial pressures of carbon dioxide were higher, and pH lower in SMDR. Also the number of capillaries per muscle fibre and the maximal oxygen uptake were larger in SMDR. These findings would suggest that the superior performance of SMDR depended more on their aerobic than on their anaerobic capacity.

Digoxin affects potassium homeostasis during exercise in patients with heart failure

OBJECTIVE The aim was to evaluate whether digitalisation of heart failure patients affects extrarenal potassium handling during and following exercise, and to assess digoxin receptor occupancy in human skeletal muscle in vivo. METHODS In a paired study of before versus after digitalisation, 10 patients with congestive heart failure underwent identical exercise sessions consisting of three bouts of increasing work rates, 41-93 W, on a cycle ergometer. The final bouts were followed by exercise to exhaustion. The femoral vessels and brachial artery were catheterised. Arterial blood pressure, heart rate, leg blood flow, cardiac output, plasma potassium, haemoglobin, pH, and skeletal muscle receptor occupancy with digoxin in biopsies were determined. RESULTS Occupancy of skeletal muscle Na/K-ATPase with digoxin was 9% (P < 0.05). Following digitalisation femoral venous plasma potassium increased by 0.2-0.3 mmol.litre-1 (P < 0.05) at work rates of 69 W, 93 W, and at exhaustion, as well as during the first 3 min of recovery. Following digitalisation the femoral venoarterial difference in plasma potassium increased by 50-100% (P < 0.05) during exercise, and decreased by 66-75% (P < 0.05) during early recovery. Total loss of potassium from the leg increased by 138%. The effects of digitalisation on plasma potassium were not the outcome of changes in haemodynamics, because cardiac output and leg blood flow increased by up to 13% and 19% (P < 0.05), nor was it the outcome of changes in haemoconcentration or pH. CONCLUSIONS Extrarenal potassium handling is altered as a result of digoxin treatment. This is likely to reflect a reduced capacity of skeletal muscle Na/K-ATPase for active potassium uptake because of inhibition by digoxin, adding to the reduction of skeletal muscle Na/K-ATPase concentration induced by heart failure per se. In heart failure patients, improved haemodynamics induced by digoxin may, however, increase the capacity for physical conditioning. Thus the impairment of extrarenal potassium homeostasis by heart failure and digoxin treatment may be counterbalanced by training.

Naloxone-provoked vaso-vagal response to head-up tilt in men

A double-blind paired protocol was used to evaluate, in eight male volunteers, the effects of the endogenous opiate antagonist naloxone (NAL; 0.05 mg· kg−1) on cardiovascular responses to 50° head-up tilt-induced central hypovolaemia. Progressive central hypovolaemia was characterized by a phase of normotensive-tachycardia followed by an episode of hypotensive-bradycardia. The NAL shortened the former from 20 (8–40) to 5 (3–10) min (median and range; (P < 0.02). Control head-up tilt increased the means of thoracic electrical impedance [from 35.8 (SEM 2.1) to 40.0 (SEM 1.8) Ω; P < 0.01 of heart rate [HR; from 67 (SEM 5) to 96 (SEM 8) beats · min−1, P < 0.02], of total peripheral resistance [TPR; from 25.5 (SEM 3.2) to 50.4 (SEM 10.5)mmHg min 1−1,P < 0.05] and of mean arterial pressure [MAP; from 96 (SEM 2) to 101 (SEM 2)mmHg, P < 0.02]. Decreases were observed in stroke volume [from 65 (SEM 12) to 38 (SEM 9) ml, P < 0.01], in cardiac output [from 3.7 (SEM 0.7) to 2.5 (SEM 0.5) 1 · mint, P < 0.01], in pulse pressure [from 55 (SEM 4) to 37 (SEM 3)mmHg, P < 0.01] and in central venous oxygen saturation [from 73 (SEM 2) to 59 (SEM 4)%, P < 0.01]. During NAL, mean HR increased from 70 (SEM 3); n.s. compared to control) to only 86 (SEM 9) beats · min−1 (P < 0.02 compared to control) and MAP remained stable. The episode of hypotensive-bradycardia appeared as mean control HR decreased to 77 (SEM 7)beats · min−1, TPR to 31.4(SEM 7.7)mmHg · min · 1−1 and MAP to 60 (SEM 5)mmHg (P < 0.01), and the volunteers were tilted supine. Cardiovascular effects of naloxone on central hypovolaemia included a reduced elevation of HR and blood pressures and provocation of the episode of hypotensive-bradycardia.

Peripheral venous oxygen saturation during head-up tilt induced hypovolaemic shock in humans

We followed central, median cubital and dorsal metacarpal venous oxygen saturations (SvO2) during 50 degrees head-up tilt (anti-Trendelenburgs position) induced central hypovolaemia in eight males. Head-up tilt resulted in slight tachycardia of 101 (60-120) beats min-1 (median with range) and a stable mean arterial pressure (MAP) of 100 (88-114) mmHg. After 13 (6-23) min presyncopal symptoms appeared, accompanied by decreases in heart rate to 75 (51-97) beats min-1 and in MAP to 59 (49-76) mmHg (p < 0.01). Cardiac output decreased 0.9 (0.3-1.6) 1 min-1 while thoracic electrical impedance increased 3.4 (-1.2-5.9) Ohm (p < 0.01). Tilt-up decreased central venous pressure, but during sustained tilt it remained unchanged. Arterial oxygen saturation did not change. Head-up tilt decreased central SvO2 by 12 (5-24)% (p < 0.01). Median cubital SvO2 decreased 8 (-5-25)% (p < 0.02) during tilting, and it remained at this level during sustained tilt. Only five of eight samples from the dorsal metacarpal vein could be obtained. In these samples SvO2 was lowered by 15 (7-26)% (p = 0.01) at the onset of presyncopal symptoms. The results indicate that loss of central blood volume is reflected in central as well as peripheral SvO2. However, for reliable monitoring of blood volume changes, central SvO2 is the most useful variable, as this SvO2 changed consistently with the central blood volume, and blood samples could be obtained readily from the central venous catheter.

Influence of Naloxone on the cellular immune response to head-up tilt in humans

Abstract To evaluate a possible role for β-endorphin in the stress-induced modulation of natural killer (NK) cells, immunologically competent blood cells were followed in eight male volunteers administered either Naloxone or saline (control) during head-up tilt maintained until the appearance of presyncopal symptoms (PS). The PS appeared more rapidly with Naloxone compared to control [5.7 (SEM 1.1) vs 22.3 (SEM 5.1) min; P = 0.01]. The NK cell activity increased threefold during PS partly due to an increase in CD16+ and CD56+ NK cells in blood. In support, NK cell activity boosted with interferon-α and interleukin 2 rose in parallel with unboosted NK cell activity and NK cell concentration and activities returned to the baseline level after 105 min. The total lymphocyte count and the concentrations of CD3+, CD4+, CD8+, CD16+, and CD56+ cells increased during PS. Head-up tilt also induced an increase in plasma adrenaline concentration during control PS and a rise in plasma cortisol and adrenocorticotropic hormone concentrations up to 30 min thereafter, whereas no significant changes were found in plasma concentrations of noradrenaline, growth hormone, or β-endorphin. The results would indicate an influence of endorphin on the increase in plasma adrenaline concentration during head-up tilt and at the same time contra-indicate a significant role for adrenaline in the provocation of PS. The influence of head-up tilt on plasma β-endorphin was too small to influence the modulation of the cellular immune system.

Digoxin Induced Dysfunction of Skeletal Muscle Potassium Homeostasis During Exercise

Digitalization has been shown to cause an occupancy of 24–34% of the Na+/K+ATPase in human heart (22–24). Furthermore, it has been shown that the Na+/K+-ATPase concentration in human heart is reduced in dilated cardiomyopathy and heart failure (19,20). Such reductions in capacity for active Na+ and K+ transport may be a potential cause of local electrolyte derangement.

Digoxin Treatment and Congestive Heart Failure in Light of Human Cardiac and Skeletal Muscle Digitalis Glycoside Receptor Studies

Previous studies carried out on various in vitro systems (1,3,19) and experimental animals (2,18) have reported an increase in Na+/K+-ATPase as a result of cardiac glycoside exposure, as have studies performed on human peripheral blood cells (4,11). This has engendered speculation about development of tolerance to the inotropic effect of cardiac glycoside treatment: The idea being that inhibition of Na+/K+-ATPase obtained initially by digitalization would be counterbalanced by Na+/K+-ATPase upregulation. However, points of concern may be raised with regard to the methodology of the underlying studies for this hypothesis: 1) The concentrations of cardiac glycoside applied to cell cultures were in micromolar concentration, i.e. toxic to humans 2) In vitro systems, peripheral blood cells and results obtained by digitalization of normal guinea pigs or rats need not mirror the effect of digitalis treatment on human cardiac and skeletal muscle in heart failure. 3) Activity measurements performed on purified membrane fractions may not be applicable for studying quantitative aspects of Na+/K+-ATPase in muscle tissue (5). On this background it was our aim to evaluate the hypothesis that cardiac glycoside treatment increases digitalis receptors by performing appropriate measurements on the tissue of relevance, i.e. cardiac and skeletal muscle from patients with heart failure. In addition we wished to assess the distribution of specifically bound digoxin to human muscular tissue during digitalization.