alkalosis and digoxin effects on plasma potassium

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Mar 30, 2012 - is consistent with the lack of DIG effect on K+ homeostasis during exercise, which ... values of work ethic, tenacity, integrity, commitment and fighting spirit ...... 1; and increased mean arterial pressure from 83 to 92 mmHg. .... were to determine the influence of exercise and alkalosis on K+, ionic, acid-base,.
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ALKALOSIS AND DIGOXIN EFFECTS ON PLASMA POTASSIUM, IONIC HOMEOSTASIS AND EXERCISE PERFORMANCE IN HEALTHY HUMANS

Submitted by Simon M. Sostaric B.App.Sc

This thesis is submitted in fulfillment of the requirements of the degree of Doctor of Philosophy Supervisor: Professor Michael J. McKenna

Muscle, Ions & Exercise Group Institute of Sport, Exercise & Active Living School of Sport & Exercise Science Faculty of Arts, Education & Human Development Victoria University, Melbourne, Australia

March 2012

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ABSTRACT Muscle contractions induce cellular potassium (K+) efflux which may contribute to impaired muscle cell membrane excitability and fatigue. The magnitude of K+ changes are dependent on the size of contracting muscle mass, duration and intensity of exercise, and health and fitness status of participants. Activation of the sarcolemmal and t-tubular bound sodium-potassium adenosine 5’ triphosphatase enzyme (Na+,K+ATPase, NKA) mediates muscle cell K+ and Na+ active exchange, and is instrumental in the maintenance of muscle cellular and plasma K+ homeostasis during exercise. Therefore modulations of NKA function might enhance or impair exercise induced K+ disturbances, and theoretically can have a profound effect on muscle excitability and exercise performance. This thesis examined the effects of two interventions designed to induce acute or short term upregulation and downregulation of NKA activity on K+ homeostasis and exercise performance in healthy humans. Study 1 investigated the effects of metabolically induced alkalosis on plasma K+ regulation during submaximal finger flexion (small muscle mass) contractions and fatigue in healthy humans. Study 2 investigated the effects of a clinically relevant dose of digoxin administration on K+ regulation, during intermittent supramaximal finger flexion contractions (small muscle mass) and fatigue in healthy humans. Study 3 investigated the effects of digoxin on K+ regulation during progressive increasing intensity submaximal leg cycling exercise (large muscle mass) and fatigue in the same healthy participants as in study 2. A secondary focus of this thesis was to examine the ionic, metabolic and acid-base disturbances during small and large muscle mass exercise and in recovery. This included the regulatory role of NKA in active (study 1 and 2) and inactive tissue (study 3), during small (study 1 and 2) and large (study 3) muscle mass exercise. Study 1 Alkalosis enhances human exercise performance, and reduces K+ loss in contracting rat muscle. We investigated alkalosis effects on K+ regulation, ionic regulation and fatigue during intense exercise in nine untrained volunteers. Concentric finger flexions were conducted at 75% peak workrate (~3 W) until fatigue, under alkalosis (ALK, NaHCO3, 0.3g.kg-1) and control (CON, CaCO3) conditions, 1 month apart in a randomised, double-blind, crossover design. Deep antecubital venous (v) and radial arterial (a) blood was drawn at rest, during exercise and recovery, to determine arteriovenous differences for electrolytes, fluid shifts, acid-base and gas exchange. Finger flexion exercise barely perturbed arterial plasma ions and acid-base status, but induced marked arterio-venous changes. ALK elevated [HCO3-] and PCO2, and lowered [H+] (P