Role of The CO 2 System in Regulating Intramuscular Hydrogen Ion Concentration during Exercise in Horses

Elimination of CO 2 from skeletal muscle ( mCO 2 ) during exercise is important for the regulation of intramuscular [ H + ] ([m H + ]). Carbonic anhydrase ( CA ) catalyses the hydration/dehydration reaction of CO 2 to facilitate its elimination. We hypothesised that extracellular CA inhibition and subsequent increase in PCO 2 will result in increased m[ H + ] and decreased exercise performance. Methods Six horses were exercised on a treadmill until fatigue without (Con) and with acetazolamide ( CA inhibitor) treatment (Acz; 30 mg/kg, 30 min before exercise). Arterial and mixed‐venous blood was sampled, and biopsies collected from gluteal muscles at fatigue. Whole blood (wb) arteriovenous difference across the muscle (a‐v) of [ N a + ], [ K + ], [ C l − ], [ Lac − ], [ SID ], and PCO 2 , mCO 2 and m[ H + ] were determined. Paired t‐test was used to assess statistical significance (P<0.05). Results Duration of exercise to fatigue was not affected by Acz. Compared to Con, Acz increased mCO 2 (Con 16.5(mean) ± 3.6( SE ), Acz 20.5 ± 2 mmol/L) and mixed‐venous and arterial PCO 2 but had no effect on VCO 2 . No difference was observed in m[ H + ] between Con (118 ± 18 nmol/L) and Acz (99 ± 16 nmol/L). Acetazolamide did not affect plasma [ H + ]. Based on the a‐v differences Acz increased [ N a + ]wb and [ K + ]wb release, increased [ C l ‐ ]wb uptake and did not affect [Lac ‐ ]wb release by the muscle. Acz decreased a‐v[ SID ]wb (Con 6.2 ± 2.8 mmol/L, Acz −0.3 ± 2 mmol/L). Conclusions Although PCO 2 and mCO 2 were elevated no difference in [m H + ] was observed. An increase in m[ H + ] due to elevated mCO 2 was attenuated by strong ion fluxes between intramuscular and vascular spaces. Strong ion exchanges are important in attenuating m[ H + ] and maintaining exercise performance. Ethical Animal Research The study protocols were approved by the A nimal Care C ommittee of the U niversity of G uelph according to the Guide to the Care and U se of Experimental Animals ( C anadian C ouncil on A nimal Care, O ttawa, O ntario). Sources of funding:  Ontario Ministry of Agriculture and Food ‐ Equine Program, Department of C linical Studies at the U niversity of G uelph, Canadian Institutes of H ealth R esearch and the S lovenian R esearch Agency grant P4‐0053. Competing interests:  none.