A modelling approach to disentangle the factors limiting muscle oxygenation in smokers

Abstract

AbstractCigarette smoking is associated with a lower exercise capacity and lower muscle fatigue resistance. This is at least partly attributable to carboxyhaemoglobin (HbCO) in the blood that via reduction in the oxygen-carrying capacity, and the left-shift of the Hb-dissociation curve would reduce tissue oxygenation. On the other hand, a reduced oxygen uptake due to mitochondrial dysfunction would result in improved oxygenation. We used previously collected capillarisation, myoglobin and estimated cellular maximal muscle oxygen consumption data derived from succinate dehydrogenase-stained sections from the vastus lateralis muscle from six smokers and five non-smokers. These data were fed into an expanded Krogh tissue oxygenation model to assess whether an impaired muscle fatigue resistance in smokers is primarily due to HbCO or impaired mitochondrial respiration. The model showed that in smokers with 6% and 20% HbCO (causing a left-shift of the Hb-dissociation curve) average muscle oxygenation was reduced by 1.9% and 7.2%, respectively. Muscle oxygenation was increased by 13.3% when maximal mitochondrial respiration was reduced by 29%. A combination of a 29% reduction in maximal mitochondrial respiration and 20% HbCO led to no significant difference in muscle oxygenation from that in non-smokers. This indicates that while HbCO may explain the reduced exercise capacity after just one smoking session, in chronic smokers impaired mitochondrial respiration appears more important in reducing oxygen extraction and exercise capacity with only a small contribution of the left-shift of the Hb-dissociation curve.