Uridine as a protector against hypoxia-induced lung injury.

The effect of the activation of the mitochondrial ATP-dependent potassium channel (mitoKATP) on the ultrastructure of rat lung in acute hypoxic hypoxia (7% of oxygen in nitrogen, exposure 30 min) was studied. It was shown that uridine, a precursor of the mitoKATP activator UDP, exerted a protective effect against hypoxic damage to the lung. The administration of uridine to animals prior to hypoxia decreased the number of mitochondria with altered ultrastructure and prevented the hypoxia-induced mitochondrial swelling. Uridine also protected the epithelial, interstitial and endothelial layers of the air-blood barrier from the hypoxia-induced hyperhydration. The protective action of uridine against hypoxia-induced lung injury was eliminated by the selective blocker of mitoKATP 5-hydroxydecanoate. These data suggest that one of the mechanisms of the positive effect of uridine is related to the activation of the mitoKATP channel, which, according to the literature and our data, is involved in the protection of tissues from hypoxia and leads to adaptation to it. A possible role of uridine in the maintenance of the mitochondrial structure upon hypoxia-induced lung injury and the optimization of oxygen supply of the organism is discussed.

Computer modeling of relationship between critical PvO2, VO2max and blood supply of skeletal muscle at working with a right-shifted blood O2 dissociation curve.

Investigations were performed on a computer model of O2 delivery and O2 consumption in the one working muscle. At working with increasing power and achieving the critical value of VO2 (VO2crit), the muscle VO2 began to lag behind the oxygen demand qO2. The model permits to find critical pO2 in effluent venous blood Pvcrit at VO2crit as well as to calculate VO2max and PvO2 at VO2max under exercise with changing muscle blood flow F and blood pH.Pvcrit was computed from the condition VO2crit = 0.9qO2, and VO2max- from the condition (dVO2/dqO2) = 0.1. VO2max, Pv at VO2max, Pvcrit, and VO2crit were calculated for: 40 < or = F < or = 120 ml/min/100 g; 6.8 < or = pH < or = 7.4. It was shown that the faster is F and the lesser is blood pH, the greater were the Pvcrit and VO2max values. With decreasing F and blood pH, the influence of F on Pvcrit and VO2max increases, whereas the influence of blood pH on these values decreases. With increasing F and, hence, an increasing VO2max, the blood supply efficiency decreases due to the important limiting factor--tissue oxygen diffusion.

Oxygen transport to skeletal muscle working at VO(2)max in acute hypoxia: theoretical predictions.

The influence of acute hypoxia (30 < or = PaO(2) < or = 100 mmHg) on the values of VO(2)max and parameters of oxygen transport in muscle working at VO(2)max was studied. We investigated muscle working under different values of blood flow F (60 < or = F < or = 120 ml/min per 100 g), blood pH (7.0-7.6), and different diffusion conditions. Investigations were performed on a computer model of O(2) delivery to and O(2) consumption in the working muscle. VO(2)max, PvO(2), pO(2)- and VO(2)-distribution in muscle fiber were calculated. It was shown that the greater the degree of arterial hypoxemia, the lower the muscle VO(2)max and blood pO(2) values. When working at VO(2)max, the average and minimal values of tissue pO(2) depend on PaO(2). The greater the blood flow through muscle, the greater the VO(2)max. However, with an increasing degree of arterial hypoxemia, the effect of F and blood pH on the value of VO(2)max is weakened. The diffusion conditions produced a powerful influence on the VO(2)max value. At reduced PaO(2) they are the most important limiting factors of O(2) supply to muscle working at maximal effort.