Experimental myocardial infarction in rats acclimated to simulated high altitude.

In rats exposed to a simulated high altitude of 3500 m or 6000 m for 6--7 weeks, myocardial necrosis was produced by ligation of the left coronary artery close to its origin, by ligation of the descending branch of the left coronary artery (true infarcts), or by administration of a large dose of isoprenaline. The same was done in control sea-level animals. The extent of the necrosis 24 hours after its induction was estimated from the activity of creatine phosphokinase in the tissue of the left ventricle and, in rats continuously exposed to 6000 m, also by measuring the surface of necrosis marked histochemically with phosphorylase activity in histological slides. In rats continuously exposed to 3500 m the extent of the isoprenaline-induced necrosis was smaller than in the controls, but there was no difference in true infarction. In rats intermittently exposed to 6000 m, no difference in the extent of any type of experimental necrosis was found when compared with sea-level rats. In rats continuously exposed to 6000 m, the extent of all types of experimental necrosis was smaller than in control animals. In histological sections of hearts with true infarctions it was possible to distinguish between the intact tissue, a zone of total necrosis and a zone of partial necrosis. Whether the main trunk or the descending branch of the left coronary artery was ligated, the extent of the zone of total necrosis in rats continuously exposed to 6000 m was smaller, the zone of partial necrosis was larger only in rats with a ligature of the trunk, and the extent of intact myocardium was not different when compared with control sea-level animals with the same type of myocardial infarction.

Coronary blood flow in rats native to simulated high altitude and in rats exposed to it later in life.

In rats exposed to a simulated high altitude of 3500 m for their whole prenatal and postnatal life a severe cardiac hypertrophy develops. In rats born and first staying 5 weeks at sea level and then being exposed to simulated high altitude, only a unilateral right cardiac hypertrophy occurs. In both groups nutritional coronary blood flow was estimated in left ventricle, right ventricle, and septum and was compared with control animals of similar age. Coronary blood flow was measured at hypoxia in all groups. At first cardiac output was determined by the Fick principle, then 86Rb was applied and the animals were killed after 55 sec. Activity of 86Rb was measured in both cardiac ventricles and septum and the fractional uptake was calculated. According to Sapirstein (1956, 1958) the distribution of 86-RB follows the distribution of cardiac output and from both these data the nutritional blood flow to the parts of the heart may be estimated. Cardiac output was similar in rats exposed to simulated high altitude later in life ('newcomers') and in control animals, but it was significantly lower in rats born in the low pressure chamber ('natives'). Fractions of cardiac output supplying cardiac ventricles and septum in rats from both hypoxic groups were significantly higher than in control animals. In the 'natives' they were significantly higher than in the 'newcomers'. The fractions of cardiac output in both 'newcomers' and 'natives' remained significantly higher than those of the control animals, also when calculated per gram of heart tissue. Nutritional coronary blood flow (in ml/min) was higher in both ventricles and septum of the 'newcomers' and in the right ventricle of the 'natives', and lower in the septum of the 'natives', when compared with control animals. Coronary blood flow per gram of heart tissue (in ml/min.g) was significantly higher in all cardiac parts of the 'newcomers', but it was about the same in all cardiac parts of the 'natives' when compared with controls. The importance of observed changes concerning myocardial tissue oxygenation is analyzed by using Krogh's cylindrical tissue model.