R. Viswanathan

Further Studies on Pulmonary Oedema of High Altitude

101 Indian soldiers, 57 of whom had developed pulmonary oedema of high altitude (POHA) and 44 who had not developed this condition in spite of being at high altitudes for over 2 years, were investigated for observing the differences, if any, in their reaction to acute hypoxic stress. Each subject was made to breathe a 10% hypoxic mixture for 5 min. Haemodynamic parameters like pulmonary artery pressure (systolic, diastolic and mean), brachial artery pressure, wedge pressure, cardiac output, minute ventilation, arterial oxygen saturation and oxygen uptake before and at the end of hypoxic breathing were estimated. In addition, results of the cold pressor test were recorded and the Vd/Vt ratio was estimated. The results obtained in the present study confirmed those obtained in our previous studies. In addition, it was observed that oxygen uptake was significantly higher and oxygen saturation lower ofter hypoxia in the POHA subjects than in the controls. Certain parameters for screening of subjects possibly susceptible to POHA have been suggested.

Effect of hypoxia on regional lung perfusion, by scanning.

Lung scanning was performed in 12 subjects who had pulmonary oedema of high altitude (POHA) before, and in 8 men who had been at high altitude without developing pulmonary oedema. Scanning done before and after 5 min 10% O2 breathing showed (a) increased perfusion in POHA subjects after hypoxia, (b) more in the lower than in upper zones, and (c) striking increase in perfusion in localised areas. In controls, however, there was significant reduction in perfusion after hypoxia in most areas. The reduction was less marked in the lower zones than in the upper zones. POHA subjects were hyperreactors to hypoxia, compared to controls. It is concluded that scanning before and after hypoxic breathing might help in differentiating hyperreactors.

Pyridine nucleotides in lung and liver of hypoxic rats

Abstract Adult male albino rats of Wistar strain in the weight range of 170–200 g were exposed to acute hypobaric hypoxia of 25,000 ft at 32°C for 90, 180, 270 and 360 min. respectively. The extramitochondrial dehydrogenases generating NADPH and the mitochondrial dehydrogenases generating NADH were studied in lung and liver. The oxidized and the reduced forms of these two nucleotides were determined at 90 min. and 360 min. of hypoxia. Hypoxia caused an initial decline in the activities of all the dehydrogenases studied. The activities of mitochondrial and pentose phosphate dehydrogenases of liver were high at 360 min. of hypoxia whereas the activities of extramitochondrial dehydrogenases of lung were generally low at all levels of hypoxic exposure. The NADPH levels of hypoxic rat lung were correspondingly low. However, the activities of liver mitochondrial dehydrogenases were elevated at 360 min. of hypoxia in spite of NADH accumulation in hypoxic rat liver. A decreased NAD/NADH ratio was observed in lung at 90 min. and 360 min. of hypoxia.

Plasma Histamine Levels Under Hypoxic Stress

Our object was to see whether the action of hypoxia on pulmonary blood vessels is due to release of a mediator like Mstamine. 30 male subjects in the age group 20–30 years were selected for this study

Effect of Furosemide on Altitude Tolerance in Experimental Animals

Furosemide which is claimed to prevent acute mountain sickness and pulmonary oedema of high altitude was tried in experimental animals to evaluate its usefulness or otherwise as a measure of prophylaxis. 90 mice, 128 rats and 44 guinea pigs--all males--were used for the studies. Half the number in each species were kept as controls. The remaining half were further divided into two batches. The first batch was given furosemide 10 mg/kg body weight. Two h later they were exposed to simulated altitude of 30,000 ft for 6 h. The second batch was given two injections of furosemide at intervals of 24 h before exposure to simulated altitude. The controls were given distilled water. Our results show that the death rate was more in the furosemide-treated groups, both under mild as well as severe dehydration in all species. The present study does not substantiate the claim than the drug can be used as prophylactic against acute mountain sickness and pulmonary oedema of high altitude.

Pulmonary Vascular Response to Ventilation Hypercapnia in Man

The effect of ventilation hypercapnia on pulmonary circulation in man was investigated through separate studies. In the first study on 44 patients with little or no airway obstruction and 20 normal men, 5% CO2 breathing produced (a) significant rise in pulmonary artery pressure (PAP), (b) no significant change in cardiac output, (c) rise in pulmonary vascular resistance, (d) rise in brachial artery pressure (BAP) and (e) no change in wedge pressure (WP). The rise in PAP was more pronounced after 2 min of 10% CO2 breathing in 12 bronchitics. The scond study was carried out in 39 bronchitics and 22 normals while breathing 10% CO2 for 1 min and showed that pulmonary vascular response was independent of systemic vascular response, in that BAP rose later and came back earlier to original level during CO2 breathing. In the third study on 26 severe bronchitics and 15 normals the observed rise in PAP during 10% CO2 breathing was independent of H-ion concentration in the blood since PAP continued to rise even when pH was maintained at air breathing level by intravenous injection of 130 mEq of sodium bicarbonate in 250 cm3 of 5% glucose solution. This study also confirmed the findings in the first study that there was minimal rise in cardiac output, no rise in WP, while PAP and pulmonary vascular resistance rose significantly during ventilation hypercapnia. The responses were pronounced compared with those observed in the first study with 5% CO2. It is postulated that the responses might be due to direct action of CO2 on muscular pulmonary arteries.

Fatty Acid Metabolism in Hypoxic Rat Liver

Fatty acid metabolism was investigated in adult male albino rats exposed to hypobaric hypoxia at 25,000 ft simulated altitude for 6 h at 32 degrees C. Oxidation and esterification of palmitic acid-1-14C and de novo lipogenesis from acetate-1-14C were studied. Palmitic acid-1-14C oxidation in liver slices was normal while acetoacetate formation was increased. In vivo esterification of palmitic acid-1-14C to form triglycerides was increased while formation of phosphatidylcholine and phosphatidylethanolamine was observed to decrease. Decreased incorporation into plasma phosphatidylcholine with unaltered total activity in plasma triglycerides was observed. The incorporation of acetate-1-14C was observed to remain unaltered in triglycerides and phospholipids of liver with a similar pattern in the plasma indicating unaltered de novo lipogenesis. There appears to be increased esterification of fatty acids with probably impaired release of triglycerides into plasma while fatty acid biosynthesis remains unaffected.

Effect of Acute Hypobaric Hypoxia on Fatty Acid Metabolism in Rat Lung

Exposure of male albino rats in the weight range of 70-200 g to 25,000 ft of simulated altitude for 6 h at 32 degrees C caused an increase in plasma free fatty acids with decreased oxidation of palmitic acid-1-14C in lung slices of hypoxic rats. The in vivo esterification of palmitic acid-1-14C to form truglycerides, phosphatidylcholine and phosphatidylethanolamine was also low indicating decreased utilization of fatty acids by hypoxic lungs. De novo lipogenesis was observed to decreased to decrease because of decreased fatty acid biosynthesis as judged from acetate---14C incorporation. The specific activities of triglycerides, phosphatidylcholine and free cholesterol were also decreased. The decreased incorporation into phosphatidylcholine affected the incorporation into phosphatidylcholine of alveolar surfactant (2,000 g sediment fraction). The results are discussed in view of possible decreased energy status of hypoxic lungs.

Effect of Acute Hypoxia on Blood Serotonin in Human Beings and Rats

The object of this study was to see if the blood level of 5-hydroxytryptamine (5-HT) increased under acute hypoxic stress in human beings and rats. Soldiers who had been stationed at high altititudes 2-7 months prior to study were selected. 17 had suffered from pulmonary oedema and the remaining eight, who had not developed the condition, acted as controls. The technique of YUWILER [18] with suitable modifications was used for estimation of 5-HT. No significant change in 5-HT levels was observed either in subjects or controls. Rats exposed to simulated high altitude for 6 h also did not show any significant change in blood 5-HT levels.

Effect of 7% CO2 Breathing on Muscular Pulmonary Arteries and on the Right Ventricle in Rats

The object of the present study was to observe the effect of 7%» CO2 breathing on pulmonary vasculature and on the right of ventricle. Two batches of twelve rats were giv-en interrupted exp