Circulatory adaptation to high altitude.
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Biomedical subjects
Publications and source records attributed to R F Grover.
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The highly reactive pulmonary vascular bed of the neonatal calf was utilized to determine whether the hypoxic pulmonary pressor response is modified by alpha-adrenergic blockade with phenoxybenzamine (Group A) or by tissue catecholamine depletion with reserpine (Group B). In addition, in Group A, the effects of hypoxia on the pulmonary circulation were compared and contrasted with those of l-norepinephrine (alpha-receptor stimulator) and isoproterenol (beta-receptor stimulator). In Group A, changes in pulmonary vascular resistance were calculated from measurements of appropriate pressures and of pulmonary blood flow (electromagnetic flowmeter). The increase in pulmonary vascular resistance produced by hypoxia was not diminished by alpha-adrenergic blockade. However, blockade abolished the pulmonary vasoconstrictor effect of norepinephrine. During hypoxic pulmonary vasoconstriction, the administration of either norepinephrine or isoproterenol lowered the pulmonary vascular resistance both before and after alpha-blockade. While this may be a true vasodepressor effect of these drugs it may also reflect passive changes in the pulmonary vessels secondary to an increased pulmonary blood flow.THE PULMONARY VASCULAR RESPONSE TO HYPOXIA IN THE RESERPINIZED CALVES (GROUP B) WAS TESTED UNDER THREE CIRCUMSTANCES: (1) in the awake animal, (2) in the anesthetized animal prepared in the same way as those in Group A, and (3) during constant flow perfusion of the left lower lobe pulmonary artery. From these studies it was concluded that tissue catecholamine depletion did not diminish the pulmonary vascular response to hypoxia.Thus, neither alpha-adrenergic blockade nor tissue catecholamine depletion prevents the hypoxic pulmonary pressor response. Furthermore, alpha-blockade prevents the pulmonary vasoconstrictor response to norepinephrine but not to hypoxia. Therefore it is concluded that hypoxic pulmonary vasoconstriction is not mediated through adrenergic receptor stimulation or release of endogenous catecholamines.
The normal relationship between red cell mass measured, with (51)chromium-labeled red cells, and arterial oxygen saturation (Sa(O2)) over the range from 97.3 to 83.4% was examined by studying 73 normal men residing at sea level and altitudes of 1600 and 3100 m. A simple, linear relationship between Sa(O2) and red cell mass was found over the entire range (r = - 0.7524, P < 0.001). In contrast, a correlation between red cell mass and arterial O(2) tension was found only over the lower half of the range of O(2) tensions where Sa(O2) was also decreased (r = - 0.7731, P < 0.005). This suggested that O(2) saturation rather than tension is the more important determinant of the erythropoietic response to chronic hypoxia. If this response is regulated by tissue O(2) tension, then it will be influenced by O(2) transport, which, in turn, is a function of blood flow and arterial O(2) content, and hence Sa(O2). In nine patients with chronic obstructive airway disease the relationship between red cell mass and Sa(O2) was also determined and was found to be steeper than in the normal subjects (P < 0.05).
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We have investigated the effects of chronic oral administration of two anorectic substances, fenfluramine and aminorex, especially on the pulmonary circulation in young pigs with one ligated pulmonary artery. The pulmonary vascular reactivity was tested by alveolar hypoxia, alveolar hyperoxia and infusion of prostaglandin F2ALPHA. No elevation of pulmonary arterial pressures or resistances were found due to the intake of fenfluramine or aminorex over a three month period. The responses to the vasoconstrictor stimuli, hypoxia and prostaglandin F2alpha, and to the vasodilator stimulus, hyperoxia, were equal and not augmented in the drug groups. Fenfluramine or aminorex could therefore could therefore not be shown to have an adverse effect on the pulmonary circulation or on the reactivity of the pulmonary vascular bed in the pig, but fenfluramine elevated systemic arterial pressure.
Methods of creating experimental complete heart block developed since 1883 are reviewed in detail. The three most commonly used techniques at present are: (I) Thoracotomy, atriotomy and ligation of the A-V bundle. (II) Thoracotomy and injection of a chemical into the A-V node or bundle. (III) Injection of a chemical through a transvenous catheter into the node or bundle. The results in different species, complications, and variations in procedure are discussed. The bibliography provides a comprehensive index of work performed in animals with experimental complete heart block. We produced complete heart block in sixteen pigs but subsequently eleven died during Stokes-Adams attacks. Pigs have not been used previously as models of heart block for experimental purposes and prophylactic pacing appears mandatory in this species.