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Biomedical subjects

R F Grover

Publications and source records attributed to R F Grover.

At least 55 records · Page 3Linked to original sources
PubMed1978

Decreased pulmonary vascular responses in dogs with increased pulmonary blood flow.

We wished to determine whether high pulmonary blood flow alters the pulmonary vascular responses to the vasoconstrictors, hypoxia and prostaglandin F2alpha (PGF2alpha). Acute or chronic left pulmonary artery (PA) occlusion was performed in dogs in order to create high pulmonary blood flow conditions. Right lung pulmonary vascular resistance (PVR) during normoxia was reduced by both acute and chronic left PA occlusion, suggesting passive vasodilatation. Increases in right lung PVR induced by hypoxia (10--15% O2) and PGF2alpha (0.8-4 microgram kg-1 min-1) were attenuated both in acute and chronic left PA occluded dogs. Since the reductions in responsiveness were similar with acute and chronic increases in blood flow, the attenuating effect of high blood flow was not dependent upon morphologic changes in the vasculature. Pulmonary vascular responsiveness was probably reduced in these animals due to their dilated pulmonary vascular beds, consequent to the increased blood flow, thereby decreasing the effectiveness of smooth muscle contraction.

Animals↗
PubMed1978

Potentiation of hypoxic pulmonary vasoconstriction by ethyl alcohol in dogs.

Pulmonary and systemic hemodynamics and arterial blood gases were measured in anesthetized and mechanically ventilated dogs before and after oral or intravenous administration of ethanol. Increases in mean pulmonary artery pressure and pulmonary vascular resistance occurred. Platelet antiserum-induced thrombocytopenia inhibition of prostaglandin synthesis with meclofenamate, or alpha-adrenergic blockade did not alter the pulmonary pressor response to ethanol. However, the increase in resistance following ethanol was abolished by hyperoxia and potentiated by hypoxia. Thus, it appears that the effect of ethanol is to augment hypoxic pulmonary vasoconstriction, whereas ethanol per se has no independent pulmonary pressor activity.

Administration, Oral↗
PubMed1978

Cold-induced pulmonary hypertension in cattle.

The frequency with which cattle develop right-heart failure during the winter at high altitude suggested that cold might contribute to hypoxic pulmonary hypertension. Indeed in a preliminary study conducted out-of-doors during early Spring, two calves with known hyperreactive pulmonary vessels showed elevated pulmonary arterial pressures attributed to their prior exposure to nighttime cold (-5 degrees C). In a second study five hyperreactive calves had increases in mean pulmonary arterial pressure from 29 to 45 Torr (+ 55%) during 48 h of exposure to cold (0 to -5 degrees C) in a climatic chamber. Three calves with less reactive lung vessels increased their pressures from 25 to 36 Torr (+ 44%). In a more complete study, six calves selected as potential hyperresponders showed increases in pulmonary arterial pressure (+ 60%), blood flow (+ 18%), and vascular resistance (+ 38%) during 48 h of cold exposure. Arterial PO2 decreased (-10 Torr) and PCO2 rose (+6 Torr) suggesting hypoventilation. Oxygen breathing returned pulmonary pressures and resistance to near control values, suggesting that cold had induced a hypoxic pulmonary vasoconstriction and an increased blood flow. Thus, a cold produced pulmonary hypertension in cattle at the modest altitude of 1,524 m and the pressor responses were greater in calves with more reactive lung vessels.

Altitude↗
PubMed1978

Exercise ventilation correlates positively with ventilatory chemoresponsiveness.

To determine the relationship of ventilatory responsiveness to hypoxia and hypercapnia to exercise hyperpnea, these responses and steady-state exercise ventilation (VE) were measured in 16 athletes during light (1/3 VO2 max) and heavy (2/3 VO2 max) exercise. Both the hypoxic and hypercapnic ventilatory responses correlated positively with VE per unit metabolic rate (VE/VCO2) at both exercise levels (P less than 0.05). The contribution of the hypoxic response to normoxic exercise VE was quantified by comparing VE in normoxia to VE during a brief (1 min) exposure to high O2 (PAO2 = 200 Torr). High O2 reduced normoxic exercise VE by a mean of 20% at either exercise intensity. Among individuals this reduction was directly dependent upon the intensity of the hypoxic response, and ranged from 7 to 42% of normoxic VE. After the variable reduction of normoxic VE by hyperoxia, all correlations of ventilatory response with exercise VE were lost except for the correlation of hypercapnic response with heavy exercise VE/VCO2. These findings indicate that the extent of VE in light or heavy exercise is modified by the strength of the hypoxic ventilatory response, and that the hypercapnic response independently correlates with VE during heavy exercise.

Adult↗
PubMed1978

Diagnosis of airflow obstruction at high altitude.

Using predicted sea level values for spirometry done at high altitude, underestimation of airway obstruction may result. We therefore established spirometric normal values for an altitude of 3,100 m for white men.

Adolescent↗
PubMed1978

Excessive polycythemia of high altitude: role of ventilatory drive and lung disease.

Persons residing at high altitude who develop excessive polycythemia are more hypoxemic than normal high-altitude residents. We investigated the causes of hypoxemia in 20 patients with excessive polycythemia residing at an altitude of 3,100 m. Lung disease evidenced by abnormal spirometric features and results of a respiratory questionnaire was present in 10 of 20 patients and resulted in increased alveolar-arterial difference for PO2 [(A-a)PO2]. The excessive hypoxemia in the patients with normal lungs was not due to increased (A-a)PO2. We measured ventilatory responses to hypoxia and to hypercapnia to determine whether blunting of these responses was a cause of this excessive hypoxemia. We found, however, that chemical drives to breathe, although blunted, were the same in patients with polycythemia as in high-altitude control subjects. However, an abnormal breathing pattern was observed; the polycythemic patients had a smaller tidal volume and a greater ratio of dead space to tidal volume than did the normal subjects. In addition, the polycythemic patients had increased minute ventilation on breathing 100 percent O2, whereas the normal subjects did not. Thus, hypoxic depression of ventilation may have been present. Our findings suggested that blunted chemical drives are not causative in this disease, and that some other cause of hypoxemia must be present.

Altitude↗
PubMed1978

Pulmonary vascular effects of endotoxin in leukopenic dogs.

We have demonstrated previously that in the dog, small doses of endotoxin abolish the pulmonary vasoconstrictor reponse to hypoxia, apparently by stimulating the production of a vasodilator prostaglandin. We previously ruled out platelets as mediators of this endotoxin effect. To evaluate leukocytes as possible mediators, we rendered dogs leukopenic by means of a leukocyte antiserum. However, this did not modify the inhibitory effect of endotoxin on hypoxic pulmonary vasoconstriction. Hence, neither leukocytes nor platelets appear to mediate the endotoxin effect. In the near absence of both platelets and leukocytes, the endotoxin effect can be prevented by inhibiting prostaglandin synthesis with meclofenamate. This suggests that endotoxin prevents hypoxic pulmonary vasoconstriction by acting on the systemic circulation or on the lung (possibly directly on the pulmonary blood vessels) to stimulate the production of a vasodilator prostaglandin.

Animals↗
PubMed1978

Platelet-mediated pulmonary hypertension and hypoxia during pulmonary microembolism: reduction by platelet inhibition.

The literature indicates that vasoactive substances released from platelets contribute to the pulmonary pressor response and hypoxemia during pulmonary microembolism. Hence, removal of the platelets or inhibition of their function should reduce these effects. The purpose of this study was, therefore, to investigate the pulmonary effects of experimental embolism with glass beads in dogs rendered thrombocytopenic with platelet antiserum and to compare these effects to the effects in dogs pretreated with sulfinpyrazone (Anturane) or heparin, both substances that affect the function of platelets, probably by inhibiting the release of platelets. In all three groups the pulmonary hypertension was reduced by more than half, and hypoxemia was lessened or abolished. The results of this study indicate the platelets contribute to the effects of pulmonary microembolism and that administration of sulfinpyrazone or heparin reduces the embolism-induced pulmonary hypertension to the same extent as the depletion of platelets. Platelet-inhibiting drugs might therefore be useful prophylactically in human pulmonary microembolism.

Animals↗
PubMed1977

Reduction of bovine pulmonary hypertension by normoxia, verapamil and hexoprenaline.

In calves with hypoxic pulmonary hypertension, resistance was reduced by 40 +/- 3% with normoxia, 19 +/- 4% with verapamil, and 60 +/- 1% with hexoprenaline. It is possible that the increased resistance during normoxia is due to partly to vasoconstriction rather than solely to vascular thickening, and that the vasoconstriction is due to an abnormality in calcium metabolism by the hypertensive vasculature.

Airway Resistance↗
PubMed1977

Oxygen-tension-dependent pulmonary vascular responses to vasoactive agents.

There have been recent indications that oxygen may nonspecifically oppose pulmonary vasoconstriction induced by a few vasoactive agents. Therefore, we examined the effect of four inspired oxygen tensions on the pulmonary vascular responses to exogenous prostaglandin F2alpha (PGF2alpha), serotonin (5-HT), 2-methylhistamine (2-MeH)(an H1-receptor agonist), histamine (after H2-receptor blockade with metiamide), and prostaglandin E1 (PGE1) in anesthetized dogs. An oxygen tension dependency on the pulmonary vascular responses to these vasoactive agents was observed, with each agent exhibiting maximal responses at different ranges of oxygen tension. PGF2alpha and PGE1 were most effective during hypoxia, while 5-HT, histamine, and 2-MeH produced maximal responses during normoxia. A comparison of dose-response curves for PGF2alpha during breathing of two inspired oxygen tensions indicated a decreased sensitivity, but not decreased reactivity, with the higher oxygen tension. The action of variable oxygen tensions on pulmonary vascular responsiveness to vasoactive agents suggests another role for oxygen in the control of the pulmonary circulation. It is not clear if oxygen acts non-specifically on the vascular smooth muscle, or if it alters the metabolic mechanisms of vasoactive agent action.

Animals↗
PubMed1977

Inhibition of hypoxic pulmonary vasoconstriction by dipyridamole is not platelet mediated.

Dipyridamole, which is known to alter platelet function, has also been shown to reduce hypoxic pulmonary vasoconstriction. This latter effect could result from dipyridamole either acting on a platelet-mediated system, or acting directly on pulmonary vascular smooth muscle. To investigate these two possibilities, normal dogs were compared with dogs rendered thrombocytopenic by a platelet antiserum. Compared with the hypoxic pressor response before drug treatment, the hypoxic response following dipyridamole was only 32% as great in the normal dogs and only 38% as great in the thrombocytopenic dogs. Thus, dipyridamole was no less effective in reducing the hypoxic pressor response in the virtual absence of platelets. This supports a direct effect of dipyridamole on pulmonary vascular smooth muscle, which could be mediated by an increase in adenosine levels.

Animals↗
PubMed1977

Lung mast cell density and distribution in chronically hypoxic animals.

Changes in the density and distribution of pulmonary mast cells were determined in six mammalian species exposed to hypobaric hypoxia (PB = 435 Torr) for 19-48 days. Control animals were studied at 1,600 m (PB = 635 Torr). Total lung mast cell hyperplasia was observed only in calves exposed to high altitude. Pigs, rats, and sheep exhibited small, but insignificant, increases in mast cell density. Perivascular mast cell proliferation adjacent to vessels of 30-500 mum in diameter was seen in both calves and pigs. Bronchial, alveolar septal, and systemic tissue (tongue) mast cell hyperplasia was not observed in any of the species. Three indices of pulmonary hypertension (right ventricular hypertrophy, medial thickness of pulmonary arteries, and pulmonary arterial pressure) correlated with perivascular mast cell density. The findings indicate that perivascular mast cell proliferation may relate more to the morphological pulmonary vascular changes and to pulmonary hypertension than to hypoxia, leading to the speculation that mast cells increase in number in response to the hypertension, rather than to mediate and maintain the hypertension.

Animals↗
PubMed1977

Platelet-mediated pulmonary hypertension: reduction by platelet inhibition.

Altering the platelet behavior with sulfinpyrazone or heparin--probably by inhibiting the platelet release reaction--reduces the emboli-induced pulmonary hypertension to the same extent as platelet depletion. Evaluation of platelet function in human pulmonary microembolism and consideration of substances which minimize or prevent platelet effects seems to be warranted on the basis of these experiments.

Animals↗
PubMed1976

Bronchoconstriction and pulmonary hypertension during abortion induced by 15-methyl-prostaglandin F2alpha.

Patients have experienced severe breathlessness during second trimester abortion initiated by the intramuscular injection of 15-methyl-prostaglandin F2alpha (15-me-PGF2alpha). In four healthy women given 400 mug of 15-me-PGF2alpha to induce abortion, pulmonary function tests showed reductions in arterial oxygen tension, maximum expired air flow and vital capacity. Residual lung volume and the slope of phase III of the closing volume curves increased.

Abortion, Induced↗
PubMed1976

Pulmonary microembolism: attenuated pulmonary vasoconstriction with prostaglandin inhibitors and antihistamines.

The mechanism(s) involved in the pulmonary vascular and airway responses to pulmonary microembolism have not been clearly defined. Therefore, we determined the effects of specific prostaglandin and histamine blockade on the hemodynamic and arterial blood gas tension responses to particulate microembolism (200 mu glass beads) in intact anesthetized dogs. The marked increases in pulmonary arterial pressure and pulmonary vascular resistance observed in the untreated dogs were attenuated, but not abolished, following both prostaglandin blockade (with either meclofenamate or polyphloretin phosphate) and histamine blockade (with chlorpheniramine and metiamide) at 5 minutes, and were still attenuated 30 minutes post embolization. Combined prostaglandin and histamine blockade further attenuated, but again did not abolish, the pulmonary vascular responses. Cardiac outputs and systemic arterial pressures were unchanged from control by embolism. The alveolar hypoventilation (decreased arterial oxygen tension and increased carbon dioxide tension) observed in the untreated embolized dogs was prevented only with the prostaglandin inhibitors. Pulmonary microembolism in intact dogs, therefore, appears to induce vasoconstriction mediated partially by prostaglandin and histamine action, and alveolar hypoventilation mediated by prostaglandin, but not histamine, action.

Airway Resistance↗