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H S Stanbrook

Publications and source records attributed to H S Stanbrook.

7 recordsLinked to original sources
PubMed1989

5-Hydroxytryptamine uptake in oxygen radical-mediated acute lung injury.

Pulmonary endothelial cell function (ECF) studies have been shown to be a sensitive indicator of chronic lung injury. We attempted to correlate changes in 5-hydroxytryptamine (5HT) uptake with an acute oxygen radical-mediated lung injury in dogs. Beta-d glucose/glucose oxidase was injected intravenously in an experimental group (n = 10), while the control group (n = 5) received saline. 5HT uptake, measured using a multiple indicator dilution technique before and 20 min after injection, was calculated for both the percent total uptake and the peak extraction ratio of 5HT during a single passage through the lung. The mean pulmonary and systemic arterial pressures (PAP, SAP), total pulmonary resistance (TPR), extravascular lung water (EVLW), and wet-to-dry weight ratios were also determined. The experimental group showed an acute rise in PAP and TPR and a fall in SAP after the injection, all returning to normal by 20 min; total 5HT uptake fell from 81 +/- 2.3% to 47 +/- 6.5% (p = 0.0002) as did the peak extraction ratio from 0.87 +/- 0.013 to 0.44 +/- 0.066 (p = 0.0001). No change in 5HT uptake was observed in the control group. EVLW did not change in either group, but wet-to-dry weight ratio was elevated in the experimental group (5.21 +/- 0.12 versus 4.73 +/- 0.06, p less than 0.01). ECF studies of 5HT uptake appear to be a sensitive indicator of acute lung injury in this large-animal, oxygen radical-induced injury model.

Acute Disease↗
PubMed1984

Prevention and reversal of hypoxic pulmonary hypertension by calcium antagonists.

There exists no agreement as to the best vasodilator drug for treatment of hypoxic pulmonary hypertension. We wondered which of 3 commonly used vasodilators - verapamil, nifedipine, or hydralazine - would be the most effective in reducing and reversing the development of hypoxic pulmonary hypertension in the conscious rat. Hemodynamic studies showed that all 3 drugs inhibited the pressor response to acute hypoxia. Given for 1 month to conscious rats during exposure to intermittent hypoxia, verapamil and nifedipine reduced pulmonary hypertension when compared with hypoxic control animals, as indicated by right ventricular hypertrophy, total pulmonary resistance, and medial thickening. Hydralazine caused similar, but smaller, changes. Nifedipine, when used to reverse established hypoxic pulmonary hypertension, reduced right ventricular hypertrophy and medial thickening. Cardiac and systemic effects were negligible. These results demonstrate that the calcium channel blockers reduce the development of hypoxic pulmonary hypertension and that nifedipine partially reverses established hypertension.

Animals↗
PubMed1983

Inhibition of glycolysis potentiates hypoxic vasoconstriction in rat lungs.

The purpose of this study was to test whether inhibition of glycolysis would potentiate hypoxic vasoconstriction in isolated rat lungs, and, if so, to evaluate whether potentiation was due to decreased aerobic production of the mitochondrial substrate, pyruvate, or to inhibition of anaerobic synthesis of ATP. In blood-perfused lungs, both iodoacetate and 2-deoxyglucose inhibited lactate production and increased pressor responses to ventilation with gases containing from 15 to 3% O2. In lungs perfused with physiological salt solution, both 2-deoxyglucose and glucose-free perfusion inhibited lactate and pyruvate production and potentiated the dose-response curve to hypoxia. Dose responses to angiotensin II and KCl were not increased by glucose-free perfusion. Lungs perfused with glucose-free salt solution containing increased levels of lactate and pyruvate did not show an increased dose response to hypoxia. In contrast, lungs perfused with the inhibitor of citric acid cycle, malonate, in addition to the increased lactate and pyruvate, did show an increased dose response to hypoxia. These results indicate that potentiation of hypoxic vasoconstriction by inhibition of glucose metabolism is due to decreased production of pyruvate, rather than to decreased glycolytic generation of ATP. The potentiation might be directly related to either limitation of mitochondrial oxidative phosphorylation in an oxygen-sensing cell or to a decreased level of some intra- or intercellular modulating peptide, fatty acid, or lipid.

Animals↗
PubMed1982

Studies of the mechanism of hypoxic pulmonary vasoconstriction.

The intrapulmonary mechanism by which airway hypoxia causes pulmonary arterial constriction is poorly understood. It is generally believed that hypoxia either elicits the release of a chemical mediator from the lung parenchyma or has a direct excitatory effect on the smooth muscle of the peripheral pulmonary arteries. We are testing the working hypothesis that hypoxia acts directly on the vascular smooth muscle to depress the rate of mitochondrial oxidative phosphorylation and to cause shifts in cytoplasmic metabolite concentrations, which then lead to membrane depolarization, calcium influx, and contraction. Results from studies of isolated perfused rat lungs with pharmacologic inhibitors of oxidative phosphorylation, glycolysis, and calcium influx have provided indirect support for the hypothesis; but a simpler in vitro preparation allowing direct measurements of energy metabolism, membrane electrical activity, calcium fluxes, and muscle tone is needed. Additional experiments have shown that inhibitors of membrane K+ conductance allow hypoxic contractions of isolated vascular smooth muscle; and such a preparation might be useful as an in vitro model of hypoxic pulmonary vasoconstriction.

Animals↗
PubMedDate not supplied

1979 George Simon Memorial Fellowsip Award. A radiologic and physiologic investigation into hypoxic pulmonary vasoconstriction in the dog.

We examined the site and mechanism of hypoxic vasoconstriction in a single lobe of the dog lung. In anesthetized dogs pulmonary arteriography in an exteriorized lung lobe showed vasoconstriction during hypoxia. The vasoconstriction was maximal in the smallest vessels studied (300-micrometer diameter), in which a 19% reduction in diameter was observed during hypoxia; no significant change in caliber occurred in vessels exceeding 2 mm in diameter. Reversal of the vascular response occurred upon withdrawal of the hypoxic stimulus. In a second study using the same model, saralasin acetate, a specific competitive antagonist of angiotensin II, failed to modify the constrictor response to hypoxia. It is concluded from these studies that the site of the increased pulmonary vascular resistance evoked by alveolar hypoxia is located predominantly in the small pulmonary arteries, and that angiotensin II plays no significant role in the mediation of the response.

Angiography↗