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Biomedical subjects

J T Reeves

Publications and source records attributed to J T Reeves.

At least 127 records · Page 7Linked to original sources
PubMed1984

Lung edema due to hydrogen peroxide is independent of cyclooxygenase products.

Active oxygen species can cause lung injury. Although a direct action on endothelial cells is proposed, the possibility exists that they might cause injury via mediators. We considered that active oxygen species would stimulate the generation of cyclooxygenase metabolites, which then alter pulmonary vasoreactivity and cause edema. We chemically produced hydrogen peroxide by adding glucose oxidase to a plasma- and cell-free, but beta-D-glucose-containing, solution, which perfused isolated rat lungs. Addition of glucose oxidase to the perfusate caused a marked decrease in pulmonary vasoreactivity, accompanied by an increase in the concentrations of prostacyclin, thromboxane A2, and prostaglandin F2 alpha. Pretreatment with catalase, a specific scavenger of hydrogen peroxide, preserved pulmonary vasoreactivity, inhibited the increase of the concentration of the measured prostaglandins, and prevented edema formation. Indomethacin effectively blocked lung prostaglandin production but neither prevented the decrease in vasoreactivity nor inhibited edema formation. From these data we conclude that hydrogen peroxide impaired pulmonary vasoreactivity and subsequently caused edema. Despite the fact that hydrogen peroxide stimulated lung prostaglandin production, cyclooxygenase-derived products neither caused the decrease in vasoreactivity nor the development of edema.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Leukotriene synthesis and receptor blockers block hypoxic pulmonary vasoconstriction.

We hypothesized that leukotrienes are involved in hypoxic pulmonary vasoconstriction, since they are pulmonary vasoconstrictors and cells capable of producing leukotrienes are located in the lung near resistance vessels. We investigated in isolated perfused rat lungs whether three structurally unrelated blockers [diethylcarbamazine citrate (DEC), U-60257, and FPL 55712] of leukotriene synthesis or action block hypoxic pulmonary vasoconstriction. DEC blocked ongoing and subsequent hypoxic pressor responses while minimally affecting the angiotensin II pressor response. The inhibition of the hypoxic pressor response by DEC was not affected by cyclooxygenase or H1-receptor blockers. Potassium-induced vasoconstriction, which is dependent on calcium entry, was largely blocked by verapamil but not by DEC, suggesting that DEC was not acting primarily as a calcium-entry blocker. U-60257 blocked the hypoxic pressor response without inhibiting the pressor response to angiotensin II or potassium chloride. FPL 55712, a leukotriene end-organ blocker, in a dose which inhibited vasoconstriction caused by exogenous leukotriene C4, inhibited the pressor response to hypoxia but not to angiotensin II. We conclude that leukotriene inhibitors preferentially inhibit hypoxic pulmonary vasoconstriction in isolated perfused adult rat lungs.

Angiotensin II↗
PubMed1984

Role of collateral ventilation in ventilation-perfusion balance.

Species with collateral ventilation have an auxiliary respiratory mechanism that could protect them, under certain circumstances, from regional alveolar hypoxia. Species without collateral ventilation may have a greater potential for routinely experiencing regional hypoxia; to maintain ventilation-perfusion balance they would have to rely on pulmonary vasoconstriction. We tested these ideas by ventilating a sublobar region of pig lung (no collateral ventilation) with 13% O2 while the rest of the lung was ventilated with 30% O2. Blood flow, as measured by radioactive microsphere distribution to the sublobar region, was reduced 50% during hypoxia. The hypoxia-induced vasoconstriction effectively defended arterial PO2. When a vasodilator was infused, regional blood flow increased to control levels; shunt fraction rose, and arterial PO2 fell. In dogs (collateral ventilation present) the same experimental maneuvers had no significant effect on regional end-tidal gases or on microsphere distribution, indicating that collateral ventilation was able to maintain ventilation-perfusion balance. When regional hypoxia was created in dogs by overcoming collateral ventilation with slightly positive airway pressure in the sublobar region, the dog acted like the pig and used hypoxic vasoconstriction to shift approximately 30% of the blood flow away from the hypoxic alveoli.

Animals↗
PubMed1984

Altering hydrodynamic variables influences PGI2 production by isolated lungs and endothelial cells.

Because deformation of lung tissue stimulates prostaglandin synthesis, we wanted to investigate whether hydrodynamic forces would affect lung prostacyclin (PGI2) production. To test the hypothesis that lung prostacyclin synthesis was flow dependent, we examined lung prostacyclin production after flow alterations. Using a salt solution that contained either Ficoll or albumin as a perfusate, we changed the flow to half and to double the control flow. When flow was changed, lung prostacyclin production followed changes in flow and pressure drop. When flow was varied in lungs treated with indomethacin, prostacyclin production was too low to be measurable. Variations in pressure pulsatility at constant mean flow had no influence on lung prostacyclin production. Since vascular distension may also stimulate prostacyclin production, we increased venous pressure. An increase in venous pressure (from 2.1 to 4.8 mmHg) had no effect on prostacyclin production; a further increase in venous pressure (to 7.5 mmHg) initiated edema and caused a large increase in prostacyclin production. When we subjected monolayers of endothelial cells cultured in wells to defined shear rates, the prostacyclin concentration in the supernatant quickly increased to a maximum. The absence of further increase with greater shear may have reflected feedback control of prostacyclin synthesis. The results indicated that hydrodynamic disturbances affect endothelial cells and stimulate arachidonate metabolism. Lung prostacyclin production may be related to flow. However, this effect is small compared with the lung prostacyclin production during edema formation.

Animals↗
PubMed1984

Actions of lipoxygenase metabolites in isolated rat lungs.

Leukotrienes constrict smooth muscle and could be important for the regulation of the pulmonary circulation. We examined the production and action of lipoxygenase metabolites in isolated lungs, where we controlled the perfusing fluid used. Arachidonate injected into isolated rat lungs perfused with cell- and protein-free physiological salt solution caused a transient pressor response. Following indomethacin, arachidonate caused a delayed slow pressure rise followed by edema. The lung effluent contracted the guinea pig ileum. High-pressure liquid chromatography (HPLC) analysis of the perfusate demonstrated the presence of leukotrienes (LTC4 and LTD4). Diethylcarbamazine, a leukotriene synthesis inhibitor, prevented the slow pressure rise and edema seen after indomethacin plus arachidonate. In lungs perfused with cell- and protein-free physiological salt solution, LTC4, but not LTD4, caused a transient pressure rise followed by a sustained pressure rise. The sustained rise was abolished by a leukotriene-receptor blocker (FPL 55712) but not by indomethacin. In blood-perfused lungs, LTC4 caused only the transient pressure rise that was not blocked by FPL 55712. In lungs perfused with physiological salt solution containing albumin, LTC4 had no effect. We concluded that 1) perfused nonsensitized rat lungs produced LTC4 and LTD4; 2) LTC4 may be a major pulmonary vasoconstrictor; and 3) albumin binding limits the pressor effect of LTC4.

Animals↗
PubMed1984

Respiratory function in normal Chinese: comparison with Caucasians.

We found that respiratory measurements in Chinese visitors to Colorado differed from those in height- and weight-matched Western residents of Denver, Colo., in the following ways (p less than 0.05): The Chinese had higher respiratory frequencies (15.5 +/- 0.93 vs. 11.4 +/- 0.85 breaths/min), lower tidal volumes (530 +/- 35.9 vs. 693 +/- 477.7 ml), lower alveolar ventilation (4.0 +/- 0.15 vs. 4.7 +/- 0.21 liters), lower forced vital capacities (4.53 +/- 0.16 vs. 5.43 +/- 0.12 liters), lower total lung capacities (6.25 +/- 0.26 vs. 7.16 +/- 0.17 liters), higher resting PaCO2 (36.3 +/- 0.94 vs. 33.6 +/- 0.74 Torr) and lower pHa (7.406 +/- 0.004 vs. 7.419 +/- 0.004). The Chinese also had lower ventilatory responses to CO2 (1.40 +/- 0.10 vs. 2.00 +/- 0.201/min/mm Hg) than did the Caucasians. The measurements made in the Chinese in Denver were similar to those reported for Chinese in China. Thus there may be differences in respiratory function between normal Chinese and normal Western subjects.

Adult↗
PubMed1984

Effects of meclofenamate on pulmonary vascular resistance correlate with postnatal age in young piglets.

We administered sodium meclofenamate, a prostaglandin synthetase inhibitor, to 15 piglets (ages 5-70 d) to test the hypothesis that endogenous prostaglandin pulmonary vasodilators influence total pulmonary resistance under both normoxic and hypoxic conditions. No significant differences in hemodynamic measurements were found between the control group and drug-treated animals more than 12-d-old. When six experimental animals less than 12 d of age were compared with six age-matched controls, meclofenamate produced a small but significant increase in mean pulmonary artery pressure (110 +/- 9 versus 97 +/- 10%, P less than 0.05) and total pulmonary resistance (135 +/- 23 versus 102 +/- 12%, P less than 0.03). The magnitude of the change in total pulmonary resistance produced by 2 mg/kg of meclofenamate during normoxia correlated inversely with postnatal age (r = 0.83, P less than 0.01). Individual changes in pulmonary hemodynamics produced by acute hypoxia after meclofenamate treatment were the same as pretreatment values and were similar in both young and older animals.

Animals↗
PubMed1984

Chronic propranolol treatment decreases pulmonary artery pressure in conscious dogs.

Daily administration of propranolol to 9 chronically instrumented, trained dogs for 2 weeks caused significant (p less than 0.05) decreases in heart rate (70 +/- 8 to 57 +/- 6 beats/min), cardiac output (3.6 +/- 0.3 to 2.9 +/- 0.2 liters/min), pulmonary arterial pressure (15.7 +/- 0.5 to 10.0 +/- 0.5 mm Hg) and total pulmonary vascular resistance (4.6 +/- 0.6 to 3.3 +/- 0.4 units). Nadolol, a structurally dissimilar beta-adrenergic receptor antagonist, caused a similar decrease in total pulmonary resistance. Acute meclofenamate administration did not return to normal pulmonary arterial pressure and resistance in the dogs chronically treated with beta-adrenergic receptor blockers. We therefore conclude that chronic beta-adrenergic receptor blockade lowered pulmonary arterial pressure and resistance by a mechanism independent of cyclooxygenase. In addition, chronic beta-adrenergic receptor blockade did not affect the potential for hypoxic vasoconstriction.

Animals↗
PubMed1984

Cardiovascular adjustments to various degrees of acute isocapnic hypoxia in dogs.

Cardiovascular responses to various degrees of acute isocapnic hypoxia were determined in spontaneously breathing anesthetized dogs. Cardiac output (CO), heart rate, stroke volume, systemic blood pressure, and systemic vascular resistance were measured at frequent intervals during 20-minute exposures to hypoxia (7% to 17% O2). Cardiac output increased during hypoxia, with the most severe degree of hypoxia producing the greatest increase in CO. Stroke volume increased significantly (P less than 0.05), whereas tachycardia was inconsistent. Systemic vascular resistance declined with hypoxia, with the greatest vasodilation observed with the most severe hypoxia. During the first 3 minutes of hypoxia, CO increased at all 3 degrees of hypoxia, whereas systemic vascular resistance remained relatively unchanged during this initial portion of the hypoxic exposures. Prevention of the hypoxia-induced increase in CO by partial caudal vena caval obstruction (reducing venous return) resulted in a maintenance of systemic vascular resistance at or above the base-line value before hypoxia. Seemingly, hypoxia can increase CO before systemic vasodilation is evident and systemic vasodilation depends, partly, on the increase in CO.

Acute Disease↗
PubMed1983

Leukotriene C4 and D4 in neonates with hypoxemia and pulmonary hypertension.

Persistent pulmonary hypertension of the newborn is a syndrome consisting of severe hypoxemia and pulmonary hypertension that appears within hours of birth. Since certain leukotrienes (C4, D4, and E4) are known to produce some of the features of persistent pulmonary hypertension of the newborn, including pulmonary vasoconstriction, bronchoconstriction, decreased lung compliance, and pulmonary edema, we studied five newborns with the syndrome to determine whether these leukotrienes were present in their airways. We found leukotriene C4 and leukotriene D4 in the lung lavage fluids of all five newborns who had the clinical diagnosis of persistent pulmonary hypertension and who required ventilatory assistance. In contrast, leukotrienes were not demonstrated in a control group of 14 infants requiring ventilatory assistance who did not have the clinical diagnosis of persistent pulmonary hypertension. We conclude that leukotrienes may have a role in persistent pulmonary hypertension of the newborn.

Animals↗
PubMed1983

Cardiopulmonary response to acute altitude exposure: water loading and denitrogenation.

In order to determine if a positive water balance would impair cardiovascular and ventilatory adjustments during acute altitude exposure, six healthy male subjects were exposed to 4570 m for 2 h with and without water loading. No significant differences in any of the measured variables were observed between normal and overhydrated subjects. In order to determine if rapid ascent to altitude involves the formation of nitrogen bubbles which could impair gas exchange, 11 subjects were exposed to 4570 m with and without denitrogenation (by breathing 100% O2 prior to ascent) and 6 subjects were exposed to normobaric hypoxia (14% O2). Prior O2 breathing reduced the hyperventilatory and alkalotic responses to altitude, tachycardia did not develop, and systemic blood pressure fell, despite the fact that arterial desaturation was similar to that during the untreated altitude exposure. Reduced urine flow and increased urine osmolality were observed in two subjects at 4570 m, but these changes were not observed in the same subjects after O2 breathing. Breathing 14% O2 also produced the same degree of arterial desaturation but the hyperventilatory response was significantly greater than in the prior altitude exposures. Heart rate, blood pressure, and urine flow and osmolality were not altered and symptoms of altitude illness were minimal. Thus, neither of our hypotheses proved to be correct; however, we did observe a prolonged effect of O2 breathing on the hypoxic ventilatory response, and a potential effect of hypobaria on ventilation.

Acclimatization↗
PubMed1983

Leukotriene E4 causes pulmonary vasoconstriction, not inhibited by meclofenamate.

Leukotriene E4 (LTE4) appears to be a rather stable product of the lipoxygenase pathway. Its action in the pulmonary circulation is unknown. Therefore we investigated its effect on the circulation of isolated rat lungs perfused with a cell- and plasma-free solution. Synthetic LTE4 in doses from .15 micrograms to 5 micrograms/.25 ml .9% NaCl injected as a bolus in the pulmonary artery during normoxia caused a fast, transient perfusion pressure increase within seconds. This was followed by a slow rise in baseline perfusion pressure (normoxia) over 25 min. In addition, 5 micrograms LTE4 caused edematogenic lung damage. Injection of 1.5 micrograms LTE4 during hypoxic vasoconstriction caused fast, transient pressure rises, similar to normoxic conditions. 6-keto-PGF1 alpha and TXB2 were measured in the lung effluent before and after LTE4 injection. Neither 6-keto-PGF1 alpha nor TXB2 production changed after LTE4 injection. Meclofenamate (.5 micrograms/ml) increased the fast, transient and the slow, sustained pressure rise. We conclude that LTE4 caused direct pulmonary vasoconstriction unrelated to cyclooxygenase products.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Thermodilution method overestimates low cardiac output in humans.

We compared 57 cardiac output measurements by the thermodilution and Fick methods in 26 patients and found that thermodilution values were higher in all 16 cases in which Fick outputs were less than 3.5 l/min. In 10 cases where Fick values were less than or equal to 2.5 l/min, thermodilution and Fick measurements differed by an average of 35%. When combined with the results of previous studies comparing the thermodilution, dye dilution, and Fick techniques, these findings suggest that the thermodilution method overestimates true cardiac output in the low output range. This overestimation probably is due to heat loss under conditions of low flow. Because the thermodilution method is used widely in patients with low output states, these findings have potentially important clinical implications.

Adolescent↗
PubMed1983

Lung vessel leak precedes right ventricular hypertrophy in monocrotaline-treated rats.

Monocrotaline induces microvascular leak and pulmonary hypertension in rats. We have hypothesized that the leak is related in some way to the pulmonary hypertension and precedes it. In rats given 40 mg monocrotaline/kg body wt subcutaneously, lung wet weight-to-dry weight ratios and lung albumin content began to increase within the first 3 days and became maximal at 1 wk. Alveolar lavage fluid showed little or no increase in protein. Right ventricular hypertrophy increased progressively from 2 through 3 wk. An increase in lung dry weight paralleled the right ventricular hypertrophy. The amount of blood retained in the lung did not account for the increased lung water, albumin, or weight. We considered that microvascular leak without leak into the alveolar space preceded pulmonary hypertension, right ventricular hypertrophy, and increased lung dry weight. In rats not given monocrotaline but exposed for 3 wk to hypobaric hypoxia, lung albumin, lung dry weight, and right ventricular weight increased. Increased lung dry weight probably reflects hyperplasia of lung cells. If so, an association of microvascular leak, lung cell hyperplasia, and right ventricular hypertrophy may occur in both monocrotaline- and hypoxia-induced pulmonary hypertension.

Albumins↗
PubMed1983

Low exercise pulmonary resistance is not dependent on vasodilator prostaglandins.

In resting conscious dogs, administration of cyclooxygenase inhibitors results in modest increases in pulmonary arterial pressure and pulmonary vascular resistance, suggesting that vasodilator prostaglandins play a role in maintaining the low vascular resistance in the pulmonary bed. To assess the role of these vasodilator prostaglandins on pulmonary vascular resistance during exercise, we studied seven mongrel dogs at rest and during exercise before and after intravenous meclofenamate (5 mg/kg). Following meclofenamate, pulmonary vascular resistance rose both at rest (250 24 vs. 300 +/- 27 dyn . s . cm-5, P less than 0.01) and with exercise (190 +/- 9 vs. 210 +/- 12 dyn . s . cm-5, P less than 0.05). Systemic vascular resistance rose slightly following meclofenamate both at rest and during exercise. There were no changes in cardiac output. The effects of cyclooxygenase inhibition, although significant, were less during exercise than at rest. This suggests that the normal fall in pulmonary vascular resistance during exercise depends largely on factors other than vasodilator prostaglandins.

Animals↗
PubMed1983

Abnormal alveolar cells in monocrotaline induced pulmonary hypertension.

Monocrotaline given to rats causes lung injury which is followed by pulmonary hypertension. A large, abnormal intraalveolar cell has been repeatedly observed. The purpose of the present study was to define the nature of the cell and to determine how it related to the lung injury. As observed by electron microscopy, the intraalveolar cell contained numerous large, dense granules, as well as lipid whorls, extensive Golgi complexes, and many small vesicles. These cells appeared to be macrophages, possibly altered by ingestion of lipid-like material which was free in the alveolar space. Enlarged type II pneumonocytes and mast cells were seen in the alveolar walls but their appearance differed from that of the free alveolar cells. The electron microscopic findings plus the presence of Fc and C3b receptors on the cells indicated they were alveolar macrophages. When the severity of pulmonary hypertension was varied by a) giving monocrotaline to rats of varying age, b) by varying the dose of monocrotaline, or c) by varying the time interval after monocrotaline administration, the number of abnormal alveolar macrophages related to the severity of the pulmonary hypertension. When we reduced the number of circulating leukocytes by whole body radiation, monocrotaline administration was followed both by accelerated pulmonary hypertension and increased numbers of abnormal alveolar macrophages. The abnormal macrophage appeared to be a marker of the monocrotaline induced pulmonary hypertension. However, neither the abnormal macrophage nor the monocrotaline injury appeared to depend on circulating leukocytes.

Animals↗