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Biomedical subjects

M H Gee

Publications and source records attributed to M H Gee.

53 records · Page 3Linked to original sources
PubMed1983

Effects of anesthesia and surgery on prostanoid concentrations in plasma and pulmonary lymph.

Comparisons were made of plasma and pulmonary lymph concentrations of 6-keto-PGF1 alpha and thromboxane B2 between chronic and acute models of the sheep lung lymph fistula preparation. Pentobarbital anesthetized sheep subjected to acute thoracotomy and artificially ventilated demonstrated significantly elevated pulmonary lymph concentrations of 6-keto-PGF1 alpha and TxB2 for two hours following surgery while venous or arterial plasma prostanoid concentrations increased to a much lesser degree over the same time period. No changes in plasma or lymph prostanoid concentrations were observed in the unanesthetized, chronic lung lymph preparation during a similar baseline observation period. The rates of decrease of pulmonary lymph prostanoid concentrations in the acute model following surgical preparation suggest the requirement of a three hour stabilization period after completion of all surgical procedures before pulmonary arachidonic acid metabolism reaches steady-state conditions.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Role of intrapulmonary release of eicosanoids and superoxide anion as mediators of pulmonary dysfunction and endothelial injury in sheep with intermittent complement activation.

In 30 anesthetized sheep, we show that repeated bolus injections of autologous zymosan-activated plasma produce pulmonary hypertension, hypoxemia, intrapulmonary thromboxane release, pulmonary leukostasis, and sustained increases in lung lymph flow and protein clearance. Studies with platelet-rich plasma demonstrated that addition of zymosan-activated plasma does not induce platelet aggregation or thromboxane release. We studied the role of cyclooxygenase products as mediators of these pathophysiological responses by pretreating sheep with either meclofenamate (4 mg/kg) or ibuprofen (12.5 mg/kg). Both drugs inhibited thromboxane release and hypoxemia. Ibuprofen, but not meclofenamate, reproducibly attenuated the hypertensive responses and the increases in lymph flow and protein clearance. Neither drug prevented pulmonary leukostasis. These results demonstrate that cyclooxygenase products mediate the development of complement-induced hypoxemia but are not sole mediators of pulmonary hypertension or increases in vascular permeability. Furthermore, ibuprofen has anti-inflammatory actions, not shared by meclofenamate, which enhance the effectiveness of this drug. Since activated leukocytes release reactive oxygen metabolites, we treated sheep with superoxide dismutase (2800 U/kg per hour) to determine the role of superoxide anions in these responses. This treatment significantly attenuated the increases in lung lymph flow and protein clearance. The results suggest that multiple mediators, which may originate from activated leukocytes sequestered in the pulmonary circulation, contribute to the pathophysiological changes seen with intermittent complement activation. Cyclooxygenase products of arachidonic acid contribute to the hypertension and are solely responsible for the hypoxemia. Reactive oxygen metabolites are important mediators of the complement-induced increases in lung vascular permeability.

Animals↗
PubMed1982

Pulmonary and coronary endothelial effects of acute myocardial ischemia in dogs.

We measured pulmonary arterial (Ppa) and left atrial (Pla) pressures, lung lymph flow rate (QL), and protein clearance in 23 anesthetized dogs with ligation (MI) dogs or sham ligation (sham-MI dogs) of a coronary artery combined with either large transient increases in Pla or moderate steady-state increases in Pla. In steady-state experiments we also collected cardiac lymph. Plasma and lymph concentrations of several prostanoids including prostacyclin (PGI2) and thromboxane B2 (TXB2) were measured. Lung lymph flow rates and protein clearances were increased in MI dogs compared with those in sham-MI dogs in experiments with transient increases in Pla. Similarly in steady-state experiments lung QL and protein clearance were increased after MI. Cardiac QL increased after MI with no change in lymph protein clearance. Lung and cardiac lymph PGI2 and plasma TXB2 concentrations increased after MI. We suggest that acute MI results in increased lung vascular permeability and that activation of formed elements in blood may be involved in mediating MI-induced vascular injury.

Animals↗
PubMed1982

alpha-Naphthylthiourea produces dose-dependent lung vascular injury in sheep.

We tested the effects of alpha-naphthylthiourea (ANTU) on lung fluid balance and prostanoid concentrations in anesthetized sheep acutely prepared for collection of pulmonary lymph. Sheep were given 20, 50, 75, or 100 mg/kg ANTU or the vehicle dimethylsulfoxide (DMSO) intravenously. The first phase of the response consisted of transient increases in pulmonary artery pressure and plasma and lymph thromboxane B2 concentrations. Lymph flow increased with no change in the lymph-to-plasma protein concentration ratio (L/P). These changes occurred in sheep given DMSO alone or DMSO with ANTU; they were not dependent on the dose of ANTU given. Two to 4 h after drug administration, pulmonary artery pressure and thromboxane concentrations were normal or near normal. Lymph flow rate reached steady-state levels averaging 1.5 (DMSO alone) to 5.3 (100 mg/kg ANTU) times base line with L/P ratios unchanged from base line. ANTU/DMSO produces transient, severe pulmonary hypertension that may be prostaglandin mediated. The sustained response consists of increased flow rate of protein-rich lymph.

Animals↗
PubMed1982

Relationships among lung extravascular fluid compartments with alveolar flooding.

We studied the relationship between lung perivascular cuff fluid and alveolar fluid in dogs with alveolar flooding. In one group of dogs, we produced edema with alloxan. We waited 1 h and injected Evans blue dye intravenously. We then caused additional alveolar flooding by a rapid fluid load. The concentration of dye in perivascular fluid cuffs averaged 40% of that in airway edema fluid. We conclude that alveolar fluid derives from microvascular filtrate in the perimicrovascular compartment rather than from fluid in the loose connective tissue spaces. In a second group of dogs, we produced alveolar flooding by mechanically increasing left atrial pressure with a simultaneous fluid load. After flooding stopped and pressures stabilized, we injected Evans blue dye. Morphological examination of lung sections showed no dye present in alveolar fluid, although dye was present in alveolar septa and perivascular cuffs. Flooding occurs during a transient period consistent with an apparent increase in alveolar epithelial permeability, after which an isolated alveolar reservoir is created.

Animals↗
PubMed1982

Changes in collateral ventilation with increased vascular pressure and edema formation.

To test the hypothesis that development of hemodynamic edema results in decreased collateral ventilation, we rapidly volume-expanded anesthetized dogs with volumes equivalent to 10 (n = 5) and 15% (n = 5) of body weight. We measured collateral resistance (Rcoll), pulmonary arterial pressure, and left ventricular end-diastolic pressure before, during, and for 1-2 h after the infusion. Lungs were subsequently processed for microscopic examination and measurement of extravascular lung water content. During the infusion, Rcoll increased modestly independent of the fluid-infusion rate or the rate of increase in vascular pressures. After the infusion, Rcoll continued to increase to maximum levels 2-33 times base line even though pressures decreased dramatically. At the end of the experiment, Rcoll returned to base line in one dog and was 3-15 times base line in the other dogs. These changes bore no relationship to the severity of edema formation. Until alveolar flooding occurs, accumulation of lung interstitial fluid and changes in collateral ventilation appear to be coincident events rather than causally related variables.

Airway Resistance↗
PubMed1981

Pulmonary injury and prostaglandin production during endotoxemia in conscious sheep.

Prostaglandins F2 alpha, E2, and I2 (as 6-keto-PGF1 alpha) and TxA2 (as TxB2) were measured by radioimmunoassay in plasma and lymph from 12 conscious sheep with chronic lung lymph fistulas given Escherichia coli endotoxin (2-10 micrograms/kg) and followed for 24 h. Endotoxin produced a two-phase pulmonary injury. Phase 1 was characterized by transient severe pulmonary hypertension and increased lymph flow rate (QL). Plasma and lymph PGF2 alpha concentrations increased from base-line values of 0.13 +/- 0.08 and 0.30 +/- 0.10 ng/ml to 0.96 +/- 0.37 and 2.8 +/- 0.80 ng/ml, respectively. Values for TxB2 increased from 0.7 +/- 0.1 to 5.5 +/- 1.1 ng/ml in lymph and to 3.2 +/- 0.6 in plasma. Plasma PGI2 increased from 0.48 +/- 0.29 to 4.97 +/- 1.21 ng/ml and lymph PGI2 from 1.80 +/- 0.73 to 14.19 +/- 2.79 ng/ml. Phase 2 was characterized by moderately elevated pulmonary vascular pressures and a maintained high flow rate of protein-rich lymph. Lung lymph and plasma PGF2 alpha concentrations returned to base line. Lymph PGI2 decreased significantly to 5.23 +/- 2.47 ng/ml, whereas plasma PGI2 decreased to 2.70 +/- 1.07 ng/ml. We conclude that prostaglandins, particularly PGF2 alpha and prostacyclin, are released from the lung after endotoxemia and appear in lung lymph as sensitive indicators of pulmonary microvascular injury. Prostanoid production appears to temporally correspond with changes in the pulmonary microcirculation.

Animals↗
PubMed1979

The flow and composition of pulmonary and systemic lymph in dogs with edema.

In animals with edema, pulmonary and systemic lymphatics may function to remove accumulated extravascular fluid in addition to responding to events as they occur in the exchanging vessels. We tested this hypothesis by measuring the flow rate and composition of thoracic duct and right duct lymph in anesthetized dogs made edematous by rapid fluid infusion. During a fluid challenge equivalent to 30% of body weight, thoracic and right duct lymph flow rates increased 30- and 60-fold, respectively. After the infusion, lymph flow rates rapidly decreased even though the dogs were edematous. During the postinfusion period, the decrease in right duct lymph flow rate was directly related to a decrease in estimated net pulmonary fluid filtration pressure. We conclude that lymph flow rate and composition reflect events occurring in the microvasculature whether or not edema is present.

Animals↗
PubMed1978

Extravascular water content of heart and lungs after acute myocardial ischemia.

We measured the extravascular water content of hearts and lungs of anesthetized dogs subjected to one of the following protocols: a)sham operation, b) circumflex artery ligation, c) increased left atrial pressure (Pla), or d) increased Pla and circumflex artery ligation. After 4 h, extravascular water of the heart and lungs increased significantly in the three experimental groups when compared with values from sham-operated dogs. After circumflex artery ligation, extravascular heart water increased 29% and lung water 8%, although Pla and calculated pulmonary microvascular pressure (Pmv) did not change. Extravascular heart water also rose 30% after increasing Pla from 23 to 37 cm H2O by inflating a left atrial baloon. In these dogs, extravascular lung water increased as a hyperbolic function of Pmv. Increasing Pla to 20 cm H2O in dogs with coronary artery ligation resulted in a 16% increase in heart water. Also at each Pmv, extravascular lung water was greater in dogs with coronary artery ligation than in dogs without. These data indicate that the increased extravascular lung water after coronary artery ligation cannot be explained solely by hemodynamic mechansims. We suggest that acute myocardial ischemia contributes to an increase in vascular permeability in the heart and lungs.

Animals↗
PubMed1977

Role of bulk fluid flow in protein permeability of the dog lung alveolar membrane.

In five anesthetized, closed-thorax dogs, we measured net tracer albumin (RISA) uptake rate from an isosmotic buffer-filled lung lobe for 6 h; 3 h at each of two different alveolar RISA concentrations. We calculated the permeability coefficient assuming a two-compartment (alveolar fluid and plasma) diffusional model. In every dog the permeability coefficient decreased after the alveolar RISA concentration was increased. After freezing the lungs terminally, we found the fluid-filled lobes had extensive free interstitial fluid perivascular cuffs, indicating a third compartment filled by bulk flow. In separate experiments, we filled isolated lung lobes with buffer containing RISA and microsampled free interstitial fluid. The free interstitial fluid RISA concentration averaged 90% of airway concentration. The interstitium appears to fill by bulk flow through low-resistance channels. Tracer protein uptake from a fluid-filled lung lobe involves three fluid compartments. We postulate fluid and protein enter the interstitium by bulk flow along a hydrostatic pressure gradient, and protein then diffuses into plasma from the interstitium.

Animals↗