O2 radicals mediate reperfusion lung injury in ischemic O2-ventilated canine pulmonary lobe

This study was undertaken to determine whether lung injury after a period of ischemia reperfusion is caused by O2 ventilation during ischemia and whether this injury is mediated by reactive O2 metabolites. Isolated canine left lower pulmonary lobes were subjected to room temperature ischemia for 6 h while being ventilated with either 100% O2, room air, or 100% N2. After the ischemic period, all lobes were perfused with autologous blood and ventilated with 100% O2 for an additional 4 h. In lobes ventilated with 100% O2 during the ischemic period, massive weight gain (228%) occurred 4 h after reperfusion. A marked increase in pulmonary shunt was noted. Lobes ventilated with room air behaved similarly. In contrast, lobes ventilated with 100% N2 gained significantly less weight (54%) and did not manifest any increase in pulmonary shunt. When lobes ventilated with 100% O2 or room air were pretreated with superoxide dismutase (SOD), the injury was significantly reduced. Pressure-volume deflation study of lobes, after ischemia only, demonstrated that ventilation with 100% O2 and with 100% N2 both equally decreased pulmonary compliance. We conclude that lung ischemia-reperfusion injury is related to O2 ventilation during ischemia and that injury can be prevented by administration of SOD or ventilation with 100% N2. This suggests that the injury is related to O2 metabolites produced during O2 ventilation in the absence of the circulation.     

Ventilatory responses to lung inflation and arterial CO2 in halothane-anesthetized dogs

Hypercapnia attenuates the effects of static airway pressure (Paw) on phrenic burst frequency (f) and the expiratory duration (TE) in chloralose-urethan-anesthetized dogs. Surgical removal of the carotid bodies abolishes this interaction. Since halothane anesthesia in hyperoxia greatly impairs peripheral chemoreflexes, experiments were conducted to determine whether hypercapnia would attenuate the effects of Paw on f and TE in halothane-anesthetized dogs (approximately 1.5 minimum alveolar concentration). Integrated activity of the phrenic nerve was monitored as a function of Paw (2-12 cmH2O) in a vascularly isolated left lung at varied levels of arterial PCO2 (PaCO2; 38-80 Torr) controlled by inspired gas concentrations ventilating the denervated but perfused right lung. Halothane was administered only to the right lung. The results were as follows: 1) integrated phrenic amplitude increased with PaCO2 but was unaffected by Paw; 2) f decreased as Paw increased but was not affected by PaCO2; 3) the inspiratory duration (TI) increased as PaCO2 increased but was unaffected by Paw; 4) TE increased as Paw increased but was unaffected by PaCO2; and 5) there was no phrenic response to intravenous sodium cyanide (50-100 micrograms/kg). Thus, unlike chloralose-urethan-anesthetized dogs, hypercapnia does not attenuate the effect of lung inflation on f or TE in halothane-anesthetized dogs. Furthermore, hypercapnia increases TI during halothane anesthesia, an effect found after carotid denervation but not found in intact chloralose-urethan-anesthetized dogs. It is suggested that these differences between chloralose-urethan- and halothane-anesthetized dogs may be due to functional carotid chemoreceptor denervation by halothane.     

CO2 and mechanical factors reduce blood flow in a collapsed lung lobe

Left lower lobe-to-total blood flow ratio (Ql/QT) was measured with electromagnetic flow probes in anesthetized open-chest dogs. There was a 66% reduction in Ql/QT during lobar collapse, a 53% reduction during lobar ventilation hypoxia with pulmonary venous PO2 and PCO2 equal to mixed venous tensions, and a 45% reduction during a similar degree of ventilation hypoxia but with normal end-tidal PCO2. We concluded that the reduction in blood flow during lobar collapse is due predominantly to hypoxic vasoconstriction, but that this mechanism is augmented by the raised PCO2 and mechanical factors present during collapse.     

Contractile responses of canine isolated pulmonary lobar arteries and veins to norepinephrine, serotonin, and tyramine.

Isolated helical strips of canine intrapulmonary lobar arteries and veins (about 4 mm in diameter) undergo dose-related tension development when exposed to increasing concentrations (10(-8) - 10(-3) M) of norepinephrine (NE), serotonin or 5-hydroxytryptamine (5-HT) and tyramine (Tyr). Venous segments were generally more sensitive while the maximum tension development was greater in the arterial strips, probably owing to their greater thickness. Both strips were more sensitive to 5-HT than NE and only responded to Tyr at high concentrations. Norepinephrine and 5-HT were nearly equally efficacious, whereas Tyr was less so. Responses to the latter were slow to develop, exhibited tachyphylaxis, and were greatly inhibited by phentolamine (10(-8) M), an alpha-adrenergic blocker. Exposure to cocaine (10(-5) M) enhanced submaximal NE responses, inhibited Tyr contractions and had no consistent effect on 5-HT responses. Phentolamine (10(-8) M) was also found to inhibit NE responses without altering 5-HT probably acts on other receptors. Tyramine may, in part, act directly on alpha-adrenergic receptors but may also release NE from surviving adrenergic nerve terminals in the preparation. Cocaine inhibits this effect and potentiates responses to lower levels of NE, presumably by blocking NE uptake into nerve terminals although a post-junctional action cannot be excluded.     

Local control of pulmonary resistance and lung compliance in the canine lung.

Local control of pulmonary resistance and lung compliance was studied in the in situ left lower lobe of the canine lung. Recirculation of blood through the lobe while the Pco2 of the ventilatory gas was varied resulted in an increase in resistance and a decrease in compliance only when the pulmonary venous pH was greater than 7.42. Alternating sodium bicarbonate and lactic acid infusion while alveolar Pco2 was maintained below 5 mmHg demonstrated the dependence of the hypocapnic response on the acid-base status of the blood perfusing the respiratory airways. The increase in resistance and decrease in compliance observed at a pulmonary venous pH of 7.64 was comparable to that observed after lobar pulmonary artery occlusion. Varying degrees of hypoxia did not significantly affect bronchomotor tone, nor was the bronchoconstriction following lobar pulmonary artery occlusion affected by the hypoxia. Vagal stimulation superimposed on a stepwise increase in pulmonary venous pH from 7.32 to 7.62 resulted in an increase in resistance which paralleled the increase in resistance when pulmonary venous pH alone was increased. Compliance was not significantly affected by vagal stimulation at any level of pulmonary venous pH.     

Crop responses to CO2 enrichment

Carbon dioxide is rising in the global atmosphere, and this increase can be expected to continue into the foreseeable future. This compound is an essential input to plant life. Crop function is affected across all scales from biochemical to agro-ecosystem. An array of methods (leaf cuvettes, field chambers, free-air release systems) are available for experimental studies of CO₂ effects. Carbon dioxide enrichment of the air in which crops grow usually stimulates their growth and yield. Plant structure and physiology are markedly altered. Interactions between CO₂ and environmental factors that influence plants are known to occur. Implications for crop growth and yield are enormous. Strategies designed to assure future global food security must include a consideration of crop responses to elevated atmospheric CO₂. Future research should include these targets: search for new insights, development of new techniques, construction of better simulation models, investigation of belowground processes, study of interactions, and the elimination of major discrepancies in the scientific knowledge base.     

Effect of CO 2 concentration on phospholipid metabolism in the isolated perfused rat lung

Studies have been carried out on the incorporation of [U-(14)C]glucose, [2-(14)C]pyruvate, [2-(14)C]acetate, and [1-(14)C]-palmitate into the phospholipids of the isolated perfused rat lung in the presence of either 6 or 45 mm total CO(2) concentration in the perfusion medium. Incorporation of [U-(14)C]glucose into total phospholipid and into the phosphatidylcholine fraction was increased 19-53% over the 2-hr perfusion period in lungs perfused with medium containing 45 as compared with 6 mm CO(2). The incorporation of [2-(14)C]acetate, [2-(14)C]-pyruvate, and [1-(14)C]palmitate was not affected by the change in medium CO(2) concentration. Increased incorporation of [U-(14)C]glucose combined with a shift toward greater incorporation into the fatty acids of the phosphatidylcholine fraction produced a maximum increase of 90% in [U-(14)C]glucose incorporation into the fatty acids of phosphatidylcholine after 2 hr of perfusion in the presence of medium containing 45 mm CO(2) as compared with 6 mm CO(2). The increase in medium CO(2) concentration produced as much as a 150% increase in [U-(14)C]glucose incorporation into palmitate derived from the phosphatidylcholine fraction. The results provide evidence that glucose functions as an important precursor of palmitate in the phosphatidylcholine fraction of lung phospholipids and that the CO(2) concentration of the perfusion medium affects the incorporation of glucose into palmitate.     

Regional and temporal variation in canine peripheral lung responses to dry air

Variation in dry airflow-induced broncho-constriction (AIB) in the canine lung periphery was examined using a wedged bronchoscope technique. Collateral system resistance (Rcs) was measured before and after dry-air challenge. Base-line Rcs was similar throughout the lung periphery, between dogs, and over time. Increasing base-line Rcs was correlated with increasing maximum Rcs 5 min postchallenge (Rcs5), increasing change in Rcs (dRcs5), and decreasing percent change in Rcs above base line (%Rcs5). In contrast to repeated challenge in which base-line Rcs was similar, the magnitude of AIB associated with consecutive challenges with unequal base lines depended on the parameter used to evaluate the response (i.e., Rcs5, dRcs5, or %Rcs5). Peripheral lung resistance then increased to a stimulus specific maximum regardless of base-line Rcs, although data expressed as %Rcs5 or dRcs5 may obscure this observation. Although a change in peripheral lung resistance does not necessarily imply airway narrowing, it is consistent with the idea that changes in Rcs are independent of the collateral system's resting tone.     

Flow-induced responses in cat isolated pulmonary arteries

Shimoda, Larissa A., Nan A. Norins, and Jane A. Madden. Flow-induced responses in cat isolatedpulmonary arteries. J. Appl. Physiol.83(5): 1617-1622, 1997.Isolated, cannulated, endothelium-intactcat pulmonary arteries, averaging 692 ± 104 µm in diameter, wereset at a transmural pressure of 10 mmHg and monitored with a videosystem. Intraluminal flow was increased in steps from 0 to 1.6 ml/minby using a syringe pump. An electronic system held pressure constant bychanging outflow resistance. Flow-diameter curves were generated inphysiological saline solution. At constant transmural pressure, thearteries constricted in response to increased intraluminal flow.Constriction was not affected by removing extracellularCa²⁺ but was abolished aftertreatment with ryanodine to deplete intracellular Ca²⁺ stores, with the endothelin-1synthesis inhibitor phosphoramidon, with the endothelin A-receptorantagonist BQ-123, with the protein kinase C inhibitor staurosporine,or with glutaraldehyde to reduce endothelial cell deformability. Theresults indicate that isolated pulmonary arteries can constrict inresponse to intraluminal flow and suggest that constriction is mediatedby endothelin-1 and depends on intracellularCa²⁺ release and protein kinase Cactivation.