6-ketoprostaglandin-f1-alpha and Hyperventilation

In the perinatal period, glucocorticoids are frequently administered to enhance pulmonary maturity or prevent chronic lung disease of prematurity. Recently, it has been suggested that the perinatal exposure to glucocorticoids can be associated with unfavorable neurologic development. We studied the hypothesis that 24-h pretreatment with glucocorticoid might modify cerebrovascular responses to high and low partial arterial CO(2) tension in newborn animals in vivo. A closed cranial window was implanted over the left parietal cortex of 20 anesthetized ventilated newborn (<3 d old) pigs. The actual experiments were carried out in 15 pigs: eight pretreated with a total dose of 6 mg/kg of dexamethasone and seven controls. Five pigs were used for preliminary experiments as described in the text. Pial arteriolar diameters were measured during 1) baseline conditions (normocapnia), 2) hypercapnia induced by ventilating the animals with a gas mixture containing 10% CO(2), or 3) hyperventilation with resultant hypocapnia. Under these conditions, the concentrations of 6-keto-PGF(1alpha) in the CSF were measured in five experimental animals and six controls. In summary, the dexamethasone pretreatment 1) attenuated the hypercapnia-induced dilator responses of pial arterioles and prevented the hypercapnia-associated fall in mean arterial blood pressure; 2) caused moderate, although not statistically significant, diminution in 6-keto-PGF(1alpha) levels in the CSF during baseline; 3) blocked hypercapnia-induced elevation of 6-keto-PGF(1alpha); and 4) enhanced vasoconstrictive arteriolar responses to hyperventilation. We speculate that in the clinical setting, the dexamethasone effects may compromise the adjustments of global or regional cerebral blood flow to changing physiologic states in neonates.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Animals, Newborn; Arterioles; Blood Pressure; Carbon Dioxide; Cerebral Arteries; Cerebrospinal Fluid; Cerebrovascular Circulation; Dexamethasone; Hydrogen-Ion Concentration; Hypercapnia; Hyperventilation; Swine; Vasoconstriction; Vasodilation

Prostacyclin is released during hyperventilation (HV); however, its role as mediator of HV-induced pulmonary vasodilation remains controversial. We have investigated this by studying the effects of HV on pulmonary artery pressure (PAP) in otherwise normal lungs versus lungs vasoconstricted with group B streptococci (GBS), with and without prior prostacyclin synthesis inhibition. Two- to 3-wk-old piglets were given tranylcypromine, a prostacyclin synthetase inhibitor (n = 6), or placebo (n = 6). Animals were mechanically ventilated normally, then hyperventilated (PCO2 1.5 +/- 0.2 kPa) and then returned to normal ventilation. After each 30-min segment, plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (prostacyclin hydrolysis product) levels and PAP were measured. Then GBS infusions were administered to both groups to induce pulmonary hypertension. With GBS, the normal ventilation/hyperventilation/normal ventilation protocol was repeated as above.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Epoprostenol; Hypertension, Pulmonary; Hyperventilation; Lung; Pulmonary Artery; Streptococcal Infections; Streptococcus agalactiae; Swine; Vasodilation

It has been reported that hyperventilation (HV) increases the release of vasodilative prostaglandins (PGs) from animal lungs. However, it has not yet been clarified whether or not the results obtained from animal experiments are applicable to humans. To confirm this point, we performed this study. Healthy male volunteers, aged 22-28 years, were divided into two groups. Group I (n = 11) breathed room air and showed respiratory alkalosis. Group II (n = 11) breathed room air containing 5% CO2 and maintained normal arterial blood pH. Each subject hyperventilated voluntarily and vigorously for 10 min. The mean values of respiratory rates, tidal volumes and minute volumes during HV were 42.1 +/- 6.2 breaths/min, 1390 +/- 280 ml and 58.5 +/- 15.2 l/min, respectively. Arterial and venous blood samples were drawn simultaneously before and after HV from brachial artery and medial cubital vein, respectively. Plasma 6-keto PGF1 alpha, a metabolite of PGI2, and PGE2 were measured by radioimmunoassay (RIA). After HV, concentrations of 6-keto PG F1 alpha and PGE2 in both arterial and venous blood were increased significantly. There were no significant differences in the levels of 6-keto PGF1 alpha and PGE2 between two groups, nor between arterial and venous blood either before or after HV. We concluded that voluntary HV stimulates the release of PGI2 and PGE2 from lung in humans and respiratory alkalosis has no significant effect on the release of PGs.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Carbon Dioxide; Dinoprostone; Epoprostenol; Humans; Hydrogen-Ion Concentration; Hyperventilation; Lung; Male; Oxygen; Partial Pressure; Reference Values; Respiration; Tidal Volume

This study was designed to determine whether the effects of hyperventilation on the pulmonary circulation of the newborn lamb were 1) due to mechanical factors or to respiratory alkalosis; and 2) mediated by prostaglandins. Six control lambs were studied during normal ventilation and during hyperventilation with, and without, decreased carbon dioxide (CO2). Five lambs were given indomethacin and studied similarly. In control lambs, hyperventilation with decreased CO2 decreased pulmonary arterial pressure from 26 +/- 2.2 to 18 +/- 1.0 (SE) Torr (P less than or equal to 0.005) and pulmonary vascular resistance from 0.099 +/- 0.035 to 0.070 +/- 0.011 Torr X kg-1 X min-1 (P less than or equal to 0.015). Hyperventilation with normal CO2 did not affect the pulmonary circulation. Hyperventilation with decreased CO2 increased pulmonary arterial concentrations of 6-ketoprostaglandin F1 alpha, a major metabolite of prostacyclin, in control lambs but not in the indomethacin-treated lambs. However, it affected the pulmonary circulation of the control- and indomethacin-treated lambs similarly. In conclusion, hyperventilation affected the pulmonary circulation by respiratory alkalosis not by mechanical factors and prostaglandins did not mediate its effects.

Topics: 6-Ketoprostaglandin F1 alpha; Alkalosis; Animals; Animals, Newborn; Blood Pressure; Carbon Dioxide; Cardiac Output; Hyperventilation; Indomethacin; Pressure; Pulmonary Circulation; Sheep

The influence of hyperventilation on the pulmonary prostaglandin (PG) release was studied in healthy volunteers. Hyperventilation was forced by adding 8% CO2 to the inhaled air and arterial and mixed venous blood was sampled for radioimmunoassays of 6-keto-PGF1 alpha and PGE2. The increased ventilation did not alter the arterio-venous PG concentration differences suggesting that hyperventilation accompanying the activation of chemoreceptors is not a physiologically significant stimulus for the pulmonary PG release in man.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Chemoreceptor Cells; Dinoprostone; Female; Humans; Hyperventilation; Lung; Male; Prostaglandins; Prostaglandins E

The influence of hyperventilation on the spontaneous generation of prostacyclin and thromboxane A2 by isolated rat lungs was studied. Both prostacyclin and thromboxane A2, as measured by RIA of their stable end-products, 6-oxo-PGF1 alpha and TXB2 respectively, were continuously released into the perfusate. However, the concentration of prostacyclin in the perfusate was higher than thromboxane A2. Under normal ventilation at a rate 40-50 breaths/min, the ratio between these two compounds was 5:1. Increasing the rate of respiration to 100 breaths/min preferentially stimulated the release of prostacyclin. During hyperventilation-stimulated release of prostacyclin and thromboxane A2. Hydroperoxy-fatty acids and tranylcypromine inhibited only the release of prostacyclin but did not affect the generation of thromboxane A2. Our findings confirm that the lung generates prostacyclin predominantly, and provide direct evidence that respiratory movements are involved in generation of pulmonary prostacyclin and thromboxane A2.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Arachidonic Acids; Aspirin; Epoprostenol; Fatty Acids; Hyperventilation; Indomethacin; Lung; Male; Prostaglandins; Prostaglandins F; Rats; Thromboxane A2; Thromboxanes; Tranylcypromine