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Decompensation of hypoxic pulmonary vasoconstriction in acutely injured lungs
WS2-I-2-03 DECOMPENSATION OF HYPOXlC PULMONARY VASOCONSTRICTION IN ACUTELY INJURED LUNGS M. Mori 1, T. Takasugi 2, A. Umeda2, Y. Oyamada2, H. Fujita 2, K. Suzuki 2, A. Miyata2, T. Aoki 2, Y. Suzuki 2, K. Yamaguchi 2 1) Health Center, Keio University, Tokyo, Japan 2) Dept. of Medicine, School of Medicine, Keio University, Tokyo, Japan
Hypoxic pulmonary vasoconstriction(HPV) is known as a compensatory mechanism to maintain the
matching of
ventilation to perfusion in the lungs. However, several authors have reported that HPV in acutely injured lungs is indeed impaired due to a diminished response of pulmonary vasculature to oxygen. Such phenomenon, i.e. decompenation of HPV sometimes worsen pulmonary gas exchange in acutely injured lungs. In order to examine possible mechanisms on decompensation of HPV, we produced acute lung injury by intravenous administration of oleic acid and investigated the effects of arachidonic acid metabolites on impaired gas exchange in canine lungs. To assess the alteration of pulmonary gas exchange in injured lungs, we measured alveolar-arterial oxygen tension difference (AaPo2) as well as retention of SF6(RsF6); indicator of the shunt-like effect. The experimental findings derived therefrom showed: (1) Hyperoxic gas breathing significantly decreased RSF6. (2) Indomethacin; a noble cyclooxygenase inhibitor, caused a considerable reduction in genesis of prostacyclin (PGI2) as well as thromboxane A2(TXA2) but little change of 5-1ipoxygenase products, leading to a significant diminution of RSF6 associated with decreasing AaPo2. (3) OKY-046; TXA2 synthase blocker, decreased the production of TXA2 but increased that of PGI2, resulting in worsened RsF6 and AaPo2. (4) intravenous administration of PGI2 augmented RSF6 accompanied by increasing AaPo2. (5) AA-861; 5-1ipoxygenase inhibitor, suppressed the synthesis of leukotrienes(LTs) and increased RsF6 and AaPo2. (6) Infusion of LTD4 improved RSF8 and AaPo2. It is thus concluded that HPV deteriorated distinctly in diseased areas of injured lungs.
This deterioration is due probably to a local accumulation of the vasodilator, PGI2 in
diseased areas. Vasoconstrictor; TXA2, may be of minor importance for modulating gas exchange in injured lungs. LTs may improve the gas exchange in acutely injured lungs due probably to a restoration of local HPV coping with vasodilation induced by PGI2.
WS2-I-2-04 EFFECT OF HYPOXIA ON CENTRAL HEMODYNAMICS, ORGAN BLOOD FLOW, ORGAN OXYGEN SUPPLY AND HEMATOPOIETIC RESPONSES IN CONSCIOUS RESTING RATS I. Kuwahira1, N. Heisler2, J. Piiperz and N. C. Gonzalez3 1) Department of Medicine, Tokai University School of Medicine, Kanagawa 259-11, Japan 2) Abteilung Physiologle, Max-Planck-institut fiir experimentelle Medizin, D-37075 G6ttingen, Germany 3) Department of Physiology, University of Kansas Medical Center, Kansas City, KS 66160-7401, USA Central hemodynamics, arterial blood gases, organ blood flow, and organ oxygen supply (organ blood flow x arterial 02 concentration) were studied in 10 chronically hypoxic rats (3 weeks, PB 370-380 Tort) breathing 10% O2 (chronic hypoxia). Controls were 10 normoxic littermates breathing air (normoxia) and 10% 02 for 30 min (acute hypoxia). Organ blood flow was determined by the reference sample microsphere method. A polyethylene catheter (PE-50) was introduced into the right common carotid artery and advanced into the ascending aorta for microsphere infusion. Another PE-50 catheter was placed into the middle portion of the caudal artery for withdrawal of the reference blood sample. Measurement was carried out after full recovery from anesthesia. At the end of the experiment, the rats were sacrificed by an overdose of pentobarbital sodium, and the organs were removed, weighed, and counted in a multichannel gamma scintillation analyzer. Total aortic blood flow and blood flow to the organs were computed from sample radioactivity and wet weight. Arterial blood pressure and heart rate were recorded from the caudal artery. Arterial blood sample for blood gas analysis was obtained from the caudal artery. Acute hypoxia produced acute respiratory alkalosis with a decrease in arterial Po 2 (Pao2) associated with a decrease in oxyhemoglobin saturation (Sao2). As a result of these changes, arterial oxygen concentration (Cao2) was decreased markedly. Aortic blood flow and heart rate increased, and total peripheral resistance decreased significantly. Blood flow and oxygen supply to brain, respiratory muscle (diaphragm), and liver increased selectively, indicating that the blood flow redistribution is the predominant mechanism contributing to changes in organ oxygen supply during acute hypoxia. In chronic hypoxia, in spite of lower Pao 2 and Sao 2, Cao 2 increased to the normoxia control level because of the marked increase in hemoglobin (Hb) concentration. Aortic blood flow and heart rate remained elevated, and total peripheral resistance remained decreased. The pattern of blood flow distribution returned towards that of the normoxia control. Oxygen supply to the organs was not significantly different from that observed in normoxia. This indicates that the blood oxygen transport system is sufficiently maintained without redistribution of blood flow and that organ oxygen supply is insured by a marked increase in Hb concentration during 3 weeks of chronic hypoxia. In order to determine the time course of changes in red blood cell counts (RBC), Hb concentration, hematocrit (I-Ict), plasma erythropoietin (EPO), and blood 2,3-diphosphoglycerate (2,3-DPG) during chronic hypoxia, five groups of rats (five rats in each) were studied for the first 18h, 72h, 7, 14, and 21 days, respectively. RBC, Hb concentration, Hct, and 2,3-DPG increased markedly within the first 7 days of hypoxia and reached to the levels of those observed at 21 days. Plasma EPO increased markedly at 18h of hypoxia, and declined within 72h during continued exposure of hypoxia. These results indicate that an increase in Hb concentration (polycythemia) plays an important role in organ oxygen supply in chronic hypoxia, and that organ oxygen supply is already insured within the first 7 days of hypoxic exposure. (Supported by NIH grant HL 39443 and Tokai University School of Medicine Research Aid).
157
Hypoxic pulmonary vasoconstriction(HPV) is known as a compensatory mechanism to maintain the
matching of
ventilation to perfusion in the lungs. However, several authors have reported that HPV in acutely injured lungs is indeed impaired due to a diminished response of pulmonary vasculature to oxygen. Such phenomenon, i.e. decompenation of HPV sometimes worsen pulmonary gas exchange in acutely injured lungs. In order to examine possible mechanisms on decompensation of HPV, we produced acute lung injury by intravenous administration of oleic acid and investigated the effects of arachidonic acid metabolites on impaired gas exchange in canine lungs. To assess the alteration of pulmonary gas exchange in injured lungs, we measured alveolar-arterial oxygen tension difference (AaPo2) as well as retention of SF6(RsF6); indicator of the shunt-like effect. The experimental findings derived therefrom showed: (1) Hyperoxic gas breathing significantly decreased RSF6. (2) Indomethacin; a noble cyclooxygenase inhibitor, caused a considerable reduction in genesis of prostacyclin (PGI2) as well as thromboxane A2(TXA2) but little change of 5-1ipoxygenase products, leading to a significant diminution of RSF6 associated with decreasing AaPo2. (3) OKY-046; TXA2 synthase blocker, decreased the production of TXA2 but increased that of PGI2, resulting in worsened RsF6 and AaPo2. (4) intravenous administration of PGI2 augmented RSF6 accompanied by increasing AaPo2. (5) AA-861; 5-1ipoxygenase inhibitor, suppressed the synthesis of leukotrienes(LTs) and increased RsF6 and AaPo2. (6) Infusion of LTD4 improved RSF8 and AaPo2. It is thus concluded that HPV deteriorated distinctly in diseased areas of injured lungs.
This deterioration is due probably to a local accumulation of the vasodilator, PGI2 in
diseased areas. Vasoconstrictor; TXA2, may be of minor importance for modulating gas exchange in injured lungs. LTs may improve the gas exchange in acutely injured lungs due probably to a restoration of local HPV coping with vasodilation induced by PGI2.
WS2-I-2-04 EFFECT OF HYPOXIA ON CENTRAL HEMODYNAMICS, ORGAN BLOOD FLOW, ORGAN OXYGEN SUPPLY AND HEMATOPOIETIC RESPONSES IN CONSCIOUS RESTING RATS I. Kuwahira1, N. Heisler2, J. Piiperz and N. C. Gonzalez3 1) Department of Medicine, Tokai University School of Medicine, Kanagawa 259-11, Japan 2) Abteilung Physiologle, Max-Planck-institut fiir experimentelle Medizin, D-37075 G6ttingen, Germany 3) Department of Physiology, University of Kansas Medical Center, Kansas City, KS 66160-7401, USA Central hemodynamics, arterial blood gases, organ blood flow, and organ oxygen supply (organ blood flow x arterial 02 concentration) were studied in 10 chronically hypoxic rats (3 weeks, PB 370-380 Tort) breathing 10% O2 (chronic hypoxia). Controls were 10 normoxic littermates breathing air (normoxia) and 10% 02 for 30 min (acute hypoxia). Organ blood flow was determined by the reference sample microsphere method. A polyethylene catheter (PE-50) was introduced into the right common carotid artery and advanced into the ascending aorta for microsphere infusion. Another PE-50 catheter was placed into the middle portion of the caudal artery for withdrawal of the reference blood sample. Measurement was carried out after full recovery from anesthesia. At the end of the experiment, the rats were sacrificed by an overdose of pentobarbital sodium, and the organs were removed, weighed, and counted in a multichannel gamma scintillation analyzer. Total aortic blood flow and blood flow to the organs were computed from sample radioactivity and wet weight. Arterial blood pressure and heart rate were recorded from the caudal artery. Arterial blood sample for blood gas analysis was obtained from the caudal artery. Acute hypoxia produced acute respiratory alkalosis with a decrease in arterial Po 2 (Pao2) associated with a decrease in oxyhemoglobin saturation (Sao2). As a result of these changes, arterial oxygen concentration (Cao2) was decreased markedly. Aortic blood flow and heart rate increased, and total peripheral resistance decreased significantly. Blood flow and oxygen supply to brain, respiratory muscle (diaphragm), and liver increased selectively, indicating that the blood flow redistribution is the predominant mechanism contributing to changes in organ oxygen supply during acute hypoxia. In chronic hypoxia, in spite of lower Pao 2 and Sao 2, Cao 2 increased to the normoxia control level because of the marked increase in hemoglobin (Hb) concentration. Aortic blood flow and heart rate remained elevated, and total peripheral resistance remained decreased. The pattern of blood flow distribution returned towards that of the normoxia control. Oxygen supply to the organs was not significantly different from that observed in normoxia. This indicates that the blood oxygen transport system is sufficiently maintained without redistribution of blood flow and that organ oxygen supply is insured by a marked increase in Hb concentration during 3 weeks of chronic hypoxia. In order to determine the time course of changes in red blood cell counts (RBC), Hb concentration, hematocrit (I-Ict), plasma erythropoietin (EPO), and blood 2,3-diphosphoglycerate (2,3-DPG) during chronic hypoxia, five groups of rats (five rats in each) were studied for the first 18h, 72h, 7, 14, and 21 days, respectively. RBC, Hb concentration, Hct, and 2,3-DPG increased markedly within the first 7 days of hypoxia and reached to the levels of those observed at 21 days. Plasma EPO increased markedly at 18h of hypoxia, and declined within 72h during continued exposure of hypoxia. These results indicate that an increase in Hb concentration (polycythemia) plays an important role in organ oxygen supply in chronic hypoxia, and that organ oxygen supply is already insured within the first 7 days of hypoxic exposure. (Supported by NIH grant HL 39443 and Tokai University School of Medicine Research Aid).
157