Sites of pulmonary vasomotor reactivity in the dog during alveolar hypoxia and serotonin and histamine infusion

Glazier, J B; Murray, John F.

doi:10.1172/jci106755

Cited by 73 publications

(29 citation statements)

References 21 publications

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“…29 " 31 Our finding of no change in lung lymph flow with the persistent elevation of pulmonary vascular resistance is further evidence that the site of vasoconstriction is proximal to the fluid exchange vessels in the lung, since more distal constriction would have caused an increase in lymph flow by a rise in vascular hydraulic pressure, as we always see when P la increases. 18 We considered the possibility that a superimposed stress, such as elevating P, a with hypoxia, or more prolonged hypoxia, might induce pulmonary edema.…”

Section: Discussionsupporting

confidence: 57%

Effects of alveolar hypoxia on lung fluid and protein transport in unanesthetized sheep.

Bland¹,

Demling²,

Selinger³

et al. 1977

Circulation Research

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SUMMARY To determine whether hypoxia directly affects pulmonary microvascular filtration of fluid or permeability to plasma proteins, we measured steady state lung lymph flow and protein transport in eight unanesthetized sheep breathing 10% O 2 in N» for 4 hours. We also studied three sheep breathing the same gas mixture for 48 hours. We surgically prepared the sheep to isolate and collect lung lymph and to measure average pulmonary arterial (P pa ) and left atrial (P la ) pressures. We placed a balloon catheter in the left atrium to elevate P la . After recovery, the sheep breathed air through a tracheostomy for 2-4 hours, followed by 4 or 48 hours of hypoxia. In 13 4-hour studies, the average arterial Po 2 fell from 97 to 38 torr; P pa rose from 20 to 33 cm H,O; and lung lymph flow and lymph protein flow were unchanged. We also found that during 48-hour hypoxia, with a sustained elevation in P pa and a decline in P la , lymph flow and protein flow did not increase. In four sheep, we also raised Pi a for 4 hours, followed by 4 hours of hypoxia with elevated P la . Again, despite the added stress of elevated P la , we found that lymph flow and lymph protein flow remained constant during hypoxia. We conclude that severe alveolar hypoxia, for 4 or 48 hours, alone or with increased pulmonary microvascular pressure, produced no change in lung fluid filtration or protein permeability, a finding supported by normal postmortem histology and extravascular lung water content.IN 1945, DRINKER concluded that "oxygen lack is the most potent and elusive cause of abnormal leakage from the lung capillaries," 1 based on the observations that flow from the right lymphatic duct of anesthetized dogs increased when the dogs breathed a 10% oxygen gas mixture.2 -3 Courtice and Korner 4 reported in 1952 that hypoxia predisposed rabbits to pulmonary edema induced by infusions of Ringer's solution, but the authors attributed the edema to heart failure and not altered vascular permeability to plasma proteins.Other investigators have been unable to substantiate Drinker's conclusion. Haddy et al. 5 showed in anesthetized dogs that hypoxia alone did not produce pulmonary edema, but only did so in the presence of elevated pulmonary venous pressure. Hemingway 6 exposed guinea pigs to gas mixtures containing as little as 2% oxygen, but found no evidence of pulmonary edema when he killed the guinea pigs and examined their lungs.Using isolated, perfused dog lungs, Nicoloff et al. 7 were unable to demonstrate an increase in lung weight with extreme hypoxia. Goodale et al. 8 found that even total absence of oxygen in the inspired gas did not alter the permeability of the alveolocapillary membrane to tracer albumin in isolated, perfused dog lungs. Fisher et al.9 saw no changes in the ultrastructure of the alveolar septum of intact dog lungs ventilated with nitrogen for 3-7 hours, and Teplitz et al. 10 were unable to elicit pulmonary edema in rats with hypobaric hypoxia equivalent to 7% oxygen in the inspired gas for up to 30 hours.Despite all of th...

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Section: Discussionsupporting

confidence: 57%

Effects of alveolar hypoxia on lung fluid and protein transport in unanesthetized sheep.

Bland¹,

Demling²,

Selinger³

et al. 1977

Circulation Research

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“…Although several investigators have presented evidence for hypoxia induced pulmonary venous constriction in both dogs (29,32) and cattle (23), Hyman and Kadowitz (20) found no evidence of pulmonary venous constriction during alveolar hypoxia in lambs that were 3-mo-old. They and other investigators have concluded that alveolar hypoxia constricts predominantly arteriolar vessels in the lung (2,12,22,26). If the site of critical tone is in the pulmonary arteriole, then the site of fluid filtration would have to be in small pulmonary arterioles, as postulated by Whayne and Severinghaus (46).…”

Section: Discussionmentioning

confidence: 92%

Lung Fluid Balance in Hypoxic Lambs

et al. 1984

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SummaryIn spontaneously breathing newborn lambs, alveolar hypoxia increases lung microvascular pressure, which causes lung lymph flow to increase and the concentration of protein in lymph to decrease. To see if this response derives from hypoxia itself rather than from the change in breathing pattern that occurs during hypoxia, we measured lung vascular pressures, pleural pressure, cardiac output, and lung lymph flow in 12 anesthetized lambs that were ventilated at a fixed rate and tidal volume, first with air, then with 10-14% O2 in nitrogen. Alveolar hypoxia did not affect pleural pressure, but pulmonary arterial pressure increased from 19 to 32 torr, lung lymph flow increased from 2.20 to 3.83 ml/h and lymph protein concentration decreased from 3.4 to 2.8 g/dl. To be certain that the increased lymph flow associated with hypoxia is not simply the result of an acute release of fluid from the lungs and to assess the effects of carbon dioxide on lymph flow during hypoxia, we next studied six unanesthetized lambs kept hypoxic for a total of 12 h. After a 2-4-h period in air the lambs breathed 9-11% 0 2 in nitrogen for 2-4 h, then 8-11% O2 and 3-5% C02 in nitrogen for 8-10 h. In these lambs we injected intravenously radioactive albumin and measured its uptake in lymph to see if sustained hypoxia alters microvascular permeability to protein in the lungs. In these experiments pulmonary arterial pressure increased from 17 to 37 torr, lung lymph flow increased from 1.74 to 3.28 ml/h, and lymph protein concentration decreased from 3.8 to 3.1 g/dl during hypoxia. Addition of C02 to the inspired gas did not affect steady state lung lymph flow. Lymph flow remained elevated throughout the 12 h of alveolar hypoxia, and postmortem lung water determinations were not different from those of controls (4.65 f 0.28 versus 4.72 f 0.14 g/g dry bloodless lung). The time required for radioactive albumin to equilibrate in lymph at one-half the specific activity of plasma was no different before and during hypoxia (130 + 7 versus 125 f 11 min). We conclude that in the newborn lamb, alveolar hypoxia increases transvascular fluid filtration by increasing microvascular hydraulic pressure without altering microvascular permeability to protein. This response is independent of changes in pleural pressure or inspired carbon dioxide. Bressack and Bland (5,6) showed that alveolar hypoxia increases lung lymph flow and decreases lymph protein concentration in newborn lambs. They concluded that alveolar hypoxia increases transvascular fluid filtration in the lung by increasing filtration pressure without altering microvascular permeability to protein.At least two issues were unanswered by the previous studies. First, because Bressack and Bland used unanesthetized lambs that breathed spontaneously, hypoxia caused hyperventilation and a resultant decrease in arterial Pco2 and pleural pressure. Arterial Pco2 may influence pulmonary vascular tone (20,25) and pleural pressure may influence lung interstitial fluid pressure (1 4,2 I, 27,38,45); it is poss...

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“…Since diphenhydramine caused left atrial pressure to rise and pulmonary artery pressure to fall, some of the effect on lymph flow could have been secondary to redistribution of vascular resistance between pre-and postcapillary vessels (16). However, in response to changes in pressure alone, lymph: plasma protein concentration ratios relate inversely to lung lymph flow (1, 2), and diphenhydramine given during the histamine response caused both lung lymph flow and lymph: plasma protein concentration ratios to fall.…”

Section: Resultsmentioning

confidence: 99%

Effects of antihistamines on the lung vascular response to histamine in unanesthetized sheep. Diphenhydramine prevention of pulmonary edema and increased permeability.

Brigham¹,

Bowers²,

Owen³

1976

J. Clin. Invest.

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A B S T R A C T To see whether antihistamines could prevent and reverse histamine-induced pulmonary edema and increased lung vascular permeability, we compared the effects of a 4-h intravenous infusion of 4 /Ag/kg per min histamine phosphate on pulmonary hemodynamics, lung lymph flow, lymph and plasma protein content, arterial blood gases, hematocrit, and lung water with the effects of an identical histamine infusion given during an infusion of diphenhydramine or metiamide on the same variables in unanesthetized sheep. Histamine caused lymph flow to increase from 6.0±0.5 to 27.0±5.5 (SEM) ml/h (P <0.05), lymph: plasma globulin concentration ratio to increase from 0.62±0.01 to 0.67±0.02 (P < 0.05), left atrial pressure to fall from 1+1 to -3±1 cm H20 (P < 0.05), and lung lymph clearance of eight protein fractions ranging from 36 to 96 A molecular radius to increase significantly. Histamine also caused increases in lung water, pulmonary vascular resistance, arterial Pco2, pH, and hematocrit, and decreases in cardiac output and arterial Po2. Diphenhydramine (3 mg/kg before histamine followed by 1.5 mg/ kg per h intravenous infusion) completely prevented the histamine effect on hematocrit, lung lymph flow, lymph protein clearance, and lung water content, and reduced histamine effects on arterial blood gases and pH. 6 mg/kg diphenhydramine given at the peak histamine response caused lymph flow and lymph: plasma protein concentration ratios to fall. Metiamide (10 mg/ Description of the preparation We used an unanesthetized, chronic sheep preparation described previously (1-4). Each animal was prepared by a series of three staged thoracotomies during which nonpulmonary contributions to a large lymph node in the posterior mediastinum (caudal mediastinal node) were resected;

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Sites of pulmonary vasomotor reactivity in the dog during alveolar hypoxia and serotonin and histamine infusion

Cited by 73 publications

References 21 publications

Effects of alveolar hypoxia on lung fluid and protein transport in unanesthetized sheep.

Effects of alveolar hypoxia on lung fluid and protein transport in unanesthetized sheep.

Lung Fluid Balance in Hypoxic Lambs

Effects of antihistamines on the lung vascular response to histamine in unanesthetized sheep. Diphenhydramine prevention of pulmonary edema and increased permeability.

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