Biomedical subjects

J V Weil

Publications and source records attributed to J V Weil.

At least 19 recordsLinked to original sources

PubMed1992

Effects of haloperidol and domperidone on ventilatory roll off during sustained hypoxia in cats.

In a previous work, we showed that the adult cat demonstrates a ventilatory decline during sustained hypoxia (the "roll off" phenomenon) and that the mechanism responsible for this secondary decrease in ventilation lies within the central nervous system (J. Appl. Physiol. 63: 1658-1664, 1987). In this study, we sought to determine whether central dopaminergic mechanisms could have a role in the roll off. We studied the effects of haloperidol, a peripheral and centrally acting dopamine receptor antagonist, on the ventilatory response to sustained isocapnic hypoxia (end-tidal PO2 40-50 Torr, 20-25 min) in awake cats. In vehicle control cats (n = 5), sustained hypoxia elicited a biphasic respiratory response, during which an initial ventilatory stimulation is followed by a 24 +/- 6% (P less than 0.01) reduction. In contrast, in haloperidol- (0.1 mg/kg) treated cats (n = 5) the ventilatory roll off was virtually abolished (-1 +/- 1%; P = NS). We also measured ventilatory, carotid sinus nerve (CSN) and phrenic nerve (PhN) responses to sustained isocapnic hypoxia in anesthetized animals (n = 6) to explore the influence of haloperidol on peripheral and central response during the roll off. Control responses to hypoxia showed an initial increase in ventilation, PhN, and CSN activity, followed by a subsequent decline in ventilation and PhN activity of 17 +/- 3 and 17 +/- 5%, respectively (P less than 0.05). In contrast, CSN activity remained unchanged during the roll off. Administration of haloperidol (1 mg/kg) reduced the initial increment in ventilation, while the initial increase in CSN activity was augmented.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Coronary vascular injury due to ischemia-reperfusion is reduced by pentoxifylline.

Myocardial ischemia and reperfusion cause coronary vascular injury involving both the large epicardial arteries and the microcirculation. Although the mechanisms are unclear, leukocytes appear to play an important role. Since the methylxanthine derivative pentoxifylline (PTX) decreases neutrophil activity in vitro, we hypothesized that it might diminish coronary vascular injury due to ischemia and reperfusion. We investigated the effects of PTX on coronary microvascular and epicardial artery injury in open chest, anesthetized dogs undergoing moderate (60 min) or more prolonged (90 min) ischemia due to left anterior descending coronary artery occlusion followed by 60 min of reperfusion. As an index of microvascular injury, we assessed regional permeability with a dual radioisotope protein leak index (PLI) method. Both ischemic periods with reperfusion increased the PLI of severely ischemic (flow less than or equal to 20/ml/min/100 g) myocardium by 2.5- and 3-fold, respectively, compared to nonischemic (flow greater than or equal to 100 ml/min/100 g) myocardium. Treated dogs received PTX (20 mg/kg bolus plus 0.1 mg/kg/min infusion) before ischemia. PTX reduced the increase in the PLI by 40% after 60 min of ischemia (PLI = 5.87 +/- 0.48 vs. 4.10 +/- 0.52 untreated vs. PTX-treated; P less than .05), and by 25% after 90 min of ischemia (6.84 +/- 0.49 vs. 4.84 +/- 0.42; P less than .05). The amount of protein leak was inversely related to ischemic blood flow, and the magnitude of this relationship was significantly reduced in PTX-treated animals. In arterial rings from untreated dogs exposed to 90 min of ischemia followed by reperfusion, there was impaired relaxation to ADP and acetylcholine, but not to sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Reactive oxygen metabolite scavengers decrease functional coronary microvascular injury due to ischemia-reperfusion.

The role of reactive oxygen metabolites in ischemia-reperfusion coronary microvascular injury is unclear. To investigate this problem, we tested the effects of the reactive oxygen metabolite scavengers superoxide dismutase (SOD) and dimethylthiourea (DMTU) on ischemia-reperfusion-induced coronary microvascular dysfunction. As an index of vascular function, we assessed microvascular permeability with a double radioisotope protein leak index (PLI) method. Anesthetized dogs underwent 60 min of ischemia via left anterior descending (LAD) occlusion followed by 60 min of reperfusion. Untreated animals (n = 7) received saline. SOD-treated animals (n = 6) received 140 U.kg-1.min-1 (6.6 mg.kg-1.min-1) bovine SOD throughout ischemia and reperfusion. DMTU-treated animals (n = 5) received a 500 mg/kg bolus 30 min before ischemia. At the beginning of reperfusion, radiolabeled autologous protein (113mIn transferrin) and red blood cells (99mTc) were given intravenously for the assessment of permeability. In untreated dogs, ischemia-reperfusion increased the PLI of ischemic (flow less than 20 ml.min-1.100 g-1) myocardium more than threefold compared with that of nonischemic (flow greater than 100 ml.min-1.100 g-1) myocardium (ischemic-to-nonischemic PLI ratio = 3.49 +/- 0.48). SOD reduced the PLI of ischemic myocardium by 45% and DMTU reduced it by 66% (PLI = 9.25 +/- 1.30, 5.04 +/- 1.18, and 3.16 +/- 0.94, untreated, SOD, and DMTU, respectively). The PLI was increased proportional to the regional severity of ischemic blood flow. Both SOD and DMTU reduced the increase in protein leak at all levels of regional ischemic blood flow. Neither SOD nor DMTU increased regional myocardial blood flow to the occluded LAD zone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Attenuated carotid body hypoxic sensitivity after prolonged hypoxic exposure.

Prolonged exposure to hypoxia is accompanied by decreased hypoxic ventilatory response (HVR), but the relative importance of peripheral and central mechanisms of this hypoxic desensitization remain unclear. To determine whether the hypoxic sensitivity of peripheral chemoreceptors decreases during chronic hypoxia, we measured ventilatory and carotid sinus nerve (CSN) responses to isocapnic hypoxia in five cats exposed to simulated altitude of 5,500 m (barometric pressure 375 Torr) for 3-4 wk. Exposure to 3-4 wk of hypobaric hypoxia produced a decrease in HVR, measured as the shape parameter A in cats both awake (from 53.9 +/- 10.1 to 14.8 +/- 1.8; P less than 0.05) and anesthetized (from 50.2 +/- 8.2 to 8.5 +/- 1.8; P less than 0.05). Sustained hypoxic exposure decreased end-tidal CO2 tension (PETCO2, 33.3 +/- 1.2 to 28.1 +/- 1.3 Torr) during room-air breathing in awake cats. To determine whether hypocapnia contributed to the observed depression in HVR, we also measured eucapnic HVR (PETCO2 33.3 +/- 0.9 Torr) and found that HVR after hypoxic exposure remained lower than preexposed value (A = 17.4 +/- 4.2 vs. 53.9 +/- 10.1 in awake cats; P less than 0.05). A control group (n = 5) was selected for hypoxic ventilatory response matched to the baseline measurements of the experimental group. The decreased HVR after hypoxic exposure was associated with a parallel decrease in the carotid body response to hypoxia (A = 20.6 +/- 4.8) compared with that of control cats (A = 46.9 +/- 6.3; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Altitude↗

PubMed1991

Influences of gender and sex hormones on hypoxic ventilatory response in cats.

Hypoxic ventilatory response (HVR) is known to be increased by female as well as male sex hormones, but whether there are differences in HVR between men and women remains unclear. To determine whether gender differences exist in HVR, we undertook systematic comparisons of resting ventilation and HVR in awake male and female cats. Furthermore to explore the potential contribution of sex hormones to gender differences observed, we compared neutered and intact cats of both sexes. Resting ventilation differed among the four groups, but differences disappeared with correction for body weight. Intact females had a lower end-tidal PCO2 than intact male cats (females: 31.6 +/- 0.4 Torr vs. males: 33.6 +/- 0.4 Torr, P less than 0.05), indicating an increased alveolar ventilation per unit CO2 production. HVR expressed as the shape parameter A was similar among the four groups of animals. However, baseline (hyperoxic; end-tidal PO2 greater than 200 Torr) minute ventilation [VI(PO2 greater than 200)] differed among the groups. Therefore we normalized HVR by dividing the shape parameter A by VI(PO2 greater than 200) to compare the relative hypoxic chemosensitivity among the various groups of animals. In addition, we further normalized HVR for body weight, because body size influences ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Pentoxifylline lessens the endotoxin-induced increase in albumin clearance across pulmonary artery endothelial monolayers with and without neutrophils.

Pentoxifylline, a methylxanthine with phosphodiesterase inhibitor activity, attenuates endotoxin-induced pulmonary vascular protein leak and decreases lung neutrophil accumulation in vivo. In vitro, pentoxifylline decreases neutrophil activation as measured by superoxide release and phagocytosis of latex beads. To test the hypothesis that the beneficial effect of pentoxifylline may be via a direct effect on the endothelial cells as well as via prevention of neutrophil activation, we incubated bovine pulmonary artery endothelial cell monolayers with endotoxin and pentoxifylline in the presence or absence of human neutrophils. Albumin clearance across the monolayers was used as an index of endothelial permeability. Endotoxin (1.0 micrograms/ml) increased albumin clearance in a dose- and time-dependent fashion (207.5 +/- 25%, P less than 0.05). Co-incubation with neutrophils enhanced this effect. Pentoxifylline significantly attenuated the endotoxin-induced increase in albumin clearance both with and without neutrophils, and lessened endotoxin-induced cell lysis (chromium release) and morphologic changes. Because increased endothelial cyclic adenosine monophosphate (cAMP) levels may decrease protein permeability and pentoxifylline increases cAMP in neutrophils, we measured cAMP levels in endothelial cells. Incubation with pentoxifylline failed to raise cAMP levels in endothelial cells, in contrast to incubation with aminophylline. In conclusion, pentoxifylline attenuates endotoxin-induced increase in albumin clearance across endothelial monolayers both in the presence and absence of neutrophils. These results suggest that part of the protective effect of pentoxifylline may be mediated via effects on endothelium. Furthermore, this pentoxifylline-mediated endothelial barrier effect appears to be independent of an effect on cAMP.

Albumins↗

PubMed1990

Serum endothelin-1 concentrations and cold provocation in primary Raynaud's phenomenon.

To determine whether the vasoconstriction in Raynaud's phenomenon is associated with raised concentrations of the endothelium-derived vasoconstrictor endothelin (ET-1), responses to cold pressor testing were examined in 7 subjects with primary Raynaud's phenomenon and in 7 control subjects. Baseline serum ET-1 levels (pg/ml), as measured by radioimmunoassay, were three times higher in Raynaud's subjects (5.3 [SEM 1.7] pg/ml) than in controls (1.7 [0.3]). With progressive local cooling digital arterial pulsatility, as measured by plethysmography, fell earlier and to a greater extent in Raynaud's subjects than in controls, with a half-maximum decrement in pulsatility occurring at 27 [2.6] degrees C and 18 [0.5] degrees C, respectively. Temperature reduction sufficient to cause loss of pulsatility in the Raynaud's subjects produced increases in ET-1 concentrations in both groups that were greater in Raynaud's (10.3 [4.4] pg/ml) than in control subjects (2.7 [0.9] pg/ml). Serum ET-1 in the contralateral arm rose in parallel to but to a lesser extent than that in the cold-challenged arm. Increases in ET-1 concentrations were temporally related to loss of pulsatility but followed the onset of symptoms. Thus the increased basal and stimulated serum endothelin concentrations in Raynaud's disease are associated with the enhanced, prolonged vasospasm of this disorder.

Adult↗

PubMed1990

Functional coronary microvascular injury evident as increased permeability due to brief ischemia and reperfusion.

Although morphological studies suggest that coronary vascular injury is a result of prolonged ischemia and subsequent reperfusion, whether functional coronary microvascular injury develops during brief in vivo ischemia is unclear. In other organs, permeability is a sensitive indicator of functional vascular injury. Therefore, a new double-indicator method of assessing vascular protein permeability, a method that is both sensitive and specific for vascular injury, was used to investigate the effects of ischemia of graded duration followed by reperfusion on coronary microvascular function. To help confirm functional coronary vascular injury, endothelium-dependent vasodilation of isolated coronary vascular rings also was examined. Microvascular permeability was quantitatively assessed as a protein leak index by measuring the rate of extravascular accumulation of radiolabeled protein (indium 113m transferrin) normalized for vascular surface area (technetium 99m erythrocytes). Anesthetized dogs underwent 0 (control), 15, 30, or 60 minutes of left anterior descending coronary artery occlusion followed by 60 minutes of reperfusion. Even 15 minutes of ischemia increased the protein leak index by 50% (3.16 +/- 0.30 ischemic vs. 2.09 +/- 0.11 control). Longer periods of ischemia increased the protein leak index in proportion to the duration of ischemia. The protein leak index increased threefold (6.51 +/- 0.60) after 60 minutes of ischemia. At each duration of ischemia, there was significant regional variation in the protein leak index that correlated with the severity of ischemic blood flow to that region measured with microspheres. Endothelial injury also was evident after 15 and 30 minutes of ischemia as impaired vasodilation of isolated coronary rings in response to the endothelium-dependent vasodilators acetylcholine and the calcium ionophore A23187. Electron microscopy and in vitro direct immunofluorescence revealed evidence of vascular injury after 60 minutes but not after 15 minutes of ischemia. We conclude that even brief ischemia and reperfusion cause functional coronary vascular injury evident as increased microvascular permeability and impaired endothelium-dependent vasodilation and that regional differences in the degree of microvascular injury correlate with differences in the severity of ischemia.

Animals↗

PubMed1990

Lessons from high altitude.

We have reviewed evidence that hypoxic chemosensitivity is variable and that this variation may be both endowed, partly through genetic mechanisms, and acquired, and may reflect fundamental changes in carotid body function. This variation may influence the nature and effectiveness of adaptation to high altitude and to hypoxic disease states such as chronic obstructive pulmonary disease. High chemosensitivity seems to be the choice for coping with the casual exposure to hypoxia; but fundamental, highly effective adaptations, presumably at the level of peripheral tissue, seem to be the strategy of choice for professionally adapted species.

Adaptation, Physiological↗

PubMed1989

Role of cyclic adenosine monophosphate in the induction of endothelial barrier properties.

Cyclic adenosine monophosphate (AMP) has numerous important effects on cell structure and function, but its role in endothelial cells is unclear. Since cyclic AMP has been shown to affect transmembrane transport, cell growth and morphology, cellular adhesion, and cytoskeletal organization, it may be an important determinant of endothelial barrier properties. To test this we exposed bovine pulmonary artery endothelial cell monolayers to substances known to increase cyclic AMP and measured their effect on endothelial permeability to albumin and endothelial cell cyclic AMP concentrations. Cholera toxin (CT), a stimulant of the guanine nucleotide binding subunit of adenylate cyclase, led to a concentration-dependent 2-6-fold increase in cyclic AMP which was associated with a 3-10-fold reduction in albumin transfer across endothelial monolayers. The effect was not specific to albumin as similar barrier-enhancing effects were also noted with an unrelated macromolecule, fluorescein isothiocyanate (FITC)-dextran (MW 70,000). Barrier enhancement with cyclic AMP elevation was also observed with forskolin, a stimulant of the catalytic subunit of adenylate cyclase. The temporal pattern of barrier enhancement seen with these agents paralleled their effects on increasing cyclic AMP, and the barrier enhancement could be reproduced by incubation with either dibutyryl cyclic AMP or Sp-cAMPS, cyclic AMP-dependent protein kinase agonists. Furthermore, the forskolin effect on barrier enhancement was partially reversed with Rp-cAMPS, an antagonist of cyclic AMP-dependent protein kinase. Since endothelial actin polymerization may be an important determinant of endothelial barrier function, we sought to determine whether the cyclic AMP-induced effects were associated with increases in the polymerized actin pool (F-actin). Both cholera toxin and forskolin led to apparent endothelial cell spreading and quantitative increases in endothelial cell F-actin fluorescence. In conclusion, increased endothelial cell cyclic adenine nucleotide activity was an important determinant of endothelial barrier function in vitro. The barrier enhancement was associated with increased endothelial apposition and increases in F-actin, suggesting that influences on cytoskeletal assembly may be involved in this process.

Actins↗

PubMed1989

Hypoxia increases plasma glutathione disulfide in rats.

We tested the hypothesis that hypoxia causes cellular oxidative stress by measuring plasma concentrations of glutathione disulfide (GSSG) in rats exposed to acute and subacute hypoxia. In awake, unanesthetized, catheter-implanted rats, exposure to 8% O2 for 10 min caused pulmonary vasoconstriction and increased plasma GSSG. This increase in plasma GSSG was reversible upon re-exposure to room air. In another group of rats exposed to 48 hours of hypobaric hypoxia (Pb 450 mmHg, equivalent to about 14,500 feet altitude), plasma GSSG, but not total glutathione, was significantly increased over control values (2.83 +/- 0.24 vs 1.84 +/- 0.14 nmol/ml, p less than 0.05). While lung tissue GSSG in high altitude-exposed rats were somewhat higher than in controls (17.4 +/- 7.0 vs 11.9 +/- 3.6 nmol/g wet lung wt.), the difference was not statistically significant. Treatment of the rats with a radical scavenger, DMSO, before altitude exposure, blocked the increase in plasma GSSG (1.86 +/- 0.16 nmol/ml). We conclude that both acute and subacute hypoxia increase plasma GSSG in rats and speculate that hypoxia induces cellular oxidative stress in vivo.

Altitude↗

PubMed1989

Endotoxin-pretreated neutrophils increase pulmonary vascular permeability in dogs.

Endotoxin causes pulmonary vascular neutrophil sequestration and injures the lung. Whether this is primarily due to a direct effect of endotoxin on the endothelium or is mediated by an action on the neutrophil is unclear. Canine neutrophils, isolated on plasma-Percoll gradients in vitro, were incubated with Salmonella enteriditis endotoxin, washed, and injected via wedged pulmonary arterial catheters into discrete lung zones of anesthetized dogs, whereas untreated neutrophils were administered into contralateral control lung zones. 113mIn-transferrin was administered intravenously 2 h before the animals were killed. Morphometry and extravascular protein accumulation were assessed at 4 h. Endotoxin treatment of neutrophils ex vivo induced a two- to three-fold increase in neutrophils in these lung zones (0.096 +/- 0.012 vs. 0.05 +/- 0.002 neutrophils/alveolar septal intercept, P less than 0.05). Extravascular-to-intravascular protein ratios in zones receiving endotoxin-treated neutrophils were significantly increased compared with control zones (0.146 +/- 0.02 vs. 0.079 +/- 0.02, P less than 0.05). Because complement fragments increase injury to endothelium in vitro, exogenous C5 fragments were administered to other dogs before administration of neutrophils but failed to significantly increase the extravascular protein signal (0.154 +/- 0.03 vs. 0.124 +/- 0.04). In summary, endotoxin treatment of neutrophils leads to neutrophil sequestration and increased pulmonary extravascular protein accumulation. C5 fragments failed to further enhance the protein accumulation. These data are consistent with an effect of endotoxin on the neutrophil to initiate neutrophil-endothelial interaction and subsequent lung injury.

Animals↗

PubMed1989

Combined effects of female hormones and metabolic rate on ventilatory drives in women.

Increased resting ventilation (VE) and hypoxic and hypercapnic ventilatory responses occur during pregnancy in association with elevations in female hormones and metabolic rate. To determine whether increases in progestin, estrogen, and metabolic rate produced a rise in VE and hypoxic ventilatory response (HVR) similar in magnitude to that observed at full-term pregnancy, we studied 12 postmenopausal women after 1 wk of treatment with placebo, progestin (20 mg tid medroxyprogesterone acetate), estrogen (1.25 mg bid conjugated equine estrogens), and combined progestin and estrogen. Progestin alone or with estrogen raised VE at rest and decreased end-tidal PCO2 (PETCO2) by 3.9 +/- 0.8 and 3.3 +/- 0.6 Torr, respectively (both P less than 0.05), accounting for approximately one-fourth of the rise in VE and three-fourths of the PETCO2 reduction seen at full-term pregnancy. The addition of mild exercise sufficient to raise metabolic rate by 33-36% produced the remaining three-fourths of the rise in VE but no further decline in PETCO2. Combined progestin and estrogen raised HVR and hypercapnic ventilatory response more consistently than progestin alone and could account for one-half of the increase in HVR seen at full-term pregnancy. Mild exercise alone did not raise HVR, but when exercise was combined with progestin and estrogen administration, HVR rose by amounts equal to that seen at full-term pregnancy. We concluded that female hormones together with mild elevation in metabolic rate were likely responsible for the pregnancy-associated increases in VE and HVR.

Adult↗

PubMed1989

Progestin and estrogen reduce sleep-disordered breathing in postmenopausal women.

Women exhibit sleep-disordered breathing syndromes less commonly than men before but not after the age of menopause, suggesting that female hormones may exert a protective effect. We sought to determine whether combined progestin and estrogen treatment decreased sleep-disordered breathing in healthy postmenopausal women. Nine ovarihysterectomized women [50 +/- 2 (SE) yr of age] were studied after 1 wk of treatment with placebo (lactose) or combined progestin and estrogen (medroxyprogesterone acetate, 20 mg tid, and Premarin, 1.25 mg bid). Subjects showed few respiratory disturbances during placebo treatment. Despite this, combined progestin and estrogen administration reduced the number of sleep-disordered breathing episodes in every subject, decreasing the average number of episodes per subject from 15 +/- 4 to 3 +/- 1. The duration of hypopneas also decreased with hormone treatment. Thus the presence of progestin and estrogen may be involved in protecting premenopausal women against sleep-disordered breathing.

Drug Combinations↗

PubMed1989

Influence of pregnancy on ventilatory and carotid body neural output responsiveness to hypoxia in cats.

Pregnancy increases ventilation and ventilatory sensitivity to hypoxia and hypercapnia. To determine the role of the carotid body in the increased hypoxic ventilatory response, we measured ventilation and carotid body neural output (CBNO) during progressive isocapnic hypoxia in 15 anesthetized near-term pregnant cats and 15 nonpregnant females. The pregnant compared with nonpregnant cats had greater room-air ventilation [1.48 +/- 0.24 vs. 0.45 +/- 0.05 (SE) l/min BTPS, P less than 0.01], O2 consumption (29 +/- 2 vs. 19 +/- 1 ml/min STPD, P less than 0.01), and lower end-tidal PCO2 (30 +/- 1 vs. 35 +/- 1 Torr, P less than 0.01). Lower end-tidal CO2 tensions were also observed in seven awake pregnant compared with seven awake nonpregnant cats (28 +/- 1 vs. 31 +/- 1 Torr, P less than 0.05). The ventilatory response to hypoxia as measured by the shape of parameter A was twofold greater (38 +/- 5 vs. 17 +/- 3, P less than 0.01) in the anesthetized pregnant compared with nonpregnant cats, and the CBNO response to hypoxia was also increased twofold (58 +/- 11 vs. 29 +/- 5, P less than 0.05). The increased CBNO response to hypoxia in the pregnant compared with the nonpregnant cats persisted after cutting the carotid sinus nerve while recording from the distal end, indicating that the increased hypoxic sensitivity was not due to descending central neural influences. We concluded that greater carotid body sensitivity to hypoxia contributed to the increased hypoxic ventilatory responsiveness observed in pregnant cats.

Animals↗

PubMed1989

Elevated intracranial pressure increases pulmonary vascular permeability to protein.

The syndrome of neurogenic pulmonary edema raises the question of whether there are neurological influences on pulmonary vascular permeability. Previous experimental models commonly produced severe hemodynamic alterations, complicating the distinction of increased permeability from increased hydrostatic forces in the formation of the pulmonary edema. Accordingly, we employed a milder central nervous system insult and measured the pulmonary vascular protein extravasation rate, which is a sensitive and specific indicator of altered protein permeability. After elevating intracranial pressure via cisternal saline infusion in anesthetized dogs, we used a dual isotope method to measure the protein leak index. This elevated intracranial pressure resulted in a nearly three-fold rise in the protein leak index (54.1 +/- 7.5 vs. 20.2 +/- 0.9). This central nervous system insult was associated with only mild increases in pulmonary arterial pressures and cardiac output. However, when we reproduced these hemodynamic changes with left atrial balloon inflation or isoproterenol infusion, we observed no effect on the protein leak index compared with control. Although the pulmonary arterial wedge pressure with intracranial pressure remained <10 mmHg, increases in the extravascular lung water were demonstrated. The results suggest the existence of neurological influences on pulmonary vascular protein permeability. We conclude that neurological insults result in increase pulmonary vascular permeability to protein and subsequent edema formation, which could not be accounted for by hemodynamic changes alone.

Animals↗

PubMed1985

Headache at high altitude is not related to internal carotid arterial blood velocity.

The cause of headache in persons going to high altitude is unknown. Relatively severe hypoxemia in susceptible subjects could induce large increases in cerebral blood flow that then could initiate the headache. Thus we measured noninvasively, by Doppler ultrasound, changes in internal carotid arterial blood velocity (velocity) in 12 subjects in Denver (1,600 m) and repeatedly up to 7 h at a simulated altitude of 4,800 m (barometric pressure = 430 Torr). Six subjects, selected because of prior history of high-altitude headache, developed comparatively severe headache at 4,800 m, and four subjects, without such history, remained well. Two subjects developed moderate headache. Velocity at 4,800 m did not correlate with symptom development, arterial O2 saturation, or end-tidal PCO2. Also, neither velocity nor blood pressure was consistently elevated above the Denver base-line values. During measurements of hypercapnic ventilatory response in Denver, velocity increased linearly with end-tidal PCO2, confirming that our Doppler method could demonstrate an increase. Also, 30 min of isocapnic or poikilocapnic hypoxia caused small increases in velocity (+8 and +6%) during the base-line measurement at low altitude. Although even a small increase in cerebral perfusion could contribute to headache symptoms at high altitude, cerebral blood flow does not appear to play a primary role.

Adult↗

PubMed1985

Sleep at high altitude.

The sensation of disrupted sleep following ascent to high altitude is associated with frequent awakenings, which may reflect sleep disruption due to respiratory dysrhythmia consisting typically of monotonously repetitive periodic breathing. This seems to arise from the combined effects of hypocapnia, which leads to suppression of respiratory effort in NREM sleep, and hypoxia, which stimulates termination of apnea and hyperpnea with consequent hypocapnia, leading to perpetuation of periodicity. Sleep disruption and periodic breathing decrease with time at altitude but may also be considerably reduced by pretreatment with acetazolamide, which may act by correction of alkalosis or through some other mechanism. In long-term residents of high altitude less distinctive, undulating respiratory dysrhythmias are described with unstable and decreased arterial oxygenation.

Acclimatization↗