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Biomedical subjects

N W Morrell

Publications and source records attributed to N W Morrell.

At least 37 records · Page 2Linked to original sources
PubMed2001

Differential adrenomedullin release and endothelin receptor expression in distinct subpopulations of human airway smooth-muscle cells.

Although adrenomedullin (ADM) is implicated in the control of airway tone, regulation of ADM release from airway smooth-muscle cells (ASMCs) has not been explored. Preliminary experiments have indicated that human ASMC populations were heterogeneous in their rate of ADM release and expression of endothelin (ET)(A) and ET(B) receptors. We isolated these phenotypically distinct ASMCs from explants derived from the same airway segment. ASMCs possessing exclusively ET(A) receptors appeared smaller and proliferated faster than ET(A)/ET(B) isolates. Macroautoradiographic analysis confirmed the presence of both receptors in human bronchi. ADM release and messenger RNA expression was greater in ET(A)/ET(B) isolates compared with ET(A) isolates. No measurable ET release was detected from ASMCs. Exogenous ET-1 (1 to 100 nM) more potently stimulated the release of ADM from ET(A)/ET(B) compared with ET(A) isolates. In addition, ET-3 (1 to 100 nM) stimulated ADM release only from ET(A)/ET(B) isolates, implicating the ET(B) receptor in this response. Exogenous ET-1 potentiated platelet- derived growth factor-stimulated [3H]thymidine uptake in ET(A)/ ET(B) but not ET(A) isolates. ET-3 did not affect [3H]thymidine uptake in either cell type. Possession of ET(A)/ET(B) receptors is associated with higher rates of ADM release and slower proliferation, but a capacity for ET-1 stimulated DNA synthesis via ET(A) receptors. These results support a paracrine role for the regulation of ADM release predominantly via the ET(B) receptor in human ASMCs.

Adrenomedullin↗
PubMed2001

Utility of echocardiography in assessment of pulmonary hypertension secondary to COPD.

Studies have confirmed the close correlation of echocardiographically estimated pulmonary arterial pressure with invasive measurements in patients with chronic obstructive pulmonary disease (COPD), but there are few data on utility of echocardiographic measurement in assessing pulmonary arterial hypertension (PH) in COPD and correlation with pulmonary function tests. Presence or absence of tricuspid regurgitation (TR) was determined by Doppler echocardiography in 73 consecutive COPD patients attending a hospital outpatient clinic. Transtricuspid pressure gradient (TTPG) was calculated. PH was defined as TTPG > or =30 mmHg. Patients also underwent spirometry, forced expiratory volume in one second (FEV1), single breath gas transfer (carbon monoxide transfer coefficient; (K(CO)) and carbon monoxide diffusing capacity of the lung; D(L,CO)) and arterial blood gas measurement. Measurable TR was observed in 56/73 patients (77%). There were no differences between the group in which TR was observed compared to that in which it was absent, with regard to age, smoking history nor pulmonary function variables. PH was seen in 31/56 cases (55%), with good reproducibility. There were statistically significant correlations of TTPG with FEV1 (r=-0.26, p=0.05), Kco (r=-0.31, p=0.04) and D(L,CO) (r = -0.42, p = 0.006) expressed as % pred. Stepwise regression analysis showed that age and K(CO) combined provide a multivariate model for prediction of TTPG. It is concluded the presence and degree of pulmonary arterial hypertension is readily and reliably determined by echocardiography in the majority of chronic obstructive pulmonary disease patients. Pulmonary arterial hypertension is common in severe chronic obstructive pulmonary disease and transtricuspid pressure gradient correlates with spirometry and indices of gas transfer, similar to previous invasive studies. In view of the adverse effects of pulmonary arterial hypertension on morbiditv and mortality routine echocardiography in patients with severe chronic obstructive pulmonary disease may be warranted.

Aged↗
PubMed2000

Prostacyclin analogues differentially inhibit growth of distal and proximal human pulmonary artery smooth muscle cells.

BACKGROUND: Prostacyclin has proved to be a beneficial treatment for patients with severe pulmonary hypertension. We postulated that the response may reflect, at least in part, inhibition of pulmonary artery smooth muscle cell (PASMC) growth. METHODS AND RESULTS: Human PASMCs were derived from distal (<1-mm external diameter, n=8) and proximal (>8-mm external diameter, n=12) pulmonary arteries obtained at transplant surgery and pneumonectomy. The effects of the stable prostacyclin analogues on [methyl-(3)H]thymidine incorporation and cell proliferation were investigated by using immunohistochemically characterized cells. Distal cells proliferated faster than did proximal PASMCs and displayed a distinct sensitivity to cicaprost and iloprost. Both analogues inhibited thymidine uptake over 24 hours (20% to 60%, P<0.001; n=8) and abolished stimulation of DNA synthesis by platelet-derived growth factor-BB (10 ng/mL) in distal but not proximal cells. The inhibitory effect of cicaprost was mimicked by isoproterenol (10(-5) mol/L), forskolin (10(-5) mol/L), and dibutyryl cAMP (5x10(-4) mol/L) and was potentiated by the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (5x10(-5) mol/L). Cicaprost (10(-10) to 10(-6) mol/L) inhibited the proliferation of PASMCs, which had been stimulated with either platelet-derived growth factor-BB or serum, and increased cAMP production. These effects were potentiated by 3-isobutyl-1-methylxanthine and attenuated by the adenylyl cyclase inhibitor 2',5'-dideoxyadenosine (10(-5) to 10(-4) mol/L). CONCLUSIONS: ++Cicaprost and iloprost inhibit DNA synthesis and proliferation to a greater extent in distal compared with proximal human PASMCs, acting at least in part via a cAMP-dependent mechanism. The results are consistent with the hypothesis that prostacyclin analogues inhibit vascular remodeling in pulmonary hypertension and demonstrate heterogeneity among human PASMCs.

Adult↗
PubMed2000

Expression of pulmonary vascular angiotensin-converting enzyme in primary and secondary plexiform pulmonary hypertension.

The hypothesis for this study was that increased local expression of vascular angiotensin-converting enzyme (ACE) may contribute to the arterial remodelling which accompanies pulmonary hypertension, since angiotensin II (ANG II) is an important mediator of pulmonary vascular cell growth. The expression of ACE was studied by immunohistochemistry in paraffin-embedded lung sections from adults undergoing heart-lung transplantation for severe primary (n=6) and secondary (n=7) pulmonary arterial hypertension (PH), compared with age-matched controls (n=11). An antigen retrieval technique was used prior to incubating sections with the anti-ACE monoclonal antibody, CG2, or the endothelial marker, monoclonal anti-CD31. In control lungs, the highest level of ACE immunostaining was seen in the alveolar capillary endothelium, with less intense staining in small intra-acinar pulmonary arteries and relatively little staining in larger preacinar arteries. ACE immunostaining was virtually absent in lymphatics and veins. In both primary and secondary PH, there was an increase in ACE immunostaining in the endothelium of intra-acinar peripheral pulmonary arteries compared with control lungs, extending to the level of alveolar ducts, as confirmed by semi-quantitative analysis. The increase in endothelial ACE expression in the intra-acinar arteries of patients with primary and secondary PH is consistent with the hypothesis that locally increased production of ANG II may contribute to the process of pulmonary vascular remodelling.

Adult↗
PubMed2000

Tumour necrosis factor-alpha gene promoter polymorphism in chronic obstructive pulmonary disease.

Tumour necrosis factor(TNF)-alpha levels are elevated in airways of patients with chronic obstructive pulmonary disease (COPD) and may contribute to its pathogenesis. A guanine to adenine substitution at position -308 of the TNF-alpha gene promoter (TNF1/2) has been associated with chronic bronchitis of various aetiologies in a Taiwanese population. The authors performed a study investigating association of the polymorphism with smoking-related COPD in Caucasians. Frequencies of TNF1/2 alleles in 86 Caucasians (52 males) with COPD were compared with 63 (52 males) asymptomatic smoker/exsmoker control subjects and a population control of 199 (99 males) blood donors. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism technique on genomic deoxyribonucleic acid (DNA) obtained from peripheral blood. There were no significant differences in TNF1/2 allele frequencies between groups: 0.85/0.15 in COPD, 0.85/0.15 in smoker control subjects, 0.83/0.17 in population control subjects. Within the COPD group there was no association of TNF1/2 alleles with indices of airflow obstruction (% predicted forced expiratory volume in one second (FEV1) and % predicted FEV1/vital capacity ratio) nor gas transfer (% predicted carbon monoxide transfer coefficient and % predicted carbon monoxide diffusing capacity of the lung). It is concluded that: 1) the tumour necrosis factor gene promoter allele does not influence the risk of developing chronic obstructive pulmonary disease in a Caucasian population of smokers; and 2) there is no association of the tumour necrosis factor gene promoter genotype with severity of airflow obstruction nor degree of emphysema in chronic obstructive pulmonary disease.

Aged↗
PubMed2000

Vascular remodeling and ET-1 expression in rat strains with different responses to chronic hypoxia.

Chronic hypoxia leads to a greater degree of pulmonary hypertension in the Wistar-Kyoto (WKY) rat than in the Fischer 344 (F-344) rat. We questioned whether this difference is associated with baseline differences in pulmonary artery anatomy, a greater degree of hypoxia-induced pulmonary vascular remodeling in the WKY rat, and/or differences in expression of endothelin (ET)-1. Male F-344 and WKY rats were maintained in normoxia or normobaric hypoxia for 21 days. Morphometry revealed that baseline pulmonary artery anatomy was similar in the two strains. However, during chronic hypoxia, the WKY rats developed a greater degree of muscularization of small pulmonary arteries. Baseline plasma and lung immunoreactive ET-1 levels were similar in the WKY and F-344 rats and increased significantly during hypoxia in the WKY rats. Northern analysis demonstrated increased lung preproET-1 mRNA during hypoxia in both strains, with a greater increase in WKY rats. Immunostaining demonstrated increased ET-1 in bronchial epithelium and peripheral pulmonary arteries during hypoxia, although to a greater degree in the WKY rats. We conclude that the WKY strain demonstrates increased susceptibility to hypoxia-induced pulmonary vascular remodeling compared with the F-344 strain and that increased lung and circulating ET-1 levels during hypoxia may partly explain this difference.

Animals↗
PubMed1999

NPR-A-Deficient mice show increased susceptibility to hypoxia-induced pulmonary hypertension.

BACKGROUND: Mice in which the gene encoding NPR-A, a guanylyl cyclase-linked natriuretic peptide receptor, has been disrupted were used to examine the contribution of natriuretic peptides to maintaining pulmonary vascular homeostasis in normal- and low-oxygen environments. METHODS AND RESULTS: Wild-type (+/+), heterozygous (+/-), and homozygous null mutants (-/-) were studied. The response of the pulmonary vasculature to atrial, B-type, and C-type natriuretic peptides (ANP, BNP, and CNP) during acute hypoxia was studied in isolated perfused lungs. Right ventricular systolic pressure (RVSP), RV weight, and pulmonary vascular remodeling were measured in each genotype exposed to normal air and after 7 and 21 days in a hypoxic atmosphere (10% O2). ANP and BNP (300 ng) reduced pulmonary artery pressure during acute hypoxia-induced pulmonary vasoconstriction in +/+ mice, but this effect was attenuated in +/- and absent in -/- mice. CNP (600 ng) had little effect in all 3 genotypes. RVSP and RV weight were similar in the 3 genotypes housed in a normal-O2 environment. Seven and 21 days of hypoxia produced a pronounced and significantly greater increase in RVSP and RV weight in -/- mice compared with +/+ or +/- mice and more rapid muscularization of distal pulmonary arterioles. CONCLUSIONS: ANP and BNP do not contribute to maintaining normal pulmonary artery pressure but play an important role in attenuating the pulmonary vascular response to hypoxia. NPR-A mediates the vasorelaxant effect of ANP in pulmonary vasculature.

Analysis of Variance↗
PubMed1999

Angiotensin II activates MAPK and stimulates growth of human pulmonary artery smooth muscle via AT1 receptors.

To determine a potential role for the renin-angiotensin system in the growth of human pulmonary artery (PA) smooth muscle, we studied the localization of angiotensin (ANG) II-receptor subtypes by autoradiography in sections of human PA and in cultured PA smooth muscle cells (PASMCs) and examined the growth responses to ANG II in vitro. Specific 125I-labeled [Sar1,Ile8]ANG II binding was demonstrated within the pulmonary arterial media, but binding to cultured cells varied between isolates. Binding in tissues and cells was inhibited by the ANG II type 1 (AT1) receptor antagonist losartan but not by the type 2 (AT2) receptor antagonist PD-123319. Microautoradiographic studies indicated that cultured PASMCs exhibit heterogeneity with regard to ANG II binding sites. Addition of ANG II to serum-deprived PASMCs, exhibiting a relatively high level of 125I-[Sar1,Ile8]ANG II binding, led to a dose-dependent stimulation of DNA synthesis at 24 h and protein synthesis at 48 h. ANG II led to an increase in cell size without an increase in cell number. These effects were inhibited by losartan but not by PD-123319. In addition, ANG II led to rapid activation of mitogen-activated protein kinase (MAPK), and ANG II-stimulated DNA synthesis was inhibited by the specific inhibitor of MAPK PD-98059. We conclude that the AT1 receptor is expressed by human PASMCs in vivo and in vitro and is coupled to activation of MAPK and increased DNA and protein synthesis in vitro. These results are consistent with the hypothesis that ANG II may be involved in human pulmonary vascular remodeling.

Angiotensin II↗
PubMed1997

Right ventricular angiotensin converting enzyme activity and expression is increased during hypoxic pulmonary hypertension.

OBJECTIVE: To determine whether local cardiac angiotensin converting enzyme (ACE) expression is upregulated during the development of hypoxia-induced right ventricular hypertrophy. METHODS: ACE activity was measured in membrane preparations from the right ventricle and left ventricle plus septum in normoxic rats and animals exposed to chronic hypoxia for 8 and 14 days. Local cardiac ACE expression was studied by immunohistochemistry using a monoclonal antibody to ACE (9B9). RESULTS: In the normal rat heart, ACE expression was confined to vascular endothelium, the valvular endocardium, and localized regions of parietal endocardium. We found that the development of pulmonary hypertension and right ventricular hypertrophy were associated with 2.6- and 3.4-fold increases in membrane-bound right ventricular ACE activity by 8 and 14 days of hypoxia, respectively. Right ventricular ACE activity was positively correlated with the degree of right ventricular hypertrophy (r = 0.83, P < 0.001). In contrast, left ventricular plus septal ACE activity was significantly reduced by approximately 40 and 60% by 8 and 14 days of hypoxia, respectively, compared to controls. In the right ventricle of chronically hypoxic rats, immunohistochemistry demonstrated increased ACE expression in areas of myocardial fibrosis. Interestingly, increased ACE expression was noted in the right ventricular epicardium in chronically hypoxic rats. In the free wall of the left ventricle there was a significant reduction in the number of myocardial capillaries which expressed ACE in chronically hypoxic rats. CONCLUSION: Chronic hypoxia has a differential effect on left and right ventricular ACE activity and that the sites of altered ACE expression are highly localized. We speculate that locally increased right ventricular ACE activity and expression may play a role in the pathogenesis of right ventricular hypertrophy secondary to hypoxic pulmonary hypertension.

Animals↗
PubMed1996

Developmental regulation of angiotensin converting enzyme and angiotensin type 1 receptor in the rat pulmonary circulation.

Factors that influence the development of the normal pulmonary vasculature are poorly understood. Since increased local production of angiotensin II (AII) by angiotensin converting enzyme (ACE) has been implicated in the medial hypertrophy of systemic and pulmonary hypertension, we questioned whether ACE and angiotensin receptor expression may influence the muscularization of the normal pulmonary vasculature during development. The approach employed measurement of lung ACE activity, assessment of local ACE expression by immunohistochemistry, and angiotensin type 1 receptor (AT1) expression by in situ hybridization in rat lungs ranging from 15 days of intrauterine life (term = 21 d) to adulthood. The temporal and spatial pattern of ACE expression was compared with that of the endothelial marker, von Willebrand factor (vWF), and the smooth muscle cell markers, alpha smooth muscle actin and smooth muscle myosin. ACE activity was first detected in lung homogenates on day 17 of gestation (1 +/- 0.2 mU/mg) and increased progressively to term (27.7 +/- 3.2 mU/mg). However, the greatest increase in lung ACE activity to adult levels (379 +/- 25.2 mU/mg) occurred between 2 and 4 wk of postnatal life. Immunohistochemistry demonstrated vWF expression by vascular endothelium throughout the lung as early as day 15 of gestation. In contrast, ACE expression was observed in the endothelium of only hilar pulmonary arteries on day 15 of gestation, and thereafter was noted to be expressed in endothelial cells of progressively more distal arteries, such that by term, endothelial cells of all muscularized arteries expressed ACE. Alveolar capillary ACE expression was not detected until day 20 of gestation, and increased dramatically after birth. Smooth muscle actin expression in lung arteries closely paralleled the expression of endothelial ACE. AT1 receptor mRNA was first expressed in the peripheral lung on day 17 of gestation by non-epithelial undifferentiated mesenchyme. In contrast, AT1 mRNA signal was much reduced in differentiated smooth muscle. We speculate that ACE expression in the fetal lung circulation may influence the muscularization of fetal pulmonary arteries by the interaction of locally produced angiotensin II with the AT1 receptor.

Animals↗
PubMed1995

Magnitude and time course of acute hypoxic pulmonary vasoconstriction in man.

Acute hypoxic pulmonary vasoconstriction has an established role in the preservation of ventilation-perfusion balance. To further characterize this homeostatic response in man we have attempted to measure both the time course and magnitude of blood flow diversion from single hypoxic lobes. Lobar hypoxia (mean PO2 38 +/- 1.5(SEM)mmHg, mean PCO2 39.9 +/- 0.9 mmHg) was induced by inflating catheter-tip balloons in left upper lobe bronchi during fibreoptic bronchoscopy under local anaesthesia in 8 normal subjects. An index of lobar blood flow was obtained by acquiring dynamic scintigraphic lung images during a continuous intravenous infusion of the short-lived radioisotope krypton-81m dissolved in 5% glucose solution. In 3 subjects blood flow to the occluded lobes was monitored while the lobes were maintained under hyperoxic conditions (mean PO2 127.8 +/- 31.5 mmHg, mean PCO2 40.2 +/- 1.3 mmHg). Under hypoxic conditions the blood flow to the occluded lobes fell to 53% of baseline after 5 min with a mean time constant of 151 +/- 24.8 sec. Under hyperoxic conditions there was no significant change from baseline blood flow. We conclude that this technique has allowed us to monitor both the dynamic and steady state responses of the pulmonary circulation to lobar hypoxia in man.

Adult↗
PubMed1995

Regional matching of ventilation and perfusion during lobar bronchial occlusion in man.

1. Ventilation-perfusion balance in the presence of airway obstruction will depend on the efficiency of hypoxic pulmonary vasoconstriction beyond obstructed airways and the matching of redistributed blood flow and ventilation to the rest of the lung. This study investigated the relative importance of these mechanisms in man during experimental bronchial occlusion. 2. The bronchus to the left lower lobe was temporarily occluded with a balloon-tipped catheter during fibreoptic bronchoscopy in eight supine normal volunteers. Respiratory gas tensions were measured within the occluded lobe with a respiratory mass spectrometer. The distribution of ventilation and perfusion was assessed under control conditions and after 5 min of bronchial occlusion by computer analysis of the regional distribution of radioactivity during inhalation of 81mKr gas and following injection of 99mTc-labelled macroaggregated albumin respectively. 3. Respiratory gas partial pressures within the occluded lobes rapidly stabilized at mixed venous gas tensions: PO2 43.4 +/- 2.2 (SEM) mmHg, PCO2 40.2 +/- 1.8 mmHg. During occlusions the arterial oxygen saturation fell from a baseline of 96.3 +/- 0.46% to a nadir of 92.1 +/- 0.43%. Bronchial occlusion produced underventilation in the left lung relative to perfusion, both in the region of the occluded lower lobe and at the lung apex. Relative overventilation occurred in the right lung. 4. It is concluded that arterial hypoxaemia during lobal bronchial occlusion is caused primarily by shunting of mixed venous blood, though the shunt fraction is reduced by approximately 50% by hypoxic pulmonary vasoconstriction. In lung adjacent to obstructed regions reduced compliance may impair ventilation more than perfusion to contribute to hypoxaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Role of angiotensin-converting enzyme and angiotensin II in development of hypoxic pulmonary hypertension.

Although angiotensin converting enzyme (ACE) inhibitors are known to attenuate the development of hypoxic pulmonary hypertension in rats, the precise mechanism of this protective effect remains unknown. Thus we utilized specific angiotensin II (ANG II)-receptor antagonists to investigate whether ANG II is involved directly in the hemodynamic and structural changes of pulmonary hypertension, and we tested whether the protective effects of ACE inhibition can be attributed partly to potentiation of bradykinin. During 14 days of hypobaric hypoxia, rats received, via intraperitoneal osmotic minipumps, either 1) the ACE inhibitor captopril, 2) captopril plus the bradykinin B2-receptor antagonist CP-0597, 3) the ANG II type 1 receptor antagonist losartan, 4) the ANG II type 2 receptor antagonist PD-123319, or 5) saline. At 14 days, mean pulmonary arterial pressure (MPAP) was reduced (P < 0.05) in hypoxic rats treated with captopril (26.6 +/- 0.8 mmHg) or losartan (24.4 +/- 1.0 mmHg) compared with saline (32.0 +/- 1.4 mmHg) but was unaffected by PD-123319 (29.5 +/- 1.7 mmHg). Right ventricular hypertrophy was reduced in hypoxic rats treated with captopril or losartan compared with saline-treated rats. Morphometry showed less medial thickening and peripheral muscularization of small pulmonary arteries in hypoxic animals treated with captopril or losartan. Coadministration of CP-0597 did not reverse the protective effects of captopril on pulmonary vascular remodeling. These results suggest a novel role for endogenous ANG II, acting through the type 1 receptor, in the vascular remodeling associated with hypoxic pulmonary hypertension. The beneficial effects of ACE inhibition in this model can be attributed to reduced ANG II production rather than potentiation of bradykinin.

Angiotensin II↗
PubMed1995

Angiotensin converting enzyme expression is increased in small pulmonary arteries of rats with hypoxia-induced pulmonary hypertension.

Previous studies suggest that while lung angiotensin converting enzyme (ACE) activity is reduced during chronic hypoxia, inhibitors of ACE attenuate hypoxic pulmonary hypertension. In an attempt to explain this paradox we investigated the possibility that whole lung ACE activity may not reflect local pulmonary vascular ACE expression. The experimental approach combined in vivo hemodynamic studies in control and chronically hypoxic rats, measurement of whole lung ACE activity, and evaluation of local pulmonary vascular ACE expression by in situ hybridization and immunohistochemistry. Total lung ACE activity was reduced to 50% of control activity by 5 d of hypoxia and remained low for the duration of the study. Immunohistochemistry showed a marked reduction of ACE staining in alveolar capillary endothelium. However, an increase in ACE staining was observed in the walls of small newly muscularized pulmonary arteries at the level of alveolar ducts and walls. In situ hybridization studies showed increased signal for ACE mRNA in the same vessels. Inhibition of ACE by captopril during chronic hypoxia attenuated pulmonary hypertension and markedly reduced distal muscularization of small pulmonary arteries. In addition, we demonstrated marked longitudinal variation in ACE expression along the normal pulmonary vasculature with the highest levels found in small muscular arteries associated with terminal and respiratory bronchioles. We conclude that local ACE expression is increased in the walls of small pulmonary arteries during the development of hypoxic pulmonary hypertension, despite a generalized reduction in alveolar capillary ACE expression, and we speculate that local arteriolar ACE may play a role in the vascular remodeling associated with pulmonary hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Changes in regional pulmonary blood flow during lobar bronchial occlusion in man.

1. Acute hypoxic pulmonary vasoconstriction is important in the restoration of ventilation-perfusion balance in the presence of regional alveolar hypoventilation. However, the magnitude and time course of this response in man has not been adequately characterized in regions smaller than an entire lung. We have studied the effectiveness of hypoxic vasoconstriction in diverting blood from hypoxic lobes in normal supine subjects, and have documented the redistribution of pulmonary blood flow under these conditions. 2. Lobar hypoxia was induced for 80-300 s by placing occluding balloon-tipped catheters in lobar bronchi during fibreoptic bronchoscopy in 10 normal subjects. Respiratory gas partial pressures within occluded lobes were measured with a mass spectrometer. The percentage reduction in blood flow to the hypoxic lobes was assessed after injection of 99mTc-labelled albumin by gamma-scintigraphy, and compared with a control scan performed 1 week later. A computer program was used to analyse changes in regional pulmonary perfusion. 3. During lobar bronchial occlusion respiratory gas partial pressures rapidly approached reported values for mixed venous partial pressures. After a mean time of occlusion of 3.5 min lobar blood flow was reduced by 47 +/- 5%. During occlusions pulmonary blood flow was not evenly redistributed, but was preferentially redistributed to more cranial lung regions. 4. We conclude that acute hypoxic pulmonary vasoconstriction in occluded lobes is more effective at rapidly diverting pulmonary blood flow away from hypoxic lung regions than has previously been reported in man during unilateral hypoxia of an entire lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗