Biomedical subjects

G R Barer

Publications and source records attributed to G R Barer.

At least 19 recordsLinked to original sources

PubMed1994

Histamine induced pulmonary vasodilatation in the rat: site of action and changes in chronic hypoxia.

Histamine constricts postcapillary lung vessels and also causes dilatation, site unknown. In chronically hypoxic rats, pulmonary arterioles are muscularized and histamine-containing mast cells increase. We wanted to determine a) whether vasoreactivity to histamine changes in chronic hypoxia; b) whether dilatation is due to H2 receptors; and c) which vessels dilate. We perfused isolated lungs of normal (C) and chronically hypoxic (CH) rats. Histamine was tested during hypoxic vasoconstriction. To examine effects on arteries alone, we raised alveolar (inflation) pressure above outflow pressure; during inflation, pressure/flow (P/Q) lines were measured during normoxia, and hypoxia, and after histamine during continued hypoxia. Dose-related dilatation was seen, which was abolished by cimetidine and enhanced in CH rats. A mast cell-discharging agent, but not exogenous histamine, caused constriction, which was abolished by chlorpheniramine. P/Q lines differed in C and CH rats in a manner which suggests that hypoxia constricts larger "extra-alveolar" vessels in C rats, but mainly muscularized arterioles exposed to alveolar pressure in CH rats. Histamine restored the P/Q line to nearly its normoxic position; it therefore dilated those vessels which constrict in hypoxia in each rat group. It is concluded that histamine has a strong H2 dilator effect, enhanced in chronic hypoxia, which might be an important attenuating factor in hypoxic pulmonary hypertension.

Animals↗

PubMed1992

Interactions between hypoxic and almitrine-induced vasoconstriction in the rat lung.

1. To test whether almitrine might improve the arterial partial pressure of O2 in patients with chronic obstructive airways disease by improvement of ventilation-perfusion matching, we looked at the interaction between hypoxic and almitrine-induced vasoconstriction in isolated rat lungs perfused with blood at constant flow. Increases in pressure represented increases in resistance. 2. Almitrine, given in increasing doses between challenges with 2% O2, enhanced hypoxic vasoconstriction at low doses but attenuated it at high doses. 3. Stimulus-response curves to hypoxia of increasing severity gave a sigmoid curve. 4. Almitrine solvent caused small changes in pulmonary artery pressure and shifted the stimulus-response curve slightly in a parallel fashion. 5. Small doses of almitrine enhanced the action of mild to moderate hypoxia, medium doses attenuated moderately severe hypoxia, whereas high doses depressed vasoconstriction due to all degrees of hypoxia. 6. These effects of almitrine on hypoxic vasoconstriction were compared with the effect of solvent by analysis of variance; the results substantiated significant enhancement of hypoxia by small doses and attenuation by large doses. 7. In patients, if similar effects apply, small doses of almitrine would assist ventilation-perfusion matching, but large doses might worsen it. 8. Almitrine-induced vasoconstriction was attenuated by a fall in perfusate temperature in a similar manner to hypoxic vasoconstriction. It was also attenuated by three drugs, chlorpheniramine, propanolol and diethylcarbamazine, all of which also decrease hypoxic vasoconstriction. The similarity between hypoxic and almitrine-induced pulmonary vasoconstriction is further confirmed.

Almitrine↗

PubMed1991

Natriuresis secondary to carotid chemoreceptor stimulation with almitrine bismesylate in the rat: the effect on kidney function and the response to renal denervation and deficiency of antidiuretic hormone.

Almitrine bismesylate simulates the effects of arterial hypoxia in producing a specific and long-lasting excitation of the peripheral arterial chemoreceptors. Previous work has shown that almitrine produces a diuresis and natriuresis when given intravenously to anaesthetised rats in a stable mannitol induced diuresis. This response is abolished by glossopharyngeal nerve section implying that it is afferently mediated via the carotid body chemoreceptors. We have studied further the efferent limb of this response. The diuresis and natriuresis occurs without significant detectable changes in effective renal plasma flow and glomerular filtration rate suggesting that it is produced mainly by inhibition of renal tubular sodium and water reabsorption. Almitrine produces a diuresis and natriuresis in rats after bilateral nephrectomy and transplantation of a kidney from a donor rat. This effect is not therefore efferently mediated by the renal nerves and probably involves a humoral agent. Almitrine produces a diuresis and natriuresis in rats after bilateral adrenalectomy and in rats with congenital hypothalamic diabetes insipidus indicating that neither adrenal hormones nor changes in antidiuretic hormone levels are implicated.

Almitrine↗

PubMed1990

Ligustrazine is a vasodilator of human pulmonary and bronchial arteries.

We have investigated the dilator effect of ligustrazine, the semisynthetic principle of a traditional Chinese herbal remedy, on human pulmonary and bronchial arteries in vitro. Ligustrazine caused a concentration-dependent relaxation of human small pulmonary arteries, which was independent of endothelium. Although ligustrazine was equally potent in inducing dilatation of pulmonary and bronchial arteries, it was about 10 times more potent in relaxing small pulmonary arteries (300-500 microns i.d.) compared with lobar pulmonary arteries (7-8 mm i.d.). By contrast, the relaxant responses of small and lobar pulmonary arteries to sodium nitroprusside was not significantly different. Ligustrazine was equally potent in relaxing prostaglandin F2 alpha- or 5-hydroxytryptamine-precontracted pulmonary arteries, suggesting that it is not a prostaglandin F2 alpha or 5-hydroxytryptamine antagonist. Preincubating the vessels with propranolol (1 microM) or indomethacin (10 microM) had no significant effect on the ligustrazine-induced vasodilatation. However, ligustrazine caused concentration-dependent inhibition of calcium-evoked contraction when applied to rat aorta in calcium-free K(+)-depolarizing medium. We conclude that ligustrazine is a dilator of human pulmonary and bronchial arteries, which is endothelium-independent and that ligustrazine preferentially relaxes pulmonary resistance vessels rather than large conduit pulmonary arteries.

Animals↗

PubMed1990

Enhanced reactivity to bradykinin, angiotensin I and the effect of captopril in the pulmonary vasculature of chronically hypoxic rats.

We compared the reactivity of pulmonary vessels to bradykinin (BK) and angiotensin I (AI) in normal and chronically hypoxic rats; the latter have pulmonary hypertension and muscularized pulmonary arterioles. These peptides are respectively inactivated and activated by the angiotensin converting-enzyme (ACE) on pulmonary endothelium. Isolated lungs were perfused at a constant flow rate when changes in pulmonary artery pressure (Ppa) reflect changes in vascular resistance. Dose-response curves to BK (1 ng-10 micrograms) were derived during normoxia and pre-constriction by hypoxia; BK both decreased and increased vascular resistance, i.e. vasodilation and vasoconstriction. In normal rats only constriction was seen in normoxia, which reflected low basal vascular tone, whereas in chronically hypoxic rats there was only dilatation which reflected high basal vascular tone. In hypoxia in normal rats, low doses caused dilatation, high doses constriction; in chronically hypoxic rats there was again only dilatation which was larger than in controls. After the ACE-inhibitor captopril, constriction was exaggerated in control rats in both normoxia and hypoxia and took place in chronically hypoxic rats after high doses in both normoxia and hypoxia; oedema often followed. Dose-response curves to AI (1 ng-micrograms) in normoxia showed greatly enhanced pressor responses in chronically hypoxic compared with normal rats, probably attributable to increased sensitivity to angiotensin II (AII) rather than enhanced conversion of AI to AII. Captopril caused a proportionate reduction in responses in both groups of rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗

PubMed1989

Effect of ligustrazine on pulmonary vascular changes induced by chronic hypoxia in rats.

1. Acute and chronic effects on the pulmonary circulation of ligustrazine, a chemically identified and synthesized principle of a Chinese herb, were studied in rats. It dilated lung vessels and reversed hypoxic pulmonary vasoconstriction. 2. In rats kept 2 weeks in 10% O2 in a normobaric chamber and simultaneously treated with ligustrazine, right ventricular hypertrophy and muscularization of pulmonary arterioles were attenuated compared with saline-treated rats. Pulmonary artery pressure, measured in isolated lungs perfused at a constant flow rate, was also less in ligustrazine-treated rats. 3. In isolated blood-perfused lungs of chronically hypoxic and control rats, the relation between pressure and flow was measured during normoxia (ventilation with air plus 5% CO2), hypoxia (2% O2 plus 5% CO2) and after ligustrazine during continued hypoxia. Alveolar pressure was always greater than left atrial pressure; thus flow was determined by the pulmonary artery minus alveolar pressure difference. 4. Pressure/flow lines were measured during normoxia in four groups of rats: (1) control, saline-treated; (2) control, ligustrazine-treated; (3) chronically hypoxic, saline-treated; (4) chronically hypoxic, ligustrazine-treated. Both chronically hypoxic groups had steeper lines (higher resistance) than the control groups, which were similar in all respects. However, in chronically hypoxic rats, the extrapolated intercept of the line on the pressure axis, probably attributable to small newly muscularized arterioles in a state of tone, was much increased in the saline-treated group but did not differ from controls in the ligustrazine-treated group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Dopamine and ventilatory effects of hypoxia and almitrine in chronically hypoxic rats.

We hypothesized that the temporary blunted ventilatory response to hypoxia seen in chronically hypoxic rats could be related to the increased amount of dopamine found in their carotid bodies. Rats, kept 2-3 wk in 10% O2, showed reduced nonisocapnic ventilatory responses to 21-12% inspiratory O2 fraction compared with control rats. Stimulus-response curves to almitrine, which simulates the action of hypoxia on the carotid body, were also depressed in chronically hypoxic rats. Responses to hypoxia and almitrine were significantly correlated in the two groups of rats. Dopamine depressed ventilation during normoxia, hypoxia, and almitrine stimulation in both groups, an action abolished by the dopamine-2 antagonist domperidone. Domperidone slightly increased responses to hypoxia and almitrine in control rats but had a greater enhancing effect in chronically hypoxic rats, such that there was no longer a difference between the responses of the two groups.

Almitrine↗

PubMed1989

Reactivity and site of vasomotion in pulmonary vessels of chronically hypoxic rats: relation to structural changes.

The high pressure muscular pulmonary circulation of chronically hypoxic (CH) rats was compared with the low pressure circuit in control (C) rats; differences were found in the effects of lung inflation, in pressure/flow relations during lung inflation, in reactivity to autocoids, and in responses to pulmonary dilator drugs. Isolated blood-perfused lungs of CH rats (2 to 3 wk in 10% O2) were compared with those of C rats kept in air. High inflation (alveolar) pressure (Palv) caused a rise in pulmonary artery pressure (Ppa) close to delta Palv in both groups; in CH rats, Ppa continued to rise, whereas it adapted to a lower level in C rats. Pressure-flow (P/Q) lines were measured at high and low Palv, all in Zone 2 state. In normoxia, high Palv caused a parallel shift in the P/Q line close to delta Palv in both C and CH rats. However, during hypoxic pulmonary vasoconstriction (HPV), high Palv caused a shift in the P/Q line less than delta Palv in C rats and greater than delta Palv in CH rats. Similar differences between C and CH rats were seen during constriction caused by almitrine, a drug that simulates HPV. Thus, these stimuli affect vessels that are functionally "extra-alveolar" in C rats but functionally "alveolar" in CH rats. We consider whether vasoconstriction by hypoxia and almitrine moves peripherally to the newly muscularized alveolar arterioles that are found in CH rats. Reactivity of lung vessels to bradykinin, angiotensin-1, and platelet-activating factor was greater in CH than in C rats, possibly also associated with muscularization of arterioles in the former.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1989

Hypoxia and the pulmonary circulation: a brief review.

Hypoxia constricts small pulmonary arteries. Local hypoxia regulates blood flow/ventilation ratios, while general hypoxia elevates pulmonary artery pressure (Ppa). There is a continuum of responses from flow reduction to Ppa elevation dependent on the proportion of lung involved. Stimulus-response curves to hypoxia show the effect is maximal within the physiological range and resemble that for the carotid body. In widespread lung disease so much of the lung becomes hypoxic, that blood flow/ventilation matching fails, hypoxaemia and pulmonary hypertension follow. In chronic hypoxia structural changes take place which maintain a high pressure even when hypoxia is removed; small arterioles become muscularized and there is right ventricular hypertrophy and polycythaemia. Animal models of hypoxic pulmonary hypertension have brought some understanding of the growth processes involved and shown that several drugs will prevent these changes. The reactivity of the restructured pulmonary vessels in chronic hypoxia is altered.

Animals↗

PubMed1988

Experimental prevention of hypoxic pulmonary hypertension in animals by drugs.

The rat model of chronic hypoxic pulmonary hypertension has been extensively studied and shows many of the features seen in man with chronic pulmonary hypertension. The development and reversibility of these changes by various treatments and by drugs is discussed. The experimental model may provide valuable clues as to the mechanisms involved in the aetiology of pulmonary hypertension in man.

Animals↗

PubMed1988

A pathophysiological study of 10 cases of hypoxic cor pulmonale.

A pathophysiological study of the pulmonary vasculature in 10 patients with hypoxic cor pulmonale and severe airways obstruction (five treated and five untreated with long-term oxygen) is presented. The media of muscular pulmonary arteries was normal or atrophic but, in the intima, there was active deposition of longitudinal muscle, fibrosis and elastosis. In the arterioles a medical coat of circular smooth muscle bounded by a new internal elastic lamina had developed, while there was deposition of longitudinal muscle and fibrosis in the intima. In five cases the lumen was subdivided into parallel tubes, found by serial section to lead into alveolar capillaries. These features are distinctive of hypoxaemia and obstructive airways disease. Changes continued until death. The conspicuous longitudinal muscle may be attributable to stretching of vessels round distorted terminal airways; further exploration into mechanisms is required. The hypothesis that vascular changes follow hypoxic vasoconstriction is no longer tenable. No correlations were found between quantitative pathological findings and arterial blood gas tensions, pulmonary artery pressure or haematocrit. There were no differences between patients treated or not treated with oxygen which might suggest that it arrests pathological changes. Thus, once a patient is given oxygen, survival probably depends as much on progressive mechanical changes in the lung as on continuing hypoxaemia.

Airway Obstruction↗

PubMed1987

Effect of alveolar pressure on pulmonary artery pressure in chronically hypoxic rats.

The effect on pulmonary artery pressure of a rise in alveolar pressure differed in chronically hypoxic rats (10% O2 for 3-5 weeks) compared with control rats. Chronically hypoxic rats have newly muscularised walls in arterioles in the alveolar region. Isolated lungs of chronically hypoxic and control rats were perfused with blood under conditions in which alveolar pressure was greater than left atrial pressure during both normoxia and hypoxia. Alveolar pressure was the effective downstream pressure. Pressure-flow lines were measured at low and high alveolar pressure (5 and 15 mmHg). During normoxia pressure-flow lines of chronically hypoxic rats had a steeper slope (higher resistance) and greater extrapolated intercept on the pressure axis (effective downstream pressure) than control rats. In both groups of rats the change from low to high alveolar pressure during normoxia caused an approximately parallel shift in the pressure-flow line similar to the change in alveolar pressure. During hypoxia, which led to an increase in slope and intercept in both groups of rats, the effect of a rise in alveolar pressure differed in chronically hypoxic from control rats. In control rats there was a small parallel shift in the pressure-flow line that was much less than the increase in alveolar pressure; in chronically hypoxic rats there was a large parallel shift in the pressure-flow line that was greater than the increase in alveolar pressure. Thus in chronically hypoxic rats hypoxic vasoconstriction probably occurred mainly in muscular alveolar vessels, whereas in control rats it probably occurred upstream in extra-alveolar vessels. At constant blood flow the relation between pulmonary artery pressure and alveolar pressure was measured while alveolar pressure was reduced from approximately 15 mmHg to zero during both normoxia and hypoxia. In control and chronically hypoxic rats the slope of this line was less than 1. At an alveolar pressure of 2-3 mmHg there was an inflection point below which the line was nearly horizontal in control but negative in chronically hypoxic rats. During hypoxia the inflection point increased in control but not in chronically hypoxic rats, whereas the preinflection slope became negative. Apart from a rise in pulmonary artery pressure at all values of alveolar pressure, which occurred in both groups of rats, there was no change in the form of the curve in chronically hypoxic rats during hypoxia. These results also suggest constriction of extra-alveolar vessels in control rats and alveolar vessels in chronically hypoxic rats during hypoxia.

Animals↗

PubMed1986

Quantitative changes in the rat pulmonary vasculature in chronic hypoxia--relation to haemodynamic changes.

The anatomical basis of resistance and compliance changes of the pulmonary arterial bed was studied in rats exposed to chronic hypoxia (10% O2, 3 weeks) and the findings were compared with those of normoxic rats. The lungs were perfused with a Ba-gelatine mixture at different pressures and studied by radiology and histology. The diameter of the pulmonary arteries (greater than 0.5 mm), measured from X-rays, was less in chronically hypoxic than normoxic rats when filled at the same perfusion pressure. Diameters increased in both groups with increasing perfusion pressure but at a given pressure those of chronically hypoxic rats were always smaller than those of normoxic rats. We found evidence that arterial length was increased in chronically hypoxic rats. Arterioles of 50 micron or less in diameter adjacent to gas exchange units were of similar external diameter in normoxic and chronically hypoxic rats, but most of the latter had developed a muscular coat and a second elastic lamina internal to the single elastic lamina of control arterioles. These changes reduced the lumen by an estimated 10-14% and would increase pulmonary arteriolar resistance in chronically hypoxic rats, resulting in a changed pressure profile. We found no evidence of arteriolar loss in chronically hypoxic rats although at a given pressure, the Ba-gelatine mixture penetrated less far for reasons which are discussed.

Angiography↗

PubMed1986

Division of type I and endothelial cells in the hypoxic rat carotid body.

The mammalian carotid body is enlarged under conditions of chronic hypoxaemia. There has been some discussion as to whether this is due to hypertrophy or to hyperplasia. We have subjected rats to 1, 2 or 7 days of 10% oxygen and, 4 h before removing the carotid bodies, injected each animal with vincristine sulphate, an inhibitor of mitosis. The results of this study indicate that numerous mitoses can be found in the carotid bodies of rats exposed to 10% oxygen, but not in control animals maintained in air. These experiments thus provide direct evidence that at least a proportion of the increase in size of the carotid body induced by chronic hypoxaemia is due to a cellular hyperplasia.

Animals↗

PubMed1984

The enlarged carotid body of the chronically hypoxic and chronically hypoxic and hypercapnic rat: a morphometric analysis.

Rats were subjected to chronic hypoxia (10% O2) or hypoxia and hypercapnia (10% O2 + 4% CO2) for 3-4 weeks and their carotid bodies (twenty-three from twenty rats) were compared with those of litter-mate controls. Both chronic exposures, which simulated high altitude or chronic lung disease, caused a 4-10-fold increase in carotid body volume. The larger increases were attributed to higher fixation-perfusion pressures. The organs were fixed by perfusion with glutaraldehyde. Semi-thin (1 micron) sections for light microscopy and ultra-thin sections for electron microscopy were cut at regular intervals and were examined by stereological techniques to determine the nature of the enlargement. The proportion occupied by blood vessels was much increased in both chronic hypoxia and hypoxia plus hypercapnia; the endothelium appeared stretched with conspicuous fenestrations. There were increased numbers of endothelial cells which suggested new growth as well as stretching of endothelium and the mean transectional area of the vessels was increased. The mean surface area of blood vessels per unit area of carotid body was unaltered but the total surface area of blood vessels in the whole carotid body was greatly increased. Both the Type 1 cell nucleus and cytoplasm were increased in size. The proportion nucleus/cytoplasm was unaltered in hypoxia but reduced in hypoxia plus hypercapnia. There were fewer Type 1 cell nuclei per unit area but the estimated total number of Type 1 cell nuclei per carotid body was increased 2-4-fold; this was interpreted as Type 1 cell hyperplasia. Some of the dense-cored vesicles in Type 1 cells were enlarged with eccentric dense cores but their number per unit area of cytoplasm was decreased. Their mean size was not significantly altered. However, the total number of vesicles per carotid body was presumed to be increased because their decreased density in the cell was offset by a greater increase in total Type 1 cell volume. The harmonic and arithmetic mean distances between endothelium and the boundary of glomus tissue were significantly reduced. The harmonic mean distance is an indication of the diffusion distance for gases to and from blood and glomus tissue. The arithmetic mean distance is a measure of the amount of tissue in between. The significance of the vascular enlargement and hyperplasia and the Type 1 cell hyperplasia cannot be assessed at present. We do not know if enlargement is associated with the same, greater, or lesser activity of the organ for a given stimulus.

Animals↗

PubMed1983

Contribution of polycythaemia to pulmonary hypertension in simulated high altitude in rats.

A rat model was used to assess the viscosity factor in pulmonary hypertension of high altitude. Rats exposed to 10% O2 for three weeks developed increased pulmonary vascular resistance (p.v.r.) and polycythaemia; the haematocrit (Hct) was 50-60%, values similar to those in normal men at high altitudes. The contribution of high Hct to the increased p.v.r. was assessed in isolated perfused lungs of chronically hypoxic rats perfused with their own high Hct blood, or normal Hct blood from control rats. Pressure/flow relationships were measured over a wide range and the slope (P/Q) of this relationship and its extrapolated intercept on the pressure axis were increased by high Hct blood. A return to low Hct blood did not restore initial conditions although a second perfusion with high Hct blood again increased p.v.r. and intercept. Lack of reversibility was attributed to changes with time in blood or lung. In a second experiment designed to eliminate time changes, chronically hypoxic or litter-mate control rats were each perfused with only one blood, their own or each other's and P/Q relations were rapidly measured. The P/Q slope and pressure intercept increased progressively in the following groups: control rats perfused with their own blood (Hct 34%), control rats perfused with chronically hypoxic blood (Hct 56%), chronically hypoxic rats perfused with control blood (Hct 35%) and chronically hypoxic rats perfused with chronically hypoxic blood (Hct 53%). To exclude factors in chronically hypoxic blood other than high Hct which might increase p.v.r., control rats were perfused with blood of different Hct obtained by centrifugation. High Hct again increased p.v.r. There was a significant relationship in all rats between pulmonary artery pressure (Ppa), which takes into account both P/Q slope, intercept and Hct. There was substantial batch variation which may reflect sensitivity to hypoxia. In chronically hypoxic rats with high Hct blood, Ppa varied from 29-47 mmHg; with low Hct blood the range was 26-38 mmHg. Comparable values for control rats were 21-29 and 17-20 mmHg. We conclude that the polycythaemic blood of chronic hypoxia contributes substantially to pulmonary hypertension. Where it is excessive, it may prejudice tissue blood flow.

Altitude↗

PubMed1983

Does almitrine bismesylate improve V/Q matching? An animal study.

Pulmonary vascular actions of almitrine bismesylate were studied in ferrets, rats, cats and dogs in conditions which simulated those of patients with hypoxic lung disease. All or part of a lung was made hypoxic or hypoventilated so that affected vessels were constricted. Rats were made chronically hypoxic (10%, O2, normobaric chamber). In vivo and isolated preparations were used. In all preparations and species almitrine bismesylate caused vasoconstriction in normoxia, constriction followed by dilation in hypoxia or hypoventilation. In hypoventilated lung there is ventilation/perfusion mismatching which was not improved by almitrine bismesylate . Ventilatory measurements in chronically hypoxic/hypercapnic rats showed that almitrine bismesylate increased tidal volume but not frequency. It is uncertain whether vascular (Q) or small ventilatory (V) changes are the cause of the improved gas tensions and V/Q matching in patients with chronic obstructive lung disease receiving almitrine bismesylate .

Almitrine↗

PubMed1982

The effects of localized hypoventilation on ventilation/perfusion (V/Q) ratios and gas exchange in the dog lung.

1. Hypoventilation of one lobe of lung was studied in open-chest anaesthetized dogs. Lobar blood flow, pulmonary-artery pressure and gas exchange were measured, the latter from breath-by-breath analysis with a mass spectrometer. 2. Hypoventilation of the lobe by reducing the respiratory pump stroke led, at each step, to a reduction in blood flow to that lobe. The flow (Q) reduction was variable, but always less than the ventilation (VE) reduction, so that the V/Q ratio to the lobe was reduced. O2 tension and pH fell and CO2 tension rose in effluent blood. Thus V/Q regulation achieved by flow reduction varied between individuals and was of low gain. 3. Anatomical or series dead space (VD series) was reduced in proportion to ventilation. When VD series was less than the apparatus dead space, some gas exchange still took place. 4. Oxygen uptake (VO2) and CO2 output (VCO2) were reduced during hypoventilation. VCO2 fell more than VO2, so that the respiratory exchange ratio (R) was reduced. 5. Whether the deterioration in gas tensions in effluent blood during hypoventilation of the lobe was due to shunt of blood past unventilated alveoli, or to V/Q mismatching, was not resolved. 6. The plateau phase of the CO2-output curves at low tidal volumes was usually regular; thus either hypoventilation was uniform, or some ventilation units were totally closed.

Animals↗