Pressure/flow relation in the peripheral pulmonary vascular bed in dogs: a preliminary study

In order to test a technique for the determination of the pressure/flow relationship in the peripheral pulmonary vascular bed, the perfusion pressure changes with increasing and then decreasing flow in a small part of the lung (around 1 ml) were studied in anaesthetized supine dogs, after insertion of a specially designed double distal lumen Swan–Ganz catheter. One lumen was used for the pressure measurement, one for infusion of saline by a pump with variable flow, from 0.1 to 1.0 ml s^-1. A conventional thermodilution Swan–Ganz catheter was also advanced in the pulmonary artery, to measure pressures in the pulmonary circulation as well as cardiac output. During infusion in the wedged catheter, right atrial, pulmonary arterial and balloon occlusion wedge pressures did not change. The pressure/flow curve of the occluded vascular bed showed a shape similar to that of collapsible tubes, with a pressure plateau at high flow, but this could also be due to vascular recruitment. The curve exhibited hysteresis, with a lower pressure when flow decreased. The slope of the initial part of the curve increased, on average, from 54±9 during normoxia to 91±27 mmHg s ml^-1during hypoxia (FIO₂= 0.10); this difference was not significant, but the perfusion pressure at high flow was significantly higher during hypoxia (P < 0.05). Using blood instead of saline would allow the determination of the peripheral pulmonary vascular resistance under physiological conditions, and further work is needed to estimate the sensitivity and the reproducibility of this technique.     

The effect of saline and hyperoncotic dextran infusion on canine ileal salt and water absorption and regional blood flow.

1. The unidirectional Na and H2O fluxes, vascular pressures and total and absorptive site blood flows in the canine ileum were determined before and during I.V. saline infusion and subsequent I.V. infusion of hyperoncotic dextran. The intestinal perfusion solutions were isotonic saline or isotonic saline and mannitol, but the effects of I.V. saline or I.V. hyperoncotic dextran infusion were generally the same for both luminal solutions. 2. Continuous I.V. infusion of saline caused a continuous increase in the unidirectional flux of Na and H2O into the ileal lumen, an increase in total blood flow, and an increase in venous pressure. 3. The net absorption of Na and H2O was decreased by I.V. saline infusion. 4. The unidirectional fluxes of Na and H2O out of the lumen, arterial pressure, and absorptive site blood flow were not affected by I.V. saline infusion. 5. I.V. hyperoncotic dextran infusion reversed most of the effects of saline infusion. 6. The unidirectional fluxes of Na and H2O into the lumen were significantly correlated with Starling forces during I.V. saline infusion. 7. It was concluded that intestinal transport of salt and water was subject to regulation by physical forces at the capillary level.     

Constant flow- vs. constant pressure-perfusion for studies of pulmonary vasoactive responses

We have compared the pulmonary vascular responses to a standardized hypoxic vasoconstrictor stimulus (F_1,0,2=0.02) obtained during 1) constant volume inflow, with pulmonary arterial pressure as the dependent variable, and 2) constant inflow pressure, with flow as the dependent variable. Isolated rat lungs were perfused at different baseline transvascular pressures. The experimental arrangement allowed changes between the two types of perfusion. Hypoxia at constant pressure perfusion gave a higher percentage rise in pulmonary vascular resistance (PVR) at all pressure levels. This advantage was however, more than offset by the finding that a) vascular closure (total or partial) often occurred, particularly below arterial pressure of 3 kPa, making detection of graded responses impossible, and b) the control situation was rarely regained. Responses obtained during constant flow were less reduced by elevations in baseline transvascular pressure, and the control situation was rapidly and completely regained. The observation that hypoxic vascular closure may occur in the pulmonary vascular bed supports the hypothesis that high altitude edema is caused by precapillary occlusion of a major part of the vascular bed, thereby subjecting still perfused regions to very high pressures and flow.     

Endothelin infusion reduces hypoxic pulmonary hypertension in pigs in vivo

Previous work has shown that the plasma levels of the potent vasoactive peptide endothelin (ET) are increased in pathophysiological conditions with increased pulmonary vascular resistance and it has been speculated that ET may play some part in hypoxic pulmonary hypertension. We have therefore evaluated the effects of ET-infusion in the porcine pulmonary circulation after hypoxia-induced hypertension. Pigs under general anaesthesia were artificially ventilated through an endotracheal tube and hypoxia was induced by decreasing the fraction inhaled 0₂ from 0.21 to 0.10. Haemodynamic parameters were continuously recorded using a Swan-Ganz catheter in combination with thermodilution for cardiac output measurements. ET-1 or ET-3 was given as an i.v. infusion through the Swan-Ganz catheter in the right ventricle. Hypoxia induced a reproducible increase in pulmonary vascular resistance (PVR), mean pulmonary artery pressure (MPAP) and right ventricular stroke work (RVSW) while the systemic vascular resistance (SVR) slightly decreased. Cumulative infusion of ET-1 (10, 25 and 50 ng kg^-1 min^-1) dose-dependently decreased MPAP and PVR; at a higher dose (100 ng kg^-1min^-1), the PVR returned to the level observed at hypoxia. ET-infusions at 50 and 100 ng kg^-1 min^-1 evoked an increase in SVR and a decrease in cardiac output (CO) and stroke volume (SV). RVSW also gradually decreased during ET-1 infusion. Infusion of ET-3 evoked effects similar to those of ET-1 infusions, although the response to ET-3 was not that rapid in onset. In a second series of animals, repeated 15 min periods of hypoxia evoked a stable, reproducible response with a consistent increase in PVR, MPAP and RVSW which returned to baseline values during normoxia. Infusion of ET-1 (25 ng kg^-1 min^-1) evoked a rapidly developing decrease in PVR and MPAP which was quickly normalized upon cessation of the ET-infusion. ET-1 infusion at this concentration did not per se influence the haemodynamic parameters during normoxia. It is concluded that in the pig, short-term ET-infusion reduces the pulmonary hypertension associated with acute hypoxia.     

Effect of hypertonic saline infusion on renal vascular resistance in anesthetized dogs.

Changes in renal vascular resistance (RVR) and their mechanisms were investigated following infusion of 7.5% hypertonic saline (4 ml/kg) in anesthetized dogs. In all animals the left kidney was perfused at a constant perfusion flow (59 +/- 6 ml/min) with heparinized blood using a pulsatile roller pump. Renal perfusion pressure (RPP), systemic blood pressure (SBP), central venous pressure (CVP), and heart rate (HR) were measured simultaneously. Electrical stimulation of renal sympathetic nerves was also performed to evaluate the neurally mediated change in renal vasculature before and after infusion of hypertonic saline. In animals with intact vagi, intravenous administration of hypertonic saline resulted in significant increases in both mean blood pressure (MBP) and CVP, and caused significant decreases in HR and RVR. These effects were not affected by bilateral cervical vagotomy. In both intact and vagotomized animals, changes in RVR in response to renal nerve stimulation were attenuated after infusion of hypertonic saline. These results suggest that reduction in RVR after intravenous infusion of hypertonic saline is not a reflex effect mediated by vagal afferents. Instead, vascular response of the renal artery to hypertonic saline may result from a suppression of neurotransmission from renal sympathetic nerve endings to renal vascular smooth muscle.     

Some Physical Properties of the Pulmonary Arterial Bed Deduced from Pulsatile Arterial Flow and Pressure

This study aimed to quantify changes of vascular compliance and resistance of the proximal and the peripheral pulmonary arterial vessels when vascular smooth muscle was stimulated. These above vascular characteristics were derived from registrations of pulsatile pressure and flow in the pulmonary artery (PA). An in situ cat lung preparation was used, with the right heart by-passed by a pulsatile blood pump. Vascular input impedance was derived from PA pulsatile pressure and flow recordings, and impedance characteristics were used for calculation of the variables of a simple lumped analog representation of the arterial bed. PA smooth muscle was stimulated by infusions of collagen suspension, by general hypoxia and by nor-adrenaline injections. Collagen caused 40% reduction of vascular compliance (C), no changes in proximal arterial resistance (Rl) and 18076 increase in peripheral vascular resistance (R2). Hypoxia caused 5096 reduced C, 20% increased R1 and 70% increased R2. Noradrenaline caused 20:6 reduced C and 30 % increased R1 and R2. These results, together with results derived from simulation of the observed impedance changes in a computer model of the lung arterial bed, indicated that collagen infusion elicited contraction of small and medium-sized arteries, with increased arterial volume as result of increased distending pressure. Hypoxia and noradrenaline, seemed both to cause contraction of the total arterial bed. This effect being most pronounced during hypoxia.     

Rapid intravenous infusion of 20 mL/kg saline alters the distribution of perfusion in healthy supine humans

Rapid intravenous saline infusion, a model meant to replicate the initial changes leading to pulmonary interstitial edema, increases pulmonary arterial pressure in humans. We hypothesized that this would alter lung perfusion distribution. Six healthy subjects (29 ± 6 years) underwent magnetic resonance imaging to quantify perfusion using arterial spin labeling. Regional proton density was measured using a fast-gradient echo sequence, allowing blood delivered to the slice to be normalized for density and quantified in mL/min/g. Contributions from flow in large conduit vessels were minimized using a flow cutoff value (blood delivered > 35% maximum in mL/min/cm(3)) in order to obtain an estimate of blood delivered to the capillary bed (perfusion). Images were acquired supine at baseline, after infusion of 20 mL/kg saline, and after a short upright recovery period for a single sagittal slice in the right lung during breath-holds at functional residual capacity. Thoracic fluid content measured by impedance cardiography was elevated post-infusion by up to 13% (p<0.0001). Forced expiratory volume in 1s was reduced by 5.1% post-20 mL/kg (p=0.007). Infusion increased perfusion in nondependent lung by up to 16% (6.4 ± 1.6 mL/min/g baseline, 7.3 ± 1.8 post, 7.4 ± 1.7 recovery, p=0.03). Including conduit vessels, blood delivered in dependent lung was unchanged post-infusion; however, was increased at recovery (9.4 ± 2.7 mL/min/g baseline, 9.7 ± 2.0 post, 11.3 ± 2.2 recovery, p=0.01). After accounting for changes in conduit vessels, there were no significant changes in perfusion in dependent lung following infusion (7.8 ± 1.9 mL/min/g baseline, 7.9 ± 2.0 post, 8.5 ± 2.1 recovery, p=0.36). There were no significant changes in lung density. These data suggest that saline infusion increased perfusion to nondependent lung, consistent with an increase in intravascular pressures. Dependent lung may have been "protected" from increases in perfusion following infusion due to gravitational compression of the pulmonary vasculature.     

Pulmonary vascular pressure profile in adult ferrets: measurements in vivo and in isolated lungs

We have determined the vascular pressure profile in lungs of adult ferrets utilizing an anaesthetized open chested preparation and have compared the pressure profile in vivo with that in isolated, perfused lungs. Ten adult ferrets, mean body weight 980 +/- 108 g, were studied. For in vivo measurements, five ferrets were anaesthetized, mechanically ventilated and the left chest wall resected. Pressures were measured in the pulmonary artery, left atrium and by micropuncture, in 20-50 microns diameter subpleural arterioles and venules. During micropuncture, ventilation was stopped for 1-2 min and the lungs kept distended at an airway pressure of 6 cmH2O. Left atrial pressure was raised to approximately 8 cmH2O with saline infusion so that lungs were in Zone 3. Cardiac output was measured by thermodilution. Lungs of five other ferrets were isolated and perfused with a steady flow roller pump. In these lungs blood flow was adjusted so that pulmonary artery pressure was similar to that in anaesthetized ferrets, with airway and left atrial pressures at 6 and 8 cmH2O respectively (Zone 3). Blood haematocrit (35 +/- 7%) was similar in the two groups. In lungs of anaesthetized ferrets total arteriovenous pressure drop was 12.1 +/- 1.9 cmH2O, with cardiac output being 210 +/- 80 ml kg body weight-1 min-1. Fractional resistance in arteries was 37%, 37% in microvessels and 26% in veins. In isolated ferret lungs, though blood flow was only 48 +/- 10 ml kg body wt-1 min-1 for the same total arteriovenous pressure drop as in vivo, the longitudinal distribution of vascular resistance was similar to that in live ferrets.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic peptide attenuates an increase in pulmonary vascular incremental resistance due to high pulmonary venous pressure.

The aim of this study was to determine whether an elevation of pulmonary venous pressure (PVP) and atrial natriuretic peptide (ANP) affects pulmonary vascular resistance (PVR) and pulmonary vascular incremental resistance (iPVR). We vascularly isolated the left lower lobe of the lung and perfused it with blood using a pulsatile pump. Blood flow (PBF) to the isolated lobe was decreased in 6 to 7 steps from about 8 to 1 ml/(kg.min). PVR was calculated from measurements of PBF and the pressure difference between pulmonary arterial pressure and PVP at four different levels of fixed PVP. iPVR was estimated from a slope of the pressure-flow relationships between effective pulmonary driving pressure and PBF at four different levels of fixed PVP. iPVR was 2.2 +/- 0.2, 2.2 +/- 0.1, 2.4 +/- 0.1, and 2.6 +/- 0.2 mmHg.min.kg/ml, when PVP was 0, 5, 10, and 15 mmHg, respectively. To test whether or not the response of the pulmonary vascular bed to the elevated PVP is modulated by ANP, iPVR was estimated before and after an administration of ANP in the perfusion circuit. Increased iPVR from 2.1 +/- 0.2 to 2.5 +/- 0.2 mmHg.min.kg/ml in response to the elevation of PVP from 0 to 15 mmHg decreased to the control level after the administration of ANP. ANP, however, did not change the control iPVR. PVR decreased with increasing PVP. ANP decreased PVR when PVP was 0 mmHg, but did not change it when PVP was 15 mmHg. These results suggest that ANP decreases PVR and restores the decreased pulmonary vascular compliance.     

Cerebrovascular responses to haemorrhagic hypotension in anaesthetized cats. Effects of alpha-adrenoceptor antagonists

Haemorrhagic hypotension induces the phenomenon of cerebrovascular autoregulation and, concomitantly, involves an activation of the sympathetic nervous system. As brain vessels in cats have an atypical adrenoceptor distribution we studied the effects of an alpha-adrenoceptor antagonist on the autoregulatory response to haemorrhage. Cortical blood flow was studied by the H2 technique in chloralose-anaesthetized cats subjected to a period of graded haemorrhage over 3 h. Three groups of cats were studied: control, i.e. those receiving saline (n = 10); yohimbine-treated (200 micrograms . kg-1 . h-1, n = 7); and prazosin-treated (50 micrograms . kg-1 . h-1, n = 6). In the control group, cortical blood flow remained relatively constant when mean arterial pressure was decreased from 102 +/- 1 mmHg (mean +/- SE) to approximately 50 +/- 1 mmHg; thereafter, blood flow decreased with decreasing perfusion pressure. In the arterial pressure range 64-55 mmHg, cortical blood flow was significantly higher in the yohimbine group (109 +/- 12 ml . 100 g-1 . min-1) compared to the control group (69 +/- 6 ml . min-1) and remained higher in the yohimbine-treated cats at more extreme levels of hypotension. Blood flow did not fall significantly in the yohimbine-treated cats until mean arterial pressures of 31 +/- 1 mmHg were attained. In the prazosin-treated cats, flow began to decrease at arterial pressures even greater than those observed in the control group. Thus, there is a sympathetic vasoconstriction of brain arteries that is primarily mediated by alpha 2-adrenoceptors in the feline cerebrovascular bed.     

犬肺动脉高压模型连续热稀释法的应用

背景：以往小动物肺动脉高压模型有创测压方法一般根据生物信号采集系统的压力波形图引导,采用右心导管法进行压力测定;由于设备技术和动物体积的限制无法应用肺动脉导管测定心输出量及肺血管阻力。 目的：在脱氢野百合碱诱导建立犬肺动脉高压模型中利用Swan-Ganz七腔漂浮导管和Vigilance系统根据连续热稀释法测定心输出量、肺血管阻力,肺动脉压力,探讨连续心排量法在肺动脉高压动物模型中的应用价值。 方法：10只比格犬随机分成2组：实验组用脱氢野百合碱右心房注射的方法建立肺动脉高压的动物模型,对照组右心房注射二甲基酰胺做对照;在用药前,用药后8周使用漂浮导管和Vigilance系统分别测定两组犬右心房收缩压、右心室收缩压、肺动脉收缩压、平均肺动脉压力、肺毛细血管楔压及心输出量。 结果与结论：实验组用药后肺血管阻力显著上升(P=0.00),实验组用药后心输出量显著减少(P < 0.05)。使用连续热稀释法测定肺血管阻力和心输出量较传统的间断热稀释法更准确稳定。利用漂浮导管和Vigilance系统根据连续热稀释法原理在脱氢野百合碱诱导的犬肺动脉高压模型中进行肺血管阻力和心输出量测定,该方法具有准确稳定、可重复操作和对实验模型创伤小的优点。     

Sympathetic responses during saline infusion into the veins of an occluded limb

Animal studies have shown that the increased intravenous pressure stimulates the group III and IV muscle afferent fibres, and in turn induce cardiovascular responses. However, this pathway of autonomic regulation has not been examined in humans. The aim of this study was to examine the hypothesis that infusion of saline into the venous circulation of an arterially occluded vascular bed evokes sympathetic activation in healthy individuals. Blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) responses were assessed in 19 young healthy subjects during local infusion of 40 ml saline into a forearm vein in the circulatory arrested condition. From baseline (11.8 ± 1.2 bursts min⁻¹), MSNA increased significantly during the saline infusion (22.5 ± 2.6 bursts min⁻¹, P < 0.001). Blood pressure also increased significantly during the saline infusion. Three control trials were performed during separate visits. The results from the control trial show that the observed MSNA and blood pressure responses were not due to muscle ischaemia. The present data show that saline infusion into the venous circulation of an arterially occluded vascular bed induces sympathetic activation and an increase in blood pressure. We speculate that the infusion under such conditions stimulates the afferent endings near the vessels, and evokes the sympathetic activation.     

A preparation of perfused small intestine for the study of absorption in amphibia

1. A preparation of amphibian small intestine perfused through its vascular system is described. Vascular perfusion with a bicarbonate Ringer solution containing a colloid is used to control the composition of the environment of the submucosal faces of the absorbing cells and to carry away for collection any material extruded from these cells. Oxygenation of the mucosal cells is derived primarily from fluid circulated through the intestinal lumen. The preparation exhibits physiological properties of transport for periods of up to 5 hr. After 5 hr perfusion the epithelial cells show no signs of gross cellular damage when examined either by light or by electron microscopy.2. The relationship between the hydrostatic pressure at the mesenteric artery and the rate of perfusion through the vascular bed is substantially linear. The pressure-flow relationships in the mesenteric bed, including an apparent ;critical closing pressure', are primarily determined by the hydrostatic pressure in the intestinal lumen. Alterations in the hydrostatic pressure in the intestinal lumen also change the relative proportions of the vascular infusate which appear in the portal venous effluent and in the fluid exuded from the serosal surface of the preparation (;sweat'). Hydrostatic distension pressures above about 10 cm H(2)O reduce the rate of collection of fluid from the portal vein and increase the rate of collection of ;sweat'.3. An increase in the rate of vascular perfusion increases the total rate of glucose appearance although the glucose concentrations in both the portal effluent and the ;sweat' are reduced.4. The glucose translocation rate is related in an alinear saturable fashion to the luminal concentration of glucose. By making a correction for metabolic loss of glucose during its passage through the intestinal cell, the relationship existing between the lumen concentration and the uptake of the sugar by the mucosal cells has been calculated. This relationship is found to fit Michaelis-Menten type kinetics. The K(m) of the intestinal translocation process for glucose in Rana pipiens was 0.45 +/- 0.13 (4) muM. The mean V(max) was 137.5 +/- 35.3 (4) muM/hr/g fat-free dry wt.5. When phlorrhizin (10(-5)M) is added to the vascular perfusate, no inhibition of glucose transport is seen for at least 60 min. When strophanthin is added to the vascular perfusate (5 x 10(-5)M), a markedly greater inhibition of glucose transport is observed than when it is introduced to the luminal circulation.6. Earlier studies of the vascular perfusion of isolated small intestine are tabulated. The experimental findings are discussed in relation to a model of the mode of action of the epithelial cell for glucose transport.     

Suggested predictive indices for high altitude pulmonary oedema

A study was conducted to evaluate the responses of chemoreceptors and pulmonary vascular bed to hypoxia, on two groups of soldiers exposed to similar altitudes, one group which did not suffer from high altitude (HA) maladies (Gp A) and the other when exposed to similar altitudes suffered from HA maladies (Gp B high altitude pulmonary edema--susceptible group (HAPE-S). Aim of this study was to find out whether these two tests could be used as a screening test for soldiers and sojourners proceeding to HA. Chemoreceptor responses were evaluated by hypoxic ventilatory response (HVR) test and the pulmonary vascular responses were studied by recording pulmonary artery pressure (PAP) changes under simulated hypoxia by breathing hypoxic gas mixtures (HGM) in both the groups. It was observed that HAPE-S subjects showed a reduced HVR response and an increase in PAP (systolic, diastolic, and mean). While Gp A subjects showed an increase in ventilation of 11.39 +/- 3.36 L, the same in Gp B subjects was 3.51 +/- 2.65 L. Thus, the comparison of increase in ventilation following HVR test between the two groups was highly significant. Under hypoxic gas mixture (HGM) breathing, systolic pressure of 28.2 +/- 6.9 and 52.6 +/- 11.0 mm Hg; diastolic pressure of 11.4 +/- 3.8 and 23.6 +/- 5.8 mm Hg and mean pressure of 17.6 +/- 4.3 and 35.0 +/- 7.4 mm Hg were recorded in pulmonary arteries in Gp A and Gp B subjects, respectively. Gp B subjects showed a highly significant increase in all the three pulmonary pressures under HGM breathing.     

Reflex responses from the main pulmonary artery and bifurcation in anaesthetised dogs

This study was undertaken to determine the reflex cardiovascular and respiratory responses to discrete stimulation of pulmonary arterial baroreceptors using a preparation in which secondary modulation of responses from other reflexes was prevented. Dogs were anaesthetised with -chloralose, artificially ventilated, the chests widely opened and a cardiopulmonary bypass established. The main pulmonary arterial trunk, bifurcation and extrapulmonary arteries as far as the first lobar arteries on each side were vascularly isolated and perfused through the left pulmonary artery and drained via the right artery through a Starling resistance which controlled pulmonary arterial pressure. Pressures distending systemic baroreceptors and reflexogenic regions in the heart were controlled. Reflex vascular responses were assessed from changes in perfusion pressures to a vascularly isolated hind limb and to the remainder of the subdiaphragmatic systemic circulation, both of which were perfused at constant flows. Respiratory responses were assessed from recordings of efferent phrenic nerve activity. Increases in pulmonary arterial pressure consistently evoked increases in both perfusion pressures and in phrenic nerve activity. Both vascular and respiratory responses were obtained when pulmonary arterial pressure was increased to above about 30 mmHg. Responses increased at higher levels of pulmonary arterial pressures. In 13 dogs increases in pulmonary arterial pressure to 45 mmHg increased systemic perfusion pressure by 24 +/- 7 mmHg (mean +/- S.E.M.) from 162 +/- 11 mmHg. Setting carotid sinus pressure at different levels did not influence the vascular response to changes in pulmonary arterial pressure. The presence of a negative intrathoracic pressure of -20 mmHg resulted in larger vascular responses being obtained at lower levels of pulmonary arterial pressure. This indicates that the reflex may be more effective in the intact closed-chest animal. These results demonstrate that stimulation of pulmonary arterial baroreceptors evokes a pressor reflex and augments respiratory drive. This reflex is likely to be elicited in circumstances where pulmonary arterial pressure increases and the negative excursions of intrathoracic pressure become greater. They are likely, therefore, to be involved in the cardio-respiratory response to exercise as well as in pathological states such as pulmonary hypertension or restrictive or obstructive lung disease.     

The effect of heparin on the haemodynamic and structural response in the rat to acute and chronic hypoxia

In the mouse, heparin administered intermittently, has been shown to reduce the right ventricular hypertrophy (RVH) caused by hypoxia. We have investigated in the rat the effect of heparin on the haemodynamic and pulmonary vascular structural remodelling produced by hypoxia, with special reference to the new muscularization of peripheral arteries. Heparin at one of two doses (30 and 50 u/kg/h) was administered by continuous intravenous infusion from a miniosmotic pump to rats during 10 days exposure to hypobaric hypoxia and its effect examined on mean pulmonary artery pressure (PPa), RVH and, using morphometric techniques, vascular structural remodelling. Hypoxia produced the haemodynamic and structural changes previously described in this model. Heparin had no significant effect on PPa; a slight reduction in RVH was seen in the high-dose heparin group. After heparin, the narrowing of the axial pulmonary artery lumen caused by hypoxia was less: heparin reduced the proportion of arteries that became muscularized, particularly at alveolar duct level where the pericyte is the precursor smooth muscle cell. Heparin did not diminish the increase in medial thickness or reduction in external diameter of muscular arteries. Some rats, after chronic hypoxia, did not respond to an acute hypoxic challenge yet were no different from 'responders' in other haemodynamic and structural features. Including all rats, the mean acute pressor response to hypoxia was unaffected by heparin: taking only responder rats, a trend was apparent that heparin reduced the rise in PPa on acute hypoxic challenge.     

Endothelin-1: increased plasma clearance, pulmonary affinity and renal vasoconstriction in young smokers.

Pulmonary and renal haemodynamics and elimination of endothelin-1 (ET-1) were studied in six young smokers in response to 20 min intravenous infusion of ET-1 (4 pmol kg(-1) min(-1)) after smoking. At 20 min of ET-1 infusion fractional ET-1 extractions in the lungs and kidneys were 60 +/- 2 and 60 +/- 7%, respectively. Cardiac output and renal blood flow (RBF) fell by 18 +/- 4% (P<0.05) and 34 +/- 5% (P<0.01). Mean systemic arterial pressure increased (P<0.05) whereas pulmonary pressures were unchanged. Compared with previously published data in non-smokers (Weitzberg et al., 1991, 1993) basal arterial ET-1 and ET-1-values during ET-1 infusion were lower with a more rapid return to basal value. Smokers had higher pulmonary extraction of ET-1 at the same pulmonary arterial concentration (P<0.05). RBF reduction was more pronounced (P<0.05). Systemic vascular resistance increased while pulmonary vascular resistance did not increase as in non-smokers. Increased plasma clearance and more efficient pulmonary elimination of ET-1 lowers the arterial level in young smokers. In addition ET-1 evokes more pronounced renal vasoconstriction in these individuals.     

Effect of nocturnal hypoxia on pulmonary hemodynamics in patients with obstructive sleep apnea

Effects of apnoea induced nocturnal hypoxia on pulmonary haemodynamics (PH) in pts with OSA are still under debate. We studied PH in 67 pts (64 M and 3 F) mean +/- SD: age 45 +/- 8 years, with severe OSA, AHI 62 +/- 22. Patients had normal spirometry: FVC 98 +/- 15% N, FEV1 97 +/- 16% N and arterial blood gases--PaO2 72 +/- 10 mmHg, PaCO2 40 +/- 4 mmHg. PH were studied using Swan-Ganz thermodilution catheter. PH were within normal range: right atrial pressure 4.2 +/- 2.7 mmHg, right ventricular systolic/enddiastolic pressure 28.1 +/- 7.1/5.0 +/- 3.3 mmHg, mean pulmonary artery pressure (PAP) 15.8 +/- 4.6 mmHg, mean pulmonary wedge pressure (PW) 6.8 +/- 3.1 mmHg, cardiac output (CO) 5.6 +/- 2.2 L/min. and pulmonary vascular resistance (PVR) 150 +/- 83 dyn.sec.cm-5. During exercise (44 pts) PAP rose from 15.8 +/- 4.3 to 29.8 +/- 9.4 mmHg, PW rose from 6.8 +/- 3.2 to 12.6 +/- 6.8 mmHg and CO from 4.9 +/- 1.9 to 9.2 +/- 4.2 L/min. All patients presented with nocturnal desaturations. Mean oxygen saturation (SaO2 mean) was: 87.4 +/- 5.4%, minimal saturation (SaO2 min) was 57.4 +/- 15.9%. Time spent in desaturation SaO2 < 90% (T90) was 50.7 +/- 26.5%. Results of PH investigations were related to results of pulse oximetry. Linear regression analysis showed week negative correlations between SaO2 mean and: PAP (r = -0.37 p = 0.003), PVR (r = -0.37 p = 0.007), and positive correlation between T90 and PAP (r = 0.37 p = 0.008). We conclude that there is no diurnal pulmonary hypertension at rest in patients with severe OSA and normal lung function even in the presence of severe overnight nocturnal desaturations. In half of studied patients we observed pulmonary hypertension during exercise.     

Endogenous NO does not regulate baseline pulmonary pressure,but reduces acute pulmonary hypertension in dogs

It has remained unclear whether endogenous production of nitric oxide (NO) plays an important role in the regulation of physiologically normal pulmonary pressures. Severe alveolar hypoxia is accompanied by decreased pulmonary NO production, which could contribute to the development of hypoxic pulmonary hypertension. On the other hand, pharmacological NO inhibition further augments this hypertensive response. AIMS: The aims of the present study were to test: (a) whether NO contributes importantly in the maintenance of baseline pulmonary pressure; and (b) to which degree NO is involved in the pulmonary haemodynamic adjustments to alveolar hypoxia. METHODS: In anaesthetized dogs (n=37), the systemic and pulmonary haemodynamic effects of the NO synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME, 20 mg kg(-1)) and substrate, L-arginine (200-500 mg kg(-1)), were determined at baseline and during alveolar hypoxia. Constant blood flows were accomplished by biventricular bypass, and systemic normoxaemia was maintained by extracorporeal oxygenation. RESULTS: The primary findings were: (a) L-NAME failed to increase baseline mean pulmonary arterial pressure (10.1 +/- 0.7 vs. 10.5 +/- 0.5 mmHg, P=ns), despite effective NO synthase inhibition as evidenced by robust increases in systemic arterial pressures; (b) L-NAME augmented the pulmonary hypertensive response to alveolar hypoxia (10.2 +/- 0.7 to 19.5 +/- 1.7 with L-NAME vs. 9.9 +/- 1.1 to 15.5 +/- 1.0 mmHg without L-NAME, P<0.05); and (c) L-arginine failed to decrease baseline or elevated pulmonary pressures. Instead, prolonged L-arginine caused increases in pulmonary pressure. CONCLUSION: These findings suggest that NO plays no significant role in the tonic physiological control of pulmonary pressure, but endogenous NO becomes an important vasodilatory modulator during elevated pulmonary pressure.     

Coronary hemodynamics during hemopump left-intraventricular assistance.

Hemopump left intraventricular pumping (HP) can permit percutaneous transluminal angioplasty (PTCA) in high-risk patients. Benefits may be related to left ventricular unloading or myocardial perfusion improvement, or both. Direct ultrasonic measurements of coronary blood flow were made in the dilated vessel after a successful PTCA in five patients. A 3 Fr intracoronary Doppler catheter was placed in the coronary artery to measure flow velocities (maximal or diastolic velocity; minimum or systolic velocity and mean velocity). A SwanGanz catheter was used to measure the cardiac index and pulmonary capillary wedge pressure. Mean aortic pressures were monitored through an 8 Fr guiding catheter. Measurements were made after a 5-min period of minimal speed (T0) of the HP to avoid retrograde regurgitation through the turbine; during the increase from minimum to maximal speed (T1); after a 5-min period of maximal HP flow (3l/min) (T2) and after HP was pulled back (T3). From T0 to T2, cardiac index rose from 1.93 +/- 0.38 to 3.26 +/- 0.35 l/min/m2 and capillary wedge pressure decreased from 18 +/- 6 to 13 +/- 5 mmHg (p less than 0.05); from T2 to T3, cardiac index decreased to 2.4 +/- 0.4 while capillary wedge pressure increased to 17 +/- 5 (p less than 0.05). Mean arterial pressure and heart rate did not change significantly throughout the study. When the hemopump flow was raised to high speed, coronary blood flow increased immediately but returned shortly to baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)