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-1 during hypoxia (FIO2 = 0.10); this difference was not significant, but the perfusion pressure at high flow was significantly higher during hypoxia (P less than 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.     

Continuous cardiac output measured with a Swan‐Ganz catheter reacts too slowly in animal experiments with sudden circulatory failure

BackgroundIn many animal experiments, it is vital to detect sudden changes in cardiac output (CO). This porcine study compared CO that was measured with a Swan‐Ganz pulmonary catheter with the gold standard (which was a transit‐time flow probe around the pulmonary artery) during interventions that caused hemodynamic instability.MethodsIn one series, 7 pigs were exposed to sudden changes in CO. In another series, 9 pigs experienced more prolonged changes in CO. All the pigs had a Swan‐Ganz catheter placed into the pulmonary artery and a flow probe around the pulmonary artery. Adrenaline infusion and controlled hemorrhage were used to increase and decrease CO, respectively. The measurements of CO before and after each intervention were compared for correlation, agreement, and the time delay that it took each method to detect at least a 30% change in CO. A Bland–Altman test was used to identify correlations and agreements between the methods.ResultsIn the first series, there was a delay of 5–7 min for the Swan Ganz catheter to register a 30% change in cardiac output, compared with the flow probe. However, during prolonged changes in CO in the second series, there was a good correlation between the 2 methods. Mixed venous oxygen saturation reacted faster to changes than did CO; both were measured via the Swan‐Ganz catheter.ConclusionsIn many animal studies, the use of Swan‐Ganz catheters is suitable; however, in experiments with sudden hemodynamic instability, the flow probe is the most advantageous method for measuring CO.     

Atrial plasma ANP and NH2-terminal proANP during right atrial pressure increase in humans

To compare plasma NT-proANP, a stable and biologically inactive N-terminal portion of ANP prohormone, with the known plasma ANP response to increased right atrial pressure a Swan–Ganz catheter was inserted into the right atrium of five normal healthy male volunteers. The elevation of right atrial pressure was produced by a head-down tilt after a hypertonic saline infusion. Blood samples were drawn from the lumen of the right atrium. After 5 min of starting the tilt the right atrial pressure had increased from 7.0±1.0 to 11.6±0.9 mmHg (P<0.05) and then began to normalize in spite of the constant tilt. Atrial plasma ANP increased in relation to the pressure increase and peaked at 15 min after the start of the tilt. The change was from 27.9±6.5 to 53.9±9.7 pmol L^-1 (P<0.05). Atrial plasma NT-proANP increased significantly from 357±91.2 to 529.1±116.0 pmol L^-1 (P<0.05) at 10 min and remained high throughout the experiment. The molar ratio of NT-proANP to ANP varied in atrial plasma from 9.5±1.2 to 13.9±2.7 showing that the plasma clearance of ANP from plasma was much higher than that of NT-proANP.     

Adenosine triphosphate treatment for meconium aspiration-induced pulmonary hypertension in pigs

To investigate the pulmonary haemodynamic effects of meconium aspiration and subsequent adenosine triphosphate (ATP) treatment, 12 anaesthetized and ventilated pigs (wt 24-28 kg) received either ATP or an equal volume of saline into the right heart in doses of 0.02 to 0.80 lmol kg^-1 min^?1 after intratracheal administration of 2 mL kg^?1 of human meconium. Meconium instillation induced significant increases in pulmonary vascular pressures and total and postarterial resistances calculated from pulmonary artery occlusion studies, but did not affect the systemic haemodynamics, except for a fall in heart rate and increase in central venous pressure. Infusion of ATP at the lowest doses (0.02 and 0.08 µmol kg^?1 min^?1) selectively decreased the pulmonary arterial pressure and vascular resistance and at 0.32 and 0.80 µmol kg^?1 min^?1 reduced both the pulmonary and systemic resistances. In the lung circulation the increasing doses of ATP reduced preferably the arterial, but also the postarterial resistance. Withdrawal of ATP infusion led to a significant rebound effect especially in the postarterial segment of the lung circulation. Meconium aspiration thus induces an acute, predominantly postarterial obstruction in the lung circulation and infusion of ATP at low doses selectively dilates the pulmonary vascular bed and may help to preclude elevation of capillary pressures in meconium aspiration-induced pulmonary hypertension.     

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.     

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.     

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.     

Dual endothelin receptor blockade with tezosentan markedly attenuates hypoxia-induced pulmonary vasoconstriction in a porcine model

Aim: Our aim was to test the hypothesis that dual endothelin receptor blockade with tezosentan attenuates hypoxia‐induced pulmonary vasoconstriction. Methods: Fourteen anaesthetized, ventilated pigs, with a mean ± SEM weight of 30.5 ± 0.6 kg, were studied, in normoxia (FiO₂ 0.21) and with tezosentan (5 mg kg^?1) infusion during (n = 7) or before (n = 7) hypoxia (FiO₂ 0.10). Results: Compared to normoxia, hypoxia increased (P < 0.05) pulmonary vascular resistance (PVR) by 3.4 ± 0.7 WU, mean pulmonary artery pressure by 13.7 ± 1.3 mmHg, mean right atrial pressure by 1.9 ± 0.4 mmHg and decreased (P < 0.02) systemic vascular resistance (SVR) by 5.2 ± 2.1 WU. Pulmonary capillary wedge pressure (PCWP), mean aortic blood pressure, heart rate, cardiac output, stroke volume and blood‐O₂‐consumption were unaltered (P = ns). Tezosentan infused during hypoxia, normalized PVR, decreased (P < 0.05) maximally mean pulmonary artery pressure by 7.5 ± 0.8 mmHg, SVR by 5.8 ± 0.7 WU, mean aortic blood pressure by 10.8 ± 3.0 mmHg and increased (P < 0.04) stroke volume by 8.5 ± 1.8 mL. Mean right atrial pressure, PCWP, heart rate, cardiac output and blood‐O₂‐consumption were unaltered (P = ns). Tezosentan infused before hypoxia additionally attenuated approx. 70% of the initial mean pulmonary artery pressure increase and abolished the PVR increase, without additionally affecting the other parameters. Conclusion: Dual endothelin receptor blockade during hypoxia attenuates the ‘sustained’ acute pulmonary vasoconstrictor response by reducing the mean pulmonary artery pressure increase by approx. 62% and by normalizing PVR. Pre‐treatment with tezosentan before hypoxia, additionally attenuates the initial hypoxia‐induced mean pulmonary artery pressure rise by approx. 70% and abolishes the PVR increase, during stable circulatory conditions, without affecting oxygenation.     

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, N^ω‐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.     

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.     

Cerebrovascular responses to haemorrhagic hypotension in anaesthetized cats. Effects of α-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 a-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/μg^-kg^-1 h^-1, n= 7); and prazosin-treated (50μg-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-100 g^-1 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 α₂-adrenoceptors in the feline cerebrovascular bed.     

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.     

Preface to the third Acta Physiologica Scandinavica international symposium on signalling mechanisms in vascular smooth muscle

To investigate the contribution of nitric oxide in the regulation of regional blood flow and metabolism in vivo, we administered incremental doses of N ^ω-L -arginine-methyl ester (L -NAME 1, 3, 10, 30 and 100 mg kg^?1, intravenously) in isoflurane anaesthetized pigs. The pulmonary vascular bed exhibited a greater sensitivity to the L -NAME-induced pressor effects compared with the systemic arterial bed as the slope of the dose–response curve was steeper (42.9 ± 4.3 vs. 24.3 ± 3.6, P < 0.05) and the dose of L -NAME required to induce a 25% pressure increase was lower (PD₂₅ of 6.2 ± 2.5 vs. 22.8 ± 5.2 mg kg^?1, P < 0.05). L -NAME infusion produced a dose-dependent reduction in cardiac output that was evenly distributed among the mesenteric, femoral, hepatic and carotid arterial circulation as demonstrated by unchanged regional blood flows-to-cardiac output ratios, except in the kidney where the L -NAME-induced vasoconstriction was most pronounced (renal blood flow/cardiac output decreased from 6.2 ± 0.6 to 3.7 ± 0.7% after 100 mg kg^–1 of L -NAME, P < 0.05). After the administration of L -NAME 30 mg kg^?1, intestinal O₂ uptake (Vo₂) increased (+39 ± 3%, P < 0.05) whereas renal Vo₂ tended to decrease (?19 ± 4%, P = 0.07) and whole body Vo₂ remained unchanged. Plasma noradrenaline and adrenaline concentrations did not change significantly with L -NAME infusion. These data demonstrate that in anaesthetized pigs, endogenous nitric oxide is most important for the regulation of pulmonary and renal blood flows and in spite of unchanged global metabolic demand, nitric oxide inhibition leads to an increase in intestinal Vo₂ associated with enhanced gut motility without rise in circulating lactate levels.     

Fibrin(ogen) degradation product peptide 6A increases femoral artery blood flow in dogs

To determine the effects of peptide 6A (a fibrinogen-degradation product) on femoral blood flow, anaesthetized dogs were given saline or peptide 6A intravenously in random order. Bolus injection of peptide 6A (10, 20 or 50pmoles) caused a short-lasting dose-dependent decrease in femoral bed resistance and an increase in femoral blood flow. Continuous infusion of peptide 6A (50 μmoles min^-1) resulted in a sustained decrease in resistance and an increase in femoral artery blood flow (54 ± 33%), with a small, insignificant decrease in femoral artery mean pressure. Indomethacin pretreatment caused only slight attenuation of the peptide 6A-induced increase in femoral blood flow. In in vitro experiments, peptide 6A relaxed rings of femoral artery, and this effect was associated with an increase in 6-keto-PGF1α in the vascular ring supernatants and in the tissue cyclic GMP concentrations. Peptide 6A-induced relaxation was abolished by de-endothelialization, but not by treatment with indomethacin. These observations suggest that peptide 6A induces vasorelaxation largely by stimulating release of endothelium-derived relaxing factor. PGI₂ release appears to play only a minor role in the vasodilator effects of peptide 6A in the femoral bed.     

Importance of nitric oxide in hepatic arterial blood flow and total hepatic blood volume regulation in pigs

The importance of nitric oxide in regulating basal arterial blood flow has been examined in several different vascular beds by intra-arterial infusion of inhibitors of nitric oxide synthesis, but not in the arterial vascular bed of the liver. In the present study, N^G-nitro-L -arginine (L -NNA), in a dose of 0.5 and 1.0 μmol mL^?1 of hepatic arterial blood flow, was infused for 5 min into the hepatic artery in seven pigs anaesthetized with pentobarbital sodium. The haemodynamic effects observed by the first infusion were not further enhanced by the second infusion. Hepatic arterial resistance increased by 143 ± 38% and hepatic arterial blood flow declined by 38 ± 10%. A systemic effect due to `spillover' was observed, as evidenced by an increase in mean aortic blood pressure of 24 ± 4 mmHg. However, no significant increase in arterial mesenteric resistance was observed and total liver blood flow remained unchanged. Hepatic arterial vasodilation in response to occlusion of the portal vein, the arterial buffer response, remained intact after inhibition of nitric oxide synthesis. Liver lobe thickness, measured by an ultrasonic technique,was not found to change with inhibition of arterial nitric oxide synthesis, excluding a significant direct effect of arterial nitric oxide on liver capacitance. In conclusion, nitric oxide is an important regulator of hepatic arterial resistance, but does not mediate the hepatic arterial buffer response and was not found to play any significant role in total hepatic capacitance regulation.     

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.     

Effect of alveolar hypoxia on segmental pulmonary vascular resistance and lung fluid balance in dogs

In a biventricular bypass preparation with constant-flow perfusion, pulmonary arterial pressure (P_pa), average pulmonary capillary pressure (P_pc), venous pressure (P_v), extravascular lung water volume (EVW_d) and capillary permeability-surface area product for urea (PS) were determined in control animals and in animals subjected to alveolar hypoxia. During hypoxia, P_pa increased in a biphasic manner, the site of hypoxic pulmonary vasoconstriction being located in the arterial upstream segment. At baseline, P_pc values were identical in control and experimental animals (3.4 ± 0.4 vs. 3.6 ± 0.2 mmHg). During 150 min of airway hypoxia, the rise in P_pc (5.1 ± 0.3mmHg) did not exceed the rise in P_pc (4.9 ± 0.5mmHg) recorded in control animals at same time interval during normoxic ventilation. EVW_d increased during hypoxia to values significantly higher than those obtained in control animals (0.559 ± 0.036 vs. 0.466 ± 0.027 mL water g^?1 lung). PS remained unchanged at baseline level throughout experiments in both groups of animals. Present data suggest that lung oedema formation during alveolar hypoxia may be caused by increased transcapillary fluid loss preferentially through transcellular hydraulic pathways in capillary endothelial cells.     

Effect of chronic hypoxia on pulmonary artery blood velocity in rats as assessed by electrocardiography-triggered three-dimensional time-resolved MR angiography

Pulmonary arterial hypertension (PAH) is a severe disease that leads to increased pulmonary vascular resistance and right heart failure. Noninvasive methods are needed to detect changes in the pulmonary artery circulation during PAH establishment and/or treatment. Pulmonary blood flow velocity can be evaluated by dynamic MR angiography, although the relevance of such data in the context of PAH remains to be demonstrated. A novel dynamic MR angiography technique was used in this work to measure blood flow velocity in the pulmonary arteries of the same living animals, before and after the establishment of chronic hypoxia‐induced PAH. Chronic hypoxia decreased significantly the blood flow velocity (43.8 ± 4.9 vs 24.3 ± 8.7 cm/s) on electrocardiography‐triggered time‐resolved angiograms. In parallel, chronic hypoxia‐induced PAH was confirmed from invasive measurements of the mean pulmonary arterial pressure (32.1 ± 4.8 vs 12.5 ± 2.2 mmHg) and the ratio of the right ventricle weight to the left ventricle plus septum weight (Fulton index: 0.54 ± 0.06 vs 0.27 ± 0.04). This study demonstrates the potential interest of dynamic MR angiography for the investigation of experimental models and for the evaluation of treatment efficacy. Copyright © 2010 John Wiley & Sons, Ltd.     

Pulmonary Vascular Resistance and Impedance in Isolated Mouse Lungs: Effects of Pulmonary Emboli

To study pulsatile pressure-flow rate relationships in the intact pulmonary vascular network of mice, we developed a protocol for measuring pulmonary vascular resistance and impedance in isolated, ventilated, and perfused mouse lungs. We used pulmonary emboli to validate the effect of vascular obstruction on resistance and impedance. Main pulmonary artery and left atrial pressures and pulmonary vascular flow rate were measured under steady and pulsatile conditions in the lungs of C57BL/6J mice (n = 6) before and after two infusions with 25 μm-diameter microspheres (one million per infusion). After the first and second embolizations, pulmonary artery pressures increased approximately two-fold and three and a half-fold, respectively, compared to baseline, at a steady flow rate of 1 ml/min (P < 0.05). Pulmonary vascular resistance and 0 Hz impedance also increased after the first and second embolizations for all flow rates tested (P < 0.05). Frequency-dependent features of the pulmonary vascular impedance spectrum were suggestive of shifts in the major pulmonary vascular reflection sites with embolization. Our results demonstrate that pulmonary artery pressure, resistance, and impedance magnitude measured in this isolated lung setup changed in ways consistent with in vivo studies in larger animals and humans and demonstrate the usefulness of the isolated, ventilated, and perfused mouse lung for investigating steady and pulsatile pressure-flow rate relationships.     

Intramuscular pressures during exercise: an evaluation of a fiber optic transducer-tipped catheter system

Summary The efficacy of a modified fibre optic transducer-tipped catheter system for measuring intramuscular pressures during exercise was determined. A microcapillary infusion technique using a catheter was employed as the standard of comparison due to its established dynamic properties. Pressures were measured in the tibialis anterior muscle of six healthy adults at rest before exercise, during isometric and concentric exercise, and at rest after exercise. The fibre optic system measured contraction pressures equal to the microcapillary infusion technique during all phases of the exercise protocols but recorded a lower relaxation pressure during isometric exercise and a lower rest pressure following 20 min of concentric exercise. Negative relaxation pressures were recorded by the fibre optic system for two subjects during continuous concentric exercise. It is hypothesized that a piston effect, due to the sliding of muscle fibres at the catheter tip following a contraction, rendered falsely low pressures during relaxation and that this artefact was reflected in the subsequent rest pressure following exercise. The larger volume (157 mm³) and area (3.49 mm²) of the fibre optic catheter in the muscle made it more prone to this effect than the conventional catheter (39 mm³ and 0.87 mm², respectively). The fibre optic system may be preferred when recording the musclecontraction pressures during complex limb movements but should not be used when assessing the relaxation pressures or the pressure at rest following exercise.This project was performed at the Division of Orthopaedics and Rehabilitation, Veterans Administration Medical Center and the University of California San Diego