Distribution Of Pulmonary Vascular Resistance Research Articles

INHIBITION OF ENDOGENOUS NITRIC OXIDE DURING ENDOTOXEMIA IN AWAKE SHEEP - EFFECTS OF N ω -NITRO-L-ARGININE ON THE DISTRIBUTION OF PULMONARY VASCULAR RESISTANCE AND PROSTANOID PRODUCTS

We examined the effects of endogenous nitric oxide (NO) inhibition on the longitudinal distribution of pulmonary vascular resistance and on arachidonic acid metabolism during endotoxemia in awake sheep. Mean pulmonary artery (Ppa), left atrial (Pla), and systemic artery pressure (Psa) were continuously measured, and cardiac output (CO) was continuously monitored by an implanted ultrasonic flow probe. We advanced a 7-French Swan-Ganz catheter into distal pulmonary artery and measured the pulmonary microwedge pressure (Pmw) with the balloon deflated, allowing calculation of upstream pulmonary vascular resistance (PVRup = [Ppa - Pmw]/CO) and down-stream PVR (PVRdown = [Pmw - Pla]/CO), respectively. In paired studies, endotoxin (1 μ g/kg) was infused over 30 minutes with and without N ω -nitro-L-arginine (NLA) treatment. NLA (20 mg/kg) was administered 30 minutes before endotoxin infusion. Endotoxin caused increases in PVRup and PVRdown. Pretreatment with NLA increases PVRup at baseline and enhanced increases in both PVRup and PVRdown during endotoxemia. Plasma level of thromboxane B 2 (TxB 2) and prostacyclin (6-keto = PGF 1 α) significantly increased 1 hour after endotoxin administration (TxB 2, 308.3 ± 94.8 [SE] to 2163.5 ± 988.5 pg ml -1, P <. 05; 6-keto=PGF 1 α, 155.6 ± 91.4 to 564.9 ± 131.8 pg ml -1, P <. 05), but the increased levels were similar to those in the NLA-pretreated animals. We conclude that endogenous NO mainly regulates precapillary vascular tone at baseline, and that NO modulated pre- and postcapillary vascular constriction during endotoxemia in sheep. It appears that cyclooxygenase production in response to endotoxin is unaffected by NO and its vascular effects.

Inhibition of nitric oxide synthesis augments pulmonary oedema in isolated perfused rabbit lung

The role of nitric oxide (NO) in precipitating pulmonary oedema in acute lung injury remains unclear. We have investigated the mechanism of involvement of NO in the maintenance of liquid balance in the isolated rabbit lung. Thirty pairs of lungs were perfused with colloid for up to 6 h, during which pulmonary vascular resistance (PVR) and capillary pressure (PCP) were measured frequently, and time to gain 5 g in weight (t5) was recorded. Four protocols with different perfusate additives were studied: (i) none (control, n = 11); (ii) 10 mmol NG-nitro-L-arginine methyl ester (L-NAME) (n = 6); (iii) 10 mmol L-NAME with 100 mumol lodoxamide, an inhibitor of mast cell degranulation (n = 7); (iv) 10 mmol L-NAME with 10 mumol 8-bromo-3',5'-cyclic guanosine monophosphate (8Br-cGMP), an analogue of cGMP that may reduce vascular permeability by relaxing contractile elements in endothelial cells (n = 6). Neither PVR nor PCP differed between protocols. L-NAME markedly reduced t5 from 248 (27) min (mean (SEM)) in protocol (i) to 144 (5) min in protocol (ii) (P < 0.05). Both lodoxamide (t5 = 178 (7) min) and 8Br-cGMP (t5 = 204 (10) min) substantially corrected the effect of L-NAME (P < 0.005). Results suggest that maintenance of a low permeability by NO may involve mast cell stabilization and endothelial cell relaxation.

Inhaled nitric oxide reduces lung fluid filtration after endotoxin in awake sheep.

We studied the effect on lung fluid filtration of 37.6 ppm inhaled nitric oxide (NO) imposed for 1 h 2.5 h after endotoxin in seven awake sheep, with seven control subjects. The effects of NO on the longitudinal distribution of pulmonary vascular resistance (PVR) before and after endotoxin were specifically addressed in six sheep. Following endotoxin, sheep developed respiratory distress; PaO2, the alveolar-arterial oxygen tension difference (AaPO2) and venous admixture (Q S/Q T) changed significantly, as did the pulmonary artery pressure (Ppa), PVR, and lung lymph flow (Q L). Inhaled NO reduced Ppa and PVR by 50%; Q L decreased from 7.8 +/- 0.34 ml/15 min to 4.7 +/- 0.80 ml/15 min (mean +/- SEM), and lymph protein clearance from 4.9 +/- 0.18 ml/15 min to 3.6 +/- 0.75 ml/15 min. Lymph/plasma protein concentration ratio (L/P) increased from 0.63 +/- 0.016 to 0.72 +/- 0.006, concomitant with the decrease in Q L. The L/P - Q L relationships shifted from left, at baseline, to the right during endotoxemia, as did the permeability surface product (PS) isolines. The rightward shift was significantly less in the NO group. Inhaled NO significantly improved PaO2, AaPO2, and Q S/Q T, reduced the increase in pulmonary microwedge pressure back to baseline and decreased upstream and downstream PVR at 3.0 through 4. 0 h. We conclude that, in sheep, inhaled NO reduces lung fluid filtration by decreasing microvascular pressure and apparently also by declining the enhanced microvascular permeability during the late phase of endotoxemia.

Effect of different doses of inhaled nitric oxide on pulmonary capillary pressure and on longitudinal distribution of pulmonary vascular resistance in ARDS

Inhaled nitric oxide lowers pulmonary capillary pressure (PCP) in animals and in patients with acute respiratory distress syndrome (ARDS). A dose-response relationship in patients with ARDS has not yet been established. Therefore, we studied the effects of four concentrations of nitric oxide (1, 10, 20 and 40 volumes per million (vpm)) in random order, on PCP in 19 patients with ARDS. PCP was estimated by visual analysis of the pressure decay curve after balloon inflation of the pulmonary artery catheter. Haemodynamic and gas exchange variables were measured at each nitric oxide concentration. Patients were classified as responders when PCP decreased by at least 2 mm Hg after nitric oxide 20 vpm. In responders (n = 8), nitric oxide decreased PCP and post-capillary vascular resistance dose-dependently and changed longitudinal distribution of pulmonary vascular resistance with a maximum effect at 20 vpm. In non-responders (n = 11), PCP did not change. In both groups, the nitric oxide-induced decrease in pre-capillary vascular resistance was small with a maximum effect at 1 vpm. In ARDS, vasodilatation of pre-capillary vessels is achieved at low concentrations of nitric oxide, whereas the effect of nitric oxide on postcapillary vessels is variable. Higher concentrations may be required for optimal post-capillary vasodilatation in a subgroup of ARDS patients.

Effects of anaphylaxis mediators on partitioned pulmonary vascular resistance during ragweed shock in dogs.

We examined the effect of anaphylactic shock on the longitudinal distribution of pulmonary vascular resistance (PVR) in ragweed-sensitized dogs in which PVR was partitioned into an upstream arterial component (Rus) and a downstream venous and capillary component (Rds). We also assessed whether Rus and Rds would be reduced by pretreatment with histamine H1- and H2-receptor blocking agents and with cyclooxygenase and lipoxygenase pathway inhibitors. Anesthetized animals were examined on separate occasions 3 wk apart in which one of the treatments was randomly given. The pulmonary arterial occlusion technique was used to determine segmental pressure drops. During ragweed challenge, PVR increased approximately 4 times compared with the preshock value (3.04 vs. 12. 07 mmHg . l-1 . min; P < 0.05). Although both Rus and Rds increased postshock, the greatest relative increase occurred in Rds. None of the treatments reduced partitioned resistances compared with no treatment. Our results show that, under conditions of anaphylactic shock, increases in Rus and Rds could not be ascribed to release of histamine or products of the cyclooxygenase and lipoxygenase pathways.

Anatomic distribution of pulmonary vascular compliance.

Previously, the pressure changes after arterial and venous occlusion have been used to characterize the longitudinal distribution of pulmonary vascular resistance with respect to vascular compliance using compartmental models. However, the compartments have not been defined anatomically. Using video microscopy of the subpleural microcirculation, we have measured the flow changes in approximately 40-micron arterioles and venules after venous, arterial, and double occlusion maneuvers. The quasi-steady flows through these vessels after venous occlusion permitted an estimation of the compliance in three anatomic segments: arteries > 40 microns, veins > 40 microns, and vessels < 40 microns in diameter. We found that approximately 65% of the total pulmonary vascular compliance was in vessels < 40 microns, presumably mostly capillaries. The transient portions of the pressure and flow data after venous, arterial, and double occlusion were consistent with most of the arterial compliance being upstream from most of the arterial resistance and most of the venous compliance being downstream from most of the venous resistance.

Positive end-expiratory pressure increases pulmonary venous vascular resistance in patients after coronary artery surgery.

To investigate the effect of positive and-expiratory pressure (PEEP) on the longitudinal distribution of pulmonary vascular resistance in patients immediately after coronary artery bypass grafting. Prospective, intervention study. Postcardiac surgery intensive care unit in a teaching institution. Twenty patients after elective coronary artery bypass grafting. The effect of PEEP on pulmonary circulation, at four different levels (0, 5, 10, and 15 cm H2O), was analyzed in 20 patients. Mean pulmonary arterial pressure, left atrial pressure, pulmonary artery occlusion pressure, and pulmonary capillary pressure were measured at each PEEP level. A model consisting of two resistances in series was used to analyze the effect of PEEP on the pulmonary circulation. The pulmonary vascular resistance for each area (arterial and venous) of the circulation was calculated. Pulmonary vascular resistance increased from 216 +/- 70 dyne.sec/cm5 at a PEEP of 0 cm H2O to 308 +/- 125 dyne.sec/cm5 at a PEEP of 15 cm H2O (p < .001). This increase, however, resulted solely from an increase in the resistance of the venous part of the pulmonary circulation from 66 +/- 29 to 134 +/- 69 dyne.sec/cm5 (p < .001), without any change in pulmonary arterial resistance. PEEP increases pulmonary vascular resistance solely by increasing pulmonary venous resistance. When applying PEEP, changes in pulmonary vascular resistance may impede the resorption of pulmonary edema fluid.

Perioperative Distribution of Pulmonary Vascular Resistance in Patients Undergoing Coronary Artery Surgery

Perioperative Distribution of Pulmonary Vascular Resistance in Patients Undergoing Coronary Artery Surgery

Meconium aspiration induces ARDS-like pulmonary response in lungs of ten-week-old pigs.

To investigate whether aspiration of meconium induces a hemodynamic and histologic pulmonary response similar to that frequently seen in experimental acute respiratory distress syndrome, twelve 10-week-old pigs with postnatally adapted lungs were studied. Six 10-week-old pigs received 3 ml/kg 20% human meconium via the endotracheal tube. Six control pigs of the same age were given sterile saline. Ventilator settings were adjusted to keep PaO2 above 8 kPa and PaCO2 below 5 kPa. The pulmonary hemodynamic response to aspiration consisted of two separate hypertensive components. An initial peak in pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) was followed by a progressive increase in PAP and PVR in the meconium group, whereas in the saline group these parameters returned to baseline levels. The distribution of PVR, determined by pulmonary artery occlusion, was characterized by an increase in the postarterial resistance immediately after meconium aspiration and a progressive increase in both arterial and postarterial resistance during the later phase. On histological examination, marked neutrophil sequestration was seen in the meconium lungs. In addition, lung edema formation was significantly enhanced in the meconium group, as shown by an increased lung wet/dry weight ratio. Thus, meconium aspiration resulted in a biphasic pulmonary pressor response and severe pulmonary inflammation. This response resembled that of models of experimental acute respiratory distress syndrome following diverse types of precipitating insults; this suggests that similar pathophysiologic mechanisms are elicited and cause similar pulmonary dysfunction following different forms of lung injury.

Perioperative Distribution of Pulmonary Vascular Resistance in Patients Undergoing Coronary Artery Surgery

This study was undertaken to measure distribution of pulmonary vascular resistance (PVR) perioperatively in patients undergoing coronary artery bypass grafting (CABG) and to examine the effects of cardiopulmonary bypass (CPB) on pulmonary capillary pressure (Pc) relative to wedge pressure (Pw).Pulmonary artery catheters were placed before anesthetic induction in 18 patients scheduled for elective CABG and systemic hemodynamic variables were measured. Pulmonary artery pressure was recorded during balloon inflation and stored for off-line determination of Pc. Data were collected prior to induction (baseline), as well as after induction and intubation, skin incision, sternotomy, protamine administration, and chest closure. At each data point, downstream (capillary plus venous segments) resistance (Rds) contributed approximately 60% of total PVR and did not change significantly during the operation. PVR decreased (P < 0.05) after CPB and protamine administration, primarily due to a decrease in the absolute magnitude of the upstream (arterial) resistance. Administration of large-dose opioid anesthesia had no significant effect (P > 0.05) on total PVR or on segmental distribution of vascular resistance. At all data points, Pc was significantly larger than Pw (P < 0.05). This study demonstrates that perioperative measurement of Pc is feasible, that during CABG under these conditions, relative contribution of arterial and venous resistances remain relatively unchanged, that Pc is always larger than Pw, and that the administration of large-dose opioid anesthesia has a minimal effect on pulmonary vascular hemodynamics. (Anesth Analg 1996;82:958-63)

Perioperative distribution of pulmonary vascular resistance in patients undergoing coronary artery surgery.

This study was undertaken to measure distribution of pulmonary vascular resistance (PVR) perioperatively in patients undergoing coronary artery bypass grafting (CABG) and to examine the effects of cardiopulmonary bypass (CPB) on pulmonary capillary pressure (Pc) relative to wedge pressure (Pw). Pulmonary artery catheters were placed before anesthetic induction in 18 patients scheduled for elective CABG and systemic hemodynamic variables were measured. Pulmonary artery pressure was recorded during balloon inflation and stored for off-line determination of Pc. Data were collected prior to induction (baseline), as well as after induction and intubation, skin incision, sternotomy, protamine administration, and chest closure. At each data point, downstream (capillary plus venous segments) resistance (Rds) contributed approximately 60% of total PVR and did not change significantly during the operation. PVR decreased (P < 0.05) after CPB and protamine administration, primarily due to a decrease in the absolute magnitude of the upstream (arterial) resistance. Administration of large-dose opioid anesthesia had no significant effect (P > 0.05) on total PVR or on segmental distribution of vascular resistance. At all data points, Pc was significantly larger than Pw (P < 0.05). This study demonstrates that perioperative measurement of Pc is feasible, that during CABG under these conditions, relative contribution of arterial and venous resistances remain relatively unchanged, that Pc is always larger than Pw, and that the administration of large-dose opioid anesthesia has a minimal effect on pulmonary vascular hemodynamics.

Pulmonary Capillary Pressure Measurement from Pulmonary Artery Occlusion Pressure Decay Profile Analysis in Sheep

Pulmonary capillary pressure (Ppc), the major factor responsible for pulmonary edema, cannot be directly measured in intact subjects but may be estimated by analysis of the pressure decay profile after pulmonary artery catheter balloon inflation. We compared three different methods of pulmonary artery occlusion pressure (Ppao) decay profile analysis to estimates of Ppc derived from lymph flow measurements in halothane-anesthesized sheep. The relationship between Ppc and lymph flow was first determined by increasing Ppc by left atrial balloon inflation, and was then used to determine Ppc during pulmonary hypertension produced by infusion of a thromboxane analog. All three methods of Ppao decay profile analysis demonstrated a correlation with Ppc estimated from lymph flow. However, the method using a single exponential analysis significantly overestimated Ppc, and none of the methods reliably estimated changes in the longitudinal distribution of pulmonary vascular resistance during pulmonary hypertension. These results suggest that Ppao decay profile analysis as currently performed has limited application.

Inhaled nitric oxide does not alter the longitudinal distribution of pulmonary vascular resistance

Because the effects of inhaled nitric oxide (NO) may be localized to its site of delivery, we studied the effects of inhaled NO on the longitudinal distribution of pulmonary vascular resistance during pulmonary hypertension in perfused rabbit lungs. Before NO administration, pulmonary hypertension was produced by infusion of the thromboxane A2 mimetic U-46619 in all lungs. Pulmonary vascular resistance was divided into arterial, microvascular, and venous components by arterial and venous occlusion techniques. In the buffer-perfused lung, all doses of inhaled NO (5, 20, and 80 ppm) produced small decreases (approximately 3 mmHg) in pulmonary arterial pressure (Ppa), with equivalent proportional reductions in all segmental vascular resistances. Similar results were obtained after an extended inhaled NO dose range of 20, 80, and 240 ppm. In the buffer-perfused lung, inhibition of endogenous NO synthesis with NG-nitro-L-arginine methyl ester (L-NAME) potentiated the effects of U-46619. Subsequent inhaled NO administration produced larger decreases (approximately 7 mmHg) in Ppa with equivalent proportional reductions in all segmental vascular resistances. In the blood-perfused lung, L-NAME did not alter baseline pulmonary pressures. Administration of inhaled NO during U-46619-induced pulmonary hypertension produced dose-related decreases in Ppa. The highest dose (80 ppm) of inhaled NO decreased Ppa by 3.5 mmHg, with equivalent proportional reductions in all segmental vascular resistances.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhaled nitric oxide lowers pulmonary capillary pressure and changes longitudinal distribution of pulmonary vascular resistance in patients with acute lung injury.

In acute lung injury (ALI), where pulmonary microvascular permeability is increased, transvascular fluid filtration depends mainly on the hydrostatic capillary pressure. In the presence of intrapulmonary vasoconstriction pulmonary capillary pressure (PCP) may increase thereby promoting transvascular fluid filtration and lung oedema formation. We studied the effect of 40 ppm inhaled nitric oxide (NO) on PCP and longitudinal distribution of pulmonary vascular resistance (PVR) in 18 patients with ALI. PCP was estimated by visual analysis of the pressure decay profile following pulmonary artery balloon inflation. Contribution of venous pulmonary resistance to total PVR was calculated as the percentage of the pressure gradient in the pulmonary venous system to the total pressure gradient across the lung. Inhalation of 40 ppm NO produced a prompt decrease in mean pulmonary artery pressure (PAP) from 34.1 +/- 6.8 to 29.6 +/- 5.7 (s.d.) mmHg; (P < 0.0001). PCP declined from 24.8 +/- 6.2 to 21.6 +/- 5.2 mmHg; (P < 0.0001) while pulmonary artery wedge pressure (PAWP) did not change. PVR decreased from 166 +/- 73 to 128 +/- 50 dyn.sec.cm-5; (P < 0.0001). Pulmonary venous resistance (PVRven) decreased to a greater extent (from 76 +/- 41 to 50 +/- 28 dyn.sec.cm-5; (P < 0.001) than pulmonary arterial resistance (PVRart) (from 90 +/- 36 to 79 +/- 29 dyn.sec.cm-5; (P < 0.01). The contribution of PVRven to PVR fell from 44.3 +/- 10.8 to 37.8 +/- 11.9%; (P < 0.01). Cardiac output (CO) remained constant. The findings demonstrate that NO has a predominant vasodilating effect on pulmonary venous vasculature thereby lowering PCP in patients with ALI.

Analysis of longitudinal distribution of pulmonary vascular resistance by use of a five element lumped model.

To analyze longitudinal distribution of pulmonary vascular resistance, we proposed a five element lumped model which partitioned pulmonary circulation into pulmonary arterial, middle and pulmonary venous segment. The validity and anatomical correlation of the model were tested in an isolated, perfused, canine lung lobe preparation with inflow/outflow occlusion techniques. With arterial occlusion, pulmonary arterial pressure fell rapidly and then exponentially. With venous occlusion, pulmonary venous pressure rose suddenly and then exponentially. Theoretical pressure profiles produced by computer simulation of the model well approximated the general characteristics of the experimental traces. Serotonin increased the pressure gradient across the pulmonary arterial segment (delta Pa), whereas histamine increased the gradient across the pulmonary venous segment (delta Pv). Neither drug altered the gradient across the middle segment (delta Pm). The results suggest that the lumped model is a useful concept to understand the longitudinal distribution of pulmonary vascular resistance, and that delta Pa, delta Pm and delta Pv reflect the resistance distribution of anatomical pulmonary arteries, alveolar vessels and pulmonary veins, respectively.

Receptor mechanism of thrombin-mediated pulmonary vasodilation in neonates

A recently identified peptide sequence exposed after proteolytic cleavage of the NH2-terminus of the thrombin receptor mimics some cellular effects of alpha-thrombin. To determine whether a proteolytic action of thrombin is required for vasoactivity, we examined the vascular effects of modified thrombins and synthetic NH2-terminus peptide sequences of the thrombin receptor (TRPs) in isolated piglet lungs. Lungs of piglets 1-6 days old were perfused with recirculating Ringer-albumin solution at a constant flow of 60 ml/min. We measured the pulmonary artery pressure (Ppa) and segmental distribution of pulmonary vascular resistance (using the double occlusion method) in response to injections of human alpha-thrombin, modified thrombins, and TRP-14 and TRP-7 (i.e., 14 and 7 amino acid NH2-terminus peptides of the cleaved thrombin receptor). alpha-Thrombin produced a rapid and transient decrease in Ppa; the magnitude and duration [time for one-half recovery (t1/2 R)] of the vasodilation responses were concentration dependent [t1/2 R values of 1.4 +/- 0.1 and 3.3 +/- 2.4 min (mean +/- SE) at concentrations of 10(-10) and 10(-9) M, respectively]. The vasodilation was due primarily to a decrease in precapillary resistance. Proteolytically active, but binding-impaired gamma-thrombin was a less potent vasodilator and proteolytically inactive D-phenylalanyl-prolyl-arginine-chloromethyl ketone (PPACK)-alpha-thrombin did not induce vasodilation. TRP-14 was also a pulmonary vasodilator with a t1/2R value of 0.8 +/- 0.09 min at a concentration of 10(-7) M; both TRP-14 and TRP-7 were approximately 3-log less potent than equimolar alpha-thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of endothelin‐1‐induced pulmonary vasodilatation in neonatal pigs.

1. We determined the contributions of three independent vasodilator mechanisms (cyclo-oxygenase metabolites, nitric oxide and ATP-sensitive potassium channels) in the mediation of pulmonary vasomotor effects of endothelin-1 (ET-1) in neonatal pigs. 2. Lungs of piglets (2.7 +/- 0.3 days old) were perfused at constant flow (60 ml min-1) with recirculating Ringer-albumin solution. We measured pulmonary artery pressure (Ppa) and the distribution of pulmonary vascular resistance using the double-occlusion method. 3. ET-1 (10(-12)-10(-9) M) produced concentration-dependent pulmonary vasodilatation. ET-1 (10(-9) M) decreased Ppa from 24.5 +/- 3.1 to 17.0 +/- 3.0 cmH2O with a nadir occurring at 1 min, followed by a slow return to baseline over 60 min (time for half-recovery (t1/2R) of 17.2 min). The decrease in Ppa was the result of pulmonary precapillary vasodilatation. Endothelin-3 (ET-3) (10(-12) and 10(-11) M) also induced vasodilatation comparable to equimolar concentrations of ET-1, whereas the selective ETB receptor agonist IRL 1620 at equimolar concentrations caused a more protracted vasodilatation response. 4. Neither the cyclo-oxygenase inhibitor indomethacin (10(-5) M) nor the KATP+ (ATP-sensitive) potassium channel blocker glibenclamide (10(-5) M) significantly altered the baseline Ppa; moreover, neither inhibitor affected the ET-1-induced vasodilatation, indicating the lack of involvement of cyclo-oxygenase metabolites and KATP+ channel activity in the mediation of the pulmonary vasodilator response to ET-1. 5. Addition of 10(-5) M reduced haemoglobin, which antagonizes the action of nitric oxide (NO), increased Ppa over prehaemoglobin levels. Haemoglobin significantly decreased the duration (t1/2R, 3.8 +/- 0.7 min) of pulmonary vasodilatation to ET-1, but did not abolish the initial phase of the response. L-N-Monomethylarginine, an inhibitor of NO synthesis, either alone or in combination with haemoglobin, similarly reduced the duration of ET-1-induced pulmonary vasodilatation. 6. The ETA receptor antagonist [Dpr1-Asp15]-ET-1 (Dpr, diaminoproprionic acid) had no effect on pulmonary vasodilatation induced by ET-1, ET-3 or IRL 1620 (suc-(Glu9,Ala11,15)-ET-1(8-21)). This finding combined with the observed relative potencies of the peptides (IRL 1620 > ET-1 = ET-3) suggests that pulmonary vasodilatation was mediated by activation of the non-selective ETB receptor. 7. The results indicate that the sustained ET-1-induced pulmonary vasodilatation in neonates is probably mediated via ETB receptor activation and that it is critically dependent on NO.

Pulmonary venodilation by isoflurane improves gas exchange during Escherichia coli bacteremia.

To determine how isoflurance affects the longitudinal distribution of pulmonary vascular resistance and pulmonary gas exchange during Escherichia coli bacteremia. Prospective, controlled study with open-label assignment of animals to two groups. Laboratory. Goehingen minipigs. Induction of acute respiratory failure by a 4-hr infusion of live E. coli bacteria in 12 animals; six animals anesthetized with methohexital/piritramide; six animals anesthetized with isoflurane. The control group consisted of four animals that received the same surgical procedure, but no E. coli infusion. Two animals were anesthetized with methohexital/piritramide and two with isoflurane, respectively. Cardiac output and pressures were measured by means of an arterial catheter, Swan-Ganz catheter, and a left atrial catheter. Effective pulmonary capillary pressure was evaluated graphically from a pulmonary artery occlusion pressure decay. Arterial-alveolar PO2 ratio was calculated to evaluate pulmonary function. Measurements were performed before and after 1, 2, and 3.5 hrs of E. coli infusion. Statistical significance was tested with analysis of variance (ANOVA). E. coli infusion caused hypodynamic shock, an increase in pre- and postcapillary pulmonary vascular resistance and respiratory failure. Postcapillary pressure gradient and effective pulmonary capillary pressure were lower in the isoflurane-group. Methohexital-anesthetized animals developed pulmonary dysfunction after 1 hr of bacteremia, whereas isoflurane-anesthetized animals developed pulmonary dysfunction after 3.5 hrs of E. coli infusion (significantly different, ANOVA, p < .05). There were no significant changes in the sham group. Isoflurane is a pulmonary venodilator. During lethal E. coli infusion, it ameliorates the increase in pulmonary capillary pressure and preserves pulmonary function until vascular permeability increases.

Effective pulmonary capillary pressure in experimental myocardial ischaemia.

Effective pulmonary capillary pressure and extravascular lung water were investigated in dogs (n = 9) with normal heart function and after development of acute myocardial ischaemia. During control, no impairment of cardiopulmonary performance was observed. Extravascular lung water was in the normal range (8.1 +/- 2.8 ml.kg-1) and the effective pulmonary capillary pressure accounted for 1.36 +/- 0.53 kPa (10.2 +/- 4 mmHg). No correlation between extravascular lung water and effective pulmonary capillary pressure was observed (r2 = 0.347, P = 0.06). Arterial (RPA) and venous pulmonary resistance (RPV) were 70 +/- 15% and 30 +/- 6%, respectively. Acute myocardial ischaemia was induced by one stage occlusion of the left anterior descending (LAD) coronary artery; measurements during the ischaemia phase were performed 60 min following LAD occlusion. Myocardial ischaemia resulted in moderate changes of cardiac output, heart rate and left ventricular end-diastolic pressure. Oxygenation deteriorated, but no hypoxaemia occurred in any animal and CO2 elimination remained unchanged. Extravascular lung water was elevated (16.5 +/- 7.9 ml.kg-1, P < or = 0.01), and effective pulmonary capillary pressure was higher when compared with the control state (2.32 +/- 1.05 kPa (17.4 +/- 7.9 mmHg), P < or = 0.01). There was a significant correlation between both parameters (r2 = 0.528, P < or = 0.05). Longitudinal distribution of pulmonary vascular resistance was altered, and RPA decreased to 60 +/- 13% (P < or = 0.05), while RPV increased to 40 +/- 8% (P < or = 0.05). It is concluded that development of lung oedema is related to elevated effective pulmonary capillary pressure in dogs with acute myocardial ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary Capillary Pressure Measurement During Global Hypoxia in Sheep

Analysis of the pressure decay following pulmonary artery occlusion can be used to determine pulmonary capillary pressure and to calculate the magnitudes of the arterial and venous components of pulmonary vascular resistance. The separation of pulmonary vascular resistance into components has been termed "the longitudinal distribution of pulmonary vascular resistance" to emphasize the fact that different pressures occur at a number of sites in the pulmonary circulation. The longitudinal distribution of pulmonary vascular resistance is closely related to pulmonary capillary pressure. Several methods of data analysis have been proposed to determine pulmonary capillary pressure from the pressure decay following pulmonary artery occlusion. In this study, three methods of data analysis were applied to the model of hypoxic pulmonary vasoconstriction to evaluate the validity of the methodology in a well known model. Pulmonary artery occlusion pressure decay curves were obtained from eight halothane-anesthetized sheep during control conditions (FIO2 = 0.99) and during hypoxic ventilation (FIO2 = 0.14). Analysis of the pulmonary artery occlusion pressure decay curves indicated the following results: 1) Hypoxia increased mean pulmonary artery pressure by 105% and increased pulmonary vascular resistance by 149%; 2) the increase in the calculated arterial component of pulmonary vascular resistance accounted for 88% of the increase in pulmonary vascular resistance with hypoxia; and 3) hypoxia produced only a 1.0 mm Hg increase in pulmonary capillary pressure. These results are consistent with other evidence showing that hypoxia primarily produces precapillary pulmonary vasoconstriction and has little effect on pulmonary capillary pressure. Pulmonary artery occlusion pressure decay curve analysis appears to be a valid technique for the measurement of pulmonary capillary pressure during hypoxia in intact anesthetized animals.