Invasive arterial BP monitoring in trauma and critical care: effect of variable transducer level, catheter access, and patient position.

OBJECTIVES: (1) To determine the validity of current recommendations for direct arterial BP measurement that suggest that the transducer (zeroed to atmosphere) be placed level with the catheter access regardless of subject positioning: and (2) to investigate the effect of transducer level, catheter access site, and subject positioning on direct arterial BP measurement. DESIGN: Prospective, controlled laboratory study. SETTING: Large animal laboratory. SUBJECTS: Five Yorkshire pigs. INTERVENTIONS: Anesthetized animals had 16F catheters placed at three access sites: aortic root, femoral artery, and distal hind limb. Animals were placed in supine, reverse Trendelenburg 35 degrees, and Trendelenburg 25 degrees positions with a transducer placed level to each access site while in every position. MEASUREMENTS AND MAIN RESULTS: For each transducer level, five systolic and diastolic pressures were measured and used to calculate five corresponding mean arterial pressures (MAPs) at each access site. When transducers were at the aortic root, MAP corresponding to aortic root pressure was obtained in all positions regardless of catheter access site. When transducers were moved to the level of catheter access, as current recommendations suggest, significant errors in aortic MAP occurred in the reverse Trendelenburg position. The same trend for error was noted in the Trendelenburg position but did not reach statistical significance. CONCLUSIONS: (1) Current recommendations that suggest placing the transducer at the level of catheter access regardless of patient position are invalid. Significant errors occur when subjects are in nonsupine positions. (2) Valid determination of direct arterial BP is dependent only on transducer placement at the level of the aortic root, and independent of catheter access site and patient position.

Videomicroscopy provides accurate in vivo assessment of pulmonary microvascular reactivity in rabbits.

When defining the mechanism of hypoxic pulmonary vasoconstriction (HPV), investigators have employed ex vivo preparations because of the belief that accurate, quantitative assessment of pulmonary microvessels could not be obtained in vivo. We hypothesize that accurate, quantitative assessment of pulmonary microvascular reactivity can be performed using a simple, in vivo preparation. Our aim was to provide this quantitative assessment in a defined animal model, and to confirm that the chosen preparation could discriminate changes in microvascular reactivity as influenced by endogenous mediators. New Zealand rabbits were instrumented for in vivo microscopy and direct measurement of subpleural arterioles. Rabbits were first randomized to either control (n = 7) or endotoxin (n = 5), infusion of Escherichia coli lipopolysaccharide (200 Fg/kg). All rabbits were then exposed to a repeated protocol of normoxia (21% O2) for 20 min and then hypoxia (15% O2) for 10 min over 2 h. The changes in arteriole diameter were measured at the end of each interval. Normal pulmonary arterioles repeatedly constrict 15+/-3.5% during hypoxia. Altering endogenous vasoactive mediators, as with infusion of endotoxin, caused a loss of hypoxia-induced vasoconstriction. The results of our study validate this experimental preparation for the reliable quantification of pulmonary microvascular reactivity and investigation of hypoxic pulmonary vasoconstriction under both normal and pathologic conditions.

Soluble tumor necrosis factor receptor prevents post-pump syndrome.

Post-pump syndrome is an acute lung injury following cardiopulmonary bypass (CPB) which is indistinguishable from the adult respiratory distress syndrome (ARDS). Tumor necrosis factor (TNF) is central to the inflammatory process and is capable of triggering the entire pathophysiologic response leading to ARDS. We hypothesized that treatment with a soluble TNF receptor-binding protein (TNFbp) would reduce the increase in serum TNF and prevent acute lung injury in our sequential insult model of ARDS following CPB. Anesthetized pigs were randomized to one of three groups: Control (n = 3), surgical preparation only; CPB + LPS (n = 6), femoral-femoral hypothermic bypass for 1 h followed by infusion of low dose Escherichia coli lipopolysaccharide (LPS; 1 microg/kg); and TNFbp + CPB + LPS (n = 4), pretreatment with intravenous TNFbp (2 mg/kg) followed immediately by both insults. CPB + LPS caused severe lung injury demonstrated by a significant fall in PaO2 and an increase in both intrapulmonary shunt and peak airway pressure as compared to all groups (P < 0.05). These changes were associated with a significant increase in plasma TNF level and pulmonary neutrophil sequestration. TNFbp significantly reduced plasma levels of TNF and prevented the lung injury typically observed with this ARDS model, but did not reduce pulmonary neutrophil sequestration. Thus, elevated serum TNF is not responsible for neutrophil sequestration but does play a role in neutrophil activation which causes lung injury. Prophylactic use of TNFbp in CPB patients may prevent neutrophil activation and reduce the incidence of post-pump ARDS.

Endotoxin-stimulated alveolar macrophage recruitment of neutrophils and modulation with exogenous surfactant.

OBJECTIVE: To determine whether endotoxin-stimulated alveolar macrophages would attract neutrophils and whether exogenous surfactant treatment would modulate this chemoattraction. DESIGN: Alveolar macrophages were harvested from bronchoalveolar lavage fluid and neutrophils from the blood of anesthetized guinea pigs. SUBJECTS: Hartley guinea pigs. INTERVENTIONS: Alveolar macrophages were suspended in RPMI 1640 and stimulated with 1 microg/mL of lipopolysaccharide (LPS), the supernatant removed and the alveolar macrophages were incubated in either RPMI or RPMI with surfactant at two different doses (292 microg/mL or 875 microg/mL) for 16 hrs. MEASUREMENTS AND MAIN RESULTS: The supernatant was extracted from the alveolar macrophages and placed in a chemotaxis plate and the migration of neutrophils was measured. Chemotaxis of all cell types to be tested was measured by a change of absorbance on a microplate reader set at 492 nm. Results were compared with alveolar macrophages not stimulated with LPS, RPMI alone, and N formyl-methionyl-leucyl-phenylalanine (FMLP). The supernatant of the stimulated alveolar macrophages increased neutrophil chemotaxis as compared with unstimulated alveolar macrophages, and RPMI (p < .05). Surfactant treatment with 292 microg/mL significantly decreased LPS-stimulated alveolar macrophages induced neutrophil chemotaxis. Treatment with 875 microg/mL of surfactant did not alter neutrophil chemotaxis. CONCLUSIONS: Alveolar macrophages stimulation with LPS increased the chemotaxis of neutrophils. Treatment with surfactant at a concentration of 875 microg/mL did not alter neutrophil migration; however, treatment with 292 microg/mL significantly decreased neutrophil chemotaxis suggesting that at low concentrations, surfactant inhibits chemokine release and may reduce pulmonary neutrophil sequestration in vivo.

Surfactant replacement in the treatment of sepsis-induced adult respiratory distress syndrome in pigs.

OBJECTIVE: To evaluate the efficacy of treating sepsis-induced adult respiratory distress syndrome (ARDS) by instillation of exogenous surfactant in a porcine endotoxin model. DESIGN: Prospective trial. SETTING: Laboratory at a university medical center. SUBJECTS: Fifteen hybrid pigs, weighing 15 to 20 kg. INTERVENTIONS: Pigs were anesthetized and surgically prepared for hemodynamic and lung function measurements. Animals were randomized into three groups: a control group (group I; n=4) that received sham Escherichia coli lipopolysaccharide (endotoxin); an endotoxin group (group II; n=6) that received endotoxin (25 micrograms/kg); and an endotoxin + surfactant (Infasurf, ONY, Amherst, NY) instillation group (group III; n=5) that received endotoxin (25 micrograms/kg) followed by surfactant (100 mg/kg) instillation; all groups were studied for 6 hrs after the start of endotoxin injection. At necropsy, lung water and surfactant function (Wilhelmy balance) were measured and the right middle lung lobe was fixed for histologic analysis. Surfactant function was expressed as the surface tension at the minimum trough area. MEASUREMENTS AND MAIN RESULTS: Surfactant treatment (group III) significantly (p<.05) decreased venous admixture (group III = 41.5 +/- 9.1%; group II = 61.6 +/- 4.7%), PaCO2 (group III = 46.6 +/- 1.3 torr [6.2 +/- 0.2 kPa]; group II = 54.4 +/- 2.6 torr [7.25 +/- 0.34 kPa], and surface tension minimum (group III = 8.8 +/- 1.8 dyne/cm; group II = 20.0 +/- dyne/cm), as compared with endotoxin without treatment (group II) 6 hrs after endotoxin infusion. However, surfactant instillation did not significantly improve PaO2 (group III = 62.8 +/- 6.8 torr [8.4 +/- 0.9 kPa2]; group II = 50.3 +/- 3.7 torr [6.7 +/- 0.49 kPa]) or reduce the amount of pulmonary edema (group III = 7.1 +/- 0.39 ratio; group II = 6.8 +/- 0.24 ratio) seen 6 hrs following endotoxin injection. Histologic analysis showed that endotoxin caused edema accumulation around airways and pulmonary vessels, and a large increase in the number of marginated leukocytes with or without surfactant treatment. Surfactant treatment significantly increased the total number of leukocytes in the pulmonary parenchyma. CONCLUSIONS: We conclude that endotoxin caused lung injury typical of ARDS as demonstrated by pulmonary edema, an increase in PaCO2, and a decrease in PaO2, a decrease in static lung compliance and inhibition of surfactant function. Exogenous surfactant treatment effected only moderate improvements in lung function (i.e., reduced venous admixture and restored surfactant function) in this sepsis-induced ARDS model.

Pulmonary surfactant function following endotoxin: effects of exogenous surfactant treatment.

In a porcine model of endotoxin-induced adult respiratory distress syndrome (ARDS) we tested the hypothesis that the severity of lung injury would vary with the concentration of endotoxin and that reestablishment of normal surfactant function with exogenous surfactant would vary with the severity of lung injury. The therapeutic effects of exogenous surfactant treatment on pulmonary surfactant function have varied greatly in animal models of ARDS. This has created discrepancies in the literature that may be due in part to a difference in the severity of the pulmonary lesion. Yorkshire pigs were anesthetized, placed on a ventilator, and surgically prepared for hemodynamic and lung function measurements. Pigs received either 25 (25LPS) or 50 (50LPS) micrograms/kg of Escherichia coli lipopolysaccharide (LPS) followed by exogenous surfactant (SURF, 100 mg/kg) instillation, and were randomized into five groups: Control = sham LPS (n = 4); 25LPS (n = 6); 50LPS (n = 6); 25LPS + SURF (n = 5); and 50LPS + SURF (n = 6). Treatments were followed by histological and surfactant function evaluation. Histological evaluation showed the hallmarks of ARDS. Pulmonary surfactant function assessed by surfaced tension minimum (Ymin) was significantly (P < .05) elevated in both the 25LPS (20.2 +/- 2, dyne/cm) and 50LPS (19 +/- 3, dyne/cm) groups as compared with the Control group (10 +/- 1, dyne/cm). Exogenous surfactant reduced Ymin in the 25LPS + SURF group (9 +/- 2 dyne/cm, p < .05 vs. 25LPS) but not in the 50LPS + SURF group (20 +/- 1 dyne/cm, p < .05 vs. Control and 25LPS + SURF). Surfactant treatment was more effective in reestablishing normal surfactant function in animals subjected to a low dose of endotoxin, compared with animals receiving a higher dose.

Comparison of exogenous surfactants in the treatment of wood smoke inhalation.

The goal of this study was to compare the effectiveness of the exogenous surfactants Infasurf and Exosurf in reestablishing surfactant function inhibited by severe smoke inhalation. Mongrel dogs (n = 17) were anesthetized, placed on a ventilator (40% O2), and surgically prepared for hemodynamic and blood gas measurements; venous admixture (QVA/QT) and static lung compliance (Cstat) were calculated. At the conclusion of the experiment, lung samples were taken for lung water and dynamic surface tension (DST, Wilhelmy balance) measurements. Following baseline measurements, dogs were randomly separated into four groups: Group I, smoke+sham instillation; Group II, smoke+saline instillation: Group III, smoke+Exosurf instillation; and Group IV, smoke+Infasurf instillation. The surfactants (Infasurf and Exosurf, 100 mg/kg) or saline (same volume as surfactants) were instilled into the lungs via suction catheter immediately following smoke exposure. Smoke inhalation caused a similar increase in QVA/QT and fall in PaO2 and Cstat in all groups that improved only with Infasurf instillation (Group IV). DST was significantly improved by Infasurf compared with all other groups. We conclude that Infasurf restores normal DST, inhibited by wood smoke, improving lung function. Exosurf was ineffective in the treatment of wood smoke inhalation.

Unilateral smoke inhalation increases pulmonary blood flow to the injured lung.

Smoke inhalation (SI) affects the homogeneity of lung perfusion possibly by increasing alveolar surface tension. Anesthetized dogs (n = 8) were ventilated with a tracheal divider and a dual ventilator. One lung (left or right) was exposed to 5 minutes of SI while the other remained on room air. Total pulmonary blood flow (cardiac output) was measured by thermal dilution and left lung blood flow was measured with an ultrasonic flow probe. Since SI is associated with elevation of alveolar surface tension (AST), we studied a second group of dogs (n = 6) in which AST was increased in one lung with aerosolized dioctyl sodium sulfosuccinate (OT). The OT elevates AST without otherwise damaging the lung. Unilateral SI resulted in systemic hypoxemia (Pao2 fell from 91 +/- 6 to 55 +/- 4 mm Hg) and increased venous admixture (9 +/- 2% to 29 +/- 4%) both of which remained different from baseline values (p < 0.05) for 2 hours. Blood flow to the smoke exposed lung increased gradually and became significantly larger than that to the contralateral normal lung 2 hours following inhalation (smoke lung = 64% +/- 6% and normal lung = 36% +/- 6% of total blood flow). Following smoke exposure, pulmonary vascular resistance (PVR) increased with time in the unexposed normal lung (baseline = 8.7 +/- 1.4; 2 hours post smoke = 22.6 +/- 7.9 mm Hg/L/min, p < 0.05); PVR did not change in the smoke injured lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of high-frequency jet to conventional mechanical ventilation in the treatment of severe smoke inhalation injury.

The pathophysiology of smoke inhalation includes surfactant inhibition and pulmonary vascular injury leading to a high permeability pulmonary oedema. It has been shown in surfactant deficient animal models that methods of ventilation (i.e. high-frequency ventilation - HFV) avoiding a large pressure excursion (i.e. pressure change from end expiration to peak inspiration) improves oxygenation and decreases hyaline membrane formation. Therefore, we compared HFV with conventional mechanical ventilation (CMV) on lung function in an acute animal model of smoke inhalation (SI). Mongrel dogs were anaesthetized, surgically prepared for haemodynamic and blood gas monitoring, and placed on either CMV (n = 6) or HFV (n = 7). Following baseline (BL) measurements both groups were ventilated with wood smoke for 10 min. Ventilator settings were not adjusted from baseline following smoke inhalation in either groups; positive and expiratory pressure (PEEP, approximately 6 mmHg) was added in both groups following smoke exposure. At the conclusion of the study (4 h postsmoke inhalation) lung samples were taken for surfactant function and lung water measurements. Smoke inhalation immediately increased the A-a gradient (CMV-BL = 6.9 +/- 2.4 to CMV-SI = 77.3 +/- 1.9; HFV-BL = 10.5 +/- 2.7; HFV-SI = 72.8 +/- 3.7 mmHg), venous admixture (CMV-BL = 6.9 +/- 2.8 to CMV-SI 69.8 +/- 6.6; HFV-BL = 7 +/- 1.7 to HFV-SI = 60.4 +/- 7.9 per cent) and decreased Pao2 (CMV-BL = 110 +/- 3.4 to CMV-SI = 28 +/- 3.5; HFV-BL = 103 +/- 3.6 to HFV-SI = 31 +/- 1.7 mmHg) to a similar level in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of a piglet model of status epilepticus: preliminary results.

STUDY OBJECTIVE: Ventilation frequently is impaired during prolonged clinical seizures and their treatment. In a pilot study, respiratory, metabolic, and hemodynamic variables were studied during induced seizures in a lightly anesthetized, spontaneously breathing piglet model. PARTICIPANTS: Weanling, mixed-breed domestic piglets. INTERVENTIONS: Piglets were instrumented with a tracheostomy, arterial catheter, and epidural electrodes. Conditions included hyperoxia, normothermia, and ketamine maintenance infusion throughout recordings. After baseline recordings, 2 mg/kg IV bicuculline was administered. For further model validation, piglets were randomized to infusions of diazepam (three), lorazepam (two), or saline (control; five) groups after ten minutes of untreated seizures. MEASUREMENTS AND MAIN RESULTS: Integrated tidal volume, respiratory rate, PaCO2, pH, arterial pressure, rectal temperature, heart rate, and bipolar EEG waveforms were recorded and compared at intervals for 60 minutes. Vigorous tonic-clonic seizures occurred in all piglets, confirmed by sudden synchronization and large-amplitude EEG waveforms. Increases in heart rate, arterial pressure, tidal volume, respiratory rate, PaCO2, minute ventilation, and base deficit occurred in all piglets during seizures as compared with baseline. Five minutes after bicuculline was administered, increases in minute ventilation (4.5 +/- 0.4 L/min at baseline to 13 +/- 2.1 L/min) were accounted for by increases in both tidal volume and respiratory rate. More abrupt decreases in respiratory rate were observed in anticonvulsant-treated piglets as compared with controls. The duration of continuous seizure activity (12 +/- 1.0 minutes versus 21 +/- 3.3 minutes; P < .05) was reduced in anticonvulsant-treated piglets. CONCLUSION: Significant increases in ventilation occur during generalized seizures in tracheostomized piglets given bicuculline. Diazepam and lorazepam infusions ameliorate seizure activity and suppress increases in respiratory rate but not minute ventilation as compared with controls. Problems with this model included baseline variability, temperature instability, and that direct respiratory stimulation from the convulsant agent may have occurred.

Graft geometry and venous intimal-medial hyperplasia in arteriovenous loop grafts.

This study explores graft geometry and hemodynamics in a reproducible canine arteriovenous loop graft model of intimal-medial hyperplasia. Untapered 6 mm diameter polytetrafluoroethylene grafts (n = 10) were paired with 4 to 7 mm taper (n = 5) or 7 to 4 mm taper (n = 5) grafts for a 12-week period. Several hemodynamic variables were assessed at multiple locations, and venous intimal-medial thickness was measured at locations corresponding to the hemodynamic measurements. Color Doppler imaging demonstrated energy transfer out of the vessel in the form of perivascular tissue vibration. This was quantitated by the distance required for Doppler signal attenuation or volume of the detected vibration signal. Differences among graft types were noted for pressure, flow velocity, tissue vibration, and venous intimal-medial thickness. Hyperplasia was significantly decreased in 4 to 7 mm taper grafts. Stepwise deletion regression indicated volume of the vibration signal had a better correlation with venous intimal-medial thickness than any other variable (r 0.9, p less than 0.001). We conclude that graft geometry can have a significant impact on hemodynamic factors and venous intimal-medial hyperplasia in arteriovenous loop grafts. Flow disturbances appear to cause energy transfer through the vessel wall and into perivascular tissue. Kinetic energy transfer in the form of perivascular tissue vibration was quantitated in vivo and correlates strongly with venous intimal-medial thickness.

Positive end-expiratory pressure accelerates lung water accumulation in high surface tension edema.

The effect of positive end expiratory pressure (PEEP) on the rate of lung water accumulation with high surface tension pulmonary edema was examined. Alveolar surface tension was elevated by inhalation of 15 mg/kg of the aerosolized detergent dioctyl sodium sulfosuccinate (OT). Hemodynamic measurements, blood gases, and colloid oncotic pressures were recorded in anesthesized dogs for 2 hours after surfactant displacement and elevation of PEEP to 10 cm H2O pressure (group II; n = 10). These data were compared with those of an identical protocol that used only 5 cm H2O PEEP (group I; n = 10). Pulmonary extravascular water volume (PEWV) was measured gravimetrically at the end of the experiment. OT inhalation resulted in an immediate fall in Pao2 and rise in venous admixture (QVa/QT), with little change in colloid oncotic pressure or left atrial pressure. In group I, Pao2 and QVa/QT did not improve significantly over 2 hours, whereas both returned to near baseline in group II. PEWV was elevated in group I compared with normal PEWV (historic controls; n = 11) (6.1 +/- 0.07 - 3.6 +/- 0.01 ml/gm dry lung; p less than 0.01); however, PEWV in group II (9.1 +/- 1.0 ml/gm dry lung; p less than 0.01) was greater than in both group I and historic controls. These data indicate that high alveolar surface tension induces pulmonary edema and PEEP accelerates this edema formation.

Beneficial effects of banding on venous intimal-medial hyperplasia in arteriovenous loop grafts.

Local hemodynamics were modified in a canine arteriovenous loop graft model by placing a flow-limiting band on femoral polytetrafluoroethylene (PTFE) grafts. Banded and unbanded grafts were implanted in a paired fashion. Hemodynamic studies included Reynolds number and phonoangiography as measures of turbulence. Intimal-medial thickness was measured 8 weeks after implantation. Reduction of the volumetric flow rate by 50 percent resulted in significant changes in flow velocity, flow pulsatility, pressure, and turbulence at the venous anastomosis. Hyperplastic lesions developed in a reproducible manner at the venous anastomosis of the unbanded but not the banded grafts, as evidenced by combined intimal-medial thickness measurements: unbanded grafts 0.68 +/- 0.13 mm (p less than 0.01 versus control), banded grafts 0.25 +/- 0.03 mm (p greater than 0.05 versus control). Stepwise regression analysis indicated Reynolds number had the best correlation with the development of hyperplasia (r = 0.915, p less than 0.005), this being the first time this correlation has been quantitatively determined. We conclude that flow disturbance or turbulence is a major factor in the development of venous intimal-medial hyperplasia in arteriovenous loop grafts.

Effect of positive end-expiratory pressure on alveolar capillary perfusion.

Positive end-expiratory pressure (PEEP) increases arterial carbon dioxide tension and alveolar dead space by reducing alveolar capillary perfusion. The two likely mechanisms by which PEEP reduces alveolar capillary perfusion are reduction of cardiac output or compression of pulmonary capillaries within interalveolar septa, or both mechanisms. This study attempts to quantitate the impact of each of these mechanisms on alveolar capillary perfusion in anesthetized dogs by restoring cardiac output to baseline values with dextran 70 infusion after application of 15 cm H2O PEEP. Alveolar capillary perfusion was assessed directly through the visceral pleura by in vivo photomicroscopy. PEEP resulted in a fall in cardiac output and alveolar capillary perfusion with a concomitant rise in alveolar dead space-tidal volume ratio and arterial carbon dioxide tension. Infusion of dextran 70 returned the cardiac output to baseline levels but only slightly increased alveolar capillary perfusion. Both dead space/tidal volume ratio and arterial carbon dioxide tension remained significantly elevated with PEEP even with normal cardiac output. Microscopically, alveolar capillaries appeared compressed and flattened by PEEP, which indicated a mechanical interruption of blood flow. Extra-alveolar vessels remained perfused with PEEP. PEEP increased dead space/tidal volume ratio 36%; restoration of cardiac output reduced dead space/tidal volume ratio only 7% and did not return alveolar capillary perfusion to baseline levels. These data indicate that most of the reduced alveolar perfusion with PEEP results from direct compression of alveolar capillaries and not from reduced cardiac output.

Surfactant displacement by meconium free fatty acids: an alternative explanation for atelectasis in meconium aspiration syndrome.

Meconium, an ether extract of meconium, and the major free fatty acids of meconium (palmitic, stearic, and oleic acids) were all found to increase the surface tension minimum of dog lung extract in a Wilhelmy balance. Each of these fractions was instilled into the lungs of dogs (15 experimental, eight saline solution controls), and cardiac output, venous and arterial blood gases, pulmonary, atrial, and systemic pressures, airway pressure, and static lung compliance were serially monitored for 2 hours. Mean airway pressure increased and static lung compliance decreased significantly in all of the experimental groups. Although arterial pH and PaCO2 and the various hemodynamic measurements did not change during the experiment, PaO2 decreased significantly and did not return to baseline in all experimental groups. Extracts from atelectatic portions of experimental dog lung had a surface tension minimum of greater than 20 dynes/cm, whereas airway foam had a surface tension minimum of less than 10 dynes/cm, suggesting that the free fatty acids of meconium are able to strip surfactant from the alveoli.

Hypothermic cardiopulmonary bypass: a comparison between alpha and pH stat regulation in the dog.

The accepted normal pH of 7.40 may not be optimal at lower temperatures. This study evaluated the effect of maintaining pH in the accepted normal range at hypothermia (group 1, pH stat) or at normothermia (group 2, alpha stat) on organ blood flow and hemodynamics in dogs. The desired pH was achieved at all temperatures by adjusting pCO2. Hypothermia to 20 degrees C was induced by high flow bypass in both groups followed by 45 min of reduced flow before rewarming. In group 1 (n = 10), pH was 7.45 +/- 0.02 at 20 degrees C and in group 2 (n = 11) it was 7.64 +/- 0.01. A greater base excess developed by the end of the low flow period in pH stat animals (-9.4 +/- 1.1 vs -2.8 +/- 0.8, P less than .001) and resulted in continued acidosis after rewarming in the pH stat group compared to those in the alpha stat group (7.32 +/- 0.03 vs 7.38 +/- 0.01, P less than .02). Expressed as a percentage of baseline, regional blood flows after rewarming for group 1 were: brain 112 +/- 8%, renal cortex 48 +/- 8% (P less than 0.005, rewarm vs baseline), renal medulla 36 +/- 9% (P less than 0.005, rewarm vs baseline), epicardium 198 +/- 40% (P less than 0.05, rewarm vs baseline), endocardium 151 +/- 25%.(ABSTRACT TRUNCATED AT 250 WORDS)

Microvascular membrane permeability in high surface tension pulmonary edema.

Pulmonary edema was induced in dogs by an aerosol of detergent dioctyl sodium sulfosuccinate. The permeability of the pulmonary microvascular membrane was assessed by cannulating an afferent tracheobronchial lymphatic and comparing the lymph-to-plasma total protein concentration (CL/CP) during high lymph flows induced by increasing left atrial (LA) pressure after detergent aerosol. Base-line CL/CP of 0.69 +/- 0.02 fell to 0.55 +/- 0.03 with increased LA pressure alone. CL/CP fell to 0.47 +/- 0.02 when LA pressure was increased following detergent, 0.51 +/- 0.04 following an aerosol of the vehicle in which the detergent was dissolved, and 0.73 +/- 0.10 following intravenous alloxan. In additional animals protein concentration of the airway edema fluid was compared with that of plasma. The ration of protein concentration of airway fluid to plasma was 0.63 +/- 0.08 following detergent aerosol, 0.64 +/- 0.10 following increased LA pressure, and 0.94 +/- 0.09 following administration of alloxan. These data indicate no major increase in pulmonary microvascular permeability following detergent aerosol and support the concept that pulmonary edema is the consequence of reduced interstitial perimicrovascular hydrostatic pressure caused by increased alveolar surface tension.

Relation of portal hemodynamics to cardiac output during mechanical ventilation with PEEP.

The relation of portal hemodynamics to cardiac output (CO) during mechanical ventilation with 15 cm H2O PEEP was studied in 12 dogs under pentobarbital anesthesia. Cardiac output was measured by thermal dilution. Portal vein flow (PF) and superior mesenteric artery flow (SMAF) were measured by electromagnetic flow probes. Intraesophageal, intraabdominal, portal vein (PVP) and intrathoracic caval (CVP) pressures, as well as the intraluminal venous pressure gradient across the liver (PVP-CVP) were measured. Intravascular volume was expanded with dextran prior to the addition of PEEP. In nine animals, dextran plus PEEP maintained CO and visceral flows within 3% of control. In three animals, CO and visceral flows fell to the same proportion. There was no increase in hepatic resistance. PF showed a linear correlation with SMAF, and SMAF had a linear correlation with CO. In these experiments, the effect of PEEP on portal hemodynamics system is primarily the consequence of reduced CO.

High surface tension pulmonary edema.

Dogs were anesthetized with pentobarbital and placed on a piston ventilator with room air. Ten animals received an endobronchial lavage of normal saline (3 mg/kg). Ten other animals received an endobronchial lavage of the same volume of a nonionic detergent, Tween 20, 5% in saline. Detergent lavage was shown by Wilhelmy balance to increase surface tension of lung extracts. Saline lavage did not alter the surface tension of lung extracts. No significant differences between the groups were noted in cardiac output, left ventricular and diastolic pressure, mean pulmonary artery pressure, or colloid oncotic pressure. Static compliance and arterial PO2 were decreased following detergent lavage. Animals were sacrificed 2 hr after lavage and pulmonary extravascular water volume (PEWV) was measured gravimetrically. Saline-lavaged lungs with normal surface tension had a PEWV of 4.3 ml/g dry lung. Tween-lavaged lungs with increased surface tension had a PEWV of 5.3 ml/g dry lung (P less than 0.005). When the estimated volume of residual lavage solution remaining in the lung parenchyma was subtracted from the total wet lung wt, the corrected PEWV was 3.62 +/- 0.12 ml/g dry lung for saline-lavaged lung and 4.76 +/- 0.19 ml/g dry lung for Tween-lavaged lung. PEWV for 11 control animals ventilated 2 hr without lavage was 3.61 +/- 0.13 ml/g dry lung. It is concluded that, experimentally, high alveolar surface tension can induce pulmonary edema even when pulmonary microvascular hydrostatic and colloid oncotic pressures are normal.