Search

Single lung inhalation injury causes tissue damage to the contralateral lung. We therefore examined airway blood flow after smoke inhalation in chronic instrumented sheep to get further information about the underlying pathophysiology. The right lung and lower trachea of 5 animals were smoke-exposed, while their left lung was air-insufflated using a split ventilation technique. Three animals, where both lungs were only air-insufflated, served as controls. Blood flow to the airway was measured using a labeled microsphere technique. All animals were studied for 24 h following smoke inhalation. Then they were sacrificed and their tissues harvested. The airway blood flow to the smoke-exposed lung was elevated 11-fold immediately after inhalation injury. The bronchial blood flow to the air insufflated lung became significantly elevated 24 h post-smoke, although to a lesser extent. The control animals did not show any changes of bronchial blood flow during the observation time. Damage to one lung can lead to pathophysiologic changes in the contralateral lung. This response appears to be mediated by hematogenous factors.

We evaluated regional blood flows in a hyperdynamic sepsis model and the reversal of increased flows by blockade of nitric oxide (NO) synthase. Seven awake sheep were continuously infused with Escherichia coli endotoxin [lipopolysaccharide (LPS), 10 ng.kg-1.min-1] for 48 h. The NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg) was injected after 24 h. Blood flows to systemic organs were determined with the radioactive microsphere technique. LPS induced elevation of cardiac index by 36% (P < 0.05) and a fall in systemic vascular resistance index by 37% (P < 0.05) at 0 h [time of L-NAME administration, 24 h after infusion of LPS had begun] L-NAME administration normalized cardiac index [6.1 +/- 0.5 at 4 h posttreatment, 6.1 +/- 0.5 l.min-1.m-2 at -24 h (baseline)] and systemic vascular resistance index (1,333 +/- 105 at 4 h posttreatment, 1,280 +/- 163 dyn.s.cm-5.m2 at -24 h) and reduced all regional blood flows to near-baseline levels for the remainder of the study period (24 h). O2 consumption was unaffected by treatment.

Nutritive (systemic arterial) airway blood flow (mL/min/100 grams tissue) was studied in various size airways at four randomized levels of positive end expiratory pressure (PEEP) in smoke injured and normal lungs. Seven sheep were studied 24 hours after an isolated injury to the left lung using cotton smoke. Radioactive 15-microns microspheres were utilized to measure this airway blood flow. These data demonstrated a marked increase in systemic arterial blood flow to the airways in the injured left lung. Increasing levels of PEEP significantly reduced this hyperemic response. PEEP did not significantly affect the uninjured right lung. Systemic airway blood flow was never reduced to below normal control levels (uninjured) in either lung despite PEEP of up to 20 cm H2O. Severe reduction in airway nutritive flow, and the possibility of airway necrosis, does not appear to occur at PEEP levels of up to 20 cm H2O.

Splanchnic ischemia has been associated with bacterial translocation and increased endotoxin absorption from the gut. To study the effects of major burn on splanchnic circulation, minipigs were randomized to receive 40% flame burn and Parkland resuscitation or sham burn and maintenance fluids. Total and fractionated blood flow, O2 delivery and consumption, mucosal pH of the intestine, and endotoxin levels in the superior mesenteric vein were measured for 48 h, and then abdominal organs were harvested for bacteriological culture and histopathological analysis. Total mesenteric blood flow and fractionated blood flow to the mucosa-submucosa of the jejunum, cecum, and colon decreased 2 and 4 h postburn. Although mesenteric O2 consumption was unchanged, mesenteric O2 delivery and intestinal mucosal pH were decreased during the early postburn period. Concomitantly, endotoxin levels in the superior mesenteric vein were significantly elevated during the first 8 h postburn. The bacteriological cultures of the systemic tissue samples showed increased bacterial translocation in the burn group. After major burns, there is a transient selective splanchnic vasoconstriction, which is associated with intestinal mucosal acidosis and increased incidence of bacterial translocation and endotoxin absorption from the gut.

We have previously utilized the technique of transcranial Doppler (TCD) ultrasound to determine cerebral perfusion in patients undergoing cardiopulmonary resuscitation (CPR). In order to assess if TCD can reliably measure alterations in cerebral perfusion under conditions of normal and low cardiac outputs, we compared TCD measured blood flow velocities in the middle cerebral artery (MCA) of six piglets with radioactive microsphere determinations of total cerebral perfusion at baseline normal sinus rhythm (NSR), during CPR, and following return of spontaneous circulation (ROSC). Peak systolic and mean blood flow velocities were compared to the microsphere perfusion results on 15 different occasions; six during NSR, five during CPR, and four following ROSC. Although qualitative alterations in TCD measurements reflected changes in microsphere perfusion, we could not find a statistically significant correlation between either peak systolic or mean MCA blood flow velocities and microsphere perfusion measurements either overall or in any subgroup. The possible reasons which may explain the findings are discussed.

This study evaluates the use of transcranial Doppler (TCD) ultrasound in assessing the changes experienced by the cerebral circulation during cardiopulmonary resuscitation (CPR) and compares it with measurements of internal carotid artery (ICA) flow rates (ultrasonic flow-meter measurements) and cerebral blood flow (CBF) (radioactive-microsphere measurements) in a porcine cardiac arrest model undergoing closed chest CPR.Sixteen piglets were anesthetized and subjected to TCD monitoring, ICA flow-rate measurements, and CBF measurements during CPR following induction of ventricular fibrillation. A total of 14 comparisons between TCD and CBF measurements, and 36 comparisons between TCD and ICA flow measurements were performed. Correlations were determined using Pearson's method, and the validity of the correlation was determined using Bonferoni's adjusted probabilities.The correlation between mean cerebral blood flow velocity and mean total ICA flow rate was 0.67 (P.01). The correlation between peak systolic blood flow velocity and CBF was 0.76 (P = .02).TCD can provide on-line information about cerebral perfusion during CPR.

OBJECTIVE: To investigate the effects of N omega-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis, on hemodynamics, gas exchange and oxygen transport in an ovine model of hyperdynamic sepsis. DESIGN: Prospective, nonrandomized, controlled study, with repeated measurements. SETTING: University research laboratory. SUBJECTS: Twenty healthy adult sheep (weighing 20 to 45 kg) were divided into two groups of 12 treated sheep and eight control sheep and studied. INTERVENTIONS: Twenty awake, chronically instrumented sheep received a continuous infusion of endotoxin (10 ng/kg/min) over 48 hrs. Twenty-four hours after the start of the endotoxin infusion, 12 sheep (treatment group) received a bolus of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester (25 mg/kg), while the other eight animals (control group) received the carrier (0.9% NaCl). MEASUREMENTS AND MAIN RESULTS: Twenty-four hours after the start of the endotoxin infusion, both groups exhibited a hyperdynamic state with increased cardiac indices, decreased systemic vascular resistance indices, impaired oxygenation, and increased pulmonary shunt fractions. In both groups, oxygen delivery was significantly increased, while oxygen consumption remained virtually unchanged, resulting in a decreased oxygen extraction ratio. In the control group, the significant alterations in systemic hemodynamics, lung function and oxygen transport persisted for the remainder of the study. Administration of N omega-nitro-L-arginine methyl ester normalized cardiac index and systemic vascular resistance index, increased mean arterial blood pressure, and decreased heart rate. Although oxygen delivery significantly decreased after administration of N omega-nitro-L-arginine methyl ester, oxygen consumption did not change, resulting in a normalization of oxygen extraction ratio. Despite a significant reduction of pulmonary shunt fraction, oxygenation did not improve. Pulmonary arterial pressure and pulmonary vascular resistance index showed a peak 2 hrs after administration of the nitric oxide synthesis inhibitor and then tended to decrease. In contrast, the effects of N omega-nitro-L-arginine methyl ester on the systemic circulation persisted for the remainder of the study. CONCLUSIONS: The data support the assumption that augmented nitric oxide production is a major cause of the hemodynamic alterations seen in hyperdynamic endotoxemia. Administration of the nitric oxide synthesis inhibitor N omega-nitro-L-arginine methyl ester normalized the endotoxin-induced hyperdynamic state, but did not impair oxygen consumption, indicating adequate tissue perfusion of metabolically active organs. Inhibition of nitric oxide synthesis may be a therapeutic option in the treatment of hyperdynamic septic patients when conventional therapy fails to maintain a minimum of cardiovascular performance.

Discrepancies exist between experimental measurements of the systemic blood flow to sheep lung by use of microsphere techniques and flow probes on the bronchial artery. In these studies, we simultaneously measured the blood flow through the bronchial artery, using a transit time flow probe, and the systemic blood flow to left lung, using radioactive microspheres. All measurements were made on conscious sheep previously prepared with chronic catheterizations of the left atrium, aorta, and vena cava and a flow probe around the bronchial artery. Inflatable occluder cuffs were placed around the pulmonary and bronchoesophageal arteries. Bronchial artery blood flow in six sheep was 25.3 +/- 5.2 ml/min or 0.4% of the cardiac output. Systemic blood flow to left lung, measured with microspheres, was 54.1 +/- 14.2 ml/min. Calculated systemic blood flow to that portion of sheep lung perfused by the bronchial artery was 127.6 +/- 35.3 ml/min or 1.9% of cardiac output. Occlusion of the bronchoesophageal artery reduced bronchial artery flow to near zero, whereas total systemic blood to the lung was reduced by only 55%. Blood flow to the intraparenchymal cartilaginous airways was reduced 60–90% after occlusion of the bronchoesophageal artery. Sheep, like most mammals, have multiple and complex systemic arterial inputs to the lungs. We conclude that multiple branches of the bronchoesophageal artery provide most but not all of the systemic blood flow to the intraparenchymal cartilaginous airways but that over one-half of the total systemic blood flow to sheep lung comes from sources other than the common bronchial artery.

Study objective: A number of studies have demonstrated a correlation between end-tidal carbon dioxide (ETco 2 ), cardiac output, and return of spontaneous circulation in experimental animals and in patients undergoing closed-chest CPR. Our study attempted to correlate ETco 2 to cerebral blood flow during cardiac arrest. Design: Sixteen piglets were anesthetized, intubated, and instrumented for cerebral blood flow studies. An ultrasonic flow probe was placed on both internal carotid arteries for continuous flow measurements. The animal was fibrillated, and closed-chest CPR was begun. Continuous ETc0 2 measurements were obtained and compared with simultaneous internal carotid, cardiac output, and cerebral blood flow measurements. Measurements and main results: Correlations between ETco 2 and carotid and cerebral blood flow were determined using Pearson's method. The correlation between ETco 2 and total internal carotid flow was .58 ( P = .01, Bonferroni's adjusted P = .30). Correlation between ETco 2 and cerebral blood flow was .64 ( P = .01, Bonferroni's adjusted P = .09). A partial correlation coefficient for ETco 2 versus cardiac output was .70, whereas it was only .30 for ETco 2 versus cerebral blood flow. Conclusion: Partial correlation coefficients suggest that ETco 2 correlates with cerebral blood flow when changes in cerebral blood flow parallel changes in cardiac output.

We investigated the contribution of the bronchial blood flow to the lung lymph flow (QL) and lung edema formation after inhalation injury in sheep (n = 18). The animals were equally divided into three groups and chronically prepared by implantation of cardiopulmonary catheters and a flow probe on the common bronchial artery. Groups 1 and 2 sheep were insufflated with 48 breaths of cotton smoke while group 3 received only room air. Just before injury, the bronchial artery of group 2 animals was occluded. The occlusion was maintained for the duration of the 24-h study period. At the end of the investigation, samples of lung were taken for determination of blood-free wet weight-to-dry weight ratio (W/D). Inhalation injury induced a sevenfold increase in QL in group 1 (7 +/- 1 to 50 +/- 9 ml/h; P less than 0.05) but only a threefold increase in group 2 (10 +/- 2 to 28 +/- 7 ml/h; P less than 0.05). The mean W/D value of group 1 animals was 23% higher than that of group 2 (5.1 +/- 0.4 vs. 3.9 +/- 0.2; P less than 0.05). Our data suggest that the bronchial circulation contributes to edema formation in the lung that is often seen after the acute lung injury with smoke inhalation.

The systemic blood flow to the airways of the left lung was determined by the radioactive microsphere technique before and 17 h after smoke inhalation in six conscious sheep (smoke group) and six sheep insufflated with air alone (sham group). Smoke inhalation caused a sixfold increase in systemic blood flow to the lower trachea (baseline 10.6 +/- 1.7 vs. injury 60.9 +/- 16.1 ml.min-1.100 g-1) and an 11- to 14-fold increase to the intrapulmonary central airways (baseline range 9.5 +/- 1.9 to 13.5 +/- 3.7 ml.min-1.100 g-1 vs. injury 104.6 +/- 32.2 to 187.3 +/- 83.6 ml.min-1.100 g-1). There was a trend for this hyperemic response to be greater as airway diameter decreased from the trachea to 2-mm-diam central airways. In airways smaller than 2 mm, the hyperemic response appeared to diminish. The total systemic blood flow to whole lung is predominantly to small peripheral airways and showed no significant increase from its baseline level of 17.5 +/- 3.7 ml.min-1.100 g-1 in the lung homogenate. Occlusion of the bronchoesophageal artery decreased central airway blood flow 60-80% and peripheral airway blood flow 40-60% in both the sham and the smoke groups.

Percutaneous transtracheal ventilation using a large gauge intravenous-type catheter can be used successfully in the setting of complete upper airway obstruction in animals. In this study, using a large animal model, satisfactory oxygenation and ventilation was achieved by inversely varying the catheter size and the inspiration to expiration ratio (I:E). Specifically, 30 to 63 kg ruminants with an obstructed upper airway were resuscitated for 30 minutes from a hypoxic, hypercarbic, and acidotic state using 12- and 14-gauge catheters connected to a 50 psi oxygen source via a two-way valve with an I:E of 1:4 and 1:9 seconds, respectively. Shorter expiratory time or increased inspiratory time with these intravenous catheters resulted in significant hemodynamic compromise, barotrauma, inadequate carbon dioxide elimination, acidemia, and frequent death.

The effects of aspiration of saline and acid on lymph albumin and pulmonary albumin contents were studied. Two radiolabeled species of albumin were used, I 125 -albumin was allowed to equilibrate while 131 I-albumin was injected at Time 0 of the experiment. One percent of total injected albumin was found in the lung in the saline and control groups for both the equilibrated and non-equilibrated varieties of albumin. Seven percent of injected dose of 125 I-albumin (equilibrated) was found in the lung after acid aspiration, while 16% of the nonequilibrated 131 I-albumin was found. The rate of “wash in” of 131 I-albumin was significantly increased in the lymph of acid aspirated animals as compared to controls. These data suggest that the previously demonstrated increase in microvascular permeability after acid aspiration results in an increase in extravascular pulmonary albumin. This effect should greatly alter the local osmotic gradient and result in altered fluid balance.

An ovine anti-neutrophil antibody has been produced by immunizing rabbits with purified sheep neutrophils. Serial intraarterial infusions of anti-neutrophil antibody in awake instrumented sheep produced selective and profound neutropenia. Intravascular infusion of endotoxin ( Escherichia coli , 1.5 μg/kg/30 min) resulted in significant and equivalent increases in pulmonary artery pressure, peripheral vascular resistance, and protein-rich pulmonary lymph flow in an endotoxin group ( n = 9) and a depletion + endotoxin group ( n = 4). Changes in cardiopulmonary parameters were most pronounced 2 to 8 hr after endotoxin administration in both groups. Cardiac index (CI) showed a precipitous and transient fall in both experimental groups at 0.5 to 1 hr after endotoxin infusion; however, by 8 hr CI rose significantly in the endotoxin group, while it remained unchanged in the depletion + endotoxin group. A significant rise in the peripheral neutrophil count was associated with the increase in CI in the endotoxin group. Plasma and pulmonary lymph levels of thromboxane -B 2 were unchanged during the depletion period with a significant increase 1 hr after endotoxin infusion. In this study questions arise regarding the exclusive role of circulating neutrophils in the microvascular permeability changes seen in sepsis-mediated adult respiratory distress syndrome.

Previous reports have suggested that the ischemic kidney develops a compression syndrome due to intracapsular edema and that decapsulation may improve function. This report evaluates renal function in ischemic kidneys with and without decapsulation. Thirteen dogs underwent creation of a split urinary bladder and the formation of bilateral cystocutaneous fistulas for measurement of split renal function. After systemic heparinization the suprarenal aorta was crossclamped for 112 hr. One kidney underwent removal of the anterior aspect of the capsule and the other intact kidney served as the control. The animals received 1000 ml/24 hr, 0.15 N NaCl solution IV postoperatively. Urine volume, osmolarity, creatinine, and sodium were quantitated during three consecutive 24-hr periods. Seventy-two hours following the ischemic injury, the dogs were reexplored. Renal interstitial pressures were measured and renal biopsies and an intravenous pyelogram performed prior to sacrifice. Significantly greater urine volume was produced by the decapsulated kidney (302 ± 35 ml/24 hr) than by the nondecapsulated kidney (173 ± 39 ml/24 hr). Urine sodium excretion/24 hr was consistently greater from the decapsulated kidney than from the intact kidney while urine osmolarity at 72 hr from the decapsulated kidney was 584 ± 76 and from the intact kidney was 325 ± 76 mosmole/liter (P < 0.05). Renal interstitial pressures were significantly greater in the intact kidney than in the decapsulated kidney. These data suggest that release of intercapsular compression can improve renal function in the ischemic canine kidney.

We have attempted to determine the membrane parameters, permeability-surface area product (PS) and reflection coefficient (sigma), necessary to describe solute exchange in the pulmonary circulation. Experimental lymph-to-plasma ratios were obtained for total protein (Rtot) and albumin (Ralb) using lung lymph collected from goats with chronic lung lymph fistulae. Lymph flow (QL) and solute flow (QS) were varied by increasing microvascular pressure in a stepwise manner by inflating a balloon in the left atrium. The increased QL and decreased Ralb from multiple experiments in four goats were used to plot PS vs. sigma using the equation of Patlak et al. (J. Theor. Biol. 5: 426–442, 1963). The region of intersection of two or more such curves should identify the two membrane constants. However, these curves rarely intersected suggesting that perhaps the lung barrier was not adequately represented by a single homoporous membrane. To evaluate heteroporosity, the three-pore model of Blake and Staub (Microvasc. Res. 12: 197–220, 1976) was investigated. By use of their pore sizes and relative pore distributions, values for the fluid filtration coefficient, PS, and sigma of each pore type were calculated, and finally QL and R were predicted at various microvascular pressures. When these calculated values of QL and R were plotted using the equation of Patlak et al., an equivalent homoporous PS and sigma could still be found. Therefore, a heteroporous membrane does not appear to explain the failure of our data plots to intersect. Possible alternative models are suggested.

This study has demonstrated in an awake goat the differential effects of infusing low dose epinephrine and norepinephrine. Epinephrine increases pulmonary fluid exchange, possibly as a result of β stimulation to the heart; whereas norepinephrine results in little change in pulmonary fluid balance, primarily affecting vascular vasoreactivity. This study underscores the importance of testing drug responses in awake animal models.

Hemostasis remains a major technical problem in surgery of the liver and spleen. A high power neodymium-doped yttrium aluminum garnet (Nd:YAG) laser has been coupled with a fiberoptic delivery system and quartz blade designed to yield maximal hemostasis and minimal tissue injury. In a series of experiments we were unable to demonstrate a significant advantage of its use in partial hepatic lobectomy.

Pure lung lymph has previously been obtained in awake sheep and goats via a cannula placed in an efferent duct of the caudal mediastinal lymph node (CMN). We describe a modification in goats wherein a segment of the thoracic duct collecting pulmonary efferents is isolated and cannulated. Lymph purity and responses to elevation of pulmonary microvascular pressure are illustrated and are found to be comparable to data obtained from a series of animals prepared by standard CMN cannulation. We have adopted the alternative procedure whenever, at cannulation may be complicated. When used in combination with the CMN approach, the overall rate of successful cannulation has increased from 50% to about 80%.

Previous reports suggest the value of renal decapsulation in the prevention of renal failure after acute ischemia. It has been suggested that this response is due to a release of "compartmental" pressure resulting in increased blood flow to the decapsulated kidney. Ten dogs were evaluated following 90 minutes of renal ischemia created by occlusion of the suprarenal aorta. Each animal underwent random unilateral decapsulation, with the contralateral kidney acting as control. Labeled 15 micron microspheres (Se85 and Ce141) were injected into the left ventricle at 15 minutes and one hour following decapsulation in six dogs. In the remaining animals the injection was carried out at 15 minutes and 48 hours. No difference in renal blood flow was found between decapsulated and control kidneys in either group. Similarly, using sectioned kidneys no difference in intrarenal distribution of blood flow was found. These data suggest that the effects caused by decapsulation are not due to hemodynamic alterations.

Lung injuries were produced by instilling 2.5 ml/kg of 0.1 N HCl into the trachea of lightly anesthetized goats with previously implanted lung lymph fistulas. Lymph flow (QL), lymph-to-plasma protein concentration ratio (L/P), pulmonary arterial and wedge pressures (Ppa, Pw), percent shunt (Qs/QT), and postmortem extravascular lung water (EVLW) were then measured for up to 48 h. QL began to increase within 15 min of injury from a baseline value of 7.2 ml/h to reach a peak of 231% of base line by 1.5 h, then decreased to 160% at 24 h and returned to base line by 48 h. Average L/P increased from 0.66 to a peak of 0.73 at 2 h. Ppa increased from 17.0 cmH2O to a first peak of 25.3 cmH2O at 15 min, then decreased to base line by 75 min. There was a second rise that peaked at 3 h before returning to base line at 24–48 h; Pw was unchanged throughout. Qs/QT increased from 8.5 to a peak of 34% at 1 h, then decreased to 15% at 4 h, and stabilized at 17–20% at 48 h. EVLW was 237% of base line at 4 h and declined somewhat but remained elevated at 194% of base line at 24 and 48 h. Qs/QT was less than expected based on the reduction in lung volume after aspiration. We conclude that microvascular permeability was increased after acid and that a protective vasoconstriction, probably due to local hypoxia, directed blood away from nonventilated alveoli.

Pressure-volume curves were obtained from excised left lungs of goats at 4, 24, and 48 h after tracheal instillation of 2.5 ml/kg of 0.1 N HCl. Air total lung capacity (TLC) at transpulmonary pressure (PL) = 35 cmH2O was 38.8 ml/kg body weight before acid, and was reduced sharply to 21.1 at 4 h, then increased to 25.6 at 24 h and 32.1 at 48 h. Excess extravascular lung water (EVLW) could account for only part of the volume reductions. Specific compliance ratio of transpulmonary pressure to total lung capacity (CL/TLC) between PL of 5 and 0 cmH2O was reduced from 0.074/cmH2O to 0.050, 0.048, and 0.053/cmH2O, respectively. Saline TLC (PL = 10 cmH2O) changed from 44.8 to 32.4, 34.3, and 45.4 ml/kg, respectively, but CL/TLC did not, suggesting airway obstruction. After injury, trapped volume at PL = 0 increased from 24.9 to 29.2, 43.3, and 37.3% TLC with air, and from 20.3 to 38.5, 33.1, and 28.5%, respectively, with saline. Air volume at a PL = 10 cmH2O on deflation fell from 82.0 to 72.1% TLC at 4 h, but was near control at 24 and 48 h. The reduction in ventilated volume was not reflected in proportionately increased shunt; therefore, some compensatory vasoconstriction must have occurred. We suggest that in affected regions increased surface forces, increased EVLW, and airway obstruction caused reductions of lung volume.