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Biomedical subjects

D L Traber

Publications and source records attributed to D L Traber.

At least 109 records · Page 6Linked to original sources
PubMed1994

Gut failure and translocation following burn and sepsis.

Sepsis with multisystem organ failure is a major cause of morbidity and mortality in burns. We studied the anatomic, physiologic, and metabolic changes of gut mucosa as a normal barrier against sepsis and systemic inflammatory response after burn and sepsis in the chronic porcine model. Flow probes were placed on the mesenteric and hepatic arteries and portal vein. Catheters were placed in the pulmonary artery (Swan-Ganz), aorta, superior mesenteric, and hepatic veins. After 5 days, baseline data were collected and studied after a 40%, third degree burn. They were resuscitated with Ringer's lactate solution (Parkland formula). Eighteen hours later, Escherichia coli endotoxin (100 micrograms/kg) was administered. All animals were sacrificed after 30 hr. The data were compared to a group of sham animals. Following thermal injury the cardiovascular status was stable. Endotoxin administration decreased systemic vascular resistance index and mean arterial pressure, but increased cardiac index. Mesenteric blood flow, vascular resistance, and oxygen consumption showed a transient fall after endotoxin infusion with 20, 23, and 40% reduction, respectively. These changes were associated with a rise in plasma levels of conjugated dienes. The intestinal ornithine decarboxylase activity was elevated at the end of the experiment, evidence of gut repair. Gut bacteria translocated into mesenteric lymph nodes, spleen, and burn wounds in 50% of the animals. We concluded that bacterial translocation into mesenteric lymph nodes, spleen, and wound is due to gut mucosal failure after burn trauma and sepsis. These pathophysiologic changes may be the result of mesenteric ischemia and reperfusion injury.

Animals↗
PubMed1994

Performance of an intravenous gas exchanger (IVOX) in a venovenous bypass circuit.

To analyze quantitatively the performance of the intravenacaval blood gas exchanger (IVOX), we developed a right atrium-pulmonary artery venovenous extracorporeal bypass circuit. Oxygen transfer and carbon dioxide removal were calculated at different blood flow rates, different hemoglobin levels, and during permissive hypercapnia. Oxygen transfer increased linearly with blood flow up to 41 mL/min. Likewise, O2 transfer increased linearly with hemoglobin levels up to 7.5 g/dL, but no further increases were achieved above this level. Carbon dioxide removal increased linearly as flow increased from 1.0 to 3.0 L/min but did not increase further for higher flows. Carbon dioxide removal was 45 mL/min at blood carbon dioxide tension of 42 mm Hg but increased to a maximum of 81 mL/min at a carbon dioxide tension of 90 mm Hg. We conclude that IVOX is a diffusion-limited device dependent on blood flow, hemoglobin content, and the gas pressure gradient across the membrane. Further engineering improvements are needed to improve the gas exchange performance of IVOX.

Animals↗
PubMed1994

Effects of nitric oxide synthesis inhibition in hyperdynamic endotoxemia.

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.

Animals↗
PubMed1994

The sequence of injury determines the degree of lung damage in both inhalation and thermal injuries.

The lung damage resulting from smoke inhalation is an important determinant of morbidity and mortality in thermally injured patients. We hypothesized that the degree of pulmonary microvascular damage seen with smoke inhalation could be affected by whether the smoke insult preceded or followed thermal injury. Fifteen chronically instrumented sheep were divided into two groups: seven were given a 40% 3rd-degree flame burn and then insufflated with smoke (smoke after burn group); eight were insufflated with smoke and then given thermal injury (smoke before burn group). Lung lymph flow and wet/dry weight ratio were significantly higher in smoke before burn group animals. We conclude that lung damage is minimized when thermal injury precedes smoke inhalation injury.

Animals↗
PubMed1994

Left ventricular dysfunction and acute lung injury induced by continuous administration of endotoxin in sheep.

Sixteen sheep were surgically prepared for chronic study. Seven days later, Escherichia coli endotoxin (10 ng/kg/min, lipopolysaccharide (LPS) group, n = 10) or an equivalent amount of 0.9% NaCl (Control group n = 6) was administered. Between 1 and 8 h post-LPS, there was a hypodynamic state with low cardiac index (CI, LPS 5.0 +/- 0.2; sham 6.3 +/- 0.4 liters/min/m2 at 4 h). During this period, the left ventricular end-systolic pressure-diameter relationship (ESPDR), a sensitive index of myocardial contractility, was also lower (LPS 10.4 +/- 1.2; sham 17.2 +/- 0.8 mmHg/mm). Mean pulmonary arterial pressure (PAP) and pulmonary vascular resistance index (PVRI) were remarkably increased 1 h after the administration of LPS (PAP:LPS 37.5 +/- 1.9; sham 21.8 +/- 0.9 mmHg, PVRI: LPS 600 +/- 58; sham 158 +/- 23 dynes x s x cm-5 x m2). The early changes in cardiopulmonary function occurred concomitantly with an elevation in tumor necrosis factor (LPS 1221 +/- 520; sham 0 +/- 0 pg/ml) and thromboxane B2 (LPS 1382 +/- 266; baseline 82 +/- 20 pg/ml) in arterial blood. Following this first phase, the sheep presented a persistent hyperdynamic state characterized by a significant increase in CI. The ESPDR continued to fall. By 24 h post-LPS the CI was 10.1 +/- 0.5 liters/min/m2 (sham, 6.3 +/- 0.3) but the ESPDR had fallen to 8.2 +/- 2.3 mmHg/mm (sham 16.0 +/- 3.0). The pulmonary hypertension was maintained for the duration of the LPS infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1994

alpha-Trinositol decreases lung edema formation after smoke inhalation in an ovine model.

Inhalation injury is a dominant cause of mortality in thermally injured individuals. After acute lung injury induced by smoke inhalation, lung lymph flow (QL) increased and pulmonary microvascular reflection coefficient to protein (sigma) decreased. alpha-Trinositol (PP56, 1D-myo-inositol 1,2,6-trisphosphate) can decrease edema formation after thermal injury. We therefore tested the hypothesis that alpha-trinositol could decrease the pulmonary edema noted with inhalation injury. Seven days after surgical preparation, sheep were insufflated with smoke from burning cotton towels. The alpha-trinositol group (n = 8) were treated with alpha-trinositol (2 mg/kg + 3.5 mg.kg-1 x h-1). The sham group (n = 7) received an equal volume of 0.9% NaCl. The sham group showed a large increase in QL (9.3 +/- 1.7 to 54.1 +/- 8.8 ml/h) and a decrease in sigma (0.79 +/- 0.03 to 0.48 +/- 0.03) 24 h after smoke inhalation. alpha-Trinositol attenuated the increase in QL (8.1 +/- 1.2 to 25.6 +/- 6.9 ml/h) and the decrease in sigma (0.76 +/- 0.03 to 0.60 +/- 0.03) noted with smoke inhalation. alpha-Trinositol thus decreased the changes in pulmonary microvascular permeability and transvascular fluid flux noted with inhalation injury.

Animals↗
PubMed1994

Pulmonary inflammatory cell response to sustained endotoxin administration.

We have developed a model of human sepsis in sheep. Twenty-four hours after continuous infusion of Escherichia coli endotoxin (lipopolysaccharide) (10 ng.kg-1.min-1) was begun, pulmonary transvascular fluid flux was almost five times the baseline values, cardiac output was nearly doubled, and mean arterial pressure was reduced by approximately 20 mmHg. At this time, the animals were killed and their lungs were fixed by endotracheal installation of 2.5% glutaraldehyde at 25 cmH2O pressure. Morphometry was performed by point counting, and data were expressed as relative volume density. Pulmonary edema and congestion were observed in sheep receiving lipopolysaccharide, whereas sham controls appeared normal. There was an increase in interstitial volume density. There was a significant increase (P < 0.01) in volume density of the pulmonary intravasculature (180%), interstitial macrophages (270%), and mast cells (240%). The volume densities of intravascular and interstitial polymorphonuclear neutrophils also showed a small insignificant increase.

Animals↗
PubMed1994

Increased organ blood flow in chronic endotoxemia is reversed by nitric oxide synthase inhibition.

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.

Amino Acid Oxidoreductases↗
PubMed1994

Thromboxane synthetase inhibition and thromboxane receptor blockade preserve pulmonary and circulatory function in a porcine burn sepsis model.

BACKGROUND: Thromboxane A2 (TxA2) is a key mediator in the pathophysiology of severe burns and sepsis. This study was performed to assess the potential benefits of TxA2 synthetase inhibition and TxA2 receptor blockade in sepsis after severe thermal injury. STUDY DESIGN: Pigs with left atrial, aortic, and pulmonary artery catheters received a 40 percent third-degree burn and, 24 hours later, 100 micrograms per kg Escherichia coli endotoxin. The antagonist treatment (BM) group was treated with the TxA2 receptor antagonist BM 13.177, the synthetase treatment (OKY) group with the TxA2 synthetase inhibitor OKY-046, and the control group received saline solution placebo. Another group without burn or endotoxin was used to assess the side effects of BM 13.177. RESULTS: Both drugs significantly attenuated the changes in pulmonary vascular resistance index, cardiac index, arterial PO2, shunt, oxygen delivery, and oxygen consumption seen after endotoxin. However, cardiac index was significantly decreased in group BM before endotoxin. In healthy pigs, BM 13.177 decreased cardiac index and oxygen delivery and increased the pulmonary vascular resistance index. CONCLUSIONS: TxA2 synthetase inhibitors and TxA2 receptor blockers are potentially useful in sepsis after severe burns. Comparison between drugs was complicated by the adverse effects of the antagonist, and further investigation with other antagonists is needed.

Animals↗
PubMed1993

Thromboxane receptor blockade with BM 13,177 following toxic airway damage by smoke inhalation in sheep.

Thromboxane may play an important role in the pathogenesis of smoked mediated injury. We studied this possibility in 13 chronically instrumented sheep, which had the left lung exposed to smoke. BM 13,177, a thromboxane receptor antagonist, was given intravenously to six animals prior to smoke inhalation and during the experimental period. Seven animals received the vehicle. All animals were studied for 24 h under ventilatory support, then killed prior to harvesting lung tissue. Airway peak and plateau pressures in the vehicle-treated animals were elevated by 27% and 25% from baseline at 24 h post smoke inhalation. Concomitantly, the left pulmonary vascular resistance index rose continuously throughout the study period (baseline = 822 +/- 58; 24 h = 1819 +/- 84 dyn.s.cm-5.m2).BM 13,177 treatment completely prevented the rise in airway pressure, while the left pulmonary vascular resistance index was significantly attenuated (baseline = 726 +/- 79; 24 h = 1470 +/- 158 dyn.s.cm-5.m2) resulting in a significantly higher percentage of cardiac output being delivered to the smoked lung, compared to vehicle-treated animals. Thromboxane receptor blockade did not prevent smoke induced pulmonary edema formation. There was likewise no effect of BM 13,177 on the systemic hemodynamic changes seen following smoke inhalation. There was a decrease in cardiac index and an increase in systemic vascular resistance index in both groups. We conclude that smoke induced changes in airway and pulmonary vascular resistances may be mediated by thromboxanes. However, thromboxanes appear to play no role in the development of pulmonary edema and elevation of systemic vascular resistance following smoke inhalation injury.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Clinical detection of LPS and animal models of endotoxemia.

The interest in the study of endotoxemia in the clinical area has increased recently as a result of a) improved and simplified endotoxin determination e.g. chromogenic-kinetic microplate methods (also an improved blood sampling tool is available), b) incidence of sepsis has increased due to improvement in early (e.g. posttraumatic) survival, c) interest in and good evidence for gut translocation as a source of endotoxemia, d) agents have developed, which can antagonize endotoxins. There is evidence that patients with positive endotoxin test in the ICU have a higher incidence of organ failure. To study the pathophysiological consequences of endotoxemia and possible ways of intervention animal models are necessary. The choice of the experimental setting depends on the aim of the study e.g. whether prolonged observation is necessary in survival studies or whether hemodynamic variables have to be measured or whether therapeutic agents only crossreact with primates. Since LPS levels are quite low in clinical studies, an important factor for selection of a relevant animal might be LPS sensitivity, or the use of additional sensitization techniques e.g. galactosamine. Another important aspect in this context is whether LPS is given as bolus or infused up to several days. In this review the dose, time, and route of LPS administration is also discussed. For screening purposes rodents are usually used, or sometimes rabbits due to their higher LPS sensitivity. Another very sensitive animal model is the sheep, which can be chronically instrumented and as a specialty allows lung lymph drainage and thus studies of LPS effects on pulmonary permeability. Pigs are used for hemodynamic studies and often in therapeutical studies if species-specificity of the drug tested is not important, in cases where a large animal is necessary. Finally the non-human primates offer a number of advantages due to human-like physiology, due to the cross-reactivity of human assay systems and accordingly also cross-reactivity of human therapeutic agents. While the chimpanzee also shares the LPS sensitivity of humans, baboons are insensitive like rodents. Thus each model serves to provide some useful purpose and the selection must be made to meet the requirements of the specific questions to be asked, with special emphasis of the chosen endotoxin model on relevance for the human sepsis state.

Animals↗
PubMed1993

Heparin in experimental hyperdynamic sepsis.

OBJECTIVE: To evaluate the hypothesis that heparin administration increases cardiac output and improves oxygenation in experimental hyperdynamic sepsis in sheep. DESIGN: Prospective trial. SETTING: Laboratory at a large university-affiliated medical center. SUBJECTS: A total of 14 sheep weighing 28 to 44 kg. INTERVENTIONS: All 14 chronically instrumented sheep received a continuous infusion of Escherichia coli endotoxin (10 ng/kg/min) over 24 hrs. Seven sheep received a fixed bolus of beef lung heparin (5000 units) every 4 hrs intravenously. The other seven sheep served as controls. MEASUREMENTS AND MAIN RESULTS: The heparinized animals showed a triphasic cardiovascular response. Cardiac index increased (p < .05), and systemic vascular resistance index decreased (p < .05) at 2 hrs after the start of the endotoxin infusion (early phase, 0 to 2 hrs). Both variables returned to approximately baseline levels at 4 hrs (second period, 2 to 4 hrs). A hyperdynamic state (in terms of an increased cardiac index), a decreased systemic vascular resistance index, and a decreased mean arterial pressure (MAP) (p < .05 for all) was observed in the third phase (8 to 24 hrs). In the control group, cardiac index, systemic vascular resistance index, and MAP showed no changes in the first period, but a slight decrease in cardiac index and a slight increase in systemic vascular resistance index in the second period. The onset of the hyperdynamic state was less pronounced in the control group and cardiac index was lower (p < .05); likewise, systemic vascular resistance index was increased (p < .05) when compared with heparinized animals. Both groups developed pulmonary hypertension during the endotoxin infusion. The gas exchange in the heparin group was significantly impaired in the first and second periods, but returned to baseline levels in the hyperdynamic phase, whereas the oxygenation of the nonheparinized animals showed only minor changes in the first and second phases, but deteriorated significantly during the third phase of endotoxemia. CONCLUSIONS: In this experimental model of hyperdynamic sepsis, heparin significantly influenced the cardiopulmonary performance. Heparin preserved gas exchange and increased cardiac output but lowered systemic vascular resistance and MAP in the hyperdynamic state.

Animals↗
PubMed1993

Exaggerated cardiopulmonary response after bacteremia in sheep with week-old thermal injury.

OBJECTIVE: To determine if thermal injury impairs pulmonary intravascular clearance of bacteria and therefore leads to exaggerated cardiopulmonary dysfunction in sheep, since endotoxin infusion has been previously shown to induce more severe pulmonary injury after thermal injury. DESIGN: Prospective, unblinded, randomized, controlled trial. SETTING: Laboratory at a large university medical center. INTERVENTIONS: Chronically instrumented, anesthetized sheep received a 40% total body surface area, third-degree thermal injury. Live Pseudomonas aeruginosa (10(7) P. aeruginosa/min for 1 hr; n = 6) were infused 7 to 10 days after thermal injury. Similarly prepared noninjured sheep received the same pseudomonas infusion (n = 7) or saline (n = 7). MEASUREMENTS AND MAIN RESULTS: Bacterial clearance, which measures phagocytosis by the pulmonary intravascular macrophages, was equally efficient in intact sheep and sheep with thermal injury. Pulmonary hypertension persisted for 18 hrs after thermal injury, compared with 8 hrs in noninjured sheep. Lung lymph flow significantly increased from 6 to 8 hrs in only the thermal injury group. Both bacteremic groups developed a hyperdynamic circulation from 6 to 8 hrs, but cardiac index was 1 to 1.5 L/min/m2 higher in thermally injured sheep. Total peripheral resistance index decreased significantly from 6 to 24 hrs in thermally injured sheep and from 6 to 12 hrs in intact bacteremic sheep. Mean arterial pressure of thermally injured sheep was increased at baseline and for the first 6 hrs compared with noninjured animals. Mean arterial pressure decreased from 6 to 24 hrs in sheep with thermal injury but did not change in intact bacteremic sheep. CONCLUSIONS: Bacterial clearance was not impaired by preceding thermal injury in sheep. Bacteremia in the presence of a preexisting thermal injury led to more persistent pulmonary hypertension and an exaggerated hyperdynamic circulation.

Animals↗
PubMed1993

Postburn gastrointestinal vasoconstriction increases bacterial and endotoxin translocation.

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.

Animals↗
PubMed1993

Left ventricular performance during continuous endotoxin-induced hyperdynamic endotoxemia in sheep.

Cardiac function was studied in an unanesthetized ovine model of hyperdynamic endotoxemia. Sixteen sheep were instrumented with ultrasonic crystals on the left ventricle to measure changes in its external diameter, a pressure transducer in the left ventricle, and aortic and Swan-Ganz catheters. The animals received either Escherichia coli endotoxin [lipopolysaccharide (LPS), 10 ng.kg-1.min-1; LPS group, n = 10] or an equivalent amount of 0.9% NaCl (sham group, n = 6). Between 1 and 8 h after LPS, a hypodynamic state with low cardiac output ensued (LPS 5.0 +/- 0.2 vs. sham 6.3 +/- 0.4 l.min-1.m-2). During this period, the end-systolic pressure-diameter relationship, a sensitive index of myocardial contractility, was reduced (LPS 10.4 +/- 1.2 vs. sham 17.2 +/- 0.8 mmHg/mm). After this first phase, the sheep developed a persistent hyperdynamic state characterized by a significant increase in cardiac output. By 24 h after LPS administration, the cardiac output was 10.1 +/- 0.5 l.min-1.m-2 (sham 6.3 +/- 0.3). Despite the marked elevation of cardiac output, the end-systolic pressure-diameter relationship had fallen to 8.5 +/- 0.9 mmHg/mm (sham 16.0 +/- 1.2). In a model of hyperdynamic state, an increased cardiac output occurs despite a significant depression in myocardial contractility.

Animals↗
PubMed1993

Pulmonary transvascular fluid flux and cardiovascular function in sheep with chronic sepsis.

We studied the mechanisms responsible for the changes in lung lymph flow (QL) in chronic sepsis induced by the continuous infusion of endotoxin [lipopolysaccharide (LPS), 10 ng.kg-1.min-1]. Sheep (n = 11) were studied in the unanesthetized state 7 days after preparation, and cardiopulmonary variables were measured. In the control group (n = 5) given lactated Ringer solution, no significant changes were observed in any measured variables. In the LPS group (n = 6), QL increased from 11.7 +/- 3.8 to 54.0 +/- 15.0 (SE) ml/h 24 h after LPS infusion had begun. This elevation in QL was associated with little or no change (P > 0.05) in reflection coefficient (0.80 +/- 0.03 to 0.87 +/- 0.05) or pulmonary microvascular pressure (14.3 +/- 0.4 to 16.7 +/- 1.2 mmHg). The filtration coefficient, however, was significantly elevated (0.018 +/- 0.006 to 0.083 +/- 0.024 ml.min-1.mmHg-1). In association with changes in QL that occur as a result of LPS administration, there was a significant increase in cardiac index (6.1 +/- 0.5 to 10.2 +/- 0.3 l.min-1.m-2) and a reduction in mean arterial pressure (90.2 +/- 4.4 to 73.7 +/- 7.3 mmHg) and systemic vascular resistance index (1,229 +/- 134 to 583 +/- 62 dyn.s.cm-5.m2), findings similar to those noted in septic humans.

Animals↗
PubMed1993

Effects of halothane anesthesia on vasoconstrictor response to NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis, in sheep.

This study tests the hypothesis that halothane-induced inhibition of the endothelium-derived relaxing factor/nitric oxide (EDRF/NO) pathway significantly contributes to cardiovascular performance and thus reduces the vasoconstrictor response to NO synthesis inhibitors in vivo. We determined the effects of the administration of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in chronically instrumented, halothane-anesthetized sheep and in awake control animals. Six sheep underwent halothane anesthesia (1.5 vol%) with mechanical ventilation. Five sheep were studied in the awake state with spontaneous breathing. Both groups received a bolus of L-NAME (25 mg/kg), followed 4 h later by L-arginine (300 mg/kg) to reverse the effects of L-NAME. L-NAME administration caused a significant increase in pulmonary and systemic vascular resistance (P < 0.05) in both groups. However, L-NAME produced a sharp increase in mean arterial and pulmonary artery pressures only in the control group, whereas the pressor response in the halothane group was attenuated. Cardiac output, which was significantly lower after L-NAME administration in both groups, increased after L-arginine. The results suggest that halothane does not significantly alter the EDRF/NO-mediated effects on the vasculature but potentiates the cardiac depressant effect of L-NAME.

Anesthesia, Inhalation↗