Search PubMed⌕ Search

Biomedical subjects

D L Traber

Publications and source records attributed to D L Traber.

At least 73 records · Page 4Linked to original sources
PubMed1997

Glucose kinetics in interstitial fluid can be predicted by compartmental modeling.

The purposes of this study were to define in sheep a compartmental model for glucose kinetics in the basal condition and to test the hypothesis that interstitial fluid obtained by sampling thoracic duct lymph (TDL) represents one or more peripheral compartments of the glucose model. A bolus of [6,6-(2)H]glucose was injected in nine animals, followed by frequent sampling of blood and TDL. Linear kinetic modeling has been applied to plasma data, indicating that a three-compartment model adequately describes glucose kinetics. Both catenary and mammillary models were identified, and their predictions for the tracer behavior in nonaccessible pools were evaluated. In all experiments, regardless of the model structure, predictions in the compartment most rapidly exchanging with blood (pool 2) well matched the measured tracer-to-tracee ratio in TDL. Furthermore, modeling analysis showed that 90-95% of the tracer in TDL comes from this pool. This supported the physiological identification of a peripheral pool of glucose kinetics as extracellular fluid represented by TDL measurements.

Animals↗
PubMed1997

A dynamic model of ventricular interaction and pericardial influence.

A mathematical model describing the dynamic interaction between the left and the right ventricle over the complete cardiac cycle is presented. The pericardium-bound left and right ventricles are represented as two coupled chambers consisting of the left and right free walls and the interventricular septum. Time-varying pressure-volume relationships characterize the component compliances, and the interaction of these components produces the globally observed ventricular pump properties (total chamber pressure and volume). The model 1) permits the simulation of passive (diastolic) and active (systolic) ventricular interaction, 2) provides temporal profiles of hemodynamic variables (e.g., ventricular pressures, volumes, and flow) that agree well with reported observations, and 3) can be used to examine the effect of the pericardium on ventricular interaction and ventricular mechanics. It can be reduced to equivalency with models previously reported by invoking simplifying assumptions. Furthermore, model-generated "dynamic interaction gains" are employed to quantify the mode and degree of ventricular interaction. The model also yields qualitative predictions of septal and free wall displacements similar to those detected experimentally via M-mode echocardiography. Such analogies may be extended easily to the study of pathophysiological states via appropriate modifications to 1) the pressure-volume characteristics of the component walls (and/or pericardium) and/or 2) the specific time course of activation of the ventricular free wall or the septum. A limited number of examples are included to demonstrate the utility of the model, which may be used as an adjunct to new experimental investigations into ventricular interaction.

Blood Volume↗
PubMed1997

Acute alterations in growth hormone-insulin-like growth factor axis in humans injected with endotoxin.

The purpose of the present study was to characterize the acute changes in the insulin-like growth factor (IGF) system in humans after administration of endotoxin (lipopolysaccharide; LPS). Escherichia coli LPS (4 ng/kg) was injected intravenously into healthy adults, and serial blood samples were collected for the next 5 h; subjects injected with saline served as time-matched controls. LPS administration resulted in a gradual decrease in the total extractable IGF-I concentration, which was reduced by approximately 20% over the final 2 h of the experiment; levels of free IGF-I were not significantly altered. LPS also produced a marked but transient elevation in growth hormone (GH) concentration. IGF-binding protein (BP)-1 levels were elevated more than fivefold 2 h after LPS injection, and thereafter levels gradually returned toward baseline. IGFBP-2 concentration also increased after LPS injection, but the maximal increase (approximately 50% above basal) was observed during the final 2 h of the protocol. In contrast, IGFBP-3 levels did not vary over the period examined in response to LPS, and there was no apparent increase in number of BP-3 proteolytic fragments. Cortisol levels were increased early and remained two- to threefold above baseline throughout the protocol. No significant alterations in serum concentration of glucose or insulin were noted. LPS also produced an early elevation in tumor necrosis factor and a later increase in interleukin-6. These data indicate that the acute changes in the GH-IGF axis in humans in response to LPS are comparable with those observed in humans in other traumatic conditions and in animal models of endotoxemia and infection.

Adolescent↗
PubMed1997

Nitric oxide and endothelial permeability.

Nitric oxide synthase inhibition reverses systemic vasodilation during sepsis but may increase endothelial permeability. To assess adverse effects on the pulmonary vasculature, 12 sheep were chronically instrumented with lung lymph fistulas and hydraulic pulmonary venous occluders. Escherichia coli endotoxin (lipopolysaccharide; 10 ng . kg-1 . min-1) was continuously infused for 32 h. After 24 h, six animals received 25 mg/kg of Nomega-nitro-L-arginine methyl ester (L-NAME), and six received saline. All sheep developed a hyperdynamic circulatory response and elevated lymph flows by 24 h of lipopolysaccharide infusion. L-NAME reversed systemic vasodilation, increased pre- and postcapillary pulmonary vascular resistance index, pulmonary arterial pressure, and, transiently, effective pulmonary capillary pressure. Lung lymph flows were not different between groups at 24 h or thereafter. Calculated as changes from baseline, however, lung lymph flow was higher in the L-NAME group than in the control animals, with a trend toward lower lymph-to-plasma protein concentration ratio at 25 h. Permeability analysis at 32 h by the venous occlusion technique showed normal reflection coefficients and elevated filtration coefficients without differences between groups. Reversal by L-NAME of the systemic vasodilation during endotoxemia was associated with high pulmonary vascular resistance without evidence of impaired pulmonary endothelial barrier function.

Animals↗
PubMed1997

Nitric oxide synthase inhibition restores hypoxic pulmonary vasoconstriction in sepsis.

Hypoxic pulmonary vasoconstriction (HPV) is inhibited by inhaled nitric oxide (NO) in healthy animals and is blunted in endotoxemia. We investigated whether the loss of HPV during sepsis could be reversed by NO synthase (NOS) inhibition. Hypoxic challenges were induced in intubated, awake sheep breathing 100% nitrogen to the left lung and 100% oxygen to the right lung. HPV was assessed as the decrease in left pulmonary blood flow during hypoxia, measured with an ultrasonic flow probe around the left pulmonary artery. Group I (n = 5) received carrier solutions and Groups II (n = 6) and III (n = 8) received an infusion containing Pseudomonas aeruginosa. After 24 h, Group III also received an infusion of 6.6 mg.kg.h-1 N omega-monomethyl-L-arginine (L-NMMA). After 24 h of sepsis, HPV decreased from 60 +/- 9% in Group II and 56 +/- 4% in Group III to 27 +/- 2% and 26 +/- 4%, respectively. Group I showed no change in HPV. During infusion of L-NMMA, HPV increased to 38 +/- 4%. Pulmonary shunt during hypoxia increased in Group III to 161 +/- 10% of its baseline value, and decreased to 121 +/- 11% during infusion of L-NMMA. We conclude that L-NMMA improves but does not restore HPV, indicating that other vasodilatory mediators besides NO also influence HPV in sepsis.

Animals↗
PubMed1997

Heparin attenuated neutrophil infiltration but did not affect renal injury induced by ischemia reperfusion.

Although heparin is better known as an anticoagulant, it also has several anti-inflammatory effects. Heparin is known to inhibit neutrophil adhesion, chemotaxis and oxygen free radical production. In addition, heparin is also known to act as an oxygen radical scavenger. Our hypothesis was that heparin would attenuate renal ischemia reperfusion injury. In this study, we investigated whether heparin had a protective effect on renal ischemia reperfusion injury. Sheep (n = 12) were prepared for the chronic study with venous, arterial and urinary catheters inserted. In addition, pneumatic occluders and ultrasonic flow probes were placed on renal arteries. After a 5-day recovery period, the sheep were randomized to either a heparin treatment group (400 IU/kg i.v. bolus 10 minutes before renal artery occlusion, followed by a continuous effusion 25,000 IU in 250 ml of 0.9% NaCl at 10 ml/hr, n = 6) or a control group (n = 6), which received an equivalent volume of 0.9% NaCl. All the sheep then underwent 90 minutes of bilateral renal ischemia followed by 24 hours of reperfusion. Blood urea nitrogen (BUN), serum creatinine (Scr), and creatinine clearance (CrCl) were determined at various intervals during both the ischemic and reperfusion periods. Kidney tissue samples were obtained at autopsy for histologic examination. As a result, there were significant differences in the degree of inflammation (1.50 +/- 1.24 Vs 0.50 +/- 0.79, P < 0.05) between the control and heparin treatment groups, but not in the degree of injury (2.83 +/- 0.44 Vs 2.33 +/- 0.28). In this study, heparin significantly attenuated polymorphonuclear leukocytes (PMNs) infiltration within the interstitium, but it did not affect the degree of renal damage as measured by urinary chemistries or renal tubular damage as assessed by histopathologic evaluation.

Animals↗
PubMed1997

Renal ischemia-reperfusion injury does not induce pulmonary dysfunction in sheep.

It has already been shown that pulmonary injury is induced after intestinal or hind limb ischemia-reperfusion injury. The purpose of this study was to determine the effect of renal ischemia-reperfusion injury on the pulmonary system. We compared the pulmonary effects of 60 and 90 minutes ischemia followed by 24 hour reperfusion in sheep kidneys. Standard hemodynamic measurements, arterial and mixed venous blood gas analysis, urine output, creatinine clearance, and blood urea nitrogen concentration were measured at baseline, during ischemia and reperfusion periods. After 24 hours of reperfusion, animals were sacrificed and underwent autopsy with collection of samples for wet/dry lung-weight ratio, lung tissue conjugated dienes, and renal histology. As expected, renal ischemia resulted in an increased serum creatinine and blood urea nitrogen concentrations, decreased creatinine clearance, and histological evidence of renal damage. There was no evidence of pulmonary hypertension or hypoxemia during renal ischemia-reperfusion. There was also no significant difference in the wet/dry lung-weight ratios or lung tissue conjugated denies between the two ischemic groups (60 and 90 minutes) and nonischemic control group. These results suggest that renal ischemia-reperfusion injury was not associated with a significant degree of pulmonary dysfunction.

Animals↗
PubMed1996

The effects of propofol on hemodynamics and renal blood flow in healthy and in septic sheep, and combined with fentanyl in septic sheep.

Sepsis is characterized by myocardial depression and systemic vasodilation, both of which are most likely mediated by nitric oxide. Propofol inhibits nitric oxide synthase and may therefore be beneficial in sepsis. On the other hand, renal blood flow, known to be only minimally affected by propofol in healthy subjects, may be drastically reduced in septic individuals, because the renal microvasculature is known to be very sensitive to nitric oxide. In this study, the effects of propofol in healthy and in septic sheep, and in combination with fentanyl, were analyzed and compared with nonanesthetized septic sheep. In healthy sheep, propofol caused only minor hemodynamic changes. In septic sheep, however, hemodynamics deteriorated. Renal blood flow was reduced to 60% +/- 10% of the preseptic baseline and to 39% +/- 4% of the septic value. This reduction was selective, since the cardiac output decreased significantly less. These adverse effects of propofol on hemodynamics and renal blood flow were reduced when propofol was combined with fentanyl.

Adjuvants, Anesthesia↗
PubMed1996

Nitric oxide synthase inhibition during experimental sepsis improves renal excretory function in the presence of chronically increased atrial natriuretic peptide.

OBJECTIVE: To test whether renal excretory function decreases after nitric oxide synthase inhibition during experimental hyperdynamic sepsis. DESIGN: Prospective, randomized, controlled animal trial. SETTING: Research laboratory at a large university medical center. SUBJECTS: Chronically instrumented Merino breed ewes (n = 18). INTERVENTIONS: Continuous infusion of Escherichia coli endotoxin (10 ng/kg/min) for the experimental period of 32 hrs. One group received a bolus of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (25 mg/kg), after 24 hrs, and the remaining sheep were given the carrier, sodium chloride 0.9%. MEASUREMENTS AND MAIN RESULTS: The sheep developed a hyperdynamic cardiovascular response characterized by a decrease in systemic vascular resistance index (p < .05), and an increased cardiac index (p < .05) by 24 hrs. The sheep retained fluid, with creatinine clearance decreasing in the presence of chronically increased atrial natriuretic peptide. After the administration of N omega-nitro-L-arginine methyl ester, systemic vascular resistance index and cardiac index returned to baseline values, fluid balance normalized, and glomerular filtration rate increased (p < .05), while the control animals continued to retain fluid and their creatinine clearance continued to decrease. The concentrations of atrial natriuretic peptide did not differ significantly between groups after N omega-nitro-L-arginine methyl ester administration. CONCLUSIONS: In this ovine model of experimental hyperdynamic sepsis, renal excretory function decreases in the presence of chronically increased concentrations of atrial natriuretic peptide. Administration of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester, reverses the vasodilatory state, thereby improving fluid balance and glomerular filtration.

Animals↗
PubMed1996

Correction of blood pH attenuates changes in hemodynamics and organ blood flow during permissive hypercapnia.

OBJECTIVES: To determine whether changes in cardiac output, regional blood flow, and intracranial pressure during permissive hypercapnia are blood pH-dependent and can be attenuated by correction of intravascular acidemia. DESIGN: Prospective, controlled study. SETTING: Research laboratory. SUBJECTS: Female Marino ewes. INTERVENTIONS: Animals were instrumented with a pulmonary artery catheter, femoral arterial and venous catheters, a catheter in the third cerebral ventricle, and ultrasonic flow probes on the left carotid, superior mesenteric, and left renal arteries 1 wk before experimentation. At initiation of the protocol, ewes underwent endotracheal intubation and mechanical ventilation under general anesthesia. Minute ventilation was reduced to induce hypercapnia with a target PaCO2 of 80 torr (10.7 kPa). In the pH-uncorrected group (n = 6), arterial blood pH was allowed to decreased without treatment. In the pH-corrected group (n = 5), 14.4 mEq/kg of sodium bicarbonate was given intravenously as a bolus to correct arterial blood pH toward a target arterial pH of 7.40 (dose calculated by the Henderson-Hasselbalch equation). MEASUREMENTS AND MAIN RESULTS: Arterial blood pH, PCO2, cardiac output, intracranial pressure, and carotid, superior mesenteric, and renal artery blood flow rates were measured at normocapnic baseline and at every hour during hypercapnia for 6 hrs. In the pH-uncorrected group, arterial blood pH decreased from 7.41 +/- 0.03 at normocapnia to 7.14 +/- 0.01 (p < .01 vs. normocapnia) as blood PCO2 increased to 81.2 +/- 1.8 torr (10.8 +/- 0.2 kPa). In the pH-corrected group, arterial blood pH was 7.42 +/- 0.02 at normocapnia and was maintained at 7.37 +/- 0.01 while PaCO2 was increased to 80.3 +/- 0.9 torr (10.7 +/- 0.1 kPa). Significant increases in cardiac output occurred with the initiation of hypercapnia for both groups (pH-uncorrected group: 4.3 +/- 0.6 L/min at normocapnia vs. 6.8 +/- 1.0 L/min at 1 hr [p < .05]; pH-corrected group: 4.1 +/- 0.4 at normocapnia vs. 5.7 +/- 0.4 L/min at 1 hr [p < .05]). However, this increase was sustained only in the uncorrected group. Changes in carotid and mesenteric artery blood flow rates, as a percent of baseline values, showed sustained significant increases in the pH-uncorrected groups (p < .05) and only transient (carotid at 1 hr) or no (superior mesenteric) significant change in the pH-corrected groups. Conversely, significant increases in renal artery blood flow were seen only in the pH-uncorrected group during the last 2 hrs of the experiment (p < .05). Organ blood flow, as a percent of cardiac output, did not change significantly in either group. Intracranial pressure increased significantly in the pH-uncorrected group (9.0 +/- 1.5 mm Hg at normocapnia vs. 26.8 +/- 5.1 at 1 hr, p < .05), and remained increased, while showing no significant change in the pH-corrected group (8.5 +/- 1.6 mm Hg at normocapnia to 7.7 +/- 4.2 at 1 hr). CONCLUSIONS: Acute hypercapnia, induced within 1 hr, is associated with significant increases in cardiac output, organ blood flow, and intracranial pressure. These changes can be significantly attenuated by correction of blood pH with the administration of sodium bicarbonate, without adverse effects on hemodynamics.

Acute Disease↗
PubMed1996

Nitric oxide synthase inhibition versus norepinephrine for the treatment of hyperdynamic sepsis in sheep.

OBJECTIVES: To investigate the effects of Nomega-mono-methyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthesis, on hemodynamics, oxygen transport, and regional blood flow in an ovine model of hyperdynamic sepsis and to compare these effects with the responses to norepinephrine. DESIGN: Prospective, nonrandomized, controlled experimental study with repeated measures. SETTING: Investigational intensive care unit at a university medical center. SUBJECTS: Twenty-five female, healthy, adult sheep of the Merino breed, divided into three groups: nine control sheep; eight sheep treated with L-NMMA; and eight sheep treated with norepinephrine. INTERVENTIONS: All sheep were chronically instrumented. After a 5-day recovery period, a continuous infusion of live Pseudomonas aeruginosa (2.5 x 10(6) colony-forming units/min) was started and maintained for the remainder of the experiment. After 24 hrs of sepsis, eight sheep received L-NMMA (7 mg/kg/hr), eight sheep received norepinephrine, and nine sheep received the vehicle alone (0.9% saline). The norepinephrine dosage was continuously and individually adjusted to achieve the same increase in blood pressure as was observed in a matched sheep of the L-NMMA group. MEASUREMENTS AND MAIN RESULTS: After 24 hrs of sepsis, all sheep developed a hyperdynamic circulatory state with increased cardiac indices and reduced arterial pressures, and systemic vascular resistances. L-NMMA reversed the hyperdynamic circulation, causing an increase in arterial pressure by peripheral vasoconstriction. Norepinephrine led to an increase in blood pressure by augmenting cardiac indices, leaving the systemic vascular resistance unaffected. The norepinephrine dose needed to keep the blood pressure high had to be continuously increased, reflecting the reduced vascular responsiveness to catecholamines during sepsis. Renal blood flow remained unaffected by all treatment forms. Norepinephrine and L-NMMA led to a dramatic increase in urine production. Blocking the nitric oxide synthase with L-NMMA did not interfere with the host's pulmonary ability to clear bacteria, nor did treatment with norepinephrine. CONCLUSIONS: Blocking nitric oxide synthase had a marked vasoconstrictive effect. Both norepinephrine and L-NMMA increased arterial pressure without reducing renal blood flow, leading to an improved renal function.

Animals↗
PubMed1996

Effects of inhaled nitric oxide and nebulized prostacyclin on hypoxic pulmonary vasoconstriction in anesthetized sheep.

OBJECTIVES: Inhaled nitric oxide has been shown to be a selective pulmonary vasodilator, leading to reduced pulmonary arterial pressure and improved ventilation/perfusion ratio in the acute respiratory distress syndrome. This local pulmonary vasodilation theoretically can be achieved by the airway application of a short-acting vasodilator, such as prostacyclin. We hypothesized that nebulized prostacyclin has the same properties for selective pulmonary vasodilation as inhaled nitric oxide. DESIGN: Prospective, experimental study in sheep. SETTING: Investigational intensive care unit in a university hospital. SUBJECTS: Six adult ewes of the Merino breed. INTERVENTIONS: Sheep (n = 6) were surgically prepared for chronic study. After 5 days of recovery, the sheep had tracheostomies performed under anesthesia. Intubation with a modified Robert-Shaw tube allowed side-separated ventilation. The entire left lung was ventilated with pure nitrogen, whereas the right lung was ventilated with pure oxygen. Nitric oxide and prostacyclin were added in different concentrations to the nitrogen, with which the left lung was ventilated. MEASUREMENTS AND MAIN RESULTS: The blood flows to the left and right lungs were measured with ultrasonic flow probes on the common and left pulmonary artery. Measurements were taken after each compound had been administered for 10 mins at a predefined dose. Both inhaled nitric oxide and nebulized prostacyclin caused effective, selective, dose-dependent pulmonary vasodilation. Inhaled nitric oxide was able to abolish hypoxic pulmonary vasoconstriction when insufflated into the animals at a concentration of 50 ppm of nitrogen, but 100 ppm of nitric oxide had no further effect. Prostacyclin, at a dosage of 10 micrograms/min, showed maximum pulmonary vasodilation, which could not be further increased by doubling the dosage. However, prostacyclin produced less dilation than high doses of nitric oxide, and its maximum pulmonary vasodilation was comparable with that effect obtained under ventilation with 20 ppm of nitric oxide. CONCLUSIONS: Both drugs selectively dilated the pulmonary vasculature in ventilated alveoli. Prostacyclin nebulization is an excellent tool to reduce pulmonary hypertension and to improve the ventilation/perfusion ratio. Prostacyclin nebulization can be used without the highly sophisticated technical equipment that is needed for controlled nitric oxide inhalation, and may therefore become a new, noninvasive therapeutic approach for treatment of adult respiratory distress syndrome in hospitals that cannot provide nitric oxide inhalation.

Administration, Inhalation↗
PubMed1996

Burn resuscitation: crystalloid versus colloid versus hypertonic saline hyperoncotic colloid in sheep.

OBJECTIVES: The present study was undertaken to assess the fluid balance and hemodynamic effects during the first 8 hrs of resuscitation in animals with a large body surface area burn, using lactated Ringer's solution, 6% hetastarch, and hypertonic saline dextran. DESIGN: A prospective, blinded, controlled, terminal study, using anesthetized animals. The initial baseline period was followed by scald injury, and three different treatment regimens were administered from coded bags to achieve a physiologic end point. SETTING: University laboratory. SUBJECTS: Eighteen female sheep (35 to 45 kg) were anesthetized with isoflurane. INTERVENTIONS: Test solutions (10 mL/kg of either lactated Ringer's solution, hetastarch, or hypertonic saline dextran) were infused 30 mins after the scald injury at a rate to restore and maintain the baseline oxygen delivery (DO2) value. MEASUREMENTS AND MAIN RESULTS: Cardiovascular hemodynamics, plasma sodium concentration, plasma colloid osmotic pressure, and fluid balance were measured before and after scalding and resuscitation. After the initial 10-mL/kg test solution dose was given, lactated Ringer's solution was infused to achieve the same end point of baseline DO2 for the remainder of the 8 hrs. The scald caused an initial 30% reduction in cardiac output, a 20% reduction in mean arterial pressure, and 10% to 15% increase in hematocrit. All three test solutions restored and maintained baseline DO2 within 1 hr. However, hetastarch and hypertonic saline dextran reduced the net fluid volume over 8 hrs by 48% and 74%, respectively, compared with lactated Ringer's solution. Edema in the burn wound was not affected by treatment, while hypertonic saline dextran reduced edema in nonburned skin compared with both lactated Ringer's solution and hypertonic saline dextran. Plasma colloid osmotic pressure was significantly higher in the hetastarch and hypertonic saline dextran groups. A continuous decrease in plasma sodium concentrations from baseline values (140 to 145 mmol/L) was measured in the lactated Ringer's solution and hetastarch groups (130 to 133 mmol/L) over 8 hrs. Plasma sodium concentrations in the group receiving hypertonic saline dextran were increased (150 to 155 mmol/L) at 4 hrs, but returned toward baseline by 8 hrs. CONCLUSIONS: Net volume loading can be reduced markedly by initial resuscitation of large body surface area burn injury using a colloid (hetastarch), and can be further reduced by use of hypertonic saline colloid. Hyponatremia was apparent in the isotonic crystalloid- and colloid-treated animals, but not in those animals treated with hypertonic saline colloid.

Animals↗
PubMed1996

Nitric oxide synthase inhibition versus norepinephrine in ovine sepsis: effects on regional blood flow.

Hypotension is a serious problem in septic patients. We investigated regional perfusion in several organs during treatment of hyperdynamic sepsis in sheep. Sepsis was induced and maintained for the entire experiment with a continuous infusion of live Pseudomonas aeruginosa. Treatment with either norepinephrine or the nitric oxide synthase inhibitor L omega-mono-methyl-arginine (L-NMMA) was begun after 24 h of sepsis and continued for 24 h. The norepinephrine dosage was adjusted to achieve the same increase in mean arterial pressure as that obtained by a fixed dose of L-NMMA (7 mg/kg/h). Blood flows were analyzed by the microsphere technique. Both compounds restored blood pressure effectively, but only L-NMMA caused a significant increase in systemic vascular resistance, concomitant with a significant fall in cardiac output. Sepsis caused an increase in myocardial blood flow and a redistribution of blood flow away from the pancreas and the stomach. Renal blood flow was not significantly elevated. During treatment with either compound, renal blood flow remained unchanged, despite a fall in cardiac output in the L-NMMA group. Unchanged renal blood flow combined with the restoration of arterial blood pressure caused a significant increase in urine output. Both L-NMMA and norepinephrine caused a redistribution of blood flow to the colon. Pancreatic blood flow was further reduced by L-NMMA but the oxygen extraction improved simultaneously, so that oxygen availability in the pancreas might have been unchanged. Because ischemic pancreatitis in sepsis is likely to trigger multiorgan failure, further investigations in that area are desirable.

Animals↗
PubMed1996

Changes in regional hemodynamics after nitric oxide inhibition during ovine bacteremia.

We studied the action of nitric oxide synthase (NOS) inhibition on changes in regional blood flow during a continuous infusion of live bacteria. Eighteen ewes were chronically instrumented. After a 7-day recovery period, an infusion of 10(6) colony-forming units/min Pseudomonas aeruginosa was begun. At 24 h, cardiac output increased significantly above baseline in all groups (5.9 +/- 0.4 vs. 8.2 +/- 0.6 l.min 1.m-2), systemic vascular resistance decreased (1,362 +/- 120 vs. 821 +/- 145 dyn.g.cm-5.m-2), and cerebral, cephalic mesenteric, and hindlimb blood flows increased. The animals were then equally and randomly assigned to a bolus of a NOS inhibitor, either 25 mg/kg N omega-nitro-L-arginine methyl ester (L-NAME) or 20 mg/kg N omega-monomethyl-L-arginine (L-NMMA), followed by a continuous infusion of 7 mg.kg-1.min-1 L-NMMA or saline. After NOS inhibition, cardiac index decreased [5.6 +/- 0.1 (L-NAME) and 5.5 +/- 0.4 l.min-1.m-2 (L-NMMA)] and remained significantly decreased for 12 h. 1-NAME decreased carotid and mesenteric blood flows to 64% of the preseptic baseline, and they remained below baseline for 20 h. L-NMMA decreased blood flows only to preseptic baseline values. NOS inhibitors may affect blood flows independently of their hemodynamic effects.

Animals↗
PubMed1996

Unilateral smoke inhalation in sheep: effect on left lung lymph flow with right lung injury.

We previously reported that smoke inhalation to the right lung will result in damage to the air-insufflated left lung. In this study we confirm these findings and determine whether this injury is associated with an elevation in lung lymph flow and pulmonary microvascular permeability to protein as indexed by changes in reflection coefficient. Sheep (n = 12) were surgically prepared by placement of a Swan-Ganz catheter and pneumatic occluders on all pulmonary veins and the left pulmonary artery. The left lung lymphatic was selectively cannulated as shown previously (Y. Kikuchi, H. Nakazawa, and D. Traber. Am. J. Physiol. 269 (Regulatory Integrative Comp. Physiol. 38): R943-R947, 1995). All afferent lymphatics from the right lung were severed, and the right pulmonary ligament was sectioned. The caudal end of the lymph node was sectioned to remove systemic lymph contamination. The sheep were studied in the unanesthetized state 7 days later. To ensure that lymph flow was exclusively from the left lung (QLL), right pulmonary microvascular pressure was increased, a procedure that resulted in little or no change in QLL, as was previously shown. The sheep were then anesthetized, and a Carlens tube was positioned to allow separate ventilation of the right and left lung. The right lungs of five sheep and the left lungs of two sheep were insufflated with cotton smoke. Insufflation of the left lung with cotton smoke produced a fourfold increase in QLL that began 4 h after insult. Insufflation of the right lung with smoke led to a doubling of QLL that began 12 h after insult. Changes in QLL were associated with increased microvascular permeability, as indexed by the reflection coefficient. Control sheep (air insufflated into both lungs, n = 5) showed no change in QLL. Injury to the right lung resulted in damage to the left air-insufflated lung, suggesting a hematogenous mediation of the response.

Animals↗