Hemodynamic changes associated with thermodilution cardiac output determination in canine acute blood loss or endotoxemia

Since the technique of thermodilution (TD) cardiac output measurement, per se, causes hemodynamic alterations, the author examined whether the alterations elicited by iced injectate are augmented in the presence of acute blood loss or endotoxemia, compromized conditions frequently associated with critically ill patients. Acute blood loss (N = 8) and endotoxemia (N = 8) were induced by withdrawing arterial blood approximately 20–30 ml kg^-1 over 30 min and by a slow intravenous infusion of E. coli endotoxin 2.5-3.0 mg kg^-l over 10 min, respectively, in anesthetized dogs. The magnitudes of decreases in mean arterial and pulmonary artery pressures during slowing of heart rate (HR) following injection of iced injectate 3 ml were slightly less in acute blood loss than in normovolemia, whereas in endotoxemia the degree of mean arterial pressure decrease during slowing of HR following iced injectate 3 ml was slightly less as compared with that before endotoxemia. However, the alterations in other hemodynamic variables following injection of iced injectate 3 ml were similar between dogs with and without acute blood loss or endotoxemia. No profound hemodynamic changes were observed during any TD cardiac output measurements under both conditions. Cardiac output estimated by TD correlated closely with pulmonary blood flow measured by electromagnetic flowmeter in endotoxemia (r > 0.9) but not during acute blood loss. These results indicate that TD cardiac output determination does not cause serious hemodynamic alterations in endotoxemia or acute blood loss, and can estimate right ventricular output accurately in endotoxemia but not in acute blood loss.     

The clearance capacity of the canine liver for a portal vein endotoxin infusion

The capacity of the livers of anesthetized dogs to clear a portal vein infusion of Escherichia coli 026 endotoxin was evaluated. Appearance of the endotoxin in arterial blood was quantitated by immunoradiometric assay. Various hemodynamic and metabolic parameters were monitored throughout the infusion to corroborate the development of systemic endotoxemia. Significant amounts of E. coli 026 endotoxin were detected in arterial blood after infusion of 240 micrograms endotoxin. As expected, systemic endotoxemia was associated with decreased cardiac index, mean arterial blood pressure, heart rate, and splanchnic (portal vein) blood flow. Changes in plasma levels of glucose, insulin, and glucagon and in the pancreatic outputs of insulin and glucagon did not occur before the development of severe hypotension and the termination of the study. It was concluded that the liver clearance capacity for endotoxin in the dog is 0.72 microgram/gm liver/hour and that severe hemodynamic alterations develop in this animal model before changes in carbohydrate balance.     

Effect of endotoxemia on hepatic portal and sinusoidal blood flow in rats

A decrease in liver blood flow leads to dysfunction of hepatocytes and Kupffer cells, with subsequent local and systemic liberation of proinflammatory mediators that may maintain systemic inflammatory response syndrome (SIRS) and may lead to multiple organ dysfunction syndrome (MODS). There is only limited knowledge on the hepatic micro- and macrocirculation during sepsis or endotoxemia. Therefore, the aim of our study was to investigate alterations in hepatic portal blood flow (PBF) and sinusoidal blood flow (SBF) during endotoxemia. In male Wistar rats endotoxemia was induced by continuous infusion of 2 mg/kg/h lipopolysaccharides from Escherichia coli 026:B6 immediately after baseline measurements (n = 8). The control group (n = 8) received an equivalent volume of Ringer's solution. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), PBF, and SBF were measured at baseline and 60 and 120 min after induction of endotoxemia. PBF was measured using an ultrasonic flow probe that was positioned around the portal vein. SBF was detected by in vivo videomicroscopy of the left liver lobe. In the LPS group MAP decreased, but CO remained at baseline values. During endotoxemia PBF decreased significantly from 23 +/- 3 to 15 +/- 4 mL/min (60 min) and 16 +/- 3 mL/min (120 min). SBF also significantly decreased to 68.5% (60 min) and 57.1% (120 min) of baseline value. Our results demonstrate that during early endotoxemia hepatic macro- and microcirculatory perfusion is significantly decreased despite unchanged CO. This early reduction of hepatic perfusion might be caused by an increased hepatic vessel resistance as a consequence of liberation of vasoconstrictive mediators or/and by a decrease in intestinal perfusion.     

Diets enriched with N-3 fatty acids ameliorate lactic acidosis by improving endotoxin-induced tissue hypoperfusion in guinea pigs.

The effect of 6 weeks dietary lipid manipulation on the acute physiologic response to 7-hour continuous endotoxin infusion in guinea pigs was examined. One diet was enriched with N-3 fatty acids, whereas the other contained N-6 fatty acids, primarily linoleic acid. Animals fed N-6 fatty acids developed significant lactic acidemia, microvascular muscle hypoperfusion, and pulmonary infiltrates in response to endotoxin infusion. N-3 fatty acid-fed animals demonstrated improved lactate levels, microvascular muscle perfusion, and lung morphology compared to N-6 fatty acid-fed animals after endotoxin infusion. There was no significant change in cardiac output, PaO2, or mean arterial blood pressure at the end of the endotoxin infusion in either group. Pretreatment with indomethacin, or BM 13505, a specific thromboxane A2 receptor blocker, ameliorated the development of metabolic acidosis in N-6 fatty acid-fed animals, demonstrating a role for prostanoids in the sequelae of endotoxemia. The ability of dietary pretreatment with N-3 fatty acids to influence favorably the physiologic response to endotoxin represents a novel nutrient-metabolic interaction with potential therapeutic implications.     

Milrinone improves intestinal villus blood flow during endotoxemia

PURPOSE: To determine whether the compromised intestinal villus blood flow in a rat model of endotoxemia could be improved by continuous infusion of the phosphodiesterase (PDE) inhibitor milrinone. METHODS: Twenty-four anesthetized and ventilated rats were laparotomized and an ileal portion was exteriorized and opened by an antimesenteric incision. The ileal segment was fixed with the mucosal surface upward. Microcirculatory parameters were assessed by intravital videomicroscopy. The animals were randomly assigned to receive one of three treatments: infusion of Escherichia coli lipopolysaccharides without phosphodiesterase inhibitor pretreatment (=LPS group); or infusion of LPS with milrinone pretreatment (= milrinone group), or without infusion of LPS or milrinone (=control group). Macrohemodynamic parameters (MAP, HR) and microhemodynamic parameters of ileal mucosa (mean diameter of central arterioles = D(A) and mean erythrocyte velocity within the arterioles= V(E)) were measured 30 min before and at 0, 60, and 120 min after induction of endotoxemia. Mucosal villus blood flow was calculated from D(A) and V(E). RESULTS: In the milrinone group MAP decreased 60 min after induction of endotoxemia whereas it remained stable in the control and the LPS group. In both groups given endotoxin V(E) decreased after start of LPS infusion. In contrast, D(A) decreased in the LPS group, but increased in the milrinone group after 120 min of endotoxemia. Thus, the endotoxin-induced decrease of intestinal villus blood flow was diminished but not fully restored by milrinone infusion. CONCLUSION: Our results indicate that milrinone has some beneficial microcirculatory effects during endotoxemia. Although it contributed to systemic hypotension, it attenuated intestinal mucosal hypoperfusion.     

The effects of olprinone (a phosphodiesterase III inhibitor) on hepatic vascular bed in a porcine model of endotoxemia

Decreased hepatic blood flow, and impaired hepatic oxygen delivery caused by endotoxin, result in hepatic metabolic deterioration followed by liver dysfunction and multiple organ failure. Among phosphodiesterase III inhibitors, only olprinone increases hepatosplanchnic blood flow. We evaluated the effects of olprinone on systemic hemodynamics, hepatic circulation, and hepatic oxygen delivery in a porcine model of endotoxemia. Fifteen pigs received a continuous infusion (1.7 microg. kg(-1). h(-1)) of endotoxin (lipopolysaccharide [LPS]) via the portal vein for 240 min. Seven of these pigs received olprinone infusion (0.3 microg. kg(-1). min(-1)) via a central vein from t = 150 min to t = 240 min, whereas the eight remaining pigs served as LPS controls. Continuous infusion of LPS caused significant reductions in hemodynamic variables and a significant increase in arterial lactate. After the administration of olprinone during the LPS infusion, portal venous flow and hepatic oxygen delivery were increased and were higher than in the LPS group. Furthermore, olprinone prevented any further increase in arterial lactate. We conclude that the administration of olprinone halted the disturbances in the hepatic circulation, especially in portal venous flow and hepatic oxygen delivery, in a porcine model of endotoxemia. IMPLICATIONS: Endotoxin is a causative factor in peripheral vascular failure, resulting in a hemodynamic depression that includes a reduction in liver blood flow. The administration of olprinone (phosphodiesterase III inhibitor) improves the liver blood flow circulation in a porcine model of endotoxemia.     

Rapid reduction of intestinal cytochrome a,a3 during lethal endotoxemia.

In vivo near-infrared spectrophotometry was used to determine whether lethal endotoxemia impairs small intestinal oxidative phosphorylation as reflected by the redox state of mitochondrial cytochrome a,a3 (AA3). Adult male Sprague-Dawley rats were anesthetized with 2.1% isoflurane in 30% O2:70% N2O, and the small intestine was partially exteriorized for spectrophotometric monitoring (OMNI-3). By 5 min after an iv bolus of Escherichia coli endotoxin (40 mg/kg, LD90, n = 7) a significant shift toward reduction in intestinal AA3 had occurred in association with hypotension and a marked fall in both superior mesenteric artery blood flow (SMAF) and cardiac output. In a separate group (n = 7) SMAF was kept at the baseline level by periodic infusions of donor rat plasma begun 1 min after endotoxin injection, and the reduction in AA3 was again found despite the fluid loading intervention which successfully maintained not only organ blood flow, but also cardiac output and mean arterial pressure in their normal ranges. Further experiments (n = 34) measuring SM vascular bed oxygen consumption indicated that intestinal VO2 remained unchanged during early endotoxemia. These findings suggest a rapid impairment of oxidative phosphorylation by endotoxin which seems to occur through direct (and/or indirect) toxic cellular effects rather than through impaired tissue perfusion.     

The effect of alpha(2) agonist-induced sedation and its reversal with an alpha(2) antagonist on organ blood flow in sheep

We investigated changes in cardiac output and organ blood flow induced by medetomidine in sheep and determined changes in cardiac output and organ blood flow after reversal of medetomidine-induced sedation by atipamezole. Eight sheep were chronically instrumented. Medetomidine was infused IV to target plasma levels of 0, 0.8, 1.6, 3.2, 6.4, and 12.8 ng/mL for 25 min each, followed by a 5-min infusion of atipamezole. Hemodynamic values and organ blood flow (using colored microspheres) were measured just before medetomidine infusion (baseline), at the end of each medetomidine infusion step, and 30 min after the administration of atipamezole. Medetomidine (12. 8 ng/mL) decreased cardiac output from 6.3 +/- 1.0 to 3.2 +/- 0.7 L/min (P < 0.0001) and increased systemic vascular resistance from 1310 +/- 207 to 3467 +/- 1299 dynes. s(-1). cm(-5) (P < 0.0001). Blood flow decreased in the cerebral cortex from 1.29 +/- 0.40 to 0. 66 +/- 0.12 mL. g(-1). min(-1) (P < 0.0001), left ventricle from 2. 11 +/- 0.61 to 1.40 +/- 0.40 mL. g(-1). min(-1) (P < 0.0001), kidney from 8.28 +/- 3.17 to 6.07 +/- 2.65 mL. g(-1). min(-1) (P < 0.0001), skin from 0.09 +/- 0.04 to 0.05 +/- 0.02 mL. g(-1). min(-1) (P < 0. 0001), intestine from 0.56 +/- 0.13 to 0.27 +/- 0.07 mL. g(-1). min(-1) (P < 0.0001), and skeletal muscle from 0.28 +/- 0.15 to 0.04 +/- 0.01 mL. g(-1). min(-1) (P < 0.0001). Blood flow in the liver (hepatic artery) increased from 0.05 +/- 0.03 to 0.24 +/- 0.16 mL. g(-1). min(-1) (P < 0.0001). After atipamezole infusion, cardiac output and systemic vascular resistance returned to baseline, but the cerebral cortex, left ventricle, and renal blood flows remained below baseline at 0.89 +/- 0.22, 1.37 +/- 0.50, and 6.25 +/- 2.76 mL. g(-1). min(-1), respectively; skeletal muscle blood flow increased above baseline to 0.44 +/- 0.27 mL. g(-1). min(-1), spleen blood flow decreased below baseline to 1.65 +/- 0.61 mL. g(-1). min(-1) (P < 0.0001), and liver, intestine, and lung blood flows returned to baseline values. In conclusion, medetomidine decreased and redistributed organ blood flow in sheep. Atipamezole reversed the medetomidine-induced hemodynamic changes, but redistributed blood flow from the brain, heart, and kidney to the skeletal muscle.     

Beneficial effects of hypertonic saline/dextran on early survival in porcine endotoxin shock

BACKGROUND: Hypertonic saline/dextran (HSD) has been shown to have beneficial effects in haemorrhagic shock. These effects, with improved haemodynamics and organ perfusion, would in theory also be of benefit in septic shock. However, this is less studied. We have therefore further evaluated the effect of additional treatment with HSD in a porcine endotoxin shock model. METHODS: Sixteen anaesthetized pigs were used. A continuous infusion of endotoxin (LPS EC) was increased stepwise during 30 min to a rate of 5 microg/kg/h. The infusion was discontinued after 3 h and the animals were observed for another 2 h. The animals received continuous basal fluid resuscitation with isotonic Ringer's glucose 2.5% at a rate of 20 ml/kg/h throughout the experiment. After 1 h of endotoxin infusion, the animals were randomized to additional treatment with HSD, 4 ml/kg over 5 min, or the same volume of isotonic saline. Every 30 min, haemodynamics and mixed venous saturation (SvO2) were measured via a pulmonary artery catheter. Regional blood flow rates were measured continuously by perivascular ultrasonic flow probes. The metabolic response was measured by arterial blood gas analysis. RESULTS: The endotoxin put all animals into a progressive hypodynamic circulatory shock during the experiment. Treatment with HSD improved survival rate to 8/8 compared with controls 3/8. There was a transient circulatory recovery with improved central and regional haemodynamics, accompanied by stabilized metabolic response. CONCLUSION: Treatment with additional HSD improves survival in an early phase of endotoxin shock. Generally improved haemodynamics and oxygenation of peripheral tissues are suggested as possible mechanisms.     

The effects of vasoactive drugs on hepatic blood flow changes induced by CO2 laparoscopy: an animal study.

Laparoscopic surgery is associated with systemic and splanchnic hemodynamic alterations. Recent data suggest that small-dose dobutamine may attenuate the reduction in splanchnic blood flow associated with increments in intraabdominal pressure. We conducted this study to analyze the effects of dopamine and dobutamine on the hepatic circulation in this setting. Twenty-one pigs were anesthetized and mechanically ventilated. A flow-directed pulmonary artery and carotid artery catheters were inserted. Perivascular flow probes were placed around the main hepatic artery and the portal vein. CO2 was insufflated into the peritoneal cavity to reach an intraabdominal pressure of 15 mm Hg. After 60 min, animals received dopamine (5 microg x kg(-1) x min(-1); n = 8), dobutamine (5 microg x kg(-1) x min(-1); n = 8), or saline (n = 5) for 30 min. Pneumoperitoneum induced significant increases in heart rate, mean arterial pressure, and systemic vascular resistance, with decreases in cardiac output and hepatic artery and portal vein blood flows. Dobutamine infusion, in contrast to dopamine, corrected, at least in part, cardiac output, systemic vascular resistance, and hepatic artery blood flow alterations, but neither drug restored total hepatic blood flow. IMPLICATIONS: Hepatic blood flow decreases during laparoscopic surgery. A small-dose infusion of neither dobutamine nor dopamine corrects the total hepatic blood flow impairment, but the former is able to restore the hepatic arterial blood supply in an animal model mimicking this condition.     

Endotoxin (LPS) increases mesenteric vascular resistance (MVR) and bacterial translocation (BT)

Endotoxemia is responsible for many of the pathophysiologic alterations that occur with Gram-negative sepsis. We utilized a chronic ovine model to determine the hemodynamic disturbances in the gastrointestinal tract during endotoxemia. Sheep with indwelling arterial, venous, and pulmonary arterial catheters were used. An ultrasonic flow probe was placed on the cephalic mesenteric artery. The animals were subjected to: 1) Ringer's lactate infusion (sham n = 6); or 2) 1.5 mcg/kg E. coli endotoxin (n = 6) over over a period of one half hour and were monitored for 48 hours. They were then sacrificed and specimens of mesenteric lymph node, liver, spleen, kidney, and lung obtained for bacteriologic cultures and histologic analysis. Sheep receiving endotoxin showed more than 50% reduction in the mesenteric blood flow. Mesenteric vascular resistance increased while non-mesenteric systemic vascular resistance decreased. The increase in the total systemic vascular resistance, noted during endotoxemia, was thus likely due to the increase in the mesenteric vascular resistance. At autopsy there were positive cultures for microorganism in the mesenteric lymph nodes in six out of six sheep with endotoxemia as compared to one out of six of control. Thus the vasoconstriction in the mesenteric areas may have resulted in bacterial translocation from the GI tract.     

Human Hepatic Blood Flow and its Relation to Systemic Circulation during Intravenous Infusion of Bupivacaine or Etidocaine

Fifteen healthy young volunteers were studied before and during an intravenous infusion of a local anaesthetic agent. Seven received bupivacaine and eight etidocaine in a dose rate of 2 mg/min over a period of 150 min. Variables of the central systemic circulation and also the hepatic blood flow were measured repeatedly. The circulatory alterations during administration of the two drug s were compared. Comparisons with previous results concerning lidocaine and a placebo were also made. It was found that bupivacaine increased the heart rate, mean arterial blood pressure and cardiac output significantly more than did etidocaine in an equal plasma concentration. Lidocaine was intermediate between bupivacaine and etidocaine. In contrast, these three drugs had the same decreasing effect upon the splanchnic vascular resistance, which caused an almost identical increase in the estimated hepatic blood flow. The calculated vascular resistance in the systemic circulation, excluding the splanchnic, was unchanged during the infusion of etidocaine, while it decreased during the infusion of bupivacaine. Most of this discrepancy was due to the different plasma concentrations of the drugs.     

Evaluation of the effects of lymph drainage by a thoracic duct fistula in experimental peritonitis

Previous studies suggest that systemic endotoxemia in peritonitis is mainly related to lymphatic transport via the thoracic duct. Rats with fecal peritonitis but with or without a lymph draining thoracic duct fistula were studied with reference to the concentrations of endogenously produced endotoxin in arterial plasma, hemodynamic parameters, organ blood flow, blood corpuscle parameters, glucose and lactate metabolism and survival. Lymph drainage significantly reduced the endotoxin concentrations in arterial plasma, but did not totally prevent systemic endotoxemia, and was related to maintained total peripheral vascular resistance. On the other hand, peritonitic rats without lymph drainage, and consequently higher endotoxin concentrations, had a significant fall in vascular resistance combined with a compensatory rise in cardiac output. Lymph drainage also contributed to a smaller decrease of platelet and leucocyte counts while no effect was observed on glucose metabolism. Despite the effect of lymph drainage on hemodynamic and hematologic responses no effect on survival time was recorded.     

Dopexamine reverses the vasopressin-associated impairment in tissue oxygen supply but decreases systemic blood pressure in ovine endotoxemia

Since arginine vasopressin (AVP) may reduce cardiac output and, in proportion, oxygen delivery, we studied the efficacy of dopexamine (DPX) as an adjunct to AVP infusion. After 1 h of continuous AVP infusion (0.04 U/min) in healthy sheep (n = 7), DPX was additionally administered in incremental doses (1, 5, and 10 microg. kg(-1). min(-1); each dose for 30 min). After a 24-h period of recovery, endotoxin was continuously infused in the same sheep to induce and maintain a hypotensive/hyperdynamic circulation. After 16 h of endotoxemia, AVP and DPX were given as described previously. AVP infusion increased systemic vascular resistance index and decreased cardiac index in both healthy and endotoxemic conditions (P < 0.001 each). This was accompanied by an augmented pulmonary vascular resistance index in endotoxemia (159 +/- 13 dynes. cm(-5). m(-2) versus 202 +/- 16 dynes. cm(-5). m(-2)) and a decrease in oxygen delivery index (health: 842 +/- 66 mL. min(-2). m(-2) versus 475 +/- 38 mL. min(-2). m(-2); endotoxemia: 1073 +/- 49 mL. min(-2). m(-2) versus 613 +/- 44 mL. min(-2). m(-2)) and mixed venous oxygen content (health: 63% +/- 2% versus 47% +/- 2%; endotoxemia: 68% +/- 2% versus 51% +/- 3%; P < 0.001 each). Small doses of DPX (1 and 5 microg. kg(-1). min(-1)) improved not only the AVP-associated depressions in cardiac index, oxygen delivery index, and mixed venous oxygen content, but also the pulmonary vasopressive effect in both groups. While large-dose DPX (10 microg. kg(-1). min(-1)) also reduced mean pulmonary arterial pressure in endotoxemia (27 +/- 1 mm Hg versus 23 +/- 1 mm Hg; P < 0.05 versus baseline), mean arterial blood pressure decreased (105 +/- 4 mm Hg versus 80 +/- 3 mm Hg) and heart rate increased (84 +/- 4 bpm versus 136 +/- 9 bpm; P < 0.001 versus AVP alone), thereby limiting its therapeutic use.     

Which vasopressor should be used to treat hypotension during magnesium sulfate infusion and epidural anesthesia?

Ephedrine restores and/or protects uterine blood flow and fetal well-being in laboratory animals. In contrast, alpha 1-adrenergic agonists worsen uterine blood flow and fetal condition. We previously demonstrated that magnesium sulfate (MgSO4) attenuates the detrimental effects of phenylephrine on uterine vascular resistance in gravid ewes. Therefore, we performed this study to determine whether ephedrine or phenylephrine better restores and protects uterine blood flow and fetal oxygenation during epidural anesthesia-induced hypotension in hypermagnesemic gravid ewes. Twelve chronically instrumented gravid ewes were each used for three experiments: 1) ephedrine, 2) phenylephrine, and 3) normal saline (NS)-control. For each experiment the protocol was as follows: 1) at time zero, intravenous infusion of MgSO4 was begun; 2) at 150 min a thoracic level of epidural anesthesia was achieved with 2% lidocaine; and 3) at 165 min, an intravenous infusion of ephedrine, phenylephrine, or NS was begun and continued through 195 min. Epidural anesthesia uniformly decreased maternal mean arterial blood pressure (MAP), heart rate, cardiac output, uterine blood flow, and fetal PO2 in each of the three groups. Both ephedrine and phenylephrine restored maternal MAP to baseline, as expected from the experimental design. Ephedrine significantly increased cardiac output and uterine blood flow when compared with NS-control, but phenylephrine did not. Phenylephrine significantly increased uterine vascular resistance when compared with NS-control, but ephedrine did not. As a result, fetal pH and PO2 were significantly greater during ephedrine infusion than during infusion of NS-control. Fetal pH was stable during ephedrine infusion, but it continued to decrease during phenylephrine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

A research on the cholestasis caused by continuous endotoxemia

Intrahepatic cholestasis is often observed in patients without obstruction of the bile duct, who are suffering from severe prolonged infection in the field of peptic surgery. Clinical data were analyzed in recently experienced 18 cases which showed this kind of jaundice. In those case, high rates of endotoxemia and high rates of gram negative bacilli were seen. This fact made us infer that endotoxins might cause jaundice. In order to clarify the mechanism of the jaundice, we made an experimental model of persistent endotoxemia in rats. Low-dose endotoxin was infused continuously to Donryu-rats and bile-output was observed with external bile-guiding tube for 24 hours. In the endotoxin group, bile-output was significantly decreased whereas it was not changed in the control group. In addition, serum bilirubin was elevated in the endotoxin group, whereas it did not change in the control group. Blood-flow of liver tissue and systemic arterial blood pressure did not show any severe decrease under the continuous endotoxemia. Data of bile-output and bile acid showed bile acid independent flow might be depressed by endotoxin infusion. This model was thought to be under non-shock condition and useful to investigate jaundice seen in patients under continuous endotoxemia.     

The effects of endotoxemia and fluid expansion on gastric hemodynamics and mucosal permeability in the baboon.

The effects of sublethal intravenous endotoxin on gastric hemodynamics and mucosal ionic permeability were studied in eight adult baboons. Each baboon had construction of an internally drained Heidenhain pouch 2 weeks prior to testing. Ionic fluxes were determined by instillation and recovery of an acid test solution (ATS) containing 80 mM HCI and 80 mM NaCl. Four hours of endotoxemia resulted in significant decreases in cardiac output and mucosal blood flow to about one-half of control values. There was a small but insignificant increase in hydrogen back diffusion from ?58 ± 26 to ?131 ± 59 μequiv/ 30 min/100 cm² and no significant change in sodium flux from + 183 ± 44 μequiv/30 min/100 cm² with shock. Endotoxic shock resulted in a significant decrease in the transmucosal electrical PD from 40 ± 3 to 29 ± 4 mV with a significant increase in potassium flux from 6 ± 2 to 11 ± 3 μequiv/ 30 min/100 cm², both indicating mucosal damage. All pouches developed acute superficial erosions. Fluid resuscitation corrected blood flow and cardiac output without significantly changing ionic fluxes or potential difference. In the baboon, endotoxemia and its attendent ischemia in the presence of acid may result in clinically significant stress ulcers without significant increases in gastric mucosal ionic permeability.     

The cardiovascular and metabolic effects of halothane in normoxic and hypoxic newborn lambs

Oxygen consumption, cardiac output, and tissue oxygen delivery were measured in normoxic and hypoxic 1-3-day-old lambs during the following six conditions: 1) (control) paralysis with pancuronium and controlled ventilation with room air; 2) paralysis, controlled ventilation and hypoxia (PaO2 = 30 +/- 3 mmHg, [SD]); 3) paralysis, controlled ventilation with room air and 0.5 MAC halothane; 4) paralysis, controlled ventilation, hypoxia, and 0.5 MAC halothane; 5) paralysis, controlled ventilation with room air, and 1 MAC halothane; and 6) paralysis, controlled ventilation, hypoxia, and 1 MAC halothane. During normoxia, 0.5 and 1 MAC halothane decreased total body oxygen consumption, cardiac output, and arterial blood pressure. One-half MAC halothane had no effect on blood flow to any organ except muscle, whose flow decreased 64%. One MAC halothane decreased blood flow to the brain, heart, kidney, muscle, and gut. Both concentrations of halothane decreased serum catecholamine levels below control values and prevented hypoxia from increasing catecholamine levels. Hypoxia decreased the oxygen consumption about 40% from the immediately previous normoxic value, whether the animals were anesthetized or not. Tissue oxygen delivery followed changes in blood flow. The cardiac output, arterial blood pressure, and heart rate of anesthetized, hypoxic animals were not different from those in the previous normoxic condition. Halothane did not prevent redistribution of blood flow to the heart and brain of hypoxic animals, nor did halothane prevent hypoxic pulmonary vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dobutamine compensates deleterious hemodynamic and metabolic effects of vasopressin in the splanchnic region in endotoxin shock

BACKGROUND: Vasopressin is a potent vasopressor in septic shock, but it may impair splanchnic perfusion. We compared the effects of vasopressin alone and in combination with dobutamine on systemic and splanchnic circulation and metabolism in porcine endotoxin shock. METHODS: Twelve pigs were randomized to receive either vasopressin (VASO, n = 6) or vasopressin in combination with dobutamine (DOBU, n = 6) during endotoxin shock (E. coli endotoxin infusion). Endotoxin infusion rate was increased to induce hypotension after which vasoactive drugs were started. We aimed to keep systemic mean arterial pressure (MAP) >70 mmHg by vasopressin; the goal of dobutamine infusion was to prevent decrease in cardiac output often associated with vasopressin infusion. Regional blood flows, oxygen delivery and consumption, arterial and regional lactate concentrations were measured. RESULTS: Mean arterial pressure >70 mmHg was achieved in both the VASO and DOBU groups. After the primary decrease of cardiac output by vasopressin, systemic blood flow remained stable in vasopressin-treated animals. However, vasopressin as a monotherapy decreased portal venous blood flow. This was prevented by dobutamine. Vasopressin also induced splanchnic lactate release and arterial hyperlactatemia, which were not observed when dobutamine was combined with vasopressin. CONCLUSION: Dobutamine prevents adverse hemodynamic and metabolic effects of vasopressin in septic shock.     

Regionally differentiated fibrinolytic responses during volume-resuscitated acute endotoxemia in pigs

BACKGROUND: Microcirculatory dysfunction and formation of microthrombi are common in sepsis as a result of a procoagulant state. A profibrinolytic change has however, been reported in early sepsis. This study investigates systemic and regional (pulmonary, preportal, hepatic, renal) fibrinolytic capacity as mirrored by fluxes of tissue-type plasminogen activator (t-PA) in response to acute endotoxemia and volume resuscitation. METHODS: Eight anaesthetized, ventilated pigs (24-29 kg) were instrumented for systemic and regional haemodynamic monitoring. Aortic, pulmonary arterial, portal, hepatic and renal venous blood samples were collected. Following baseline stabilisation, Escherichia coli endotoxin was infused for 120 min. During the last 30 min of infusion, volume resuscitation was initiated targeting baseline cardiac output, and animals were observed for 3 h. Total tPA was analyzed by ELISA calibrated for porcine tPA. Net organ tPA fluxes were calculated based on in/outflowing plasma concentrations and regional blood flows. RESULTS: Preportal release and hepatic extraction of tPA was observed at baseline. Pulmonary and renal net fluxes of tPA were not significantly different from zero. Endotoxemia increased plasma tPA levels in all investigated vascular beds. Preportal tPA release increased approximately 10-fold and hepatic extraction increased approximately 12-fold in non-resuscitated acute endotoxemia. No significant changes in pulmonary or renal tPA fluxes were observed. Volume resuscitation restored net fluxes to baseline values while plasma levels remained elevated approximately twofold compared with baseline. CONCLUSION: Acute endotoxemia induces a prompt, marked and regionally differentiated pro-fibrinolytic response that cannot be discerned based on systemic levels of circulating tPA and that was normalized during volume resuscitation.