Effects of dobutamine on splanchnic tissue perfusion during partial superior mesenteric artery occlusion

OBJECTIVE: To evaluate the effects of dobutamine and fluid treatment on splanchnic hemodynamics and tissue oxygenation during partial superior mesenteric artery occlusion. DESIGN: Prospective, open randomized, full-factorial design. SETTING: University research laboratory. SUBJECTS: Forty-eight female pigs. INTERVENTIONS: In 24 anesthetized pigs (ischemic group), superior mesenteric artery (SMA) blood flow was reduced to 30% from the baseline for 120 mins; 24 pigs (sham group) served as nonischemic controls. The animals were further assigned into four treatment arms. In the control arm, the animals were administered only basic fluid therapy. In the fluid therapy arm, pulmonary artery occlusion pressure was maintained at 10 mm Hg with fluids. In the dobutamine treatment arm, dobutamine hydrochloride was infused at a dose of 10 microg/min/kg. In the combined dobutamine-fluid therapy arm, dobutamine at 10 microg/min/kg was administered and pulmonary artery occlusion pressure was maintained at 10 mm Hg with fluids. MEASUREMENTS AND MAIN RESULTS: Systemic and regional hemodynamics and oxygen transport, as well as jejunal intramucosal pH, intramucosal-arterial PCO2 gradient, and portal venous-arterial lactate gradient were measured. Ischemia did not modify the effects of fluids or dobutamine on systemic hemodynamics and oxygen transport. Dobutamine-treated animals had a higher cardiac index compared with control animals (218 +/- 22 vs. 135 +/- 13 mL/min/kg; p = .012), and the effect was enhanced when dobutamine was combined with fluid treatment (365 +/- 23 mL/ min/kg; p = .019). Fluid treatment alone did not influence cardiac index, whereas it increased SMA blood flow compared with control groups (15 +/- 2 vs. 12 +/- 2 mL/min/kg; p = .023). Dobutamine also decreased the proportion of SMA blood flow of cardiac output compared with control groups (6 +/- 1 vs. 9% +/- 1%; p = .024). Other treatments had no effect on SMA blood flow. Ischemia increased intramucosal-arterial Pco2 gradient to 54.8 +/- 10.7 torr (7.31 +/- 1.43 kPa) (p = .002 vs. sham control) and decreased intramucosal pH to 7.13 +/- 0.06 (p = .028 vs. sham control). In the ischemic animals, dobutamine without fluid therapy reduced intramucosal pH further to 7.00 +/- 0.09 (p = .023 vs. ischemic control) and increased portal venous-arterial lactate gradient (p = .033). CONCLUSIONS: Dobutamine alone worsened splanchnic tissue perfusion during partial superior mesenteric artery occlusion. As compared with fluid treatment alone, the combination of fluid and dobutamine therapy did not improve tissue perfusion.     

Continuous arterial infusion of prostaglandin E(1) via the superior mesenteric artery in the treatment of postoperative liver failure.

Impaired hepatic blood flow is one of the causative factors in postoperative liver failure. To restore the hepatic blood flow in case of hepatic artery interruption (HAI), the effect of continuous arterial infusion of prostaglandin E(1) (PGE(1)), which has a strong vasodilatory effect on vascular smooth muscles, was assessed experimentally and clinically. Twelve pigs underwent ligation and division of the hepatic artery and were divided into 2 groups. In the control group, saline was infused in the superior mesenteric artery (SMA), and in the PGE(1) group, 0.02 microg/kg/min of PGE(1) was infused continuously in the SMA. Hepatic oxygen delivery (HDO(2)) in the control group was 87.8 +/- 8.9 ml/min before HAI and decreased to 43.1 +/- 2.6 ml/min at 60 min after HAI, showing 50.9% decrease by HAI. On the contrary, HDO(2) in the PGE(1) group was 86.7 +/- 9.1 ml/min before HAI and was 76.6 +/- 12.2 ml/min at 60 min after HAI, showing only 11.6% decrease by HAI. Clinically, a 65-year-old female suffering from cholangiocellular carcinoma underwent extended left hepatic lobectomy. At operation, the branch of the hepatic artery to the anterior segment of the liver was ligated, and the right branch of the portal vein became stenotic unavoidably. Postoperatively, severe liver dysfunction developed so that continuous PGE1 infusion in the SMA was initiated at a rate of 0.01 microg/kg/min on the eighth postoperative day and continued for 9 days. Plasma exchange was performed twice concomitantly. Portal venous flow increased from 612 ml/min to 1,192 ml/min, and bile flow from external biliary drainage tube doubled by the PGE(1) infusion. The liver function was ameliorated after PGE(1) infusion.     

Hepatosplanchnic blood flow control and oxygen extraction are modified by the underlying mechanism of impaired perfusion

OBJECTIVE: To assess the effects of low hepatosplanchnic blood flow on regional blood flow control and oxygenation. DESIGN: Three randomized, controlled animal experiments. SETTING: Two university experimental research laboratories. SUBJECTS: Pigs of either gender. INTERVENTIONS: Isolated abdominal blood flow reduction: An extracorporeal shunt with reservoir and roller pump was inserted between proximal and distal aorta in 11 pigs. Abdominal aortic blood flow was reduced by 50% by activating the shunt. Mesenteric ischemia: In seven pigs, superior mesenteric arterial flow was reduced to 4 mL.kg.min for 4 hrs. Cardiac tamponade: In 12 pigs, aortic blood flow was reduced by cardiac tamponade to 50 mL (moderate tamponade) and further to 30 mL.kg.min (severe tamponade) for 1 hr each. In each experimental condition, the same number of control animals was used. MEASUREMENTS AND MAIN RESULTS: Abdominal blood flow reduction, acute mesenteric ischemia, and moderate tamponade resulted in a portal venous flow (QPV) reduction to 51 +/- 23%, 52 +/- 18%, and 61 +/- 25% (mean +/- sd) of baseline flow, respectively. During abdominal blood flow reduction, QPV and hepatic arterial flow (QHA) decreased proportionally, whereas in moderate tamponade and acute mesenteric ischemia QPV reduction was associated with an increase in QHA of 30 +/- 39% and 102 +/- 108%, respectively (p = .001 and .018). Prolonged mesenteric ischemia restored total hepatic blood flow (Qliver) completely. During all conditions, decreasing mesenteric oxygen consumption was partly prevented by increased mesenteric oxygen extraction (p < .001 for all conditions). In contrast, decreasing hepatic oxygen delivery was associated with increased oxygen extraction in tamponade (p = .009) but not in abdominal blood flow reduction. CONCLUSIONS: Blood flow redistribution can restore Qliver totally when mesenteric blood flow is reduced selectively, partially when cardiac output is reduced, and not at all during abdominal blood flow reduction. Since hepatic oxygen extraction does not increase in abdominal blood flow reduction, hepatic oxygenation is at risk in this condition.     

Occlusive mesenteric ischemia and its effects on jejunal intramucosal pH, mesenteric oxygen consumption and oxygen tensions from surfaces of the jejunum in anesthetized pigs

Objective: To investigate the effects of superior mesenteric artery (SMA) flow reduction on the jejunal intramucosal pH (pH_i) and to compare these effects with corresponding changes of mesenteric oxygen transport variables and oxygen tensions on the surfaces of the jejunal serosa and mucosa. Design: Prospective, randomized, controlled, experimental study. Setting: Animal research laboratory. Subjects: 20 domestic pigs. Interventions: Mechanical flow reduction in the SMA. The animals were randomized to have an SMA flow of 0%, 25%, 38%, 50% or 100% (control). Measurements and main results: Measurements (baseline, ischemia, reperfusion) consisted of hemodynamic and oxygen transport variables, SMA blood flow, mesenteric oxygen transport variables, pH_i and oxygen tensions of the jejunal serosa and mucosa. Flow reduction in the SMA resulted in a significant decrease of pH_i indicating ischemia earlier than mesenteric oxygen transport variables. The relationship between mesenteric oxygen delivery (DO_2ms) and pH_i during acute ischemia is best described by a sigmoid curve. There was a linear correlation between the changes of the jejunal surface oxygen tensions and pH_i due to SMA flow reduction. Conclusion: The sigmoid relationship between pH_i and DO_2ms indicated that pH_i is a sensitive parameter for detecting ischemia at 50% of the baseline oxygen delivery and that below 25% there was no further decrease of pH_i. In contrast, mesenteric and whole body oxygen transport parameters were not indicative of impaired mucosal oxygen supply. Received: 11 March 1996 Accepted: 4 October 1996     

Jejunal luminal microdialysate lactate in cardiac tamponade--effect of low systemic blood flow on gut mucosa

OBJECTIVE: To assess gut mucosal metabolic response and susceptibility to dysoxia during low systemic blood flow induced by cardiac tamponade. DESIGN: A randomized, controlled animal experiment. SETTING: National laboratory animal center. INTERVENTIONS: Cardiac tamponade was induced in six pigs, while six additional pigs served as controls. In the tamponade group, fluid was injected into the pericardial space to reduce aortic flow, aiming first at a flow of 50 ml/kg per min and then at 30 ml/kg per min. Each step lasted for 60 min. MEASUREMENTS AND RESULTS: We measured luminal lactate by microdialysis and mucosal PCO(2) by tonometry in the mid-jejunum. Aortic and superior mesenteric artery blood flow, arterial and mesenteric venous lactate, pyruvate and ketone bodies and regional lactate exchange were measured. The distribution of aortic blood flow to superior mesenteric artery remained unchanged (baseline 14 (12-16)%; median (interquartile range), stepwise flow reduction 11 (10-17)% and 13 (12-19)%, NS) during reduction of aortic blood flow from 81 (61-95) ml/kg per min to 49 (47-49) ml/kg per min and 23 (21-27) ml/kg per min. Systemic hyperlactatemia developed early, whereas gut luminal lactate increased only after 60 min of hypoperfusion and could be largely explained by arterial hyperlactatemia. Mesenteric venous lactate-to-pyruvate (L/P) ratio increased after 30 min of tamponade, but both venous-arterial lactate and pyruvate gradients turned negative (gut lactate and pyruvate uptake). Mesenteric venous ss-hydroxybutyrate to acetoacetate ratio increased after 60 min. No changes were observed in the controls. CONCLUSIONS: Jejunal mucosal dysoxia and anaerobic metabolism occurs late during low systemic blood flow induced by experimental cardiac tamponade.     

Effect of fat digestion on superior mesenteric artery blood flow in humans

BACKGROUND AND AIM: Intraluminal nutrients stimulate superior mesenteric artery (SMA) blood flow. Of the macronutrients, especially fat affects the magnitude of the SMA blood flow response to a meal. Little is known however on the influence of fat hydrolysis on SMA flow. METHODS: We compared in eight healthy volunteers the SMA flow response (Doppler ultrasonography) to continuous intraduodenal fat perfusion (LCT, 240 kCal h(-1)) during conditions with normal hydrolysis (placebo, control), increased hydrolysis (pancreatic enzyme supplementation; 50 kU lipase) and impaired hydrolysis (orlistat 240 mg). RESULTS: Intraduodenal LCT significantly (P<0.01) increased SMA flow in all experiments over basal. The SMA flow response to fat during pancreatic enzyme supplementation (1.49 +/- 0.1 l min(-1)) was significantly (P<0.05) higher compared with placebo (1.11 +/- 0.16 l min(-1)). Lipase inhibition with orlistat did not significantly affect fat stimulated SMA flow compared with placebo: 0.89 +/- 0.08 l min(-1) versus 1.11 +/- 0.16 l min(-1). CONCLUSIONS: Administration of pancreatic enzymes significantly increases fat stimulated SMA flow. Fat digest products in the intestinal lumen contribute to the regulation of SMA blood flow.     

Enalaprilat improves systemic and mesenteric blood flow during resuscitation from hemorrhagic shock in dogs

We investigated the systemic and mesenteric cardiovascular effects of administering enalaprilat during resuscitation from hemorrhage. Dogs were hemorrhaged (mean arterial pressure [MAP] 40-45 mmHg for 30 min, then 30-35 mmHg for 30 min) and were then resuscitated with intermittent lactated Ringer's solution (200 mL/kg/h during first 40 min, and 60 mL/kg/h during the following 130 min, MAP 75-80 mmHg). A constant-rate infusion of saline with or without enalaprilat (0.02 mg/kg/h) was initiated after 40 min of resuscitation. Blood flows declined with hemorrhage, increased with resuscitation, and then declined during the initial 40 min of resuscitation. Enalaprilat administration resulted in blood flow increases not seen in the controls (ending values for cardiac index: 2.8 +/- 0.4 L/min/m2 vs. 1.6 +/- 0.3 L/min/m2; celiac arterial flow 314 +/- 66 L/min/m2 vs. 139 +/- 13 mL/min/m2; and portal venous flow 596 +/- 172 L/min/m2 vs. 414 +/- 81 mL/min/m2 for enalaprilat versus controls, respectively). The greater flows with enalaprilat appeared to be due to prevention of the increases in afterload noted in the controls (ending arterial elastance values 3.73 +/- 0.97 mmHg/m2/mL vs. 7.74 +/- 1.80 mmHg/m2/mL for enalaprilat versus controls, respectively). We conclude that administration of a constant-rate infusion of enalaprilat during resuscitation can be used to improve systemic and mesenteric blood flow.     

Endothelin-1 blockade corrects mesenteric hypoperfusion in a porcine low cardiac output model

OBJECTIVE: To study the importance of endothelin-1-induced vasoconstriction in a model of acute and maintained low cardiac output, by investigating regional changes within the mesenteric and particularly the intestinal mucosal circulation. DESIGN: Prospective, controlled animal study. SETTING: University-affiliated research laboratory. SUBJECTS: Thirteen fasted, anesthetized, mechanically ventilated landrace pigs. MEASUREMENTS AND MAIN RESULTS: Cardiac output, portal venous blood flow, renal arterial flow, jejunal mucosal microcirculation by laser Doppler flowmetry, jejunal capnotonometry (Pco2 gap), and jejunal mucosal oxygenation (tPo2) were monitored. Cardiac tamponade was established to reduce portal venous blood flow to a preset end point at two thirds of baseline. Measurements were made at baseline, after 90 mins of cardiac tamponade, and 90 mins after the administration of the combined endothelinA/endothelinB antagonist tezosentan at 1 mg.kg-1.hr-1 during tamponade in seven animals. Six animals served as time controls and received only the vehicle. Cardiac tamponade decreased portal venous blood flow, renal arterial flow, and laser Doppler flowmetry, whereas the Pco2 gap increased. The change in tPo2 failed to gain statistical significance (p =.08). Administration of tezosentan during tamponade restored portal venous blood flow and laser Doppler flowmetry to baseline values, increased tPo2 above baseline, and decreased Pco2 gap. No effect on renal arterial flow was observed. Investigated variables remained unchanged in control animals after induction of cardiac tamponade. CONCLUSIONS: Endothelin-1 blockade in acute cardiac failure improves mesenteric, but not renal, perfusion, illustrating the regional importance of endothelin-1-induced vasoconstriction. Importantly, endothelin-1 blockade restored mucosal blood flow and oxygenation, which might be particularly interesting considering the implications for maintenance of mucosal barrier integrity in low output states.     

Dobutamine restores intestinal mucosal blood flow in a porcine model of intra-abdominal hyperpressure

OBJECTIVE: To assess the effects of dopamine and dobutamine administration on the systemic and mesenteric (macro- and microvascular) circulatory disturbances induced by intra-abdominal hyperpressure. DESIGN: Prospective, randomized study. SETTING: Animal research laboratory in a university hospital. SUBJECTS: Twenty-five pigs of either gender, weighing 30-35 kg. INTERVENTIONS: Animals were anesthetized, and their lungs were mechanically ventilated. Pulmonary artery flotation and carotid artery catheters were inserted for hemodynamic monitoring and blood sampling. A perivascular flow probe was placed around the superior mesenteric artery, and a laser Doppler probe was positioned in the lumen of the ileum to measure arterial and intestinal mucosal blood flows, respectively. CO2 was insufflated into the peritoneal cavity to reach an intra-abdominal pressure of 15 mm Hg, and 60 mins later, animals received dopamine (5 microg/kg/min; n = 10), dobutamine (5 microg/kg/min; n = 10), or saline (n = 5) for 30 mins. MEASUREMENTS AND MAIN RESULTS: Peritoneal CO2 insufflation induced significant increases in heart rate, arterial pressure, and systemic vascular resistance with concomitant decreases in cardiac output and superior mesenteric arterial and intestinal mucosal blood flows. Although dobutamine infusion reversed the decrease in cardiac output, it failed to restore superior mesenteric artery blood flow; however, intestinal mucosal blood flow returned to baseline levels. Dopamine also attenuated the decrease in cardiac output, but it had no beneficial effect on splanchnic hemodynamic variables. CONCLUSIONS: Low-dose infusion of dobutamine, but not dopamine, corrects the intestinal mucosal perfusion impairment induced by moderate increases in intra-abdominal pressure.     

Effect of lipopolysaccharide on intestinal intramucosal hydrogen ion concentration in pigs: evidence of gut ischemia in a normodynamic model of septic shock

We tested the hypothesis that lipopolysaccharide (LPS) leads to an imbalance between mesenteric oxygen delivery (DO2) and gut metabolic demand for oxygen, even when cardiac index (CI) is within the normal range. Two groups of pentobarbital-anesthetized pigs (13 to 17 kg) were studied. The first group (LPS; n = 9) was infused over 20 min with Escherichia coli LPS (100 micrograms/kg) and resuscitated with normal saline (1.2 ml/kg.min). The second group (NS; n = 5) was not infused with LPS, but was resuscitated in the same way as the LPS group. Superior mesenteric arterial (SMA) blood flow and ileal intramucosal hydrogen ion concentration, [H+], were determined using a Doppler-shift probe and a tonometric catheter, respectively. Infusing LPS did not affect CI, although mean arterial pressure and systemic vascular resistance were significantly reduced. SMA flow and mesenteric DO2 decreased significantly in the LPS group. Although mesenteric oxygen utilization was well preserved in both groups, ileal intramucosal [H+] was significantly higher in endotoxic animals. These data support the idea that mesenteric oxygen consumption is flow-limited in this clinically relevant porcine model of septic shock.     

Effects of vasopressin and epinephrine on splanchnic blood flow and renal function during and after cardiopulmonary resuscitation in pigs

OBJECTIVE: To compare the effects of vasopressin versus epinephrine on splanchnic blood flow during and after cardiopulmonary resuscitation (CPR), and to evaluate the effects of these vasopressors on renal function in the postresuscitation phase. DESIGN: Prospective, randomized laboratory investigation using an established porcine CPR model with instrumentation for continuous measurement of splanchnic and renal blood flow. SETTING: University hospital experimental laboratory. SUBJECTS: A total of 12 anesthetized, 12- to 16-wk-old domestic pigs weighing 30-35 kg. INTERVENTIONS: After 4 mins of cardiac arrest, and 3 mins of CPR, 12 pigs were randomly assigned to receive either 0.4 units/kg vasopressin (n = 6) or 45 microg/kg epinephrine (n = 6). Defibrillation was performed 5 mins after drug administration; all animals were observed for 6 hrs after return of spontaneous circulation (ROSC). MEASUREMENTS AND MAIN RESULTS: Mean +/- SEM superior mesenteric artery blood flow was significantly (p < .05) lower after vasopressin compared with epinephrine at 90 secs after drug administration (13+/-3 vs. 129+/-33 mL/min); at 5 mins after drug administration (31+/-18 vs. 155+/-39 mL/min); at 5 mins after ROSC (332+/-47 vs. 1087+/-166 mL/min); and at 15 mins after ROSC (450+/-106 vs. 1130+/-222 mL/min); respectively. Mean +/- SEM left renal and hepatic artery blood flow after ROSC was comparable in both groups ranging between 120-290 mL/min (renal blood flow), and 150-360 mL/min (hepatic blood flow), respectively. Median urine output after ROSC showed no difference between groups, and highest values (180-220 mL/hr) were observed in the first 60 mins after ROSC. Median calculated glomerular filtration rate showed no difference between groups with values ranging between 30 and 80 mL/min in the postresuscitation phase. Calculated fractional sodium excretion and osmolar relationship between urea and plasma indicated no evidence for renal tubular dysfunction. CONCLUSIONS: In the early postresuscitation phase, superior mesenteric blood flow was temporarily impaired by vasopressin in comparison with epinephrine. With respect to renal blood flow and renal function after ROSC, there was no difference between either vasopressor given during CPR. Vasopressin given during CPR did not result in an antidiuretic state in the postresuscitation phase.     

The hemodynamic effects of dobutamine infusion in the chronically instrumented newborn piglet

OBJECTIVE: To determine the systemic, pulmonary, mesenteric, and renal hemodynamic effects of short and prolonged infusions of dobutamine. DESIGN: Prospective randomized unblinded study. SETTING: University research laboratory. SUBJECTS: Thirteen newborn (1-3 days old) piglets. INTERVENTIONS: Piglets were instrumented and studied 48 hrs later. Fifteen-minute infusions of dobutamine at 5, 10, 20 and 50 microg/ kg x min were randomly given with 15-min rests between the doses. After a 1-hr hiatus, a dose of 10 microg/kg x min was continuously administered for 2 hrs. MEASUREMENTS AND MAIN RESULTS: Systemic and pulmonary arterial pressures, cardiac index (thermodilution), and superior mesenteric and renal artery flows were measured. Vascular resistance values were calculated. MAIN RESULTS: Fifteen-minute infusions: Dobutamine dose-dependently increased cardiac index with tachycardia but not stroke volume (from 187 +/- 43 to 238 +/- 51 mL/kg x min at baseline and 50 microg/ kg x min, respectively, p < .05; values expressed as mean +/- SD). Systemic, but not pulmonary, vascular resistance decreased, resulting in a significant decrease in systemic to pulmonary arterial pressure ratio (from 3.8 +/- 0.8 at baseline to 3.2 +/- 1.0 at 50 microg/ kg x min). Superior mesenteric and renal flows were not affected. Two-hour infusion at 10 microg/kg x min: Cardiac index progressively increased from 173 +/- 34 to 240 +/- 58 mL/kg x min at baseline and 120 mins, respectively, (p < .05). The initial tachycardia was transient, and stroke volume was significantly increased at 60 mins and thereafter. Although systemic and pulmonary vascular resistance values fell simultaneously, systemic to pulmonary arterial pressure ratio decreased significantly to 3.4 +/- 0.9 at 120 mins from 3.9 +/- 0.7 at baseline. Superior mesenteric and renal artery flows increased significantly with vasodilation after 60 mins. CONCLUSIONS: Short infusions of dobutamine dose-dependently increase cardiac output due to tachycardia, without significant effect on mesenteric and renal blood flows. Prolonged infusion of dobutamine at 10 microg/kg x min progressively increases cardiac output and stroke volume with transient tachycardia, and increases mesenteric and renal blood flows. Caution is required in the treatment of critically ill neonates with dobutamine, which could also reduce systemic to pulmonary arterial pressure ratio.     

Arginine vasopressin,but not epinephrine,improves survival in uncontrolled hemorrhagic shock after liver trauma in pigs

OBJECTIVE: Epinephrine is widely used for treatment of life-threatening hypotension, although new vasopressor drugs may merit evaluation. The purpose of this study was to determine the effects of vasopressin vs. epinephrine vs. saline placebo on hemodynamic variables, regional blood flow, and short-term survival in an animal model of uncontrolled hemorrhagic shock and delayed fluid resuscitation. DESIGN: Prospective, randomized, laboratory investigation that used a porcine model for measurement of hemodynamic variables and regional abdominal organ blood flow. SETTING: University hospital laboratory. SUBJECTS: A total of 21 pigs weighing 32 +/- 3 kg. INTERVENTIONS: The anesthetized pigs were subjected to a penetrating liver injury, which resulted in a mean +/- sem loss of 40% +/- 5% of estimated whole blood volume within 30 mins and mean arterial pressures of <20 mm Hg. When heart rate declined progressively, pigs randomly received a bolus dose and continuous infusion of either vasopressin (0.4 units/kg and 0.04 units.kg-1.min-1, n = 7), or epinephrine (45 microg/kg and 5 microg.kg(-1).min(-1), n = 7), or an equal volume of saline placebo (n = 7), respectively. At 30 mins after drug administration, all surviving animals were fluid resuscitated while bleeding was surgically controlled. MEASUREMENTS AND MAIN RESULTS: Mean +/- sem arterial blood pressure at 2.5 and 10 mins was significantly (p <.001) higher after vasopressin vs. epinephrine vs. saline placebo (82 +/- 14 vs. 23 +/- 4 vs. 11 +/- 3 mm Hg, and 42 +/- 4 vs. 10 +/- 5 vs. 6 +/- 3 mm Hg, respectively). Although portal vein blood flow was temporarily impaired by vasopressin, it was subsequently restored and significantly (p <.01) higher when compared with epinephrine or saline placebo (9 +/- 5 vs. 121 +/- 3 vs. 54 +/- 22 mL/min and 150 +/- 20 vs. 31 +/- 17 vs. 0 +/- 0 mL/min, respectively). Hepatic and renal artery blood flow was significantly higher throughout the study in the vasopressin group; however, no further bleeding was observed. Despite a second bolus dose, all epinephrine- and saline placebo-treated animals died within 15 mins after drug administration. By contrast, seven of seven vasopressin-treated animals survived until fluid replacement, and 60 mins thereafter, without further vasopressor therapy (p <.01). Moreover, blood flow to liver, gut, and kidney returned to normal values in the postshock phase. CONCLUSIONS: Vasopressin, but not epinephrine or saline placebo, improved short-term survival in a porcine model of uncontrolled hemorrhagic shock after liver injury when surgical intervention and fluid replacement was delayed.     

Intracardiac echocardiography identifies pericardial fluid and can monitor the success of pericardiocentesis: experimental studies.

Pericardial tamponade is a complication of cardiac catheterization. Our purpose was to evaluate the ability of intracardiac echocardiography (ICE) to identify pericardial fluid and the success of pericardiocentesis in an experimental model. Seven dogs were studied with the use of a 10F, 10-MHz ICE catheter in the left ventricle. Normal saline was injected into the pericardial space while heart rate and arterial pressure were continuously monitored. The ability of ICE to identify the presence of pericardial fluid and the maximum pericardial separation and to monitor fluid accumulation and withdrawal was evaluated. Thirteen sequences of saline injection/withdrawal were studied. ICE correctly identified the presence or absence of pericardial fluid in all 13 injection/withdrawal sequences. The average sonolucent space separating epicardium from pericardium was 12 +/- 7 mm, generated from 148 +/- 65 mL of saline and producing a 35 +/- 23 mm Hg decrease in systolic blood pressure. ICE readily identified the accumulation and removal of pericardial fluid in this experimental model and should be an excellent tool to monitor pericardiocentesis in the catheterization laboratory.     

Jejunal mucosal nitric oxide production and substrate dependency during acute mesenteric hypoperfusion in pigs

OBJECTIVE: Jejunal nitric oxide (NO) formation is impaired during mucosal hypoperfusion. This study was undertaken to investigate whether this phenomenon could result from a restricted mucosal availability of NO-synthase substrates, ie, oxygen and/or L-arginine. DESIGN: Controlled study using laboratory animals. SETTING: University animal research laboratory. SUBJECTS: Eighteen chloralose-anesthetized, ventilated, juvenile Landrace domestic pigs. INTERVENTIONS: Mesenteric hypoperfusion was induced by intrapericardial infusion of Ringer's solution to achieve decreased cardiac output by creation of cardiac tamponade. MEASUREMENTS AND MAIN RESULTS: Animals were prepared for jejunal intraluminal perfusion with 150 mM NaCl or 3 mM L-arginine solution in an isolated intestinal segment and then subjected to cardiac tamponade. Jejunal mucosal NO formation was measured with a tonometric technique. Mesenteric blood flow was measured as portal blood flow, and mucosal perfusion was measured by laser Doppler flowmetry. Regional oxygen consumption and delivery were calculated from arterial and portal blood samples. Cardiac tamponade reduced jejunal NO formation (-52%), mesenteric oxygen delivery (-75%), oxygen consumption (-39%), and mucosal perfusion (-43%). Oxygenation of the jejunal intraluminal perfusate completely restored the intestinal NO levels within 30 mins, whereas presence of L-arginine was without effect. CONCLUSIONS: The study indicates that oxygen rather than L-arginine is the rate-limiting factor for mucosal NO production during acute reduced splanchnic perfusion.     

Norepinephrine and vital organ blood flow

OBJECTIVE: To test whether norepinephrine (NE) infusion at 0.4 microg kg(-1) min(-1) adversely affects regional blood flow in the normal mammalian circulation. DESIGN AND SETTING: Randomized cross-over experimental animal study in a university-affiliated physiology institute. SUBJECTS: Six merino ewes. INTERVENTIONS: Staged insertion of transit-time flow probes around the ascending aorta and circumflex coronary, superior mesenteric and left renal arteries. In conscious animals with chronically embedded flow probes randomization to either 6 h of placebo (saline) or drug (NE at 0.4 microg kg(-1) min(-1)). MEASUREMENTS AND RESULTS: Compared to placebo, NE significantly increased mean arterial pressure (84.4 vs. 103.8 mmHg), heart rate (61.0 vs. 74.6 bpm) and cardiac output (3.76 vs. 4.78 l/min). These changes were associated with an increase in coronary blood flow (24.2 vs. 37.4 ml/min) and renal blood flow (215.2 vs. 282.0 ml/min) but no change in mesenteric blood flow. The increase in renal and coronary blood flow was associated with an increase in regional conductance (regional vasodilatation), while mesenteric conductance fell (mesenteric vasoconstriction). Urine output (91+/-17 vs. 491+/-360 ml/h) and creatinine clearance (61+/-18 vs. 89+/-12 ml/min) increased during NE infusion. CONCLUSIONS: NE infusion does not induce vital organ ischaemia in the normal mammalian circulation. Furthermore, it results in a significant increase in coronary and renal blood flow with a concomitant improvement in urine output and creatinine clearance.     

Early albumin infusion improves global and local hemodynamics and reduces inflammatory response in hemorrhagic shock

OBJECTIVE: To evaluate the effects of an early, short-term albumin infusion on mesenteric microcirculation and global hemodynamics in hemorrhagic shock. DESIGN: A prospective, randomized study. SETTING: Animal laboratory at a university medical clinic. SUBJECTS: Seventeen Sprague-Dawley rats weighing 250-400 g. INTERVENTIONS: The rats underwent median laparotomy and exteriorization of an ileal loop for intravital microscopy of the mesenteric microcirculation. Volume-controlled hemorrhagic shock was provoked by arterial blood withdrawal (2.5 mL/100 g body weight for 60 mins), followed by a 4-hr reperfusion period. Albumin (20%) or 0.9% NaCl was administered intravenously as a continuous infusion for 30 mins at the beginning of reperfusion. Reperfusion time mimicked a "prehospital" phase of 30 mins followed by a quasi "in-hospital" phase of 3.5 hrs. The "in-hospital" phase in both groups was initiated by substitution of blood followed by reperfusion with normal saline. MEASUREMENTS AND MAIN RESULTS: Central hemodynamics, mesenteric microcirculation, and arterial blood gas parameters were monitored before, during, and 60 mins after hemorrhagic shock, and for a 240-min follow-up period after initiation of reperfusion. Application of albumin markedly reduced rolling and adherent leukocytes, maximum velocity, and shear rate in the mesenteric microcirculation. Later, after improvement of mesenteric microcirculation, an intermittent increase of central venous pressure and abdominal blood flow and decrease of hematocrit was observed. CONCLUSIONS: Albumin treatment of hemorrhagic shock improves microcirculation and global hemodynamics and attenuates the inflammatory response to reperfusion. It may provide clinical benefit when applied at an early stage of reperfusion during hemorrhagic shock.     

Gut luminal lactate release during gradual intestinal ischemia

OBJECTIVES: Gut ischemia induced by occlusion of the superior mesenteric artery (SMA) results in release of lactate into the gut lumen. We studied the threshold of SMA flow reduction that leads to increased gut luminal lactate during stepwise reduction in SMA blood flow. DESIGN AND SETTING: A randomized, controlled animal experiment in a university experimental research laboratory. INTERVENTIONS: Anesthetized, normoventilated, normovolemic domestic pigs were randomized to ischemia ( n=7) and sham groups ( n=7). SMA blood flow was reduced stepwise at 15-min intervals by 22%, 44%, 66%, and 88% and kept constant thereafter for 60 min. MEASUREMENTS AND RESULTS: Jejunal luminal microdialysate lactate and mucosal pCO(2) were measured every 15 min. The luminal lactate increased over the upper normal limit of 0.2 mmol/l at a median SMA blood flow of 9.6 ml kg(-1) min(-1) (range 7.5-23.7). In five of seven animals the increase in luminal lactate was preceded by or accompanied by an increase in the mucosal-arterial pCO(2) gradient. CONCLUSIONS: There is a threshold of SMA blood flow below which gut luminal lactate increases, indicating mucosal anaerobic metabolism. Measurement of gut luminal lactate by microdialysis can be used to assess the adequacy of gut perfusion and the onset of anaerobic metabolism.     

Antioxidant LY231617 enhances electrophysiologic recovery after global cerebral ischemia in dogs

OBJECTIVE: The potent antioxidant LY231617 (2,6-bis(1,1-dimethylethyl)-4-[[(1-ethyl)amino]methyl]phenol hydrochloride) is cytoprotective in models of focal and global cerebral ischemia. We tested the hypothesis that administration of LY231617, before the insult, would improve recovery of cerebral electrical activity and metabolic function after transient global cerebral ischemia by improving cerebral blood flow (CBF) during the reperfusion period. DESIGN: Randomized, controlled, prospective study. SETTING: Research laboratory at a university teaching hospital. SUBJECTS: Twenty-four male beagle dogs. INTERVENTIONS: All experiments were performed under pentobarbital anesthesia and controlled conditions of normoxia, normocarbia, and normothermia. Twelve control dogs received 20 mL/kg saline (vehicle) bolus into the right atrium and 0.01 mL/kg/min i.v., beginning 20 mins before 13 mins of global cerebral ischemia (by aortic occlusion). The dogs in the drug-treated group received LY231617 as a 10-mg/kg bolus 20 mins before ischemia and 5 mg/kg/hr throughout reperfusion (n = 12). CBF was measured using radiolabeled microspheres. MEASUREMENTS AND MAIN RESULTS: Total CBF, cerebral oxygen consumption, and somatosensory evoked potentials (SEP) were measured during 240 mins of reperfusion. CBF was similar in both vehicle- and LY231617-treated animals at baseline and throughout the experimental period. In all animals, SEP became isoelectric between 60 and 100 secs after cross-clamping of the ascending aorta. SEP amplitude recovery was significantly higher in drug-treated animals compared with controls (73%+/-15% vs. 39%+/-14% [mean+/-SEM] from baseline at 120 mins [p<.05] and 86%+/-12% vs. 49%+/-14% from baseline at 240 mins [p< .05]). CONCLUSIONS: LY231617 improves recovery of cerebral electrical function after complete transient global ischemia via mechanisms unrelated to cerebral circulatory effects.     

Endorphin mediation of mesenteric blood flow after endotoxemia in sheep.

BACKGROUND AND METHODS: The administration of endotoxin in small dosages to sheep results in an acute decrease followed by an increase in cardiac output. It has previously been determined that the initial decrease in output was the result of a reduction in blood flow to the mesenteric areas. These changes were associated with increased blood concentrations of beta endorphin. The present study was accomplished to determine if the systemic cardiovascular response to endotoxin could be affected by the administration of an opiate receptor-blocking agent. Female range sheep (n = 12) were prepared for chronic study by implantation of cardiopulmonary catheters and a flow probe on the cephalic mesenteric artery. Endotoxin (Escherichia coli, 1 microgram/kg) was administered to these animals. Half of the sheep were treated with naloxone (2 mg/kg + 2 mg/kg.hr), and the remainder with an equivalent volume of sodium chloride (0.9%). RESULTS: In untreated sheep, cardiac indices decreased by 15% to 20% (5.1 +/- 0.1 to 4.2 +/- 0.4 L/min.m2) between 0 and 1 hr and 2 and 5 hrs after endotoxin (4.5 +/- 0.2 L/min.m2), and then increased to a value 40% (7.2 +/- 0.6 L/min.m2) above baseline by 12 hrs. Flow in the cephalic mesenteric artery decreased in a pattern similar to the reduction in cardiac index (962 +/- 152 [time, T = 0] to 379 +/- 111 [T = 0.8] and 384 +/- 88 mL/min [T = 4.0], p less than .05) but did not increase to the same extent (1008 +/- 153 mL/min [T = 4.0], p greater than .05). There was a concomitant increase in the plasma beta-endorphin concentrations as the blood flow decreased (5 +/- 4 [T = 0] to 40 +/- 15 pg/mL [T = 0.8; untreated group], p less than .05; and 10 +/- 4 to 50 +/- 7 pg/mL [T = 0.8; naloxone-treated group], p less than .05). In the naloxone-treated group, the same pattern of cardiac output change was noted with endotoxin; however, reduction of mesenteric artery flow was only 30% (1118 +/- 129 to 908 +/- 122 mL/min, p less than .05) of the value seen in the untreated animals (962 +/- 152 to 379 +/- 111 mL/min, p less than .05). These changes in mesenteric blood flow were statistically significant from one another. As the cardiac output increased in the sheep treated with the opiate antagonist, mesenteric blood flows increased 20% above the baseline value (1391 +/- 199 mL/min, p less than .05). CONCLUSIONS: The decrease in cardiac output noted with endotoxin can be accounted for by the decrease in the blood flow in the cephalic mesenteric artery. This phenomenon can be attributed, at least in part, to the release of endorphins. There is both a vasodilation and constriction during endotoxemia in the ovine model.