Comparison of lactated Ringer's, gelatine and blood resuscitation on intestinal oxygen supply and mucosal tissue oxygen tension in haemorrhagic shock

Objectives. To evaluate the effects on intestinal oxygen supply,and mucosal tissue oxygen tension during haemorrhage and afterfluid resuscitation with either blood (B; n=7), gelatine (G;n=8), or lactated Ringer's solution (R; n=8) in an autoperfused,innervated jejunal segment in anaesthetized pigs. Methods. To induce haemorrhagic shock, 50% of calculated bloodvolume was withdrawn. Systemic haemodynamics, mesenteric venousand systemic acid–base and blood gas variables, and lactatemeasurements were recorded. A flowmeter was used for measuringmesenteric arterial blood flow. Mucosal tissue oxygen tension(PO₂muc), jejunal microvascular haemoglobin oxygen saturation(HbO₂) and microvascular blood flow were measured. Measurementswere performed at baseline, after haemorrhage and at four 20min intervals after fluid resuscitation. After haemorrhage,animals were retransfused with blood, gelatine or lactated Ringer'ssolution until baseline pulmonary capillary wedge pressure wasreached. Results. After resuscitation, no significant differences inmacrohaemodynamic parameters were observed between groups. Systemicand intestinal lactate concentration was significantly increasedin animals receiving lactated Ringer's solution [5.6 (1.1) vs3.3 (1.1) mmol litre^–1; 5.6 (1.1) vs 3.3 (1.2) mmol litre^–1].Oxygen supply to the intestine was impaired in animals receivinglactated Ringer's solution when compared with animals receivingblood. Blood and gelatine resuscitation resulted in higher HbO₂than with lactated Ringer's resuscitation after haemorrhagicshock [B, 43.8 (10.4)%; G, 34.6 (9.4)%; R, 28.0 (9.3)%]. PO₂mucwas better preserved with gelatine resuscitation when comparedwith lactated Ringer's or blood resuscitation [20.0 (8.8) vs13.8 (7.1) mm Hg, 15.2 (7.2) mm Hg, respectively]. Conclusion. Blood or gelatine infusion improves mucosal tissueoxygenation of the porcine jejunum after severe haemorrhagewhen compared with lactated Ringer's solution.     

Pharmacologic effects of gastrointestinal hormones on intestinal oxygen consumption and blood flow.

The vasoactive effects of cholecystokinin-octapeptide (CCK-OP), pentagastrin, synthetic secretin, glucagon, and acetylcholine were assessed in the intestinal circulation of the dog. In pharmacologic doses of glucagon, CCK-OP, and, to a lesser degree, pentagastrin significantly increased blood flow and oxygen consumption. Atropine blocked the vasodilator effects of CCK-OP, pentagastrin, and acetylcholine but did not block those of glucagon. Neither the alpha-adrenergic blocker, phenoxybenzamine, nor the beta-adrenergic blocker, propranolol, blocked the vasodilator response to pentagastrin. Synthetic secretin had no significant effect on either blood flow or oxygen consumption in the intestinal segment. The vasodilator response to CCK-OP and pentagastrin appears to be mediated specifically through cholinergic receptors.     

Effects of intra-aortic balloon occlusion on intestinal perfusion, oxygen metabolism and gastric mucosal PCO2 during experimental hemorrhagic shock

BACKGROUND: Aortic occlusion has been suggested for the initial treatment of severe uncontrolled hemorrhagic shock. Our objective is to determine the impact of aortic occlusion, during hemorrhagic shock, on splanchnic mucosal perfusion and to correlate these findings with other systemic and regional markers of splanchnic ischemia. METHODS: Fourteen dogs (17 +/- 1.7 kg) anesthetized with pentobarbital were bled to a mean arterial pressure (MAP) of 40 mm Hg. After 30 min, the animals were randomly assigned to controls (no aortic occlusion, n = 7) and transfemoral aortic occlusion (TAO) at T9 level (n = 7). Superior mesenteric artery blood flow (SMABF, ultrasonic flow probe), gastric mucosal PCO2 (gastric tonometry) and splanchnic oxygen extraction ratio (O2ERsplanc) were evaluated for 120 min. RESULTS: Hemorrhage caused a marked reduction in SMABF and increases in PCO2-gap and O2ERsplanc in both groups. TAO significantly improved MAP and further increased the PCO2-gap and O2ERsplanc, with a decreased SMABF. After reperfusion, SMABF, MAP and O2ERsplanc returned to pre-occlusion values, although the PCO2-gap remained higher in the TAO group. CONCLUSION: Aortic occlusion promotes blood pressure restoration with an additional insult to mucosal perfusion, which could be adequately predicted by global and/or splanchnic oxygen-derived variables during ischemia, but not during the early reperfusion period.     

The effect of stored blood on mesenteric oxygen extraction during endotoxin shock

Storage of blood in acid-citrate-dextrose (ACD) solution gradually depletes red cell 2,3-diphosphoglycerate (DPG) and increases the affinity of hemoglobin for oxygen. We examined the effect of exchange transfusion of DPG-depleted blood on mesenteric blood flow and oxygen consumption in dogs subjected to endotoxin shock. Two groups of 6 dogs each were anesthetized and subjected to exchange transfusion with either fresh ACD blood or 21-day-old ACD blood prior to administration ofEscherichia coli endotoxin (2 mg/kg). Mesenteric blood flow, arteriovenous oxygen content difference and systemic arterial blood pressure were monitored continuously before and for 60 min after endotoxin. Mesenteric blood flow was reduced from 250±21 ml/min before endotoxin to 114±15 ml/min at 5 min, 157±29 ml/min at 30 min, and 112±17 ml/min at 60 min after endotoxin in the dogs exchanged with fresh blood. Corresponding values for intestinal oxygen consumption were 10.4±1.0, 7.5±0.8, 8.4±1.0, and 6.8±0.7 ml/min. In dogs transfused with 21-day-old blood, pre-endotoxin blood flow was 208±2 ml/min and declined to 115±12, 93±5, and 80±8 ml/min at 5, 30, and 60 min post-endotoxin. Corresponding values for intestinal oxygen consumption were 8.1±0.9, 6.6±0.7, 6.2±0.5, and 5.5±0.7 ml/min. There was no significant difference (p>0.1) in responses of blood flow or oxygen consumption to endotoxin shock between the two groups of dogs. These findings indicate that exchange transfusion with DPG-depleted blood does not impair oxygen extraction by the ischemic intestine.

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Résumé L'entreposage du sang dans une solution d'acidecitrate-dextrose (ACD) s'accompagne d'une perte graduelle du 2,3 diphosphoglycerate (DPG) contenu dans les globules rouges et augmente l'affinité de l'hémoglobine pour l'oxygène. Noux avons examiné l'effet des transfusions d'échange de sang pauvre en DPG sur la consummotion d'oxygène et le flot sanguin mèsentérique chez des chiens soumis à un choc endotoxique. Deux groupes de six chiens furent anesthésiés, transfusés soit avec du sang ACD frais ou du sang ACD entroposé pendant 21 jours puis reÇurent une injection d'endotoxine d'E. coli (2mg/kg). Le flot mésentérique, la différence du contenu en oxygène entre le sang veineux et artériel et le pression artérielle furent engregistrés continuellement avant puis durant 60 minutes suivant l'injection d'endotoxine. Le flot mésentérique, de 250±21 ml/min, avant l'injection d'endotoxine, fut réduit à 114±15 ml/min, après 5 minutes, à 157±29 ml/min, après 30 minutes et à 112±17 ml/min, après 60 minutes suite à l'injection d'endotoxine chez les chiens ayant reÇus des transfusions d'échange de sang frais. Les valeurs correspondentes pour la consommotion d'oxygène par l'intestin furent 10.4±1, 7.5±0.8, 8.4±1.0 et 6.8±0.7 ml/min. Chez les chiens transfusés avec du sang âgé de 21 jours, le flot sanguin mésentérique fut mesuré à 208±2 ml/min, avant l'injection d'endotoxine, et à 5, 30 et 60 minutes après injection, fut réduit respectivement à 115±12, 93±5 et 80±8 ml/min. Les valeurs correspondantes pour la consommotion intestinale d'oxygène furent 8.1±0.9, 6.6±0.7, 6.2±0.5 et 5.5±0.7 ml/min. En réponse au choc endotoxique, la différence ne fut pas significative entre les 2 groupes de chiens (p>0.1) quand au flot sanguin et la consommotion en oxygène. Les auteurs concluent que les transfusions d'échange avec du sang pauvre en DPG ne diminuent pas l'extraction de l'oxygène par l'intestin ischémique.

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These investigations were supported in part by a grant from the National Institutes of Health (AM/HL 18629-01)     

Comparison of catecholamine effects on canine myocardial metabolism and regional blood flow during and after cardiopulmonary bypass

The acute metabolic and hemodynamic effects of dopamine, dobutamine (both at 10 micrograms . kg-1 . min), and isoproterenol (at 0.05 or 0.1 micrograms . kg-1. min) were determined in dogs following 20 minutes of normothermic global myocardial ischemia. The catecholamines were started 10 minutes before cardiopulmonary bypass (CPB) was discontinued and were continued for 1 hour after bypass. Regional myocardial and systemic blood flow distribution was measured by means of the radioactive microsphere technique. On bypass all catecholamines sharply increased heart rate, myocardial oxygen consumption, and left ventricular blood flow (p less than 0.01). Because the hearts were unloaded, these data suggest that velocity of contraction is an important component of myocardial oxygen consumption. Although these drugs did not lower myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) levels, the significant rise in oxygen consumption suggested that inotropic treatment on bypass may not be beneficial. Furthermore, renal blood flow was diminished in dobutamine-treated dogs (p less than 0.01) and tended to decrease with isoproterenol infusion. No change was seen with dopamine infusion. After bypass, dobutamine treatment increased cardiac output (p less than 0.01) and stroke volume (p = 0.017) with no change in heart rate, myocardial oxygen consumption, high-energy phosphate levels, and total or transmural distribution of left ventricular blood flow. Dopamine infusion did not change cardiac output but did increase oxygen consumption (p less than 0.01). Isoproterenol showed a slight inotropic effect, but frequent ventricular arrhythmias were present during weaning from bypass. In all treatment groups, blood flow in the other systemic beds (cerebral, gastrointestinal, and renal) was similar to that in control dogs. These data suggest that dobutamine is the most efficient of the drugs tested for support of the heart following global myocardial ischemia but, when given during bypass, it appears to decrease renal blood flow.     

The effects of sepsis on gut mucosal blood flow in rats.

BACKGROUND AND OBJECTIVE: The effects of sepsis on gut mucosal blood flow have not been fully clarified. We designed an experiment to explicitly describe the effects of sepsis on gut mucosal blood flow in rats using an advanced intravital microscopy technique. METHODS: This work was performed as a prospective, controlled laboratory experiment. Twenty-four hours after sham laparotomy or laparotomy and caecal ligation and perforation to create sepsis, rats were anaesthetized and their lungs mechanically ventilated (n=7 per group). Intravital videomicroscopy was performed on 6-12 villi of ileum mucosa. Video recordings were analysed off-line using computerized image analysis. RESULTS: Intercapillary area size (inversely related to capillary density) was increased in sepsis as compared with the control group (941 +/- 92 vs. 669 +/- 79 microm(2), P < 0.05). In the central villus arteriole, blood flow was similar between groups (control: 3.5 +/- 0.4 nL min(-1); caecal ligation and perforation group: 3.6 +/- 0.5 nL min(-1)). There were no relevant changes in arteriolar red cell velocity and diameter. CONCLUSIONS: In the gut mucosa of rats, sepsis resulting from caecal ligation and perforation depressed the perfused capillary density without affecting blood flow in the central villus arteriole. Mucosal hypoperfusion at the level of the capillary networks may occur in the presence of precapillary shunting in the villus microcirculation.     

Effect of increased intra-abdominal pressure on mesenteric arterial and intestinal mucosal blood flow.

The effects of increased intra-abdominal pressure (IAP) on intestinal blood flow were studied in eight anesthetized pigs. Mesenteric artery blood flow (MABF), intestinal mucosal blood flow (IMBP), tonometric intramucosal pH (pHi), mean BP (MAP), cardiac output (CO), and pulmonary artery wedge pressure (PAWP) were measured as IAP was raised to 10, 20, 30, and 40 mm Hg by infusing lactated Ringer's solution (LR) into the peritoneal cavity. The MAP was kept constant with IV LR. Cardiac output fell slightly from 5.4 +/- 1.1 at baseline to 4.0 +/- 1.2 L/min at an IAP of 40 mm Hg (p less than 0.05). An IAP of 20 mm Hg caused significant decreases in MABF (73% +/- 22% of baseline) (p less than 0.05) and IMBF (61% + 12% of baseline) (p less than 0.05). These changes became progressively greater as the IAP was increased to 40 mm Hg. The pHi fell to 6.98 +/- 0.14 at 40 mm Hg IAP (p less than 0.01), indicating severe mucosal ischemia. Thus increased IAP can cause severe intestinal ischemia, which may be more important than the cardiac, pulmonary, and renal changes usually described.     

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 vasopressin on systemic and splanchnic hemodynamics and metabolism in endotoxin shock

We compared the effects of vasopressin and norepinephrine on systemic and splanchnic circulation and metabolism in endotoxin shock in pigs. Twenty-one pigs were randomized to endotoxin shock (Escherichia coli endotoxin infusion) (n = 6), endotoxin and vasopressin (VASO; n = 6), endotoxin and norepinephrine (NE; n = 6), and controls (n = 3). Endotoxin infusion was increased to induce hypotension, after which vasopressin or norepinephrine was started to keep systemic mean arterial blood pressure >70 mm Hg. Regional blood flows and arterial and regional lactate concentrations were measured. Tonometers with microdialysis capillaries were inserted into the stomach, jejunum, and colon. Systemic mean arterial blood pressure >70 mm Hg was achieved in the VASO and NE groups. Vasopressin decreased cardiac output, superior mesenteric artery, and portal vein blood flow, whereas hepatic arterial blood flow increased. Arterial lactate concentration increased from 2.0 mM (1.6-2.1 mM) to 4.7 mM (4.7-4.9 mM) (P = 0.007). Systemic and mesenteric oxygen delivery and consumption decreased and oxygen extraction increased in the VASO group. Vasopressin increased mucosal-arterial PCO(2) gradients in all three locations, whereas luminal lactate release occurred only in the jejunum. Animals in the NE group remained stable. Vasopressin reversed hypotension but decreased systemic and gut blood flow. This was associated with hyperlactatemia, signs of visceral dysoxia, and jejunal luminal lactate release. IMPLICATIONS: Although vasopressin induces vasoconstriction in visceral region, its effects on splanchnic circulation and metabolism during septic-endotoxin shock are still poorly characterized. We evaluated the metabolic and hemodynamic effects of vasopressin and norepinephrine within the splanchnic area in porcine endotoxin shock.     

The effect of glycerol on regional cerebral blood flow, blood volume and oxygen metabolism

Using positron emission tomography with 15O-labelled CO2 O2 and CO gases, the effects of glycerol on regional cerebral blood flow (CBF), blood volume (CBV) and oxygen metabolism (CMRO2) were investigated in 6 patients with meningioma accompanying peritumoral brain edema. The same study was done in 5 normal volunteers. The changes of blood gases, hematocrit and hemoglobin were also examined. After a drip infusion of glycerol, the regional CBF increased not only in the peritumoral cortex and white matter but also in the intact cortex and white matter on the contralateral side. The increase of CBF was extensive and substantially there were no regional differences. In contrast, the changes of CMRO2 were not significant. This was derived from the increase in oxygen extraction fraction throughout extensive areas including the peritumoral area. There were no changes in CBV. Hematocrit and hemoglobin decreased to a small degree. In the normal volunteers, the same findings were noted. Thus, glycerol increases the functional reserve for cerebral oxygen metabolism, not only in the peritumoral regions but also in the intact regions. The effects of glycerol on hemodynamics and metabolism were discussed with reference to some differences from mannitol.     

Effects of endotoxin on intestinal hemodynamics, glutamine metabolism, and function

The purpose of this study was to investigate the intestinal hemodynamics and gut glutamine metabolism during endotoxemia, and their correlation with altered intestinal absorptive capacity and permeability. Seventeen Sprague-Dawley rats were used in the study. The endotoxin group (ENDO) recieved endotoxin (10 mg/kg intraperitoneally,n=9), while the control group (CONT,n=8) received saline injection. Twelve hours later, D-xylose (0.5 g/kg) and fluorescein isothiocyanate-dextran (FITC-dextran, 750 mg/kg) were given by oral gavage. One hour later abdominal aortic (AA) blood flow, superior mesenteric venous (SMV) flow, mean arterial pressure (MAP), central venous pressure (CVP), and SMV pressure (SMVP) were also measured. The MAP, AA, and SMV blood flow decreased (P<0.05), while the CVP and SMVP increased (P<0.05) in the ENDO group as compared with the CONT group. The ENDO group showed significant decreases for both intestinal glutaminase activity and net intestinal glutamine uptake (P<0.05). The D-xylose concentration in SMV decreased significantly (P<0.05) in the ENDO group as compared with the CONT group. However, the plasma FITC-dextran concentration showed no significant difference between the groups. Endotoxin produced a hypodynamic effect in rats 12h after intraperitoneal administration in association with both a decreased intestinal glutamine metabolism and an absorptive capacity.     

Influence of cold on stress ulceration and on gastric mucosal blood flow and energy metabolism.

"Ice-cold" gastric lavage is an important part of the treatment of bleeding from stress ulceration. The purpose of this study was to find out if cooling modifies ischemic injury of the gastric mucosa. Four series of experiments were performed in rabbits. In the first, we studied the influence of cooling on the rate of breakdown of gastric mucosal high energy phosphates during complete, ex vivo ischemia achieved by rapid excision of the stomach. We then studied the influence of cold versus warm gastric lavage on the severity of gastric mucosal injury and on the rate of breakdown of gastric mucosal adenosine phosphates during hemorrhagic shock. In a fourth series of experiments, we examined the influence of cold versus warm gastric lavage on gastric mucosal blood flow measured by injection of radioactive microspheres. Although the rate of breakdown of mucosal high energy phosphates was less rapid during a short period of complete, ex vivo ischemia when the stomach was cooled, this rate was more rapid during hemorrhagic shock under in vivo conditions when the stomach was lavaged with cold solution. The latter also increased the severity of shock-induced gastric mucosal injury. Cold gastric lavage reduced gastric mucosal blood flow before, during and after hemorrhagic shock.     

Effects of short-term fenoldopam infusion on gastric mucosal blood flow in septic shock

BACKGROUND: Inadequate splanchnic perfusion in septic shock is associated with increased morbidity and mortality. As result of splanchnic ischemia, mucosal permeability increases. Considering the implication of improved mucosal perfusion in terms of maintenance of mucosal barrier integrity, dopamine-1 receptor stimulation could be helpful in septic shock. The goal of the current study was to determine the effects of fenoldopam on systemic hemodynamic parameters and gastric mucosal perfusion in patients with septic shock. Furthermore, the authors tested the hypothesis that the addition of fenoldopam (0.1 microg x kg(-1) x min(-1)) to a combination of norepinephrine and dobutamine (5 microg x kg(-1) x min(-1)) may improve gastric mucosal perfusion in septic shock. METHODS: Patients with septic shock were randomized to a double-blind 2-h infusion of fenoldopam (n = 20) or placebo (n = 20). Each group received dobutamine (5 microg x kg(-1) x min(-1)), and the dosage of norepinephrine was adjusted to achieve a mean arterial pressure between 70 and 80 mmHg. A laser-Doppler probe and tonometer were introduced into the gastric lumen. RESULTS: A significant increase in gastric mucosal perfusion, detected by laser-Doppler flowmetry, was observed in the group treated with fenoldopam (P < 0.05). In addition, this increase in microcirculatory flow occurred despite the fact that systemic flow remained unchanged. Differences in gastroarterial partial pressure of carbon dioxide values were not statistically significant in the fenoldopam and placebo groups. CONCLUSIONS: The study showed that, for the same mean arterial pressure, short-term fenoldopam infusion increased gastric mucosal perfusion in patients with septic shock.     

Influence of induced hyperthermia on intestinal blood flow, translocation of endotoxin and other factors in mongrel dogs

This study was undertaken to investigate the effects of induced hyperthermia over 3 hr at 42.5 degrees C on intestinal blood flow, plasma endotoxin, cardiovascular system and other factors under a constant CVP level in 38 mature mongrel dogs. During hyperthermia, blood flow of the small intestine and colon showed no remarkable changes. The perfusion rates (blood flow/CI) showed a downward trend above 42 degrees C but there were no significant changes. At 42.5 degrees C, plasma endotoxin level in 9 of 14 dogs increased over 100 pg.ml-1 on the quantitative analysis. On qualitative analysis, 10 of 16 dogs that were positive for plasma endotoxin did not survive. The cardiac index increased gradually at temperature above 40 degrees C and increased significantly during hyperthermia at 42 degrees C and 42.5 degrees C. It then decreased gradually. The platelet counts decreased significantly at 42.5 degrees C over 1 hour, and white blood cell counts increased significantly at 42 degrees C and 42.5 degrees C, decreasing gradually thereafter. The red cell counts showed no significant change. Blood sugar level decreased significantly during hyperthermia at 42.5 degrees C and 42.5 degrees C for 1 hour. Lactate level increased significantly after hyperthermia at 42.5 degrees C for 1 hour, and pH decreased significantly over 3 hours at 42.5 degrees C. However, PaO2 was always maintained over 300 mmHg, and PaCO2 was maintained at 35-40 mmHg. Form the above results, it is conceivable that hyperthermia may have led to leakage of endotoxin into the systemic circulation, because reduced splanchnic blood flow and hypoxemia were not observed. The endotoxemia may be a contributing factor in the pathogenesis of heat stroke.