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We investigated the systemic and regional hemodynamic effects of early crystalloid infusion in an experimental model of septic shock induced by intravenous inoculation with live Escherichia coli. Anesthetized dogs received an intravenous infusion of 1.2 x 10(10) cfu/kg live E. coli in 30 min. After 30 min of observation, they were randomized to controls (no fluids; N = 7), or fluid resuscitation with lactated Ringer's solution, 16 ml/kg (N = 7) or 32 ml/kg (N = 7) over 30 min and followed for 120 min. Cardiac index, portal blood flow, mean arterial pressure, systemic and regional oxygen-derived variables, blood lactate, and gastric PCO2 were assessed. Rapid and progressive cardiovascular deterioration with reduction in cardiac output, mean arterial pressure and portal blood flow (approximately 50, approximately 25 and approximately 70%, respectively) was induced by the live bacteria challenge. Systemic and regional territories showed significant increases in oxygen extraction and in lactate levels. Significant increases in venous-arterial (approximately 9.6 mmHg), portal-arterial (approximately 12.1 mmHg) and gastric mucosal-arterial (approximately 18.4 mmHg) PCO2 gradients were also observed. Early fluid replacement, especially with 32 ml/kg volumes of crystalloids, promoted only partial and transient benefits such as increases of approximately 76% in cardiac index, of approximately 50% in portal vein blood flow and decreases in venous-arterial, portal-arterial, gastric mucosal-arterial PCO2 gradients (7.2 +/- 1.0, 7.2 +/- 1.3 and 9.7 +/- 2.5 mmHg, respectively). The fluid infusion promoted only modest and transient benefits, unable to restore the systemic and regional perfusional and metabolic changes in this hypodynamic septic shock model.

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.

Standard-of-care, large volume crystalloid infusion, in the setting of uncontrolled bleeding, has been challenged and it is not known if fluid resuscitation increases retroperitoneal hemorrhage. We developed an experimental model of retroperitoneal haemorrhage to correlate haemodynamic and metabolic alterations with the blood volume loss. Anaesthetised, spontaneously breathing dogs (17.1±0.56 kg) were randomised to unilateral (UL, n =11) or bilateral (BL, n =11) iliac artery puncture, using a metallic device introduced through the femoral arteries and followed for 120 min. Initial and final blood volumes were determined using radioactive tracers, 99m TC and 51 Cr, respectively. UL was associated with a stable arterial pressure and a moderate decrease in cardiac output and oxygen delivery. BL induced an abrupt and sustained decrease in mean arterial pressure, from 131.9±5.9 to 88.6±10.8 mmHg, and a much greater reduction in cardiac output, oxygen delivery and consumption than UL throughout the experiment. Total retroperitoneal blood loss after BL was 36.8±3.2 ml/kg, while after UL was 25.1±3.4 ml/kg ( P =0.0262). We conclude that a transfemoral bilateral iliac artery puncture produces a clinically relevant model of uncontrolled retroperitoneal haemorrhage, with hypotension and low flow state, while a unilateral iliac artery lesion causes a compensated shock state.

Background It has been suggested that measurement of continuous cardiac output (CCO) is an advancement in the management of critically ill patients. Our objective was to determine the accuracy of CCO during the rapid hemodynamic changes induced by hemorrhage and resuscitation. Methods In 12 anesthetized dogs (20.2+/-0.9 kg), pulmonary artery blood flow, our "gold standard" cardiac output, was measured with an sonographic flowprobe, whereas CCO, intermittent bolus cardiac output (ICO), and mixed venous oxygen saturation were measured with a thermodilution fiberoptic pulmonary artery catheter with a thermal filament. A graded hemorrhage (20 mL/min) was produced to a mean arterial pressure of 40 mm Hg, which was maintained at this level for 30 minutes. Total shed blood volume (701+/-53 mL) was retransfused at a rate of 40 mL/min, over 30 minutes, after which a massive hemorrhage (100 mL/min) was produced over 10 minutes. Results Hemorrhage induced significant decreases in mean arterial pressure, mixed venous oxygen saturation, and oxygen delivery, which were all restored during early resuscitation. However, CCO showed a delayed response after hemorrhage and resuscitation, compared with pulmonary blood flow, throughout the study (r = 0.549), matching only at baseline and at the end of both graded hemorrhage and resuscitation periods. There was a good correlation between ICO and pulmonary artery blood flow (r = 0.964) and no significant differences between them throughout the study. Conclusion CCO has a delayed response during acute hemodynamic changes induced by hemorrhage and resuscitation. When sudden changes in mean arterial pressure or in mixed venous oxygen saturation are detected, cardiac output must be estimated by the standard bolus thermodilution technique, not by CCO.

This study evaluates the hemodynamic effects of the administration of 10% pentastarch solution (PS) during the initial treatment of hypovolemia in trauma patients. This prospective randomized phase II study included trauma patients admitted to the emergency room with hemorrhagic hypovolemia: systolic blood pressure (SBP)90 mmHg. Upon admission, the patients were randomized to receive 10% PS (n = 12) or isotonic 0.9% NaCl solution (IS) (n = 11), infused intravenously in 250-ml boluses, repeated until SBP100 mmHg. Blood pressure, infused volumes necessary to maintain SBP, and overall survival rates were determined and compared between groups. SBP increased significantly following either IS (from 64.4 +/- 9.2 mmHg to 111.1 +/- 6.3 mmHg), or PS (from 63.7 +/- 10.6 mmHg to 108.1 +/- 9.8 mmHg) when compared to admission values (p0.05). Endovenous volumes infused were greater (p = 0.001) in IS patients (1420 +/- 298 ml) than in PS patients (356 +/- 64 ml). No blood was transfused into PS patients, compared to 370 +/- 140 ml of red blood cells transfused into IS patients (p = 0.015). Mortality rates were similar in the two groups (p = 0.725). We concluded that PS is a safe, efficient method for inducing hemodynamic recovery of hypovolemic trauma patients, with a clear reduction in the intravenous volumes required for acute resuscitation.

The mode of action of serotonin (complex of creatinine + 5-hydroxytryptamine) was studied upon the isolated guinea-pig ileum. The stimulating effect of serotonin on the gut was blocked by atropine and appeared, therefore, to be cholinergic in nature. Tachyphylaxis could be observed with small doses (10 μg./15 ml.) if they were added at intervals of less than 3 minutes. Total, though transitory, tachyphylaxis was observed after repeated additions of 40 μg./15 ml. of serotonin. With higher doses, a quick contraction followed by spontaneous return to the normal tonus (while the drug still was in the bath) was observed. For a certain interval of time thereafter the muscle remained refractory to smaller doses of serotonin, but still reacted to other drugs, including nicotine. Sensitivity to small doses of serotonin progressively reappeared. Moderate paralysing doses (50 to 100 μg.) of nicotine depressed or abolished the responses to serotonin and also depressed the responses to histamine, acetylcholine, and bradykinin. If much higher doses (200 to 800 μg.) of nicotine were added, the muscle “escaped” from inhibition by nicotine, responding again to serotonin and increasing in sensitivity to the other drugs, although continuing to be irresponsive to nicotine itself. Decamethonium and hexamethonium had no inhibitory effect upon serotonin action. In some experiments, hexamethonium even potentiated serotonin action. d-Tubocurarine in concentrations that had no effect upon histamine depressed the effects produced by serotonin or nicotine. The action of serotonin was completely blocked by cocaine in doses (10 to 100 μg.) that did not affect histamine or acetylcholine. From these observations the provisional conclusion is drawn that serotonin acts upon the post-ganglionic cholinergic fibres of the intramural nervous system of the guinea-pig ileum.

Background Hepatic artery thrombosis is a rare but extremely troublesome condition after liver transplantation. Recently, urgent arterial revascularization has been used as rescue therapy, leading to improved graft and patient survivals. Hepatic artery ligation produces a progressive reduction in portal vein blood flow. Theoretically, a hyperemic response may be expected following hepatic artery reperfusion (hepatic artery buffer response, HABR). In this study, we tested the hypothesis that HABR can maintain adequate liver oxygenation after temporary liver dearterialization. Methods Seven dogs (19.7 ± 1.2 kg) subjected to 60 minutes of hepatic artery occlusion were observed for 120 minutes thereafter. Systemic hemodynamics was evaluated through Swan-Ganz and arterial catheters, and splanchnic perfusion by portal vein and hepatic artery blood flows (PVBF and HABF) via an ultrasonic flowprobe. Liver enzymes (ALT and LDH) and systemic and hepatic oxygen delivery (DO 2 hepat) were calculated using standard formulae. Results Hepatic artery occlusion induced a progressive reduction in PVBF and DO 2 hepat. A complete restoration of HABF after hepatic artery declamping was observed; however, the DO 2 hepat (33.3 ± 5.9 to 16.5 ± 5.9 mL/min) did not return to the baseline levels. Conclusion Temporary hepatic artery occlusion induced a progressive decrease in portal vein blood flow during ischemia, an effect that continued during the reperfusion period. The hepatic artery blood flow was promptly restored after declamping. However, HABR was not able to restore hepatic oxygen delivery to baseline levels during the reperfusion period.

FIBRINOLYSIS in peptone and anaphylactic shock can be demonstrated either directly, by estimation of flbrinogen in samples taken after the injection of the respective agent, or by adding protamine in order to counteract the effect of the heparin which is discharged into the blood stream. We have shown1 that even the addition of an excess of a powerful preparation of human thrombin is unable to correct the decrease in fibrinogen, which can be estimated by the method of Cullen and Van Slyke2. Since thrombin was able to correct the inhibitory effect of heparin added in amounts such as those appearing in anaphylactic shock, we conclude that a drop in fibrinogen actually occurs during anaphylactic and peptone shock. Moreover, in the case of peptone shock, fibrinolysis can be directly observed, since in several cases the blood clots very quickly and the coagulum redissolves after a few hours. Apparently, Nolf3 was the first to describe this flbrinolytic effect as occurring after peptone injection, in animals in which the liver had been removed or the circulation reduced to the upper part of the body, by ligaturing the thoracic aorta and inferior vena cava, just above the diaphragm. It is now clear that in Nolf's experiments, the removal of the liver prevented the discharge of heparin, since it has been proved that heparin comes from the liver in peptone and anaphylactic shock4.

IN the two preceding papers 1 of this series we have described the main features of the shock produced in the dog by the intravenous injection of deproteinized and dialyzed extracts from Ascaris lumbricoides. We have shown that histamine and heparin are discharged in conspicuous amounts from liver cells when the extracts are injected into the intact animal and that glycogen inhibits this release when injected before the extracts. This effect of liver glycogen was ascribed to its capacity for reducing the number of leukocytes and platelets of circulating blood by allocating them to nonspecified organ structures all over the body. On the contrary, in anaphylactic shock or in the shock produced by Ascaris extracts it should be a preferential allocation of clumped leukocytes and platelets to the structure of the shock organs. As regards the rabbit, pulmonary capillaries have been shown by Dragstedt and co-workers 2 to retain leukocytes

IT is a well known fact that leukopenia and thrombopenia regularly accompany anaphylactic shock in every species of animals.1In 1924 Webb2made an extensive study of the leukopenia which occurs in sensitized dogs as a consequence of the injection of the antigen. Recently, Kopeloff and associates3and Kinsell and co-workers4have shown that a decrease in platelets is definitely proportionate to the gravity of the anaphylactic shock in monkeys and rabbits. They have also postulated that a rupture of those hematologic elements might help to explain the liberation of histamine, since rabbit platelets are especially rich in histamine.5In the case of dogs, however, it is not so easy to explain the increase of histamine in the blood as a consequence of an explosion of platelets, since those elements are very poor carriers of histamine in this species of animal. Moreover, it has been

ConclusionsFrom the results described in this paper, it appears evident that peptone produces shock in the dog by a mechanism very similar to that leading to anaphylactic shock. Participation of the white blood elements (leucocytes and platelets) in the discharge of histamine and heparin from liver cells is definitely suggested by the fact that the severity of the shock is closely connected with the incapacity of those blood elements to return to blood stream, and also by experiments with isolated liver, in which it became apparent that peptone is unable by itself to release those substances from liver cells, and that the presence and retention of blood elements (leucocytes and platelets) is an indispensable step leading to the discharge of those substances. That the final mediator for the release of these substances is activated plasma trypsin is strongly suggested by the fact that platelets contain a kinase for plasma trypsin and that there actually occurs activation of this enzyme, as shown by fibrinol...

1. Quantitative data are given on the effect of variations in the time of contact and the proportions of the reactants on the quantity of complement combining component nitrogen (C'1 N) found in active guinea pig serum. 2. C'1 N was the same when determined with precipitates containing excess antibody or excess antigen. 3. Finely divided specific precipitates took up the complement combining component (C'1) from subsequently added guinea pig serum almost as well as specific precipitates formed in the presence of complement.

Hypertonic saline, or saline-dextran resuscitation is normally achieved with an Na+ load of 4.8 to 7.2 mEq/kg given in a small volume (typically 4 to 6 ml/kg NaCl 7.5%). Na+ can also be administered saturated in a smaller volume, e.g., 1 to 1.5 ml/kg NaCl 25%, with similar results. Such reduction in administered volume would be an asset in prehospital trauma management. In the present experiments, severely bled (45 ml/kg) dogs were treated with one of three NaCl/dextran-70 solutions: S1, 25% NaCl + 24% dextran (1.5 ml/kg); S2, 15% NaCl + 14.4% dextran (2.5 ml/kg); S3, 7.5% NaCl + 6% dextran (5 ml/kg). S1, S2, and S3 were pump-infused in 10 min into a peripheral vein; S1 and S2 were also given into the right atrium. S1, S2, or S3 produced a number of similar responses irrespective of the route of administration; arterial pressure, cardiac index, and base excess reverted to near control levels, plasma Na+ was raised to 155-158 mEq/L, and 5-day survival was high and comparable. Plasma volume, and total and mean red cell volumes were similarly affected in all groups; however, peripheral injections of S1 and S2 induced severe hemolysis (plasma Hgb: 53 +/- 6 and 34 +/- 4 mg/dl, respectively), while right atrial S1 and S2 caused mild hemolysis (22 +/- 3 and 14 +/- 3 mg/dl, respectively). In contrast, S3 never induced hemolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

The inotropic effect of Krebs-Henseleit solution rendered hyperosmotic by addition of NaCl or sucrose (increments of 50, 100, 150 and 200 mOsm/l) on myocardial contractile activity was studied in rat isolated left atria paced at 4, 16 and 64 stim/min. The solutions did not affect the peak tension (Tp) at 4 stim/min, whereas sucrose caused a dose-dependent increase in Tp at 16 stim/min and NaCl decreased Tp at 64 stim/min. The total time duration of the contraction was increased in a dose-dependent fashion by both solutes, but the effect of NaCl was attenuated at 64 stim/min. The results showed that, in the isolated rat atrial tissue exposed to hyperosmotic NaCl solutions, the negative inotropic effect of increased Na+ concentration overcomes the positive influence of hyperosmolality only at higher pacing rates (about 1 Hz).

Despite the evolution of transplant techniques, the great number of donated organs continues to proceed from donors in brain death (BD). The need for stabilization in patients with BD, in the view of the triggered autonomic storm, is basic in such a way that knowledge of the physiopathologic, hemodynamic and metabolic disturbances becomes essential.

Volume replacement is one of the cornerstones in the management of sepsis. The type and amount of fluid are still controversial.

Small volumes of 7.5% NaCl (2400mOsm/L) have been extensive evaluated in animal models of hemorrhagic shock and in clinical trials of post-traumatic hypotension and as volume support for complex cardiovascular procedures. Hypertonic solutions promote immediate blood volume expansion, restore cardiac output and regional blood flows, improve microcirculation and modulate immune responses, thereby decreasing inflammatory responses triggered by shock and trauma. A large number of very interesting in vivo and in vitro experiments highlighted that hypertonic saline resuscitation may decrease susceptibility to post-traumatic sepsis, modulate trauma and sepsis-induced immune dysfunction, inflammatory response and apoptosis. All those long-term benefits associated with hypertonic resuscitation may be of potential relevance for the management of severe sepsis and septic shock In this review, we describe the mechanisms of action of hypertonic saline based on experimental studies as well as its efficacy and safety based on its clinical use. We believe those studies support the need for additional experimental and clinical studies before the widespread use of hypertonic solutions for the treatment of severe sepsis and septic shock.

In this study, we evaluated the systemic and regional pCO2 gradients changes induced by arterial and venous mesenteric blood flow obstruction. In addition, we sought to obtain evidence that systemic markers of splanchnic hypoperfusion can detect the initial changes after intestinal ischemia induced by arterial or venous blood flow interruption.

Postoperative complications after intestinal transplantation can be attributed to hypothermic storage and reperfusion injury. In this study, we sought to obtain evidence that intestinal pCO2 measurement can be a useful method for monitoring graft perfusion and early histological changes after small-bowel transplantation. Additionally, we evaluated the initial effects of isolated intestinal hypothermic perfusion (IHP) (at 4°C) on mucosal and serosal blood flow distribution, and we correlated these findings with other systemic and regional markers of mesenteric ischemia.

Portal triad occlusion (PTO) is often performed during hepatic resections for trauma or malignancies to minimize intraoperative blood loss. The pringle maneuver is also regularly required during liver transplantation. This maneuver leads to temporary hepatic ischemia and may be associated with splanchnic blood flow congestion, promoting undesirable hemodynamic disturbances in some patients. Veno-venous bypass is a useful, easily performed technique that may avoid those deleterious hemodynamic effects of PTO. We tested the hypothesis that an active spleno-femoral shunt maintains hemodynamic stability and promotes complete decompression of the mesenteric bed, avoiding intestinal mucosal blood congestion, during PTO. Methods Seven dogs (17.2 ± 0.9 kg) were subjected to 45 minutes of hepatic ischemia during which there was an active spleno-femoral shunt. Systemic hemodynamics were evaluated through Swan-Ganz and arterial catheters. Splanchnic perfusion was assessed by portal vein blood flow and hepatic artery blood flow (PVBF and HABF, ultrasonic flowprobe), intestinal mucosal-arterial pCO 2 gradient (D t-a pCO 2 , tonometry), and regional O 2 -derived variables. Results No significant changes in systemic and regional parameters were observed during the ischemia period. During reperfusion, a significant decrease in mean arterial pressure, PVBF, and arterial pH was observed. A significant increase in ALT and D t-a pCO 2 (4.8 ± 2.5 to 18.9 ± 3 mm Hg) was also observed following hepatic blood flow restoration. Conclusion Spleno-femoral shunt maintains systemic hemodynamic stability, with an effective decompression of the splanchnic bed during portal triad occlusion. The deleterious hemodynamic and metabolic effects observed during reperfusion period, such as transitory hypotension, high D t-a pCO 2 , and acidemia, were associated with an isolated hepatic ischemia-reperfusion injury, not with the blood congestion in the splanchnic bed.

The impact of acute normovolemic hemodilution (HD) on splanchnic perfusion was evaluated in 21 anesthetized (fentanyl and vancuronium) mongrel dogs (16 ± 1 kg). They were randomized to controls (n = 7, no HD), moderate HD (hematocrit 25 ± 3%, n = 7) or severe HD (hematocrit 15 ± 3% ml/kg), through an isovolemic exchange of whole blood and 6% hydroxyethylstarch at a 20 ml/min rate, to the target hematocrit. The animals were followed 120 min after HD. Cardiac output (ml/min), portal vein blood flow (ml/min), portal vein-arterial CO2 gradient (mmHg) and PCO2 gap (gas tonometry, mmHg), and splanchnic perfusion were evaluated through portal vein blood flow and gas tonometry.

The effects of various hypertonic solutions on the intraventricular conduction, ventricular repolarization and the arrhythmias caused by the intravenous (iv) injection of bupivacaine (6.5 mg/kg) were studied in sodium pentobarbital-anesthetized mongrel dogs. Hypertonic solutions, given iv 5 min before bupivacaine, were 7.5% (w/v) NaCl, 5.4% (w/v) LiCl, 50% (w/v) glucose (2,400 mOsm/l, 5 ml/kg), or 20% (w/v) mannitol (1,200 mOsm/l, 10 ml/kg). Bupivacaine induced severe arrhythmias and ventricular conduction and repolarization disturbances, as reflected by significant increases in QRS complex duration, HV interval, IV interval and monophasic action potential duration, as well as severe hemodynamic impairment. Significant prevention against ventricular electrophysiologic and hemodynamic disturbances and ventricular arrhythmias was observed with 7.5% NaCl (percent increase in QRS complex duration: 164.4 +/- 21.8% in the non-pretreated group vs 74.7 +/- 14.1% in the pretreated group, P

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.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.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.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.

Prehospital fluid resuscitation, before hemorrhage control, of hypotensive trauma victims sustaining blunt or penetrating abdominal trauma is highly controversial, largely due to concerns related to increased blood loss or rebleeding.

Treatment of severe hemorrhage offers few theoretical problems, but in practice, severe blood loss usually occurs out of hospital, often in more or less inaccessible scenarios. Controversy rages over ideal fluid, ideal volume, and minimum O2 carrying capacity, but all agree that pre-hospital, isotonic resuscitation is unfeasible. The effects of highly hypertonic 7.5% NaCl (HS) was first described in 1980, when we showed that it induced immediate and long lasting hemodynamic restoration. The addition of 6% dextran-70 to (HSD) significantly enhances the duration and intensity of volume expansion, with no loss of hemodynamic effects. HS/HSD restores cardiac output, arterial pressure, base excess and oxygen availability, induce pre-capillary vasodialtion, moderate hyperosmolarity and hypernatremia, reversal of high glucose and lactate. It interferes with endocrine secretions when administered to animals in hemorrhagic hypotension. HS acts through transient plasma volume expansion, positive inotropic effect on cardiac contractility, precapillary vasodilation through a direct action on vascular smooth muscle. Expansion of circulating volume is part of the mechanism, the extra volume coming from the intracellular compartment fluid, especially from endothelial and red blood cells, which facilitate microcirculatory flow. The new field of interactions of hypertonicity with the immune mechanisms may provide insight into the long lasting effects of hypertonic solutions. Randomized double blind prospective studies on the effects of HS, or HSD, used as first treatment of shock show that both are safe and free from collateral, toxic effects. These studies show an early significant rise in arterial blood pressure and a non-significant trend towards higher levels of survival. HSD administration to patients about to undergo cardiopulmonary bypass for cardiac surgery results in higher cardiac output before, and immediately following cardiopulmonary bypass, as well as zero fluid balance.

Background: Diagnostic laparoscopy has been used in abdominal trauma patients, although its role is not well defined. The safety of laparoscopic evaluation in trauma patients with severe intraabdominal hemorrhage has not yet been analyzed. The purpose of this study is to evaluate the hemodynamic and metabolic effects of CO2 pneumoperitoneum (COI) in hemorrhaged animals through a retroperitoneal hematoma (RH). Methods: Twenty-two 15–20-kg mongrel dogs were monitored for systemic and pulmonary hemodynamics, inferior vena cava pressure, and arterial blood gases. After 1 h of baseline, all animals were submitted to a RH. After 45 min the dogs were randomized into two groups. Control (CTR): dogs were submitted only to a RH; pneumoperitoneum (PN): dogs were submitted to a RH and 45 min later they were insufflated to an intraabdominal pressure of 10 mmHg with medical-grade CO2 gas for 30 min. Echocardiography was performed, only in PN animals, at baseline, 45 and 60 min after RH. Results: RH induced a shock condition with low, sustained levels of arterial pressure, cardiac index, left ventricular stroke index, base excess, and oxygen delivery which were further depressed following COI. Three deaths occurred in the PN group, all of them toward the end of COI. During COI, hypercapnia was observed in one animal. COI did not impair systolic function or ejection fraction. Conclusions: COI with an IAP of 10 mmHg may be deleterious in animals with hemorrhagic shock due to an intraabdominal lesion. These findings could be clinically significant in abdominal trauma patients.

Hypertonic acetate solution in small volumes greatly improves cardiac output and corrects acid-base disturbances in hemorrhaged animals. We hypothesized that the combination of alpha alpha-crosslinked human hemoglobin (alpha alpha Hb), an oxygen carrier and vasoconstrictor, with hypertonic sodium acetate (HAHb), a vasodilator, may be effective for small volume resuscitation of hemorrhagic shock. Six pigs hemorrhaged to a mean arterial pressure of 40 mmHg for 60 min (bled volume: 23.6 +/- 2.5 ml.kg-1) received a single bolus of 4 ml.kg-1 of HAHb infused over two min. HAHb restored arterial pressure, increased systemic vascular resistance and caused a modest increase in cardiac output and SvO2, while pulmonary arterial pressure and vascular resistance were markedly increased. In two animals, transient severe hypotension and low cardiac output may have been due to acute pulmonary hypertension during injection. Compared to our previous study, in which animals received 4 ml-kg-1 of alpha alpha Hb alone, HAHb produced higher cardiac output and a smaller increase in systemic and pulmonary vascular resistance. However, slower, titrated infusions may be needed when hemoglobin solutions are combined with drugs or solutions that cause vasodilation in order to decrease the likelihood of acute hemodynamic instability.

Hypertonic saline-dextran (HSD) solutions have been used for hemorrhagic shock, aortic aneurysm, and cardiopulmonary bypass surgery (CPB). Jehovah's Witness patients refuse blood and derivatives even under life-threatening conditions. A negative fluid balance for Jehovah's Witnesses would avoid further hemodilution. In this study we compared clinical, hemodynamic, laboratory evolution, and fluid balance of 20 Jehovah's Witnesses over the first 72 h following CPB. Ten received HSD immediately prior to CPB. All patients survived and were maintained in stable hemodynamic and metabolic condition throughout the study period. HSD induced high cardiac output, low vascular resistance immediately after administration. Vascular resistance remained low until the end of CPB. HSD patients ran a slightly negative fluid balance, while control patients ran a large positive fluid balance. HSD pretreatment is now used routinely for Jehovah's Witnesses undergoing CPB in our facility.

In pressure-driven hemorrhage (PDH), where the rate of bleeding is a function of prevailing arterial pressure, survival time, arterial pressure, cardiac output, oxygen consumption, and base excess are functions of initial bleeding rate. The quantitative rate of transcapillary refill (TR) throughout PDH leading to death was determined in splenectomized dogs, through serial analysis of Cr51-tagged red cell dilution. Mild, moderate, and severe levels of PDH were produced by varying initial bleeding rate (10, 25, and 50 ml/min, respectively). The rate of TR is a function of the severity of PDH, but does not correlate with arterial pressure, cardiac output, or systemic resistance. The volume of transferred fluid represents an ever increasing fraction of total plasma volume, and accounts for more than 75% of plasma volume in preterminal stages of shock. TR sustains a relatively fixed level of plasma volume, equivalent to two-third of the initial plasma volume, irrespective of the rate of bleeding. Hypertonic NaCl (7.5%) enhances TR, while isotonic NaCl reverses it.

To study the early hemodynamic effects of the rapid infusion of 7.5g/dl NaCl/ 6g/dl dextran-70 solution in dogs submitted to hemorrhagic shock.Mongrel dogs were anesthetized with pentobarbital and a electromagnetic flowmeter probe was placed around the ascending aorta or the portal vein. By external bleeding the arterial pressure was lowered to 40mmHg and held for 30min. The animals received a 4ml/kg infusion of the hypertonic solution in 90s. Arterial blood pressure and flow were registered continuously during 3min and the derived hemodynamic variables were calculated at regular time intervals.The total plasma protein concentration decreased and the cardiac output showed a continuous elevation during the infusion. The arterial blood pressure showed two oscillations and then decreased during a short period of time. This moment was coincident with the initial increase of the portal flow and preceded the elevation of the systemic vascular resistance and the arterial pressure.The rapid infusion of hypertonic NaCl/dextran solution to dogs in hemorrhagic shock determines immediate and intense hemodynamic effects. During the infusion period there is volemic expansion and the cardiac output increases rapidly. The arterial pressure shows oscillations and decreases as a consequence of visceral arterial dilation before starting its final elevation that occurs as the vascular resistance increases.

Two different hypertonic (2400 mOsm/L) isochloremic dextran solutions (sodium acetate, HAD; and sodium lactate, HLD; in 0.9% NaCl + 6% dextran 70) were compared with HSD (2400 mOsm/L NaCl + 6% dextran 70) as initial treatment for severe uninterrupted arterial bleeding. The substitution of dextran 70 for lactated Ringer's solution as the maintenance isotonic infusion fluid was also analyzed. Experiments were performed in pentobarbital-anesthetized dogs. A recently developed model, pressure-driven hemorrhage (PDH), which mimics uninterrupted arterial bleeding, was employed. It was found that (1) the substitution of dextran 70 for lactated Ringer's as isotonic fluid makes no difference in hemodynamic terms; (2) isochloremic hypertonic solutions are similar in their hemodynamic resuscitative effect, representing an improvement over hypertonic NaCl in terms of cardiac output, O2 delivery and O2 consumption; (3) HAD proved superior to HLD in terms of O2 consumption and correction of pH/base excess.

Research on hemorrhage has concentrated on its effects rather than the manner of occurrence. A new experimental method in which the rate of bleeding is a function of prevailing arterial pressure is proposed and described. The effects of standard crystalloid volume expansion and of small volume hypertonic treatment on this protocol are demonstrated. In pressure-driven hemorrhage, survival time and the decay of arterial pressure, cardiac output, oxygen consumption, and base excess are functions of the bleeding rate, but plasma proteins and hematocrits are independent. The decay of arterial pressure is also a complex function of blood volume deficit, but this relation is not dependent on the rate of blood removal. Volume expansion induces a recovery of circulatory function despite enhanced blood loss. A comparison between equiosmolar solutions of hypertonic sodium chloride and acetate shows that acetate produces a smaller pressor (hence less blood loss) but larger blood flow (hence higher O2 availability) effect. The possible importance of the isochloremic nature of the response to acetate is highlighted.

The hemodynamic effects, after infusion of 4 ml/kg of hypertonic (7.5%) saline solution (HS), were evaluated in six patients (mean age = 56.6 years) with cardiogenic shock (CS) due to right ventricular infarction (RVI). Basal condition data (mean +/- SEM) were as follows: cardiac index (CI) = 1.9 +/- 0.1 1/min/m2, arterial pressure (AP) = 66.5 +/- 0.9 mmHg, and systemic vascular resistance (SVR) = 31.3 +/- 1.0 mmHg/1/min/m2. Five- and 240-minute post-HS infusion data (respectively) revealed: CI = 3.3 +/- 0.1* and 2.9 +/- 0.1* 1/min/m2, AP = 87.7 +/- 1.6* and 80.7 +/- 2.2* mmHg, and SVR = 22.5 +/- 0.6* and 24.5 +/- 1.1* mmHg/1/min/m2 (*P less than 0.05 compared to baseline values). These data suggest that small-volume infusion of HS induced an important acute and sustained hemodynamic improvement in these patients with CS due to RVI.

The effects of various hypertonic solutions on the intraventricular conduction disturbances and on the cardiac arrhythmias caused by the intravenous (i.v.) injection of bupivacaine were studied in sodium pentobarbital anesthetized mongrel dogs. Bupivacaine was injected in 2 doses: 3.0 mg/kg and 6.5 mg/kg. Hypertonic solutions, given intravenously 5 minutes before bupivacaine, were 7.5% NaCl, 5.4% LiCl or 50% glucose (2,400 mOsm/l, 5 ml/kg), or 20% mannitol (1,200 mOsm/l, 10 ml/kg). The highest dose of bupivacaine induced severe cardiac arrhythmias and intraventricular conduction disturbances, as reflected by significant increases in QRS complex duration, HV interval and IV interval, as well as a severe hemodynamic impairment. Significant prevention against intraventricular conduction disturbances and ventricular arrhythmias was observed with 7.5% NaCl (QRS complex duration percent increase: 164 +/- 21% in the non pretreated group vs. 75 +/- 14% in the pretreated group, P less than .01; HV interval percent increase: 131 +/- 16% in the non pretreated group vs. 58 +/- 7% in the pretreated group, P less than .01; cardiac index percent decrease: 46 +/- 6% in the non pretreated group vs. 28 +/- 5% in the pretreated group, P less than .025). The three other hypertonic solutions were ineffective. These findings suggest an involvement of sodium ions in the mechanism of hypertonic protection.

Fifty pentobarbital anesthetized dogs were subjected to pressure driven hemorrhage (PDH) in which (a) an initial bleeding rate (25 ml/min) was set, and (b) reset min-to-min in proportion to prevailing mean arterial pressure (MAP). When blood loss reached 40 ml/kg, experimental time was set to zero and dogs were divided into five groups: (1) CTR (untreated controls); (2) HSD (NaCl 7.5%-Dextran70 6%, 6 ml/kg, at zero time); (3) LR (lactated Ringers, 25 ml/min from 0-60 min); (4) HSD-LR (combines HSD and LR); (5) DBL-HSD-LR (as HSD-LR, plus second HSD injection, 4 ml/kg, at 30 min). PDH was continued throughout the postresuscitation period. CTR dogs bled 55.5 +/- 2.1 ml/kg and survived to 34.7 +/- 5.0 min postzero; HSD dogs bled 78.6 +/- 2.0 ml/kg, and survived to 51.2 +/- 2.9 min with transient recovery of MAP, cardiac output (CO), and O2 availability (O2A); LR dogs bled 94.5 +/- 3.4 ml/kg and survived for over 60 min, with sustained, partial recovery of MAP, CO, and O2A. HSD-LR dogs bled 111.5 +/- 3.7 ml/kg and survived for over 60 min with improved hemodynamic and metabolic response. In DBL-HSD-LR dogs, the second HSD produced higher MAP, CO, and O2A, but hematocrit was lowered to a critical level. Thus, standard LR resuscitation is effective in PDH, in spite of increased blood loss; a single HSD lengthens survival when used alone and improves recovery when added to LR.