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Background: Use of high-dose inhalational anesthesia during open fetal surgery may induce maternal-fetal hemodynamic instability and fetal myocardial depression. The authors' preliminary human retrospective study demonstrated less fetal bradycardia and left ventricular systolic dysfunction with lower dose desflurane supplemented with propofol and remifentanil IV anesthesia (SIVA). In this animal study, the authors compare maternal-fetal effects of high-dose desflurane anesthesia (HD-DES) and SIVA., Methods: Of 26 instrumented midgestational ewes, data from 11 animals exposed to both SIVA and HD-DES in random sequences and six animals exposed to HD-DES while maternal normotension was maintained were analyzed. Maternal electroencephalography was used to guide comparable depths of anesthesia in both techniques. Hemodynamic parameters, blood gas, and fetal cardiac function from echocardiography were recorded., Results: Compared with SIVA, HD-DES resulted in significant maternal hypotension (mean arterial pressure difference, 19.53 mmHg; 95% CI, 17.6-21.4; P < 0.0001), fetal acidosis (pH 7.11 vs. 7.24 at 150 min, P < 0.001), and decreased uterine blood flow. In the HD-DES group with maternal normotension, uterine blood flow still declined and fetal acidosis persisted, with no statistically significant difference from the group exposed to HD-DES that had maternal hypotension. There was no statistically significant difference in fetal cardiac function., Conclusion: In sheep, SIVA affects maternal hemodynamics less and provides better fetal acid/base status than high-dose desflurane. Fetal echocardiography did not reflect myocardial dysfunction in this model.

Background: During hemorrhagic hypotension, sympathetic vasoconstriction crucially contributes to gut mucosal damage. Sympathetic blockade by thoracic epidural anesthesia has been shown to increase mucosal microvascular perfusion and to improve survival after severe hemorrhage in laboratory animals. This study investigates the effects of thoracic epidural anesthesia on intestinal microvascular perfusion during hemorrhagic hypotension in rats., Methods: In 32 anesthetized Sprague-Dawley rats either lidocaine 2% (thoracic epidural anesthesia) or normal saline (control) was infused via thoracic epidural catheters. Hemorrhagic hypotension (mean arterial pressure 30 mmHg for 60 min) was induced by withdrawal of blood, which was subsequently retransfused for resuscitation. Functional capillary density and erythrocyte velocity in the mucosa and muscularis were determined by intravital microscopy. Leukocyte-endothelium interaction was studied in postcapillary venules and sympathetic nerve fibers of the intestinal wall were identified by immunohistochemistry., Results: During hypotension functional capillary density was significantly (P < 0.001) lower in the muscularis of the control group (median [25/75 percentile]: -46.5% [-59.6/-20.8%] change from baseline) as compared with animals that received thoracic epidural anesthesia (-6.1% [-13.4/1.1%]). There were no differences in erythrocyte velocity between groups throughout the experiment. Leukocyte rolling increased significantly (P < 0.001) after resuscitation in control (12 [6/15] vs. baseline 2.5 [1/8]) but not in thoracic epidural anesthesia (4 [2.3/7] vs. baseline: 5 [3/15.5]). Sympathetic nerve fibers were identified in the muscularis and submucosa but not in the mucosa., Conclusions: During hemorrhagic hypotension and after resuscitation, thoracic epidural anesthesia has beneficial effects on intestinal microvascular perfusion. Because of blockade of sympathetic nerves, thoracic epidural anesthesia prevents perfusion impairment of the muscularis during hypotension and attenuates leukocyte rolling after resuscitation.

Background: Liver dysfunction as a result of impaired oxygen availability frequently occurs following hemorrhage and contributes to delayed mortality. Artificial oxygen carriers may improve oxygen supply to vital organs while avoiding the need for allogeneic transfusion., Methods: Rats were subjected to hemorrhagic hypotension (mean arterial pressure = 35-40 mmHg for 120 min) and were subsequently resuscitated with (1) stored whole rat blood, (2) pentastarch, or (3) pentastarch combined with perflubron emulsion (PFE; 2.7 or 5.4 g/kg body weight), a second-generation artificial oxygen carrier. Recovery of liver adenosine triphosphate, hepatocellular injury, and expression of glutamine synthetase 1, a gene that is induced by exposure of hepatocytes to low partial pressure of oxygen, were studied at 4 h of resuscitation., Results: Stored whole blood or pentastarch failed to restore liver adenosine triphosphate concentrations after prolonged shock as compared to sham controls and resulted in increased gene expression of glutamine synthetase 1. Addition of 2.7 g PFE/kg restored liver adenosine triphosphate to control, whereas 5.4 g PFE/kg resulted in adenosine triphosphate concentrations significantly above control. Improved hepatocellular oxygen supply was also confirmed by restoration of the physiologic expression pattern of glutamine synthetase 1. Serum enzyme concentrations were highest after resuscitation with stored blood, whereas addition of PFE failed to further decrease enzyme concentrations as compared to pentastarch alone., Conclusions: Resuscitation with PFE is superior to stored blood or asanguineous resuscitation with respect to restoration of hepatocellular energy metabolism. The improved hepatocellular oxygen availability is reflected in normalization of oxygen-dependent gene expression. However, improved oxygen availability failed to affect early hepatocellular injury.

Background: Decreased arterial partial pressure of oxygen (PaO2) during volatile anesthesia is well-known. Halothane has been examined with the multiple inert gas elimination technique and has been shown to alter the distribution of pulmonary blood flow and thus PaO2. The effects of isoflurane and sevoflurane on pulmonary gas exchange remain unknown. The authors hypothesized that sevoflurane with a relatively high minimum alveolar concentration (MAC) would result in significantly more gas exchange disturbances in comparison with isoflurane or control., Methods: This study was performed in a porcine model with an air pneumoperitoneum that generates a reproducible gas exchange defect. After a baseline measurement of pulmonary gas exchange (multiple inert gas elimination technique) during propofol anesthesia, 21 pigs were randomly assigned to three groups of seven animals each. One group received isoflurane anesthesia, one group received sevoflurane anesthesia, and one group was continued on propofol anesthesia (control). After 30 min of volatile anesthesia at 1 MAC or propofol anesthesia, a second measurement (multiple inert gas elimination technique) was performed., Results: At the second measurement, inert gas shunt was 15 +/- 3% (mean +/- SD) during sevoflurane anesthesia versus 9 +/- 1% during propofol anesthesia (P = 0.02). Blood flow to normal ventilation/perfusion (V(A)/Q) lung areas was 83 +/- 5% during sevoflurane anesthesia versus 89 +/- 1% during propofol anesthesia (P = 0.04). This resulted in a PaO2 of 88 +/- 11 mmHg during sevoflurane anesthesia versus 102 +/- 15 mmHg during propofol anesthesia (P = 0.04). Inert gas and blood gas variables during isoflurane anesthesia did not differ significantly from those obtained during propofol anesthesia., Conclusions: In pigs with an already existent gas exchange defect, sevoflurane anesthesia but not isoflurane anesthesia causes significantly more gas exchange disturbances than propofol anesthesia does.

Background: The development of metabolic acidosis during cardiopulmonary bypass (CPB) is well recognized but poorly understood. The authors hypothesized that the delivery of pump prime fluids is primarily responsible for its development. Accordingly, acid-base changes induced by the establishment of CPB were studied using two types of priming fluid (Haemaccel, a polygeline solution, and Ringer's Injection vs. Plasmalyte 148) using quantitative biophysical methods., Methods: A prospective, double-blind, randomized trial was conducted at a tertiary institution with 22 patients undergoing CPB for coronary artery bypass surgery. Sampling of arterial blood was performed at three time intervals: before CPB (t1), 2 min after initiation of CPB at full flows (t2), and at the end of the case (t3). Measurements of Na+, K+, Mg2+, Cl-, HCO3-, phosphate, Ca2+, albumin, lactate, and arterial blood gases at each collection point were performed. Results were analyzed in a quantitative manner., Results: Immediately on delivery of pump prime fluids, all patients developed a metabolic acidosis (base excess: 0. 95 mEq/l (t1) to -3.65 mEq/l (t2) (P < 0.001) for Haemaccel-Ringer's and 1.17 mEq/l (t1) to -3.20 mEq/l (t2). The decrease in base excess was the same for both primes (-4.60 vs. -4.37; not significant). However, the mechanism of metabolic acidosis was different. With the Haemaccel-Ringer's prime, the metabolic acidosis was hyperchloremic (Delta Cl-, +9.50 mEq/l; confidence interval, 7.00-11.50). With Plasmalyte 148, the acidosis was induced by an increase in unmeasured anions, most probably acetate and gluconate. The resolution of these two processes was different because the excretion of chloride was slower than that of the unmeasured anions (Delta base excess from t1 to t3 = -1.60 for Haemaccel-Ringer's vs. +1.15 for Plasmalyte 148; P = 0.0062)., Conclusions: Cardiopulmonary bypass-induced metabolic acidosis appears to be iatrogenic in nature and derived from the effect of pump prime fluid on acid-base balance. The extent of such acidosis and its duration varies according to the type of pump prime.

Background: Preoperative acute normovolemic hemodilution (ANH) is an excellent model for evaluating the effects of different colloid solutions that are free of bicarbonate but have large chloride concentrations on acid-base equilibrium., Methods: In 20 patients undergoing gynecologic surgery, ANH to a hematocrit of 22% was performed. Two groups of 10 patients each were randomly assigned to receive either 5% albumin or 6% hydroxyethyl starch solutions containing chloride concentrations of 150 and 154 mm, respectively, during ANH. Blood volume (double label measurement of plasma and red cell volumes), pH, Paco2, and serum concentrations of sodium, potassium, chloride, lactate, ionized calcium, phosphate, albumin, and total protein were measured before and 20 min after completion of ANH. Strong ion difference was calculated as serum sodium plus serum potassium minus serum chloride minus serum lactate. The amount of weak plasma acid was calculated using a computer program., Results: After ANH, blood volume was well maintained in both groups. ANH caused slight metabolic acidosis with hyperchloremia and a concomitant decrease in strong ion difference. Plasma albumin concentration decreased after hemodilution with 6% hydroxyethyl starch solution and increased after hemodilution with 5% albumin solution. Despite a three-times larger decrease in strong ion difference after ANH with 6% hydroxyethyl starch solution, the decrease in pH was nearly the same in both groups., Conclusions: ANH with 5% albumin or 6% hydroxyethyl starch solutions led to metabolic acidosis. A dilution of extracellular bicarbonate or changes in strong ion difference and albumin concentration offer explanations for this type of acidosis.

Background: Microvascular reperfusion failure of splanchnic organs is a crucial hallmark in organ damage induced by hemorrhagic shock, which should be prevented by a resuscitation solution. Because the vasoactive properties of the hemoglobin-based oxygen carrier diaspirin cross-linked hemoglobin (DCLHb) could adversely influence restoration of pancreatic capillary perfusion during resuscitation, the authors investigated its effects on the microcirculation of the rat pancreas in comparison with whole blood and 6% hydroxyethylstarch resuscitation from severe hemorrhagic shock., Methods: Twenty-eight pentobarbital-anaesthetized rats were bled to a mean arterial pressure (MAP) of 40 mmHg and maintained at this level for 1 h. Using an intravital microscope, mean arterial pressure, the length of erythrocyte-perfused pancreatic capillaries per observation area (functional capillary density), the adherence of leukocytes in postcapillary venules, and pancreatic lipid peroxidation, measured as thiobarbituric acid-reactive material in pancreatic tissue, were determined in animals resuscitated by volumes of hydroxyethylstarch, DCLHb, and whole blood (WB) equivalent to the shed blood volume or in control animals without shock induction for a period of 2 h after resuscitation., Results: Compared with control animals (366+/-28 cm(-1)), animals resuscitated with DCLHb (294+/-45 cm(-1)), WB (306+/-11 cm(-1)), and hydroxyethylstarch (241+/-34 cm(-1)) showed a significant reduction of functional capillary density after 2 h of resuscitation. DCLHb was as effective as WB and superior to hydroxyethylstarch in restoring functional capillary density and mean arterial pressure. Leukocyte adherence in postcapillary venules was not enhanced by DCLHb (369+/-148/mm2) infusion when compared with hydroxyethylstarch- (615+/-283/mm2) and WB-treated (510+/-415/mm2) animals. Lipid peroxidation of pancreatic tissue was significantly elevated after treatment with both oxygen-carrying solutions compared with hydroxyethylstarch., Conclusion: DCLHb is as effective as WB for preservation of the pancreatic microcirculation.

Background: Historically, ephedrine has been the vasopressor of choice for treatment of most cases of hypotension in obstetric patients. However, the choice of vasopressor in the parturient receiving a beta-adrenergic agent for tocolysis has not been evaluated extensively. The current study evaluated whether ephedrine or phenylephrine better restores uterine blood flow and fetal oxygenation during ritodrine infusion and epidural anesthesia-induced hypotension in gravid ewes., Methods: Fourteen chronically instrumented gravid ewes between 0.8 and 0.9 timed gestational age were used. On separate days, each animal underwent the experimental protocol with one of three agents: ephedrine, phenylephrine, and normal saline-control. The experimental protocol was as follows: (1) at time zero, intravenous infusion of ritodrine was begun; (2) at 120 min, 2% lidocaine was given epidurally to achieve a sensory level of at least T6; and (3) at 135 min, an intravenous bolus of either ephedrine, phenylephrine, or normal saline-control was given, followed by a continuous intravenous infusion of the same agent for 30 min. In the ephedrine and phenylephrine experiments, the rate of infusion was adjusted to maintain maternal mean arterial pressure close to baseline., Results: Ritodrine infusion alone significantly increased maternal heart rate and cardiac output in all three groups. Epidural anesthesia during ritodrine infusion significantly decreased maternal mean arterial pressure, heart rate, cardiac output, uterine blood flow, and fetal arterial oxygen tension for each of the three groups. Both ephedrine and phenylephrine restored maternal mean arterial pressure to baseline, as designed. Ephedrine significantly increased uterine blood flow and fetal arterial oxygen tension when compared with normal saline--control, but phenylephrine did not. Phenylephrine significantly increased uterine vascular resistance when compared with normal saline--control, but ephedrine did not., Conclusions: Although ephedrine and phenylephrine provided similar restoration of maternal mean arterial pressure, ephedrine was superior to phenylephrine in restoring uterine blood flow during ritodrine infusion and epidural anesthesia-induced hypotension in gravid ewes. Also, ephedrine, but not phenylephrine, significantly improved fetal oxygenation, when compared to normal saline--control.

Background: The effects of propofol on uterine blood flow are not understood well. This is a relatively new agent that is finding increased use for nonobstetric surgical procedures during pregnancy and induction of anesthesia for cesarean section., Methods: The effects of induction and maintenance of anesthesia with propofol were studied on maternal and fetal cardiovascular and acid-base variables in a chronically instrumented pregnant sheep model. Anesthesia was induced with a 2 mg/kg bolus of propofol and maintained with of one of three continuous infusions: 150, 300, and 450 micrograms.kg-1 x min-1. The control group received thiopental for induction, and anesthesia was maintained with isoflurane., Results: The use of propofol did not adversely affect maternal or fetal mean arterial pressure, heart rate, or base excess, fetal heart rate variability, or uterine blood flow. Uterine blood flow transiently decreased during induction and intubation with thiopental but remained stable during induction with propofol. However, administration of succinylcholine for intubation in the presence of propofol resulted in a transient, but severe, maternal bradycardia. Continuous infusion of 300 micrograms.kg-1.min-1 of propofol appeared to provide satisfactory anesthesia in the ewe., Conclusions: Assuming the applicability of ovine data to humans, these findings suggest that induction and maintenance of anesthesia with propofol and 50% nitrous oxide in oxygen has no adverse fetal effects but warrants caution because of the potential risk of severe maternal bradycardia during induction of anesthesia using the combination of propofol and succinylcholine.

During cardiopulmonary resuscitation (CPR), arterial pH and carbon dioxide tension (PCO2) do not reflect the marked acidosis and hypercapnia seen in venous blood samples during CPR. Epinephrine causes an increase in myocardial and cerebral blood flow during CPR, but the influence on regional venous PCO2 and pH is as yet unknown. Fourteen pigs were allocated to receive either 0.9% saline (n = 7), or 45 micrograms/kg epinephrine (n = 7) after 5 min of ventricular fibrillation and 3 min of open-chest CPR. Blood samples were obtained during CPR from the aorta, pulmonary artery, great cardiac vein, and sagittal sinus before and 90 s and 5 min after drug administration. Regional blood flow was measured with tracer microspheres. Plasma catecholamines were quantified by high-performance liquid chromatography in arterial blood. PCO2 90 s after drug administration in arterial, mixed venous, myocardial venous, and cerebral venous blood were (means +/- SD) 36 +/- 8, 67 +/- 9, 74 +/- 14, and 79 +/- 19 mmHg in the control group and 35 +/- 11, 62 +/- 12, 73 +/- 10, and 71 +/- 14 mmHg in the epinephrine group. pH values 90 s after drug administration in the same blood samples were 7.29 +/- 0.11, 7.11 +/- 0.09, 7.04 +/- 0.09, and 7.07 +/- 0.10 in the control group and 7.31 +/- 0.13, 7.17 +/- 0.07, 7.08 +/- 0.08, and 7.07 +/- 0.12 in the epinephrine group. Despite a significant increase in myocardial and cerebral blood flow after epinephrine, PCO2 and pH in all blood samples were not different from those of the control group. (ABSTRACT TRUNCATED AT 250 WORDS)

Morphine, 20 mg X kg-1, sc, halved the plasma clearance of sulfobromophthalein (BSP) while tripling hepatic tissue levels of this dye. Since narcotics depress respiration, effects of hypoxia, hypercapnia, and acidosis on BSP disposition were studied. Ambient gases breathed by rats were adjusted to achieve blood gas levels identical to those of morphine-induced respiratory depression. Saline-treated rats breathing room air had PAO2 of 87 +/- 3 mmHg (mean +/- SE) and PaCO2 of 40 +/- 2 mmHg. After intraarterial injection of BSP, 100 mg X kg-1, plasma clearance of this dye was 7.1 +/- 1.1 ml X min-1 and BSP levels in the liver at 40 min after injection were 163.3 +/- 19.8 micrograms X g-1. After morphine, 20 mg X kg-1, PaO2 decreased to 47 +/- 4 mmHg and PaCO2 increased to 89 +/- 5 mmHg. In these rats BSP clearance dropped to 3.5 +/- 0.4 ml X min-1, and 40-min liver dye levels were increased to 596.4 +/- 60.4 micrograms X g-1. Similar hypoxia and hypercapnia caused by breathing 9% O2 and 8% CO2 in the absence of morphine caused plasma BSP clearance to be decreased to 4.4 +/- 0.2 ml X min-1 and 40-min hepatic BSP to be increased to 292.5 +/- 31.8 micrograms X g-1. Hypercapnia and acidosis alone did not affect BSP disposition, while hypoxia without hypercapnia decreased its plasma clearance to 5.5 +/- 0.3 ml X min-1 and increased liver levels to 339.1 +/- 35.1 micrograms X g-1. Hypoxia was reversed completely in morphine-treated rats by placing them in 40% O2. In these animals, despite normal oxygen, plasma BSP clearance was decreased to 4.4 +/- 0.6 ml X min-1, and liver BSP was increased to 497.9 +/- 65.6 micrograms X g-1. Thus, respiratory depression with hypoxia may contribute to morphine-induced effects on BSP disposition, but altered blood gases cannot account fully for these narcotic effects.

If further sympathetic stimulation is neither possible nor desirable during moderate hypovolemia, anesthetic agents capable of sympathetic stimulation would not be advantageous for induction of anesthesia during hypovolemia. To test this hypothesis, 21 swine were studied during normovolemia and after 30% of their estimated blood volume was removed. Swine were divided randomly into three equal groups to receive no anesthetic or the minimal anesthetic dose of ketamine (6.65 +/- 0.38 mg/kg, iv) or thiopental (5.77 +/- 0.21 mg/kg, iv). After the initial response to hypovolemia, animals given no drug did not exhibit further changes during the hypovolemic period. Five minutes after induction of anesthesia in the hypovolemic state, ketamine, but not thiopental, caused large increases in plasma epinephrine, norepinephrine, and renin activity. Despite these differences, both anesthetics equally depressed systemic vascular resistance, mean systemic arterial blood pressure, heart rate, and cardiac output. Ketamine, but not thiopental, decreased stroke volume. Neither anesthetic affected oxygen consumption. Both anesthetics caused similar increases in blood lactate concentration. Thirty minutes after induction of anesthesia, plasma epinephrine, norepinephrine, and renin activity remained higher in animals given ketamine than in those given thiopental. Stroke volume, systemic vascular resistance, cardiac output, and oxygen consumption did not differ among groups; however, only the animals given ketamine showed further increase in blood lactate concentration and base-deficit. Thirty minutes after infusion of shed blood, cardiac output and blood lactate concentration were greater in the animals given ketamine than in those given thiopental or no anesthetic. Ninety minutes after infusion of shed blood, no differences existed among groups. The authors conclude that after moderate hemorrhage, further increase in circulating catecholamines is possible but that the levels achieved either exceed the maximal effective concentration at site(s) of action or their effects are overwhelmed by the depressant effects of ketamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Using the chronic maternal-fetal sheep preparation, nine pregnant ewes were studied to determine the effects of intravenous dantrolene sodium on maternal and fetal physiology, with particular reference to its placental passage, and its effects on uterine blood flow and uterine tone. Two doses of dantrolene sodium were studied: 1.2 mg/kg and 2.4 mg/kg. After 2.4 mg/kg, maternal cardiac output increased 29% (P less than 0.05) after 1 min and returned to normal after 30 min. Maternal mean arterial pressure increased 13% after 1 min and remained significantly elevated (P less than 0.01) for 3 h. No significant changes (P greater than 0.05) were observed in maternal heart rate, uterine artery blood flow, or central venous pressure. Maternal arterial pH declined from 7.42 to 7.39 (P less than 0.01) after 1 min and returned to baseline values after 10 min. Fetal heart rate decreased 24% (P less than 0.01) after 3 min and returned to normal after 10 min; the mean fetal arterial pressure remained unchanged (P greater than 0.05). Fetal arterial pH declined from 7.29 to 7.27 (P less than 0.05) after 1 min and remained significantly decreased for 120 min. Similar changes of lesser magnitude and shorter duration were seen following the 1.2 mg/kg dose. Maternal levels of dantrolene were less than 3 micrograms/ml. Although an equilibrium between maternal and fetal plasma dantrolene concentrations was apparent at 5 min, the fetal levels of dantrolene were approximately 10% of the mother's. The results indicate that the administration of intravenous dantrolene at 1.2 mg/kg or 2.4 mg/kg has no clinically significant adverse effect on mother or fetus in the sheep model.

The central nervous system toxicities of etidocaine, bupivacaine, and lidocaine were studied during constant-rate intravenous infusions in rhesus monkeys. Comparison of drug effects was achieved by determining the drug dosages and arterial plasma concentrations that induced electrical seizure activity. The central nervous system toxicity of etidocaine was similar to that of bupivacaine. The toxicity of each was four times greater than that of lidocaine. Since the drug infusion rates were proportional to anesthetic potencies in clinical usage, the therapeutic-toxic ratios of these three drugs are similar.

The central-nervous-system toxicities of local anesthetic mixtures consisting of lidocaine and etidocaine or lidocaine and tetracaine, administered intravenously to four healthy, non-medicated rhesus monkeys, were evaluated. Toxicities were compared by determining seizure dosages for each drug alone and then in a lidocaine-etidocaine-tetracaine mixture. Arterial plasma levels of lidocaine and etidocaine at which electrical seizure activity occurred also were measured when the drugs were administered alone and in combination. The seizure dosages and arterial plasma levels for the drug mixtures studied were equal to the sums of the dosages and thresholds for individual constituents of the mixtures. Under the conditions of this investigation local anesthetic toxicity was additive. (Key words: Anesthetics, local, lidocaine; Anesthetics, local, etidocaine; Anesthetics, local, tetracaine; Brain, seizure thresholds; Toxicity, convulsions.)

Transient hypotension has been observed in patients after rapid intravenous administration of mannitol, 25 per cent, in clinical doses. These studies were conducted to determine the mechanism for the hypotension, to determine dose and rate of injection response curves in rabbits, and to determine which vascular beds were most reactive. Studies in six patients showed mean decreases in blood pressure of 23 +/- 6.0 per cent (+/-SE) and in total peripheral resistance of 38 +/- 7 per cent after infusion of mannitol. Studies in 18 patients during cardiopulmonary bypass with mechanically fixed cardiac output demonstrated decreases in mean blood pressure of 30 +/- 5 to 40 +/- 3 per cent, depending on dose and rate of administration of mannitol. Patients not on bypass compensated for large decreases in total peripheral resistance by increases in cardiac output (3.6 +/- .4 at baseline to 4.4 +/- .4 l/min) during mannitol-induced hypotension with no change in heart rate. Serum osmolality increased as blood pressure decreased. Significant but clinically unimportant decreases in sodium and potassium ions, hemoglobin, pH, and base excess values were observed. Studies in 18 rabbits showed that the greater the dose or rate of injection of mannitol the greater the decrease in blood pressure. Injection of radiolabeled microspheres in rabbits demonstrated a near doubling of blood flow to skeletal muscle tissue during the hypotension. This occurred with both equiosmotic hypertonic glucose (17 +/- 3 to 32 +/- 7 per cent) and mannitol (17 +/- 1 to 31 +/- 5 per cent), but not after isotonic saline solution. Changes in blood flow to other organ beds were variable and unimportant. The results suggest that hypotension following the intravenous administration of hyperosmotic solutions is due primarily to vasodilation in skeletal muscle.