Small-volume

Hypertonic

Resuscitation

from Canine

Dextran Endotoxin Shock

Saline

JURETA W. HORTON, PH.D., and PAULA B. WALKER, B.S. From the Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, Texas

This study evaluated resuscitation of endotoxin shock with 7.5% hypertonic saline dextran (HSD 2400 mOsm) by measuring hemodynamic and regional blood flow responses. Endotoxin challenge (1 mg/kg) in adult dogs caused a significant decrease in mean arterial blood pressure (MABP), cardiac output (CO), left ventricular ± dP/dt max, and regional blood flow (radioactive microspheres). Cardiocirculatory dysfunction and acid-base derangements persisted throughout the experimental period in untreated endotoxin shock (group 1, n = 10). In contrast both regimens of fluid resuscitation (group 2, n = 11: bolus of 4 mL/kg HSD followed by a constant infusion of lactated Ringer's ILRI to maintain MABP and CO at baseline values; group 3, n = 10; LR alone given as described for group 2) improved regional perfusion and corrected acid-base disturbances similarly in all dogs. Hypertonic saline dextran enhanced all indices of cardiac contraction and relaxation more than LR alone. The total volume of LR required to maintain MABP and CO at baseline values was less in the HSD group (59.2 ± 6.8 mL/kg) than in the LR alone group (158 ± 16 mL/kg, p = 0.01). The net fluid gain (infused volume minus urine output and normalized for kilogram body weight) was five times greater in the LR (24.8 ± 6.2 mL/ kg) than in the HSD group (4.6 ± 1.2 mL/kg, p = 0.01). Lung water was similar in all dogs, regardless of the regimen of fluid resuscitation. Hypertonic saline dextran effectively resuscitates endotoxin shock in this canine model.

shown to improve cardiac output and mean arterial blood pressure to near baseline values while reducing the total volume requirements of resuscitation. Recently Holcroff and colleagues'3 reported that small-volume hypertonic saline dextran (HSD) resuscitation during helicopter transport of severely injured patients significantly improved blood pressure and survival more than an identical volume of isotonic resuscitation solution, providing evidence that this solution safely and effectively resuscitates injured patients. In the present study, we evaluated the resuscitation of endotoxin shock with HSD 70 solution by measuring cardiodynamic, metabolic, and hormonal responses as well as regional perfusion of various organs. The study was designed to determine if HSD could effectively reduce the volume of traditional isotonic resuscitation from endotoxin shock.

P_ REVIOUS STUDIES HAVE shown that endotoxin

shock in dogs depresses cardiocirculatory function, and, if unresuscitated, is associated with a significant mortality rate. 1-6 Fluid resuscitation of the septic subject improves survival but the volume of isotonic fluid required to restore cardiocirculatory function is large, often promoting edema. Recent work by us and others has shown that a small volume of sodium chloride (2400 mOsm), 6% dextran 70 effectively resuscitates subjects in hemorrhagic7-'0 or burn shock'"1"2 as well in subjects with acute pancreatitis.'2 This resuscitation regimen has been

Materials and Methods Thirty-one adult male mongrel dogs (weighing between 21 and 35 kg) were housed for several days in individual cdges until a complete blood count and negative screen for microfilaria were obtained. All animals were allowed water ad libitum but no food starting 20 hours before the experiment. After sedation with intramuscular acepromazine (0.005 mL/kg), a peripheral venous catheter was placed. Intravenous sodium pentobarbital (15 mg/kg) was administered to induce anesthesia. Each dog was intubated and allowed to breathe spontaneously. Anesthesia was maintained with intravenous alpha chloralose (50 mg/kg) in solution with polyethylene glycol 200. Each animal was instrumented as previously described by this laboratory.'4"15 Body temperature was measured with a rectal

Address reprint requests to Jureta W. Horton, Ph.D., Department of Surgery, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9031. Accepted for publication July I1, 1990.

64

Vol. 214 -No.lI

HYPERTONIC RESUSCITATION OF ENDOTOXIN SHOCK

probe (Telethermometer, Yellow Springs, Inc., Yellow Springs, OH). Urine was collected in a closed drainage bag and volume determined every 60 minutes with a graduated cylinder. Both femoral arteries were catheterized for continuous blood pressure recording (Statham Transducer, Model P23ID, Spectromed, Oxnard, CA) and for simultaneous blood withdrawal for measurement of regional blood flow using the microsphere technique. A microtipped pressuresensitive transducer (no. 7 French, Model PC470, Millar Instruments, Houston, TX) was placed in the left ventricle by retrograde cannulation of the left carotid artery. This catheter was used for injection of microspheres and for continuous measurement of left heart pressures. The right femoral artery catheter was attached to a Gilford syringe pump (Model 105-S, Gilford Laboratories, Oberlin, OH) to allow blood withdrawal through the cardiac output densitometer (Model COR-100, Waters Instruments, Rochester, MN) during injection of 2.5 mg ofcardiogreen dye. A balloon-tipped Swan-Ganz catheter (Model 93A831H-7-5F, American Edwards, Irvine, CA) was introduced into the right jugular vein, threaded through the right heart and into the pulmonary artery under fluoroscopic guidance. Position was subsequently confirmed by waveform monitoring. A catheter in the left jugular vein was advanced under fluoroscopy into the coronary sinus and subsequent catheter position was confirmed at autopsy. Systemic anticoagulation was achieved by administration of intravenous heparin (100 units/kg). Regional blood flow in the heart, pancreas, kidney, and splanchnic organs was determined by the radioactive microsphere technique. Six radioactive labels (1 25-I, 95-Nb, 46-Sc, 85-Sr, 57-Co, and 113-Sn) measuring 10 ,u in diameter were used. For each measurement of flow, a bolus of labeled microspheres (approximately 1.5 million) was injected into the left ventricle and the catheter flushed with 10 mL of warm saline. Simultaneous with the injection of microspheres and continuing for 120 seconds, duplicate reference blood samples were obtained from the femoral arteries, each at a constant withdrawal rate of 12 mL/minute (Holter Pump, Model 911, Critikon Laboratories, Tampa, FL). After completing each experiment, an overdose of barbiturates was administered to the dog. The heart, right and left kidneys, and all splanchnic organs were removed. After fixation, the heart was divided into anterior and posterior septum and anterior and posterior left ventricular free wall segments. Each section of left ventricle was then divided further into endocardial and epicardial regions of equal thickness. At least 100 g of each organ was collected for blood flow measurement. Blood and tissue samples were weighed to the nearest milligram and counted for 5 minutes in a multichannel autogamma scintillation spectrometer (Model 5320, Packard Inst., Legona Hills, CA). For each set of samples, vials

65

containing aliquots of each microsphere were used to determine the energy level setting on the scintillation counter. From the standards of each microsphere used to set the energy level and the blood samples containing the highest count of microspheres injected, the cross-talk fraction or overlap of gamma energy was calculated for each of the microspheres. The contribution of overlap of gamma energy of each microsphere was subtracted and a nuclide reference factor (mL/min/count) was calculated. For each tissue sample, the background counts were subtracted and the counts for each isotope were multiplied by the nuclide reference factor to obtain mean blood flow rate. Only animals with less than 15% disparity between right and left kidney flows were used for data analysis. Flows were calculated using a DEC-10 (Digital Equipment Co., Maynard, MA) computer program and expressed as

mL/min/g. Left ventricular pressure, systemic blood pressures, and pulmonary artery pressures were measured continuously. Heart rate was calculated from the left ventricular pressure tracing and recorded at a paper speed of 100 mm/second. Maximal rate of left ventricular pressure increase (+dP/ dt max) was obtained with a derivative computer (model 8814A, Hewlett-Packard, Richardson, TX). The dP/dt at a developed pressure of 40 mmHg (dP/dt-DP40), a parameter that is affected minimally by changes in preload and afterload, was calculated as previously described.16 Total peripheral resistance, pulmonary vascular resistance, and stroke work were calculated as previously described by this laboratory.'5 Pulmonary and peripheral artery as well as coronary sinus blood samples were withdrawn before the injection of endotoxin, 30 minutes after endotoxin challenge, and hourly after initiating fluid resuscitation. Blood gases, pH, and oxygen content were measured (model ABL 300, Radiometer Blood Gas Analyzer, Radiometer American, Inc., Dallas, TX). Enzymatic methods were used to determine concentrations of lactate in arterial and coronary sinus blood (Sigma Chemical Co., St. Louis, MO). Oxygen delivery, extraction, and consumption by the myocardium were calculated as previously described by this laboratory.'5 Serum sodium, potassium, and chloride levels were measured before endotoxin injection and hourly thereafter (Nova Model 5, Electrolyte Analyzer, Nova Biochemical, Waltham, MA). At each sampling period, blood was collected from the arterial catheter and assayed for plasma glucose concentration (Semiautomated analyzer). Serum insulin, somatostatin, and glucagon concentrations were measured by radioimmunoassay courtesy of Dr. Roger Unger's laboratory (VA Medical Center, Dallas, TX).'7"18 Immediately after instrumentation, all baseline hemodynamic and metabolic parameters were measured. A microsphere was injected to measure regional blood flow.

66

HORTON AND WALKER

The animals then were given an injection of endotoxin (1 mg/kg body weight); 30 minutes after endotoxin challenge, all parameters were measured again and the animals were divided randomly into three groups. In group 1 (10 dogs), no fluid resuscitation was initiated and these animals served as the untreated endotoxin group. In group 2 (11 dogs), each dog was given intravenously 4 mL/kg body weight HSD (2400 mOsm sodium chloride, 6% dextran 70; Macrodex, Pharmacia, Piscataway, NJ). Lactated Ringer's (LR) solution was infused during a period of 4 hours as required to maintain mean arterial blood pressure and cardiac output at baseline values. In group 3 (10 dogs), endotoxin was injected as described for group 1. Resuscitation consisted of LR solution, infused to maintain mean arterial pressure and cardiac output as described for group 2. After 4 hours of fluid resuscitation, animals were killed with an overdose of barbiturates according to the guidelines set by the National Institutes of Health and The University of Texas Southwestern Medical School Committee for Animal Use. At autopsy the gross appearance of the organs in the abdominal and thoracic cavity was noted and tissues for dry/wet weight ratios and for blood flow studies were collected. Intrathoracic catheter placement was verified. All data are presented as mean ± standard error of the mean (SEM). For data with multiple points in the experiment, an analysis of variance and a repeated measures

Ann. Surg. * July 1991

procedure (Newman-Keuls) were used to evaluate significant differences between groups with regard to hemodynamic and metabolic parameters as well as changes in regional blood flow. Differences were considered significant at p < 0.05. Results

One of the ten untreated dogs died 65 minutes after endotoxin injection (10% mortality rate); in contrast all of the treated dogs survived the entire experimental period, regardless of the regimen offluid resuscitation. There was no significant difference in the immediate response to endotoxin challenge in the three experimental groups. Thirty minutes after endotoxin injection, mean arterial blood pressure had decreased similarly in all groups (-42%); a significant decrease in cardiac output and stroke volume (-34% and -32%, respectively) was accompanied by no change in heart rate and peripheral vascular resistance (Table 1). Impaired left ventricular function after untreated endotoxin challenge was indicated by a progressive decrease in the rate of left ventricular pressure rise (+dP/ dt max) and fall (-dP/dt max) as well as dP/dt at a developed pressure of 40 mmHg (Fig. 1). In contrast both regimens of fluid resuscitation from endotoxin shock increased ±dP/dt max above baseline values; however 3 and 4 hours after initiating resuscitation, ±dP/dt max and

TABLE 1. Hemodynamic Response to Endotoxin Challenge Cardiac Output (L/min)

Groups Control

ENDO

LR

Heart Rate (beats/min)

Peripheral Vascular Resistance (units)

Stroke Volume (mL)

HSD/LR

ENDO

LR

HSD/LR

ENDO

LR

HSD/LR

ENDO

LR

HSD/LR

86 ±6

88 ±5

81 ±4

38.02 ±2.72

39.03 ±3.69

41.80 ±3.80

33.77 ±2.33

33.94 ±3.89

30.20 ±2.93

± 0.32

96 ±8

94 ±6

84 ±8

± 3.10

27.83 ±4.09

29.09 ± 1.92

29.98 ± 3.70

111

96 ±3

± 1.49

97 ±5

± 1.45

86 ±5

± 1.54

3.31

3.44

3.50

± 0.19

± 0.28

± 0.29

Endotoxin 30 minutes

2.18t ± 0.22

2.10t ± 0.19

2.25t

26.00t

22.00t

29.92t

± 1.38

± 5.22

33.87* ±4.15

±3.32

34. 10* ±4.05

± 3.50

± 1.68

42.30* ±4.15

± 1.60

Resuscitation Initiated After resuscitation 60 minutes 120 minutes 180 minutes

240 minutes

±0.14

±0.28

3.64* ±0.35

105 ±9

± 12

1.38t ±0.12

2.44* ±0.26

3.65* ±0.31

119 ±7

± 11

1.66t ±0.15

3.40* ±0.30

3.41* ±0.32

108 ±4

± 11

1.48t

1.48t ± 0.13

3.43*

3.51* ± 0.34

3.86* ± 0.32

103 110

12.28t

104

110

96

±5

± 10

±5

All values are mean ± SEM. Groups include group ENDO, endotoxin challenge only, no treatment, n = 10; group HSD, endotoxin challenge treated with a bolus of hypertonic saline dextran (HSD) plus lactated Ringer's, n = I 1; group LR, endotoxin challenge treated with

13.73t

15.66t

13.64t ± 1.19

31.79* ±2.79

37.02* ± 4.37

37.81* 37.95

36.73* ± 3.21

21.87t ± 1.50

23.65t 20.02t 39.37t ± 3.95

18.60t ± 1.13

24.34t ± 1.58

24.34t ± 1.58

22.46t ±2.34 24.71 ± 2.82

30.20 ±4.50

24.20

30.00

± 2.14

± 3.72

lactated Ringer's only, n = 10. * Indicates a significant difference between groups at p < 0.05. t Indicates a significant change from baseline within a group at p < 0.05.

0-* Endotoxin Only O--

0

Ar-A Left Ventricular End Diastolic Pressure (mm Hg)

Ringers Resusdtation Lactated Ringers + HSD Resuscitation Lactated

9.0 6.0 3.0 0

140

Left Ventricular Pressure (mm Hg)

(+) dP/dt

(mm Hg * sec-1)

100

60 5000 4000 3000 2000

)

0

4000

_ -

+

+

+

+

*

*

*

*

3000 dP/dt at DP 40 2000 (mm Hg * sec1) 1000 _

O' 4000 3000

(-) dP/dt (mm Hg

* sec"')

67

HYPERTONIC RESUSCITATION OF ENDOTOXIN SHOCK

Vol. 214-No. I

2000

-

+

-

+ -

%000-Z

1000 Control t 30 t 60

Endotoxin

Resucitation

Challenge

Initiated

120

'p-180

significant decrease in myocardial oxygen extraction, and by 3 hours after initiating volume replacement, extraction ratio was significantly lower in both treated groups compared to the untreated endotoxin dogs. Untreated endotoxin challenge produced a significant acidosis, as indicated by a decrease in the arterial blood pH and serum bicarbonate level and an increase in arterial and coronary sinus lactate (p = 0.01) (Table 2). Arterial P02 was not altered significantly by endotoxin challenge. Arterial PCO2 decreased significantly after endotoxin injection due to an increase in respiratory rate (from 16 ± 1 to 26 ± 2 breaths per minute). Hematocrit ratio progressively increased after untreated endotoxin shock, while serum protein content, serum sodium, potassium, and chloride concentration remained unchanged (Fig. 3). Resuscitation of endotoxin shock with either LR solution alone or with HSD plus LR solution caused a 35% decrease in plasma total protein concentration, while hematocrit remained unchanged. Serum sodium, potassium, and chloride remained unchanged from baseline values in the endotoxin group resuscitated with LR solution alone. While a moderate increase in serum sodium (from

240 Minutes

FIG. 1. Cardiodynamic responses to endotoxin challenge and fluid resuscitation. All values are mean ± SEM. *Indicates a significant difference between groups at p < 0.05. + Indicates a significant change from baseline at p < 0.05.

0-* Endotoxhi Only

0- - 0

R uscitation

2.1

Coronary Blood Flow (ml * min * g)

1A.50 -~~~~~~ 0.! 50

4

dP/dt at DP40 were increased to a significantly greater extent in the HSD-treated compared to the LR solutiontreated group. After endotoxin injection, coronary blood flow, myocardial oxygen delivery, endocardial/epicardial flow ratio, and coronary vascular resistance decreased progressively from baseline values in the untreated dogs while myocardial oxygen extraction increased during this time (Fig. 2). The initial decrease in coronary blood flow in response to endotoxin challenge (from 1.58 ± 0.15 to 0.69 ± 0.13 mL/min/g) was followed by progressive increase in coronary perfusion throughout the experimental period; however coronary blood flow remained significantly less than baseline values throughout the experimental period in the untreated group (0.99 ± 0.1 mL/min/g at 3 hours after endotoxin injection). Similarly endocardial/epicardial flow ratio remained less than control values while coronary vascular resistance and myocardial oxygen delivery returned to control values. Both regimens of fluid resuscitation increased coronary blood flow and myocardial oxygen delivery above baseline values, and there was no significant difference in these parameters 3 hours after initiating fluid resuscitation. Fluid resuscitation caused a

Lactd Ringe

r--A Lactated Rines + HSD Resucftton

Coronary Vascular Resistance (dynes * sec * cm )

90

80

50

+

40

ENDO/EpI Ratio

1 1.61 11.4 11.3 11.2 1 11.0

Myocardil 02 Delivery (ml min g) -

-

o60~~~ Myocardial 02

80 a

Extracton (%)

40

Controlt

3

t

60

Endotoxin

Resucltation

Challenge

InWiated

120

180

240 Minutes

FIG. 2. Coronary blood flow and myocardial oxygen metabolism after endotoxin challenge and fluid resuscitation. All values are mean ± SEM. *Indicates a significant difference between groups at p < 0.05. + Indicates a significant change from baseline at p < 0.05.

68

Ann. Surg. - July 1991

HORTON AND WALKER

TABLE 2. Acid-Base Balance After Endotoxin Challenge Arterial pH Groups Control

Arterial pCO2 (mmHg)

Arterial pO2 (mmHg)

ENDO

LR

HSD/LR ENDO

7.33 + 0.02

7.34 ± 0.01

7.32 ± 0.01

LR

HSD/LR ENDO

99.2 ±5.4

89.6 ±4.4

99.6 ±7.6

104.9

93.5

95.0

38.9 ± 1.7

LR 35.6 ± 1.9

Arterial HCO3 (mm/L)

HSD/LR ENDO 37.4 ± 1.3

20.1 ±0.3

LR 19.1 ±0.4

Arterial Lactate (mm/L)

HSD/LR ENDO 18.8 ±0.1

0.747

HSD/LR

LR 0.848

0.841

± 0.094 ± 0.232 ± 0.167

Endotoxin 30 minutes

7.29t

7.31

+0.01 ±0.02 Resuscitation Initiated

After resuscitation 60 minutes 120 minutes

7.28t 7.25t 7.27t +0.03 ±0.03 ±0.01

7.23t

7.22t + 0.03

240 minutes

31.7t

±5.2 ±9.6 ±8.1

±2.1i

104.3 ±7.2

±2.5

25.1t

1.3

30.7t

±0.8

14.7t

12.4t

±0.8 ±0.7

14.5t

2.190

2.625

2.719

±0.6 ±0.116 ±0.587 ±0.486

-

+ 0.02

180 minutes

7.28t

±0.01

7.21t + 0.04

7.27t ± 0.04

7.31* ± 0.03

7.33* ± 0.02

7.29t ± 0.01

7.29* ± 0.02

7.33* ± 0.02

107.5

93.8

±9.5

±8.9

109.7

86.8

101.2

± 6.5

± 8.4

± 6.3

108.7

88.3

103.1

± 5.9

± 6.6

± 6.7

97.6

86.1

96.5

± 7.1

± 6.4

± 7.1

30.5t 26.4t ± 1.3

28.0t ± 1.4

28.2t ± 1.9

28.3t 26.7t 1.6 ± 1.8

±

25.4t ± 2.5

25.3t ± 1.5

23.9t ±0.8

27.4t ± 1.3

26.6t ± 0.6

23.9t ± 0.4

12.8t ±0.5

10.8t ± 0.6

11.1t ± 0.6

11.1t ± 1.0

12.5t ±0.5

13.2t ± 0.4

13.0t ± 0.5

12.9t ± 0.3

12.0t ±0.3

12.7t ± 0.5

12.5t ± 0.4

12.3t ± 0.4

2.770 3.574 2.501 ±0.181 ±0.754 ±0.479 2.842

3.147

2.291

± 0.196 ± 0.674 ± 0.442

2.813

3.255

2.378

± 0.239 ± 0.747 ± 0.529

2.248

3.139

2.095*

± 0.268 ± 0.366 ± 0.215

All values are mean ± SEM. Groups include group ENDO, endotoxin challenge only, no treatment, n = 10; group HSD, endotoxin challenge treated with a bolus of hypertonic saline dextran (HSD) plus lactated Ringer's, n = I 1; group LR, endotoxin challenge treated with

lactated Ringer's only, n = 10. * Indicates a significant difference between groups at p < 0.05. t Indicates a significant change from baseline within a group at p

139 ± 1 to 150 ± 1 mEq/L, p = 0.05) occurred in those dogs given HSD plus LR solution, serum potassium and chloride remained at baseline values. Acidosis persisted transiently after fluid resuscitation from endotoxin challenge; however 4 hours after initiating fluid resuscitation, arterial pH returned to baseline values in all treated dogs. Hypocapnia persisted in all dogs after fluid resuscitation due to sustained increases in respiratory rate. Arterial and coronary sinus lactate levels remained above baseline values throughout the experimental period in all dogs. However 4 hours after initiating fluid resuscitation, arterial lactate was significantly lower in the HSD compared to the LR group (p = 0.05). Peripheral blood flow (pancreas, spleen, stomach, small bowel, colon, renal blood flow, and non-nutritive lung blood flow) decreased similarly in all dogs immediately after endotoxin challenge. Both regimens of fluid resuscitation improved regional blood flow, and 4 hours after initiating fluid resuscitation there was no significant difference in any measured regional blood flow parameter (Tables 3 and 4). Endotoxin challenge produced diarrhea in all dogs and this was unchanged by either regimen of fluid resuscitation. Urine output decreased significantly in all dogs after endotoxin injection and urine output remained less than 10 mL/hr in the untreated dogs. Urine flow increased after resuscitation with both regimens of fluid resuscita-

tion, but the 97% increase in flow in the LR group exceeded the 40% increase measured in the HSD group. In the 4.5 hours after administration of endotoxin, the total urine output was 408 ± 48 mL in the LR group and 318 ± 20 mL (p < 0.05) in the HSD group. Renal blood flow decreased significantly and progressively throughout the experimental period in untreated endotoxin shock; in contrast renal blood increased to near-baseline values in the dogs given volume replacement, regardless of the regimen of fluid resuscitation. The total volume of LR required to maintain mean arterial blood pressure and cardiac output at baseline values was 158 16 mL/kg in those dogs given LR alone, and 59.2 6.8 mL/kg (p = 0.001) in the HSD group. The net fluid gain, calculated as the infused volume minus urine output and normalized for kilogram body weight, was five times greater in the LR group (24.8 6.2 mL/kg) than in the HSD group (4.6 ± 1.2 mL/kg, p = 0.01) (Fig. 4). Despite the significantly larger volume of crystalloid infused and the greater net fluid gain in the endotoxin dogs treated with LR alone, lung water, calculated by the gravimetric method, was similar in all dogs, regardless of the regimen of fluid resuscitation. The hormonal response .to endotoxin challenge and fluid resuscitation from endotoxin shock are summarized in Table 5. Baseline plasma glucose, insulin, glucagon, and somatostatin were similar in all dogs. Thirty minutes

< 0.05.

Discussion

0-*

Endotoxin Only CO Lactated Rlnrom Resusdtabnf *--A LactatedRlingers + HSD Resuscift -

-

L-

Previously

m

60 Serum

di--W,dW,O%

-

.fi

_-__

40

__

(mg/ml) 0

50

pass

45 35

+

16(

+

+

Serum CL-

(mEq/L)

consistent with previous reports of hemodynamic and metabolic derangements after endotoxin challenge.26 Cardiocirculatory dysfunction after endotoxin injection included hypotension, reduced preload, decreases in cardiac output and

3.'%r 3.C 2.' 14( 13(

pressure,

1iC

t

240 120 180 60 Endotoxin Resucitatiorn Initiated Challenge FIG. 3. Endotoxin-mediated changes in serum protein, hematocrit, and electrolyte concentration. Na+, sodium; K+, potassium; CL, chloride. All values are mean ± SEM. *Indicates a signkificant difference between groups at p < 0.05. + Indicates a significant (change from baseline at P

30

0.05.

after endotoxin challenge, plasma E lucose, insulin, and glucagon increased significantly (131%, p = 0.05; 57%, p = 0.01; and 80%, p = 0.01, respective-ly) and somatostatin was unchanged. Four hours after in itiating fluid resuscitation from shock, plasma glucose a nd insulin levels had decreased significantly (-43% and -60% from baseline values, p = 0.05, respectively), while plasma glucagon increased 420% during this time (p = (0.01). These changes in circulating hormones occurred r egardless of whether HSD or LR solution was used to resuscitate endotoxin shock. Four hours after initiating flu uid resuscitation, somatostatin decreased 42% from basi,eline values in those dogs given LR solution alone but v vas unchanged from baseline values in the HSD-treated Igroups. -

are

stroke volume and ±dP/dt; in addition redistribution of regional blood flow and profound metabolic acidosis occurred. Lactated Ringer's solution alone and HSD plus LR solution were equally effective in restoring cardiac output and regional perfusion. While fluid resuscitation restored cardiac function in all dogs, all indices of left ventricular contraction-relaxation (systolic left ventricular

ara

12(