J. Biomedical Science and Engineering, 2013, 6, 1077-1084 JBiSE
http://dx.doi.org/10.4236/jbise.2013.611135 Published Online November 2013 (http://www.scirp.org/journal/jbise/)
Physio-pathology of induced endotoxaemia in bovine and
its treatment regimen
Irtiza Nabi1, Digvijay Singh1, Naresh Kumar Sood2
1Department of Veterinary Physiology and Biochemistry, College of Veterinary Science, Guru Angad Dev Veterinary and Animal
Sciences University, Ludhiana, India
2Department of Veterinary Pathology, College of Veterinary Science, Guru An gad Dev Veteri nary and Animal Sciences University,
Ludhiana, India
Received 30 September 2013; revised 2 November 2013; accepted 18 November 2013
Copyright © 2013 Irtiza Nabi et al. This is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Endotoxic shock was induced in five apparently healthy
male buffalo calves by i.v infusion of Escherichia coli
endotoxin at 5microgram/kilogram (μg/Kg) body
weight/hour (BW/hr) for 3 hours. Endotoxin infusion
caused clinical signs of restlessness, respiratory dis-
tress, snoring, diarrhoea, profuse salivation along with
the significant hypoproteinemia, hypoalbuminemia and
hypokalemia in all the animals. The animals were ob-
served up to day 4 or death, whichever was earlier.
The treatment with one time intravenous infusion of
hypertonic saline solution @ 4milliliter/Kilogram body
weight (ml/Kg·BW), dextran-40 @ 10 ml/Kg·BW, flu-
nixin meglumine @ 1.1 milligram/Kg·BW (mg/Kg·BW)
and blood @ 20 ml/Kg·BW to these animals alleviated
the clinical signs and significantly raised the circulat-
ing glucose level at 4.5 and 5.5 hrs. The treatment led
to survival of three of the five endotoxemic buffalo cal-
ves. The significant hypoproteinemia, hypoalbumine-
mia, hypokalemia and hypoglobulinemia continued
even after treatment. Gross and histopathologic find-
ings of congestion, haemorrhage, necrosis in vital or-
gans viz., lungs, liver, kidneys, brain and intestines
were suggestive of endotoxin induced hypoxia and
multi-organ failure. Additionally, emphysema and fi-
brinous thrombi in microvasculature of lungs were
salient histopathological findings indicating terminal
respiratory failure in the remaining two dead endo-
toxemic buffalo calves. From clinical signs, plasma
chemistry and pathological lesions, it was concluded
that endotoxemia led to a disruption of critical life
processes, but a timely and effective treatment could
counter these deleterious effects and save precious
lives.
Keywords: Blood; Buffalo Calves; Dextran-40;
Endotoxemia; Flunixin Meglumine; Hypertonic Saline;
Physiology; Pathology
1. INTRODUCTION
Endotoxic shock is an acute circulatory failure occurring
in the presence of severe infection and represents an im-
balance between the body’s oxygen demand and supply.
It is principally of the distributive type, although cardio-
genic and hypovolemic components may also be invol ved
[1]. Endotoxin is an integral component of the outer me m-
brane of gram-negative bacteria and the effects of expo-
sure of host cells to it include the un controlled release of
cytokines and eicosanoids, kinins and other short, me-
dium and long-term reactants that upset the balance be-
tween pro-inflammatory and anti-inflammatory pathways,
causing hypotension, disseminated intravascular coagula-
tion, abortion and death [2]. Endotoxemia is a life-thr ea te n-
ing inflammatory condition, which can lead to shock, mul-
tiple organ failure, suppression of immune system and in-
terferes with wound-healing processes [3].
Despite many limitations, animal models remain es-
sential for the development of new therapeutic regimens
of endotoxic shock, which can’t be replicated by in-vitro
studies [4].
Therefore, the present investigation was planned with
the objectives to study the major physio-pathological
changes during induced endotoxemia in buffalo calves
and the effects of treatment regimen of hypertonic saline
solution, Dextran-40, Flunixin meglumine and whole blo od
infusion on these profiles. The studies could also help in
finding suitable therapeutic regimens applicable in other
species of animals and man.
2. MATERIAL AND METHODS
Five apparently healthy 6-month to one-year-old male

I. Nabi et al. / J. Biomedical Science and Engineering 6 (2013) 1077-1084 1078
buffalo calves with body weight range of 70 - 140 Kg
were used in the present investigation. These calves were
kept under the good managemental conditions as are
practiced at the university dairy farm. All the animals
were de-wormed and vaccinated against haemorrhaegic
septicemia well before the start of the experiment.
The Endotoxin1 was reconstituted by dissolving it in
normal saline solution (0.9%NaCl) to make a stock solu-
tion of 1 mg/ml. Endotoxin concentration of 5 µg/ml was
prepared by dissolving 1 ml of stock solution in 199 ml
of normal saline to make a total volume 200 ml. The en-
dotoxin was then infused intravenously through jugular
vein @ 5 µg/kg BW/hr for 3 hours, followed immedi-
ately by a rapid infusion of hypertonic saline solution @
4 milliliter/Kilogram body weight (ml/Kg·BW), dextran-
40 @ 10 ml/Kg·BW, flunixin meglumine @ 1.1 milli-
gram/Kg·BW (mg/Kg·BW) and blood @ 20 ml/Kg·BW
Body as one time treatment. The HSS had been prepared
by dissolving 72 gm of sodium chloride in one liter of
double distilled water (7.2% Nacl aqueous solution) and
autoclaved at a pressure of 15 lbs for 20 minutes, 16 - 18
hrs prior to infusion.
The animals were casted in right lateral recumbency
on operation table. Before endotoxin infusion, an area
over jugular furrow was shaved and disinfected. The lo ca l
anesthetic Lignocaine (2%) @ 90 - 120 ml was injected
subcutaneously and intra-muscularly before catheteriza-
tion of the jugular vein and the carotid artery. The blood
samples from jugular vein of the experimental buffalo
calves were collected in heparin immediately before and
after 1.5, 2.5, 3.5, 4.5, 5.5, 6.5 hrs of the start of endo-
toxin infusion, follow ed by samples at 24 hr of last sam-
ple of day 1, upto 4th day. The following physiological
constituents like the plasma total protein, acute phase
proteins like albumin, fibrinogen, globulins, alkaline phos-
phatase, creatinine, glucose, sodium, potassium, calcium
and phosphorus were estimated by dry stat clinical chem-
istry analyser2. Plasma fibrinogen was estimated using a
portable refractometer by comparing the protein in non-
heated plasma and that in the respective sample heated to
56˚ to 58˚ Celsius for 3 minutes [5]. The data so gener-
ated was pooled and analysed with CRD Anova [6]. All
the values obtained were compared with the normal pre-
infusion values within the group. The study design and
animal experimental protocols were approved by the In-
stitutional Animal Ethics Committee (IAEC) of the Uni-
versity.
3. RESULTS AND DISCUSSION
3.1. Clinical Signs
Clinical signs observed due to endotoxemia consisted of
restlessness, respiratory distress, forceful abdominal res-
piration, diarrhoea and profuse salivation. Three endoto xe-
mic buffalo calves out of five animals survived beyond
the observation period, whereas, the remaining two buf-
falo calves d ied duri ng the observ ation pe r iod.
3.2. Clinical Chemistry
The results of the physiological p rofiles estimated during
present investigation are presented in Table 1 and Fig-
ures 1-3.
The normal mean pre-infusion total protein was found
to be 6.62 ± 0.17 g/dl, which is close to 6.82 ± 0.24 g/dl
reported by Sobti et al. (1981) [7], 6.40 ± 0.19 g/dl [8],
but lower than 7.54 ± 0.25 g/dl [9]. In the present study,
however, a significant (P < 0.05) hypoproteinemia was
observed at 3.5 hr after the endotoxin infusion (Figure 1).
[10,11] also observed hypoproteinemia on E. coli endotoxin
infusion in bovine calv e s.
The hypoproteinemia as observed in present investiga-
tion was perhaps due to increased protein catabolism
coupled with decreased ability of anoxic liver to metabo-
lize amino acid to synthesize protein, besides sequestra-
tion of plasma proteins into tissues [8].
A significant (P < 0.05) hypoproteinemia continued
even after treatment with HSS, Dextran-40, flunixin me-
glumine and blood at 4.5, 5.5 and 6.5 hrs., which may be
attributed to the rapid plasma volume expansion and the
redirected splanchnic perfusion following HSS infusion
[12]. In fact, the HSS acutely increases the plasma osmo-
larity and draws intra cellular and interstitial water in to t he
vascular space. There was plasma volume expansion of
3ml for every 1ml of hypertonic saline infused [13].
The pre-infusion plasma albumin was found to be 2.78
± 0.10 g/dl, which is similar to 2.70 ± 0.12g/dl [14] but
lower than 3.29 ± 0.13 g/dl and 3.20 ± 0.19 g/dl [15,16].
A significant (P < 0.05) hypo-albumine mia was observed
throughout th e endotox in infusion (Figure 1). Hypoalb u-
minemia persisted even after treatment at 4.5, 5.5 and 6.5
hrs. in a previous study [8]. A significant (P < 0.05) hy-
poalbuminemia in endotoxin infused buffalo calves was
also observed [8]. The fall in albumin can be attributed to
loss of blood and plasma in tissues, besides diarrhoea,
the common manifestations in endotoxic shock. The hy-
po-albuminemia, in turn, might contribute to hypoprote-
inemia [15].
The pre-infusion mean plasma fibrinogen recorded was
0.24 ± 0.04 g/dl, which is lower than 0.30 to 0.8 gm/dl [5]
and 0.35 to 0.60 g/dl [16]. In the pr esent study, only non-
significant post-infusion alterations in fibrinogen level
were observ ed throughout th e experiment (Figure 1).
The normal or pre-infusion mean plasm a globulins were
found to be 3.54 ± 0.22 g/dl, which is close to 3.90 ±
0.39 g/dl [14], but higher than 3.24 ± 0.24 g/dl [15], 2.34
± 0.25 g/dl [17] and 2.79 ± 0.13 g/dl [18]. In the present
1Escherichia coli endotoxin Lyophilized (Phenol extracted) 0111:B4
lipopolysacharide, SIGMA Chemicals USA.
2Dr
y
stat clinical dr
y
chemist
r
y
anal
y
ser, Johnson & Johnson, USA.

I. Nabi et al. / J. Biomedical Science and Engineering 6 (2013) 1077-1084 1079
Table 1. Clinical chemistry (Mean + S.E.) at different stages of endotoxic shock and after treatment with HSS, Dextran-40, Flunixin
meglumine and Blood.
Group Endotoxic shock After treatment
0 h 1.5 h 2.5 h 3.5 h 4.5 h 5.5 h 6.5 h Day2
Total protein(g/dl) 6.62 ± 0.17 6.04 ± 0.39 5.96 ± 0.235.20* ± 0.214.44* ± 0.284.50* ± 0.16 4.88* ± 0.07 6.32 ± 0.39
Albumin(g/dl ) 2.78 ± 0.10 2.20* ± 0.08 2.26* ± 0.071.98* ± 0.581.60* ± 0.09*1.58* ± 0.07 1.78* ± 0.11 2.54 ± 0.28
Fibrinogen(g/dl) 0.24 ± 0.04 0.24 ± 0.04 0.44 ± 0.190.40 ± 0.09 0.36 ± 0.04 0.57 ± 0.27 0. 60 ± 0.22 0.64 ± 0.20
Globulins(g/dl) 3.54 ± 0.22 3.60 ± 0.31 3.26 ± 0.402.82 ± 0.27 2.48* ± 0.272.36* ± 0.33 2.50* ± 0.29 3.14 ± 0.39
Glucose(mg/dl) 92.00 ± 2.17 101.60 ± 10.64 93.80 ± 8.26130.20 ± 10.18175.00* ± 12.17154.40* ± 15.20 110.60 ± 17.33 130.20 ± 33.44
Creatinine(mg/dl) 1.52 ± 0.15 1.60 ± 0.14 1.74 ± 0 .181.54 ± 0.09 1.52 ± 0.10 1.56 ± 0.10 1.7 4 ± 0 .23 2.12* ± 0.29
Sodium(mmol/l) 133.60 ± 2.21 131.60 ± 2 .64 134.40 ± 1.72135.40 ± 1.29131.20 ± 2.91130.00 ± 3.74 136.00 ± 2.12 132.60 ± 2.04
Potassium(mmol/l) 3.36 ± 0.15 2.72* ± 0.12 2.78* ± 0.222.64* ± 0.122.40* ± 0.152.38* ± 0.07 2.46* ± 0.11 2.92 ± 0.22
Calcium(mg/dl) 9.82 ± 0.72 8.02* ± 0.34 7.46* ± 0.236.86* ± 0.146.56* ± 0.226.74* ± 0.28 7.28* ± 0.38 7.88* ± 0.43
Phosphorus(mg/dl) 5.16 ± 0.31 5.14 ± 0.16 5.02 ± 0.244.92 ± 0.15 4.58 ± 0.29 4.66 ± 0. 22 4.68 ± 0.30 5.74 ± 0.60
Alkaline
Phosphatase(U/l) 63.40 ± 18.62 70.60 ± 21 .95 71.40 ± 19.3578.00 ± 26.9078.00 ± 15.9074.20 ± 20.95 84.80 ± 21.0 77.80 ± 19.20
No. of animals in group = 5; *Significant at 5% level.
creatinine
0
0.5
1
1.5
2
2.5
0 hr
1.5 hr 2.5 hr 3.5 hr 4.5 hr 5.5 hr 6.5 hr
2 day
time
conc. mg/dl
creatinine
Figure 1. Total protein, Albumin, globulin and fibrinogen dur-
ing and after endotoxic shock and treatment. Figure 2. Creatinine during and after endotoxic shock and
treatment.
study, buffalo calves did not show any significant change
in plasma globulins during endotoxin infusion. After tr eat-
ment, a significant (P < 0.05) fall in globulins at 4.5, 5.5
and 6.5 hrs. was observed, which may be due to the in-
creased protein breakdown as also reflected by hypopro-
teinemia, in the present study. The pre-infusion mean
plasma creatinine observed was within the physiological
range i.e., 1.52 ± 0.15 mg/dl [15], which is also close to
1.10 to 1.30 ± 0.10 mg/dl [12]. A non-significant varia-
tion in plasma creatinine (Figure 2) was ob served during
the intravenous infusion of the endotoxin. However, plasma
creatinine increased significantly after treatment on day 2
of observation in comparison to pre-infusion level. It ma y
probably be due to the protracted endotoxin induced re-
nal damage as observed grossly and histopathologically
in the present study.
glucose
0
20
40
60
80
100
120
140
160
180
200
0 hr1.5
hr 2.5 hr 3.5 hr 4.5 hr 5.5 hr 6.5 hr 2 day
time
conc. m g/dl
glucose
Figure 3. Plasma glucose during and after endotoxic shock and
treatment.
The normal mean b lood gluco se observed w as 92.00 ±
2.17 mg/dl, which is higher th an 67.50 ± 1.74 mg/dl and
75.30 ± 0.97 mg/dl. [14], [8]. In the present study, the
plasma glucose level showed a non-significant alteration
during i.v. infusion of endotoxin. However, after treat-
ment, a significant (P < 0.05) hyperglycemia at 4.5 and
5.5 hrs. was observed (Figure 3), suggesting probable
beneficial effects of Dextran-40, which gets converted
into glucose through metabolism in liver. Hyperglycemia
may also be due to release of epinephrine due to the
stress of ca theterization, besides sh o ck.
The pre-infusion mean plasma calcium observed was
9.82 ± 0.72 mg/dl, which is within the physiological
range of 8.7 - 11.4 mg/dl [15] and 9.7 - 12.4 mg/dl [19].
In the present study, a significant (P < 0.05) hypocalca-
emia was observed throughout the experiment as also

I. Nabi et al. / J. Biomedical Science and Engineering 6 (2013) 1077-1084 1080
reported previously [20]. The pre-infusion mean plasma
phosphorus observed was 5.16 ± 0.31 mg/dl., which is
close to physiological value of 5.6 - 6.5 mg/dl [19] and
the plasma phosphorus did not show any significant va r ia -
tion during and after the intravenous infusion of endo-
toxin and the treatment.
The pre-infusion mean plasma sodium observed was
133.6 ± 2.21 mmol/l, which is close to 136.6 ± 5.51
mmol/l [16 ], 134.48 ± 4.07 mmol/l [9] an d 133.40 ± 3.19
mmol/l [20]. However, a generalized non-significant in-
crease in sodium was noticed throughout the period of
experiment as also recorded in endotoxemic cows [21]
and buffalo calves [14], previously. In the present inves-
tigation, the mean sodium level at the end of the obser-
vation period was almost equal to pre-infusion level. Ab-
sence of any significant increase in plasma sodium even
after infusion of HSS seems to be advantageous as it
makes the infusion of HSS safe [22].
The pre-infusion mean plasma potassium ranged be-
tween 3.36 ± 0.15 mmol/l, which is close to 3.60 ± 0.2
mmol/l [21] but higher than 2.28 ± 0.18 mmol/l [9]. A
significant (P < 0.05) hypokalemia was observed at 1.5,
2.5 and 3.5 hrs. i.e., throughout the endotoxin infusion
and even after treatment at 4.5, 5.5 and 6.5 hrs. This fall
in potassium level may be regarded as an attempt by the
body to sequester potassium as a part of the mechanism,
whereby endotoxins promote the release of endogenous
pyrogens from leucocytes. Decrease in potassium level
could also be attributed to release of histamine during en-
dotoxic shock, which increases the capillary permeability,
besides regulating the secretion of adrenaline and nor-
adrenaline together [23]. Hypokalemia after treatment
can rather be attributed to rapid volume expansion fol-
lowing HSS infusion [12]. Decrease in plasma levels of
sodium and potassium may furthermore be attributed to
the greatly diminished active transport of sodium and po-
tassium across the cell membrane [23].
The pre-infusion mean plasma alkaline phosphatase
was 63.40 ± 18.62 U/l, which is lower than 173 ± 40 U/l
as reported by [12]. A non-significant variation in plasma
alkaline phosphatase was recorded throughout the period
of observation.
4. PATHOLOGICAL LESIONS
Two out of five endotoxemic buffalo calves that died
during observ ation period were su bjected to necrop sy ex-
amination in order to study the gross and histopathologi-
cal changes.
4.1. Gross Lesions
Gross lesions varied from mild to clear cut haemorrhages
along with congestion and emphysema in lungs (Figure
4) in both the endotoxemic buffalo calves. In addition,
congestion, odema and dilation of intestines (Figure 5),
haemorrhages on its mucosal surface as well as in medi-
astinal lymph nodes and in the gall bladder mucosa were
noticed. Severe congestion leading to reddish discolora-
tion of cortex of the kidneys (Figure 6) was conspicuous.
The gross lesions were suggestive of toxemia, enteropa-
thy and pulmonary insult accompanying endotoxic shock.
Figure 4. Lung-haemorrhages and emphysema.
Figure 5. Intestines-congestion, edema and dilatation with di-
arrheic contents.
Figure 6. Kidney-marked congestion in cortex.

I. Nabi et al. / J. Biomedical Science and Engineering 6 (2013) 1077-1084 1081
4.2. Histopathology
Histopatholgically, the lesions were more specific and
the common findings in both the animals were conges-
tion, haemorrhages and emphysema in lungs (Figure 7),
necrotic enteritis (Figure 8) with mononuclear cell infil-
teration, congestion and lower nephron nephrosis in kid-
neys (Figure 9), mild sinusoidal congestion and hepato-
cellular degeneration (Figure 10), besides focal necrosis
in liver. In gall bladder, haemorrhages along with s lough -
ing of mucosa (Figure 11) were also recorded. These
findings indicated muti-organ failure as the cause of death
in endotoxaemia [4]. The small intestine revealed a very
characteristic segmental necrosis of the villi (Figure 8),
possibly related to ischemia or marked hypoxia. Morpho-
logical and functiona l damage in human intestinal epithe-
lium has been correlated to induced iNOS synthesis by
endotoxin causing in crease in epithelial permeability and
secretory diarrhea [24].
Figure 7. L u n g - m a r k e d c o n g e s t i o n a n d e m p h y s e m a ( H . E.X150).
Figure 8. Intestine-necrosis of villi (H. E.X150).
Figure 9. Kidney-diffuse necrosis of tubular epithelium (lower
nephron nephrosis) along with congestion in a glomerulus (H.
E.X300).
Figure 10. Liver-congestion and mild vacuolar degeneration of
hepatocytes (H. E.X300).
Figure 11. Gall bladder-haemorrhages along with sloughing of
mucosa (H.E.X150).

I. Nabi et al. / J. Biomedical Science and Engineering 6 (2013) 1077-1084 1082
Atelactasis, congestion, haemorrhages and emphysema
in lungs, edema in intestinal mucosa along with exten-
sive coagulative necrosis of epithelial cells of villi, dif-
fuse coagulative necrosis of convoluted tubules of kidney
and congestion, haemorrhages with fatty degeneration and
coagulative necrosis in liver was previously observed.
[25] Edema, congestion and haemorrhages in lungs,
nephritic changes in kidney, areas of coagulative necro-
sis of the hepatocytes and necrosis of the intestinal villi
with infiltration of polymorphs was also reported earlier
[26].
In one of the endotoxemic buffalo calves, degenerative
changes of cardiac myocytes along with mononuclear
cell infiltration in perivascular region of the myocardium
(Figure 12) were also noticed, suggesting cardiomyopa-
thy. Hackel et al. (1974) [27] reported myocytic necrosis
and haemorrhage in the sub-endocardial region of myo-
cardium in endotoxaemia.
In the second buffalo calf, congestion, haemorrhages,
neuronal degeneration and mild edema in the cerebrum
(Figure 13) indicated endotoxin induced encephalopathy
[28]. Nagaraja (1979) [10] and Sokkar (2003) [25] also
reported numerous haemorrhages and edema in cerebrum
of endotoxemic calves and rams, respectively. These
changes were suggestive of toxemia related vascular in-
jury, particularly the haemorrhage in the brain might be
of greater relevance.
Fibrinous thrombi in the microvasculature of lungs
were also noticed in one buffalo calf (Figure 14). Naga-
raja et al. (1979) [10] also observed fibrin thrombi in ar-
terioles and capillaries of lungs in endotoxemic calves.
These findings led to the belief that there was setting up
of intravascular coagulation. There are considerable in-
terspecies differences in sensitivity to endotoxin, how-
ever, humans and ruminants show a relatively similar and
Figure 12. Heart-Mild mononuclear infiltration and degenera-
tion (H.E.X300).
Figure 13. Cerebrum-congestion, haemorrhages, neuronal dege-
neration and mild edema (H. E.X150).
Figure 14. Lung-congestion and fibrinous emboli in vessel (H.
E.X75).
enhanced response to endotoxin. Therefore, in the present
investigation, bovine was selected as animal model to si-
mulate human endotoxic shock [4].
4.3. Treatment
Treatment of endotoxemia is difficult because of the nu-
merous mediators involved. There are three possible ap-
proaches in treating endotoxemia. The interaction of en-
dotoxin with target cells can be blocked by inducing tol-
erance, decreasing plasma endotoxin concentrations, or
interfering with endotoxin binding [29]. According to Ei-
cosanoids are responsible for many of the clinical m an if e s-
tations of endotoxemia [30]. NSAIDS inhibit the produc-
tion of eicosanoids and TXA-2. Among NSAIDS, flu-

I. Nabi et al. / J. Biomedical Science and Engineering 6 (2013) 1077-1084 1083
nixin meglumine is the most effective and is anti-endo-
toxic at doses much lower than those required for anal-
gesia. Administration of hypertonic saline leads to reen-
try of extravascular fluid s into the vascular compartment
to produce a more rapid response and marked haemody-
namic effects than conventional use of isotonic solutions
[31]. Endotoxemia also leads to protein loss and reduced
colloidal oncotic pressure. The use of colloid therapy, in-
cluding synthetic and natural colloids, is therefore indi-
cated to mainta in the colloidal o ncotic pr ess ure and to r e-
plenish the protein loss [32]. The fluids are critical in the
pathogenesis and early resuscitation of septic shock. Ad-
ministration of fluids especially colloids and crystalloids
modulate inflammation, improve micro - v asu l ar p erf u si on ,
impact organ function and thereby outcome. The combi-
nation of all these factors might have led to survival of 3
out of 5 calves in the present st udy .
5. CONCLUSION
A perusal of clinical signs, clinical chemistry and patho-
logical lesions in dead calves indicated that there is a
muti-organ damage and pathologies induced by entotoxic
shock are critical for maintenance of life processes. If the
damage becomes irreparable, the animal may die. How-
ever, constituting timely therapeu tic regimens co ns is ti n g
of hypertonic saline solution, dextran-40, flunixin me-
glumine and whole blood infusion as used in the present
study could counter or reverse some of the deleterious
effects of endotoxins and th ereby save lives.
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