Objective—To evaluate systemic effects of IV infusion
of ATP-MgCl2 subsequent to infusion of a low
dose of endotoxin in horses.
Animals—12 adult horses.
Procedure—Horses were administered endotoxin
(lipopolysaccharide [LPS]) or saline (0.9% NaCl) solution,
IV, during a 30-minute period. Immediately thereafter,
horses in each group were infused IV with ATP-MgCl2 or
saline solution. Two weeks later, horses were administered
the opposite solution (LPS or saline solution), but
it was followed by the same infusion as 2 weeks previously
(ie, ATP-MgCl2 or saline solution). Cardiopulmonary
and clinicopathologic variables, cytokine activity, and
endothelin (ET) concentrations were recorded.
Results—IV infusion of ATP-MgCl2 after administration
of a low dose of endotoxin failed to attenuate the
cardiopulmonary, clinicopathologic, and cytokine alterations
that develop secondary to endotoxin exposure.
The combination of LPS and ATP-MgCl2 potentiated
pulmonary hypertension, leukopenia, and neutropenia
when compared with the combination of LPS and
saline solution. The combination of LPS and ATP-MgCl2
resulted in thrombocytopenia. Endothelin concentration
was increased in jugular venous and pulmonary
arterial plasma in horses receiving LPS and
ATP-MgCl2. Similar increases were not observed with
LPS and saline solution.
Conclusions and Clinical Relevance—Administration
of ATP-MgCl2 did not protect horses from systemic
effects of experimentally induced endotoxemia.
Furthermore, the use of ATP-MgCl2 during endotoxemia
may worsen the cardiopulmonary and clinicopathologic
status of affected horses. Because ATP and
other adenine nucleotides are released from cells during
shock, their potential role in the development of
hemodynamic derangements, leukocyte adherence,
and coagulopathies during endotoxemic episodes warrants
further investigation. (Am J Vet Res 2004;65:
Objective—To characterize alterations in systemic
and local colonic hemodynamic variables associated
with IV infusion of ATP-MgCl2 in healthy anesthetized
Animals—12 adult horses.
Procedure—Six horses were given ATP-MgCl2, IV,
beginning at a rate of 0.1 mg of ATP/kg of body
weight/min with incremental increases until a rate of
1.0 mg/kg/min was achieved. The remaining 6 horses
were given an equivalent volume of saline (0.9%
NaCl) solution over the same time period. Colonic and
systemic hemodynamic variables and colonic plasma
nitric oxide (NO) concentrations were determined
before, during, and after infusion.
Results—Infusion of ATP-MgCl2 caused a rate-dependent
decrease in systemic and colonic vascular resistance,
principally via its vasodilatory effects. A rate of
0.3 mg of ATP/kg/min caused a significant decrease in
systemic and colonic arterial pressure and colonic vascular
resistance without a significant corresponding
decrease in colonic arterial blood flow. Consistent alterations
in NO concentrations of plasma obtained from
colonic vasculature were not detected, despite profound
vasodilatation of the colonic arterial vasculature.
Conclusions and Clinical Relevance—Results
revealed that IV infusion of ATP-MgCl2 may be beneficial
in maintaining colonic perfusion in horses with
ischemia of the gastrointestinal tract, provided a sufficient
pressure gradient exists to maintain blood flow.
(Am J Vet Res 2001;62:1240–1249)
Objective—To evaluate the in vitro effects of adenosine
tryphosphate (ATP) on vasomotor tone of equine
Sample Population—Arteries and veins from the left
ventral colon of 14 mixed-breed horses euthanatized
for reasons unrelated to cardiovascular or gastrointestinal
Procedures—Endothelium-intact and -denuded arterial
and venous rings were precontracted with 10–7 and
1.8 × 10–8M endothelin-1, respectively. In 1 trial,
endothelium-intact rings were also incubated with
10–4M Nω-nitro-L-arginine methyl ester (L-NAME) to
inhibit nitric oxide (NO) production. Adenosine
triphosphate (10–8 to 10–3M) was added in a noncumulative
manner, and relaxation percentage versus time
curves were generated. Areas under the curves (ie,
percentage of relaxation time) were calculated.
Results—Relaxation response of arterial and venous
rings to ATP was dose-dependent. Percentage of
relaxation time in response to 10–4 and 10–3M ATP was
significantly greater, compared with that for rings not
treated with ATP. Removal of endothelium attenuated
but did not eliminate the relaxation response. Addition
of L-NAME did not attenuate the relaxation response
in arteries. At higher concentrations, the vascular
response to ATP was biphasic.
Conclusions and Clinical Relevance—ATP applied to
equine colonic arterial and venous rings with and without
intact endothelium induced a biphasic response
characterized by transient contraction followed by slow,
substantial, and sustained relaxation. This ATP-induced
response is possibly mediated by a mechanism other
than NO. Adenosine triphosphate may be a useful
treatment to modulate colonic vasomotor tone in horses
with strangulating volvulus of the ascending colon.
(Am J Vet Res 2001;62:1928–1933)