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Effects of infusion of adenosine triphosphatemagnesium chloride on cardiopulmonary and clinicopathologic variables, cytokine activity, and endothelin concentration in horses administered a low dose of endotoxin

Joanne Tetens DVM, PhD1,2, Rustin M. Moore DVM, PhD3,4,5, Giselle L. Hosgood BVSc, PhD6, Susan C. Eades DVM, PhD7, Michael L. Keowen BS8, and David W. Horohov PhD9,10
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  • 1 Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410.
  • | 2 Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410.
  • | 3 Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410.
  • | 4 Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410.
  • | 5 Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410
  • | 6 Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410.
  • | 7 Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410.
  • | 8 Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410.
  • | 9 Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803-8410.
  • | 10 Present address is Gluck Equine Research Center, University of Kentucky, Lexington, KY 40506.

Abstract

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: 225–237)

Abstract

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: 225–237)