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Heflin et al
Heparin and Anaphylactoid Shock in a Porcine Model
trends did not reach statistical significance. Because of this result, heparin is not recommended as a replacement for standard therapy. The saline group had the most dramatic response to A23187, but this was not statistically significant.This study demonstrates the ability of A23187 to induce shock, with flushing and elevation of serum histamine levels in a porcine model. The dose of A23187 used was capable of producing hypotension severe enough to cause rapid death if untreated, indicating that A23187 has potential as a model for studying rapid onset of shock. Standard treatment with diphenhydramine and epinephrine and treatment with heparin alone were efficacious in reversing hypotension in all animals, but a saline placebo had no efficacy. Further investigation is needed to determine whether unfractionated heparin has a role in the treatment of shock related to anaphylaxis. This result has potential value to the practice of emergency medicine in that patients with cardiovascular disease may have relative contraindications to epinephrine and some patients may be refractory to standard therapy. No recommendations for the use of heparin in treating anaphylactoid shock in humans can be made on the basis of this pilot study. Supervising editor: Stephen R. Thom, MD, PhD WJM conceived the study and designed the trial. CRH, KLB, JBH, and WJM supervised the conduct of the trial and data collection. KLB provided statistical advice on study design and analyzed the data. CRF drafted the manuscript, and all authors contributed substantially to its revision. WJM takes responsibility for the paper as a whole. Funding and support: The authors report this study did not receive any outside funding or support. Publication dates: Received for publication October 12, 2005. Revisions received January 5, 2006, and February 9, 2006. Accepted for publication February 22, 2006. Available online June 26, 2006.
Reprints not available from the authors. Address for correspondence: William J. Meggs, MD, PhD, Department of Emergency Medicine, Brody School of Medicine at East Carolina University, 600 Moye Boulevard, Room 3ED311, Greenville, NC 27834; 252-744-2954, fax 252-744-3589; E-mail [email protected] REFERENCES 1. Rabenstein DL, Bratt P, Peng J. Quantitative characterization of the binding of histamine by heparin. Biochemistry. 1998;37: 14121-14127. 2. Chuang WL, Christ MD, Peng J, et al. An NMR and molecular modeling study of the site-specific binding of histamine by heparin, chemically modified heparin, and heparin-derived oligosaccharides. Biochemistry. 2000;39:3542-3555. 3. Dolowitz DA, Dougherty TF. Allergy as inflammatory reactions. Ann Allergy. 1971;29:410-417. 4. Gordan BF. Heparin use in allergy emergency management 1993: symposium on heparin use in allergy and illness. November 19, 1993. 5. Warren Jr CM. Treatment of allergic emergencies: symposium on allergy in otolaryngologic practice. Otolaryngol Clin North Am. 1971;4:599-608. 6. Diamant B, Patkar SA. Stimulation and inhibition of histamine release from isolated rat mast cells: dual effects of the ionophore A23187. Int Arch Allergy Appl Immunol. 1975;49:183-207. 7. Kondorosi E, Kay JE. The role of calcium in lymphocyte activation by the ionophore A23187 and phytohaemagglutinin [proceedings]. Biochem Soc Trans. 1977;5:967-970. 8. Silbaugh SA, Sofia MJ, Hamill RL. Pulmonary responses of the guinea pig to inhaled A23187: a brief review. Agents Actions. 1992;11:188-190. 9. Hashimoto M, Ishida Y, Naruse I, et al. Prolonged cold storage abolishes endothelium-dependent relaxing responses to A23187 and substance P in porcine coronary arteries. J Vasc Res. 1992; 29:64-70. 10. Boulanger C, Schini VB, Moncada S, et al. Stimulation of cyclic GMP production in cultured endothelial cells of the pig by bradykinin, adenosine diphosphate, calcium ionophore A23187 and nitric oxide. Br J Pharmacol. 1990;101:152-156. 11. Laroche D, Vergnaud MC, Sillard B, et al. Biochemical markers of anaphylactoid reactions to drugs: comparison of plasma histamine and tryptase. Anesthesiology. 1991:75:945-949.
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Volume , . : August
Annals of Emergency Medicine 193
Heparin and Anaphylactoid Shock in a Porcine Model
trends did not reach statistical significance. Because of this result, heparin is not recommended as a replacement for standard therapy. The saline group had the most dramatic response to A23187, but this was not statistically significant.This study demonstrates the ability of A23187 to induce shock, with flushing and elevation of serum histamine levels in a porcine model. The dose of A23187 used was capable of producing hypotension severe enough to cause rapid death if untreated, indicating that A23187 has potential as a model for studying rapid onset of shock. Standard treatment with diphenhydramine and epinephrine and treatment with heparin alone were efficacious in reversing hypotension in all animals, but a saline placebo had no efficacy. Further investigation is needed to determine whether unfractionated heparin has a role in the treatment of shock related to anaphylaxis. This result has potential value to the practice of emergency medicine in that patients with cardiovascular disease may have relative contraindications to epinephrine and some patients may be refractory to standard therapy. No recommendations for the use of heparin in treating anaphylactoid shock in humans can be made on the basis of this pilot study. Supervising editor: Stephen R. Thom, MD, PhD WJM conceived the study and designed the trial. CRH, KLB, JBH, and WJM supervised the conduct of the trial and data collection. KLB provided statistical advice on study design and analyzed the data. CRF drafted the manuscript, and all authors contributed substantially to its revision. WJM takes responsibility for the paper as a whole. Funding and support: The authors report this study did not receive any outside funding or support. Publication dates: Received for publication October 12, 2005. Revisions received January 5, 2006, and February 9, 2006. Accepted for publication February 22, 2006. Available online June 26, 2006.
Reprints not available from the authors. Address for correspondence: William J. Meggs, MD, PhD, Department of Emergency Medicine, Brody School of Medicine at East Carolina University, 600 Moye Boulevard, Room 3ED311, Greenville, NC 27834; 252-744-2954, fax 252-744-3589; E-mail [email protected] REFERENCES 1. Rabenstein DL, Bratt P, Peng J. Quantitative characterization of the binding of histamine by heparin. Biochemistry. 1998;37: 14121-14127. 2. Chuang WL, Christ MD, Peng J, et al. An NMR and molecular modeling study of the site-specific binding of histamine by heparin, chemically modified heparin, and heparin-derived oligosaccharides. Biochemistry. 2000;39:3542-3555. 3. Dolowitz DA, Dougherty TF. Allergy as inflammatory reactions. Ann Allergy. 1971;29:410-417. 4. Gordan BF. Heparin use in allergy emergency management 1993: symposium on heparin use in allergy and illness. November 19, 1993. 5. Warren Jr CM. Treatment of allergic emergencies: symposium on allergy in otolaryngologic practice. Otolaryngol Clin North Am. 1971;4:599-608. 6. Diamant B, Patkar SA. Stimulation and inhibition of histamine release from isolated rat mast cells: dual effects of the ionophore A23187. Int Arch Allergy Appl Immunol. 1975;49:183-207. 7. Kondorosi E, Kay JE. The role of calcium in lymphocyte activation by the ionophore A23187 and phytohaemagglutinin [proceedings]. Biochem Soc Trans. 1977;5:967-970. 8. Silbaugh SA, Sofia MJ, Hamill RL. Pulmonary responses of the guinea pig to inhaled A23187: a brief review. Agents Actions. 1992;11:188-190. 9. Hashimoto M, Ishida Y, Naruse I, et al. Prolonged cold storage abolishes endothelium-dependent relaxing responses to A23187 and substance P in porcine coronary arteries. J Vasc Res. 1992; 29:64-70. 10. Boulanger C, Schini VB, Moncada S, et al. Stimulation of cyclic GMP production in cultured endothelial cells of the pig by bradykinin, adenosine diphosphate, calcium ionophore A23187 and nitric oxide. Br J Pharmacol. 1990;101:152-156. 11. Laroche D, Vergnaud MC, Sillard B, et al. Biochemical markers of anaphylactoid reactions to drugs: comparison of plasma histamine and tryptase. Anesthesiology. 1991:75:945-949.
Did you know?
You can save your online searches and get the results by e-mail.
Visit www.annemergmed.com today to see what else is new online!
Volume , . : August
Annals of Emergency Medicine 193