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The preischemic combination of the sodium-hydrogen exchanger inhibitor cariporide and the adenosine agonist AMP579 acts additively to reduce porcine myocardial infarct size.
J Am Coll Surg. 2004 Oct; 199(4):586-94.JA

Abstract

BACKGROUND

We tested whether the combination of two known cardioprotective agents, the type-1 sodium-hydrogen exchanger inhibitor cariporide plus the adenosine A(1)/A(2a) receptor agonist AMP579 ([1S-[1a,2b,3b, 4a(S*)]]-4-[7-[[2-(3-chloro-2-thienyl)-1-methylpropyl]amino]-[(3)H]-imidazo[4,5-b]pyridyl-3-yl]cyclopentane carboxamide), acted additively to reduce myocardial infarct size.

STUDY DESIGN

Pigs underwent 1 hour of coronary artery occlusion and 3 hours reperfusion. Vehicle-treated controls were compared with animals treated before ischemia with low-dose and high-dose cariporide and AMP579, and low-dose cariporide plus AMP579. The effects of both agents, alone and in combination, were also tested in isolated porcine polymorphonuclear neutrophils (PMNs). The PMN respiratory burst was induced with phorbol 12-myristate 13-acetate and quantified by the increase in 2',7'-dichlorofluorescein fluorescence, measured by flow cytometry.

RESULTS

Infarct size in the control pigs was 65 +/- 1% of the area at risk. Cariporide dose-dependently reduced infarct size to 39 +/- 2% and 24 +/- 3% in the low- and high-dose groups, respectively. Infarct size was 54 +/- 3% in the low-dose AMP579 group and 47 +/- 3% with high dose. The combination of low doses of cariporide and AMP579 reduced infarction to 25 +/- 6% of the area at risk. In the PMN studies, cariporide and AMP579 alone had no effect on 2',7'-dichlorofluorescein fluorescence, but the combination of the two agents reduced the PMN 2',7'-dichlorofluorescein increase to 79 +/- 5% of the vehicle control response.

CONCLUSIONS

The preischemic combination of low doses of cariporide and AMP579 decreased myocardial infarct size more than either agent used alone in low concentration, indicating an additive effect of the two agents. Given the effects that cariporide plus AMP579 combination exerted on PMN activity, it appears that this combination has the potential to reduce PMN-mediated effects during myocardial reperfusion.

Authors+Show Affiliations

Department of Surgery, University of Kentucky, College of Medicine, Lexington, KY 40536-0084, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Evaluation Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15454144

Citation

Kristo, Gentian, et al. "The Preischemic Combination of the Sodium-hydrogen Exchanger Inhibitor Cariporide and the Adenosine Agonist AMP579 Acts Additively to Reduce Porcine Myocardial Infarct Size." Journal of the American College of Surgeons, vol. 199, no. 4, 2004, pp. 586-94.
Kristo G, Yoshimura Y, Ferraris SP, et al. The preischemic combination of the sodium-hydrogen exchanger inhibitor cariporide and the adenosine agonist AMP579 acts additively to reduce porcine myocardial infarct size. J Am Coll Surg. 2004;199(4):586-94.
Kristo, G., Yoshimura, Y., Ferraris, S. P., Jahania, S. A., Mentzer, R. M., & Lasley, R. D. (2004). The preischemic combination of the sodium-hydrogen exchanger inhibitor cariporide and the adenosine agonist AMP579 acts additively to reduce porcine myocardial infarct size. Journal of the American College of Surgeons, 199(4), 586-94.
Kristo G, et al. The Preischemic Combination of the Sodium-hydrogen Exchanger Inhibitor Cariporide and the Adenosine Agonist AMP579 Acts Additively to Reduce Porcine Myocardial Infarct Size. J Am Coll Surg. 2004;199(4):586-94. PubMed PMID: 15454144.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The preischemic combination of the sodium-hydrogen exchanger inhibitor cariporide and the adenosine agonist AMP579 acts additively to reduce porcine myocardial infarct size. AU - Kristo,Gentian, AU - Yoshimura,Yukihiro, AU - Ferraris,Suellen P, AU - Jahania,Salik A, AU - Mentzer,Robert M,Jr AU - Lasley,Robert D, PY - 2003/12/30/received PY - 2004/05/05/revised PY - 2004/05/11/accepted PY - 2004/9/30/pubmed PY - 2004/11/4/medline PY - 2004/9/30/entrez SP - 586 EP - 94 JF - Journal of the American College of Surgeons JO - J Am Coll Surg VL - 199 IS - 4 N2 - BACKGROUND: We tested whether the combination of two known cardioprotective agents, the type-1 sodium-hydrogen exchanger inhibitor cariporide plus the adenosine A(1)/A(2a) receptor agonist AMP579 ([1S-[1a,2b,3b, 4a(S*)]]-4-[7-[[2-(3-chloro-2-thienyl)-1-methylpropyl]amino]-[(3)H]-imidazo[4,5-b]pyridyl-3-yl]cyclopentane carboxamide), acted additively to reduce myocardial infarct size. STUDY DESIGN: Pigs underwent 1 hour of coronary artery occlusion and 3 hours reperfusion. Vehicle-treated controls were compared with animals treated before ischemia with low-dose and high-dose cariporide and AMP579, and low-dose cariporide plus AMP579. The effects of both agents, alone and in combination, were also tested in isolated porcine polymorphonuclear neutrophils (PMNs). The PMN respiratory burst was induced with phorbol 12-myristate 13-acetate and quantified by the increase in 2',7'-dichlorofluorescein fluorescence, measured by flow cytometry. RESULTS: Infarct size in the control pigs was 65 +/- 1% of the area at risk. Cariporide dose-dependently reduced infarct size to 39 +/- 2% and 24 +/- 3% in the low- and high-dose groups, respectively. Infarct size was 54 +/- 3% in the low-dose AMP579 group and 47 +/- 3% with high dose. The combination of low doses of cariporide and AMP579 reduced infarction to 25 +/- 6% of the area at risk. In the PMN studies, cariporide and AMP579 alone had no effect on 2',7'-dichlorofluorescein fluorescence, but the combination of the two agents reduced the PMN 2',7'-dichlorofluorescein increase to 79 +/- 5% of the vehicle control response. CONCLUSIONS: The preischemic combination of low doses of cariporide and AMP579 decreased myocardial infarct size more than either agent used alone in low concentration, indicating an additive effect of the two agents. Given the effects that cariporide plus AMP579 combination exerted on PMN activity, it appears that this combination has the potential to reduce PMN-mediated effects during myocardial reperfusion. SN - 1072-7515 UR - https://www.unboundmedicine.com/medline/citation/15454144/The_preischemic_combination_of_the_sodium_hydrogen_exchanger_inhibitor_cariporide_and_the_adenosine_agonist_AMP579_acts_additively_to_reduce_porcine_myocardial_infarct_size_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1072-7515(04)00803-8 DB - PRIME DP - Unbound Medicine ER -