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Cardioprotection with adenosine-regulating agent, GP531: effects on no-reflow, infarct size, and blood flow following ischemia/ reperfusion in the rabbit.
J Cardiovasc Pharmacol Ther. 2010 Mar; 15(1):60-7.JC

Abstract

GP531, a potent, second-generation adenosine-regulating agent, is pharmacologically silent under basal conditions but increases localized endogenous adenosine during ischemia. GP531 improves functional recovery after myocardial ischemia, but its effects on infarct size and no-reflow have not been reported. The objective was to determine whether GP531 reduces necrosis and the anatomic no-reflow defect and to evaluate its effects on regional myocardial blood flow (RMBF). GP531 was given as a loading dose plus infusion at 2 doses (700 microg/kg and 10 microg/kg per minute or 2100 microg/kg and 30 microg/kg per minute) or vehicle, starting 12 minutes before a 30-minute coronary occlusion and throughout 3 hours reperfusion in rabbits. Risk zone was delineated by blue dye, necrosis by tetrazolium staining, RMBF by radioactive microspheres, and no-reflow defect by thioflavin S. The extent of the ischemic risk zone was similar in all groups. Low-dose GP531 reduced infarct size by 34% (0.33 +/- 0.4 of the risk zone) compared with vehicle (0.50 +/- 0.4, P < .01) and reduced the extent of the anatomic no-reflow zone by 31% compared with vehicle (0.25 +/- 0.3 of the risk zone vs 0.36 +/- 0.4 in the vehicle group, P < .05). Infarct size and zone of no-reflow in the high dose were reduced by 22% and 16%, respectively (P = NS vs the other 2 groups). GP531 did not affect hemodynamics or blood flow. Thus, GP531 was effective at the lower dose evaluated in this study, reducing the severity of ischemic/reperfusion injury, without inducing the adverse hemodynamic effects associated with adenosine administration such as bradycardia and hypotension.

Authors+Show Affiliations

The Heart Institute of Good Samaritan Hospital, Los Angeles, CA 90017, USA. sharon.hale@netscape.comNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20133497

Citation

Hale, Sharon L., and Robert A. Kloner. "Cardioprotection With Adenosine-regulating Agent, GP531: Effects On No-reflow, Infarct Size, and Blood Flow Following Ischemia/ Reperfusion in the Rabbit." Journal of Cardiovascular Pharmacology and Therapeutics, vol. 15, no. 1, 2010, pp. 60-7.
Hale SL, Kloner RA. Cardioprotection with adenosine-regulating agent, GP531: effects on no-reflow, infarct size, and blood flow following ischemia/ reperfusion in the rabbit. J Cardiovasc Pharmacol Ther. 2010;15(1):60-7.
Hale, S. L., & Kloner, R. A. (2010). Cardioprotection with adenosine-regulating agent, GP531: effects on no-reflow, infarct size, and blood flow following ischemia/ reperfusion in the rabbit. Journal of Cardiovascular Pharmacology and Therapeutics, 15(1), 60-7. https://doi.org/10.1177/1074248409357742
Hale SL, Kloner RA. Cardioprotection With Adenosine-regulating Agent, GP531: Effects On No-reflow, Infarct Size, and Blood Flow Following Ischemia/ Reperfusion in the Rabbit. J Cardiovasc Pharmacol Ther. 2010;15(1):60-7. PubMed PMID: 20133497.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardioprotection with adenosine-regulating agent, GP531: effects on no-reflow, infarct size, and blood flow following ischemia/ reperfusion in the rabbit. AU - Hale,Sharon L, AU - Kloner,Robert A, PY - 2010/2/6/entrez PY - 2010/2/6/pubmed PY - 2010/4/23/medline SP - 60 EP - 7 JF - Journal of cardiovascular pharmacology and therapeutics JO - J Cardiovasc Pharmacol Ther VL - 15 IS - 1 N2 - GP531, a potent, second-generation adenosine-regulating agent, is pharmacologically silent under basal conditions but increases localized endogenous adenosine during ischemia. GP531 improves functional recovery after myocardial ischemia, but its effects on infarct size and no-reflow have not been reported. The objective was to determine whether GP531 reduces necrosis and the anatomic no-reflow defect and to evaluate its effects on regional myocardial blood flow (RMBF). GP531 was given as a loading dose plus infusion at 2 doses (700 microg/kg and 10 microg/kg per minute or 2100 microg/kg and 30 microg/kg per minute) or vehicle, starting 12 minutes before a 30-minute coronary occlusion and throughout 3 hours reperfusion in rabbits. Risk zone was delineated by blue dye, necrosis by tetrazolium staining, RMBF by radioactive microspheres, and no-reflow defect by thioflavin S. The extent of the ischemic risk zone was similar in all groups. Low-dose GP531 reduced infarct size by 34% (0.33 +/- 0.4 of the risk zone) compared with vehicle (0.50 +/- 0.4, P < .01) and reduced the extent of the anatomic no-reflow zone by 31% compared with vehicle (0.25 +/- 0.3 of the risk zone vs 0.36 +/- 0.4 in the vehicle group, P < .05). Infarct size and zone of no-reflow in the high dose were reduced by 22% and 16%, respectively (P = NS vs the other 2 groups). GP531 did not affect hemodynamics or blood flow. Thus, GP531 was effective at the lower dose evaluated in this study, reducing the severity of ischemic/reperfusion injury, without inducing the adverse hemodynamic effects associated with adenosine administration such as bradycardia and hypotension. SN - 1940-4034 UR - https://www.unboundmedicine.com/medline/citation/20133497/Cardioprotection_with_adenosine_regulating_agent_GP531:_effects_on_no_reflow_infarct_size_and_blood_flow_following_ischemia/_reperfusion_in_the_rabbit_ L2 - https://journals.sagepub.com/doi/10.1177/1074248409357742?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -