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Pretreatment with an adenosine A1 receptor agonist and lidocaine: a possible alternative to myocardial ischemic preconditioning.
J Thorac Cardiovasc Surg. 2005 Aug; 130(2):371-7.JT

Abstract

OBJECTIVE

The heart possesses an extraordinary ability to remember short episodes of sublethal ischemia and reperfusion (angina), which protects the myocardium and coronary vasculature from a subsequent lethal insult, a phenomenon known as ischemic preconditioning. A therapeutic goal for more than 2 decades has been to develop a pharmacologic mimetic comparable with ischemic preconditioning. Our aim was to investigate the preconditioning effect of a new combinatorial therapy targeting adenosine A1 receptors and voltage-dependent sodium fast channels in the in vivo rat model of regional ischemia.

METHODS

Ischemia-reperfusion was achieved by placing a reversible tie around the left coronary artery in anesthetized and ventilated Sprague-Dawley rats (n = 37). Rats were randomly assigned to 1 of 5 groups: (1) saline control (n = 13); (2) ischemic preconditioning (n = 6); (3) lidocaine only (608 microg . kg -1 . min -1 , n = 5); (4) adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 5 microg/kg, n = 7); and (5) CCPA plus lidocaine (n = 6). Ischemic preconditioning was achieved by using 3 cycles of ischemia and reperfusion lasting 3 minutes each. Lidocaine was infused continuously 5 minutes before and throughout 30 minutes of ischemia and ceased at reperfusion. A bolus of CCPA was infused 5 minutes before ligation along with a constant infusion of lidocaine (as above). All animals were reperfused for 120 minutes for infarct size measurement.

RESULTS

Fifty-four percent of saline control rats, 17% of ischemic preconditioning-treated rats, and 29% of CCPA-treated rats died during ischemia from ventricular fibrillation. Infarct size of saline control animals was 61% +/- 5%. Pretreating with CCPA and lidocaine infusion resulted in no deaths, no severe arrhythmias, and significant infarct size reduction compared with that seen in saline control animals (P < .05). Remarkably, infarct size reduction in CCPA plus lidocaine-treated rats (12% +/- 4%) was equivalent to that achieved with ischemic preconditioning (11% +/- 3%), whereas infarct size in rats undergoing CCPA-only and lidocaine-only treatments was 42% +/- 7% and 60% +/- 6%, respectively. Although CCPA plus lidocaine treatment reduced heart rate, mean arterial pressure, and systolic pressure during ischemia, no correlation was found between these variables and infarct size reduction.

CONCLUSION

We conclude that activating adenosine A1 receptor subtype with CCPA and concomitantly modulating sodium fast channels with lidocaine was comparable with ischemic preconditioning and might offer a new therapeutic window to minimize myocardial damage during surgical ischemia and reperfusion.

Authors+Show Affiliations

Department of Physiology and Pharmacology, James Cook University, Queensland, Australia.No affiliation info available

Pub Type(s)

Evaluation Study
Journal Article

Language

eng

PubMed ID

16077401

Citation

Canyon, Sarah J., and Geoffrey P. Dobson. "Pretreatment With an Adenosine A1 Receptor Agonist and Lidocaine: a Possible Alternative to Myocardial Ischemic Preconditioning." The Journal of Thoracic and Cardiovascular Surgery, vol. 130, no. 2, 2005, pp. 371-7.
Canyon SJ, Dobson GP. Pretreatment with an adenosine A1 receptor agonist and lidocaine: a possible alternative to myocardial ischemic preconditioning. J Thorac Cardiovasc Surg. 2005;130(2):371-7.
Canyon, S. J., & Dobson, G. P. (2005). Pretreatment with an adenosine A1 receptor agonist and lidocaine: a possible alternative to myocardial ischemic preconditioning. The Journal of Thoracic and Cardiovascular Surgery, 130(2), 371-7.
Canyon SJ, Dobson GP. Pretreatment With an Adenosine A1 Receptor Agonist and Lidocaine: a Possible Alternative to Myocardial Ischemic Preconditioning. J Thorac Cardiovasc Surg. 2005;130(2):371-7. PubMed PMID: 16077401.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pretreatment with an adenosine A1 receptor agonist and lidocaine: a possible alternative to myocardial ischemic preconditioning. AU - Canyon,Sarah J, AU - Dobson,Geoffrey P, PY - 2005/8/4/pubmed PY - 2005/10/21/medline PY - 2005/8/4/entrez SP - 371 EP - 7 JF - The Journal of thoracic and cardiovascular surgery JO - J Thorac Cardiovasc Surg VL - 130 IS - 2 N2 - OBJECTIVE: The heart possesses an extraordinary ability to remember short episodes of sublethal ischemia and reperfusion (angina), which protects the myocardium and coronary vasculature from a subsequent lethal insult, a phenomenon known as ischemic preconditioning. A therapeutic goal for more than 2 decades has been to develop a pharmacologic mimetic comparable with ischemic preconditioning. Our aim was to investigate the preconditioning effect of a new combinatorial therapy targeting adenosine A1 receptors and voltage-dependent sodium fast channels in the in vivo rat model of regional ischemia. METHODS: Ischemia-reperfusion was achieved by placing a reversible tie around the left coronary artery in anesthetized and ventilated Sprague-Dawley rats (n = 37). Rats were randomly assigned to 1 of 5 groups: (1) saline control (n = 13); (2) ischemic preconditioning (n = 6); (3) lidocaine only (608 microg . kg -1 . min -1 , n = 5); (4) adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA; 5 microg/kg, n = 7); and (5) CCPA plus lidocaine (n = 6). Ischemic preconditioning was achieved by using 3 cycles of ischemia and reperfusion lasting 3 minutes each. Lidocaine was infused continuously 5 minutes before and throughout 30 minutes of ischemia and ceased at reperfusion. A bolus of CCPA was infused 5 minutes before ligation along with a constant infusion of lidocaine (as above). All animals were reperfused for 120 minutes for infarct size measurement. RESULTS: Fifty-four percent of saline control rats, 17% of ischemic preconditioning-treated rats, and 29% of CCPA-treated rats died during ischemia from ventricular fibrillation. Infarct size of saline control animals was 61% +/- 5%. Pretreating with CCPA and lidocaine infusion resulted in no deaths, no severe arrhythmias, and significant infarct size reduction compared with that seen in saline control animals (P < .05). Remarkably, infarct size reduction in CCPA plus lidocaine-treated rats (12% +/- 4%) was equivalent to that achieved with ischemic preconditioning (11% +/- 3%), whereas infarct size in rats undergoing CCPA-only and lidocaine-only treatments was 42% +/- 7% and 60% +/- 6%, respectively. Although CCPA plus lidocaine treatment reduced heart rate, mean arterial pressure, and systolic pressure during ischemia, no correlation was found between these variables and infarct size reduction. CONCLUSION: We conclude that activating adenosine A1 receptor subtype with CCPA and concomitantly modulating sodium fast channels with lidocaine was comparable with ischemic preconditioning and might offer a new therapeutic window to minimize myocardial damage during surgical ischemia and reperfusion. SN - 0022-5223 UR - https://www.unboundmedicine.com/medline/citation/16077401/Pretreatment_with_an_adenosine_A1_receptor_agonist_and_lidocaine:_a_possible_alternative_to_myocardial_ischemic_preconditioning_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022522305002084 DB - PRIME DP - Unbound Medicine ER -