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Remifentanil limits infarct size but attenuates preconditioning-induced infarct limitation

Kuzume, Koha; Kuzume, Kazuyoa; Wolff, Roger A.a; Chien, Grace L.b c; Van Winkle, Donna M.a b c

Therapy and Prevention
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Objectives We investigated the influence of the narcotic anesthetic remifentanil on irreversible myocardial ischemic injury.

Methods New Zealand White rabbits were anesthetized with propofol (0.7–1.8 mg·kg−1·min−1) and then subjected to 30 min regional myocardial ischemia and 3 h reperfusion (CON). Some animals also underwent ischemic preconditioning, elicited by either one (IP1) or two (IP2) cycles of 5 min ischemia and 5 min reperfusion, and/or remifentanil, administered either as a transient infusion mimicking the preconditioning protocol (RP2, 10 μg·kg−1·min−1) or as a continuous infusion (R, 3–10 μg·kg−1·min−1). Rabbits were randomly assigned to experimental groups. Infarct size was assessed with tetrazolium. Results are reported as mean±SD.

Results Non-preconditioned infarct size was ∼50% of the area-at-risk (49.6±20.1% CON). Both one and two cycles of ischemic preconditioning markedly reduced infarct size (49.6±20.1% CON versus 18.6±8.6% IP and versus 7.5±7.6% IP2; both p<0.001). Preconditioning with remifentanil modestly reduced infarct size (49.6±20.1% CON versus 29.3±8.5% RP2; p<0.01). However, sustained administration of remifentanil did not provide protection (49.6±20.1% CON versus 43.9±16.2% R), and it attenuated the protection offered by preconditioning (49.6±20.1% CON versus 35.6±20.7% R+IP1, p=NS; and versus 14.5±14.5% R+IP2; p<0.05).

Conclusion Transient pre-ischemic administration of remifentanil modestly reduces infarct size in propofol-anesthetized rabbits, but continuous administration of remifentanil increases the threshold for ischemic preconditioning-induced infarct limitation.

We investigated the influence of the narcotic anesthetic remifentanil on irreversible injury following regional myocardial ischemia-reperfusion in propofol anesthetized rabbits. Some animals also received ischemic preconditioning, reminfentanil preconditioning, or continuous remifentanil. Rabbits were randomly assigned to experimental groups. Results are reported as mean±SEM. Ischemic preconditioning reduced infarct size by 63% and 85% (1 and 2 cycles respectively; both p<0.001), and remifentanil preconditioning reduced infarct size by 41% (p<0.01). However, sustained administration of remifentanil did not provide protection (49.6±20.1% CON vs. 43.9±16.2% R), and in the presence of sustained remifentanil preconditioning only limited infarct size by 28% and 71% (1 and 2 cycles respectively; p=ns and p<0.05). Thus, transient pre-ischemic administration of remifentanil limits infarct size in propofol anesthetized rabbits, but continuous administration of remifentanil increases the threshold for ischemic preconditioning-induced infarct limitation.

aResearch Service, Veterans Affairs Medical Center, Portland, OR

bDepartment of Anesthesiology, Oregon Health and Science University, Portland, OR

cAnesthesiology Service, Veterans Affairs Medical Center, Portland, OR, USA

Correspondence and requests for reprints to Donna M. Van Winkle, Ph.D., Veterans Affairs Medical Center, Anesthesiology Service, P3ANES, 3710 SW US Veterans Hospital Road, Portland, OR 97239-2999, USA

Tel: +1 (503) 220 8262 x57404; fax: +1 (503) 721 7956;

e-mail: Donna.Vanwinkle@med.va.gov

Received 16 March 2004 Revised 9 July 2004 Accepted 23 July 2004

© 2004 Lippincott Williams & Wilkins, Inc.