Remifentanil limits infarct size but attenuates preconditioning-induced infarct limitation

Abstract

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.

In Brief

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.