Effects of sevoflurane and adenosine receptor antagonist on the sugammadex-induced recovery from rocuronium-induced neuromuscular blockade in rodent phrenic nerve-hemidiaphragm tissue specimens

Abstract

Sevoflurane affects on the A1 receptor in the central nervous system and potentiates the action of neuromuscular blocking agents. In the present study, we investigated whether sevoflurane (SEVO) has the ability to potentiate the neuromuscular blocking effect of rocuronium and if the specific antagonist of adenosine receptor (SLV320) can reverse this effect. In this study, phrenic nerve-hemidiaphragm tissue specimens were obtained from 40 Sprague-Dawley (SD) rats. The specimens were immersed in an organ bath filled with Krebs buffer and stimulated by a train-of-four (TOF) pattern using indirect supramaximal stimulation at 20 s intervals. The specimens were randomly allocated to control, 2-chloroadenosine (CADO), SEVO, or SLV320 + SEVO groups. In the CADO and SLV320 + SEVO groups, CADO and SLV320 were added to the organ bath from the start to a concentration of 10 μM and 10 nM, respectively. We then proceeded with rocuronium-induced blockade of >95% depression of the first twitch tension of TOF (T1) and TOF ratio (TOFR). In the SEVO and SLV320 + SEVO groups, SEVO was added to the Krebs buffer solution to concentration of 400-500 μM for 10 min. Sugammadex-induced T1 and TOFR recovery was monitored for 30 min until >95% of T1 and >0.9 of TOFR were confirmed, and the recovery pattern was compared by plotting these data. T1 recovery in the SEVO and CADO groups was significantly delayed compared with the control and SLV320 + SEVO groups (p < .05). In conclusion, sevoflurane affects on the A1 receptor at the neuromuscular junction and delays sugammadex-induced recovery from neuromuscular blockade.

Keywords: acetylcholine; neuromuscular blockade; neuromuscular blocking agent; rocuronium; sevoflurane; sugammadex.

FIGURE 1

Study protocol. Study drugs (CADO, SLV320) were administered from the start of the experiment. Sevoflurane exposure time was set as 10 min. CADO, 2‐chloroadenosine; SD, Sprague–Dawley rats; SEVO, sevoflurane; T1, the first twitch tension of train‐of‐four stimulation; TOF, train‐of four stimulation

FIGURE 2

Progression of T1 twitch tension recovery of control (●, solid line), SEVO (△, dashed line), and SEVO + SLV320 (◇, dash‐dot line) group when the zero point was set as the time of sugammadex administration (A). Data obtained from CADO group were not included because most of the data failed to reach 100% twitch height recovery within 30 min. Comparisons of omegas of T1 recovery are shown at (B). We set the equation for T1 recovery as y = 50 + 50sin(Ωx + b), where y is the % recovery of T1 twitch tension and x is time. It was inclined to show delayed recovery progression of T1, although we failed to obtain statistical significances of Ω between the groups. CADO, 2‐chloroadenosine; SEVO, sevoflurane; T1, the first twitch tension of TOF; TOF, train‐of‐four stimulation; TOFR, TOF ratio

FIGURE 3

Progression of T1 twitch tension recovery of control, and CADO (□, dash‐dot‐dot line) group when the zero point was set as the time when the recovery of the T1 twitch tension was 10% (A). Comparisons of omegas of T1 recovery are shown at (B). We set the equation for T1 recovery as y = 50 + 50sin(Ωx + b), where y is the % recovery of T1 twitch tension and x is time. *p < .050 compared with the control (p = .008 with control vs. SEVO; p = .010 with control vs. CADO). ^† p < .050 compared with SEVO + SLV320 group (p = .035 with SEVO + SLV320 vs. SEVO; p = .044 with SEVO + SLV320 vs. CADO). CADO, 2‐chloroadenosine; SEVO, sevoflurane; T1, the first twitch tension of TOF; TOF, train‐of‐four stimulation; TOFR, TOF ratio