ABSTRACT
Background@#We investigated the effects of sevoflurane exposure on the expression of matrix metalloproteinase (MMP), expression and ablation of natural killer group 2, member D (NKG2D) ligands (UL16-binding proteins 1–3 and major histocompatibility complex class I chain-related molecules A/B), and natural killer (NK) cell-mediated cytotoxicity in breast cancer cells. @*Methods@#Three human breast cancer cell lines (MCF-7, MDA-MB-453, and HCC-70) were incubated with 0 (control), 600 (S6), or 1200 μM (S12) sevoflurane for 4 h. The gene expression of NKG2D ligands and their protein expression on cancer cell surfaces were measured using multiplex polymerase chain reaction (PCR) and flow cytometry, respectively. Protein expression of MMP-1 and -2 and the concentration of soluble NKG2D ligands were analyzed using western blotting and enzyme-linked immunosorbent assays, respectively. @*Results@#Sevoflurane downregulated the mRNA and protein expression of the NKG2D ligand in a dose-dependent manner in MCF-7, MDA-MB-453, and HCC-70 cells but did not affect the expression of MMP-1 or -2 or the concentration of soluble NKG2D ligands in the MCF-7, MDA-MB-453, and HCC-70 cells. Sevoflurane attenuated NK cell-mediated cancer cell lysis in a dose-dependent manner in MCF-7, MDA-MB-453, and HCC-70 cells (P = 0.040, P = 0.040, and P = 0.040, respectively). @*Conclusions@#Our results demonstrate that sevoflurane exposure attenuates NK cell-mediated cytotoxicity in breast cancer cells in a dose-dependent manner. This could be attributed to a sevoflurane-induced decrease in the transcription of NKG2D ligands rather than sevoflurane-induced changes in MMP expression and their proteolytic activity.
ABSTRACT
The authors report a case of newly manifested severe junctional bradycardia following dexmedetomidine administration during spinal anesthesia in a polypharmacy patient. A 77-year-old woman receiving multiple medications, including a beta-blocker and a calcium channel blocker, underwent right total knee arthroplasty. After spinal anesthesia, intravenous dexmedetomidine was initiated as a sedative; her heart rate decreased, followed by junctional bradycardia (heart rate, 37–41 beats/min). Dexmedetomidine was discontinued, and a dopamine infusion was initiated. Seven hours after surgery, junctional bradycardia persisted; a temporary transvenous pacemaker was inserted, and the beta-blocker and calcium channel blocker were discontinued. The patient was discharged on postoperative day 11 without any sequelae. Anesthesiologists should be aware of dexmedetomidine’s inhibitory effects on the cardiac conduction system, especially in geriatric patients taking medications with negative chronotropic effects and in combination with neuraxial anesthesia.