SUPPRESSION OF THE SMALL INTESTINE SHRINKABLE ACTIVITY AFTER USAGE OF THE ANESTHETIC KETAMINE

Abstract

The work is devoted to the problem of general anesthetics side effects during surgical interventions. In particular, some of the common complications of anesthetics usage are intestinal motility disorders (eg, ileus), nausea and vomiting. We analyzed a clinical data of 60 patients who underwent analgosedation (AS) during coronary artery stenting. They were divided into 2 groups (1 group - AS with Diazepam and Fentanyl, 2 group - AS with Ketamine, Fentanyl and Propofol). Significantly more frequent manifestations of nausea in the perioperative period were identified in the group where ketamine was used. This formed the basis of the study of the molecular and cellular mechanisms of the effects of ketamine on the contractile activity of the smooth muscles of the small intestine. Anesthetics are known to interact with receptors, G-proteins and ion channels, including transient receptor potential channels (TRP channels). The member of this superfamily, TRPC4 channel, which is coupled to muscarinic receptors (M2/M3 type) through G-protein activation and causes cholinergic excitation and contraction of small intestinal smooth muscles, may be a potential target for ketamine. Thus, we aimed to investigate the effects of ketamine (100 μM) on the muscarinic cation current (mICAT), which underlies cholinergic excitation-contraction coupling of visceral smooth muscles. All experiments were performed on single ileal myocytes freshly isolated from the longitudinal layer of the mouse ileum using patch-clamp techniques in the whole-cell configuration. mICAT was recorded using symmetrical Cs+ solutions (containing Cs+125 mM). [Ca2+]i was ‘clamped’ at 100 nM using 10 mM BAPTA/4.6 mM CaCl2 mixture. Measurements of isometric contractile force of the small intestinal smooth muscles were recorded using tensiometry techniques. It was showed that 100 μM ketamine inhibits mICAT . mICAT initiated by the application of CCh (50 μM) was suppressed on 64% (n=5) and mICAT, induced by intracellular GTP γ s (200 μM) that interacts directly with the G-proteins (when muscarinic receptors are bypassed) was inhibited on 42% (n=5). Ketamine inhibited intestinal smooth muscle contractions evoked by carbachol (50 μM) by about 40 % (n=5). Thus, we can conclude that both muscarinic receptors and G-proteins (or their coupling) are affected by ketamine, but the main sites of ketamine action appear to be the G-proteins. These data will provide basis for the molecular mechanisms of postoperative motility disorders and thus may be important for the development of novel approaches to the correction of such states.