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Biomedical subjects

K Shakunaga

Publications and source records attributed to K Shakunaga.

6 recordsLinked to original sources

Ketamine suppresses the production and release of endothelin 1 from cultured bovine endothelial cells.

UNLABELLED: Endothelins play important roles in the regulation of vascular tone. We examined the effect of ketamine on the secretion of endothelin 1 (ET-1) and its precursor, "big" ET-1, from bovine carotid artery endothelial cells (BCAECs). After confluent BCAEC cultures were incubated for 24 h with various concentrations of ketamine, the antigen levels for both ET-1 and big ET-1 in the culture medium were determined by using sandwich enzyme-linked immunosorbent assays. The precursor protein ET-1 (preproET-1) mRNA levels were assessed by using Northern blotting. On incubation in fresh medium, the BCAECs time-dependently produced and secreted ET-1 into the culture medium. The exposure of BCAECs to ketamine dose-dependently decreased the secretion of ET-1 and big ET-1 in both the serum-free and serum-containing conditions. Approximately 40% inhibition was attained by treatment with 100 microM ketamine for 24 h. The mRNA encoding preproET-1 was expressed much more slowly and to a lesser extent in the presence of ketamine. These results suggest that ketamine suppresses the production and release of big ET-1 and, therefore, the level of mature ET-1 in vascular endothelial cells. IMPLICATIONS: Endothelins are important in the regulation of vascular tone. The effect of anesthetics on the production of endothelins is unknown. We examined the effect of an anesthetic agent, ketamine, on the production and secretion of endothelin 1 from cultured vascular endothelial cells and found that ketamine suppressed them.

Anesthetics, Dissociative

[Efficacy of epidural analgesia in minimally invasive direct coronary artery bypass surgery].

Minimally invasive direct coronary artery bypass surgery (MIDCAB), coronary bypass grafting with small thoracotomy using no cardiopulmonary bypass (CPB), became popular recently. To attenuate perioperative stress-response, we used epidural analgesia (EPI) with general anesthesia for MIDCAB operation. In this study, we compared retrospectively 11 cases of MIDCAB managed with EPI [ED (+)], and 14 cases of MIDCAB anesthetized without using EPI [ED (-)], concerning extubation time, ICU stay, hospital stay and perioperative complications. The mean time from cessation of general anesthesia to extubation was significantly shorter in ED (+) patients (0.5 hours) when compared to ED (-) patients (18.2 hours). Mean periods of ICU stay and hospital stay were, also, shorter in ED (+) patients (2.1 days, 30.5 days, respectively) when compared to ED (-) (4.3 days, 45.1 days, respectively) patients. We experienced ventricular tachycardia in three patients of ED (-). No major complication occurred in ED (+) patients. These results suggest that EPI shortened extubation time, ICU and hospital stay for MIDCAB patients.

Aged

Differences in midazolam-induced breathing patterns in healthy volunteers.

Sex differences, and the influence of drug dosage and additional upper airway obstruction were studied in midazolam-induced breathing patterns and sedation in 30 healthy volunteers (8 males and 22 females). After administration of 0.1 mg.kg-1 midazolam (8 male and 8 female subjects), the rib cage (RC) motion increased in 6 males and the abdominal wall (ABD) motion and SaO2 decreased in all males. In contrast, the RC and ABD motions and SaO2 decreased in all females. Snoring and loss of consciousness occurred in 7 males and in 2 females. There were significant differences in the RC motion, SaO2, the incidence of snoring and the sedative state between male and female subjects. A bolus dose of 0.5 mg of flumazenil completely antagonized the sedative effect of midazolam and restored the breathing pattern, whereas it did not completely restore SaO2. A higher dose (0.2 mg.kg-1) of midazolam was administered to an additional 8 females. It caused a loss of consciousness in all subjects and increased the RC motion in only one subject. Partial obstruction of the nasal cavity was effected with cotton balls in the remaining 6 females who were sedated with 0.1 mg.kg-1 midazolam. An increase in the RC motion occurred similar to that observed in males. These findings suggest a difference in midazolam-induced sedation and breathing patterns between male and female subjects with midazolam administration on a mg.kg-1 basis.

Abdominal Muscles

The vasodilatory effects of ketamine on isolated rabbit portal veins.

The vasodilation mechanism induced by ketamine was investigated in isolated smooth muscle strips of rabbit portal veins. Ketamine inhibited both the phasic and tonic components of K(+)-induced contraction at concentrations greater than 500 microM and 100 microM, respectively. This effect was reversible and concentration-dependent with concentration-dependent with concentrations up to 1 mM. These effects were similar to those produced by verapamil. In the presence of 60 mM K+, application of Ca2+ (2.5 mM) in the perfusing solution caused tonic contraction of the smooth muscle, and ketamine at concentrations larger than 10 microM strongly inhibited this Ca(2+)-induced contraction. Ketamine (100 microM) also inhibited the K(+)-induced contractions significantly in the absence and presence of guanethidine, tetrodotoxin and propranolol. Ketamine produced similar concentration-dependent relaxations in the tissues with and without endothelium. These results indicate that in rabbit portal vein, vasodilation produced by ketamine is not endothelium-dependent but is likely to be due to blockade of the voltage-gated influx of extracellular Ca2+.

Animals

[Flumazenil antagonism of midazolam-induced respiratory depression].

Flumazenil, a benzodiazepine antagonist, reliably reverses midazolam-induced sedation, but its effect on respiratory depression has not been clarified completely. Ten healthy male volunteers received midazolam 0.1 mg.kg-1. Then they received flumazenil 0.5 mg (n = 9) and 1.0 mg (n = 1), intravenously. Rib-cage (RC) and abdominal wall (ABD) movement was measured by mercury-in-silastic strain gauge. Nasal air flow (FLOW), genioglossal electromyogram (EMG) and oxygen saturation (SaO2) were recorded simultaneously. Midazolam caused significant increases of RC movement and respiratory rate, and decreases of ABD movement, FLOW, EMG and SaO2. After administration of flumazenil, although respiratory rate returned to the pre-midazolam values, RC movement decreased on the contrary. ABD movement, FLOW, EMG, SaO2 did not recover to the pre-midazolam values. These data suggest that flumazenil 0.5 mg reverses midazolam-induced sedation completely, but is partially effective for some parameters related to respiratory depression.

Adult

[Pneumothorax during laparoscopy].

A 28-year-old female was scheduled for laparoscopy under general anesthesia. Her history and physical examination were unremarkable. Trachea was intubated uneventfully following intravenous administration of thiopental 200 mg and vecuronium 8 mg. Anesthesia was maintained with 40% O2, 60% N2O and sevoflurane. Shortly after pneumoperitoneum was introduced, airway resistance increased and breathing sounds were hardly audible over the right side of the chest. A chest radiograph showed the right pneumothorax. Immediately after evacuating the peritoneal gas, the chest radiograph and a blood gas analysis showed that the pneumothorax had improved. Pneumothorax can occur subsequently to pneumoperitoneum due to passage of gas through weak points or defects in the diaphragm. Breathing sound should be monitored carefully during the laparoscopic surgery. Anesthetic gas analyzer and capnometer are considered to be useful to confirm the cause of the pneumothorax.

Adult