The hemodynamic effects of landiolol, an ultra-short-acting beta1-selective blocker, on endotracheal intubation in patients with and without hypertension.

BACKGROUND: The ultra-short-acting beta1-selective blocker, landiolol, is widely used in Japan. We investigated the effects of landiolol on intubation-induced adrenergic response in 88 patients. METHODS: General anesthesia was induced and maintained with target-controlled infusion of propofol at an effect-site concentration of 5 microg/mL. Muscle relaxation was obtained with 0.1 mg/kg vecuronium, and endotracheal intubation was performed 4 min after vecuronium injection. We first investigated the optimal time point for landiolol to be administered before intubation in 43 normotensive patients. Then we examined whether landiolol was as effective as fentanyl to prevent tachycardia after intubation in 45 hypertensive patients. RESULTS: Landiolol at 0.1 mg/kg was most effective against intubation-induced tachycardia when infused 4 min before intubation in normotensive patients. However, 0.2 mg/kg landiolol was necessary to prevent tachycardia after intubation in hypertensive patients. Landiolol had no significant effects on arterial blood pressure or bispectral index at any dose throughout the study period. In contrast, 2 mug/kg fentanyl frequently caused hypotension just before and 5 min after intubation. CONCLUSION: Low doses of landiolol can effectively prevent tachycardia after intubation without significant effects on arterial blood pressure.

[Intraoperative anaphylactic shock induced by methylergometrine and oxytocin].

We report a case of intraoperative anaphylactic shock in a 32-year-old multigravida woman undergoing elective cesarean section for partial placenta previa. Anesthesia was performed using combined spinal and epidural technique. After the baby was born, methylergometrine was administered i.v. simultaneously with oxytocin, the latter injected directly into the uterine muscle by an obstetrician. Several minutes later, she presented with dyspnea and became agitated. Because of the potential risk of pulmonary embolism, the patient was immediately intubated and mechanical ventilation was started. Her systolic blood pressure decreased to 50 mmHg and SpO2 to 87% under 100% oxygen administration. After catecholamine infusion, however, her respiratory condition soon improved. Postoperatively, her conjunctiva and vulva were not edematous. From the clinical course, it was considered that the patient was very likely to have suffered an anaphylactic reaction to oxytocin or methylergometrine. Forty days later, serological examinations as well as skin tests for those two drugs were carried out. While the serological tests were negative, the skin tests indicated the patient was allergic to both drugs. It is concluded that the endogenous peptide oxytocin can induce anaphylactic shock in multiparous women.

[The combined use of laryngoscope and Trachlight: another option for endotracheal intubation in patients with large epiglottic cysts].

Epiglottic cysts often cause difficulty in airway management. A 71-year-old man had extraction for an epiglottic cyst of 4 cm in diameter. Anesthesia was induced with small divided doses of propofol. After verifying that mask ventilation was possible under light anesthesia, vecuronium was used for muscle relaxation. Because of the size of the cyst, it was impossible to observe directly the larynx using a laryngoscope. Therefore, while moving the tongue to the left with the laryngoscope, an endotracheal tube was inserted into the trachea using the Trachlight. The operation was finished in 55-min and the patient was extubated 15 min after the end of the operation. His postoperative course was uneventful and he was discharged from the hospital three days after the operation. The authors conclude that the combined use of the laryngoscope and Trachlight is helpful for endotracheal intubation in patients with large epiglottic cysts.

[Hypoxemia after gastrointestinal endoscopy under general anesthesia in a patient with unilateral diaphragmatic paralysis].

A 59-year-old woman with suspected hypopharyngeal cancer was scheduled for biopsy using direct laryngoscopy. Her preoperative chest X-ray showed asymptomatic left unilateral diaphragmatic paralysis. Anesthesia was induced with propofol and maintained with oxygen, nitrous oxide and sevoflurane. The region was difficult to reach during direct laryngoscopy. Therefore, gastrointestinal endoscopy was performed. Air was injected through the scope to aid viewing. After tracheal extubation, oxygen saturation as indicated by pulse oximetry (SpO2) decreased to 91% from 97% although oxygen was delivered via a mask at 6 l x min(-1). A chest radiograph showed that the air-filled gastrointestinal tract had elevated the left dome of the diaphragm. After the stomach was suctioned via a nasogastric tube, respiration was assisted via a mask with continuous positive airway pressure. Then, SpO2 returned to 99%. An air-filled dilated stomach may increase the risk of respiratory dysfunction in patients with unilateral diaphragmatic paralysis.

Fetal and postnatal development of Ca2+ transients and Ca2+ sparks in rat cardiomyocytes.

OBJECTIVE: The aim of this study was to characterize the spatio-temporal dynamics of [Ca(2+)](i) in rat heart in the fetal and neonatal periods. METHODS: Using confocal scanning laser microscopy and the Ca(2+) indicator fluo-3, we investigated Ca(2+) transients and Ca(2+) sparks in single ventricular myocytes freshly isolated from rat fetuses and neonates. T-tubules were labeled with a membrane-selective dye (di-8-ANEPPS). Spatial association of dihydropyridine receptors (DHPR) and ryanodine receptors (RyR) was also examined by double-labeling immunofluorescence. RESULTS: Ca(2+) transients in the fetal myocytes were characterized by slower upstroke and decay of [Ca(2+)](i) compared to those in adult myocytes. The magnitude of fetal Ca(2+) transients was decreased after application of ryanodine (1 microM) or thapsigargin (1 microM). However, Ca(2+) sparks were rarely detected in the fetal myocytes. Frequent ignition of Ca(2+) sparks was established in the 6-9-day neonatal period, and was predominantly observed in the subsarcolemmal region. The developmental change in Ca(2+) sparks coincided with development of the t-tubule network. The immunofluorescence study revealed colocalization of DHPR and RyR in the postnatal period, which was, however, not observed in the fetal period. In the adult myocytes, Ca(2+) sparks disappeared after disruption of t-tubules by glycerol incubation (840 mM). CONCLUSIONS: The sarcoplasmic reticulum (SR) of rat ventricular myocytes already functions early in the fetal period. However, ignition of Ca(2+) sparks depends on postnatal t-tubule formation and resultant colocalization of DHPR and RyR.

Single-channel activity of L-type Ca2+ channels reconstituted with the beta2c subunit cloned from the rat heart.

We recently cloned the beta(2c) subunit of the L-type Ca(2+) channel as a functional type of beta subunit from the rat heart. In order to clarify the contribution of the beta(2c) subunit to native Ca(2+) channel function, we investigated the single-channel properties of Ca(2+) channels reconstituted with beta(2a) or beta(2c) subunits and compared them with the properties of native channels. In contrast to the Ca(2+) channel with beta(2a) subunit, long-lasting closings were dominant in the Ca(2+) channel with beta(2c) subunit and the native channel. The ensemble-averaged current of the cells with beta(2c) subunits was comparable to that of the native cardiomyocytes. Many high P(o) sweeps (mode 2) were observed in the cells with beta(2a) subunits, while only a few high P(o) sweeps were observed in the cells with beta(2c) subunits and the native cells. These findings suggest that the beta(2c) subunit is one of the functional beta subunits in the rat heart.

Development of excitation-contraction coupling in cardiomyocytes.

The excitation-contraction (E-C) coupling system during the development of heart can be investigated because of marked progression in electrophysiology and microfluorescence studies. During the developmental period, Ca2+ influx mediating the E-C coupling is mainly through the L-type Ca2+ channels. In the fetal period, T-type Ca2+ channels and the reverse mode of the Na-Ca exchange system also contribute to Ca2+ influx. These contributions probably reduce gradually until adulthood. The contraction of fetal cardiomyocytes has been thought to depend mainly on the Ca2+ influx. However, recent studies reveal that immature sarcoplasmic reticulum (SR) already works in the early fetal period. Ca2+ spark, a local and unitary movement of Ca2+, can be observed in adult cardiomyocytes by the use of a confocal microscope. On the other hand, no Ca2+ spark is observed in fetal cardiomyocytes. The frequency of Ca(2+)-spark evocation increases during the postnatal period. Therefore a close distance between the L-type Ca2+ channel and the SR Ca(2+)-release channel is essential to the establishment of the Ca2+ spark.

The effects of low-dose midazolam for induction of high-dose fentanyl anesthesia for coronary artery bypass graft.

A small dose of midazolam 0.06 mg/kg or diazepam 0.15 mg/kg was used for induction of high-dose fentanyl (50 µg/kg) anesthesia in patients undergoing coronary artery bypass grafting operation. Hemodynamic variables were measured 5 min after the injection of midazolam or diazepam, after the end of the fentanyl infusion, and following endotracheal intubation. Midazolam and diazepam caused a slight but significant decrease in mean arterial pressure (-9.8%) and -11.8%), respectively) and a further significant depression was observed in the diazepam group but not in the midazolam group after fentanyl. Although the cardiac index was maintained in patients who received madazolam, a significant decrease was observed in the diazepam group (-28.5%) after administration of fentanyl. Heart rate was decreased in the diazepam group but not in the midazolam group. Therefore, a small dose of midazolam may be a suitable induction agent for high-dose fentanyl anesthesia in patients with coronary artery disease.

[Anesthetic management for laparoscopic repair of Morgagni-Larry hernia in a child].

A 5-year-old asymptomatic boy was shown to have bowel loops in the thoracic cavity incidentally in a chest radiograph. A barium swallow confirmed the diagnosis of Morgagni hernia. Laparoscopic repair under CO2 pneumoperitoneum was performed. Anesthesia was induced and maintained with air, oxygen and sevoflurane. After pulling the transverse colon and the greater omentum into the abdomen, it was found that a part of the liver was also herniated into the right sternocostal hiatus (Larry hernia). The patient showed uneventful recovery. However, we should realize that dissection of adhesions between the viscera and peritoneal sac may be dangerous with possibility of pneumomediastinum or pneumothorax under pneumoperitoneum.

[Remaining of a safety clip within the hub of the Surshield Surflow II i.v. catheter].

Terumo's Surshield Surflow II i.v. catheter automatically engages a stainless steel clip to shield its needle tip when the needle goes out from the catheter hub. However, in our experience the safety clip of Surshield Surflow II remains in the catheter hub in a high proportion of cases when the catheter hub is held with a pair of forceps. The hub wall is so thin that the force existed to hold the hub can be easily transmitted to the safety clip. Another factor is the loose attachment of the safety clip to the needle tip. To prevent needle stick injury, further improvement of safety i.v. catheters is necessary to lead their increased use.

[The use of propofol combined with nitrous oxide and fentanyl in anesthetic management of a patient with mitochondrial encephalomyopathy].

A 49-year-old female with mitochondrial encephalomyopathy underwent surgery for implantation of an artificial cochlear device. She had some characteristic clinical features, including muscle weakness, deafness and dementia. Anesthesia was induced with 5 mg.kg-1 of propofol, and the trachea was intubated without a muscle relaxant. The patient was mechanically ventilated also without a relaxant, and anesthesia was maintained with a continuous infusion of 4-8 mg.kg-1.hr-1 of propofol, a bolus injection of 50-100 micrograms of fentanyl, and nitrous oxide (66%) in oxygen (33%). Bispectral index (BIS) was monitored and maintained at approximately 40. No cardiovascular instabilities or increase in plasma lactate concentration were observed during surgery. The patient had a smooth recovery from the propofol anesthesia, and the BIS value returned to the pre-anesthetic level 10 min after completion of the anesthesia, suggesting that the use of propofol is a safe means for inducing and maintaining anesthesia in patients with mitochondrial encephalomyopathy.

The beginning of the calcium transient in rat embryonic heart.

Although many researchers have tried to observe the beginning of the heartbeat, no study has shown the beginning of the calcium transient. Here, we evaluate the beginning of the calcium transient in the Wistar rat heart. We first tried to reveal when the heart of the Wistar rat begins to contract because no previous study has evaluated the beginning of the heartbeat in Wistar rats. Observation of embryos transferred to a small incubator mounted on a microscope revealed that the heart primordium, the so-called cardiac crescent, began to contract at embryonic day 9.99-10.13. Observation of embryos loaded with fluo-3 AM revealed that the beginning of the calcium transient precedes the initiation of contraction which precedes the appearance of the linear heart tube. Nifedipine (1 µM), but not ryanodine (1 µM), abolished the calcium transients. These results indicate that calcium transients in the early embryonic period involve exclusively calcium entry through L-type calcium channels in contrast to the situation in mature hearts. This study provides the first demonstration of the relationship between morphological changes in the heart primordium and the beginning of the calcium transient and contraction.

Effects of halothane and enflurane anesthesia on sympathetic beta-adrenoreceptor-mediated pulmonary vasodilation in chronically instrumented dogs.

BACKGROUND: The authors previously reported that the pulmonary vasodilator response to the sympathetic beta-adrenoreceptor agonist isoproterenol is potentiated during isoflurane anesthesia compared with the conscious state. In the present in vivo study, the authors tested the hypothesis that halothane and enflurane anesthesia also enhance sympathetic beta adrenoreceptor-mediated pulmonary vasodilation. The authors also used the membrane-permeable analog of cyclic adenosine monophosphate (cAMP), dibutyryl cAMP, to help delineate the site in the signaling pathway for an anesthesia-induced effect on beta adrenoreceptor-mediated pulmonary vasodilation. METHODS: Mongrel dogs were chronically instrumented to measure the left pulmonary vascular pressure-flow (LPQ) relationship. LPQ plots were measured on separate days in the conscious, halothane-, and enflurane-anesthetized states at baseline, after preconstriction with the thromboxane analog U46619, and during the cumulative intravenous administration of isoproterenol. LPQ plots were also measured in conscious, halothane-, and isoflurane-anesthetized dogs after U46619 preconstriction and during the cumulative intravenous administration of dibutyryl cAMP. RESULTS: Compared with the conscious state, neither halothane nor enflurane had an effect on the baseline LPQ relationship. The magnitude of the pulmonary vasodilator response to isoproterenol was potentiated during halothane anesthesia but unchanged during enflurane anesthesia. The pulmonary vasodilator response to dibutyryl cAMP was not altered during either halothane or isoflurane anesthesia compared with the conscious state. CONCLUSIONS: These results indicate that inhalational anesthetic agents can exert differential effects on the pulmonary vasodilator response to sympathetic beta-adrenoreceptor activation. The potentiated vasodilator response observed during halothane and isoflurane anesthesia is the result of effects proximal to cAMP accumulation in the beta-adrenoreceptor signaling pathway.

Role of endothelium-derived hyperpolarizing factor in phenylephrine-induced oscillatory vasomotion in rat small mesenteric artery.

BACKGROUND: In small mesenteric arteries, endothelium-derived hyperpolarizing factor (EDHF) in addition to endothelium-derived relaxing factors (EDRFs) including NO plays an important role in acetylcholine-induced vasodilation. It has been reported that EDRFs play an important role in alpha(1)-adrenoceptor agonist-induced oscillatory vasomotion and in limiting vasoconstrictor response to the agonists; however, contribution of EDHF to the alpha(1)-agonist-induced oscillation is unknown. METHODS: Rat small mesenteric arteries were isolated and cannulated at each end with a glass micropipette. The vessels were immersed in a bath (37 degrees C) containing physiologic saline solution. Changes in vessel diameter were measured using an optical density video detection system. RESULTS: Denudation of the endothelium and inhibition of NO synthesis caused a leftward shift in the concentration-response relation for phenylephrine in the mesenteric arteries, whereas inhibition of cyclooxygenase by indomethacin had no effect. Blockade of Ca2+-activated K+ (K(Ca)) channels by charybdotoxin and apamin caused a further leftward shift in the concentration-response relation in the vessels pretreated with Nomega-nitro-l-arginine methylester and indomethacin. Phenylephrine at concentrations higher than 10(-6) m caused endothelium-dependent oscillatory vasomotion, which was reduced but not abolished after combined inhibition of the cyclooxygenase and NO synthase pathways. However, the K(Ca) channel blockers completely abolished the remaining component of oscillation. CONCLUSIONS: Endothelially-derived NO is an important modulator of sustained agonist-induced vasoconstriction. NO, as well as endothelially-derived cyclooxygenase products and EDHF, also contribute significantly to phenylephrine-induced oscillatory vasomotion.

Inhibitory effects of the anesthetics propofol and sevoflurane on spontaneous lymphatic vessel activity in rats.

BACKGROUND: The effects of propofol and sevoflurane on lymphatic vessel activity are unknown. This study aimed to clarify the effects of these anesthetics on lymphatic vessel activity in rats by the use of a technique for mechanical removal of the endothelium. METHODS: The authors first examined the effects of propofol (8 mg/kg) and sevoflurane (2.0%) on in vivo lymphatic flow by injection of dye into the femoral regions of rats. In the in vitro study, the ends of the vessel segments of rat thoracic duct were connected to a syringe and stopcock, respectively. Spontaneous changes in diameter of each segment were monitored, and the extraluminal side of each segment was exposed to propofol (1 x 10(-6) approximately 3 x 10(-5) M) or sevoflurane (0.5 approximately 2.0%). Endothelial function was eliminated by perfusion of air into the lumen. RESULTS: In the dye uptake study, 80% of iliac lymphatic nodes were positively stained in a control group, whereas only 10% and 20% were positively stained in propofol and sevoflurane groups, respectively. In the in vitro study, both of the anesthetics significantly decreased the amplitude of spontaneous activity of lymphatic vessels with or without endothelial function. Sevoflurane inhibited the frequency of lymphatic vessel activity but propofol had no effect on it. When the endothelial function was eliminated, both anesthetics decreased the frequency of spontaneous activity of lymphatic vessels. CONCLUSIONS: Propofol and sevoflurane seem to have some different effects on endothelial function, which regulates the pacemaking of spontaneous contraction of lymphatic vessels.

Comparison of adjuvant anesthetics for propofol induction.

PURPOSE: Fentanyl was compared with nitrous oxide/sevoflurane as an adjuvant anesthesia to propofol during induction. METHODS: Two-hundred sixty-three patients of American Society of Anesthesiologists physical status 1 or 2 undergoing minor surgery were randomly divided into two groups. Group F patients (n = 125) received 2 microg x kg(-1) fentanyl and 1.8 mg x kg(-1) propofol, and were ventilated by mask with oxygen. Group S patients (n = 138) received 1.8 mg x kg(-1) propofol, followed by inhalation of 4% sevoflurane in N2O (41 x min(-1)) and oxygen (21 min(-1)) by mask. The trachea was intubated exactly 2, 3, 4, or 5 min after injection of 0.1 mg x kg(-1) vecuronium, and the conditions of endotracheal intubation were scored according to the patients' responses to laryngoscopy and endotracheal intubation. Systolic blood pressure (SBP) and heart rate (HR) were measured before and after endotracheal intubation. The cost of anesthetics was also calculated. RESULTS: No significant differences in SBP were observed between the groups throughout the induction period. HR did not change from preanesthetic values in group F. In contrast, HR in group S patients increased by 9-18 beats x min(-1) (bpm) after inhalation of N2O/sevoflurane and further increased by 17-21 bpm following endotracheal intubation. Significant differences in HR were noticed between the groups (P < 0.001). The conditions of endotracheal intubation were similar in the two groups and were satisfactory when mask ventilation exceeded 3 min. Fentanyl was less expensive than sevoflurane/N2O anesthesia when mask ventilation exceeded 3 min. CONCLUSION: From the standpoints of hemodynamics and drug cost, fentanyl is preferable to N2O/sevoflurane inhalation as an adjuvant to propofol during induction, because mask ventilation for more than 3 min was required for satisfactory endotracheal intubation.

Propofol anesthesia enhances the pressor response to intravenous ephedrine.

UNLABELLED: The induction of anesthesia with propofol is often associated with a decrease in arterial blood pressure (BP). Although vasopressors are sometimes required to reverse the propofol-induced hypotension, little is known about the effect of propofol on these drugs. We studied the effects of propofol and sevoflurane on pressor response to i.v. ephedrine. Thirty adult patients were randomly assigned to one of two groups. In the Propofol group (n = 15), patients received propofol 2.5 mg/kg i.v. for induction followed by 100 microg x kg(-1) x min(-1) i.v. for maintenance. In the Sevoflurane group (n = 15), anesthesia was induced with sevoflurane 3%-4% in oxygen and maintained with sevoflurane 2% in oxygen. All patients in both groups received ephedrine 0.1 mg/kg i.v. before and after the anesthetic induction. Ephedrine increased the heart rate significantly (P < 0.05) in awake patients in both study groups. In contrast, there was no increase in heart rate after the ephedrine administration under propofol or sevoflurane anesthesia. In awake patients, transient increases in mean BP were observed after i.v. ephedrine in both groups. In the Propofol group, 2 min after the administration of ephedrine, mean BP increased 16% +/- 10% under anesthesia but increased only 4% +/- 6% when the same patients were awake. The magnitudes of the pressor responses to ephedrine during propofol anesthesia were significantly greater (P < 0.05) than during the awake state. However, ephedrine 0.1 mg/kg i.v. showed no significant increases in BP during sevoflurane anesthesia. We conclude that propofol, not sevoflurane, anesthesia augments the pressor responses to i.v. ephedrine. IMPLICATIONS: The effect of anesthetics on vasopressor-mediated cardiovascular effects is poorly understood. We evaluated the pressor response to ephedrine during propofol or sevoflurane anesthesia. Our study suggests that anesthesia-induced hypotension may be easier to reverse with ephedrine during propofol anesthesia than during sevoflurane anesthesia.

Contribution of KChIP2 to the developmental increase in transient outward current of rat cardiomyocytes.

The Ca(2+)-independent, voltage-gated transient outward current (I(to)) displays a marked increase during development of cardiomyocytes. However, the molecular mechanism remained unclear. In rat adult ventricular myocytes, I(to) can be divided into a fast (I(to,f)) and a slow (I(to,s)) component by recovery process from inactivation. Voltage-gated K(+) channel-interacting proteins 2 (KChIP2) has recently been shown to modify membrane expressions and current densities of I(to,f). Here we examined the developmental change of I(to) and the putative molecular correlates of I(to,f) (Kv4.2 and Kv4.3) and KChIP2 in rat ventricular myocytes. Even in rat embryonic day 12 (E12) myocytes, we detected I(to). However, I(to) in E12 was solely composed of I(to,s). In postnatal day 10 (P10), we recorded much increased I(to) composed of two components (I(to,f) and I(to,s)), and I(to,f) was dominant. Thus, the developmental increase of I(to) from E12 to P10 can be explained by the dramatic appearance of I(to,f). Real-time RT-PCR revealed that Kv4.2 and Kv4.3 mRNA levels were slightly changed. By contrast, KChIP2 mRNA level increased from E12 to P10 by 731-fold. Therefore, the huge increase of KChIP2 expression was likely to be the cause of the great increase of I(to,f). In order to confirm that KChIP2 is crucial to induce I(to,f), we used adenoviral gene transfer technique. When KChIP2 was over-expressed in E12 myocytes, a great amplitude of I(to,f) appeared. Immunocytochemical experiments also demonstrated that KChIP2 enhanced the trafficking of Kv4.2 channels to cell surface. These results indicate that KChIP2 plays an important role in the generation of functional I(to,f) channels during development.

A truncated splice variant of KCNQ1 cloned from rat heart.

KCNQ1 encodes a pore-forming subunit of potassium channels. Mutations in this gene cause inherited diseases, i.e., Romano-Ward syndrome and Jervell and Lange-Nielsen syndrome. A truncated isoform of KCNQ1 was reported to be expressed physiologically and to suppress a delayed rectifier potassium current dominant-negatively in human heart. However, it is not known whether this way of modulation occurs in other species. We cloned another truncated splice variant of KCNQ1 (tr-rKCNQ1) from rat heart. Judging from the deleted sequence of the tr-rKCNQ1, the genomic structure of rat in this portion might be different from those of human and mouse. Otherwise, an unknown exon might exist. RT-PCR analysis demonstrated that the tr-rKCNQ1 was expressed in fetal and neonatal hearts. When this gene was expressed along with a full-length KCNQ1, it suppressed potassium currents, whether a regulatory subunit minK was co-expressed or not.