Yuri Nakae

Propofol inhibits Ca(2+) transients but not contraction in intact beating guinea pig hearts.

We investigated whether propofol inhibits Ca2+ transients and left ventricular pressure (LVP) in intact beating guinea pig hearts at clinical concentrations and whether an inhibition of Ca2+ transients by propofol results from an impairment of sarcolemmal or of sarcoplasmic reticulum (SR) function. By using a Langendorff’s preparation, transmural left ventricular phasic intracellular Ca2+ concentration ([Ca2+]i) was measured by the fluorescence ratio of indo-1 emission at 385 nm and 456 nm and was calibrated to Ca2+ transients (in nM). The Ca2+ transients during each contraction were defined as available [Ca2+]i. Sixty hearts were perfused with modified Krebs-Ringer’s solution containing lipid vehicle and propofol (1 and 10 &mgr;M) in the absence and presence of ryanodine, thapsigargin, and nifedipine, while developed LVP and available [Ca2+]i were recorded. Propofol (10 &mgr;M) decreased available [Ca2+]i by 11.0% ± 1.3% without decreasing developed LVP (% of control, P < 0.05). Propofol (10 &mgr;M) caused a leftward shift in the curve of developed LVP as a function of available [Ca2+]i. Propofol (10 &mgr;M) with nifedipine (1 &mgr;M), but not with ryanodine (1 &mgr;M) or thapsigargin (1 &mgr;M), decreased available [Ca2+]i by 15.5% ± 1.7% (P < 0.05). Propofol decreases available [Ca2+]i without decreasing cardiac contraction, and it enhances myofilament Ca2+ sensitivity in intact beating hearts at clinical concentrations. The inhibition of available [Ca2+]i by propofol may be mainly mediated by an impairment of sarcoplasmic reticulum Ca2+ handling rather than the sarcolemmal L-type Ca2+ current. Implications This is the first study of the effects of propofol on intracellular Ca2+ concentration and myofilament Ca2+ sensitivity under physiologic conditions in intact isolated beating guinea pig hearts.

The direct effects of diazepam and midazolam on myocardial depression in cultured rat ventricular myocytes.

We examined the direct myocardial depressant effects of diazepam and midazolam and determined whether a benzodiazepine receptor antagonist, flumazenil, or an L-type Ca2+ channel agonist, Bay K 8644, affects the myocardial depression induced by diazepam and midazolam in cultured rat ventricular myocytes. Ventricular myocytes of neonatal rats were obtained by enzymatic digestion with collagenase and cultured for 6-7 days. The myocytes were stabilized in serum-free medium, and the spontaneous beating rate and amplitude were measured by determining displacement with a fiberoptic sensor. Myocytes were exposed to either diazepam or midazolam at concentrations of 0.1, 1, 10, and 100 micro M. The beating rate and amplitude were measured 4 min after diazepam or midazolam administration. In other cells, either diazepam or midazolam was administered at each concentration in the presence of flumazenil or Bay K 8644. Midazolam and diazepam decreased the beating rate and amplitude concentration-dependently. These myocardial depressant effects were prevented by Bay K 8644 and, to a lesser degree, by flumazenil. Thus, the L-type Ca2+ channel is important in the direct myocardial depression caused by diazepam and midazolam. Implications: This study describes the direct effect of midazolam and diazepam on intrinsic myocardial contraction using cultured rat ventricular heart cells. Both of these drugs have a direct myocardial depressant effect at the cellular level, which is mainly mediated by an inhibition of the sarcolemmal L-type Ca2+ channel. (Anesth Analg 1997;85:729-33)

Isoproterenol enhances myofilament Ca2+ sensitivity during hypothermia in isolated guinea pig beating hearts

Isoproterenol is often required to treat acute left ventricular dysfunction during separation from cardiopulmonary bypass for cardiac surgery. We hypothesized that heart rate and intracellular Ca2+ concentration ([Ca2+]i) homeostasis may be important factors when isoproterenol improves the cardiac function during hypothermia. Accordingly, we investigated the effect of isoproterenol on the cardiac functional variables, [Ca2+]i, and myofilament Ca2+ sensitivity under spontaneous beating during hypothermia. Intact guinea pig hearts were perfused with a modified Krebs-Ringer solution (baseline) and Krebs-Ringer solution containing isoproterenol (1 nM) at 37°C, 32°C, and 27°C while all cardiac variables and [Ca2+]i were recorded. Isoproterenol increased developed left ventricular pressure (LVP), maximum rate of increase in LVP, and coronary inflow at 27°C, and it also increased heart rate and maximum rate of decrease in LVP at each temperature (P < 0.05). Isoproterenol produced a leftward shift of the curve of developed LVP as a function of available [Ca2+]i at 32°C and 27°C (P < 0.05), without changing available [Ca2+]i. Isoproterenol improves the cardiac function, especially systolic ventricular function, by enhancement of myofilament Ca2+ sensitivity under spontaneous beating during hypothermia in intact guinea pig hearts.

Comparison of the Jackson-Rees circuit, the pediatric circle, and the MERA F breathing system for pediatric anesthesia.

The purpose of this study was to compare the Jackson-Rees circuit with the pediatric circle and MERA F breathing system (MERA F system) for pediatric anesthesia from the viewpoint of work of breathing (WOB). Twenty-three children (2-10 yr old) were studied during spontaneous breathing under endotracheal anesthesia with 4 L/min nitrous oxide, 2 L/min oxygen, and 1% end-tidal concentration of sevoflurane. WOB, inspiratory and expiratory airway resistance, dynamic compliance (CDYN), pressure time product (PTP), and arterial blood gasses were measured in the three circuits. The inspiratory WOB was estimated directly by measuring the esophageal pressure-volume loop using the Campbell technique. In a laboratory study, we measured the compliances of the Jackson-Rees circuit, the pediatric circle, the MERA F system, and the adult circuit. WOB differed among the three circuits (MERA F system > pediatric circle > Jackson-Rees circuit). Inspiratory and expiratory resistances, and arterial carbon dioxide tension in the Jackson-Rees circuit were significantly lower than those of both the pediatric circle and MERA F system. The CDYN and PTP in the MERA F system were significantly higher than those in both the Jackson-Rees circuit and the pediatric circle. The MERA F system had significantly higher compliance than the Jackson-Rees circuit and pediatric circle. It is concluded that the Jackson-Rees circuit is most efficient, the pediatric circle is intermediate, and the MERA F system is the least efficient from the viewpoint of WOB during spontaneous breathing for pediatric anesthesia. (Anesth Analg 1996;83:488-92)

Morphine enhances myofilament Ca2+ sensitivity in intact guinea pig beating hearts

UNLABELLED We investigated whether morphine alters intracellular Ca(2+) concentration ([Ca(2+)](i)), left ventricular pressure (LVP), and myofilament Ca(2+) sensitivity under physiologic conditions in intact guinea pig beating hearts and whether delta(1), delta(2), and kappa opioid stimulations are related to the direct cardiac effects of morphine. Transmural LV phasic [Ca(2+)](i) was measured from fluorescence signals at 385 nm and 456 nm. The Ca(2+) transients during each contraction were defined as available [Ca(2+)](i). The hearts were perfused with modified Krebs-Ringer solution containing morphine in the absence and presence of delta(1) (BNTX), delta(2) (NTB), and kappa (nor-BNI) antagonists, while developed LVP and available [Ca(2+)](i) were recorded. Morphine (1 microM) decreased available [Ca(2+)](i) by 44 +/- 12 nM without decreasing developed LVP at 2.5 mM of [CaCl(2)](e) (P < 0.05). Morphine (1 microM) caused a leftward shift in the curve of developed LVP as a function of available [Ca(2+)](i) (P < 0.05). BNTX (1 microM), but not nor-BNI (1 microM) or NTB (0.1 microM) blocked morphine (1 microM) effects to decrease available [Ca(2+)](i). Morphine decreases available [Ca(2+)](i) but not LVP, and it enhances myofilament Ca(2+) sensitivity under physiologic conditions at clinical concentrations in intact isolated beating guinea pig hearts. The delta(1) opioid stimulation modifies the effects of morphine on Ca(2+) transients and myofilament Ca(2+) sensitivity. IMPLICATIONS Morphine modifies myofilament Ca(2+) sensitivity and Ca(2+) transients in guinea pig hearts at concentrations that are clinically relevant.

Preoperative anxiety and volume and acidity of gastric fluid in children

Forty‐three patients aged 3–6 years, undergoing minor surgery were studied. Parents staying with their children were asked to evaluate the anxiety of their children and themselves by a visual–analogue scale the night before surgery (VAS‐N) and just before premedication in the morning (VAS‐M). After induction, gastric fluid was collected and the volume and pH were measured. Patients with a VAS‐M lower than 5 were considered the low‐anxiety group ( L‐group; n=24) and the remainder comprised the high‐anxiety group (H‐group; n=19). The gastric volume of the H‐group was significantly lower than that of the L‐group. No difference was found in pH. A significant overall correlation of VAS‐N was found between patients and their parents. These results suggest that the low level anxiety of children and their parents could not reduce the volume and acidity of gastric fluid and consequently the risk of aspiration pneumonia.

Triggering delay time and work of breathing in three paediatric patienttriggered ventilators

PurposeTo compare the effectiveness of three patient-triggered ventilators by evaluating triggering delay time and pressure-volume loops during initiation of inspiration.MethodsIn a two-part study, a model lung was used in part 1 and 20 children, after tracheal intubation, in part 2. Triggering delay time and work of breathing (WOB) during pressure support ventilation using three patient-triggered ventilators: Servo Ventilator 300™ VIP Bird™, and SLE 2000 Neonatal Ventilator™. Triggering delay time was from the beginning of negative deflection in the oesophageal pressure trace, to the onset of inspiration. The WOB was estimated directly by measuring the oesophageal pressure-volume loop.ResultsThe Servo demonstrated superior triggering delay time and reduced WOB in the model study. The VIP Bird demonstrated shorter triggering delay and reduced WOB in the clinical component of the study. In the model lung, triggering delay time in the Servo 300 [62 ± 6 msec (mean ± SD)] was shorter than that in the VIP Bird (76 ± 7 msec) (P < 0.05), and WOB with the SLE 2000 (202 ± 37 g cm) was greater than with other ventilators, (Servo 300, 112 ± 32 g·cm and VIP Bird 72 ± 41 g·cm) (P < 0.05). In the clinical study, triggering delay time in the VIP Bird (52 ± 19 msec) was shorter than in the other ventilators, Servo 300 (66 ± 14 msec), SLE 2000 (68 ± 65 msec) (P < 0.05). The Servo 300 (56 ± 34 g·cm) required higher WOB than the other ventilators: VIP Bird (22 ± 12 g·cm), SLE 2000 (l4±3g·cm)(P< 0.05).ConclusionComparative model lung performance of these ventilators does not correspond with their clinical performance. In our clinical evaluation, the VIP Bird ventilator demonstrated superior performance with shorter triggering delay time, low WOB needed to initiate inspiration, and little air leak.RésuméObjectifComparer l’efficacité de trois respirateurs déclenchés par le patient en évaluant le délai et les courbes pression-volume durant la phase initiale de l’inspiration.MéthodesDans cette étude en 2 volets, un modèle pulmonaire a été utilisé pour la première partie et 20 enfants intubés pour la deuxième. On a étudié le délai de déclenchement de l’appareil et le travail respiratoire (TR) durant la ventilation selon le mode pression de support en utilisant trois respirateurs déclenchés par le patient: le ventilateur Servo 300®, le Bird VIP® et le SLE 2000 Neonatal Ventilator®. Le délai de déclenchement de l’appareil a été calculé à partir du début de la défection négative sur le tracé de pression oesophagienne jusqu’au début de l’inspiration. Le TR a été estimé directement en mesurant la boucle pression-volume oesophagienne.RésultatsLe Servo a démontré un meilleur délai de déclenchement et un TR réduit dans l’étude utilisant le modèle pulmonaire. Le Bird VIP a démontré un délai plus court et un TR diminué dans la partie clinique de l’étude. Dans le modèle pulmonaire, le délai de déclenchement du Servo 300 (62 ± 6 msec (moyenne + écart type)) a été plus court que celui du Bird VIP (76 ± 7 msec) (P< 0,05), et le TR avec le SLE 2000 (202 ± 37 g·cm) a été plus grand qu’avec les deux autres ventilateurs (Servo 300, 112 ± 32 g·cm et Bird VIP 72 ± 41 g·cm) (P< 0,05). Dans la partie clinique de l’étude, le délai de déclenchement du Bird VIP (52 ± 19 msec) a été plus court qu’avec les autres ventilateurs, Servo 300 (66 ± 14 msec) et SLE 2000 (68 ± 65 msec) (P< 0,05). Le TR du Servo 300 (56 ± 34 g·cm) a été plus élevé que celui des deux autres ventilateurs: Bird VIP (22 ± 12 g·cm) et SLE 2000 ( 14 ± 3 g·cm) (P< 0,05).ConclusionLa performance de ces ventilateurs dans le modèle pulmonaire ne correspond pas à leur performance clinique. Au cours de notre évaluation clinique, le Bird VIP a démontré une performance supérieure aux autres avec un délai de déclenchement moindre, un faible TR pour initier l’inspiration et peu de fuites d’air.

Difference in the effect of pancuronium and vecuronium on baroreflex control of heart rate in humans.

The effects of pancuronium and vecuronium, each in doses of 0.05 and 0.08 mg·kg−1, on the baroreflex control of the heart rate were studied in 40 adult patients of either sex (21 men and 19 women) during stable nitrous oxide-oxygen-fentanyl anesthesia. The blood pressure was elevated by intravenous infusion of phenylephrine (4 μgg·kg−1·min−1) for the pressor test, and lowered by a bolus injection of nitroglycerin (0.3–0.5 mg) for the depressor test. Baroreflex sensitivity was judged from the slope of the regression of the systolic blood pressure on the succeeding R-R intervals on the ECG. There was no significant difference between the baseline blood pressure at which both tests were carried out. Nitrous oxide-oxygen-fentanyl anesthesia alone suppressed the baroreflex sensitivity to a level which was at the lower limit of the physiological and non-anesthetized state. The 0.08 mg·kg−1 dose of pancuronium significantly suppressed the reflex sensitivity in both the pressor and depressor tests. However, the 0.05 mg·kg−1 dose of pancuronium and both doses of vecuronium did not cause any significant change in the test results.

Humidification during low-flow anesthesia in children

PurposeThe aim of this study was to compare the effect of low-flow anesthesia with or without a heat and moisture exchanger with high-flow anesthesia on airway gas humidification in children.MethodsOne hundred twenty children were randomly assigned to one of three groups: low-flow anesthesia with 0.5l·min−1 of total gas flow (LFA,n=40), low-flow anesthesia with 0.5l·min−1 using a heat and moisture exchanger (HME,n=40), and high-flow anesthesia with 6l·min−1 (HFA,n=40). The temperature and relative humidity of the inspired gas were measured throughout anesthesia.ResultsThe relative humidity of the inspired gas in the HME group was increased compared with that of the LFA and HFA groups 20 min after induction (p<0.05). The airway humidification in the LFA group was higher than that in the HFA group 10 min after induction (p<0.05). The temperature of the inspired gas in the HME group was increased compared with that in the LFA and HFA groups after 70 min (P<0.05).ConclusionLow-flow anesthesia is less effective in providing adequate humidification of inspired gas than low-flow anesthesia with a heat and moisture exchanger, but significantly better than high-flow anesthesia in children.

Anesthetic management for magnetic resonance imaging of children.

Magnetic resonance imaging (MRI) has been performed in Hokkaido Childrens Medical Center since 1993. MRI requires absolute immobilization of patients during the procedure, which lasts approximately 40 min. Children undergoing MRI examination therefore require deep sedation or general anesthesia with tracheal intubation [1,2]. The high magnetic field created by MRI interferes with monitors and ferromagnetic components of commonly used anesthetic equipment [3,4]. Moreover, the narrow and deep confines of the MRI tunnel limits access to monitor patients. Thus, adequate equipment and monitors are essential for MRI examinations. In this paper we describe our anesthetic management of children with an MRI-compatible anesthesia machine, a ventilator, and monitoring devices. Satisfactory monitoring of ECG, percutaneous 02 saturation (SpO2), end-tidal CO 2 tension (PETCO2), and the concentrations of the anesthetic gases was obtained. All scans were diagnostically adequate and none of the monitoring techniques described interfered with MR function or produced image artifacts. Indications for MRI under general anesthesia in our institution are: (1) patients who have severe upper airway obstruction, high intracranial pressure, or epilepsy, and (2) critically ill patients who are being mechanically ventilated. Informed consent for MRI under general anesthesia was obtained from the patients parent or guardian. We studied 20 patients, which include 15 in neurosurgery, 2 in abdominal surgery, 2 in cardiac surgery, and i in pediatrics. The mean age and body weight were 14.0 months (range 2 months to 14 years) and