L-ornithine attenuates corticotropin-releasing factor-induced stress responses acting at GABAA receptors in neonatal chicks.

I.c.v. injection of L-ornithine has been shown to have sedative and hypnotic effects on neonatal chicks exposed to acute stressful conditions. To clarify the mechanism, we conducted three experiments under strengthened stressful conditions with corticotropin-releasing factor (CRF). In Experiment 1, the effect of i.c.v. injection of CRF, L-ornithine (0.5 µmol) or CRF with L-ornithine on the stressful response of chicks was investigated. Compared with the vehicle control, CRF increased distress vocalizations and the time spent in active wakefulness. L-ornithine increased the time spent in sleeping posture, even following stimulation with CRF. In Experiment 2, dose-dependent effects of L-ornithine were investigated using i.c.v. administration with vehicle, CRF alone or CRF plus L-ornithine (0.125, 0.25 or 0.5 µmol). L-ornithine decreased the CRF-stimulated distress vocalizations in a dose-dependent manner. In Experiment 3, the chicks were injected i.c.v. with either CRF, CRF plus L-ornithine (0.5 µmol), CRF plus the γ-aminobutyric acid (GABA)A receptor antagonist picrotoxin or L-ornithine with picrotoxin. The sedative and hypnotic effects induced by L-ornithine were blocked with co-administration of picrotoxin. These results suggest that L-ornithine could attenuate CRF-stimulated stress behaviors acting at GABAA receptors.

Intracerebroventricular injection of orexin-A, but not orexin-B, induces arousal of layer-type neonatal chicks.

In order to determine if orexins affect arousal in neonatal chicks, we intracerebroventricularly (ICV) injected either orexin-A or orexin-B to layer and broiler type chicks (Gallus gallus) and measured their behaviors and food intake following injection. Layer chicks treated with orexin-A at 0.2 and 2.0 nmol had increased arousal but their food intake was not affected. However, arousal was not affected in broiler chicks treated with orexin-A, but they spent less time feeding. When orexin-B was administered to layer and broiler chicks, neither had altered arousal and their food intake was not affected. Therefore, the orexin peptides may differentially affect arousal in the two stocks tested; orexin-A causes a stock dependant increase whereas orexin-B does not affect either.

Effect of anaesthesia maintained with sevoflurane and propofol on surgical site infection after elective open gastrointestinal surgery.

Perioperative increase in oxidative activity in surgical patients reportedly prevents postoperative surgical site infection (SSI). Several clinical studies have shown that oxidative activity under sevoflurane anaesthesia was higher than that under propofol anaesthesia. Therefore, we hypothesised that sevoflurane anaesthesia would discourage SSI compared with propofol anaesthesia. To examine the effect of anaesthesia maintained with sevoflurane and propofol on SSI, a total of 265 consecutive adult patients, with American Society of Anesthesiologists physical status 1-3, who underwent elective open gastrointestinal surgery under general anaesthesia, were surveyed for SSI between January 2007 and December 2008. Sevoflurane or propofol was selected to maintain anaesthesia in 95 and 170 patients, respectively. A propensity score was used for pairwise matching of these patients to avoid selection biases between the two methods of anaesthesia. Propensity matching yielded 84 pairs of patients. We compared standardised infection ratios (SIRs), i.e. the quotient of the number of SSI cases observed and the number of SSI cases expected, calculated using data from the National Nosocomial Infection Surveillance, between sevoflurane and propofol anaesthesia. After propensity matching, SIR after sevoflurane anaesthesia was 1.89 [95% confidence interval (CI): 1.46-2.32], which was significantly lower than after propofol anaesthesia (4.78; 95% CI: 4.30-5.27) (P=0.02). This study suggests that sevoflurane tends to suppress SSI after elective open gastrointestinal surgery compared with propofol.

Intracerebroventricular injection of L-proline and D-proline induces sedative and hypnotic effects by different mechanisms under an acute stressful condition in chicks.

The central effects of L-proline, D-proline and trans-4-hydroxy-L-proline were investigated by using the acute stressful model with neonatal chicks in Experiment 1. Sedative and hypnotic effects were induced by all compounds, while plasma corticosterone release under isolation stress was only attenuated by L-proline. To clarify the mechanism by which L-proline and D-proline induce sedative and hypnotic effects, the contribution of the strychnine-sensitive glycine receptor (glycine receptor) and N-methyl-D-aspartate glutamate receptor (NMDA receptor) were further investigated. In Experiments 2-3, the glycine receptor antagonist strychnine was co-injected intracerebroventricular (i.c.v.) with L-proline or D-proline. The suppression of isolation-induced stress behavior by D-proline was attenuated by strychnine. However, the suppression of stress behavior by L-proline was not attenuated. In Experiment 4, the NMDA receptor antagonist (+)-MK-801 was co-injected i.c.v. with L-proline. The suppression of stress behavior by L-proline was attenuated by (+)-MK-801. These results indicate that L-proline and D-proline differentially induce sedative and hypnotic effects through NMDA and glycine receptors, respectively.

[On line display of the reconstructed pressure waves of the radial artery from the monitored output pressure waves at the same site].

The input-output relationship of transducer and catheter system is described by linear, second-order differential equation with three coefficients: inductance (L), resistance (R), and capacitance (C). Once the natural frequency (fo) and the damping ratio (beta) of the monitoring system have been measured, three coefficients of the differential equation are uniquely obtained. We measured the frequency response of the monitoring system, which we usually use in our hospital, to obtain fo and beta, and reconstructed the original input arterial pressure wave from output signal on the display using the simple time-domain approach. The analysis of this linear, second-order differential equation, is applicable in on-line bedside monitoring, because the calculation of this equation is simpler than that using Fourier's translation. The pressure waves of the radial artery both monitored (output) and restored (input) were depicted on the same display at the same time. We can evaluate the changes in systemic circulation from the changes in the wave shapes of arterial blood pressure.

Single-beat estimation of end-systolic elastance using bilinearly approximated time-varying elastance curve.

BACKGROUND: Although left ventricular end-systolic elastance (E(es)) has often been used as an index of contractility, technical difficulties in measuring volume and in changing loading conditions have made its clinical application somewhat limited. By approximating the time-varying elastance curve by 2 linear functions (isovolumic contraction phase and ejection phase) and estimating the slope ratio of these, we developed a method to estimate E(es) on a single-beat basis from pressure values, systolic time intervals, and stroke volume. METHODS AND RESULTS: In 11 anesthetized dogs, we compared single-beat E(es) with that obtained with caval occlusion. Although the decrease (but not the increase) in contractility (5.3 to 11.4 mm Hg/mL) and the change in loading conditions (3.7 to 34.0 mm Hg/mL) over wide ranges significantly altered the slope ratio, the estimation of E(es) was reasonably accurate (y=0.97 x 0.46, r=0. 929, SEE=2.1 mm Hg/mL). CONCLUSIONS: E(es) can be estimated on a single-beat basis from easily obtainable variables by approximating the time-varying elastance curve by a bilinear function.

The pharmacokinetics of trinitroglycerin and its metabolites in patients with chronic stable angina.

AIMS: To study the pharmacokinetics of trinitroglycerin (GTN) and its four metabolites in angina patients during their transient use of transdermal GTN tape following intravenous administration of GTN. METHODS: Four patients received a GTN tape following intravenous administration of 0.1 microg kg-1 min-1 GTN, and the other four patients received two GTN tapes following intravenous administration of 0.2 microg kg-1 min-1 GTN. RESULTS: Plasma concentrations of GTN in both groups during tape application showed a slight decrease for the hour after the application of the tape and then were con- stant for 24 h. In contrast, the concentrations of dinitroglycerins (GDNs) and mononitroglycerins (GMNs) depended on the duration of previous intravenous administration of GTN. Neither significant cardiovascular changes nor undesirable complications were observed during the study. CONCLUSIONS: The results suggest that appropriate replacement of intravenous GTN administration with transdermal tape application could maintain a therapeutic GTN level.

[An anesthetic experience of epileptic focus resection in a nine month-old girl under monitoring by electrocorticography].

We report a successful electrocorticography (ECoG) monitoring for a epileptic cortical focus resection in a 9-month-old girl with uncontrollable epileptic seizures. Anesthesia was induced and maintained with nitrous oxide, oxygen, and sevoflurane with vecuronium. After the craniotomy, ECoG monitoring was used to locate the epileptic cortical lesion. During the procedure of subpial resection and gyrectomy, ECoG was repeatedly recorded. It was necessary to maintain adequate depth of anesthesia throughout the procedure to clarify the epileptic waves. For this purpose, sevoflurane (2.5%) with and oxygen (97.5%) under controlled-hyperventilation (PaCO2 30 mmHg), was useful for monitoring the epileptic seizure wave from cortical focuses properly.

[Midazolam-atropine lollipop for pediatric premedication].

Strawberry flavored sweet lollipop containing midazolam (5 mg) and atropine (0.25 mg) was evaluated for the premedication of pediatric patients as judged by sedative and anti-anxious effects and gastric fluid volume and acidity. The subjects of this prospective, double blind, random and controlled study were 175 children aged between 6 months and 10 years. They were divided into three groups: group A patients receiving the lollipop containing only 5 mg midazolam (n = 78), group B patients receiving the lollipop containing only 0.25 mg atropine (n = 21), and group C patients receiving the lollipop containing 5 mg midazolam and 0.25 mg atropine (n = 76). The plasma midazolam concentration was measured in ten children in group A. The sedative and anti-anxious effects were scaled with four levels. The children receiving the lollipop containing midazolam (group A and C) showed a better level of the sedative and anti-anxious state. The volume of gastric fluid of group A was more than those of group B and C. The pH of group A gastric fluid was also higher than those of other groups. The correlation equation of the plasma midazolam concentration (y ng.ml-1) against time (t min) was y = 149 x e(-t/64), (r = 0.775). These results suggest that midazolam-atropine lollipop is one of the favorable choices as the premedication for pediatric patients.

Single-beat estimation of ventricular end-systolic elastance-effective arterial elastance as an index of ventricular mechanoenergetic performance.

BACKGROUND: The ratio of ventricular end-systolic elastance (Ees) to effective arterial elastance (Ea) is known to reflect not only ventricular mechanical performance but also energetic performance. Despite these useful features, technical difficulties associated with estimating Ees make the clinical application of Ees/Ea impractical. We developed a framework to estimate Ees/Ea without measuring ventricular volume or altering the loading condition. METHODS: To achieve this goal, we approximated the ventricular time-varying elastance curve with two straight lines, one for the isovolumic phase and the other for the ejection phase, and characterized the curve with the slope ratio, k, of these two straight lines. Using the concept of the pressure-volume relationship, Ees/Ea is algebraically expressed as Ees/Ea = Pad/Pes (1 + k. ET/PEP) - 1, where Pes is end-systolic pressure, Pad is aortic diastolic pressure, ET is ejection time, and PEP is pre-ejection period. In 11 anesthetized dogs, we recorded arterial and ventricular pressures and ventricular volume and estimated Ees and Ea under various contractile states and loading conditions. RESULTS: An empirical relation between k and Ees/Ea was found as k = 0.53 (Ees/Ea)0.51. Simultaneous solution of these two equations yielded Ees/Ea as a function of Pad/Pes and ET/PEP. The estimated Ees/Ea values correlated well with the measured Ees/Ea values ([Measured Ees/Ea] = 0.96 [Estimated Ees/Ea] + 0.098, r = 0.925, SEE = 0.051). CONCLUSIONS: The proposed framework is capable of estimating Ees/Ea from ventricular and aortic pressure.

[On-line data management system using a portable blood gas analyzer in the operating room].

It is very important to establish a clinical testing system which is not only prompt, simple and accurate but also safe for the patients and medical staff in the operating room, emergency room and intensive care unit. In our institution an i-STAT portable blood gas analyser has been widely used for point of care testing in all the operating rooms. This clinical testing system has been upgraded by adding an i-STAT communication protocol to our online data management system. The analysed data transmitted by the i-STAT as an infrared signal is transformed to an electronic signal through the IR link and sent to the central data station (CDS) via RS232C. The data received by the CDS is then sent to the upper grade computer system where the data is recorded on the hard disk. One advantage of this system is that it is connected to the hospital computer system. Not only does this new system meet the need for accurate, safe, effective and economical laboratory testing, but also retrospective and multifactorial analysis of intraoperative events can be easily carried out. In the future this system can be applied to telemedicine through the Internet and contribute to the treatment of critically ill patients.

[General anesthesia for a patient with primary aldosteronism complicated with hypertrophic nonobstructive cardiomyopathy].

We report a patient with primary aldosteronism (PA) complicated with hypertrophic nonobstructive cardiomyopathy (HNCM) who underwent resection of a left adrenal tumor. Amrinone was administered to improve the features of congestive heart failure induced by retention of body fluid. Maintaining adequate preload and afterload and preventing excessive increases in contractility are important in the anesthetic management of patients with hypertrophic obstructive cardiomyopathy (HOCM). Although the preoperative diagnosis may be HNCM, stenosis of the left ventricular outflow tract may occur due to hemodynamic changes during surgery. Therefore amrinone is not often used for patients with HNCM. We inserted a pulmonary arterial catheter (Swan-Ganz CCO Thermodilution Catheter) and measured the cardiac output continuously to monitor hemodynamic changes. The symptoms of pulmonary edema were diminished one month after the surgery. These findings suggest that the increased blood volume induced by PA is a main factor aggravating preoperative congestive heart failure with HNCM.

[Intraoperative transient incomplete left bundle branch block in a patient with left axis deviation in pre-anesthetic electrocardiogram].

We encountered a case of transient incomplete left bundle branch block (TILBBB) during standard mastectomy under general anesthesia. The patient was a 40 year-old female (70 kg, 164 cm) without any abnormalities on preanesthetic examinations except -61 degrees left axis deviation in exercise electrocardiogram. Adriamycin 20 mg was administered preoperatively. After the skin incision, heart rate increased from 104 min-1 to 130 min-1 and the cardiac axis gradually rotated leftward with increasing Q wave depth on leads I and aVL. We diagnosed this as blockade of the anterior branch in the left bundle branch. After the administration of fentanyl (0.2 mg) and sevoflurane (3%), the heart rate decreased to 105 min-1 and the electrocardiogram returned to the initial wave form. This anesthetic course indicated that adriamycin had slightly damaged the cardiac muscle and inadequate anesthesia had caused tachycardia and transient left bundle branch block. Left axis deviation on preoperative exercise electrocardiogram suggests that the left bundle branch can easily be blocked with an increasing heart rate. Adequate depth of anesthesia would have prevented the increase in heart rate and abnormality in the cardiac conduction process.

[Analysis of fusion waves created with temporal pacing].

Fifty-five beats of fusion waves were recorded continuously with an audio digital tape and the tape was re-played for analysis. A 45-year-old male (56 kg, 175 cm) with cervical spondylosis was scheduled to undergo laminoplasty of the cervical vertebral (C2-C6). A temporal ventricular (VVI mode) pacing lead was inserted from the right cubital vein to the right ventricular apex for preventing bradycardia while manipulating the medulla. The height of the R wave decreased gradually and the depth of S wave increased in the earlier period of fusion beats and it was reversed later. The narrow QRS width indicated that the electrode was placed near the cardiac conducting system. The gradually increasing intervals between P waves activated the pacing, and the P wave intervals recovered inhibiting the pacing. During the recovery phase, some beats were still activated by pacing instead of depressing the rate below the original rate. These beats suggest the importance of considering the atrial-ventricular conducting time. Arterial pressure fluctuated only slightly during the 'fusion beats, suggesting that despite the abnormality in the cardiac conduction system due to pacing, contraction of the ventricular muscles was only slightly affected in this case.

[Potency of CPR without artificial breathing].

Recent experimental studies reported by several independent groups demonstrated that in the initial interventions of cardiopulmonary resuscitation (CPR), airway protection (A) and artificial breathing (B) are not essential for successful recovery from cardiac arrest. In this study, we reviewed and compared those reports to investigate individual effects of A and B on initial CPR. Airway protection: Spontaneous gasping during cardiac arrest is accompanied by upper airway protective reflexes such as head tilt and open mouth. Gasping promoted CO2 elimination from the nose in animals without A. Breathing: Gasping and precordial compression generated ventilation up to 150 and 100 ml.kg-1. min-1 respectively during cardiac arrest. Arterial blood gas analyses demonstrated that CPR without B developed hypercarbia, but maintained oxygen tensions in physiological levels. The frequency of chest compression is in the range of high frequency ventilation, which might allow for successful oxygenation regardless of limited tidal volumes. A series of experimental studies for CPR without A or B call for establishment of a simple CPR method for bystanders, namely "Just compress the chest".

Alpha- and beta-adrenergic mechanisms in the control of vascular capacitance by the carotid sinus baroreflex system.

We examined the active and passive contributions of the alpha- and beta-adrenergic receptor mechanisms to the changes in systemic vascular capacitance caused by the carotid sinus baroreflex system in anesthetized, vagotomized dogs. The carotid sinuses were isolated from the systemic circulation and perfused with controlled pressures. To determine the changes in vascular capacitance, a constant flow, constant venous pressure cardiopulmonary bypass was used. The changes in unstressed vascular volume were calculated when carotid sinus pressure was reduced from 200 to 50 mmHg without any adrenergic receptor antagonist, with either an alpha- (phentolamine) or a beta- (propranolol) antagonist and then with both. The reflex change in unstressed vascular volume in the systemic circulation (22.6 +/- 9.0 ml/kg without any antagonist) was reduced by 72% with phentolamine, by 35% with propranolol, and by 73% with both antagonists. Our results suggest that the alpha-adrenergic mechanisms contribute significantly to active changes in systemic venous capacity. In addition, the beta-adrenergic system has very little effect on active changes in venous vessels but does contribute to the overall capacity changes by dilating the hepatic outflow resistance when the carotid sinus baroreflex system is activated.

Extravascular fluid uptake during cardiopulmonary bypass in hypertensive dogs.

We investigated the effects of increases in central venous pressure (CVP) and carotid baroreceptor-induced vasodilation on the rate of extravascular fluid uptake during cardiopulmonary bypass in normotensive and Goldblatt hypertensive dogs. Carotid sinus baroreceptors were selectively perfused to control the level of vasodilation. Central venous pressure was controlled by changing the height of the venous outflow cannula. Extravascular fluid uptake was determined from the rate of change in reservoir volume. After 3 hours of bypass, total fluid accumulation was 56.11 +/- 14.16 mL/kg in normotensive dogs, significantly less than in hypertensive dogs (110.90 +/- 23.20 mL/kg) (p < 0.05). Raising CVP from 1 to 5 mm Hg increased the rate of extravascular fluid uptake in both normotensive (from 0.05 +/- 0.25 to 0.85 +/- 0.22 mL.kg-1.min-1; p < 0.05) and hypertensive dogs (from 0.68 +/- 0.28 to 2.57 +/- 0.46 mL.kg-1.min-1; p < 0.01)). At a constant CVP, baroreceptor-induced vasodilation increased the rate of extravascular fluid uptake in normotensive (from 0.25 +/- .15 to 0.81 +/- .22 mL.kg-1.min-1) and in hypertensive dogs (from 0.84 +/- .12 to 1.72 +/- .32 mL.kg-1.min-1; p < 0.05). Hypertensive dogs were more sensitive to changes in CVP and to baroreceptor-induced vasodilation. The results of this study imply that elevations in CVP or the use of vasodilators may lead to increased extravascular fluid uptake during bypass; this effect may be exacerbated in the hypertensive state.

Arterial pressure-flow relationships in hypertensive dogs: effect of carotid sinus baroreflex.

The effect of the carotid sinus baroreflex reflex on arterial pressure-flow relationships was studied in Goldblatt hypertensive and normotensive dogs on cardiopulmonary bypass. Dogs were anesthetized with pentobarbital sodium, vagotomized, and the carotid sinuses were isolated at controlled carotid sinus pressures (CSP). The mean arterial pressure-flow relationships were measured at different levels of CSP. The arterial pressure-flow relationship was found to be linear except at extreme levels of flow. The slopes derived from the linear regression of the pressure-flow relationships [total peripheral resistance (TPR)] were 1.466 +/- 0.111 and 0.786 +/- 0.13 mmHg.ml-1 x min.kg at CSP of 50 and 200 mmHg in the normotensive group and 1.758 +/- 0.183 and 0.937 +/- 0.114 mmHg.ml-1 x min.kg at CSP of 50 and 250 mmHg in the hypertensive group. The increases in slope measured when CSP was decreased from saturation to threshold were 0.68 mmHg.ml-1 x min.kg (187% increase) in the normotensive group and 0.82 mmHg.ml-1 x min.kg (188% increase) in the hypertensive group. Zero-flow arterial pressures at CSP of 50, 125, and 200 mmHg were found to be 23.1 +/- 2.9, 21.7 +/- 2.2, and 17.1 +/- 1.8 mmHg in the normotensive group and 28.4 +/- 2.2, 23.8 +/- 1.5, and 20.0 +/- 1.2 mmHg in the hypertensive group. A nonlinear model fit was found to give a significantly better fit [coefficient of determination (r2) = 0.932 linear, 0.956 nonlinear] of the arterial pressure-flow relationships. We conclude that, in experimental hypertension, carotid baroreflex control of TPR is shifted to a higher operating point without any reduction in overall reflex gain.