Effects of adrenaline and vasopressin on cerebral microcirculation at baseline and during global brain ischemia and reperfusion in rabbits.

BACKGROUND: During cardiopulmonary resuscitation, the brain becomes ischemic. Adrenaline and vasopressin have been recommended for use during cardiopulmonary resuscitation. We aimed to investigate the direct effects of adrenaline and vasopressin on the cerebral microvasculature at baseline and during ischemia and reperfusion in rabbits. METHODS: The closed cranial window method was used to visualize the cerebral microcirculation and changes in the pial arteriole diameter in rabbits. Adrenaline and vasopressin were administered topically on the brain tissue. First, the effects of adrenaline and vasopressin on pial arterioles were evaluated in 7 rabbits that were given 4 different concentrations of adrenaline, and another 7 rabbits that received 4 different concentrations of vasopressin. Second, the effects of adrenaline and vasopressin were determined during the global brain ischemia and reperfusion, which was induced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. An additional 21 rabbits were randomly assigned to receive artificial cerebrospinal fluid (aCSF) (n = 7), adrenaline 10-5 mol/L (n = 7), or vasopressin 10-7 mol/L (n = 7). Each drug was continuously infused from 5 min after the initiation of ischemia until 120 min after reperfusion. The pial arteriole diameters were recorded before and during ischemia, and after reperfusion. RESULTS: At baseline, adrenaline and vasopressin did not affect the cerebral pial arterioles. During ischemia, vasopressin, but not aCSF and adrenaline constricted the pial vessels. Late in the reperfusion phase, pial diameter became reduced in the vasopressin and aCSF groups whereas pial diameter was higher in the animals treated with adrenaline. CONCLUSIONS: Adrenaline and vasopressin did not affect pial arterioles at baseline. During reperfusion, adrenaline may counteract the cerebral vasoconstriction.

Influence of pneumoperitoneum and head-down maneuver on the cerebral microvasculature in rabbits.

BACKGROUND: With recent advances in robot-assisted techniques, an increasing number of surgeries are being performed with pneumoperitoneum and head-down maneuver (HDM) that may affect the cerebral microcirculation. For the first time, this study investigated the direct influence of pneumoperitoneum and HDM on the cerebral microvasculature in rabbits. METHODS: Adult male rabbits were randomly allocated to the following groups (n = 7 each): control, pneumoperitoneum alone (P), and pneumoperitoneum with HDM (P + HDM) for 120 min. A closed cranial window was installed above the parietal bone to visualize the pial microvasculature. Pial arteriolar diameter and hemodynamic and blood gas parameters were measured during the 140-min observation period. Brain edema was assessed by evaluation of the brain water content at the end of the experiment. RESULTS: Rabbits in the P and P + HDM groups exhibited a similar degree of immediate pial arteriolar dilation following the initiation of both P and P + HDM (P: 1.11 ± 0.03, p = 0.0044 and P + HDM: 1.07 ± 0.02, p = 0.0004, relative changes from the baseline value by defining the baseline as one). In the P + HDM group, pial arteriole diameter returned to the baseline level following the discontinuation of pneumoperitoneum and HDM (1.05 ± 0.03, p = 0.0906, vs. baseline). In contrast, the pial arterioles remained dilated as compared to the baseline level in the P group after discontinuation of pneumoperitoneum. There were no changes in pial arteriole diameter in the animals in the control group. Heart rate, blood gas parameters, and brain water content were not significantly different between the groups. CONCLUSION: The pial arterioles dilated immediately after pneumoperitoneum with or without HDM. The pial arterioles remained dilated 20 min after discontinuation of pneumoperitoneum alone but constricted upon discontinuation of pneumoperitoneum plus HDM. Pneumoperitoneum and HDM for 2 h did not cause brain edema.

Changes of cerebral regional oxygen saturation during pneumoperitoneum and Trendelenburg position under propofol anesthesia: a prospective observational study.

BACKGROUND: We evaluated the change of cerebral regional tissue oxygen saturation (rSO2) along with the pneumoperitoneum and the Trendelenburg position. We also assessed the relationship between the change of rSO2 and the changes of mean arterial blood pressure (MAP), heart rate (HR), arterial carbon dioxide tension (PaCO2), arterial oxygen tension (PaO2), or arterial oxygen saturation (SaO2). METHODS: Forty-one adult patients who underwent a robotic assisted endoscopic prostatic surgery under propofol and remifentanil anesthesia were involved in this study. During the surgery, a pneumoperitoneum was established using carbon dioxide. Measurements of rSO2, MAP, HR, PaCO2, PaO2, and SaO2 were performed before the pneumoperitoneum (baseline), every 5 min after the onset of pneumoperitoneum, before the Trendelenburg position. After the onset of the Trendelenburg position, rSO2, MAP, HR were recorded at 5, 10, 20, 30, 45, and 60 min, and PaCO2, PaO2, and SaO2 were measured at 10, 30, and 60 min. RESULTS: Before the pneumoperitoneum, left and right rSO2 were 67.9 ± 6.3% and 68.5 ± 7.0%. Ten minutes after the onset of pneumoperitoneum, significant increase in the rSO2 was observed (left: 69.6 ± 5.9%, right: 70.6 ± 7.4%). During the Trendelenburg position, the rSO2 increased initially and peaked at 5 min (left: 72.2 ± 6.5%, right: 73.1 ± 7.6%), then decreased. Multiple regression analysis showed that change of rSO2 correlated with MAP and PaCO2. CONCLUSIONS: Pneumoperitoneum and the Trendelenburg position in robotic-assisted endoscopic prostatic surgery did not worsen cerebral oxygenation. Arterial blood pressure is the critical factor in cerebral oxygenation. TRIAL REGISTRATION: Japan Primary Registries Network (JPRN); UMIN-CTR ID; UMIN000026227 (retrospectively registered).

The effects of Y-27632 on pial microvessels during global brain ischemia and reperfusion in rabbits.

BACKGROUND: Global brain ischemia-reperfusion during propofol anesthesia provokes persistent cerebral pial constriction. Constriction is likely mediated by Rho-kinase. Cerebral vasoconstriction possibly exacerbates ischemic brain injury. Because Y-27632 is a potent Rho-kinase inhibitor, it should be necessary to evaluate its effects on cerebral pial vessels during ischemia-reperfusion period. We therefore tested the hypotheses that Y-27632 dilates cerebral pial arterioles after the ischemia-reperfusion injury, and evaluated the time-course of cerebral pial arteriolar status after the ischemia-reperfusion. METHODS: Japanese white rabbits were anesthetized with propofol, and a closed cranial window inserted over the left hemisphere. Global brain ischemia was produced by clamping the brachiocephalic, left common carotid, and left subclavian arteries for 15 min. Rabbits were assigned to cranial window perfusion with: (1) artificial cerebrospinal fluid (Control group, n = 7); (2) topical infusion of Y-27632 10-6 mol · L-1 for 30 min before the initiation of global brain ischemia (Pre group, n = 7); (3) topical infusion of Y-27632 10-6 mol · L-1 starting 30 min before ischemia and continuing throughout the study period (Continuous group, n = 7); and, (4) topical infusion of Y-27632 10-6 mol · L-1 starting 10 min after the ischemia and continuing until the end of the study (Post group, n = 7). Cerebral pial arterial and venule diameters were recorded 30 min before ischemia, just before arterial clamping, 10 min after clamping, and 5, 10, 20, 40, 60, 80, 100, and 120 min after unclamping. RESULTS: Mean arterial blood pressure and blood glucose concentration increased significantly after global brain ischemia except in the Continuous group. In the Pre and Continuous groups, topical application of Y-27632 produced dilation of large (mean 18-19%) and small (mean; 25-29%) pial arteries, without apparent effect on venules. Compared with the Control and Pre groups, arterioles were significantly dilated during the reperfusion period in the Continuous and Post groups (mean at 120 min: 5-8% in large arterioles and 11-12% in small arterioles). CONCLUSIONS: Y-27632 dilated cerebral pial arterioles during reperfusion. Y-27632 may enhance recovery from ischemia by preventing arteriolar vasoconstriction during reperfusion.

Effects of hyperventilation on cerebral oxygen saturation estimated using near-infrared spectroscopy: A randomised comparison between propofol and sevoflurane anaesthesia.

BACKGROUND: Near-infrared spectroscopy estimates cerebral regional tissue oxygen saturation (rSO2), which may decrease under hyperventilation. Propofol and sevoflurane act differently on cerebral blood vessels. Consequently, cerebral blood flow during hyperventilation with propofol and sevoflurane anaesthesia may differ. OBJECTIVES: The first aim of this study was to compare the changes in rSO2 between propofol and sevoflurane anaesthesia during hyperventilation. The second aim was to assess changes in rSO2 with ventilation changes. DESIGN: A randomised, open-label study. SETTING: University of Yamanashi Hospital, Yamanashi, Japan from January 2014 to September 2014. PARTICIPANTS: Fifty American Society of Anesthesiologists physical status 1 or 2 adult patients who were scheduled for elective abdominal surgery were assigned randomly to receive either propofol or sevoflurane anaesthesia. Exclusion criterion was a known history of cerebral disease such as cerebral infarction, cerebral haemorrhage, transient ischaemic attack and subarachnoid haemorrhage. INTERVENTIONS: After induction of anaesthesia but before the start of surgery, rSO2, arterial carbon dioxide partial pressure (PaCO2) and arterial oxygen saturation were measured. Measurements were repeated at 5-min intervals during 15 min of hyperventilation with a PaCO2 around 30 mmHg (4 kPa), and again after ventilation was normalised. MAIN OUTCOME MEASURES: The primary outcome was the difference of changes in rSO2 between propofol anaesthesia and sevoflurane anaesthesia during and after hyperventilation. The second outcome was change in rSO2 after the initiation of hyperventilation and after the normalisation of ventilation. RESULTS: Changes of rSO2 during hyperventilation were -10 ±â€Š7% (left) and -11 ±â€Š8% (right) in the propofol group, and -10 ±â€Š8% (left) and -9 ±â€Š7% (right) in the sevoflurane group. After normalisation of PaCO2, rSO2 returned to baseline values. Arterial oxygen saturation remained stable throughout the measurement period. The rSO2 values were similar in the propofol and the sevoflurane groups at each time point. CONCLUSION: The effects of hyperventilation on estimated rSO2 were similar with propofol and sevoflurane anaesthesia. Changes in rSO2 correlated well with ventilation changes. TRIAL REGISTRATION: Japan Primary Registries Network (JPRN); UMIN-CTR ID; UMIN000010640.

The effects of topical and intravenous JM-1232(-) on cerebral pial microvessels of rabbits.

BACKGROUND: JM-1232(-) is a novel anesthetic agent which acts through gamma-aminobutyric acid receptors. Cerebral pial vascular effects of JM-1232(-) are unknown. We thus evaluated topical and intravenous effects of JM-1232(-) on cerebral pial microvessels in rabbits, and the extent to which carbon dioxide (CO2) reactivity is preserved. METHODS: Closed cranial windows were used to visualize cerebral pial circulation in 29 Japanese white rabbits. In the first experiment, the cranial window was superfused with increasing concentrations of JM-1232(-): 10(-11), 10(-9), 10(-7), 10(-5) mol/L, n = 8 per concentration. In the second experiment, we examined the effects of an intravenous bolus of 1 mg/kg bolus of JM-1232(-), followed by the continuous infusion at 0.3 mg/kg/minute on cerebral pial vascular alteration (n = 9). In the third, we examined CO2 reactivity of cerebral pial vessels under JM-1232(-) (n = 6) or sevoflurane anesthesia (n = 6). RESULTS: Topical application of JM-1232(-) did not change pial venular diameter, and constricted arterials only at the highest concentration. Intravenous administration of JM-1232(-) produced cerebral pial constriction which gradually diminished over time. Under intravenous administration of JM-1232(-) and inhaled sevoflurane, diameters of vessels increased in parallel with CO2 partial pressure. Slopes of linear regression and correlation coefficients in arterioles and venules were comparable for JM-1232(-) anesthesia and sevoflurane anesthesia. CONCLUSIONS: Topical application of JM-1232(-) had little effect on cerebral pial vessels. Intravenous administration produced vasoconstriction of cerebral pial arterioles and venules, however those changes were clinically unimportant. In addition, JM-1232(-) did not impair CO2 responsiveness. At least from the perspective of vascular reactivity, JM-1232(-) thus appears safe for neurosurgical patients.

Direct effects of Rho-kinase inhibitor on pial microvessels in rabbits.

PURPOSE: Rho-kinase inhibitor is widely used for prevention of cerebral vascular spasm. However, the cerebral pial vascular action of Rho-kinase inhibitor has not been investigated. We therefore evaluated the direct effects of Y-27632, a Rho-kinase inhibitor, on pial microvessels. METHOD: Experiments were performed on anesthetized rabbits. A closed cranial window was used to visualize the pial microcirculation. After baseline hemodynamic and pial vascular measurements, the cranial window was superfused with four increasing concentrations of Y-27632 (10(-9), 10(-7), 10(-6), 10(-5) mol l(-1); n = 7) dissolved in artificial cerebrospinal fluid for 7 min each. We measured the diameters of pial vessels, mean arterial pressure (MAP), heart rate (HR), and rectal temperature at 7 min after application of each Y-27632 concentration. RESULTS: MAP, HR, rectal temperature, arterial pH, PaCO2, PaO2, and plasma Na(+), K(+) and glucose concentrations did not change significantly during the experimental period. Y-27632 at 10(-9) to 10(-7) mol l(-1) did not produce any significant change in pial arterioles. Topical application of Y-27632 at 10(-6) and 10(-5) mol l(-1) produced pial large (8.4 ± 5.7 and 19.8 ± 12.7 %) and small (10.1 ± 8.5 and 18.1 ± 12.3 %) arterioles dilation. However, Y-27632 did not produce any change in pial large and small venules. CONCLUSION: We evaluated the direct effects of Y-27632 on pial microvessels. Y-27632 dilates only pial arterioles in a concentration-dependent manner, and most at a concentration of 10(-5) mol l(-1). Y-27632 is a potent cerebral pial arteriolar dilator but is not a venular dilator.

[Epidural fentanyl delayed emergence from anesthesia].

An 83-year-old man (158 cm, 42 kg) was scheduled for cholecystectomy. He had a history of hypertension and atrial fibrillation. The patient received no premedication. An epidural catheter was inserted via the T9-10 interspace and 2% mepivacaine 7 ml was injected, producing a sensory block from T4 to T12. Anesthesia was induced with propofol and remifentanil, and was maintained with propofol, remifentanil, and nitrous oxide in oxygen. Rocuronium was given to provide neuromuscular block. Just before the completion of surgery, a bolus epidural injection of 2% mepivacaine 2 ml with fentanyl 50 microg was performed. Then epidural solution of ropivacaine 0.1% with fentanyl 6.25 microg x ml(-1), and droperidol 25 microg x ml(-1) was infused at 4 ml x hr(-1). Soon after the surgery, the patient developed atrial fibrillation that was treated with external electrocardioversion with 100 watt x sec. After the restoration of sinus rhythm, anesthetics were discontinued. The patient did not emerge from anesthesia though he breathed spontaneously Doxapram was slightly effective, but he did not respond to the verbal command. Epidural infusion was stopped and the patient was transferred to the ward. The patient fully recovered from anesthesia after 2 hours. Epidural infusion was restarted 17 hours later, and the patient fell asleep. He woke up after stopping epidural infusion. Epidurally administered fentanyl must have been the cause of delayed recovery from anesthesia. He could have been highly sensitive to fentanyl. Patient controlled epidural anesthesia may have been useful for this patient.

Anti-adhesive membrane for pleural cavity.

An anti-adhesive membrane containing a large amount of glycerin was developed for lung surgery and was tested in the pleural cavity of six dogs. The test membranes were put between the lung and the chest wound of the pleural cavity wall to separate them. In five of the animals, no adhesion was observed after 3 weeks in the area where the membrane had been inserted, but the area without the membrane showed firm adhesion between the lung and the pleural cavity wall. A sixth animal observed for 3 months also showed no adhesion. Seprafilm, which is the product of choice for peritoneal surgeries, was used as a control in six dogs. Seprafilm could not prevent adhesion in the pleural cavity of all six animals after 3 weeks observation. The new test membrane contained glycerin, which gathered and dispersed abundant water. Together with this, growth factors are also dispersed, resulting in dilution of excessive growth factors at the wound sites. In general, fibroblasts do not migrate in an extremely hydrous gel matrix. Migration of fibroblasts into the membrane is minimized, resulting in the prevention of formation of adhesion tissue composed of fibroblasts and collagen fibers. From the results, we assume that water can prevent adhesion after surgery.

[Combined spinal-epidural anesthesia for abdominal surgery in a patient with chronic obstructive pulmonary disease].

A 69-year-old man (150 cm, 57 kg)who had been diagnosed as having COPD, was admitted to our hospital because of abdominal pain and drowsiness. He was diagnosed as CO2 narcosis and perforation of appendix. When he recovered from CO2 narcosis, he was scheduled for elective ilectomy. Because his pulmonary function was impaired, combined spinal and epidural anesthesia was selected. With the patient in the right lateral position, an epidural catheter was inserted at T12-L1 interspace, and spinal anesthesia was performed at L3-4 interspace with 0.5% isobaric bupivacaine 4 ml. When the patient was positioned laterally, SpO2 decreased from 82% to 77%. After completion of injection, the patient was returned to the supine position, and SpO2 immediately recovered. Spinal block level was not satisfactory, and fentanyl 0.1 mg and 2% mepivacaine 4 ml were administered through epidural catheter to achieve a T4 level of block. Because severe intraperitoneal inflammation was observed, ilectomy was changed to drainage of intra-abdominal abscess. The patient did not complain of dyspnea, pain, or nausea, intraoperatively. SpO2 was 85-93% with O2 inhalation at 1l x min(-1) during the operation. Post-operative course was uneventful. Although lateral position is popular in performing epidural and spinal anesthesia, sitting position could be suitable for this patient. Decrease in SpO2 may have occurred due to ventilation-perfusion mismatch. Since combined spinal and epidural anesthesia can preserve spontaneous respiration and it is possible to titrate anesthetic level, it would be preferable for abdominal surgery in patients with COPD.

[Anesthetic managements for emergency cesarean section and craniotomy in patients with intracranial hemorrhage due to ruptured cerebral aneurysm and arteriovenous malformation].

We report two cases of anesthetic management for emergency cesarean sections and craniotomies in patients with intracranial hemorrhage. Case 1: A 32-year-old woman at 33 weeks gestation suffered from subarchnoid hemorrhage due to the rupture of cerebral aneurysm. Case 2: A 38-week-pregnant woman aged 32 developed intracerebral hematoma resulting from ruptured arteriovenous malformation. The weights of the fetuses were estimated to be 1756 g and 1996 g respectively, and they were expected premature. Discussions with obstetricians, neurosurgeons and neonatologists encouraged us to schedule cesarean section followed by craniotomy under general anesthesia. Before deliveries we selected isoflurane and avoided excessive hyperventilation to maintain uteroplacental circulation. After deliveries, isoflurane was changed to propofol and prostaglandin E1 was infused to control blood pressure and to avoid uterine atonic bleeding. Uneventful anesthetic course resulted in both the mothers and the fetuses surviving. It is important to develop good relationships among the specialists for the management of pregnant woman with intracranial hemorrhage.

Optimal doses of sevoflurane and propofol in rabbits.

BACKGROUND: Although sevoflurane and propofol are commonly used anesthetics in rabbits, optimal doses of remain unclear. We thus assessed the optimal hypnotic doses of sevoflurane and propofol, and evaluated the influence of dexmedetomidine on sevoflurane and propofol requirements. METHODS: Twenty-eight Japanese white rabbits were randomly assigned to one of four groups (n=7 each). Rabbits were given either sevoflurane, propofol, sevoflurane+dexmedetomidine, or propofol+dexmedetomidine (injected 30 µg∙kg(-1)∙hr(-1) for 10 min followed by an infusion of 3.5 µg∙kg(-1)∙hr(-1)). Hypnotic level was evaluated with Bispectral Index (BIS), a well-validated electroenchalographic measure, with values between 40 and 60 representing optimal hypnosis. BIS measurements were made 10 minutes after the adjustment of target end-tidal sevoflurane concentration in the sevoflurane group and sevoflurane+dexmedetomidine group, and at 10 min after the change of infusion rate in the propofol group and propofol+dexmedetomidine group. RESULTS: BIS values were linearly related to sevoflurane concentration and propofol infusion rate, with or without dexmedetomidine. Sevoflurane concentration at BIS=50 was 3.9±0.2% in the sevoflurane group and 2.6±0.3% in the sevoflurane+dexmedetomidine group. The propofol infusion rate to make BIS=50 was 102±5 mg∙kg(-1)∙hr(-1) in the propofol group, and 90±10 mg∙kg(-1)∙hr(-1) in the propofol+dexmedetomidine group. CONCLUSIONS: The optimal end-tidal concentration of sevoflurane alone was thus 3.9%, and optimal infusion rate for propofol alone was 102 mg∙kg(-1)∙hr(-1). Dexmedetomidine reduced sevoflurane requirement by 33% and propofol requirement by 11%.

Tissue-specific regulation of type III iodothyronine 5-deiodinase gene expression mediates the effects of prolactin and growth hormone in Xenopus metamorphosis.

Prolactin (PRL) and growth hormone (GH) are known to be able to act as antimetamorphic hormones. From investigations of how PRL inhibits Xenopus tail regression in vitro, it was found that the both hormones could, in addition to their known antimetamorphic actions, upregulate mRNA expression of type III iodothyronine 5-deiodinase (5D), an enzyme that inactivates thyroid hormones (TH). Conversely, both PRL and GH were found to downregulate 5D mRNA expression in the liver. Blockage by PRL of TH-induced tail regression in organ culture was released by treatment with iopanoic acid (IOP, an inhibitor of 5D activity). The IOP-released tail regression displayed a unique morphology of the larger fins retained on the regressing tails, consistent with the finding that mRNA for both PRL receptor and 5D were enriched in the fin. The results suggest that the metamorphosis-modulating actions of PRL and GH are mediated, at least partially, by tissue-specific regulation of 5D mRNA expression.