Peter P. C. Tan

Concentration and regional distribution of propofol in brain and spinal cord during propofol anesthesia in the rat

We evaluated the pharmacokinetics and regional distribution of propofol in the brain and spinal cord during propofol anesthesia in Sprague-Dawley rats, using high-performance liquid chromatographic determination of propofol concentration in brain, whole blood and plasma. We found that the concentration of propofol in the brain increased and decreased expeditiously during and after a 15-min and 30-min period of i.v. infusion of an anesthetic dose (60 mg/kg per h) of propofol. Furthermore, propofol was evenly distributed in the brain and spinal cord during infusion, with a significant inter-individual variation. Upon the establishment of anesthesia 15 and 30 min following intravenous infusion of propofol, the concentration of propofol in the brain, whole blood and plasma was respectively 15.7 +/- 1.9 and 39.4 +/- 2.7 micrograms/g, 4.5 +/- 1.2 and 13.6 +/- 1.3 micrograms/ml and 1.8 +/- 0.5 and 5.1 +/- 0.9 micrograms/ml (mean +/- SEM, n = 6 or 7). These high brain/blood and brain/plasma ratios during anesthesia suggest that propofol manifests a pharmacokinetic profile that is different from at least thiopental.

Video-Assisted Cardiac Surgery in Closure of Atrial Septal Defect

BACKGROUND Video-assisted endoscopy has been applied in the management of a variety of intrathoracic vascular lesions. Here we report its use in the correction of intracardiac congenital defects. METHODS Eight patients (3 male and 5 female) underwent operation for closure of an atrial septal defect. The patients ranged in age from 2.0 to 60.9 years (mean, 19.2 +/- 19.0 years). The patients weighed 11 to 66 kg (mean, 41.3 +/- 23.5 kg). The ratio of pulmonary blood flow to systemic blood flow ranged from 2.0 to 6.0 (mean, 3.4 +/- 1.3). The mean pulmonary artery pressure was 19.7 +/- 4.0 mm Hg (range, 13 to 24 mm Hg). The operations were performed through a right anterior minithoracotomy and guided by video-assisted endoscopic techniques under femorofemoral or femoral-right atrial extracorporeal circulation. The aorta was not cross-clamped, and the myocardium was protected by continuous coronary perfusion with hypothermic fibrillatory arrest (rectal temperature, 22.0 degrees +/- 2.0 degrees C). Transesophageal echocardiographic monitoring was maintained during the operations. The right atrium was entered after pericardiotomy. Primary closure of the defect was performed successfully in all patients. Conventional nondisposable instruments were used for dissection, grasping, suturing, and hemostasis. RESULTS The durations of extracorporeal circulation and operation ranged from 47 to 126 minutes (mean, 80 +/- 31 minutes) and from 2.2 to 4.5 hours (mean, 3.1 +/- 0.8), respectively. All patients recovered from the operation rapidly with an uneventful postoperative course. CONCLUSIONS Our experience demonstrates that video-assisted cardiac surgery is technically feasible and can be used with excellent results for the repair of congenital heart defects in general.

Video-assisted mitral valve operations

BACKGROUND Video-assisted endoscopy has been applied frequently in the management of a variety of surgical diseases. However, it has rarely been applied in mitral valve surgery. METHODS We report 2 patients who received emergency operations for thrombosis of a mitral prosthesis (patient 1, a 68-year-old man) and acute mitral regurgitation due to rupture of anterior chordae (patient 2, a 75-year-old woman). They both had severe congestive heart failure. Cardiogenic shock was noted in patient 2. The mitral valve was approached through a right anterior minithoracotomy with the aid of an endoscope by means of projected images on the video monitor under femorofemoral cardiopulmonary bypass. The aorta was not cross-clamped, and the myocardium was protected by continuous coronary perfusion with hypothermic fibrillatory arrest. The left atrium was entered posterior to the interatrial groove. Thrombectomy and mitral valve repair were performed successfully. RESULTS The duration of extracorporeal circulation was 204 and 147 minutes, respectively. Both patients recovered from the operation rapidly with uneventful postoperative courses. CONCLUSIONS Our preliminary results suggest that video-assisted endoscopic cardiac surgery is technically feasible and could be performed in the milieu of open heart surgery.

Minimally Invasive Cardiac Surgical Techniques in the Closure of Ventricular Septal Defect: An Alternative Approach

BACKGROUND Minimally invasive cardiac surgical techniques recently have been applied in the management of a variety of intracardiac lesions. METHODS Fourteen patients (6 boys and 8 girls; age, 8.9 +/- 5.5 years; body weight, 29.0 +/- 13.5 kg) were operated on using minimally invasive cardiac surgical techniques for the closure of a ventricular septal defect (subarterial in 11 patients and perimembranous in 3 patients). The operations were performed through a left anterior minithoracotomy and were guided by video-assisted endoscopic techniques under femorofemoral cardiopulmonary bypass. The myocardium was protected by continuous coronary perfusion with hypothermic fibrillatory arrest. The right ventricular outflow tract was entered after pericardiotomy was performed. RESULTS Closure of the defect (directly in 4 patients and by patch in 10 patients) was performed successfully in all patients. A right ventricular outflow tract obstruction and ruptured sinus of Valsalva aneurysm also were repaired in 1 patient each. The duration of cardiopulmonary bypass was 41 +/- 10 minutes (range, 28 to 100 minutes) and the total operative time was 2.2 +/- 0.8 hours (range, 1.3 to 3.5 hours). All the patients recovered rapidly from their operation and had an uneventful postoperative course. Follow-up (mean, 6.2 months; range, 6 to 9 months) was complete in all patients. There were no late deaths. Transthoracic echocardiographic examination showed no residual shunt and no aortic regurgitation in all patients. CONCLUSIONS Our experience demonstrates that minimally invasive cardiac surgical techniques are technically feasible and an alternative option for the repair of a ventricular septal defect.

Modulation of naloxone-precipitated morphine withdrawal syndromes in rats by neuropeptide FF analogs

Neuropeptide FF (NPFF) has been reported to be an endogenous anti-opioid peptide that has significant effects on morphine tolerance and dependence. In the present study, we examined the chronic effects of NPFF and its synthetic analogs: the putative agonist, PFRFamide, and the putative antagonists, dansyl-PQRamide and PFR(Tic)amide on naloxone-precipitated morphine withdrawal syndromes in rats. After a 5-day co-administration with morphine [5 mg/kg, intraperitoneally (i.p.), twice per day (b.i.d.)] and the tested peptide [intracerebroventricularly (i.c.v.) or i.p., b.i.d.], naloxone (4 mg/kg, i.p.) was given systemically to evaluate the severity of the morphine withdrawal syndromes. Our results revealed that NPFF significantly potentiated the overall morphine withdrawal syndromes and, on the contrary, dansyl-PQRamide attenuated these syndromes. These results clearly indicate that modulation of the NPFF system in the mammalian central nervous system has significant effects on opiate dependence. In addition, morphine withdrawal syndromes could be practically applied as a valid parameter to functionally characterize the putative NPFF agonists and antagonists.

Modulations of spinal serotonin activity affect the development of morphine tolerance.

To test whether modulations of spinal serotonin (5-HT) levels would affect the development of morphine tolerance, we treated rats with either intrathecal 5-HT or 5,7-dihydroxytryptamine (5,7-DHT; a 5-HT neurotoxin) in addition to systemic infusion with morphine (2 mg · kg−1 · h−1). Continuous infusion of 5-HT (10 &mgr;g · 6 &mgr;L−1 · h−1) into the lumbar subarachnoid space of rats for 9 h accelerated the development of morphine tolerance. The area under the curve for the tail-flick latency test was 454.1 ± 35.1 in the Sham Control group vs 327.6 ± 41.0 in the 5-HT-Infused group. &mgr;-opioid receptor binding in the lumbar spinal cord showed a decrease in the Bmax (maximal binding −46.5%), but not the binding affinity (Kd), in 5-HT-infused rats. However, intrathecal injection of 5,7-DHT (50 &mgr;g), which resulted in a 48% reduction in 5-HT and 51% reduction in 5-hydroxyindoleacetic acid concentrations, led to an attenuation of morphine tolerance (the area under the curve was 613.0 ± 24.7 in the 5,7-DHT-Lesioned group). The binding study indicated that the affinity of lumbar &mgr;-opioid receptors decreased 196% in 5-HT-depleted rats, whereas there was no effect on apparent binding. The infusion of 5-HT (10 &mgr;g · 6 &mgr;L−1 · h−1) was not analgesic and the 5,7-DHT-induced lesion did not affect acute morphine-induced analgesia. We conclude that activity of spinal 5-HT-containing neurons plays a crucial role during the development of morphine tolerance.

Propofol anesthesia increases dopamine and serotonin activities at the somatosensory cortex in rats: a microdialysis study.

We sought to estimate the activities of dopamine and serotonin in animals receiving propofol anesthesia.The in vivo microdialysis technique was used in Sprague-Dawley rats (n = 6) to measure the major metabolites of dopamine and serotonin, i.e. 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (4-hydroxy-3-methyphenylacetic acid; HVA) and 5-hydroxy indole acetic acid (5-HIAA) in the somatosensory cortex. We also measured the levels of propofol in the brain and blood by microdialysis sampling in another group of rats (n = 6). During the experiment, the rat was infused intravenously (IV) with propofol at a rate of 10 mg [centered dot] kg-1 [centered dot] h-1 for 60 min and 60 mg [centered dot] kg-1 [centered dot] h-1 for 40 min. We found that IV infusion of propofol at a rate of 60 mg [centered dot] kg-1 [centered dot] h-1 significantly increased DOPAC, HVA, and 5-HIAA. We also determined that these changes correlated well with propofol levels in the brain and blood. We concluded that anesthetic doses of propofol increased the functional activities of dopamine and serotonin in the cortex. These increases correlate well with propofol levels in the cortex and blood. (Anesth Analg 1997;84:1344-8)

Neurotensin excitation of serotonergic neurons in the rat nucleus raphe magnus: ionic and molecular mechanisms

To understand the cellular and molecular mechanisms by which neurotensin (NT) induces an analgesic effect in the nucleus raphe magnus (NRM), whole-cell patch-clamp recordings were performed to investigate the electrophysiological effects of NT on acutely dissociated NRM neurons. Two subtypes of neurons, primary serotonergic and secondary non-serotonergic cells, were identified from acutely isolated NRM neurons. During current-clamp recordings, NT depolarized NRM serotonergic neurons and evoked action potentials. Voltage-clamp recordings showed that NT excited serotonergic neurons by enhancing a voltage-insensitive and non-selective cationic conductance. Both SR48692, a selective antagonist of subtype 1 neurotensin receptor (NTR-1), and SR 142948A, a non-selective antagonist of NTR-1 and subtype 2 neurotensin receptor (NTR-2), failed to prevent neurotensin from exciting NRM serotonergic neurons. NT-evoked cationic current was inhibited by the intracellular administration of GDP-beta-S. NT failed to induce cationic currents after dialyzing serotonergic neurons with the anti-G(alphaq/11) antibody. Cellular Ca(2+) imaging study using fura-2 showed that NT induced the calcium release from the intracellular store. NT-evoked current was blocked after the internal perfusion of heparin, an IP(3) receptor antagonist, or BAPTA, a fast Ca(2+) chelator. It is concluded that neurotensin enhancement of the cationic conductance of NRM serotonergic neurons is mediated by a novel subtype of neurotensin receptors. The coupling mechanism via G(alphaq/11) proteins is likely to involve the generation of IP(3), and subsequent IP(3)-evoked Ca(2+) release from intracellular stores results in activating the non-selective cationic conductance.

Epidural dexamethasone reduces the incidence of backache after lumbar epidural anesthesia

We performed a prospective, randomized, double-blind study to compare the effect of epidural dexamethasone on the incidence of postepidural backache after nonobstetric surgery. One thousand unpremedicated, ASA physical status I or II patients scheduled for hemorrhoidectomy were randomly assigned to two groups: Group I patients received 25 mL 2% lidocaine with epinephrine 1:200,000 and 1 mL normal saline epidurally and Group II patients received 25 mL 2% lidocaine with epinephrine 1:200,000 and 1 mL dexamethasone (5 mg) epidurally. Patients were interviewed at 24, 48, and 72 h postoperatively using a standard visual analog scale (VAS) for evaluation of postepidural backache. A patient was considered to have postepidural backache when the postoperative VAS score was higher than the preoperative score. The incidences of postepidural backache in Group I patients for the 3 days were 22.8%, 17.4%, and 9.2%, all of which were significantly more frequent than observed in Group II patients (7.4%, 5.6%, and 2.8%, P < 0.01). The severity and duration of postepidural backache were also significantly decreased in Group II patients. In our study, there was a significant association between postepidural backache and multiple attempts at epidural needle insertion. In summary, epidural dexamethasone reduced the incidence and severity of postepidural backache. (Anesth Analg 1997;84:376-8)

Surgical closure of atrial septal defect. Minimally invasive cardiac surgery or median sternotomy

AbstractBackground: Closure of ostium secundum atrial septal defect (ASD) vis median sternotomy (MS) is a simple procedure for most cardiac surgeons. Minimally invasive cardiac surgery (MICS) has recently been applied in the management of intracardiac lesions. Methods: We report our experience in surgical closure of isolated ASD via MICS in 60 patients and via MS in 58 patients. There was no difference between these two groups in gender, age, body weight, ratio of systemic to pulmonary blood flow, and pulmonary arterial pressure. Results: The duration of cardiopulmonary bypass was significantly longer in the MICS group than in the MS group [27 to 126 min (42 ± 12) and 14 to 158 min (27 ± 11), respectively; (p < 0.001]. However, the length of incision, incidence of temporary pacemaker wire insertion rate, duration of endotracheal intubation, timing of oral intake, postoperative day drainage amount, incidence of parenteral analgesic injection, postoperative length of stay, and return to normal activity interval were significant shorter and lower in patients of the MICS group than in those of the MS group. All the patients recovered rapidly from the surgery. Follow-up was complete in all patients, with no late complications and no residual shunt. Conclusion: Our results suggest that MICS is a good option for surgical closure of ASD.