Biomedical subjects

Akira Asada

Publications and source records attributed to Akira Asada.

At least 19 recordsLinked to original sources

PubMed2006

Repeated dexmedetomidine infusions, a postoperative living-donor liver transplantation patient.

Here we report on a postoperative living-donor liver transplantation (LDLT) patient who received nightly infusions of dexmedetomidine (DEX), a specific alpha2-adrenergic receptor agonist, to treat agitation and insomnia during an intensive care unit stay. The infusion rate was adjusted according to the Ramsay sedation score. The actual plasma concentrations were higher than the values predicted by RugLoop software package simulation 9 h after the DEX infusion. However, all of the measurements were within the therapeutic range for DEX. Thus, DEX infusion could be safely used in the postoperative LDLT patient by employing a simple consciousness scale.

Adrenergic alpha-Agonists↗

PubMed2006

Epinephrine increases the extracellular lidocaine concentration in the brain: a possible mechanism for increased central nervous system toxicity.

BACKGROUND: Local anesthetics exert central nervous system (CNS) toxicity by inhibiting intracerebral neuronal activity, while epinephrine augments the CNS toxicity of intravenously administered local anesthetics. Viewed together, increases of extracellular concentrations of local anesthetics in the brain may be directly associated with increased CNS toxicity. The authors examined the hypothesis that epinephrine enhances the CNS toxicity of lidocaine by increasing the extracellular concentration in the brain. METHODS: An awake, spontaneously breathing rat model was used. Twenty male Sprague-Dawley rats received an intravenous infusion of lidocaine (3 mg x kg x min; group C) or lidocaine with epinephrine (3 mg x kg x min and 2 microg x kg x min, respectively; group E) for 10 min (n = 10 in each group). Effects of epinephrine on the convulsive dose and concentrations of total (protein-bound and unbound) and unbound lidocaine in plasma were examined. Concentrations of extracellular lidocaine in the cerebral nucleus accumbens were quantitatively determined by a microdialysis method. RESULTS: The convulsive dose of lidocaine was significantly lower in group E than in group C (22.4 +/- 5.5 vs. 27.9 +/- 3.1 mg/kg, respectively; P < 0.05). Overall concentrations and area under the plasma concentration-versus-time curve of unbound lidocaine in group E were significantly higher than those in group C. Concentrations of extracellular lidocaine in the nucleus accumbens in group E were comparable to those of unbound fraction in plasma and were also significantly higher than those in group C. CONCLUSIONS: Concomitant administration of epinephrine significantly enhanced the CNS toxicity of intravenously administered lidocaine. Increased extracellular concentration in the brain would be related to this mechanism.

Animals↗

PubMed2006

Duration of dialysis is a significant predictor of prolonged postoperative mechanical ventilation in dialysis-dependent patients undergoing cardiac surgery.

Prolonged mechanical ventilation is reported to correlate with increased risk of mortality after cardiac surgery. We designed the present study to determine the preoperative and intraoperative risk factors that could predict postoperative prolonged mechanical ventilation in dialysis-dependent patients undergoing cardiac surgery with cardiopulmonary bypass. Forty-four dialysis-dependent patients were divided into two groups; patients of group E were tracheally extubated within 24 h after admission to the intensive care unit postoperatively (n = 19) and patients of group L (n = 25) required more than 24 h of mechanical ventilation. All patients received hemofiltration during cardiopulmonary bypass and continuous veno-venous hemodialysis postoperatively. A multiple logistic regression analysis showed that duration of dialysis (>10 yr) and duration of surgery (>8 h) were independent risk factors of prolonged mechanical ventilation (>24 h). On admission to the intensive care unit, Pao2/Fio2 of group L was significantly lower than that of group E (294 +/- 135 versus 415 +/- 99 mm Hg) and the circulatory status of group L was worse than that of group E. The median (interquartile range) duration of intensive care unit stay in group E was 3 (3.00) days, which was significantly shorter than that of group L (5 [2.75] days). It is possible that longer surgery increases the likelihood of cardiac dysfunction and poor oxygenation in patients with a long history of dialysis.

Aged↗

PubMed2006

Nitrous oxide induces paradoxical electroencephalographic changes after tracheal intubation during isoflurane and sevoflurane anesthesia.

In this randomized, double-blind, controlled study, we tested the hypothesis that nitrous oxide (N2O) affects bispectral index (BIS) and 95% spectral edge frequency (SEF95) in response to tracheal intubation during anesthesia with isoflurane and sevoflurane. In protocol 1, we randomly allocated 90 ASA physical status I patients to 6 groups (n = 15 each). Anesthesia was induced with isoflurane or sevoflurane with 0%, 33%, or 66% N2O. The concentration of isoflurane and sevoflurane was gradually increased and end-tidal concentrations were maintained at 1.1% and 1.7%, respectively. Tracheal intubation was performed 12 min after induction of anesthesia. BIS was significantly increased 1 min after tracheal intubation compared before laryngoscopy in patients receiving only isoflurane or sevoflurane (P = 0.001 and 0.007, respectively). In patients receiving 66% N2O-isoflurane or 66% N2O-sevoflurane, both BIS and SEF95 were significantly decreased after tracheal intubation and significantly lower than in those patients receiving only isoflurane or sevoflurane, respectively (P < 0.01 for both). In protocol 2, 3 microg/kg of IV fentanyl completely abolished the decrease of BIS and SEF95 after tracheal intubation during anesthesia with 66% N2O-isoflurane and 66% N2O-sevoflurane (n = 10). We conclude that 66% N2O induced a paradoxical decrease of BIS in response to tracheal intubation during anesthesia with isoflurane and sevoflurane.

Adult↗

PubMed2006

[The use of questionnaires for rotating residents in evaluating training in anesthesiology].

BACKGROUND: We prepared questionnaires for the rotating residents during their assignment for anesthesiology in the novel Japanese residency programs for the year 2004. METHODS: Questionnaires consisting of 39 items with 235 model answers for these items were prepared. The residents underwent three interviews by these questionnaires over the three-month training period. The number of correct answers for these questionnaires was recorded and evaluated using a computer database software. RESULTS: There was no significant correlation between the results of these questionnaires and the subjective evaluation by supervisors conducted during clinical training. On stepwise regression analysis, the results of the questionnaires for "American Society of Anesthesiologists Physical Status", "contraindications for epidural anesthesia", "complications of general anesthesia" and "initial procedures for patients in the operating room" correlated with the subjective evaluation by supervisors. CONCLUSIONS: Stepwise regression analysis was shown to be helpful in improving the questionnaires regarding the training in anesthesiology.

Anesthesiology↗

PubMed2006

The application of the hemoglobin saturation sensor and indocyanine green (ICG) for blood flow measurement.

BACKGROUND: The aim in this study is to evaluate a new blood flow measurement applying a hemoglobin saturation sensor and indocyanine green (ICG) in circuit and animal models. METHODS: 1) In the basic study, the blood was mixed in a tube with ICG, and a near-infrared sensor was placed in this tube. The standard curve of the relationship between ICG concentration and optical density was obtained. 2) In the circuit model, the blood was circulated by the roller pump. ICG was injected in this circuit and its concentration was calculated from the change in optical density at 810 nm. Rate of flow was calculated based on the Fick's principle. The validity of this method was evaluated by Bland and Altman analysis. 3) In the animal model, a hemoglobin saturation sensor was inserted into three anesthetized dogs via the jugular vein, and iced ICG was injected for calculating cardiac output. Cardiac output was calculated by the same theory of the circuit model. The validity of this method was also evaluated by Bland and Altman analysis. RESULTS: 1) A standard curve was drawn from 11 different points (r2=0.99). 2) The calculated flow rate correlated well with the actual flow rate (r2=0.97). 3) The calculated cardiac output correlated well with results obtained with the thermodilution method. CONCLUSIONS: Application of a hemoglobin saturation sensor and ICG to blood flow measurement was reliable and useful in both circuit and animal models. This method may be clinically useful for measurement of blood flow.

Animals↗

PubMed2005

Risk factors for prolonged ICU stay in patients following coronary artery bypass grafting with a long duration of cardiopulmonary bypass.

PURPOSE: Risk factors for prolonged stay in the intensive care unit (ICU) in patients following coronary artery bypass grafting (CABG) have been reported in many previous studies. However few have focused on circulatory and respiratory status as immediate postoperative risk factors. Therefore we examined immediate postoperative risk factors for prolonged ICU stay after CABG with a long duration of cardiopulmonary bypass (CPB). METHODS: We studied retrospectively 100 consecutive patients undergoing elective CABG with CPB. Patients were excluded from this study if the duration of aortic cross-clamping was less than 60 min. Patients were divided into three groups according to the duration of the ICU stay. Patients in group A (n = 68) were discharged from the ICU on the next morning after surgery, those in group B (n = 19) stayed for 3 days, and group C (n = 13) stayed for more than 3 days. Perioperative variables were compared among the three groups and we demonstrated risk factors for prolonged (more than 3 days) ICU stay. RESULTS: There were significant differences in duration of CPB (157 +/- 34 versus 184 +/- 48 minutes, P < 0.05) and aortic cross-clamping (119 +/- 32 versus 141 +/- 40 min) between groups A and B. On the other hand, there were significant differences in age (62.8 +/- 7.8 versus 67.4 +/- 6.2 years), mean pulmonary artery pressure (MPAP) (17 +/- 2 versus 22 +/- 3 mmHg), and Pa(O2)/FI(O2) (PF ratio) (409 +/- 94 versus 303 +/- 108 mmHg) on admission to the ICU between groups A and C. There were no significant differences in intraoperative fluid balance and duration of CPB. Multiple logistic regression analysis identified age (>65 years), MPAP (>21 mmHg), and PF ratio (<300 mmHg) as independent risk factors for more than a 3-day ICU stay. CONCLUSION: Advanced age, increased MPAP, and decreased PF ratio on admission to the ICU were significant risk factors for a prolonged ICU stay of more than 3 days.

Aged↗

PubMed2005

Cesarean section at 28 weeks' gestation with resection of pheochromocytoma: perioperative antihypertensive management.

Pregnancy complicated by pheochromocytoma is potentially fatal. Pregnancy and labor increase the risk of hypertensive crisis as it may occur with the sudden release of catecholamine accompanying uterine contractility and straining. However, antepartum diagnosis reduces both maternal and fetal mortality, allowing for safe cesarean section and resection of tumor. We describe the management of perioperative hypertension for combined cesarean section and pheochromocytoma resection.

Adrenal Gland Neoplasms↗

PubMed2005

Dexmedetomidine decreases the convulsive potency of bupivacaine and levobupivacaine in rats: involvement of alpha2-adrenoceptor for controlling convulsions.

Dexmedetomidine, a highly selective alpha(2)-adrenoceptor agonist, is used in combination with local anesthetics for sedation and analgesia. We tested the hypothesis that dexmedetomidine used for sedation alters the convulsive potency of racemic bupivacaine and levobupivacaine in awake, spontaneously breathing rats. In the first experiments, male Sprague-Dawley rats were randomly divided into six groups: bupivacaine with no dexmedetomidine (bupivacaine control; BC), bupivacaine with small-dose dexmedetomidine (BS), bupivacaine with large-dose dexmedetomidine (BL), levobupivacaine with no dexmedetomidine (levobupivacaine control; LC), levobupivacaine with small-dose dexmedetomidine (LS), and levobupivacaine with large-dose dexmedetomidine (LL) (n = 10 for each group). Continuous infusion of dexmedetomidine (Groups BC and LC, 0 microg x kg(-1) x h(-1); Groups BS and LS, 3.6 microg x kg(-1) x h(-1); and Groups BL and LL, 10.8 microg x kg(-1) x h(-1)) was started after bolus injection (Groups BC and LC, 0 microg/kg; Groups BS and LS, 0.5 microg/kg; and Groups BL and LL, 1.5 microg/kg). Fifteen minutes after the start of the dexmedetomidine infusion, continuous infusion of bupivacaine (Groups BC, BS, and BL) or levobupivacaine (Groups LC, LS, and LL) at 1 mg x kg(-1) x min(-1) was started and continued until tonic/clonic convulsions occurred. Dexmedetomidine achieved significantly different sedation levels both in Groups BC, BS, and BL and in Groups LC, LS, and LL (P < 0.05). Convulsive doses of bupivacaine and levobupivacaine were significantly larger in Groups BL and LL than in Groups BC and LC, respectively (P < 0.01 for both). Concentrations of bupivacaine and levobupivacaine in plasma and in brain at the onset of convulsions were also larger in Groups BL and LL than in Groups BC and LC (P < 0.01 for both). In the second experiment, yohimbine (1 mg/kg) administered 10 min before and 5 min after the start of dexmedetomidine infusion completely reversed the sedative effect of dexmedetomidine (bolus 1.5 microg/kg, followed by 10.8 microg x kg(-1) x h(-1)). Convulsive doses and plasma and brain concentrations of bupivacaine and levobupivacaine at the onset of convulsions in rats receiving yohimbine and dexmedetomidine were significantly smaller than in those receiving only dexmedetomidine (P < 0.05 for all) and were similar to those without dexmedetomidine or yohimbine. We conclude that dexmedetomidine used for sedation decreases the convulsive potency of both bupivacaine and levobupivacaine in rats. Alpha(2)-adrenoceptor agonism may be involved in this anticonvulsant potency.

Animals↗

PubMed2005

The short-acting beta1-adrenoceptor antagonists esmolol and landiolol suppress the bispectral index response to tracheal intubation during sevoflurane anesthesia.

In this randomized, double-blind, controlled study, we tested the hypothesis that the short-acting beta(1)-adrenoceptor antagonists esmolol and landiolol suppress hemodynamic changes and bispectral index (BIS) increases, both of which are induced by tracheal intubation under general anesthesia with sevoflurane alone. Forty-five patients were randomly assigned to the control, esmolol, and landiolol groups (n = 15 each). Anesthesia was induced with sevoflurane in oxygen, with an end-tidal concentration maintained at 1 minimum alveolar anesthetic concentration (MAC). Infusion of saline (control group), esmolol (bolus of 1 mg/kg and then 0.25 mg x kg(-1) x min(-1); esmolol group), or landiolol (bolus of 0.125 mg/kg and then 0.04 mg x kg(-1) x min(-1); landiolol group) was started 5 min after the induction of anesthesia and was continued throughout the study. Tracheal intubation was performed 12 min after anesthesia induction. There were no differences in overall changes of mean arterial blood pressure among the three groups, whereas, at 1-5 min after tracheal intubation, heart rate increased in all groups but was significantly slower in the esmolol and landiolol groups than in the control group (P < 0.05). BIS was between 96 and 98 for all patients at baseline and decreased during the induction of anesthesia. There were no differences in BIS among the three groups before laryngoscopy (39 +/- 5, 39 +/- 5, and 38 +/- 4 in the control, esmolol, and landiolol groups, respectively). BIS increased significantly in the control group (54 +/- 10; P < 0.05) 1 min after intubation, whereas it remained unchanged in the esmolol and landiolol groups (45 +/- 10 and 41 +/- 6, respectively). In conclusion, the increase in both heart rate and BIS after tracheal intubation under 1 MAC sevoflurane anesthesia was suppressed by the concomitant administration of either esmolol or landiolol.

Adrenergic beta-1 Receptor Antagonists↗

PubMed2005

[General anesthesia by propofol infusion for delivery by cesarean section compared with sevoflurane anesthesia using bispectral index (BIS) monitoring].

BACKGROUND: We compared the postoperative effects of propofol and sevoflurane used for anesthesia during elective cesarean section, using bispectral index (BIS) monitoring. METHODS: Fourteen parturients were randomized into two groups (Propofol group; P group, Sevoflurane group; S group). All patients received thiopental and suxamethonium for induction and had orotracheal intubation in rapid sequence. All patients received 1% sevoflurane until delivery. In the P group, sevoflurane was stopped after delivery and propofol infusion was started, to achieve target BIS values below 60; the infusion rate was 6. 17 +/- 0.98 mg x kg(-1) x h(-1). Patients in the S group received 1% sevoflurane. All patients were given fentanyl and vecuronium as required. RESULTS: There were no significant differences between the two groups in their times for beginning drinking, walking, eating or removal of urinary catheters after the operations. There were no significant differences in total blood loss or intraoperative dose of oxytocin, but postoperative and total doses of oxytocin were significantly higher in those in the P group. CONCLUSIONS: Comparing the effects of propofol and sevoflurane on the postoperative condition of parturients, no differences could be detected. We can choose to use propofol instead of sevoflurane for cesarean section.

Adult↗

PubMed2005

[Lumbar epidural morphine for postoperative analgesia in children undergoing Nuss procedure].

BACKGROUND: We examined the effects of lumbar epidural morphine for postoperative analgesia in children after the Nuss procedure for funnel chest. METHODS: An epidural catheter was inserted from the L 3-4 interspace preoperatively (epidural group). Epidural morphine 30 microg x kg(-1) was given at the beginning of the operation. Postoperatively, epidural morphine 3 microg x kg(-1) x hr(-1) was infused. The frequency of demand for postoperative analgesia was retrospectively compared with that of children who had not received epidural morphine (control group). RESULTS: On the 0th postoperative day, the epidural group required fewer analgesics than the control group (0.50+/-0.30 vs. 2.50+/-1.00 x day(-1)). However, after the 1st postoperative day, the demand for analgesia did not differ between the two groups. CONCLUSIONS: Epidural morphine 30 microg x kg(-1) given at the beginning of operation provided effective analgesia on the 0th postoperative day after the Nuss procedure. However, epidural infusion of morphine 3 microg x kg(-1) x hr(-1) was not effective after the 1st postoperative day. Further study is needed to determine the lumbar epidural infusion dose of morphine adequate for use after the Nuss procedure.

Analgesia, Epidural↗

PubMed2005

[A comparison of propranolol with esmolol for the treatment of tachycardia during emergence from anesthesia].

BACKGROUND: Treating tachycardia occurring during emergence from general anesthesia is of the highest priority, because it frequently induces myocardial ischemia. Therefore we retrospectively compared the efficacy of esmolol with that of propranolol against such tachycardia. METHODS: Propranolol (n=22) or esmolol (n= 29) was given intravenously when the heart rate was above 100 beats x min(-1) during emergence from anesthesia. The drugs were titrated to decrease the heart rate the level before the induction of anesthesia. RESULTS: The total dose of propranolol was 0.52+/-0.21 mg (mean+/-SD), which decreased the heart rate significantly from 109.2 +/- 19.0 to 89.2 +/-11.8 beats x min(-1). The total dose of esmolol was 32.8 +/- 16.2 mg, which decreased the heart rate significantly from 110.0+/-13.9 to 84.9+/-10.7 beats x min(-1). The time required for the maximum effect of esmolol (3.2 1.8 min) was significantly shorter than that of propranolol (8.2 +/- 4.9 min). There were no episodes of adverse effects in either group. CONCLUSIONS: Both propranolol and esmolol are equally effective and safe for the treatment of tachycardia during emergence from anesthesia. The time required for the maximum effect of esmolol was shorter than that of propranolol, indicating an advantage of esmolol.

Adrenergic beta-Antagonists↗

PubMed2005

A new method for measuring total coronary blood flow using the lithium dilution method.

BACKGROUND: The aim in this study is to evaluate a new method of measuring total coronary blood flow (TCBF) in (1) an in vitro model and in (2) an animal model by the lithium dilution method. METHODS: (1) Ringer's solution was circulated in a closed circuit with the main flow as a systemic circulation, and the side flow as a coronary circulation by a roller pump. Two peaks originating from the main and side flow were recorded by the lithium dilution method. The flow was calculated using the Fick principle based on the ratio of the areas under the curve. The validity of this method was evaluated by Bland Altman analysis. (2) Four beagles were anesthetized and subjected to insertion of two pulmonary artery catheters. The position of the catheters was confirmed as being in the pulmonary artery and in the right atrium. Lithium chloride solution was injected into the pulmonary artery and the change in lithium concentration at the right atrium was recorded. TCBF was estimated by the method used in the in vitro study. RESULTS: (1) The calculated flow correlated well with the actual flow (r2 = 0.86). (2) The estimated TCBF at baseline, with low-dose nitroglycerin, and with high-dose nitroglycerin was 206 +/- 43.0 mL/min, 304 +/- 50.3 mL/min, and 348 +/- 50.1 mL/min, respectively (mean +/- SE). TCBF was significantly increased by nitroglycerin infusion. CONCLUSION: A new method of measuring TCBF using the lithium dilution method was reliable and useful both in vitro and in an animal model. This may be clinically useful method for measuring TCBF.

Animals↗

PubMed2004

Comparative effects of valsartan versus amlodipine on left ventricular mass and reactive oxygen species formation by monocytes in hypertensive patients with left ventricular hypertrophy.

OBJECTIVES: To compare the effects of the angiotensin receptor blocker (ARB) valsartan versus the calcium channel blocker amlodipine, reactive oxygen species (ROS) formation by monocytes, C-reactive protein (CRP), and left ventricular (LV) mass were studied in 104 hypertensive patients with left ventricular hypertrophy (LVH). BACKGROUND: There is evidence that ARBs have blood pressure (BP)-independent effects on LV mass. Whether regression of LV mass by ARBs is correlated to ROS formation by monocytes and CRP is not fully understood yet. METHODS: A cross-sectional and prospective study was performed. Participants were randomly assigned to either the 80-mg valsartan (n = 52) or 5-mg amlodipine (n = 52) group and were treated for eight months. The left ventricular mass index (LVMI) was calculated from two-dimensional M-mode echocardiography. Formation of ROS by monocytes was measured by gated flow cytometry. In addition, CRP, plasma renin activity, plasma aldosterone, and traditional risk factors were assessed. RESULTS: Multiple regression analysis showed a significant correlation between LVMI and ROS formation by monocytes and between LVMI and CRP. Treatment reduced BP to a similar extent in both groups. Valsartan significantly reduced LVMI after eight months, but amlodipine had less effect (16% vs. 1.2%, n = 50, p < 0.01). Formation of ROS by monocytes was reduced to a greater extent with valsartan than with amlodipine (28% vs. 2%, n = 50, p < 0.01). Valsartan but not amlodipine reduced CRP levels. A significant correlation between changes in ROS formation by monocytes and LVMI or between CRP and LVMI was observed. CONCLUSIONS: The ARB valsartan has BP-independent effects on LVH, ROS formation by monocytes, and CRP in hypertensive patients with LVH.

Amlodipine↗

PubMed2004

Effects of carvedilol on oxidative stress in polymorphonuclear and mononuclear cells in patients with essential hypertension.

PURPOSE: To compare the effects of carvedilol and propranolol on oxidative stress in leukocytes and C-reactive protein levels in patients with hypertension. METHODS: Sixty hypertensive patients were randomly assigned to carvedilol (20 mg; n = 30) or propranolol (60 mg; n = 30) for 6 months. Thirty normotensive subjects who were given placebo served as controls. Oxidative stress in polymorphonuclear cells and mononuclear cells were measured by gated flow cytometry. C-reactive protein levels were measured by immunonephelometric assay. RESULTS: Oxidative stress in polymorphonuclear cells and mononuclear cells was increased significantly in hypertensive patients compared with in normotensive controls. After 6 months of treatment, carvedilol decreased oxidative stress significantly in polymorphonuclear cells by a mean of 45 arbitrary units (95% confidence interval [CI]: 32 to 59 arbitrary units; P <0.001) and propranolol decreased oxidative stress significantly by 20 arbitrary units (95% CI: 7 to 33 arbitrary units; P <0.003; P = 0.001 for difference between treatments). Carvedilol also decreased oxidative stress significantly in mononuclear cells by 23 arbitrary units (95% CI: 15 to 31 arbitrary units; P <0.001), whereas propranolol decreased oxidative stress by 2 arbitrary units (95% CI: 7 to 12 arbitrary units; P = 0.62; P = 0.002 for difference between treatments). Carvedilol decreased C-reactive protein levels significantly by a median of 0.073 mg/dL (interquartile range, 0.034 to 0.112 mg/dL; P <0.001), whereas propranolol decreased levels by 0.012 mg/dL (interquartile range, 0.009 to 0.032 mg/dL; P = 0.26; P = 0.003 for difference between treatments). CONCLUSION: These findings suggest that carvedilol inhibits oxidative stress in polymorphonuclear and mononuclear cells, as well as lowers C-reactive protein levels, to a greater extent than does propranolol in hypertensive patients.

Adrenergic beta-Antagonists↗

PubMed2004

Pharmacological and clinical studies with temocapril, an angiotensin converting enzyme inhibitor that is excreted in the bile.

Temocapril is an angiotensin converting enzyme inhibitor (ACEI), a prodrug with a thiazepine ring. Its active form, temocaprilat, is slightly more potent than enalaprilat in inhibiting ACE isolated from rabbit lung. The inhibitory potency of temocaprilat on isolated rat aorta is 3 times that of enalaprilat. Temocapril is excreted in the bile and urine and can be used in patients with renal insufficiency. It reduces blood pressure without causing any significant change in heart rate or cardiac output. Temocapril has been reported to improve endothelial dysfunction in vitro by suppressing increased oxidative stress. In vivo it improves reactive hyperemia in patients with essential hypertension. It has been reported to prevent coronary vascular remodeling in vivo by suppressing local ACE and increased oxidative stress. In humans temocapril has been found to improve insulin resistance partly by increasing adiponectin levels. Cardiac remodeling was improved by temocapril not only in experiment animals but also in humans. It improves renal function and decreases urinary albumin excretion in diabetics as well as in hypertensive patients. Temocapril is currently marketed only in Japan. Considering its beneficial effects and unique pharmacokinetics, temocapril, is likely to be introduced in other countries as well.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2004

Vasodilation increases the threshold for bupivacaine-induced convulsions in rats.

UNLABELLED: Bupivacaine affects the vascular resistance by peripheral and central nervous system (CNS) mechanisms. As vasoconstrictors increase the CNS toxicity of IV bupivacaine, vasodilators may decrease its CNS toxicity. We examined the hypothesis that vasodilators decrease the CNS toxicity of bupivacaine in awake, spontaneously breathing rats. Male Sprague-Dawley rats were randomly divided into control (C), nicardipine (N), and phentolamine (P) groups (n = 12 in each group). Racemic bupivacaine was administered IV at 1 mg/kg/min until tonic/clonic convulsions occurred. Saline, nicardipine (0.4 microg/min), and phentolamine (10 microg/min within 5 min, 50 microg/min thereafter) were simultaneously administered with bupivacaine in groups C, N, and P, respectively. Mean arterial blood pressure was significantly increased by infusion of bupivacaine in group C and was maintained at baseline levels before the onset of convulsions in groups N and P. The convulsive dose of bupivacaine in group C was 5.8 +/- 1.5 mg/kg, but was significantly larger in groups N and P (7.6 +/- 1.5 and 8.1 +/- 1.1 mg/kg, P = 0.02 and 0.001, respectively). However, there were no differences in total or protein-unbound plasma concentration of bupivacaine or in concentration of bupivacaine in the brain at the onset of convulsions among the 3 groups. We conclude that nicardipine and phentolamine increase the cumulative dose but do not affect the threshold plasma or brain concentrations required for bupivacaine-induced convulsions. IMPLICATIONS: Bupivacaine, a long-acting local anesthetic, induces central nervous system toxicity when its plasma concentration is increased. Nicardipine and phentolamine increased the cumulative dose but did not affect the threshold plasma concentrations, required for bupivacaine-induced convulsions, suggesting that both nicardipine and phentolamine inhibited the increase in the plasma concentration of bupivacaine by inducing peripheral vasodilation.

Adrenergic alpha-Antagonists↗