Differential Effects of Etomidate and Midazolam on Vascular Adenosine Triphosphate-sensitive Potassium Channels: Isometric Tension and Patch Clamp Studies

Background: The aim of this study was to investigate the effects of two imidazoline-derived intravenous anesthetics, etomidate and midazolam, on vascular adenosine triphosphate-sensitive potassium (KATP) channel activity.

Methods: In isolated rat aorta, isometric tension was recorded to examine the anesthetic effects on vasodilator response to levcromakalim, a selective KATP channel opener. Using the patch clamp method, the anesthetic effects were also examined on the currents through (1) native vascular KATP channels, (2) recombinant KATP channels with different combinations of various types of inwardly rectifying potassium channel (Kir6.0 family: Kir6.1, 6.2) and sulfonylurea receptor (SUR1, 2A, 2B) subunits, (3) SUR-deficient channels derived from a truncated isoform of Kir6.2 subunit (Kir6.2[DELTA]C36 channels), and (4) mutant Kir6.2[DELTA]C36 channels with reduced sensitivity to adenosine triphosphate (Kir6.2[DELTA]C36-K185Q channels).

Results: Etomidate (>= 10-6 m), but not midazolam (up to 10-6 m), inhibited the levcromakalim-induced vasodilation, which was sensitive to glibenclamide (IC50: 7.21 x 10-8 m; maximum inhibitory concentration: 1.22 x 10-4 m). Etomidate (>= 3 x 10-6 m), but not midazolam (up to 10-4 m), inhibited the native KATP channel activity in both cell-attached and inside-out configurations with IC50 values of 1.68 x 10-5 m and 1.52 x 10-5 m, respectively. Etomidate (10-5 m) also inhibited the activity of various types of recombinant SUR/Kir6.0KATP channels, Kir6.2[DELTA]C36 channels, and Kir6.2[DELTA]C36-K185Q channels with equivalent potency.     

Effects of diet with or without exercise on leptin and anticoagulation proteins levels in obesity.

Obesity is a risk factor for cardiovascular disease and thromboembolic events. We investigated the effects of weight reduction by a 12-week calorie-restricted diet with or without aerobic exercise (diet group and diet plus exercise group) on leptin and anticoagulation proteins levels. Forty-two obese nondiabetic individuals were evaluated for blood levels of leptin, protein C activity, free protein S antigen and for body fat area calculated on computerized tomography before and after intervention. Before intervention, serum levels of leptin and free protein S antigen correlated positively with several adiposity-related parameters. After the program, body weight and fat area were significantly decreased in both groups. Body mass index and leptin levels decreased in both groups, with a larger change in the diet plus exercise group than in the diet group. Although protein C activity levels did not change in both groups, free protein S antigen levels decreased significantly in the diet plus exercise group. In conclusion, the 12-week programs had significant effects on the initial weight reduction and body fat mass, decreasing lepin levels in obese nondiabetic individuals. To clarify whether aerobic exercise has additional or direct effects on the anticoagulation system, a study in a large number of individuals is needed.     

Oxygen Hyperbaric Pressure Therapy (OHPT) for Decubitus Ulcers

Aim:  This study aims to establish a pressure ulcers model that visualizes the microcirculation, and to examine the participation of ischemia‐reperfusion injury in the pathophysiology of pressure ulcers.
Methods:  An original system composed of a new skinfold chamber and compression device allowed loading quantitative vertical stress to the skin. An intravital microscopic technique enabled direct visualization of the microcirculation in the physiological condition and in response to pressure application. To estimate the effect of ischemia‐reperfusion injury, animals were divided into two groups: the compression‐release group in which the animals received four cycles of compression‐release which consisted of 2 hours of compression followed by 1 hour of pressure release; and the compression alone group in which the animals underwent continuous compression for 8 hours. Functional capillary density was quantified before the compression procedure and on day1 (35 hours) after the first evaluation.
Results and Conclusions:  The cyclic compression‐release procedure significantly decreased functional capillary density as compared to continuous compression, indicating that in our experimental setting repetition of ischemia‐reperfusion cycle more severely damaged the microcirculation than single prolonged ischemic insult. The finding supports the significant contribution of ischemia‐reperfusion injury to the pathophysiology of pressure ulcers at the level of dynamic in vivo microcirculation.     

Movement of the lateral and medial poles of the working condyle during mastication in patients with unilateral posterior crossbite.

Patients with unilateral posterior crossbite often show reverse sequential jaw movement patterns on the frontal view during mastication on the crossbite side. Recent studies show that such patients are prone to suffer from temporomandibular joint (TMJ) disc displacement, particularly the lateral portion. The purpose of this study was to examine the movement of the lateral and medial poles of the working condyle during mastication in such patients. Subjects were 12 consecutive patients with unilateral posterior crossbites and without TMJ disc displacements and 12 normal subjects. An optoelectronic jaw-tracking system with 6 degrees of freedom was used to record the motion of the lateral and medial poles of the working condyle during mastication of standardized hard, gummy jelly. The data from the first 10 cycles were analyzed. The lateral and medial poles of the condyle on the crossbite side moved more in the medial direction and less in the lateral direction during mastication in the crossbite patients than the condyle in the normal subjects. The lateral pole of the working condyle moved more in the posterior and inferior directions and less in the anterior direction than the medial pole in all subjects. These results suggest that these condylar movements in patients with unilateral posterior crossbites might be related to the susceptibility to TMJ disc displacement, particularly the lateral portion.     

A case of acute disseminated encephalomyelitis (ADEM) associated with peripheral neuropathy]

A 17-year-old boy with high fever, headache, and neck stiffness was admitted to our hospital. Spinal fluid showed a protein level of 215 mg/dL with myelin basic protein (579 pg/mL), 347/ microl cells (330 mononuclear cells), and a glucose level of 53 mg/dL. One week later, urinary retention, flaccid paraplegia, and sensory disturbance below the 10th thoracic level developed. MRI of the spinal cord revealed swelling and T2-high intensity area in the cord at the 11th and 12th thoracic level. Although high-dose of methylprednisolone was administered, consciousness disturbance and respiratory failure that required mechanical ventilation occurred. Bilateral abducens nerve palsy, nystagmus, and flaccid tetraparesis also occurred. Brain MRI revealed T2-high intensity area in the midbrain and pons. Nerve conduction study showed diminished amplitudes and prolonged latencies or absence of F waves. The patient was administered a combination of intravenous immunoglobulin and a high-dose of methylprednisolone. He showed improvement within one week after the treatment. Two weeks later, he recovered from respiratory failure and weakness of the upper limbs. He remained paraplegic, but gradually improved and was able to walk with support one and a half years later. We suggest the combination therapy of intravenous immunoglobulin and a high-dose of methylprednisolone is effective for patients with combined ADEM and peripheral neuropathy.     

Bicuspid aortic valve stenosis with single coronary artery.

A 56-year-old female with congestive heart failure was transferred to our institution. Aortography demonstrated aortic valve stenosis (AS) with a congenitally bicuspid valve and dilatation of the ascending aorta. Preoperative coronary angiography showed a left single coronary artery. Replacement of the aortic valve and ascending aorta was performed. She had an uneventful postoperative course. We report the case of aortic bicuspid valve stenosis with single coronary artery as an extremely rare congenital cardiac anomaly combination.     

Late-onset hemorrhagic infarction in patients with patent foramen ovale: reports of two cases]

We presented here two patients with hemorrhagic infarction occurred during subacute phase of brain embolism. The patients were 71-year-old and 73-year-old men who suffered from brain infarction of the left posterior cerebral artery and right middle cerebral artery territory, respectively. Both of them were diagnosed as having cryptogenic stroke and patent foramen ovale. After transferred to rehabilitation hospitals taking aspirin for a secondary prevention of stroke, they developed hemorrhagic infarction at day 17 and day 19, respectively. Their blood pressure remained within normal range throughout acute and subacute phase. Although most of hemorrhagic infarction occurs within 24 hours of stroke onset, some patients develop symptomatic hemorrhagic infarction even after 10 days. We need to be careful about late-onset hemorrhagic infarction, because many patients are now transferred early to rehabilitation hospitals to facilitate dedicated systematic rehabilitation.     

Chemosensitivity of neurons in the dorsal motor nucleus of the vagus that responded to portal infusion of hypertonic saline in rats

Neural responses in the dorsal motor nucleus of the vagus (DMV) to topical administrations of sodium and portal infusions of hypertonic saline were investigated electrophysiologically by using multibarrel electrodes in anesthetized rats. Of 102 neurons that showed antidromic response to electrical stimulation of the ventral gastric vagus or the accessory celiac vagus, 51 neurons increased and 13 neurons decreased their discharge rates in response to the electrophoretic administration of sodium. The other 38 neurons did not respond to this stimulation. The portal infusion of hypertonic saline elicited neural responses of some DMV neurons whose axons are involved into either the ventral gastric or the accessory celiac vagus. Further, effects of the topical administration and the portal infusion of hypertonic saline were examined on 33 neurons. Typical response was characterized by an increase in discharge rate responding to both of the portal infusion and the topical administration. In conclusion, the DMV neurons receiving the afferent inputs from hepatoportal osmoreceptors may have an enteroceptor function detecting the change in osmotic pressure of their environment.