Presence of store-operated Ca2+ entry in C57BL/6J mouse ventricular myocytes and its suppression by sevoflurane.

BACKGROUND: Store-operated Ca(2+) entry (SOCE) has been implicated in various pathological conditions of the heart including ischaemia/reperfusion and ventricular hypertrophy. This study investigated the effects of sevoflurane on SOCE. METHODS: Fluorescence imaging was performed on fluo-3- and mag-fluo-4-loaded mouse ventricular myocytes to measure the cytosolic and intraluminal sarcoplasmic reticulum (SR) Ca(2+) levels, respectively, using a confocal laser scanning microscope. Whole-cell membrane currents were recorded using the patch-clamp technique. Ventricular myocytes were exposed to thapsigargin and angiotensin II to deplete SR Ca(2+) stores and thereby activate SOCE. RESULTS: The combined application of thapsigargin and angiotensin II to the Ca(2+)-free medium evoked a significant decrease in the SR Ca(2+) levels, which was followed by the elevation of cytosolic Ca(2+) and the development of cellular hypercontracture upon subsequent addition of extracellular Ca(2+). This cytosolic Ca(2+) elevation was inhibited by 2-aminoethoxydiphenyl borate but not by verapamil and KB-R7943, which indicates that SOCE was present in mouse ventricular myocytes. Sevoflurane concentration-dependently inhibited the SOCE-mediated Ca(2+) overload (IC(50) of 137 µM, which corresponds to 0.96%) with a significant reduction occurring at concentrations of ≥2%. Patch-clamp experiments revealed that the SOCE current was also concentration-dependently blocked by sevoflurane (IC(50) of 144 µM, which corresponds to 1.0%). CONCLUSIONS: Sevoflurane at concentrations of ≥2% significantly inhibits the SOCE activity and prevents the resultant cellular Ca(2+) overload that leads to hypercontracture in ventricular myocytes. This inhibitory action may be involved in the cardioprotective effect of sevoflurane against Ca(2+) overload-mediated injury.

[Pleomorphic carcinoma of the lung; report of a case].

A 83-year-old male was referred to our hospital for further examination of abnormal shadow on chest radiography. Chest computed tomography (CT) showed a tumor mass in his right lung. Bronchoscopy brushing cytology revealed non-small cell lung carcinoma and right middle lobectomy was performed. Histological findings showed large cell carcinoma comprised of spindle cell component, finally diagnosing as pleomorphic carcinoma of the lung. Although he was diagnosed as pT2N0M0 (stage IA) after the operation, massive liver metastasis was found 7 months later. We report this case with references to the literatures on pleomorphic carcinoma of the lung.

High-flow Neonatal Macrocerebral Arteriovenous Fistulas in Hereditary Hemorrhagic Telangiectasia.

Although some cases of vein of Galen aneurysmal malformation (VGAM) present initial clinical symptoms such as cardiopulmonary disturbance in the neonatal period, pial arteriovenous fistula is very seldom present as a clinical symptom immediately after birth. A neonatal patient, the first-born to his family, presented with tachypnea postpartum. This baby had a family history of hereditary hemorrhagic telangiectasia. A cerebral MR image revealed multiple macrocerebral arteriovenous fistulas (MCAVFs), resulting in a large partially thrombosed venous pouch within the cerebral cortex. Trans-arterial embolizations of the main two fistulas were performed using N-butyl cyanoacrylate (NBCA) with tantalum powder six months after birth. Post-embolization angiography confirmed the obliteration of the fistulas and magnetic resonance imaging (MRI) revealed thrombosis and reduction in size of the venous component. His tachypnea disappeared completely. There were no neurological complications due to the treatment. The prognosis of multiple MCAVFs mainly depends on the presence of medullar signs and symptoms and a delay before treatment. Pure glue endovascular intervention, as used in our case, is considered to be the first therapeutic choice to decrease the risk of neurological consequences.

Posttransplant bilioportal fistula with portal vein thrombosis: a case report.

An 8-year-old female patient, known to have post-Kasai biliary atresia with mild intrapulmonary shunting, underwent living donor liver transplantation because of recurrent cholangitis. After the treatment of postoperative biliary stricture with percutaneous transhepatic biliary drainage, the patient subsequently developed hematochezia with portal vein thrombosis. The intraoperative findings showed portal vein thrombosis with a bilioportal fistula. We performed closure of the bilioportal fistula and reconstruction of the portal vein with a native internal jugular vein interposition graft. A bilioportal fistula due to percutaneous hepatobiliary procedures is a reportedly a rare complication following liver transplantation. The patient is currently doing well after a successful surgical intervention.

[Pleomorphic carcinoma of the lung with idiopathic interstitial pneumonia; report of a case].

A 69-year-old man was referred to our hospital for further examination of the abnormal shadow on chest radiography. Chest computed tomography (CT) showed a tumor mass, 4 cm in size, in his right lung (S6) and interstitial pneumonia in the surrounding lung parenchyma Bronchoscopic brushing cytology revealed squamous cell carcinoma cells. Right lower and middle lobectomy was performed due to the metastasis to interlober lymph node. Histological findings showed squamous cell carcinoma comprised of spindle cell component, and there were also fibroblastic foci and fibroid thickness in the interstitium. Therefore he was diagnosed as pleomorphic carcinoma and usual interstitial pneumonia (UIP). About 7 months after the operation, the patient died of mainly multiple bone metastases. Pleomorphic carcinoma with UIP is very rare, so we report this case with references to the literatures.

Isoflurane attenuates myoglobin release during ischemic and/or reperfusion periods.

BACKGROUND: Recently, we have developed cardiac microdialysis for detection of protein leakage from the injured myocardium. We examined whether the exposures to isoflurane would exert a beneficial effect on myocardial injury caused by ischemia or reperfusion. METHODS: A dialysis probe was implanted into the left ventricle free wall in the rabbits. The dialysate myoglobin level served as an index of myocardial interstitial myoglobin levels. Rabbits were randomly assigned to one of three groups: (1) without exposure to isoflurane (vehicle, n=6), (2) inhale 1 MAC isoflurane once for 30 min (ISO30-1, n=6), and (3) twice for 30 min (ISO30-2, n=6). All rabbits underwent 30 min of coronary occlusion and 60 min of reperfusion. To determine whether the isoflurane induced myocardial protection against chemical hypoxia, sodium cyanide (30 mM) was administered and dialysate myoglobin levels were measured with (n=6) and without pre-exposure to isoflurane twice for 30 min (n=6). RESULTS: In all three groups dialysate myoglobin levels were increased by coronary occlusion and furthermore augmented by reperfusion. In comparison with the vehicle group, the ISO30-1 group suppressed only the increase in the dialysate myoglobin level during reperfusion. The ISO30-2 group suppressed during both the ischemic and reperfusion periods. Cyanide induced increases in dialysate myoglobin levels. These increments in dialysate myoglobin levels were suppressed by repeated exposure to isoflurane. CONCLUSION: Repeated exposure to isoflurane suppressed myocardial myoglobin release caused by both ischemia and reperfusion injury. Isoflurane may provide protection against myocardial ischemia/reperfusion and hypoxic injuries.

Prenatal diagnosis of fetal hydrometrocolpos secondary to a cloacal anomaly by magnetic resonance imaging.

Fetal female urogenital anomalies are often difficult to evaluate by ultrasonography, especially in late gestation. We report a case of fetal hydrometrocolpos detected at 35 weeks of gestation. Ultrasonography revealed a large retrovesical septate hypoechogenic mass in the fetal abdomen, however the sonographic findings were inconclusive. Magnetic resonance imaging (MRI) confirmed that the abdominal mass was fluid-filled with a mid-plane septum in the midline posterior to the bladder, and showed a connection to the dilated uterus that was duplicated. These findings were consistent with a diagnosis of hydrometrocolpos with septate vagina and uterus didelphys. The neonate showed abdominal distension, ambiguous genitalia and anal atresia with a single perineal opening. Hydrometrocolpos was secondary to a urethral type of cloacal anomaly. Aspiration of the mass and a colostomy were performed on the first postnatal day, followed by anorectoplasty at 19 months of age. MRI is a useful complementary tool for assessing fetal urogenital anomalies when ultrasonography is inconclusive.

Dietary fructooligosaccharides up-regulate immunoglobulin A response and polymeric immunoglobulin receptor expression in intestines of infant mice.

We examined whether or not dietary fructooligosaccharides (FOS) in infancy can have a beneficial effect on the mucosal immune system. Newborn BALB/c mice, accompanied by their dams until 21 days of age, were fed either a control diet based on casein [FOS- diet group] or a FOS- diet supplemented with 5% (w/w) FOS [FOS+ diet group]. Total IgA levels in tissue extracts from the intestines of mice in the FOS+ diet group at 38 days of age were about twofold higher (P < 0.05) than those in the FOS- diet group in the jejunum, ileum and colon. Ileal and colonic polymeric immunoglobulin receptor (pIgR) expression in the FOS+ diet group at 36 days of age was 1.5-fold higher than in the FOS- diet group (P < 0.05). Consistent with these results, the ileal IgA secretion rate of the FOS+ diet group at 37 days of age was twofold higher than that of the FOS- diet group (P < 0.05). Moreover, the percentage of B220(+)IgA+ cells in Peyer's patches (PP) was significantly higher in the FOS+ diet group than in the FOS- diet group (6.2%versus 4.3%, P < 0.05), suggesting that isotype switching from IgM to IgA in PP B cells might be enhanced in vivo. Taken together, our findings suggest that dietary FOS increases the intestinal IgA response and pIgR expression in the small intestine as well as the colon in infant mice.

[Preparation of a manual for treatment of patients refusing blood transfusion].

We prepared a concise and simple manual for the treatment of a patient refusing blood transfusion. In this manual, we present the idea that our medical staff will respect the intention of adult patients but not the intention of juveniles below 18 years of age. If an unconscious adult patient is carrying a blood refusal card, we would regard the card as a document indemnifying the hospital from responsibility and we would treat the patient without blood transfusion. However, we would treat a juvenile patient below 18 years of age with blood transfusion if necessary, even if they and their parents refused blood transfusion. By following the manual, we can cope with the patient who refuses blood transfusion, promptly and precisely and we are rarely prosecuted by them. We respect the right of patients to make decisions regarding medical treatment and to resolve problems regarding medical expenses. We recommend that all medical institutions prepare a manual for the treatment of the patient refusing blood transfusion and officially announce the institution's policies on this matter.

Effects of optic tract stimulation on baroreflex vagal bradycardia in rats.

1. Arterial baroreflexes are suppressed in stressful conditions. Intense visual stimuli can cause a threatening sensation and produce defensive reactions. 2. The present study was designed to determine whether and how electrical stimulation of the optic tract (OT) affects arterial baroreflexes, especially the heart rate component, baroreflex vagal bradycardia (BVB), in rats. In chloralose- urethane anaesthetized, beta-adrenoceptor-blocked rats, BVB was evoked by electrical stimulation of the aortic depressor nerve. 3. Electrical stimulation of the OT was found to not only increase blood pressure and heart rate, but also to inhibit BVB. To determine whether these responses were mediated by the lateral genticulate body and/or the superior colliculus, which are major target sites to which the OT projects, each was activated with electrical and chemical stimulation. 4. The lateral genticulate body did not respond to either electrical or chemical stimulation, whereas the superior colliculus increased blood pressure and heart rate while suppressing BVB following electrical stimulation. Essentially similar responses were observed following microinjection of the GABA antagonist bicuculline methiodide. 5. Optic tract-induced inhibition of BVB was abolished by bilateral destruction of the superior colliculus. Furthermore, this inhibition was also largely attenuated by destruction of the midbrain periaqueductal grey (PAG). 6. In conclusion, electrical stimulation of the OT increases blood pressure, heart rate and inhibits BVB. These responses are not mediated by the lateral genticulate body but are mediated by the superior colliculus. The PAG may participate in the subsequent mediation of the responses to electrical stimulation of the OT and the OT-induced inhibition of BVB may contribute to expression of a light-induced defence reaction.

[A case of adrenal metastasis of lung cancer treated by carboplatin and docetaxel].

A 42-year-old male was referred to our hospital in October 1998, suffering from severe cough accompanied by repeated hemosputa. Serum NSE slightly increased and cytology of sputum indicated class V. Chest X-P and CT revealed a large tumor in the right upper lobe and hilar lymphadenopathy. Abdominal CT revealed bilateral adrenal tumors. For continuous bloody sputum, a right upper lobectomy and lymphadenectomy were performed and the pathologic diagnosis was large cell carcinoma. After surgery, we chose radiation and chemotherapy. The new chemotherapeutic agent docetaxel (60 mg/m2 in combination with carboplatin (CBDCA: AUC 6,800 mg/m2) was administered, resulting in the remarkable reduction in the size of adrenal metastasis by 50% after 3 courses of chemotherapy. Furthermore, 12 months later, the right adrenal metastasis was remarkably reduced (5 x 3 cm-> 0.5 x 1.0 cm), and the left adrenal metastasis had disappeared on abdominal CT. These findings may suggest the efficacy of newly developed docetaxel in cases of non-small cell lung cancer.

Effects of profound hemodilution on small-intestinal wound healing in rabbits.

BACKGROUND: Wound healing is influenced by tissue oxygen tension and blood perfusion, but not by moderate anemia or hemodilution. The effect of perioperative profound hemodilution on small-intestinal wound healing remains unclear. METHODS: We performed jejunectomy followed by end-to-end anastomosis in rabbits subjected to a variety of perioperative hemodilutions: HD((HES)), hemodiluted with hydroxyethylstarch; HD((P+HES)), hemodiluted with autologous plasma and hydroxyethylstarch; HD((HES))/R, hemodiluted with hydroxyethylstarch and retransfused afterward. Intraoperative hemoglobin levels were 5 g 100 ml(-1). On Postoperative Day 5, the tensile strength (TS) of the anastomosis was measured and histological specimen was obtained. The time courses of hemoglobin, serum albumin (Alb), plasma fibrinogen (Fbg), and plasma activity of factor XIII (F XIII) were measured. RESULTS: TS in HD((HES))/R (236.0 +/- 52.2 gf) was similar to that in control (266.5 +/- 41.6 gf); however, TS in HD((HES)) (179.8 +/- 17.9 gf) and HD((P+HES)) (165.5 +/- 14.7 gf) decreased significantly. The histological findings in HD((HES))/R were similar to those of control, whereas they demonstrated a delayed healing process in HD((HES)) and HD((P+HES)). Hemoglobin levels were still lower on Postoperative Day 5 in HD((HES)) and HD((P+HES)), but increased to 10.0 g 100 ml(-1) after retransfusion in HD((HES))/R. Hemodilution caused significant decreases in Alb, Fbg, and F XIII, but the values after retransfusion in HD((HES))/R were similar to postoperative values in HD((P+HES)). CONCLUSION: Intraoperative profound hemodilution does not interfere with small-intestinal wound healing as long as postoperative hemoglobin levels were maintained above 10 g 100 ml(-1). Postoperative levels of other plasma constituents may not influence wound healing.

Control system for an implantable rotary blood pump.

Rotary blood pumps can be used for long-term left ventricular assist devices. These pumps have several advantages over the conventional pulsatile pumps including smaller size, higher efficiency, and simple design and construction. However, one of the difficulties associated with the rotary blood pump is the proper control method to maintain an optimum flow rate in different physiological conditions. The rotary blood pump can be controlled by two methods. The first is to utilize the measured pump flow rate from its servo signal. The second is to detect and avoid abnormal pumping conditions such as; back flow and sudden increase in the pressure head. This abnormal situation typically occurs from excessive suction of blood when there is a functional or mechanical occlusion in the inflow cannula. The ultrasound flow meter is durable and reliable but it is difficult to continually monitor the blood flow rate of an implantable pump. Therefore, another method is needed instead of the continuous flow monitoring. One chronic calf having an LVAD was subjected for the development of this control system. This calf survived more than 6 months. Voltage, current, motor speed, heart rate and the pump flow rate were recorded and stored at 30-min intervals in a computer. Utilizing these parameters, attempts were made (1) to achieve indirect flow assessments and (2) to reveal abnormal operating parameters of the centrifugal pump (1). Indirect flow measurement, the predicted pump flow rate was calculated from these pump derived parameters (required power, motor speed and heart rate). The value of the coefficient of determination (R) between the measured and estimated pump flow rate was 0.796. (2) Abnormal operating indicator, there was an association between the required current and pump flow waves. The current was differentiated, and then calculated to the power of the differentiated current. The normal range of this value was 0.02+/-0.54. In abnormal conditions, this abnormal operating indicator increased 500 times. The predicted flow estimation method and abnormal operating indicator were available from intrinsic operating parameters of the pump and need no sensors. These two methods were simple, yet they are possibly effective and reliable servo control methods for a rotary blood pump.

Nicorandil stimulates release of adenyl purines from porcine coronary artery.

1. To clarify the mechanism of the cardioprotective effect of nicorandil (2-nicotinamidoethyl-nitrate ester), the effects of nicorandil and nitric oxide (NO) donors on the release of ATP, ADP, AMP and adenosine from arterial segments and cultured endothelial cells of the porcine coronary artery were examined. 2. Nicorandil significantly increased the release of total adenyl purines from arterial segments and from cultured endothelial cells. 3. Cromakalim, an ATP-sensitive K+ channel opener, did not affect the release of total adenyl purines from coronary artery segments. 4. s-Nitroso-N-acetyl-D,L-penicillamine and isosorbide dinitrate, NO donors, significantly increased the release of total adenyl purines from coronary artery segments. 5. These results demonstrate that nicorandil stimulates ATP release from the coronary artery by acting not as an ATP-sensitive K+ channel opener, but as a nitrate, thus suggesting the cardioprotective properties of nicorandil.

Inhibition of baroreflex vagal bradycardia by activation of the rostral ventrolateral medulla in rats.

In stressful conditions, baroreflex vagal bradycardia (BVB) is often suppressed while blood pressure is increased. To address the role of the rostral ventrolateral medulla (RVL), a principal source of sympathetic tone, in inhibition of BVB, we microinjected DL-homocysteic acid (DLH, 6 nmol) into the RVL of chloralose-urethan-anesthetized, sinoaortic-denervated rats to examine the effect on BVB. The BVB was provoked by electrical stimulation of the aortic depressor nerve ipsilateral to the injection sites. DLH microinjection was found to suppress BVB while increasing blood pressure. The inhibition of BVB was observed even during the early phase in which DLH transiently suppressed central inspiratory activity. The inhibition was not affected either by upper spinal cord transection or suprapontine decerebration. Similar results were obtained by microinjection of bicuculline methiodide (160 pmol), a GABA antagonist, into the RVL of carotid sinus nerve-preserved rats due to withdrawal of a tonic GABA-mediated, inhibitory influence including the input from arterial baroreceptors. In conclusion, activation of the RVL inhibits BVB at brain stem level independently of central inspiratory drive.

[A case of biloma caused by early complications of hepatic artery infusion chemotherapy].

We report a 70-year-old male who had biloma as an early complication of hepatic artery infusion chemotherapy. The patient had a history of subtotal gastrectomy for a advanced gastric cancer. Two years after the primary operation on the stomach, a solitary metastatic liver tumor was indicated by follow-up abdominal CT, and a segmental hepatectomy was performed. Soon after the hepatectomy, intraarterial catheter placement was performed via the left subclavian artery for preventive chemotherapy. Infusion chemotherapy of 10.5 g 5-FU and 75 mg CDDP was administered for a month, during which time the patient had liver dysfunction, fever, tenderness, and abdominal fullness. Abdominal CT revealed a large low density mass at a lateral segment of the liver which could not be seen on the previous CT image. Also, extravasation of contrast media was identified by angiography via the reservoir catheter. Using an interventional technique, percutaneous transhepatic drainage for biloma and extubation of the reservoir catheter were performed. The present case is thought to be of an early and rare complication of hepatic artery infusion chemotherapy. The etiology is discussed herein.

Heart preservation in HTK solution: role of coronary vasculature in recovery of cardiac function.

BACKGROUND: Poor myocardial tolerance to prolonged cold ischemia remains a major concern in heart transplantation. In this study, we estimated superiority of Histidine-Tryptophan-Ketoglutarate (HTK) over University of Wisconsin (UW) as a cardiac preservation solution. METHODS: Isolated rat hearts were mounted on a Langendorff apparatus to estimate the baseline cardiac function. The hearts were arrested and stored at 4 degrees C in UW and HTK solution for 8 hours, and then reperfused. The aortic flow, coronary flow, cardiac output, rate pressure product, and left ventricular dp/dt in the HTK group recovered significantly more than the UW group. The values of myocardial total adenine nucleotides and the adenosine triphosphate to adenosine diphosphate ratio were higher in the HTK than in the UW group. We also examined coronary vascular responsiveness using left coronary arteries dissected from the rat hearts before flushing, before storage, after storage, and after reperfusion. RESULTS: The maximal relaxation response to acetylcholine was significantly higher in the HTK than in the UW group after reperfusion, although there were no significant differences at each stage before reperfusion. In addition, the endothelium-independent relaxation response to sodium nitroprusside in the HTK group was also well preserved after reperfusion. CONCLUSIONS: These results indicate that HTK is superior to UW solution for cardiac preservation. HTK protects coronary vasculature during preservation, which together with reperfusion might lead to improved functional cardiac recovery following preservation.