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Biomedical subjects

W G Kim

Publications and source records attributed to W G Kim.

At least 37 records · Page 2Linked to original sources
PubMed2000

Time dependency of the action of nitric oxide in lipopolysaccharide-interferon-gamma-induced neuronal cell death in murine primary neuron-glia co-cultures.

We investigated the time-dependency of the action of nitric oxide (NO) on glia-mediated neuronal cell death. Cortical neuron-glia co-cultures were treated with lipopolysaccharide and interferon gamma (LPS/IFNgamma). The production of NO was first detectable 9 h after the exposure to LPS/IFNgamma and increased for up to 48 h. A significant neuronal cell death was observed 36-48 h after treatment with LPS/IFNgamma. The NO generated at the initial stage of NO synthesis (about 12 h) following exposure to LPS/IFNgamma was found to be critical for LPS/IFNgamma-induced neurotoxicity. Furthermore, the rate of NO production at the initial stage of NO synthesis was correlated linearly with the extent of neuronal cell death. These findings suggest that the maximal rate of NO synthesis, instead of the accumulated NO(2)(-) level, is a sensitive index for predicting endotoxin-induced cytotoxicity.

Animals↗
PubMed2000

Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia.

Inflammation in the brain has been increasingly associated with the development of a number of neurological diseases. The hallmark of neuroinflammation is the activation of microglia, the resident brain immune cells. Injection of bacterial endotoxin lipopolysaccharide (LPS) into the hippocampus, cortex, or substantia nigra of adult rats produced neurodegeneration only in the substantia nigra. Although LPS appeared to impact upon mesencephalic neurons in general, an extensive loss of dopaminergic neurons was observed. Analysis of the abundance of microglia revealed that the substantia nigra had the highest density of microglia. When mixed neuron-glia cultures derived from the rat hippocampus, cortex, or mesencephalon were treated with LPS, mesencephalic cultures became sensitive to LPS at a concentration as low as 10 ng/ml and responded in a dose-dependent manner with the production of inflammatory factors and a loss of dopaminergic and other neurons. In contrast, hippocampal or cortical cultures remained insensitive to LPS treatment at concentrations as high as 10 microg/ml. Consistent with in vivo observations, mesencephalic cultures had fourfold to eightfold more microglia than cultures from other regions. The positive correlation between abundance of microglia and sensitivity to LPS-induced neurotoxicity was further supported by the observation that supplementation with enriched microglia derived from mesencephalon or cortex rendered LPS-insensitive cortical neuron-glia cultures sensitive to LPS-induced neurotoxicity. These data indicate that the region-specific differential susceptibility of neurons to LPS is attributable to differences in the number of microglia present within the system and may reflect levels of inflammation-related factors produced by these cells.

Animals↗
PubMed2000

Post-transcriptional inhibition of lipopolysaccharide-induced expression of inducible nitric oxide synthase by Gö6976 in murine microglia.

Glia in the brain respond to various toxins with an increased expression of inducible nitric oxide synthase (iNOS) and an increased production of nitric oxide (NO). Here, we report that lipopolysaccharide (LPS)-induced expression of iNOS was down-regulated post-transcriptionally through the destabilization of iNOS mRNA by the indolocarbazole compound, Gö6976, in murine microglia. This Gö6976 effect is specific for iNOS since tumor necrosis factor alpha was unaffected by the compound. Interestingly, the post-transcriptional effects ascribed to Gö6976 were not observed with other inhibitors of protein kinase A, C (PKC), G, or protein tyrosine kinases. Instead, these kinases appear to affect the iNOS/NO system at the transcriptional level. In the past, Gö6976 has been reported to be a rather specific inhibitor of PKC in vitro. Results from our experiments, through prolonged treatment with phorbol esters and with the various PKC inhibitors including phorbol ester-insensitive PKC isotype inhibitor, suggest that the Gö6976-mediated post-transcriptional regulation of iNOS gene expression and NO production in microglia is not mediated through its reputed effects on PKC activity. Since the effects of various neurotoxins and certain neurodegenerative diseases may be manifested through alterations in the iNOS/NO system, post-transcriptional control of this system may represent a novel strategy for therapeutic intervention.

Animals↗
PubMed2000

Development of a centrifugal pump with thick blades.

We have developed a centrifugal blood pump with thick impeller blades (60% of pitch) to obtain a small tip clearance. An unshrouded impeller with 6 backward curved thick blades was used to reduce the dead zone between the shroud and upper casing. A streamline angle in volute was uniform in circumferential direction by continuity and angular momentum conservation. To prove the effectiveness of small tip clearance, performance and hemolysis tests were conducted on pumps with a tip clearance of 0.5, 1.5, and 2.0 mm at exit with the blade thickness of 60% of pitch, and with that of 1.0, 2.0, and 2.5 mm at exit with the thickness of 40% of pitch. The results showed that the smaller the tip clearance, the better the hydrodynamic and hemolytic performance. The best result was seen in the pump with tip clearance of 0.5 mm with a blade thickness of 60% of pitch. These results suggest that a centrifugal pump with thick blades and a small tip clearance can be a promising alternative as a cardiopulmonary bypass pump.

Animals↗
PubMed2000

Is avoidance of air contact necessary for the in vitro evaluation of thrombogenicity in mechanical circulatory assist devices?

An effective in vitro protocol for the investigation of thrombogenicity can provide many advantages in the development of mechanical circulatory assist devices. Strict avoidance of air contact with blood recently was proposed for reliable in vitro evaluation. This study was performed to confirm the necessity of avoidance of air contact for the in vitro test of thrombogenicity in a rotary pump. Two sets of mock circuits with the same rotary blood pumps, reservoirs, and connecting tubes were made. In one system, blood came in contact with air while the other did not. The test blood was heparinized at the dose of 1 IU per 1 ml of blood. The tests were terminated at an activated coagulation time of 1.5 times the control value. The levels of hematocrit, platelet, factors VIII and XII, fibrinogen, thromboxane B2, and plasma-free hemoglobin were measured during the procedures. After the experiments, the thrombi formed were observed, measured, and compared with those formed in in vivo circumstances. The tests were repeated 12 times. There were no statistically significant differences between the 2 groups in hematologic parameters and the amounts of thrombi formed. The thrombi observed in both groups showed the same pathologic findings as those formed in vivo with the exception of intermittent multiple air bubbles found in thrombi of the air-contact group. In conclusion, the effect of air contact in the in vitro investigation of thrombogenicity was negligible while the proposed in vitro test models of thrombogenesis in the mechanical circulatory assist device proved to be reliable.

Air↗
PubMed2000

Implantation of one piece biventricular assist device by left thoracotomy in an ovine model.

In this report, we describe an operative procedure for our implantable 1 piece biventricular assist device (BiVAD) based on a moving actuator mechanism, using an ovine model. Our implantable BiVAD is a volumetric coupled 1 piece unit including right and left blood sacs and an actuator assembly based on the moving actuator mechanism. The BiVAD was controlled by fixed rate control with 75 bpm for the most part. Both the left and the right full ejection modes with the maximum stroke angle were selected to minimize blood stasis in the blood sacs because of low assist flow condition. Three Corriedale sheep were used for the device implantation by a left thoracotomy incision. Cannulation was successfully performed in all cases. Although exposability of the right atrial appendage varied from animal to animal, the insertion of the cannula was easily performed. The cannulas were connected to the pump-actuator assembly in the preperitoneal pocket. All 3 animals survived the experimental procedure. During implantation of the device, in the 1 month survival animal, pump flow was maintained between 2.0 L/min and 2.5 L/min, mean aortic pressure was 90-110 mm Hg, and mean pulmonary artery pressure was 20-30 mm Hg. The left and right atrial pressure were maintained between 0 and 5 mm Hg. In conclusion, this ovine model for implantation of the 1 piece BiVAD can be an effective alternative for testing in vivo biocompatibility of the device although it needs more consideration for anatomical fittability for future human application.

Animals↗
PubMed2000

Scanning electron microscopic analysis of arterial line filters used in cardiopulmonary bypass.

The clinical value of arterial line filters is still a controversial issue. Proponents of arterial line filtration argue that filters remove particulate matter and undissolved gas from circulation while opponents argue the absence of conclusive clinical data. We conducted scanning electron microscope (SEM) studies of arterial line filters used clinically in the cardiopulmonary bypass circuits during adult cardiac surgery and analyzed the types and characteristics of materials entrapped in the arterial line filters. Twelve arterial line filters were obtained during routine hypothermic cardiopulmonary bypass in 12 adult cardiac patients. The arterial line filter was a screen type with a pore size of 40 microm (Baxter Health Care Corporation, Bentley Division, Irvine, CA, U.S.A. ). After opening the housing, the woven polyester strands were examined with SEM. All segments examined (120 segments, each 2.5 x 2. 5 cm) contained no embolic particles larger in their cross-sectional area than the pore size of the filter (40 microm). The origins of embolic particulates were mostly from environmental foreign bodies. This may suggest a possible need for more aggressive filtration of smaller particulates than is generally carried out at the present time.

Adult↗
PubMed2000

Vasoconstrictive eicosanoid responses to extracorporeal circulation with or without an oxygenator in fetal lambs.

INTRODUCTION: This study measured levels of vasoconstrictive eicosanoids during ovine fetal cardiac bypass and compared the measurements between two groups: (1) a group in which the placenta functioned as the only source of oxygen supply during the bypass (the placenta group), and (2) a group in which an artificial oxygenator, instead of the placenta, was included in the bypass circuit (the oxygenator group). MATERIALS AND METHODS: A total of 16 fetal lambs were randomly assigned into either the oxygenator group or the placenta group. Following anesthesia, the fetal cardiac bypass procedure was performed. The placenta group used a centrifugal pump as the pumping device without an oxygenator during the bypass. The bypass circuit in the oxygenator group consisted of a roller pump and a membrane oxygenator. The fetal cardiac bypass procedure was performed for 30 minutes at normothermia in both groups. For the measurements of thromboxane B2(TXB2) and prostaglandin E2 (PGE2), blood samples were taken before the bypass, at 5 minutes, 15 minutes, and 30 minutes after the start of cardiac bypass, and at 15 minutes after weaning from the bypass. TXB2 and PGE2 levels were determined by radioimmunoassay with PGE2(125I) and TXB2(125I) assay systems. Hemodynamic observations and arterial blood gas analyses were done every 10 minutes. RESULTS: The mean arterial pressure and heart rate ranged from 69.8 to 82.6 mmHg and 169 to 182/min during the bypass in the oxygenator group, and from 14.4 to 44.7 mmHg and 64.3 to 75/min in the placenta group. Arterial blood gas analysis showed severe hypercapnia and hypoxemia with acidosis during and after the bypass in the placenta group. Bypass flow rates were maintained at 140.3-164.0 ml/kg/min in the oxygenator group, while flow rates were suboptimal (74.3-97.0 ml/kg/min) in the placenta group. There were no statistically significant differences in PGE2 concentrations before, during, or after bypass, although the placenta group displayed a tendency to higher measurements during bypass, compared to the oxygenator group. The placenta group also showed higher TXB2 measurements than the oxygenator group during the bypass (p = 0.0457). CONCLUSIONS: We have demonstrated increase measurements of PGE2 and TXB2 in the placenta group when compared with the oxygenator group in an ovine fetal cardiac bypass model, although the PGE2 difference failed to reach statistical significance.

Animals↗
PubMed2000

Tissue-engineered heart valve leaflets: an effective method for seeding autologous cells on scaffolds.

BACKGROUND: A precondition for the successful formation of tissue-engineered heart valves is the generation of a proper matrix on biodegradable scaffolds over a limited period of time. The aim of this study was to find an effective method of seeding autologous cells on these scaffolds to create a new matrix for heart valves. METHODS: Myofibroblasts and endothelial cells were isolated and cultured from an ovine artery. A synthetic biodegradable scaffold consisting of polyglycolic and polylactic acids was seeded first with the myofibroblasts, then coated with endothelial cells. Three different methods of myofibroblast seeding were compared: I) daily seeding of myofibroblasts (1x10(6)) for ten days and culture for four days; II) seeding of myofibroblasts (1x10(7)) and culture for 14 days with the use of a simple medium; III) seeding of myofibroblasts (1x10(7)) with the use of a medium containing collagen and culture for 14 days. Light and electron microscopic analyses were performed. RESULTS: The group that used the medium containing collagen showed the best results in terms of seeding efficiency. CONCLUSION: Seeding autologous cells with a medium containing collagen onto the scaffold showed the largest cell population and might generate the best matrix on the scaffold.

Absorbable Implants↗
PubMed2000

Comparative analysis of alpha-stat and pH-stat strategies with a membrane oxygenator during deep hypothermic circulatory arrest in young pigs.

Using young pigs, this study compared the strategies of alpha-stat and pH-stat during deep hypothermic circulatory arrest (DHCA) for the cooling time of brains during the induction of hypothermia and rewarming time with cardiopulmonary bypass (CPB); the cerebral perfusion rate and metabolism rate, and the ratio of these 2 rates; and the extent of the cerebral edema development after circulatory arrest. Fourteen young pigs were assigned to 1 of 2 strategies of gas management. Cerebral blood flow was measured with a cerebral venous outflow technique. With CPB, core cooling was initiated and continued until the nasopharyngeal temperature fell below 20 degrees C. The flow rate was set at 2,500 ml/min. Once the temperature reached below 20 degrees C, the animals were subjected to DHCA for 40 min. During the cooling period, the acid-base balance was maintained using either alpha-stat or pH-stat strategy. After DHCA, the body was rewarmed to the normal body temperature. The animals then were sacrificed, and we measured the brain water content. The cerebral perfusion and metabolism rates were measured before the onset of CPB, before cooling, before DHCA, 15 min after rewarming, and upon the completion of rewarming. The cooling time was significantly shorter with alpha-stat than with pH-stat strategy while no significant differences were observed in the rewarming time between groups. Also, no significant differences were found in cerebral blood flow volume, metabolic rate, or flow/metabolic rate ratio between groups. In each group, the cerebral blood flow volume, metabolic rate, and flow/metabolic rate ratio showed significant differences in body temperature. Brain water content showed no significant differences between the 2 groups. In summary, this study found no significant differences between alpha-stat and pH-stat strategies, except in the cooling time. The cooling time was rather shorter with the alpha-stat than with the pH-stat strategy.

Acid-Base Equilibrium↗
PubMed1999

Nitrofen-induced congenital malformations of the heart and great vessels in rats: an animal model.

BACKGROUND: Nitrofen (2,4-dichloro-4'-nitrodiphenyl ether), a diapheny ether herbicide, is known to induce in rat fetuses a variety of congenital cardiovascular anomalies, together with diaphragmatic hernia and hydronephrosis. The purpose of the current study was to produce congenital cardiovascular anomalies in rat fetuses by oral nitrofen administration at the indicated doses and days of gestation, and to determine the characteristics of resulting nitrofen-induced cardiovascular anomalies. METHODS: All the observed fetuses were removed from pregnant Sprague-Dawley rats killed on the 21st day of gestation. They were preserved in 10% formalin, and dissection for examination was carried out under a dissecting microscope. RESULTS: The following results were based on dissecting microscopic findings of 482 offspring: (1) The 11th day of gestation was the most sensitive for nitrofen induction of congenital cardiovascular anomalies. The incidence of these was dose related. (2) Ventricular septal defect was the most common single cardiovascular anomaly, representing more than half of all such irregularities. The next most common were aortic arch anomalies and tetralogy of Fallot. (3) Cardiac anomalies derived from infundibular maldevelopment such as tetralogy of Fallot and pulmonary atresia with ventricular septal defect were observed only in the group treated with nitrofen on the 11th gestational day. (4) Aortic arch anomalies were very frequent; the great majority were anomalous right subclavian artery with left aortic arch. CONCLUSION: This animal model is suitable for further embryological investigation of the development of congenital cardiovascular anomalies.

Animals↗
PubMed1999

Clinical application of the M-numbers of aortic cannulas during hypothermic cardiopulmonary bypass in pediatric patients.

A standardized system to describe the pressure-flow characteristics of a given cannula has recently been proposed and has been termed the M-number system. Using 3 different sizes of aortic cannulas in 50 pediatric cardiac patients on hypothermic cardiopulmonary bypass, we analyzed the correlation between experimentally and clinically derived M-numbers and found it to be positive. Clinical M-numbers were typically 0.35 to 0.55 greater than experimental M-numbers and correlated inversely with a patient's temperature change; this was most probably due to increased blood viscosity arising from hypothermia. This inverse relationship was more marked in higher M-number cannulas. The clinical data obtained in this study suggest that the experimentally derived M-number correlates strongly with the clinical performance of the cannula and that the influence of temperature is significant.

Aorta↗
PubMed1999

Rabbit model of cardiopulmonary bypass.

Mainly because of technical problems, the use of rabbits as a cardiopulmonary bypass (CPB) animal model with direct cannulation of the ascending aorta is known to be extremely difficult. The objectives of this study were the establishment of a CPB model in rabbits with direct cannulation of the ascending aorta, and the evaluation of the protective effect of steroid on the development of brain edema during circulatory arrest (CA) in an established rabbit CPB model. Fifteen New Zealand white rabbits were divided into three groups; control CA group, CA with Trendelenberg position, and CA with Trendelenberg position and steroid administration. After anesthetic induction and tracheostomy, median sternotomy was performed. An aortic cannula (3.3 mm) and a venous cannula (14 Fr) were inserted into the ascending aorta and the right atrium, respectively. The CPB circuit consisted of a roller pump and a bubble oxygenator. With 120-150 ml of blood, the priming volume of the circuit was approximately 450 ml, and CPB at a flow rate of 80-85 ml/kg/min was initiated. Blood in the priming solution was obtained from donor rabbits through cardiac puncture. Ten minutes later, CA with cessation of CPB was established for 40 min at 20 degrees C (rectal temperature). After CA, CPB was restarted with a 20 min period of rewarming. Ten minutes after weaning, the animal was sacrificed. Between 1 and 2 g of the brain was removed and the water content was determined and compared between groups. CPB with CA was successfully performed in all cases, with a flow rate of 60-100 ml/kg/min maintained throughout the CPB procedure. At that time, blood gases were reasonably maintained and aortic pressure ranged from 35 to 55 mmHg. After weaning from CPB, all hearts resumed beating spontaneously. Among the three groups, there were no statistically significant differences in the water content of the brain. These results indicate that: (1) if the proper technique is used, CPB in rabbits with direct cannulation of the ascending aorta is a reliable procedure, and (2) the effect of steroid on the prevention of brain edema related to the Trendelenburg position during CA is not established within the scope of this study.

Animals↗
PubMed1998

Clinical significance of intrahepatic biliary stricture in efficacy of hepatic resection for intrahepatic stones.

In the Far East, hepatic resection is the definitive treatment for complicated intrahepatic stones (IHS). However, many investigators have reported that the associated intrahepatic biliary stricture is the main cause of treatment failure. A retrospective comparative study was undertaken to clarify the long-term efficacy of hepatic resection for treatment of IHS and to investigate the clinical significance of intrahepatic biliary stricture in treatment failure after hepatic resection performed in 44 patients with symptomatic IHS. The patients were divided into two study groups: group A, with intrahepatic biliary stricture (n = 28) and group B, without stricture (n = 16). Residual or recurrent stones, recurrence of intrahepatic biliary stricture, late cholangitis, and final outcomes were analyzed and compared statistically between the two groups. The patients were followed up for a median duration of 65 months after hepatectomy. The overall incidence of residual or recurrent stones was 36% and 11%, respectively, in groups A and B. The initial treatment failure rate was 50% in group A and 31% in group B. Intrahepatic biliary stricture recurred in 46% of patients in group A, while none of the group B patients had biliary stricture recurrence (P = 0.001). More than two-thirds of the restrictures in group A were identified at the primary site. The incidence of late cholangitis was higher in group A (54%) than in group B (6%) (P = 0. 002). Three-quarters of the patients with cholangitis in group A had severe cholangitis, that was recurrent, and related to stones and strictures (n = 11). They and 2 asymptomatic patients in group B required secondary procedures done at a median of 12 months after hepatectomy. Final outcomes after hepatectomy with or without secondary management were good in 80%, fair in 16%, and poor in 4% of our 44 patients. Most recurrent cholangitis after hepatectomy in patients with IHS was related to recurrent intrahepatic ductal strictures. Therefore, to be effective, hepatic resection should include the strictured duct. However, with hepatectomy alone it is difficult to clear the IHS or relieve the ductal strictures completely, particularly in patients with bilateral IHS, so perioperative team approaches that include both radiologic and cholangioscopic interventions should be combined for the effective management of IHS.

Bile Ducts, Intrahepatic↗
PubMed1998

Implantable control, telemetry, and solar energy system in the moving actuator type total artificial heart.

The moving actuator type total artificial heart (TAH) developed in the Seoul National University has numerous design improvements based upon the digital signal processor (DSP). These improvements include the implantability of all electronics, an automatic control algorithm, and extension of the battery run-time in connection with an amorphous silicon solar system (SS). The implantable electronics consist of the motor drive, main processor, intelligent Li ion battery management (LIBM) based upon the DSP, telemetry system, and transcutaneous energy transmission (TET) system. Major changes in the implantable electronics include decreasing the temperature rise by over 21 degrees C on the motor drive, volume reduction (40 x 55 x 33 mm, 7 cell assembly) of the battery pack using a Li ion (3.6 V/cell, 900 mA.h), and improvement of the battery run-time (over 40 min) while providing the cardiac output (CO) of 5 L/min at 100 mm Hg afterload when the external battery for testing is connected with the SS (2.5 W, 192.192, 1 kg) for the external battery recharge or the partial TAH drive. The phase locked loop (PLL) based telemetry system was implemented to improve stability and the error correction DSP algorithm programmed to achieve high accuracy. A field focused light emitting diode (LED) was used to obtain low light scattering along the propagation path, similar to the optical property of the laser and miniature sized, mounted on the pancake type TET coils. The TET operating resonance frequency was self tuned in a range of 360 to 410 kHz to provide enough power even at high afterloads. An automatic cardiac output regulation algorithm was developed based on interventricular pressure analysis and carried out in several animal experiments successfully. All electronics have been evaluated in vitro and in vivo and prepared for implantation of the TAH. Substantial progress has been made in designing a completely implantable TAH at the preclinical stage.

Algorithms↗
PubMed1998

Roller pump induced tubing wear of polyvinylchloride and silicone rubber tubing: phase contrast and scanning electron microscopic studies.

Tubing wear and spallation have long been recognized as complications of roller pumps used in cardiopulmonary bypass (CPB) although the reported results of studies of polyvinylchloride (PVC) and silicone rubber tubing wear are still controversial. We conducted phase-contrast microscope (PCM) and scanning electron microscope (SEM) studies of roller pump induced tubing wear. A closed CPB circuit was constructed, and both PVC and silicone rubber tubing (1/2 inch internal diameter [ID]) were tested under normal and tight occlusions of a dual roller pump at a typical CPB flow rate (4,500 ml/min) for 1, 2, 4, and 6 h in quintet. After each pump run, the tubing was removed. It was first examined with PCM, and suspicious portions were then analyzed in detail using SEM. In silicone rubber tubing of longer running time, the external diameter often decreased. Wear was invariably found on the luminal surfaces at the junction of the inner and outer walls of both the PVC and silicone rubber tubing with no significant differences between normal and tight occlusion. The grooves in the PVC tubing were narrow and continuous with occasional deep cracks in the tubing after more than 3 h of pump run. The grooves in the silicone rubber tubing were wide and often interrupted with occasional V-shaped elevated areas. Craters of less than 50 microns occurred sporadically in both types of tubing. Neither PVC nor silicone rubber tubing offers advantages in terms of roller pump induced tubing wear and spallation.

Cardiopulmonary Bypass↗
PubMed1998

Diagnostic pitfalls of Merkel cell carcinoma and dramatic response to chemotherapy.

Merkel cell carcinoma (MCC) is an unusual malignant tumor that arises from neuroendocrine cells with features of epithelial differentiation. We describe a MCC patient with unusual clinical, histopathological, and immunohistochemical features. Although the microscopic, immunohistochemical, and ultrastructural characteristics of MCC have been well defined, diagnostic difficulties remain, particularly in distinguishing it from lymphoma involving the skin, as suggested by our case. This is an unusual case in which dense lymphoid infiltration masked the true tumor. All the immunohistochemical markers of MCC except neuron-specific enolase (NSE) were negative. The dramatic response to primary chemotherapy was also very noteworthy.

Adult↗