Recently, autologous bone marrow cell transplantation (CTx) for angiogenesis and myogenesis in ischemic myocardium has been extensively investigated to improve heart functions. This study was designed to evaluate the effects of CTx with off-pump coronary artery bypass grafting (OPCAB) in patients who were not feasible for complete revascularization. Material and Method: Four male patients underwent CTx and OPCAB simultaneously. Bone marrow was aspirated from iliac bone. Mean 1.5 ${\times}$ 10$^{9}$ mononuclear cells including mean 6.7 ${\times}$ 10$^{6}$ CD34 + cells and 3.7 ${\times}$ 10$^{6}$ AC133 + cells were obtained and concentrated with 10 cc. These cells were transplanted into non-graftable ischemic myocardium after OPCAB. The heart function of all patients were evaluated using the MIBI scan, echocardiogram and MRI preoperatively. The effects of CTx was evaluated using MIBI scan and echocardiogram at 1 month postoperatively. Result: An average of 2 grafts were bypassed to left anterior descending artery territory. Other territories were transplanted with isolated mononuclear cell. All patients had uncomplicated postoperative course. After 1 month follow up, there were improvement in symptom, ejection fraction (from 49% to 55%) on echocardiogram and myocardial perfusion on MIBI scan in all patients. Conclusion: These preliminary data showed improvement of heart function and myocardial perfusion and also showed the feasibility and safety of combined therapy with OPCAB and CTx in ischemic myocardium. However, the effectiveness of CTx alone cannot be readily assessed. Further randomized, controlled studies are required to evaluate the effectiveness of CTx alone.
Joo, Chan Uhng;Juhng, Woo Suk;Kim, Jae Cheol;Yi, Ho Keun
Clinical and Experimental Pediatrics
/
v.45
no.9
/
pp.1106-1113
/
2002
Purpose : Nuclear ($factor-{\kappa}BNF-{\kappa}B$) is now recognized as playing a potential role in programmed cell death and the adaptive response to various stress. Cellular hypoxia is a primary manifestation of many cardiovascular diseases. It seems that vascular endothelial growth factor (VEGF) and insulin like growth factor-I(IGF-I) have a function as a protective molecule in the heart against several stress including hypoxia. In this study, the role of $NF-{\kappa}B$ to the cellular response and regulation of protective molecules against the acute hypoxia in the heart was studied. Methods : To cause acute hypoxic stress to the heart, Sprague Dawley rats were exposed to hypoxic chamer($N_2$ 92% and $O_2$ 8%). After the hypoxic exposure, nuclear proteins, total proteins and mRNA were isolated from heart. Translocation of the transcription factors $NF-{\kappa}B$, NF-ATc, AP-1 and NKX-2.5 were evaluated by electrophoretic mobility shift assay(EMSA). The expression of IGF-I and VEGF were studied before and after the hypoxic stress by competitive-PCR, Northern hybridization and Western hybridization. To confirm the role of the $NF-{\kappa}B$ in the heart, the rats also were pretreated with diethyl-dithiocarbamic acid(DDTC) into peritoneal cavity to block $NF-{\kappa}B$ translocation into nucleus. Results : The expression of $NF-{\kappa}B$, AP-1 and NF-ATc were increased by the hypoxic stress. Increased expression of the VEGF and IGF-I were also observed by the hypoxic stress. However, the blocking of the $NF-{\kappa}B$ translocation reduced those expressions of VEGF and IGF-I. Conclusion : These results suggest that $NF-{\kappa}B$ has a protective role against the acute hypoxia through several gene expression, especially VEGF and IGF-I in heart muscle.
Chang, Yun Sil;Sung, Dong Kyung;Kang, Saem;Park, Soo Kyung;Jung, Yu Jin;Seo, Hyun Joo;Choi, Seo Heui;Park, Won Soon
Clinical and Experimental Pediatrics
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v.51
no.8
/
pp.874-878
/
2008
Purpose : This study was undertaken to develop an animal model of periventricular leukomalacia (PVL) induced by in utero clamping of pregnant rat aorta in fetal rats. Methods : A timed pregnanct Sprague-Dawley rat on embryonic day 21 just prior to delivery was sedated and anesthetized, and a Harvard ventilator for small animals was applied. Following laparotomy, the maternal aorta was clamped reversibly for 40 minutes using a surgical clip. The fetal rats were then delivered by Cesarean section, resuscitated if necessary, and reared by a surrogate mother rat until postnatal day 21 to obtain the brain specimen. After systemic perfusion and fixation, $10{\mu}m$ thick serial brain sections were obtained and stained for pathologic examination and assessment of ventriculomegaly. Ventriculomegaly was assessed by the measured ventricle to total brain volume ratio. Results : Eight out of eleven fetal rats (73%) survived in the ischemia group after induction of in utero ischemia by clamping maternal rat aorta, and all ten survived in the control group. Body and brain weights measured at postnatal day 21 were significantly lower in the ischemia group compared to the control group. In pathologic findings, significant ventriculomagaly ($3.67{\pm}1.21%$ vs. $0.23{\pm}0.06%$) was observed in the ischemia group compared to the control group; although cystic lesion was not observed, mild (n=6) and moderate (n=2) rerefaction of the brain tissue was observed. Conclusion : A fetal rat model of PVL induced by in utero clamping of pregnant rat aorta was developed.
Background: The washing of packed red blood cells could remove pro-inflammatory mediators, cell debris, and micro-particles contained in packed red blood cells, and the preci-rculation-ultrafiltration (recirculation and ultrafiltration of circuit itself before cardiopulmonary bypass) could attenuate the initial inflammatory reaction and remove the initial proinflam-matory mediators. This study was performed to evaluate whether the washing of packed red blood cells and precirculation-ultrafiltration can reduce the production of cytokines that have an important role in myocardial reperfusion injury. This study investigated the effects of washing the packed red blood cells and precirculation-ultrafiltration on the production of cytokines during and after cardiopulmonary bypass and open heart surgery. Material and Method: Forty eight infants with VSD undergoing open heart surgery under cardiopulmonary bypass were randomized into control group (group C, n=12), washing group (group W, n= 12), precirculation-ultrafiltration group (group F, n: 12), and combined group(washing and precirculation-ultrafiltration, group WF, n=12). Blood samples were obtained before, during, and after the bypass to assess plasma level of tumor necrosis factor-$\alpha$(TNF-$\alpha$), interleukin-6(IL-6), and interleukin-8 (IL-8). Results: Expressions of TNF-$\alpha$ were significantly reduced in combined group (group WF) compared with group C, group W, and group F (p<0.05). Expression of IL-6 were significantly reduced in group W, group F, and group WF compared with group C (p<0.05), but similar among group W, group F, and group WF (p=0.053). Expression of IL-8 were reduced in group W and group WF compared with group C (p<0.05), but similar among group W, group F, and group WF (p=0.067). Conclusion: In conclusion, the washing of packed red blood cells and precirculation-ultrafiltration blunted the increase of TNF-$\alpha$ , IL-6, and IL-8 during and after open heart surgery with cardiopulmonary bypass. However, the clinical benefits of these treatments remains unproven.
This experiment was carried out to determine the optimum freezing and thawing rates of the hamster embryos. The female hamsters were induced to superovulate by intraperitoneal injections of 30 i.u. PMSG and mated with males of the same strain of 4 days the PMSG injection. They were killed and embryos were flushed from the oviduct and uterine horn on 3 days after mating. Embryos were flushed with a modified Dulbecco's phosphate-buffered saline and equilibrated with 1.5 M-dimethylsulphoxide by a 3-step procedure. The freezing rates of the samples were $1^{\circ}C/min$ from room temperature to $-6^{\circ}C$ and the samples were seeded at $-6^{\circ}C$. After being held for 3 min at the seeding temperature, the rates were $0.3^{\circ}C/min$ from $-6^{\circ}C$ to $-35^{\circ}C$. From $-35^{\circ}C$ to $-70^{\circ}C$, the rates were divided into $0.1^{\circ}C/min$, $1^{\circ}C/min$ and $10^{\circ}C/min$, respectively. At $-70^{\circ}C$ the samples were plunged directly into liquid nitrogen. The samples were thawed at $4^{\circ}C/min$ and $12^{\circ}C/min$ from $-196^{\circ}C$ to $37^{\circ}C$, and for 2 min in $37^{\circ}C$ water bath, respectively. The average numbers of ovulation points and embryos recovered were 35.1 and 27.0 appearing 77.0% recovery rates. Eight cell embryos in the embryos recovered were 24.8. The survival rates of embryos according to the freezing rates were 55.5~67.7% at $0.1^{\circ}C/min$, 58.8~64.9% at $1^{\circ}C/min$ and 40.5~44.7% at $10^{\circ}C/min$, respectively. The survival rates at $10^{\circ}C/min$ were significantly low. The survival rates of embryos according to the thawing rates were 53.5% at $4^{\circ}C/min$, 53.7% at $12^{\circ}C/min$ and 59.1% in $37^{\circ}C$ water bath. The survival rates, in $37^{\circ}C$ water bath were slightly higher, but we did not find any differences among them. In conclusion, the best freezing rates of hamster embryos were $1^{\circ}C/min$ from the room temperature to $-6^{\circ}C/min$, $0.3^{\circ}C/min$ from $-6^{\circ}C/min$ to $-35^{\circ}C$ and $-0.1^{\circ}C/min$ or $1^{\circ}C/min$ from $-35^{\circ}C$ to $-70^{\circ}C$. The hamster embryos thawed for 2 min in $37^{\circ}C$ water bath showed the best survival rates.
Park Kuhn;Lee Jong Ho;Kim Jin Ho;Jin Ung;Kwon Jong Bum;Kim Chi Kyeong;Wang Young Pil
Journal of Chest Surgery
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v.38
no.12
s.257
/
pp.807-814
/
2005
Background: Cardiopulmonary bypass is an essential process to maintain circulation for saving life during the cardiac surgery, But it is a process in which systemic inflammation was evoked inevitably because of the exposure of blood to foreign surface. The injuries to distal organs during the cardiopulmonary bypass were resulted from systemic inflammation and the disturbances of micro-circulations in the organs. We designed this study to research the effects of leukocyte depletion from pump-oxygenator priming solution on the systemic inflammation, and the micro-circulation of gastric mucosa that is suggested by the gastric mucosal $CO_{2}$ partial pressure and acidity. Material and Method: The dogs were divided into three groups according to the different pump-oxygenator priming solutions; non-hemic crystalloid solution; leukocyte-depleted homologous blood; and non leukocyte-depleted homo-logous blood. Each priming solution group contained five dogs. In all three groups, 2 hours of cardiopulmonary bypass, and 4 consecutive hours of general anesthesia was maintained on the mechanical ventilation. Each dog was evaluated for the gastric mucosal pH, $CO_{2}$ partial Pressure, arterial pH, $CO_{2}$ partial pressure, the exhaled air $CO_{2}$ partial pressure and the level of IL-8 on before the cardiopulmonary bypass, 1 hour after the cardiopulmonary bypass, 2 hours after the cardiopulmonary bypass, 2 hours after the restoration of normal circulation, and 4 hours after the restoration of normal circulation after the cardiopulmonary bypass. The levels of IL-8 were measured with ELISA (enzyme linked immunosorbent assay) technique. Result: 1. There were significant differences of gastric mucosal $CO_{2}$ partial pressure between the leukocyte-depleted homologous blood group and other two groups(vs non leukocyte-depleted homologous blood group; P=0.02, vs non-hemic crystalloid solution group; P=0,01). 2. The gastric mucosal pH of leukocyte-depleted homologous blood group was significantly different from non leukocyte-depleted homologous blood group (p=0.01). 3. The levels of IL-8, which examine the systemic inflammation, showed signi- ficantly better results in leukocyte-depleted homologous blood group and non-hemic crystalloid solution group than non leukocyte-depleted homologous blood group (p=0.01, 0.01). Conclusion: Based upon these results, we concluded that the leukocyte depletion from the pump-oxygenator priming solution has a beneficial effects in reducing systemic inflammation and the preserving of gastric mucosal micro-circulation.
Purpose : To report our clinical experience with cardiac 3.0 T MRI in patients compared with 1.5 T using individually optimized imaging protocols. Materials and Methods: We retrospectively reviewed 30 consecutive patients and 20 consecutive patients who underwent 1.5 T and 3 T cardiac MRI within 10 months. A comparison study was performed by measuring the signal-to-noise ratio (SNR), the contrast-to-noise ratio (CNR) and the image quality (by grading each sequence on a 5-point scale, regarding the presence of artifacts). Results: In morphologic and viability studies, the use of 3.0 T provided increase of the baseline SNRs and CNRs, respectively (T1: SNR 29%, p < 0.001, CNR 37%, p < 0.001; T2-SPAIR: SNR 13%, p = 0.068, CNR 18%, p = 0.059; viability imaging: SNR 45%, p = 0.017, CNR 37%, p = 0.135) without significant impairment of the image quality (T1: $3.8{\pm}0.9$ vs. $3.9{\pm}0.7$, p = 0.438; T2-SPAIR: $3.8{\pm}0.9$ vs. $3.9{\pm}0.5$, p = 0.744; viability imaging: $4.5{\pm}0.8$ vs. $4.7{\pm}0.6$, p = 0.254). Although the image qualities of 3.0 T functional cine images were slightly lower than those of 1.5 T images ($3.6{\pm}0.7$ vs. $4.2{\pm}0.6$, p < 0.001), the mean SNR and CNR at 3.0 T were significantly improved (SNR 143% increase, CNR 108% increase, p < 0.001). With our imaging protocol for 3.0 T perfusion imaging, there was an insignificant decrease in the SNR (11% decrease, p = 0.172) and CNR (7% decrease, p = 0.638). However, the overall image quality was significantly improved ($4.6{\pm}0.5$ vs. $4.0{\pm}0.8$, p = 0.006). Conclusion: With our experience, 3.0 T MRI was shown to be feasible for the routine assessment of cardiac imaging.
Background : Many patients with isoniazid and rifampin-resistant pulmonary tuberculosis have organisms that are also resistant to other first-line drugs. Despite of aggressive retreatment chemotherapy, the results are often unsuccessful, with a failure rate approaching 40%. Recently, there has been a revival of resectional surgery for the treatment of multidrug-resistant pulmonary tuberculosis. Methods : A retrospective analyses of the case records and radiographic findings were done. Between January 1991 and December 1995, 14 human immunodeficiency virus (HIV)-seronegative patients with multidrug-resistant pulmonary tuberculosis were selected for resection to supplement chemotherapy. All patients had organisms resistant to many of the first-line drugs, including both isoniazid and rifampin. Results : Despite of aggressive therapy for median duration of 9.5 months, 12 of the 14 patients (86%) were still sputum smear and/or culture positive at the time of surgery. The disease was generally extensive. Although main lesions of the disease including thick-walled cavities were localized in one lung, lesser amounts of contralateral disease were demonstrated in 10 of 14 (71%). Types of surgery performed were pneumonectomy including extrapleural pneumonectomy in six patients, lobectomy or lobectomy plus in six patients, and segmentectomy in two patients. The resected lung appeared to have poor function ; preoperative perfusion lung scan showed only 4.8% of the total perfusion to the resected portion of the lung. There were no operative deaths. Two patients had major postoperative complications including empyema with bronchopleural fistula and prolonged air leak, respectively. Of the 14 patients, 13 (93%) remained sputum-culture-negative for M. tuberculosis for a median duration of 23 months and one remained continuously sputum smear and culture positive for M. tuberculosis. Conclusion : On the basis of comparison with historical controls, adjunctive resectional surgery appears to play a significant beneficial role in the management of patients with multidrug-resistant pulmonary tuberculosis if the disease is localized and there are adequate reserve in pulmonary function.
Background: Paraplegia is a serious complication of thoracic or thoracoabdominal aortic operations, which is related to ischemic injury of the spinal cord induced by low perfusion pressure during cross clamping of the aorta. Ischemic preconditioning of heart or brain with reversible sublethal ischemic injury induces resistance to subsequent lethal ischemia. The aim of this study is to investigate whether ischemic tolerance could be induced by the preconditioning of the spinal cord using swine model. Material and Method: The animals were randomly assigned to three groups: sham group(n=3), control group(n=6) and pre-conditioning group(n=8). In the sham group, we performed the left thoracotomy only without any ischemic injury. In the preconditioning group, the swine received reversible spinal cord ischemic injury by aortic clamping for 20 minutes, whereas control group had no previous aortic cross- clamping. Forty-eight hours later, the aorta was clamped for 30 minutes in both groups. Neurological examination was done 24 hours later, then the animals were euthanized for histopathology and malonedialdehyde(MDA) spectrophotometry assay of the spinal cord. Result: Statistically significant difference in neurological outcome was observed between the control and preconditioning groups at 24 hours after ischemic injury. The incidence of paraplegia and severe paresis was 100% in the control group, and 62.5% in the preconditing group(p=0.028). There was no statistically significant difference in histopathology and MDA assay of the ischemic spinal cord between these two groups with borderline statistical difference in MDA assay(p=0.0745). Conclusion: In the present swine study, ischemic preconditioning could induce tolerance against 30 minute ischemic insult of the spinal cord, although the animals did not completely recover(stand-up or walk). We expect that combining this preconditioning with other currently existing protection methods might lead to a synergistic effect, which warrants further investigation.
Blood cardioplegia is known as an established cardioplegic solution during open heart surgery. Recently, the Histidine-Tryptophan-Ketoglutarate (HTK) solution has been introduced as a cardioplegia in Korea. This study was designed to compare the myocardial protective effect between the cold blood cardioplegia (CBC) and HTK solution. Material and Method: Forty patients who underwent valve surgery or coronary artery bypass surgery were randomly divided into CBC group (n=20) and HTK group (n=20). The perioperative hemodynamic and clinical data were analyzed. The concentration of CK-MB, Troponin 1 and Lactate from coronary sinus and radial arterial blood were compared for the evaluation of the myocardial damage. The postoperative serial CK-MB levels were measured. Result: The characteristics of preoperative patients were similar in two groups. The hemodynamic parameters and postoperative clinical data were also similar between the two groups. There were no statistical significances between the CBC and HTK group in the difference of biochemical markers: Δ CK-MB (15.3$\pm$26.0 vs 19.3$\pm$14.3), ΔTro-1 (2.4$\pm$4.9 vs 2.0$\pm$2.20), ΔLac (1.6$\pm$1.0 vs 1.9$\pm$2.5). The serial CK-MB levels were not significantly different between the two groups. Conclusion: These results suggested that the myocardial protective effect of HTK solution was similar to cold blood cardioplegia during open heart surgery.
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