• Title/Summary/Keyword: Hearts-on

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Whole body hypoxic preconditioning-mediated multiorgan protection in db/db mice via nitric oxide-BDNF-GSK-3β-Nrf2 signaling pathway

  • Li, Yuefang;Huang, Yan;Cheng, Xi;He, Youjun;Hu, Xin
    • The Korean Journal of Physiology and Pharmacology
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    • v.25 no.4
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    • pp.281-296
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    • 2021
  • The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetes-induced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholine-induced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O2 for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (L-NAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IR-induced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.

Effects of Gastrodia Rhizoma Extracts on Global Coronary Circulation in Rats (천마 Extracts가 백서의 국소적 관상순환기능에 미치는 영향)

  • Kim, Eun-Ji;Ji, Geun-Eog;Kang, Young-Hee
    • Korean Journal of Food Science and Technology
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    • v.26 no.3
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    • pp.213-220
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    • 1994
  • Gastrodia (G) Rhizoma has been used clinically as an oriental herbal medicine with sedative, anticonvulsive, and depressor effects. The present study tested effects of G. Rhizoma extracts on the coronary circulation and myocardial oxygen consumption in perfused rat hearts. Sprague Dawley rats (SD) and spontaneously hypertensive rats (SHR) were employed as experimental animals and nonworking Langendorff heart perfusion technique introduced for heart experiments. G. Rhizoma extracts were prepared from grinding G. Rhizoma into powder, extracting in water and 50% ethanol for 4 or 16 hr and diluting with Krebs-Henseleit bicarbonate perfusion buffer to be 70%. Hearts were perfused with bicarbonate buffer oxygenated with 95% $O_{2}:$ 5% $CO_{2}$ at constant coronary perfusion pressure of $90cmH_{2}O$. The diluted extracts were infused into coronary arteries in a concentration of $1{\sim}5\;{\mu}M$ for $7{\sim}8 min. While in SD water- or ethanol-extracts of G. Rhizoma extracted for 16 hr increased coronary perfusate flow (CPF) and decreased coronary vascular resistance (CVR), ethanol-extracts in SHR produced coronary vasoconstriction associated with enhanced CVR. G. Rhizoma extracts-induced increase in CPF reduced myocardial oxygen extraction, and thus myocardial oxygen consumption ($MVO_{2}$) remained at that observed prior to infusion of extracts. In SD and SHR 16 hr-water-extracts markedly altered coronary venous effluent pH and $Pco_{2}$ and evoked metabolic acidosis, which could be a coronary vasodilator mechanism decreasing CVR. In this study, the extracts decreasing CVR in SD and SHR did not augment the lactate production. Therefore, although the effects of the extracts on cardiac function and coronary circulation depended on solvents and duration for extraction, the 16hr-water-extracts, at least, exhibited coronary vasodilation in SD and SHR. Conversely, ethanol-extracts constricted coronary arteries in SHR. G. Rhizoma extracts-induced vasodilation might be due to the metabolic acidosis rather than due to the increased lactate production. The results indicate that G. Rhizoma extracts obtained from proper extracting procedures can be used as a safe and clinically applicable herbal medicine in the cardiovascular diseases such as coronary artery disease and hypertension for vasodilatory and antihypertensive actions.

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Hunting for the Hurt in Chaucer′s Book of the Duchess

  • Vaughan, Miceal F.
    • Lingua Humanitatis
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    • v.2 no.2
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    • pp.85-107
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    • 2002
  • The word play on h(e)art-hunting has become a virtual commonplace in criticism of Chaucer′s Book of the Duchess. Less widely discussed is the third meaning of ME herte, "hurt." The "hart"/ "heart" pun is, however, only implicit in the poem, while the rhyme of "heart" and "hurt" in lines 883-84 makes clear the close association of the terms for Chaucer. Earlier commentators insisted that this was in fact an instance of rime riche or "identical rhyme," but if it is so it is striking that it is the unique instance of the rhyme in Chaucer, whose works are full of occasions for hurt hearts. The essay argues that this is, instead, an instance of near-rhyme and that the confusion in scribal spellings of ME hurten(with ′u,′ ′0,′ ′i,′ ′y,′ and ′e′ ) suggests uncertainties about its root vowel that modem linguistic study has not clarified completely. If the rhyme of herte ("hurt") with herte ("heart") is, however, established by these lines in BD, then it is probably reasonable to ask about all the occasions where characters in the poem are hurt by emotional or physical distress. In the cases of A1cyone and the Man in Blak, the hurt is revealed plainly as the death of a loved one, and Alcyone′s death and the Man in Blak′s return "homwarde" offer contrasting responses to the realization and acknowledgement of their loss. In the case of the Narrator, however, the exact nature of his "hurt" is nowhere made clear and the questions this Jack of clarity raises for the reader remain unanswered when the poem declares its "hert-huntyng" done. Further examination of the Narrator′s character and his role in the poem may reveal him to be a physician himself in need of healing, and this reading of his character may identify him as an ancestor as much of Chaucer′s Pardoner as of the Pilgrim Narrator of Canterbury Tales.

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Ginseng total saponin attenuates myocardial injury via anti-oxidative and anti-inflammatory properties

  • Aravinthan, Adithan;Kim, Jong Han;Antonisamy, Paulrayer;Kang, Chang-Won;Choi, Jonghee;Kim, Nam Soo;Kim, Jong-Hoon
    • Journal of Ginseng Research
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    • v.39 no.3
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    • pp.206-212
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    • 2015
  • Background: Ginseng total saponin (GTS) contains various ginsenosides. These ginsenosides are widely used for treating cardiovascular diseases in Asian communities. The aim of this study was to study the effects of GTS on cardiac injury after global ischemia and reperfusion (I/R) in isolated guinea pig hearts. Methods: Animals were subjected to normothermic ischemia for 60 minutes, followed by 120 minutes of reperfusion. GTS significantly increased aortic flow, coronary flow, and cardiac output. Moreover, GTS significantly increased left ventricular systolic pressure and the maximal rate of contraction ($+dP/dt_{max}$) and relaxation ($-dP/dt_{max}$). In addition, GTS has been shown to ameliorate electrocardiographic changes such as the QRS complex, QT interval, and RR interval. Results: GTS significantly suppressed the biochemical parameters (i.e., lactate dehydrogenase, creatine kinase-MB fraction, and cardiac troponin I levels) and normalized the oxidative stress markers (i.e., malondialdehyde, glutathione, and nitrite). In addition, GTS also markedly inhibits the expression of interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, and nuclear factor-${\kappa}B$, and improves the expression of IL-10 in cardiac tissue. Conclusion: These data indicate that GTS mitigates myocardial damage by modulating the biochemical and oxidative stress related to cardiac I/R injury.

Studies on Digitalis Receptor Desensitization in Rat Ventricle

  • Lee, Shin-Woong-;Jang, Tae-Soo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.04a
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    • pp.301-301
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    • 1994
  • $^3$H〕Ouabain binding parameters(K$\_$D/ and B$\_$max/,) in homogenates prepared fpom control rat ventricular strip and Langendorff preparations which were not previously exposed to ouabain were compared to those in homogenates from ventricular strip and Langendorff preparations that had been first exposed to a complete ouabain dose-response curve(10$\^$-7/M to 10$\^$-4/ M). In rat ventricular strips and Langendorff perfused rat heart preparations, cumulative dose-response cruves of ouabain revealed biphasic positive inotropic effects, a "low-dose" and a "high-dose" effect with ED$\_$50/ values of 0.5${\mu}$M and 35${\mu}$M ouabain, respectively- The "low-dose" effect in rat ventricular strips disappeared or was diminished significantly when the ouabain dose-response curve wag repeated after the washout of the effects of the first curve, whereas the maximal "high-dose" effect was identical in both exposures to oubain. However, there was no change in the "low-dose" effects in both sets of the Langendorff perfused hearts. The contractile activity of the pre-exposed strips did not indicate the presence of residual ouabain since their basal contractile force was decreased 10% compared to initial control. 〔$^3$H〕Ouabain binding parameters, K$\_$D/ and B$\_$max/, were not changed comparing homogenate of control ventricular strips with that of strips pre-exposed to ouabain. These results suggest that digitalis receptor desensitization in the rat ventricular strip may due to the change of post-receptor events induced by ouabain binding to a high affinity site(${\alpha}$$_2$ isoform).

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The hybrid perventricular closure of apical muscular ventricular septal defect with Amplatzer duct occluder

  • Kim, Soo Jin;Huh, June;Song, Jin Young;Yang, Ji-Hyuk;Jun, Tae-Gook;Kang, I-Seok
    • Clinical and Experimental Pediatrics
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    • v.56 no.4
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    • pp.176-181
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    • 2013
  • Purpose: Apical muscular ventricular septal defects (MVSDs), especially in small infants, can be difficult to manage using surgical and percutaneous closure. An intraoperative perventricular procedure is a good option for closing apical MVSDs in small children with or without associated cardiac anomalies. We evaluated the results of hybrid perventricular closure of apical MVSDs performed using an Amplatzer duct occluder (ADO). Methods: We retrospectively reviewed the medical records of 5 patients who underwent hybrid perventricular closure of MVSDs with ADOs, from March 2006 to May 2011. The median patient age at the time of the procedure was 12 months (range, 25 days to 25 months), and the median body weight was 9.1 kg (range, 4.3 to 15 kg). Two patients had multiple ventricular septal defects (VSDs; additional perimembranous VSD in 1 patient and multiple MVSDs in the other) and 3 patients had associated cardiac anomalies; complete transposition of the great arteries in 1 patient and an atrial septal defect in 2 patients. All the procedures were performed on beating hearts, exception in 1 case. The ADO selected for the aortic side was at least 1 to 2 mm larger than the largest VSD in the left ventricle side. Results: The procedure was successful in all patients and each device was well positioned. During the median follow-up of 2.4 years, a small residual VSD was noted in 2 patients who had multiple VSDs and no leakage was seen in the other 3 patients. Conclusion: Perventricular closure of MVSD with an ADO is a good option for patients with apical MVSD. However, careful manipulation is important, especially in the case of small infants.

Reduction of Muscarinic $K^+$ Channel Activity by Transferrin in Ischemic Rat Atrial Myocytes

  • Park, Kyeong-Tae;Kang, Da-Won;Han, Jae-Hee;Hur, Chang-Gi;Hong, Seong-Geun
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.6
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    • pp.333-339
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    • 2003
  • It has been demonstrated that an unidentified cytosolic factor(s) reduces $K_{ACh}$ channel function. Therefore, this study attempted to elucidate the cytosolic factor. Fresh cytosol isolated from normal heart (FC) depressed the $K_{ACh}$ channel activity, but cytosol isolated from the ischemic hearts (IC) did not modulate the channel function. Electrophorectic analysis revealed that a protein of ${\sim}80 kDa was markedly reduced or even lost in IC. By using peptide sequencing analysis and Western blot, this 80 kDa protein was identified as transferrin (receptor-mediated $Fe^{3+}$ transporter, 76 kDa). Direct application of transferrin (100 nM) to the cytoplasmic side of inside-out patches decreased the open probability ($P_o$, 12.7${\pm}6.4%, n=4) without change in mean open time (${\tau}_o$, $98.5{\pm}1.3$%, n=4). However, the equimolar apotransferrin, which is free of $Fe^{3+}$, had no effect on the channel activity (N*$P_o$, $129.1{\pm}13.5$%, n=3). Directly applied $Fe^{3+}$ (100 nM) showed results similar to those of transferrin (N*$P_o$: $21.1{\pm}3.9$%, n=5). However $Fe^{2+}$ failed to reduce the channel function (N*$P_o$, $106.3{\pm}26.8$%, n=5). Interestingly, trivalent cation La3+ inhibited N*$P_o$ of the channel ($6.1{\pm}3.0$%, n=3). Taken together, these results suggest that $Fe^{3+}$ bound to transferrin can modulate the $K_{ACh}$ channel function by its electrical property as a polyvalent cation.

Traditional oriental herbal medicine, Jukyeoondam-tang, occludes aconitine-induced ventricular arrhythmia in hearts

  • Ha, Ki-Chan;Chae, Han-Jung;Piao, Cheng-Shi;Chae, Soo-Uk;Kim, Hyung-Ryong;Chae, Soo-Wan
    • Advances in Traditional Medicine
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    • v.4 no.3
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    • pp.157-161
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    • 2004
  • We showed the effects of the traditional herbal medicine, Jukyeoondam-tang (JO-T, Zhu-ru-Wen-Dan-Tang in Chinese), on ventricular arrhythmia induced by aconitine. Electrophysiological experiments with conventional microelectrode techniques revealed that JO-T potently suppressed the aconitine-induced arrhythmias in ventricular strips of the rat. In the aconitine-induced arrhythmia model of the rat, pretreatment with JO-T $(100\;{\mu}g/ml)$ completely occluded the appearance of ventricular tachyarrhythmia (VT) or ventricular fibrillation (VF) induced by aconitine. Furthermore, the aconitine-induced ventricular arrhythmia was occluded by $Na^+$ channel blocker quinidine but was not occluded by $K^+$ channel blocker glibenclamide $(3\;{\mu}mol/L)\;and\;Ca^{2+}$ channel blocker nifedipine $(10\;{\mu}mol/L)$. We also confirmed the effect of JO-T in the ischemia-reperfusion (I/R)-induced arrhythmia model of the rat. JO-T did not affect the I/R-induced arrhythmias in rats. JO-T may alleviate the risk of ventricular arrhythmias following aconitine. These results suggest that JO-T is a potent antiarrhythmic drug having a$Na^+$ channel-blocking action.

A Study on Design of Diseases of Mind Ontologies for Juvenile Consultation (청소년 상담을 위한 마음의 병 온톨로지 설계에 관한 연구)

  • Baek, Hyeon-Gi
    • Journal of Digital Contents Society
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    • v.13 no.4
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    • pp.547-557
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    • 2012
  • Youths express their own negative experiences and feelings come from their deeply wounded mind. They seek the root cause of these wounded hearts from other people or external environment. Youths revisited the past to heal painful memories. This study designed ontology in order to provide information about the causes and symptoms of illness of the mind for youth counseling. Application ontology enables high-volume and intricate knowledge not only to get set up systematically but also to be stored as the meaningful information. It is also very useful as an integrating tool of the existing complex counseling nomenclature. And ultimately, through revitalization of the sharing and reuse of materials, it becomes possible to provide client-centered counseling services. Therefore, this study built ontology of the mind-illness as a way to analyze the causes and symptoms of the disease in the client mind for providing personalized youth counseling services.

Experimental Implantation of Moving Actuator Type Total Artificial Heart in Sheep (양에서 시행한 이동작동기 형태(MOVING ACTUATOR TYPE) 인공심장의 삽입실험)

  • 김원곤
    • Journal of Chest Surgery
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    • v.28 no.6
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    • pp.533-541
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    • 1995
  • We recently developed a new model of moving actuator type totally implantable artificial heart[TIAH , based on the reverse position of the aortic and pulmonary conduits. This concept was proposed by one of surgeons in our team[Joon-Ryang Rho, M.D. to facilitate anatomical fitting of TIAHs. The moving actuator type electromechanical TIAH consisted of the left and right blood sacs, and the moving actuator including a motor. The inverted umbrella type polyurethane valves were used in the blood pumps. The aortic conduit was positioned anterior to the pulmonary conduit, which was the opposite relation to the conventional configuration of other total artificial hearts. We also adapted slip-in connectors for the aortic and pulmonary conduits. Two sheep , weighing 60-69 kg, were used for implantation. After small cervical incision and trans-sternal bilateral thoracotomy, cardiopulmonary bypass [CPB was administered using an American Optical 5-head pump and a membrane oxygenator[Univox-IC, Bentley . The anterior and posterior vena cavae were drained separately for venous return. An arterial return cannula was inserted into the right common carotid artery. During CPB, almost all of the ventricular myocardium was excised down to the atrioventricular groove and the artificial heart was implanted. We achieved 3-day survival in the first sheep and 2-day survival in the second. The day after operation the first sheep was successfully extubated and the second sheep was weaned from a respirator with good condition. After extubation, the first sheep walked around in the cage and fed herself. Serial laboratory and hemodynamic examinations were done during the experiments. In both sheep, pulmonary dysfunction was gradually developed, which was accompanied by acute renal failure. The animals were sacrificed and autopsy was done. Unexpected pregnnacy was incidentally found in both sheep. To our knowledge this is the first report of significant survival cases in the orthotopic implantation of electric TIAH using sheep.

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