• Title/Summary/Keyword: Cardiovascular protection

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Direct Action of Genistein on the Hypothalamic Neuronal Circuits in Prepubertal Female Rats : Estrogen Receptor Beta($ER{\beta}$) Pathway? (미성숙한 암컷 흰쥐 시상하부의 신경회로에 미치는 Genistein의 직접 작용 : 에스트로겐 수용체 베타아형 경로?)

  • Heo, Hyun-Jin;Lee, Sung-Ho
    • Development and Reproduction
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    • v.15 no.2
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    • pp.179-185
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    • 2011
  • Some phytoestrogens in soy and red wine, for example, might have beneficiary rather than adverse effects. In particular, dietary soy intake seems to be highly correlated with protection of breast cancer, osteoporosis and cardiovascular disorders. However, questions persist on the potential adverse effects of the main soy constituent genistein (GS) on female reproductive physiology. Previously we found that prepubertal exposure to GS could activate the reproductive system of immature female rats leading to precocious puberty onset, and intracerebroventricularly (ICV) injected GS could directly activate hypothalamic kisspeptin-GnRH neuronal circuits in adult female rats. The present study was performed to examine the hypothalamus-specific GS effects in prepubertal female rats and which subtype of estrogen receptor is mediated in this GS effect. Prepubertal female rats (PND 30) were anaesthetized, treated with single dose of GS (3.4 ${\mu}g$/animal), and sacrificed at 2 hrs post-injection. To determine the transcriptional changes of reproductive hormone-related genes in hypothalamus, total RNAs were extracted and applied to the semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). ICV infusion of GS significantly lowered the transcriptional activities of mTOR (1:$0.361{\pm}0.058$ AU, p<0.001) but increased that of GAD67 (1:$1.285{\pm}0.099$ AU, p<0.05), which are known to act as an upstream modulator of kisspeptin and GnRH neuronal activities in the hypothalamus, respectively. GS administration enhanced significantly the mRNA levels of KiSS-1(1:$1.458{\pm}0.078$ AU, p<0.001), and exerted no effect on the mRNA level of kisspeptin receptor GPR-54 (1:$1.29{\pm}0.08$ AU). GnRH gene expression was significantly decreased in GS-treated group compared to control group (1:$0.379{\pm}0.196$ AU, p<0.05). There was no difference in the mRNA level of $ER{\alpha}$ in the GS-treated group compare to control group (1:$1.180{\pm}0.390$ AU, Fig. 3A). However, icv infusion of GS significantly increased the transcriptional activities of $ER{\beta}$ (1:$4.209{\pm}0.796$ AU, p<0.01, Fig. 3B). Taken together, the present study indicated that the acute exposure to GS could directly alter the hypothalamic GnRH modulating system in prepubertal female rats. Our study strongly suggested the involvement of $ER{\beta}$ pathway in GS's hypothalamus-specific action, and this idea is consistent with the GS's well-known $ER{\beta}$-mediated protective action in breast cancer.

Repair of Acute Aortic Arch Dissection with Hypothermic Circulatory Arrest and Retrograde Cerebral Perfusion (저체온순환정지와 역행성 뇌관류에 의한 대동맥궁을 침범한 급성 대동맥 박리증의 수술결과)

  • 이삼윤
    • Journal of Chest Surgery
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    • v.37 no.1
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    • pp.43-49
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    • 2004
  • Background: Acute thoracic aortic dissections involving the aortic arch differ in diagnosis, surgical procedures, and operative results compared to those that do not involve the aortic arch. In general cerebral perfusion under deep hypothermic circulatory arrest (HCA) is performed during the repair of the aortic arch dissection. Here, we report our surgical results of the aortic arch dissection repair using retrograde cerebral perfusion (RCP) and its safety. Material and Method: Between January 1996 and June 2002, 22 consecutive patients with aortic arch dissection underwent aortic arch repair. In 20 of them RCP was performed under HCA. RCP was done through superior vena cava in 19 patients and by systemic retrograde venous perfusion in 1, in whom it was difficult to reach the SVC. When the patient's rectal temperature reached 16 to 18$^{\circ}C$, systemic circulation was arrested, and the amount of RCP amount was 481.1 $\pm$292.9 $m\ell$/min with perfusion pressure of 20∼30 mmHg. Result: There were two in-hospital deaths (4.5%) and one late death (9.1%). Mean circulatory arrest time (RCP time) was 54.0$\pm$ 13.4 minutes (range, 7 to 145 minutes). RCP time has no correlation with the appearance of consciousness, recovery of orientation, or ventilator weaning time (p=0.35, 0.86, and 0.92, respectively). Ventilator weaning was faster in patients with earlier recovery of consciousness and orientation (r=0.850, r=926; p=0.000, respectively). RCP of more than 70 minutes did not affect the appearance of consciousness, recovery of orientation, ventilator weaning time, exercise time, or hospital stay (p=0.42, 0.57, 0.60, 0.83, and 0.51, respectively). Conclusion: Retrograde cerebral perfusion time under hypothermic circulatory arrest during repair of aortic arch dissection may not affect recovery of orientation, ventilator weaning time, neurologic complications, and postoperative recovery.

Use of Undiluted Potassium Solution in Intermittent Antegrade Warm Blood Cardioplegia (IAWBC) (간헐적 전방온혈심정지액에서 희석되지 않은 고농도 포타슘의 사용)

  • 백완기;손국희;김영삼;윤용한;김혜숙;임현경;이춘수;김광호;김정택
    • Journal of Chest Surgery
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    • v.37 no.8
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    • pp.660-664
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    • 2004
  • Background: Dilution of blood cardioplegia is not needed in IAWBC as it is in cold blood cardioplegia because it does not aggregate red blood cells on normal body temperature and does not compromise micro coronary circulation. This study was designed to evaluate the safety and efficacy of undiluted potassium solution in IAWBC. Material and Method: Thirty patients who underwent CABG with IAWBC were grouped into dilutedplegia (n=14) and microplegia (n=16). Potassium was delivered conventionally with 4 : 1 delivery kit in the dilutedplegia group. The undiluted potassium was directly connected on the blood of oxygenator in the microplegia group. Result: There were no differences in sex, age, left ventricular ejection fraction, number of grafts, aortic cross clamping time, and the value of perioperative myocardial enzyme between the two groups. There were no perioperative myocardial infarction and hospital mortality. The amount of crystalloid cardioplegia was 1346$\pm$597 mL in dilutedplegia (mean$\pm$standard deviation, and 28$\pm$9 mL in microplegia (p<0.0001). The hematocrit during cardiopulmonary bypass was 21$\pm$4% in dilutedplegia and 24$\pm$3% in microplegia (p>0.05). 11 patients in dilultedplegia received blood transfusion, but 4 patients in microplegia received blood transfusion (p<0.05). The amount of urine and hemofiltration during the operation were more in dilutedplegia (1250$\pm$810 mL, 1689$\pm$548 mL) than in microplegia (959$\pm$410 mL, 1461$\pm$784 mL; p<0.05). Conclusion: The undiluted potassium of IAWBC in CABG operation is a safe, effective technique for myocardial protection to prevent fluid overload, and blood transfusion. There is no need to use the delivery kit.

Protective Effects of Adenosine-enriched Cardioplegic Solution in Ischemic Myocardium (Adenosine을 함유한 심정지액의 심근보호 효과)

  • 이호철;정태은
    • Journal of Chest Surgery
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    • v.29 no.2
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    • pp.199-207
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    • 1996
  • Ischemic myocardial damage is inevitable to cardiac surgery. Myocardial damage after initiation of reperfusion through the coronary arteries is one of the most important determinants of a successful surgery. Adenosine is a potent vasodilator, and is also known to induce rapid cardioplegic arrest by its property of antagonizing cardiac calcium channels and activating the potassium channel. Thus, we initiated this study with adenosine to improve postischemic recovery in the isolated rat heart. We tested the hypothesis that adenosine could be more effective than potassium in inducing rapid cardiac arrest and enhancing postischemlc hemodynamic recovery. Isolated rat hearts, connected to the Langendorff appratus, were perfused with Krebs-Henseleit buffer and all hearts were subjected to arrest for 60 minutes. Three groups of hearts were studied according to the composition of cardioplegic solutions : Group A (n=10), adenosine 10mmo1/L+potassium free modified St. Thomas cardioplegia : Group B (n=10), adenosine 400mo1/L+S1. Thomas cardioplegia:Group C(control, n=10), St. Thomas cardioplegia. Adenosine-treated groups (group A & B) resulted in more rapid cardiac arrest than control group (C) (p< 0.01). There was greater improvement in recovery of coronary blood flow at 20 and 30 minutes of reperfusion in group A and at 20 minutes in group B when compared with control group(p<0.01). Recovery of systolic blood pressure at 10 minutes after reperfusion in group A and B was significantly superior to that in group C (p<0.01). Recovery of dp/dt at 10 minute after reperfusion in group A was also significantly superior to group C (p<0.05). Group A and B showed better recovery rates than control group in aortic blood flow, cardiac output, and heart rate, but there were no statistical differences. CPK levels of coronary flow in group A were significantly low (p< 0.01). We concluded that adenosine-enriched cardioplegic solutions have better effects on rapid cardiac arrest and postischemic recovery when compared with potassium cardioplegia.

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The Comparison of Protective Effects of Adenosine Included Cardioplegia According to Adenosine Dosage (심정지액 속에 포함된 아데노신의 용량에 따른 심근보호 효과 비교)

  • 유경종;강면식;이교준;임상현;박한기;김종훈;조범구
    • Journal of Chest Surgery
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    • v.31 no.9
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    • pp.837-844
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    • 1998
  • Background: Adenosine is secreted by myocardial cells during myocardial ischemia or hypoxia. It has many beneficial effects on arrhythmias, myocardial ischemia, and reperfusion ischemia. Although many investigators have demonstrated that cardioplegia that includes adenosine shows protective effects in myocardial ischemia or reperfusion injury, reports of the optimal dose of adenosine in cardioplegic solutions vary. We reported the results of beneficial effects of single dosage(0.75 mg/Kg/min) adenosine by use of self-made Langendorff system. But it is uncertain that dosage was optimal. The objective of this study is to determine the optimal dose of adenosine in cardioplegic solutions. Material and Method: We used a self-made Langendorff system to evaluate the myocardial protective effect. Isolated rat hearts were subjected to 90 minutes of deep hypothermic arrest(15$^{\circ}C$) with modified St. Thomas' Hospital cardioplegia including adenosine. Myocardial adenosine levels were augmented during ischemia by providing exogenous adenosine in the cardioplegia. Three groups of hearts were studied: (1) group 1 (n=10) : adenosine - 0.5 mg/Kg/min, (2) group 2(n=10): adenosine -0.75 mg/Kg/min, (3) group 3 (n=10) : adenosine -1 mg/Kg/min. Result: Group 3 resulted in a significantly rapid arrest time of the heart beat(p<0.05) but significantly slow recovery time of the heart beat after reperfusion(p<0.05) compared to groups 1 and 2. Group 2 showed a better percentage of recovery(p<0.05) in systolic aortic pressure, aortic overflow volume, coronary flow volume, and cardiac output compared to groups 1 and 3. Group 1 showed a a better percentage of recovery(p<0.05) in the heart rate compared to the others. In biochemical study of drained reperfusates, CPK and lactic acid levels did not show significant differences in all of the groups. Conclusion: We concluded that group 2 [adenosine(0.75 mg/Kg/min) added to cardioplegia] has better recovery effects after reperfusion in myocardial ischemia and is the most appropriate dosage compared to group 1 and 3.

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Detection of TNF-alpha in Serum as the Effect of Corticosteroid to the Myocardial Protection in Cardiopulmonary Bypass (체외순환시 스테로이드의 심근보호효과에 관한 혈청내 TNF-alpha 측정의 의의)

  • 최영호;김욱진;김태식;조원민;김학제
    • Journal of Chest Surgery
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    • v.31 no.5
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    • pp.502-508
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    • 1998
  • Proinflammatory cytokines such as tumor necrosis factor-$\alpha$(TNF-$\alpha$) have been implicated in myocardial and organ dysfunction associated with postperfusion syndrome. We tested the hypothesis that cytokine productions are depressed by preoperative cortiosteroid injection for cardiopulmonary bypass(CPB) and the postoperative courses will be better than without steriod pretreated cases. Cardiac surgery was performed in randomized blind fashion for 20 patients from June 1996 to September 1996. In the steroid group(n=10), corticosteroid(dexamethasone 1 mg/kg) was injected 1 hour before anesthetic induction, but in the control group(n=10), nothing was injected. Each of groups were sampled 11 times as scheduled for TNF-$\alpha$ bioassays. We have checked EKG, cardiac enzymes(CPK, LDH with isoenzyme), WBC count preoperative day, one day and three days after operation. Viatal signs were continuously monitored for three postoperaive days. In the postoperative period three patients in the control group had elevated body temperature and four patients had hypotension that required considerable intravenous fluid administration. But steroid injected patients showed normal body temperture and acceptable blood pressures without supportive treatment. CPK enzymes rose in control group higher than steroid group at postoperative 1st and 3rd day(CPK; 1122$\pm$465 vs 567$\pm$271, 864$\pm$42 vs 325$\pm$87), and CPK-MB enzymes rose in control group higher than steroid group at postoperative 1st day(106.4$\pm$115.1 vs 29.5$\pm$22.4)(P=0.02). Arterial tumor necrosis factor-$\alpha$ rose during cardiopulmonary bypass, peaking at 5 minutes before the end of aortic cross clamping(ACC-5min) in steroid group(11.9$\pm$4.7 pg/ml), and 5 minutes before the end of cardiopulmonary bypass(CPB-5min) in control group(22.3$\pm$6.8 pg/ml). The steroid pretreated patients had a shorter period of time in respirator suport time, ICU stay day, hospital admission day. We conclude that corticosteroid suppress cytokine production during and after cardiopulmonary bypass, and may improve the postoperative course through inhibition of reperfusion injury such as myocardial stunning and hemodynamic instability.

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Coronary Artery Bypass Graft in Patient with Advanced Left Ventricular Dysfunction (중등도 이상의 좌심실 기능 부전 환자에서의 관상동 우회술의 임상 분석)

  • 정종필;김승우;신제균
    • Journal of Chest Surgery
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    • v.34 no.12
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    • pp.901-908
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    • 2001
  • Background : Coronary artery bypass graft(CABG) in patients with advanced left ventricular dysfunction has often been regarded as having high mortality rate, despite the great improvement in operative result of CABG. With recent advances in surgical technique and myocardial protection, surgical revascularization improved the symptom and long-term survival of these high risk patients more than the medical conservative treatment. Material and Methold : Clinical data of 31(4.1%) patients with preoperative ejection fraction less than 30% among 864 CABGs performed between January 1995 and March 1999 were retrospectively analyzed and pre- and postoperative changes of the ejection fraction on echocardiography were analyzed. There were 26 men and 5 women. The mean age was 60.7 years(range 41 to 72 years). History of myocardial infarction(30 cases, 98%) was the most common preoperative risk factor. There were seven irreversible myocardial infarction on thallium scan. Most patients had triple vessel diseases(26 cases, 84%) and first degree of Rentrop classification(16 cases, 52%) on coronary angiography. The mean number of distal anastomosis during CABG was per patient was 4.9${\pm}$0.8 sites in each patient. In addition to long saphenous veins, the internal mammary artery was used in 20 patients. Total bypass time was 244.7${\pm}$3.7 minutes(range, 117 to 567 minutes), and mean aortic cross-clamp time was 77.9 ${\pm}$ 1.6 minutes(range, 30 to 178 minutes). There were five other reparative procedures such as two left ventricular aneurysrmectomy, two mitral repair, and one aortic valve replacement. There were twelve postoperative complications such as three cardiac arrhythmia, two bleeding(re-operation), one delayed sternal closure, eleven usage of intra-aortic balloon counterpulsation for low cardiac output. Two patients died, postoperative mortality was 6.5% . Twenty-nine patients were relieved of chest pain and left ventricular ejection fraction after operation was significantly higher(38.5${\pm}$11.6%, p 0.001) as compared with preoperative left ventricular ejection fraction(25.3${\pm}$2.3%). The follow up period of out patient was 25. 3 months. Conclusion: In patients with coronary artery disease and advanced left ventricular dysfunction, coronary artery bypass grafting can be performed relatively safely with improvement in left ventricular function, but it will be necessary to study long term results.

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Cardioprotective Effect by Preconditioning with Calcium-free Solution (칼슘결핍용액 투여 전처치에 의한 심근보호 효과)

  • 조대윤;이종화;김호덕
    • Journal of Chest Surgery
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    • v.32 no.9
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    • pp.773-780
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    • 1999
  • Background: It has been demonstrated that brief periods of calcium depletion and repletion (calcium-free preconditioning, CP) have cardioprotective effects as seen in ischemic preconditioning(IP) which enhances the recovery of post-ischemic contractile dysfunction and reduces the incidence of reperfusion-induced arrhythmia or infarct size after a prolonged ischemia. In the present study, we tested this paradoxical phenomenon in isolated rabbit hearts. Material and Method: Hearts isolated from New Zealand white rabbits(1.5∼2.0 Kg body weight) were perfused with Tyrode solution using the Langendorff technique. After stabilizing the baseline hemodynamics, the hearts were subjected to 45 minutes of global ischemia followed by 120 minutes of reperfusion with IP(IP group, n=7) or without IP (ischemic control group, n=7). IP was induced by a single episode of 5 minutes global ischemia and 10 minutes reperfusion. In the CP group(n=7), the hearts were subjected to perfusion with Tyrode solution with calcium depletion for 5 minutes and repletion for 10 minutes, and 45 minutes of ischemia and 120 minutes of reperfusion. Left ventricular function including developed pressure, dP/dt, heart rate, left ventricular end-diastolic pressure and coronary flow was measured. Infarct size was determined by staining with 1% triphenyltetrazolium chloride and planimetry. Data were analyzed by a one-way analysis of variance and Tukey's post-hoc test. Result: In comparison with the ischemic control group, IP significantly enhanced the recovery of the left ventricular function including the left ventricular developed pressure, contractility, and coronary flow; in contrast, these functional parameters of the CP group tended to be lower than those of the ischemic control group. However, the infarct size was significantly reduced by IP or CP(p<0.05). Conclusion: These results suggest that in isolated Langendorff-perfused rabbit heart model, CP(induced by single episode of 5 minutes calcium depletion and 10 minutes repletion) could not improve the post-ischemic contractile dysfunction(after a 45-minute global ischemia) but it has an infarct size-limiting effect.

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In Vitro Anti-aging and Hair Follicle Dermal Papilla Cells Activation Effects of Usnea diffracta Vain Extract (송라 추출물의 세포 수준에서 항노화 및 모유두세포 활성화 효과)

  • Min Jeong Kim;Won Yeoung Choi;Hyun Woo Shim;Eun Jin Shin;Jung No Lee;Sung Min Park;Hwa Sun Ryu
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.50 no.1
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    • pp.37-48
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    • 2024
  • Songla (Usnea diffracta Vain.) is one of the lichens belonging to the genus Usnea, and pharmacological activities such as antioxidant, antimicrobial, anti-inflammatory, anti-tumor and cardiovascular protection have been reported in previous studies, but its efficacy in skin and hair is not well known. In this study, the effect of Usnea diffracta extract (UDE) on anti-aging and dermal papilla cell proliferation was verified in vitro. As a result of the experiment, it was confirmed that the UDE significantly reduced the expression of MMP-1 and the activity of MAPKs (ERK, p38, JNK) and AP-1 (c-Fos, c-Jun), which were increased by UVA in HDFn. In addition, the UDE significantly increased the proliferation of HFDPC and significantly increased the mRNA expression of VEGF and KGF, which are hair growth factors. Accordingly, the phosphorylation of ERK/CREB involved in hair proliferation and expression of growth factors was increased in a concentration-dependent manner. The main component represented by the main peak was separated and purified using Prep LC by concentrating the UDE, which was confirmed as diffractaic acid through NMR and Mess analysis. Isolated diffractaic acid significantly reduced the expression of MMP-1 increased by UVA in HDFn and increased the proliferation of HFDPC in a concentration-dependent manner. The result suggest that UDE proved its usability as a natural cosmetic material with anti-aging and dermal papilla cell activation effects.

Cardioprotective Effect of Calcium Preconditioning and Its Relation to Protein Kinase C in Isolated Perfused Rabbit Heart (적출관류 토끼 심장에서 칼슘 전처치에 의한 심근보호 효과와 Protein Kinase C와의 관계)

  • 김용한;손동섭;조대윤;양기민;김호덕
    • Journal of Chest Surgery
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    • v.32 no.7
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    • pp.603-612
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    • 1999
  • Background : It has been documented that brief repetitive periods of ischemia and reperfusion (ischemic preconditioning, IP) enhances the recovery of post-ischemic contractile function and reduces infarct size after a longer period of ischemia. Many mechanisms have been proposed to explain this process. Recent studies have suggested that transient increase in the intracellular calcium may have triggered the activation of protein kinase C(PKC); however, there are still many controversies. Accordingly, the author performed the present study to test the hypothesis that preconditioning with high concentration of calcium before sustained subsequent ischemia(calcium preconditioning) mimics IP by PKC activation. Material and Method : The isolated hearts from the New Zealand White rabbits(1.5∼2.0 kg body weight) Method: The isolated hearts from the New Zealand White rabbits(1.5∼2.0 kg body weight) were perfused with Tyrode solution by Langendorff technique. After stabilization of baseline hemodynamics, the hearts were subjected to 45-minute global ischemia followed by a 120-minute reperfusion with IP(IP group, n=13) or without IP(ischemic control, n=10). IP was induced by single episode of 5-minute global ischemia and 10-minute reperfusion. In the Ca2+ preconditioned group, perfusate containing 10(n=10) or 20 mM(n=11) CaCl2 was perfused for 10 minutes after 5-minute ischemia followed by a 45-minute global ischemia and a 120-minute reperfusion. Baseline PKC was measured after 50-minute perfusion without any treatment(n=5). Left ventricular function including developed pressure(LVDP), dP/dt, heart rate, left ventricular end-diastolic pressure(LVEDP) and coronary flow(CF) was measured. Myo car ial cytosolic and membrane PKC activities were measured by 32P-${\gamma}$-ATP incorporation into PKC-specific pepetide. The infarct size was determined using the TTC (tetrazolium salt) staining and planimetry. Data were analyzed using one-way analysis of variance(ANOVA) variance(ANOVA) and Tukey's post-hoc test. Result: IP increased the functional recovery including LVDP, dP/dt and CF(p<0.05) and lowered the ascending range of LVEDP(p<0.05); it also reduced the infarct size from 38% to 20%(p<0.05). In both of the Ca2+ preconditioned group, functional recovery was not significantly different in comparison with the ischemic control, however, the infarct size was reduced to 19∼23%(p<0.05). In comparison with the baseline(7.31 0.31 nmol/g tissue), the activities of the cytosolic PKC tended to decrease in both the IP and Ca2+ preconditioned groups, particularly in the 10 mM Ca2+ preconditioned group(4.19 0.39 nmol/g tissue, p<0.01); the activity of membrane PKC was significantly increased in both IP and 10 mM Ca2+ preconditioned group (p<0.05; 1.84 0.21, 4.00 0.14, and 4.02 0.70 nmol/g tissue in the baseline, IP, and 10 mM Ca2+ preconditioned group, respectively). However, the activity of both PKC fractions were not significantly different between the baseline and the ischemic control. Conclusion: These results indicate that in isolated Langendorff-perfused rabbit heart model, calcium preconditioning with high concentration of calcium does not improve post-ischemic functional recovery. However, it does have an effect of limiting(reducing) the infart size by ischemic preconditioning, and this cardioprotective effect, at least in part, may have resulted from the activation of PKC by calcium which acts as a messenger(or trigger) to activate membrane PKC.

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