• 약학회지
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• 제41권6호
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• pp.802-816
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• 1997

In order to investigate the pharmacological properties of New Woohwangehungsimwon Pill (NWCH). Effects of Woohwangehungsimwon Pill (WCH) and NWCH were compared using various experimental models. In isolated rat aorta, NWCH and WCH showed the relaxation of blood vessels in maximum contractile response to phenylephrine ($10^{-6}$M) without regard to endothelium containing or denuded rings of the rat aorta. Furthermore, the presence of the inhibitors of NO synthase and guanylate cyclase did not affect significantly the relaxative effects of NWCH and WCH. NWCH and WCH inhibited the vascular contractions induced by acethylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats(SHRs), NWCH and WCH decreased significantly heart rate. These, at high doses, had a negative inotropic effect that was a decrease of LVDP and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, these had no effects on parameters of action potential at low doses, whereas inhibited the cardiac, contractility at high doses. Furthermore, these had a significant inhibitory effects on heart acceleration in normotensive rats and SHRs. These results suggested that NWCH and WCH have weak cardiovascular effects, and that there is no significant differences between two preparations.

• 약학회지
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• 제44권6호
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• pp.558-565
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• 2000

SK-1080 is one of the newly developed orally active nonpeptide angiotensinII $AT_1-receptor$ antagonist that selectively acts at $AT_1$ receptor with high affinity. The cardiac effect on ischemia/reperfusion injury of SK-1080 was compared with those of losartan, a prototype of this class, in isolated rat hearts. Isolated perfused rat heart was pretreated with drug for 10 min and then subjected to global ischemia for 30 min followed by reperfusion with- or without drug for 30 min. The possible additive effect of SK-1080 on the platelet aggregation and coagulation in human blood was also studied. We investigated whether SK-1080 effects the platelet aggregation induced by ADP, a platelet agonist partially dependent on $thromboxaneA_2$. The clotting times in the prothrombin time (PT) and activated partial thromboplastin time (APTT) were also examined in human plasma in vitro as coagulation screening test. SK-1080 improved reperfusion function (LVDP, left ventricular developed pressure; PRP, rate-pressure product) in a dose-dependent manner. SK-1080 reduced ADP-induced platelet aggregation compared with vehicle but less than losartan, and did not affect clotting times.

• The Korean Journal of Physiology and Pharmacology
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• 제8권1호
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• pp.43-50
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• 2004

Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in a marked cardiac contractile dysfunction. Amrinone, a specific inhibitor of phosphodiesterase 3, has an antioxidant activity against PMNs. Therefore, we hypothesized that amrinone could attenuate PMNs-Induced cardiac dysfunction by suppression of reactive oxygen species (ROS) produced fby PMNs. In the present study, we examined the effects of amrinone on isolated ischemic (20 min) and reperfused (45 min) rat hearts perfused with PMNs. Amrinone at $25\;{\mu}M$, given to hearts during the first 5 min of reperfusion, significantly improved coronary flow, left ventricular developed pressure (P<0.001), and the maximal rate of development of left ventricular developed pressure (P<0.001), compared with ischemic/reperfused hearts perfused with PMNs in the absence of amrinone. In addition, amrinone significantly reduced myeloperoxidase activity by 50.8%, indicating decreased PMNs infiltration (p< 0.001). Superoxide radical and hydrogen peroxide production were also significantly reduced in fMLP- and PMA-stimulated PMNs pretreated with amrinone. Hydroxyl radical was scavenged by amrinone. fMLP-induced elevation of $[Ca^{2+}]_i$ was also inhibited by amrinone. These results provide evidence that amrinone can significantly attenuate PMN-induced cardiac contractile dysfunction in the ischemic/reperfused rat heart via attenuation of PMNs infiltration into the myocardium and suppression of ROS release by PMNs.

• 약학회지
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• 제41권6호
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• pp.829-836
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• 1997

Studies on the effect of quinones on cardiac function has been conducted with normal hearts. But not with injured hearts, I.e. ischemia/reperfusion-injured heart. Quinone compounds are known to produce oxygen free radicals during metabolism, and for this reason, quinones are implicated in the aggravation of ischemia/reperfusion injury or cardioprotection, as in the case of ischemic preconditioning depending on the experimental conditions. The present study was carried out to examine the effect of 2-chloro-3-(4-cyanophenylamino)-1.4-naphthoquinone (NQ-Y15) on cardiac function of ischemic/reperfused and normal rat hearts. In isolated perfused hearts, various functional parameters such as left ventricular developed pressure (LVDP), left ventricular end-diastolic pressure (EDP) and maximum positive and negative dP/dt ($[\pm}dP/dt_{max}$), time to contracture, heart rate (HR) and coronary flow rate (CFR) were measured before and 30 min after dosing and following 25 min ischemia/30min reperfusion. NQ-Y15 increased LVDP, +dP/$d_{max}$and -dP/$dt_{min}$ by 18%. 30%, and 40%, respectively. There were no significant changes in other haemodynamic parameters. After ischemia/reperfusion injury, pretreatment with NQ-Y15 induced a significant decrease in LVDP and $[\pm}dP/dt_{max}$, but an increase in EDP. LDH-release was not significantly increased. These results suggested that NQ-Y15 may augment the ventricular contractility but it makes hearts more vulnerable to ischemia/reperfusion injury.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.199-199
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• 1998

In this study, the effects of ursodeoxycholic acid (UDCA) on ischemia/reperfusion injury were investigated on retrograded aortic perfusion model. Hearts from Sprague-Dawley rats were perfused with oxygenated Krebs-Henseleit solution (pH 7.4, 37) on a Langendorff apparatus. After equilibration, hearts were treated with ursodeoxycholic acid 10, 20, 40 and 800 M or vehicle (0.04% DMSO) for 10 min before the onset of ischemia. Following 25 min of global ischemia, ischemic hearts were reperfused and allowed to recover for 30 min. The physiological (i.e. heart rate, left ventricular diastolic pressure, coronary flow and time to contracture formation) and biochemical (lactate dehydrogenase, LDH) endpoints were evaluated. In vehicle group, time to contracture formation (TTC) value was 19.5 min during ischemia, LVDP was 20.8 mmHg at the endpoint of reperfusion and LDH activity in reperfusate was 59.7 U/L. Cardioprotective effects of UDCA following ischemia/reperfusion consisted of a reduced TTC (EC$\_$25/ = 16.10 M), reduced LDH release and enhanced recovery of contractile function during reperfusion. Especially, the treatments of UDCA 80 M remarkably increased LVDP (68.1 mmHg) and reduced LDH release (33.2 U/L). Our findings suggest that UDCA ameliorates ischemia/reperfusion-induced myocardial damage, in agreement with physiological and biochemical parameters.

• 대한한방내과학회지
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• 제18권2호
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• pp.220-228
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• 1997

Background The stenosis of the coronary artery may decrease myocardial oxygen supply and occur myocardial ischemia or infarction. Soojeomsan, one of analgesics is generally regarded to have the effect of vitalizing blood, expelling blood stasis and alleviation cardiac pain. Methods The purpose of this experimental study is to find the influence of Soojeomsan on cardiac enzyme (CPK, Na-K ATPase) of ischemic and reperfused rat hearts which are isolated under the Langendorff apparatus. Ischemia was induced In isolated hearts of Sprague-Dawley rats by ceasing the perfusion for 20 minutes. The experiments were divided into a normal saline orally administered group(control group), a Soojeomsan orally 20ml administered group(sample A) and a Soojeomsan orally 30ml administered group(sample B). The CPK (creatinine phosphokinase) and Na-K ATPase activity of this three group were measured and compared in order to assess the influence of Soojeomsan on protection of isolated rat hearts from ischemia. Results 1. CPK was significantly reduced in Sample A group and Sample B group in comparison with control group in reperfusion(P<0.01), and there were no significant difference between Sample A and B. 2. Na-K ATPase activity was significantly increased in Sample A group and Sample B group in comparison with control group in ischemia(P<0.001), and the activity was significantly higher in Sample B then in Sample A.(P<0.01) 3. There were no significant difference in Na-K ATPase activity of the three groups after reperfusion. Conclusion Soojeomsan has effects to decrease CPK activity and activate Na pump. This result in protection of the myocardium of isolated rat hearts from ischemia.

• Journal of Chest Surgery
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• 제29권3호
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• pp.255-262
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• 1996

본 연구는 횐 쥐의 적출심장을 이용한 질식사심장의 기능평가로서,기도압박에 의한 질식으로 심정 지가 일어난 후, 10분 지나서 심장을 적출하고 체외관류장치에 연결하여, 80cmH20높이에서 37C의 Krebs-Henseleit용액을 적출 심장에 관류시켜, 그 기능을 평가하여 다음과 같은 결과를 얻었다. Sprague-Dawley계 흰 쥐를, 제 1군(10마리)은 대조군, 제2군(10마리)은 위스콘신대학용액 저장군, 제3 군(10마리)은 스탠포드심정 지용액-생 리식 염수 저장군, 제4군(10마리)은 질식사군으로 분류하여 실험을 시행하였다. 자연 제세동시간은, 모든 군에서 대조군보다 길었으며, 제2군에 비 해서 제3군과 제4군의 제 세동시간도 길었다(p < 0.05). 좌심실내압은, 관류 15분, 30분, 45분에서, 대조군 및 제2군에 비하여 제3 군이 모두 낮았으며,제4군은 관류 15분에, 대조군과 제2군의 15분에 비하여 낮았고, 관류 30분과45분 에는 대조군에 비하여 낮았다(p < 0.05). 관류 15분, 30분, 45분에 측정한 심박동수와 좌심실내압을 곱한 간은, 제3군에서 대조군과 제2군에 비하여 모두 낮았으며, 제4군에서는 대조군에 비하여 모두 낮았고, 제4군의 15분값은 제2군의 15분값에 舟漫\ulcorner\ulcorner낮았다(p<0.05).관류45분에 측정한심근의 수축예비 력은, 대조군과 비교하여 제3군과 제4군이 모두 낮았으며, 제3군은 제2군에 비하여도 낮았다(p < 0.05). 이상의 결과로 보아,질식사로 사망한 조기 적출심장의 기능은, 허혈손상이 없는 대조군과 위스콘신 대학용액에 저장한 심장의 기능에 비하여 그 성적이 불리하나,스탠포드심정지용액-생리식염수 저장군 의 심기능 평가 결과와는 유의한 차이가 없어, 공여심장으로서의 심기능은 비교적 만족할 만한 것으로 볼 수 있다.

• Journal of Chest Surgery
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• 제29권8호
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• pp.807-815
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• 1996

허혈전처치(ischemic preconditioniiIE)의 허혈심장 보호효과와 그 기전을 규명하기 위한 일환으로 citric oxide(HO)가 허혈전처치의 심보호 효과에 미치는 영향을 검토하였다. 흰쥐 적출심장의 Langendorrr관류표본에서 실험적인 허할(30분)-재관류(30분) 손상을 유도하였고, 허혈전처치는 재관류손상 유도 전에 5분 허혈 - 5분 재관류를 3회 반복하여 시행하였다. 허혈심근 손상의 지표로 심수축기능 세질효소 유출 및 미세형태학적 변화를, 그리고 HO 합성 억제제인 L-HAME 를 투여하여 허혈전처치와 비전처치 허혈-재관류 심장들에서 손상의 정도를 비교하였다. 그 결과 허혈- 재관류 심장에서 심기능의 저하및 세포질 유출이 현저하게 증가하였고 전자현미경상의 미세구조에서도 세포내 소기관 및 myofibril의 파괴가 관찰되 어 심근손상이 심함을 알 수 있었다. 허 혈-재관류에 의한 심 장손상은 허혈전처치를 시행한 허혈-재관류 심장에서는 현격하게 감소돼 심회복률이 77%로 증가하였 고 세포질유출도 현저하게 감소되었으며 미세소견에서도 세포구조가 비교적 잘 보존되었다. 허혈전처 치에 의한 심보호 효과에 NO가 관여하는지를 관찰하기 위하여 NO합성 억제제인 L-NAME를 투여하 여 허혈전처치를 시행하였다. 결과 L-UAME투여로 허혈전처치에 의하여 회복된 심기능 및 LDH유출 감소에 아무런 영향을 주지 않았고 허혈전처치에 의하여 비교적 잘 보존된 미세구조 역시 영향을 받지 않았다. 이상의 결과들로부터 허혈전처치는 세포수준에서 허혈심근의 재관류손상을 방지하며, NO합성의 증가가 횐쥐 적출 심장에서 허혈전처치에 의한 허혈심장 보호효과에 크게 기여하지 않을 것으로 사료되었다.

• 한국식품위생안전성학회지
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• 제2권2호
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• pp.57-65
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• 1987

한국에서 재배된 영지의 혈압 강하 작용을 검색한 결과, 두 종류의 영지 자실체에서 모두, 용량을 증가시킴에 따라 심박수, 수축기 혈압 및 확장기 혈압을 강하시킴을 관찰하였다. 또, 이러한 혈압을 강하시키는 유효 성분은 fraction B에 많이 포함되어 있음을 확인할 수 있었는데, 선천성 고혈압 쥐에 체중당 10mg을 정맥내 투여했을 때, 대조군과 비교하여 유의한 차이를 가지고 혈압을 강하시켰다. 혈액 관류 심장 표본에서의 영지의 작용을 관찰해 본 결과, sample J의 경우는 용량에 따라 심박수 및 심실 수축력을 증가시켰으나 sample K의 경우 용량을 증가시킴에 따라 심박수 및 심방 수축력을 오히려 감소시켰으며, 심실 수축력은 거의 변화가 없었고, 또, 관상동맥 혈류량을 용량의존적으로 증가시켰다. 심장에 대한 위의 모든 반응은 fraction A와 B에서만 나타났고, fraction C는 영향을 끼치지 못했다.

• Journal of Chest Surgery
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• 제33권8호
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• pp.605-612
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• 2000

Background: Ischemic preconditioning enhances the tolerance of myocardium against ischemia/reperfusion injury, with the enhancement of the recovery of post-ischemic myocardial function. This study was disigned to assess whether the protective effect of ischemic preconditioning could provide one additional hour of myocardial preservation in four hour myocardial ischemia in a rate heart. Material and method: Fourty four Spargue-Dawley rats, weighing 300~450gm, were divided into four groups. Group 1(n=7) and group 3(n=12) were subjected to 30 minutes of aerobic Langendorff perfusion without ischemic preconditioning and then preserved in saline solution at 2~4$^{\circ}C$ for 4 hours and 5 respectively. Group 2(n=7) and group 4(n=18) were perfused in the same way for 20 minutes, followed by 3 minutes of global mormothermic ischemia and 10 minutes of perfusion and then preserved in the same cold saline solution for 4 hours and 5 hours respectively. Heart rate, left ventricular developed pressure(LVDP), and coronary flow were measured at 15 minutes during perfusion as baseline. Spontaneous defibrillation time was measured after reperfusion. Heart rate, LVDP, and coronary flow were also recorded at 15 minutes, 30 minutes, and 45 minutes during reperfusion. Samples of the apical left ventricular wall were studied using a transmission electron microscope. Result: Time of spontaneous defibrillation(TSD) was significantly longer in group 4 than in group 1(p<0.001), and TSD in group 1 was significantly longer in comparision to that of group 2(p<0.05). Heart rate at 45 minutes was significantly higher in group 1 than in group 4(p<0.05). Heart rate at 15 min was significantly higher in group 2 than in group 1(p<0.001) and in group 4 than in group 3(p<0.05). Left ventricular developed pressure(LVDP) at 30 minutes and 45 minutes was higher in group 1 than in group 4(p<0.01), LVDP at 45 minutes was higher in group 4 than in group 3(p<0.05). Rate-pressure product(RPP) at 30 minutes and 45 minutes was higher in group 1 than in group 4(p<0.05). RPP at 15 minutes was higher in group 2 than in group 1(p<0.01). RPP at 30 minutes and 45 minutes was higher in group 4 than in group 3(p<0.05). Group 2 showed relatively less sarcoplasmic edema and less nuclear chromatin clearance than group 1. Group 4 showed less myocardial cell damage than group 3, group 4 showed less myocardial cell damage than group 3, group 4 showed more myocardial cell edema than group 1. Conclusion: Ischemic preconditioning enhanced the recovery of postischemic myocardial function after 4 hours and 5 hours preservation. However, it was not demonstrated that ischemic preconditioning could definitely provide one additional hour of myocardial preservation in four hour myocardial ischemia in a rat heart.