• 약학회지
• /
• 제33권3호
• /
• pp.167-174
• /
• 1989

KR-1008 and KR-30006 are 1,4-dihydropyridine derivatives, new vasodilatory calcium antagonists from KRICT. Calcium antagonistic properties of the compounds were studied in the isolated heart (Langendorff preparation), pulmonary artery (vasodilation), and in the papillary muscle (negative inotropic effect) of the guinea pig. Antihypertensive effect were also investigated after i.v. or oral administration in the SHR (spontaneously hypertensive rat). They produced a sigificant inhibition of Ca-induced contraction in the guinea pig pulmonary artery at the concentrations of above $10^{-8}M$. The negative inotropic effect of the electrically stimulated papillary muscle appeared from the concentration of $10^{-6}M$, which is about hundred times higer than the concentration of vasodilation effect. Left ventricular pressure also decreased from the concentration of $3\;{\times}\;10^{-6}M$ in KR-1008 and KR-3006 in the Langendorff heart preparations. Coronary flow rate increased from $10^{-6}M$ in KR-1008 and nicardipine and appeared no change in KR-30006. The antihypertensive effect of KR-1008 (EC 20: $2.9\;{\mu}g/kg$) was potent more than nicardipine (EC 20: $3.4\;{\mu}g/kg$) and than Kr-30006 (EC 20: $6.8\;{\mu}g/kg$) was, after i.v. bolus injection in the anesthetized SHR. The antihypertensive effect in the conscious SHR appeared 30 minutes after oral administration of 10 mg/kg and persisted 4 hrs in KR-1008 and 12 hrs in KR-30006. Heart rate tended to increase for 0.5-1 hr after oral administration of the test compounds.

• Journal of Chest Surgery
• /
• 제23권1호
• /
• pp.9-15
• /
• 1990

This study was designed to investigate the protective effect of chlorpromazine against the reperfusion injury of myocardium after high potassium cardioplegic arrest. Langendorff`s preparations of rat heart were infused with high potassium cardioplegic solution[St. Thomas Hospital Solution] at 25oC. Chlorpromazine [10-7Ｍ] increased the recovery of myocardial contractility[dp/dt], left ventricular pressure[LVP], and coronary flow rate of the reperfused heart. Both in control and experimental groups, the restoration of myocardial activity could not reach to the level of preplegic control. These results suggest that the etiologic factors of the reperfusion injury include the influence of high potassium cardioplegic solution and/or reperfusion itself, and that chlorpromazine protects myocardium from the reperfusion injury.

• Journal of Chest Surgery
• /
• 제35권5호
• /
• pp.336-342
• /
• 2002

배경: 최근 들어 심부전증을 가진 심장에 세포이식을 이용하여 심장기능을 개선시키고자 하는 연구가 활발히 진행되고 있다. 이 연구는 확장성 심근증을 가진 햄스터 심장에 배양한 평활근 세포와 심근세포를 이식한 후 심장기능의 변화를 관찰하였다. 대상 및 방법: 심근세포와 평활근세포는 BIO 53.58 햄스터의 심장과 옃션 deferens에서 분리하여 배양하였다. 실험군은 각각 10마리로서 심근세포 (1군)와 평활근세포 (2군) 및 배양액 (3군)을 17주된 BIO 53.58 햄스터의 좌심실에 이식하였고 Cyclosporine (5mg/Kg)을 1군에 한하여 수술 직후부터 매일 피하주사하였다. sham군 (4군) 은 세포나 배양액의 이식 없이 단순 흉부수술만을 시행하였다. 세포나 배양액의 이식 4주 후에 Langendorff 체외순환 모델을 이용하여 좌심실기능을 측정하였다. 결과: 조직학적 검사상 모든 군에서 심한 심근괴사가 있었고, 1군과 2군에서는 수여심장의 심근 내에서 새로운 근육조직이 형성되었다. 좌심실기능의 평가에서 1군과 2군은 3군과 4군에 비해 통계적으로 유의하게 우수하였고 (p<0.01), 2군은 1군에 비해 수축기 좌심실압과 발생기압이 통계적으로 유의하게 우수하였다 (p<0.05). 그러나 3군과 4군 사이에는 통계적인 유의성이 없었다. 절론 확장성 심근증을 가진 햄스터 심장에 배양한 평활근 세포와 심근세포를 이식한 결과 수여심장의 심근 내에서 근육조직을 형성하고 좌심실기능을 개선시켰으며, 이 중 평활근세포를 이식한 심장이 수축기 좌심실압과 발생기압이 더 우수한 좌심실기능 개선효과를 보여주었다.

• 대한한의학회지
• /
• 제18권2호
• /
• pp.340-354
• /
• 1997

Background : The stenosis of the coronary artery results in a decrease in the myocardial oxygen supply, ischemia and infarction. Jakamchotang as a drug of liquid is generally regarded to have the effect of arrythmia, palpitation from Heart disease and promoting the flow of Ki and Blood. Methods : The purpose of this experimental study is to find whether Jakamchotang is effective or not in curing ischemia in isolated perfused rat hearts and to measure the degree of its curing effect. In this study, under the Langendorff apparatus, ischemia was induced in isolated Sprague-Dawley rat hearts by ceasing the perfusion for 20 minites. Subjects were divided into a normal saline orally administered group(control group), an Jakamchotang orally 100mg administered group (sample A), an Jakamchotang orally 300mg administered group (sample B), and an Jakamchotang injection perfused group(sample C). The heart rates, left ventricular pressure, myocardial dilatation/contraction, cardiac perfusion flow and cardiac ezyme(LDH, CPK) of the four group were measured and compared in order to assess the influence of Jakamchotang on isolated perfused rat hearts recovering abillity from ischemia and infarction. results : 1. Heart rates were increased significantly in Jakamchotang orally 100mg administered group, Jakamchotang orally 300mg administered group and Jakamchotang injection perfused group on perfusion and reperfusion(p<0.01). 2. Left ventricular pressure were increased significantly in Jakamchotang orally 100mg administered group and 300mg administered and Jakamchotang injection perfused group(p<0.01) in comparison with control group on perfusion, but every group did not significant on reperfusion. 3. While there were no differances in each group's abillities of myocardial dilatation, the ability of myocardial constriction of Jakamchotang 100mg administered group only on perfusion was significantly greater than that of control group(p<0.05). 4. CBF was no significant on perfusion and reperfusion in comparison with control group(N.S.) 5. LDH was not significantly decreased on perfusion, but significactly decreased in Jakamchotang orally 100mg administered group, Jakamchotang orally 300mg administered group on reperfusion. 6. CPK was significantly decreased in Jakamchotang orally 100mg administered group, 300mg administered and Jakamchotang injection perfused group on perfusion(p<0.01), but was not significantly in Jakamchotang 300mg administered group only on reperfusion(P<0.05) Conclusion : According to the result above, Jakamchotang have an effect to recover in the isolated perfused rat hearts. Especially, the effect of Jakamchotang in orally adminstered group is greater than that of Jakamchotang injection perfused group on preischemia. The followings are the two important results of this study: First, the effect of Jakamchotang used traditionally on heart disease was proved statistcally under the Langendorff apparatus. Second, on the basis of this study, the effect of other type medications on myocardial ischemia can be evaluted in further studies.

• Journal of Chest Surgery
• /
• 제23권6호
• /
• pp.1074-1083
• /
• 1990

This study was evaluated the metabolic, physiologic and histologic effects of myocardial protection of verapamil[isoveratril]on isolated rat hearts to 90 minutes of ischemic arrest. Heart was perfused with a modified Kreb’s Henseleit bicarbonate buffer with glucose and arrested with retrograde coronary perfusion by glucose insulin[GI], potassium and verapamil. Mean aortic systolic pressure, heart rate, coronary flows were measured and morphologic changes were examined during working heart perfusion. Perfusion and arrest were controlled four groups subjected 60 isolated rat hearts. Four groups hearts reperfused during 40 minutes after 90 minutes global ischemia for physiologic recovery. 15 hearts of four groups were assayed to histological morphologic changes. GI treated hearts recovered less than 28% of function and changed more than 80% of mitochondria of control group. Verapamil hearts[0.2, 0.1 gm/kg] recovered more than 88% of function and permitted the maintenance of continuous cellular level of Serum Glutamic Oxalaxetate Transaminase[SGOT], but declined 28% of Phosphate Kinase[CP], GI treated heart showed widespread evidence of extensive damage of mitochondria. The damage was that interstitial huge edema are present and there was contraction band formation within the swollen cells. The verapamil and potassium group were not found morphologic change compared with control group. Their functions were shown that metabolic and physiologic action of verapamil-group lasted 20 minutes longer than potassium group.

• 대한한방소아과학회지
• /
• 제21권1호
• /
• pp.173-187
• /
• 2007

Objectives : In order to verify the cardiovascular hemodynamic function of Kammaegdaejo-tang, the experiment was performed in the rats. Methods : Twelve hearts removed from male Sparague-Dawley rats weighing between 250g and 300g were perfused by the Langendorff technique with modified 37 Krebs-Henseleit's buffer solution at a constant perfusion pressure. They were randomly assigned to one of two groups, supplied with either normal saline or Kammaegdaejotang administration. Heart rate, left ventricular pressure, +dp/dt maximum, -dp/dt maximum, and -dp/dt/ +dp/dt ratio were evaluated at baseline after the administration of either normal saline or Kammaegdaejotang. Results : Kammaegdaejotang made the heart rate increasing significantly (p<0.05). Kammaegdaejotang did not effectively work on left ventricular pressure of the isolated heart(p=0.11, no significance). The significant effects of Kammaegdaejotang were observed on +dp/dt max and -dp/dt max(p<0.05). Kammaegdaejotang did not effectively work on -dp/dt/ +dp/dt ratio(p=0.24, no significance).

• Biomolecules & Therapeutics
• /
• 제2권2호
• /
• pp.114-119
• /
• 1994

[$^3$H]Ouabain binding parameters ( $K_{D}$ and $B_{max}$) to control rat ventricular strips and Langendorff preparations which were not previously exposed to ouabain were compared with those to both preparations that had been first exposed to a complete ouabain dose range of dose-response curve (10$^{-8}$ to 10$^{4}$M). In rat ventricular strips and Langendorff perfused heart preparations, cumulative dose-response curves of ouabain revealed biphasic positive inotropic effects, a "low-dose" effect and a "high-dose" effect with E $d_{50}$ values of 0.5 $\mu$M and 35 $\mu$M ouabain, respectively. The "low-dose" effect in ventricular strip disappeared or was diminished significantly when the ouabain dose-response curve was repeated after the washout of the effects of the first dose-response curve, whereas there were no significant differences in the maximal "high-dose"effect in both exposures to oubain. However, both of the control and ouabain-preexposed Langendorff perfused hearts revealed the same low-dose effects. The $K_{D}$ value for [$^3$H] ouabain binding and the ouabain binding site concentration ( $B_{max}$) estimated by [$^3$H]ouabain displacement assay in control preparations were 230 nM and 2 pmol/mg protein, respectively. [$^3$H]Ouabain binding parameters were not changed by repeated exposure to high concentrations of 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).).).).).

• Biomolecules & Therapeutics
• /
• 제7권4호
• /
• pp.354-361
• /
• 1999

In this study, the effects of tauroursodeoxycholic acid (TUDCA) on ischemia/ reperfusion injury were investigated on isolated heart perfusion models. Hezrts were perfused with oxygenated Krebs-henseleit solution (pH 7.4, $37^{\cire}C$) on a Langendorff apparatus. After equilibration, isolated hearts were treated with TUDCA 100 and 200 $\mu\textrm{M}$ or vehicle (0.02% DMSO) for 10 min before the onset of ischemia in single treatment group. In 7 day pretreatment group. TUDCA 50, 100 and 200 mg/kg body weight were given orally for 7 days before operation. After global ischemia (30 min), ischemic hearts were reperfused for 30 min. The physiological (i.e. heart rate, left ventricdular developed pressure, coronary flow, double product, time to contracture formation) and biochemical (lactate dehydrogenase; LDH) parameters were evaluated. In vehicle-treated group, time to contracture formation was 810 sec during ischemia, LVDP was 34.0 mmHg at the endpoint of reperfusion and LDH activity in total reperfusion effluent was 34.3 U/L. Single treatment with TUDCA did not change the postischemic recovery of cardiac function, LDH and time to contractur compared with ischemic control group. TUDCA pretreatment showed the tendency to decrease LDH release and to increase time to contracture and coronary flow. Our findings suggest that TUDCA does not ameliorate ischemia/reperfusion-reduced myocardial damage.

• Journal of Chest Surgery
• /
• 제30권1호
• /
• pp.11-16
• /
• 1997

The Increasing use of coronary perfusates for the protection of the human heart during ischemic cardiac arrest has placed great emphasis on the need for a rational and safe formulation. For the purpose of this study isolated rat hearts were connected to retrograde nonworking perfusion system proposed by Langendorff, and then perfused for 20 minutes by coronary infusates of magnesium concentration of 1.66 m Mol per liter(group A, n: 10) or 15mMo1 per liter(group B, n: 10). After 20 minutes perfusion, cold cardioplegic solution (modified St. Thomas'Hospital solution) was infused for 2 minutes, and prepared within 4$^{\circ}C$ Krebs-Henseleit solution. Finally, 20 minutes of cononay reprsfuslon was reestablished after I hour of cold ischemic cardiac arrest. Hemodynamic parameters (heart rate, left ventricular pressure, $\pm$ dp/dt max. and coronany flow) and enzymes assay (creatine phosphokinase, lactic dehydrogenase and flutamic oxaloacetic transaminase) were performed each other at whic rat heart was perfused for 20 minutes and reperfused for 20 minutes thereafter. There were significant differences in the recovery rate of heart rate, systolic left ventricular pressure, + dp/dt max, and coronary flow and reperfusion-perfusion ratio of creatine phosphokinase(P < 0.05). But, there were no signicant differences in the recovery rate of dp/dt max, and reperfunion-perfusion ratio of lactic dehydrogenase and glutamic oxaloacetic acid (P > 0.05).

• 대한약리학회지
• /
• 제32권1호
• /
• pp.31-37
• /
• 1996

허혈전처치(IP)의 히혈-재관류손상에 대한 심근 보호작용의 기전을 규명하기 위한 일환으로 denosine에 의한 PKC자극이 허혈전처치의 주요 기전으로 작용할 가능성을 조사하였다. 흰쥐 적출심장의 Langendorff 관류 표본에서 실험적인 허혈(30분)-재관류(20분)손상을 유도하였고, 허혈전처치는 허혈-재관류 손상 유도 전에 5분 허혈-5분 재관류를 3회 반복하여 시행하였다. 심근 손상의 지표로 심수축기능, 세포질효소 유출을 측정하였다. Adenosine이 허혈전처치의 심보호 효과에 관여하는지를 관찰하기 위하여 adenosine수용체 억제제인 8-(p-sulfophenyl)-theophylline(SPT), Xanthine amine congener(XAC) 및 8-cyclopentyl-1,3-dipropylxanthine (DPCPX)을 허혈전처치 유도 전에 투여하였다. 또한 PKC가 허혈전처치의 세포내 매개인자로 관여 할 가능성을 관찰하기 위하여 PKC활성 억제제인 polymyxin B 및 chelerythrine과 PKC translocation 억제제인 colchicine을 허혈전처치 유도 전에 투여하였다. 연구성적은 다음과 같다. 1) 허혈전처치는 허혈재관류 심장의 심기능의 저하를 현저히 회복시켜 심기능 회복률은 75%에 달하였다. 2) 허혈-재관류 심장에서 lactate dehydrogenase유출증가는 허혈전처치에 의해 현저히 저하되었다. 3) Adenosine 비선택적 차단제인 SPT와 Al 선택적 차단제인 DPCPX 및 XAC의 투여가 허혈전처치에 의한 심기능회복 및 LDH 유출 감소에 영향을 미치지 않았다. 4) PKC활성 억제제인 polymyxin B 와 chelerythrine을 처치시 히혈전처치 심장의 심기능 회복률이 현저히 감소되었으며 LHD 유출 역시 대조군 심장의 수준으로 증가하였다. 5) PKC translocation을 방해하는 colchicine도 허혈전처치의 심보호 효과를 억제시켰다. 이상의 결과들로부터 adenosine은 흰쥐 심장에서 허혈전처치의 심보호효과에 중요한 세포외 매개물질로 작용할 가능성이 희박하며, PKC는 흰쥐 심장에서 허혈전처치시 세포내 매개 인자로 관여하여 허혈전처치에 의한 심보호효과에 중요한 역할을 할 수 있으리라 사료된다.