• 한국임상수의학회지
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• 제6권2호
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• pp.281-290
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• 1989

To gain insight into the relationship between the occurrence of occlusive arrhythmia(OA) and the incidence of reperfusion arrhythmia(RA), this study used 25 open-chest dogs anesthetized with halothan, these were ligated between anterior ventricular branch and marginal branch of left circumflex artery for 30 minutes and occlusive arrhythmia were observed during the ligation. After releasing of the ligation, TA were observed during 5 minutes. The results were summerized as follow； 1. Such arrhythmias as ventricular fibrillation(VF), short run type VPC Premature contraction(VPC), Venticular tachycardia(VT), ventricularc and trigeminy VPC(TVPC) were observed during occlusion and reperfusion. 2. The cases occurred VT, SRVPC and TVPC during occlusion necessarily were Incidence of RA. 3. RA never occurred without appearence of occlusive arrhythmias. 4. The occurrence rate of OA showed 55.5% in the incidence group of RA and 24.6％ in the non incidence group of RA. 5. The occurrence rate of VPC during occlusion showed 9.9＋5.85(episode/min) in the incidence group of RA and 4.46＋5.88(episode/min) in the non-incidence group of RA. These results may be estimated that the occurrence of VT, SRVPC and TVPC, and the high occurrence rate of VPC during occlusion can be predicted the incidence.

• 한국임상약학회지
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• 제6권2호
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• pp.32-40
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• 1996

The electrophysiological effects of benzopyran potassium channel openers (PCOs: lemakalim, KR-30450 and KR-30818) on the ischemia/reperfusion-induced arrythmias were investigated. In anesthetized rats, subjected to 45 min occlusion of the left anterior descending coronary artery (LAD) followed by 90 min reperfusion, ventricular arrythmias were identified according to the Lambeth Conventions by lead II ECG. Rats were intravenously given vehicle ($1\%$ DMSO), lemakalim, KR-30450, and KR-30818 alone or in combination with a selective $K_{ATP}$ blocker glibenclamide, 30 min prior to coronary occlusion. Compared to vehicle, lemakalim ($30{\mu}g/kg$ i.v.), the active enantiomer of cromakalim, had a tendancy to increase the duration of ventricular tachycardia (Vl) and ventricular fibrillation (VF), the number of premature ventricular complexes (PVC) and the incidence of VF, especially in the early post-occlusion peroid ($0\~15$ min), while increasing ST-segment elevation. Both KR-30450 ($30{\mu}g/kg$, i.v.) and KR-30818 (30, $100{\mu}g/kg$, i.v.) showed similar proarrhythmic effects to lemakalim (PVC, duration of VT, and incidence of VF) with a tendancy to decrease the duration of VF and ST-segment elevation. Unlike other PCOs, however, glibenclamide (0.3, 1.0 mg/kg) had opposite effects on the induction of arrhythmias (PVC, the duration of VF); it had a tendancy to increase the duration of VT with a slight elevation of ST-segment. It seems likely that glibenclamide (0.3 mg/kg, i.v.), reduced the effects of lemakalim or KR-30450 ($30{\mu}g/kg$, i.v.) on arrhythmias (PVC, VT, VF and ST-segment). These results indicate that, in the coronary occluded rat model of ischemia, lemikuiln and KR-30450 exert a proarrhythmic activity, the effect being considered related to the opening of KATP channel.

• The Korean Journal of Physiology and Pharmacology
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• 제4권4호
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• pp.319-324
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• 2000

The causal relationship between heat shock protein (HSP) and second window of cardioprotective effect is still undetermined. In the present study, we assessed whether HSP-producing substances, amphetamine and ketamine, afforded protection against reperfusion-induced ventricular fibrillation (VF) and these protective effect remained after the inhibition of HSP72 production by quercetin, a mitochondrial ATPase inhibitor. Adult mongreal male cats $(n=60,\;2.5{\sim}4\;kg)$ were used in this study. Experimental animals were divided into five groups; control group (n=15), amphetamine ('A', n=11) group, ketamine ('K', n=9) group, amphetamine-ketamine ('AK', n=16) group and amphetamine-ketamine-quercetin ('AKQ', n=9) group. Twenty-four hours after the drug treatment, an episode of 20-min coronary artery occlusion was followed by 10-min reperfusion. The incidence of reperfusion-induced VF in the AK and AKQ groups was significantly lower than that in control group (p＜0.01). After the ischemia/reperfusion procedure, western blot analysis of HSP72 expression in the myocardial tissues resected from each group was performed. HSP72 production in the AK group was marked, whereas HSP72 was not detected in the AKQ and control groups. These results suggest that the suppressive effect against reperfusion-induced VF induced by amphetamine and ketamine is not mediated by myocardial HSP72 production but by other mechanisms.

• The Korean Journal of Physiology and Pharmacology
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• 제3권1호
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• pp.47-52
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• 1999

Blood flow restoration to ischemic zone of the heart is essential to salvage of ischemic tissue. However, there is a large body of evidence documenting that the reperfusion can induce reperfusion injury like reperfusion-induced malignant arrhythmias. In the present study, employing a cat model of regional cardiac ischemia, we examined if reperfusion rendered in a gradual fashion could lower the incidence of reperfusion-induced ventricular fibrillation (VF), which usually precipitated within a few to several tens of seconds after abrupt reperfusion. The experiments were conducted with male mongrel cats (n=46, 2.5-5 kg). The animals in the control and 30 MIN groups were subjected to an episode of 20- and 30-min left anterior descending coronary artery occlusion, respectively, followed by abrupt reperfusion. The animals in 5 G and 10 G groups received gradual reperfusion over a 5- and 10-min period, respectively, following a 20-min occlusion. The proportion of animals that exhibited VF during the reperfusion phase was 11/15 in the control, 7/10 in the 30 MIN, 5/10 in the 5 G and 2/11 in the 10 G groups. The incidence of VF in the 10 G group was significantly lower than that in the control or 30 MIN group subjected to abrupt reperfusion. These results suggest that the gradual reperfusion is a useful procedure against reperfusion-induced VF.

• Advances in Traditional Medicine
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• 제4권3호
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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.

• 한국임상수의학회지
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• 제18권4호
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• pp.402-410
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• 2001

This study was performed to investigate the hemodynamic changes which occur after occlusion of coronary artery and relation to reperfusion arrhythmias(RA) which occur when occlusion materials were removed form coronary artery in dogs. The occlusion of coronary artery was designed by temporary ligation of left circumflex branch of coronary artery during 30 minutes in 16 dogs. During occlusion of coronary artery, cardiac output(CO), mean aortic pressure (mAP), aortic systolic pressure(ASP), aortic diastolic pressure(ADP). left ventricular systolic pressure(LVSP), left ventricular maximum dp/dt (LV max. dp/dt) and left ventricular end-diastolic pressure (LVEDP) were measured. The occurrence of RA were observed for 5 minute after reperfusion by explained of ligation. As a results, cardiac arrest occurred in 4 dogs during occlusion of coronary artery, and RA was not observed in 5 dogs while it was seen in 5 dogs when explained ligation(reperfusion) after 30 minutes, the rest 2 dogs occurred temporary tachycardia. In hemodynamics changes, LVSP decreased by 10.9% and LV max. dp/dt by 5.4 % in comparison to control value which not ligated coronary artery, and LVEDP increased by 73.3%. The CO/min and mAP also decreased by 10.7% and by 11.3% expectedly. In the relationship to occurrence RA and hemodynamics changes, the LVSP and LV max. dp/dt at the time of occlusion in the RA group decreased by 11.9% and 0.8% in comarison to the control value while the decrease was 7.7% and 10% in the non-RA group. But the LVEDP in creased by 109.1% in the RA group while the decreased was 44.6% in the non-RA group. Referring CO/min, the drop was 8.8% in the RA occurrence group and 12.9% in the non-occurence group. These parameters of LVEDP, LV max. dp/dt, and CO were significant difference(p<0.05). The mAP also decreased by 11.9 in the RA group and by 9.8% in the non-RA group, but these defference were not the significant difference.

• Biomolecules & Therapeutics
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• 제13권1호
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• pp.20-25
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• 2005

The present study was performed to evaluate antiarrhythmic effects of KR-32570, a novel inhibitor of sodium hydrogen exchanger subtype-1 (NHE-1), in rat arrhythmia induced by focal ischemia and reperfusion. During ischemia, KR-32570 significantly decreased the number of premature ventricular contraction (PVC) from 152.0 times to 75.5, 52.4 and 20.0 times for 0.1, 0.3 and 1.0 mg/kg, respectively (p<0.05) and the duration of ventricular tachycardia (VT) from 88.1 s to 35.8, 7.7 and 1.3 s, respectively(p<0.05) in anesthetized rats subjected to 10-min coronary occlusion of coronary artery. Similarlt to ischemia-induced arrhythmia, KR-32570 significantly decreased reperfusion-induced arrhythmia including PVC (41.3, 21.5, 11.3 and 6.6 times at vehicle, 0.1, 0.3 and 1.0 mg/kg, respectively, p<0.05) and VT (100.5, 64.2, 25.8 and 25.2 s, respectively, p<0.05), and VF (86.9, 27.5, 6.9 and 0 s, respectively, p<0.05). Moreover, KR-32570 dose-dependently decreased the incidence of mortality occurring after reperfusion (41, 27, 18 and 0% at vehicle, 0.1, 0.3, 1.0 mg/kg, respectively). These results suggest that KR-32570 has a potent antiarrhythmic effect in rat arrhythmia induced by ischemia and reperfusion.

• Journal of Chest Surgery
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• 제30권9호
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• pp.847-853
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• 1997

Although the effects of adenosine on the heart, including the clinical suppression of cardiac arrhythmias, have been recognized for more than half a century, it is only in the last decade that the therapeutic potential of adenosine has been recognized. The objective of this study was to determine if augmentation of myocardial adenosine levels during global ischemia improves functional recovery after reperfusion. We used to modified Langendonf system to evaluate myocardial protective effect. Isolated rat hearts were subjected to 90 minutes of deep hypothermic arrest(15$^{\circ}C$) with modified St. Thomas'Hospital cardioplegic solution used to provide myocardial protection. Myocardial adenosine levels were augmented during ischemia by providing exogenous adenosine in the cardioplegic solution. Two groups of hearts w re studied: (1) control group(n=10) cardioplegia alone; (2) adenosine group(n=10) adenosine(0.75mg/kg/min) added to the cardioplegic solution. Significantly better percent recovery(p<0.01) in hemodynamics(except heart rate) at 60 minutes after reperfusion was evident compared to baseline values in the adenosine group. (systolic no란ic pressure : 78.5$\pm$3.6% vs 66.6$\pm$5.9%, airtic overflow volume : 61.7$\pm$ 11.6% vs 37.2$\pm$ 15.4%, coronary flow volume 77.1$\pm$7.5% vs 57.2$\pm$ 11.1%, and cardiac output : 65.6$\pm$ 11.5% vs 44.2$\pm$ 12.4%). Heart rate was similar in two groups(94.4$\pm$4.8% vs 95.3 $\pm$ 6.8%). Adenosine groups resulted in significantly rapid recovery time of heart beat after reperEusion(p<0.01) (24.5$\pm$7.6 sec. vs 179.0$\pm$ 131.1sec.). In biochemical study, CPK levels(0.1 $\pm$0.3U/L vs 1.4$\pm$0.8U/L) and lactic acid levels(0.08$\pm$0.Immol/L vs 0.34$\pm$0.2 mmol/L) were significantly low in adenosine groups(p<0.01). We concluded that adenosine included cardioplegia have better recovery effects after r perfusion in myocardial ischemia compared to adenosine free cardioplegia.

• Journal of Chest Surgery
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• 제22권4호
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• pp.580-588
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• 1989

The potential for enhancing myocardial protection by adding high-energy phosphate to cardioplegic solutions [St. Thomas Hospital solution] was investigated in a rat heart model of cardiopulmonary bypass and ischemic arrest. Creatine phosphate was evaluated as an additive to the St. Thomas Hospital cardioplegic solution. Creatine phosphate 10.0 mmol/L as the optimal concentration which improved recovery of aortic flow and cardiac output after a 30 minute period of normothermic [37oC] ischemic arrest. In comparing mechanical function in both groups the mean postischemic recoveries of aortic flow, cardiac output, stroke volume and stroke work [expressed as a percentage of its preischemic control] were significantly greater in STH-CP group than in CP- free control group. In addition to improving function and decreasing CK release, CP reduced reperfusion arrhythmias significantly decreasing the time between cross-clamp removal and return to regular rhythm from 81.8 * 13.9 [sec] in CP-free group to 35.9 * 6.8 [sec] in CP group [P< 0.05] so, exogenous CP exerts potent protective and antiarrhythmic effects when added to the St. Thomas Hospital cardioplegic solution. However, the mechanism of action remains to be elucidated.

• Journal of Chest Surgery
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• 제31권9호
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• pp.837-844
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• 1998

배경: 아데노신은 심근의 허혈상태에서 심근세포로부터 분비되어 부정맥과 심근허혈 및 수술후 재관류손상을 억제시키는 호르몬으로 알려져 있다. 아데노신의 심근보호 효과에 대한 연구는 주로 심정지액 속에 포함시킨 아데노신의 효과에 대하여 이루어 지고 있으나, 심정지액 속에 포함된 아데노신의 적정용량에 대해서는 보고가 다양하다. 저자들은 자체제작한 심폐체외순환 모델을 이용하여 단일용량의 아데노신(0.75 mg/Kg/min)이 우수한 심근보호효과를 나타낸 결과를 보고한 바 있으나 적절한 용량이었는지에 대한 확신은 없다. 따라서 본 연구의 목적은 심정지액 속에 포함된 아데노신의 적정용량을 알아보는데 있다. 대상 및 방법: 연구방법은 쥐를 이용하여 심정지시 심정지액(St. Thomas 심정지액)에 첨가한 아데노신의 용량에 따라 1군(0.5 mg/Kg/min), 2군(0.75 mg/Kg/min) 및 3군(1 mg/Kg/min) 으로 나누어 각각 10마리씩 실험하여 비교하였다. 마취 후 적출된 쥐심장의 대동맥과 좌심방에 도관을 삽관한 후에 심폐체외순환 모델에 연결하여 비작업성 순환과 작업성 순환을 시행하면서 혈역학적 수치를 측정하여 이를 대조값으로 이용하였다. 심정지액을 주입하여 심정지를 유도한 후에 90분간 허혈상태로 유지한 다음 비작업성 순환을 시행 후 작업성 순환으로 바꿔 10분, 30분 및 60분에 혈역학적 수치(심박동수, 수축기 대동맥압, 1분간 대동맥 박출량 및 관동맥관류량)를 측정하고, 생화학적 검사(CPK, Lactic Acid) 및 심장의 수분함유량도 측정하였다. 측정된 수치는 심정지 전 측정한 대조값에 대한 백분율로 환산하여 비교하였다. 결과: 실험 결과 심정지 전에 측정한 대조값 사이에는 세군 사이의 통계적인 유의성이 없었다. 심정지액의 주입 후 3군에서 가장 빨리 심정지가 일어났으며(p<0.05), 재관류 후 심박동이 돌아온 시간은 1군과 2군이 3군에 비하여 통계학적으로 유의하게 심박동이 빨리 돌아 왔다 (p<0.05). 그러나 1군과 2군 사이에는 유의성이 없었다. 심장의 재관류 후 측정한 심박동수의 회복률에서 10분에 측정한 값은 세군 사이에 유의성이 없었으나, 30분과 60분 에 측정한 값은 1군이 2군과 3군에 비하여 유의하게 높았으며(p<0.05), 2군도 3군에 비하여 유의하게 높았다(p<0.05). 수축기 대동맥압의 회복률, 1분 동안의 대동맥 박출량 및 심박출량(1분 동안의 대동맥 박출량과 관동맥관류량을 합산한 값)은 10분, 30분 및 60분에서 모두 2군이 1군과 3군에 비하여, 1군은 3군에 비하여 유의하게 높았다(p<0.05). 관동맥관류량의 회복률은 10분과 30분에 측정한 값은 2군이 1군과 3군에 비하여, 1군은 3군에 비하여 유의하게 높았으며(p<0.05), 60분에 측정한 값은 1군과 2군이 3군에 비하여 유의하게 높았다(p<0.05). 심근의 수분함유량과 관상동맥 관류량의 생화학적 검사결과 CPK와 Lactic Acid는 세군 사이에 유의성이 없었다. 결론 : 이상의 결과로 아데노신을 심정지용액에 첨가시 비교적 적정 용량은 0.75 mg/Kg/min 을 투여하는 것이 적절할 것으로 생각된다.