• Journal of Veterinary Clinics
• /
• 제6권2호
• /
• pp.281-290
• /
• 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.

• Korean Journal of Clinical Pharmacy
• /
• 제6권2호
• /
• pp.32-40
• /
• 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
• /
• 제4권4호
• /
• pp.319-324
• /
• 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
• /
• 제3권1호
• /
• pp.47-52
• /
• 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
• /
• 제4권3호
• /
• pp.157-161
• /
• 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.

• Journal of Veterinary Clinics
• /
• 제18권4호
• /
• pp.402-410
• /
• 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
• /
• 제13권1호
• /
• pp.20-25
• /
• 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
• /
• 제30권9호
• /
• pp.847-853
• /
• 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
• /
• 제22권4호
• /
• pp.580-588
• /
• 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
• /
• 제31권9호
• /
• pp.837-844
• /
• 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.