• Journal of Chest Surgery
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• v.23 no.1
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• pp.1-8
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• 1990

This experiment was carried out under the postulation that activation of an intracellular calcium-calmodulin complex may play an important role in myocardial injury induced by ischemia and reperfusion. Trifluoperazine[TFP], a calmodulin antagonist, was added to the potassium cardioplegic solution and used just before ischemia, and its protective effect from ischemic injury was investigated, using Langendorff rat heart model. TFP group had better post-ischemic functional recovery and lower post-ischemic contracture after 30 minutes of normothermic ischemia. Creatine kinase leakage was also decreased in TFP group but there was no statistical difference between control group and TFP group. We concluded that TFP has some protective effect from myocardial ischemic injury and its effect might be due to prevention of activation of intracellular calcium-calmodulin complex.

• Journal of Chest Surgery
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• v.23 no.6
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• pp.1090-1106
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• 1990

This study was undertaken to investigate whether adenosine administered during cardioplegic arrest could enhance myocardial protection and improve recovery of function after ischemia. Isolated Langendorff-perfused rat hearts were subjected to 40 minutes of normothermic [37oC] ischemia. Control hearts [n=10] received modified St. Thomas’ cardioplegic solution, and the remaining hearts received modified St. Thomas’ cardioplegic solution with either 20 \ulcornerM [n=10], 200 \ulcornerM [n=10] adenosine. After ischemia of 40 minutes and 30 minutes of reperfusion, left ventricular contractility was superior in all groups of adenosine-treated hearts compared with control hearts. Furthermore, there was a significant incremental increase in functional recovery with increasing dose of adenosine. Post-ischemic diastolic stiffness was significantly better in all adenosine groups compared with controls. No differences were noted in coronary flow or myocardial water content between adenosine-treated and control hearts. These data demonstrate that adenosine administered in these concentrations provides myocardial protection, preservation of myocardial ATP and creatine phosphokinase and improved post-ischemic functional hemodynamic recovery after normothermic ischemia, presumably metabolically by reducing depletion of adenosine triphosphate, inducing rapid cardiac arrest and enabling improved post-ischemic recovery.

• Journal of Chest Surgery
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• v.24 no.11
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• pp.1058-1067
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• 1991

High potassium cardioplegia is a widely accepted procedure to enhance myocardial protection from ischemic injuries associated with open heart surgery. Maintaining optimum osmolarity of the cardioplegic solution is one of the required conditions for an ideal cardioplegic solution Albumin is an frequently added component for maintaining optimum osmolarity of clinically used cardioplegic solutions. But the source of albumin is human blood so that the supply is limited and the cost of manufacturing is relatively high. Recently there are moves to minimized the use of blood product for fear of blood-associated infections or immunological disorders. In this experiment, we substituted mannitol or glucose for albumin added to the cardioplegic solution which has been used at the Wonju Medical College, To determine whether addition of mannitol or glucose instead of albumin in the cardioplegic solution can produce satisfactory myocardial protection during ischemia, three different groups of isolated rat heart perfused by modified Langendorff technique were studied. Wonju Cardioplegic Solution was selected as a standard high potassium[18mEq/L of K+] cardioplegic solution. Three kinds of cardioplegic solution were made by modifying the composition maintaining the same osmolarity[339$\pm$1mOsm/Kg] Isolated rat heart were perfused initially with retrograde nonworking mode and then changed to working mode. After measuring the heart rate, systolic aortic pressure, aortic flow, coronary flow, ischemic arrest by aorta cross clamp and cardioplegia was made maintaining the temperature of water jacket at 10oC. The heart was rewarmed and reperfused after 60min of ischemic arrest with intermittent cardioplegia at the 30min interval. The time to return of heart beat and the time required to get. Regular heart beat were observed after reperfusion. The recovery rate of the functional variables-heart rate, systolic aortic pressure, aortic flow, coronary flow and cardiac output were calculated and compared among the three groups of different cardioplegia-albumin, mannitol, and glucose. The wet weight and dry weight was measured and the water content of the heart as figured out for comparison. The time to return of heart beat was fastest in the albumin group, The functional recovery rates were best in the albumin group also. In the above conditions, albumin was the best additive to the cardioplegic solution compared to the mannitol or glucose.

• 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.

• YAKHAK HOEJI
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• v.26 no.4
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• pp.239-251
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• 1982

The rate of deterioration of contractile force of isolated hearts from control and panax ginseng treated rats was determined and response of contractile force of the hearts from ginseng treated rats to several autonomic and other drugs was investigated. Rats weighing 150-250g were administrered orally with ginseng ethanol extract (100mg/kg) and total ginseng saponin (50mg/kg/day) for a week. Ginsenoside Rb$_{1}$ (5mg/kg/day) and ginsenoside Re (5mg/kg/day) were administered respectively for a week. The isolated hearts from rats were perfused with Krebs-Henseleit solution by using Langendorff perfusion apparatus. The control group was only able to maintain approximately 75.5% of their initial strength after 60 min of perfusion, whereas ginseng ethanol extract, total ginseng saponin treated hearts were able to sustain nearly their initial strength even after 60 min. Ginsenoside Rol treated hearts also sustained 93% of their initial strength, but there was no significant difference in the deterioration percentage of the contractile force of ginsenoside Re treated hearts. Experiments were conducted to study the response to perfusion of ginseng treated animal heart with epinephrine, isoproterenol, propranolol, and phenobarbital. The isolated hearts were perfused with Krebs-Henseleit solution containing epinephrine (10$^{-6}$ M), isoproterenol ($10^{-7}$M), propranolol ($10^{-6}$M) and phenobarbital (7{\times}10^{-3}M$) respectively. The maximum inotropic effect of epinephrine and isoproterenol was observed after 2~3 minutes of drug perfusion. Effect of epinephrine on ginseng ethanol extract and total ginseng saponin treated hearts was reduced compared with control. On the other hand, this phenomenon was not observed in ginsenoside Re treated rats but on ginsenoside $Rb_{1}$ treated rats. The positive inotropic effect of isoproterenol was reduced in the hearts from ginseng treated rats compared with control heart, Propranolol or phenobaribital decreased the contractile force in the control rats. The depressant effect of propranolol and phenobarbitat on ginseng treated rat hearts was less than those of control rat hearts. The result suggest that ginseng ethanol extract , ind total ginseng saponin and ginsenoside $Rb_{1}$ may protect the deterioration of contractile force of the heart and may attenuate the response to several drugs on hearts.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.281-296
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• 2021

The beneficial effects of hypoxic preconditioning are abolished in the diabetes. The present study was designed to investigate the protective effects and mechanisms of repeated episodes of whole body hypoxic preconditioning (WBHP) in db/db mice. The protective effects of preconditioning were explored on diabetes-induced vascular dysfunction, cognitive impairment and ischemia-reperfusion (IR)-induced increase in myocardial injury. Sixteen-week old db/db (diabetic) and C57BL/6 (non-diabetic) mice were employed. There was a significant impairment in cognitive function (Morris Water Maze test), endothelial function (acetylcholine-induced relaxation in aortic rings) and a significant increase in IR-induced heart injury (Langendorff apparatus) in db/db mice. WBHP stimulus was given by exposing mice to four alternate cycles of low (8%) and normal air O₂ for 10 min each. A single episode of WBHP failed to produce protection; however, two and three episodes of WBHP significantly produced beneficial effects on the heart, brain and blood vessels. There was a significant increase in the levels of brain-derived neurotrophic factor (BDNF) and nitric oxide (NO) in response to 3 episodes of WBHP. Moreover, pretreatment with the BDNF receptor, TrkB antagonist (ANA-12) and NO synthase inhibitor (L-NAME) attenuated the protective effects imparted by three episodes of WBHP. These pharmacological agents abolished WBHP-induced restoration of p-GSK-3β/GSK-3β ratio and Nrf2 levels in IR-subjected hearts. It is concluded that repeated episodes of WHBP attenuate cognitive impairment, vascular dysfunction and enhancement in IR-induced myocardial injury in diabetic mice be due to increase in NO and BDNF levels that may eventually activate GSK-3β and Nrf2 signaling pathway to confer protection.

• Journal of Pharmacopuncture
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• v.25 no.4
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• pp.369-381
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• 2022

Objectives: Hyperlipidemia (HL) is a major cause of ischemic heart diseases. The size-limiting effect of ischemic preconditioning (IPC), a cardioprotective phenomenon, is reduced in HL, possibly because of the opening of the mitochondrial permeability transition pore (MPTP). The objective of this study is to see what effect pretreatment with Inula racemose Hook root extract (IrA) had on IPC-mediated cardioprotection on HL Wistar rat hearts. An isolated rat heart was mounted on the Langendorff heart array, and then ischemia reperfusion (I/R) and IPC cycles were performed. Atractyloside (Atr) is an MPTP opener. Methods: The animals were divided into ten groups, each consisting of six rats (n = 6), to investigate the modulation of I. racemosa Hook extract on cardioprotection by IPC in HL hearts: Sham control, I/R Control, IPC control, I/R + HL, I/R + IrA + HL, IPC + HL, IPC + NS + HL, IPC + IrA+ HL, IPC + Atr + oxidative stress, mitochondrial function, integrity, and hemodynamic parameters are evaluated for each group. Results: The present experimental data show that pretreatment with IrA reduced the LDH, CK-MB, size of myocardial infarction, content of cardiac collagen, and ventricular fibrillation in all groups of HL rat hearts. This pretreatment also reduced the oxidative stress and mitochondrial dysfunction. Inhibition of MPTP opening by Atr diminished the effect of IrA on IPC-mediated cardioprotection in HL rats. Conclusion: The study findings indicate that pretreatment with IrA e restores IPC-mediated cardioprotection in HL rats by inhibiting the MPTP opening.

• The Korean Journal of Pharmacology
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• v.30 no.3
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• pp.321-330
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• 1994

The protective effect of 'ischemic preconditioning (PC)' on ischemia-reperfusion injury of heart has been reported in various animal species, but without known mechanisms in detail. In an attempt to investigate the cardioprotective mechanism of PC, we examined the effects of PC on the myocardial oxidative injuries and the oxygen free radical production in the ischemia-reperfusion model of isolated Langendorff preparations of rat hearts. PC was performed with three episodes of 5 min ischemia and 5 min reperfusion before the induction of prolonged ischemia (30 min)-reperfusion(20 min). PC prevented the depression of cardiac function (left ventricular pressure x heart rate) observed in the ischemic-reperfused heart, and reduced the release of lactate dehydrogenase during the reperfusion period. On electron microscopic pictures, myocardial ultrastructures were relatively well preserved in PC hearts as compared with non-PC ischemic-reperfused hearts. In PC hearts, lipid peroxidation of myocardial tissue as estimated from malondialdehyde production was markedly reduced. PC did not affect the activity of xanthine oxidase which is a major source of oxygen radicals in the ischemic rat hearts, but the myocardial content of hypoxanthine (a substrate for xanthine oxidase) was much lower in PC hearts. It is suggested from these results that PC brings about significant myocardial protection in ischemic-reperfused heart and this effect may be related to the suppression of oxygen free radical reactions.

• Journal of Chest Surgery
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• v.33 no.8
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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.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.3
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• pp.209-217
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• 2024

In addition to cellular damage, ischemia-reperfusion (IR) injury induces substantial damage to the mitochondria and endoplasmic reticulum. In this study, we sought to determine whether impaired mitochondrial function owing to IR could be restored by transplanting mitochondria into the heart under ex vivo IR states. Additionally, we aimed to provide preliminary results to inform therapeutic options for ischemic heart disease (IHD). Healthy mitochondria isolated from autologous gluteus maximus muscle were transplanted into the hearts of Sprague-Dawley rats damaged by IR using the Langendorff system, and the heart rate and oxygen consumption capacity of the mitochondria were measured to confirm whether heart function was restored. In addition, relative expression levels were measured to identify the genes related to IR injury. Mitochondrial oxygen consumption capacity was found to be lower in the IR group than in the group that underwent mitochondrial transplantation after IR injury (p < 0.05), and the control group showed a tendency toward increased oxygen consumption capacity compared with the IR group. Among the genes related to fatty acid metabolism, Cpt1b (p < 0.05) and Fads1 (p < 0.01) showed significant expression in the following order: IR group, IR + transplantation group, and control group. These results suggest that mitochondrial transplantation protects the heart from IR damage and may be feasible as a therapeutic option for IHD.