• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.31-37
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• 1996

The protective effect of 'ischemic preconditioning (IP)'on ischemia-reperfusion injury of heart has been reported in various animal species, but the mechanism is unclear. In an attempt to elucidate the mechanism of IP, we examined the effects of blockers against adenosine and protein kinase C in preconditioned heart of rat. The hearts perfused with oxygen-saturated Krebs-Henseleit solution by Langendorff method were exposed to 30 min global ischemia followed by 20 min reperfusion. IP was performed with three episodes of 5 min ischcmia and 5 min reperfusion just before ischemia-reperfusion. IP prevented the depression of contractile function and the myocardial contracture in the ischemic-reperfused heart and reduced the release of lactate dehydrogenase during the reperfusion period. Polymyxin B, chelerythrine and colchicine, PKC inhibitors, attenuated almost completely the anti-ischemic effect of IP, while adenosine receptor antagonists did not. These results indicate that PKC may be a crucial intracellular mediator in anti-ischemic action of IP in ischemic-reperfused rat heart, while adenosine may not be involved in the mechanism of IP.

• Journal of Chest Surgery
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• v.23 no.6
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• pp.1107-1117
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• 1990

The regulatory role of the post \ulcorner1-and \ulcorner2-adrenoceptors on cardiac function, particularly in coronary flow rate, was investigated in the isolated rat heart treated with 10-6 M propranolol. When introduced into the left atrium of the heart, phenylephrine[10-7-10-2 M] decreased coronary flow rate and increased mean coronary resistance in a dose related fashion, but did not affect heart rate. Methoxamine also elicited the increment of coronary resistance and the decrement of coronary flow rate, though the effects of methoxamine were weaker than those by phenylephrine. The effect of phenylephrine was inhibited by 1\ulcornerM prazosin and shifting the dose-response curve to the right. The effects of clonidine, a selective \ulcorner2-adrenoceptor agonist, were studied in the heart taken from reserpinized rats. Clonidine increased coronary resistance, decreased heart rate and coronary flow rate with a dose-dependent manner. These effects were abolished by 10-6 M yohimbine, a selective \ulcorner2-antagonist, and were not affected by 10-6M prazosin. Clonidine also decreased coronary flow and increased mean coronary resistance in electric paced heart. These effects were inhibited by rawoulscine, a selective ca-antagonist. These results indicate that the stimulation of both post \ulcorner1-and \ulcorner2-adrenoceptor causes coronary vasoconstiction. And it is inferred that this model of sympathomimetics-induced coronary vasospasm may provide a useful tool for investigating spasmolytic agents which are of benefit in the treatment of variant angina.

• Archives of Pharmacal Research
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• v.29 no.9
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• pp.777-785
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• 2006

Nelumbinis Semen (NS), or lotus seed, is one of the most well-known traditional herbal medicines and is frequently used to treat cardiovascular symptoms in Korea. The anti-ischemic effects of NS on ischemia-induced isolated rat heart were investigated through analyses of changes in blood pressure, aortic flow, coronary flow, and cardiac output. The subjects in this study were divided into two groups: a control, untreated ischemia-induced group, and an ischemia-induced group treated with NS. There were no significant differences in perfusion pressure, aortic flow, coronary flow and cardiac output between the groups before ischemia was induced. The supply of oxygen and buffer was stopped for ten minutes to induce ischemia in isolated rat hearts, and NS was administered during ischemia induction. NS treatment significantly prevented decreases in perfusion pressure, aortic flow, coronary flow and cardiac output under ischemic conditions (p<0.01). In addition, the mechanism of the anti-ischemic effects of NS was also examined through quantitation of intracellular calcium content in rat neonatal cardiomyocytes. NS significantly prevented intracellular calcium increases induced by isoproterenol (p<0.01). These results suggest that NS has distinct anti-ischemic effects through calcium antagonism.

• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.358-363
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• 1998

Intravenous lipid emulsion is used extensively as a major component of parenteral nutrition for patients in the surgical intensive care unit. Abnormal cardiovascular function related to lipid infusion has been reported although conflicting results exist. In the present study, we investigated the effects of intravenous emulsions of long-chain triglyceride (LCT) and medium-chain triglyceride (MCT) on myocardial ischemia/ reperfusion injury and on platelet aggregation in rat. There was no difference between LCT and MCT considering the effects on left ventricular developed pressure (LVDP) and coronary flow rate (CFR) before and after ischemia/reperfusion in isolated rat heart. On the other hand, a difference was found between LCT and MCT with regard to their effects on heart rate (HR) and end diastolic pressure (EDP) after ischemia/reperfusion. After ischemia/reperfusion, HR was significantly (P<0.05) reduced and EDP significantly (P<0.05) inc.eased by LCT (18$\pm$2.0% and 42.8$\pm$8.9%, respectively), but not by MCT Ex vivo platelet aggregation induced by collagen was reduced by LCT infusion, but not by MCT These findings suggest that MCT may have slightly more favorable effect than LCT on the myocardial function after ischemia/reperfusion in rat.

• Korean Journal of Veterinary Research
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• v.39 no.3
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• pp.463-471
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• 1999

Magnesium($Mg^{2+}$) is one of the most abundant intracellular divalent cation. Although recent studies demonstrate that adrenergic receptor stimulation evokes marked changes in $Mg^{2+}$ homeostasis, the regulation of $Mg^{2+}$ by dopaminergic receptor stimulation is not yet known. In this work, we used dopaminergic agents to identify which type(s) of receptors were involved in the mobilization of $Mg^{2+}$ by dopaminergic receptor stimulation in the perfused rat hearts, isolated myocytes and circulating blood. The $Mg^{2+}$ content was measured by atomic absorbance spectrophotometry. Dopamine(DA), apomorphine(APO) and pergolide stimulated $Mg^{2+}$ efflux in the perfused rat hearts and these effects were inhibited by haloperidol or fluphenazine, nonselective dopaminergic antagonists. SKF38393, a selective doparminergic agonist, increased $Mg^{2+}$ efflux from the perfused hearts in dose dependant manners and SKF38393-induced $Mg^{2+}$ efflux was blocked by haloperidol. However, dopaminergic agonists-induced $Mg^{2+}$ efflux was potentiated in the presence of sulpiride or eticlopride, $D_2$-selective antagonist, from the perfused hearts. This increase of $Mg^{2+}$ efflux was blocked by haloperidol or imipramine. DA or pergolide increased in circulating $Mg^{2+}$ from blood. By contrast, PPHT stimulated $Mg^{2+}$ influx(a decrease in efflux) from the perfused hearts and circulating blood. PPHT-induced $Mg^{2+}$ influx was blocked by fluphenazine in the perfused hearts. DA-stimulated $Mg^{2+}$ efflux was inhibited by dopaminergic antagoinst in the isolated myocytes. In conclusion, the flux of $Mg^{2+}$ is modulated by DA receptor activation in the rat hearts. The efflux of $Mg^{2+}$ can be increased by $D_1$-receptor stimulation and decreased by $D_2$-receptor stimulation, respectively.

• Journal of Chest Surgery
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• v.23 no.4
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• pp.646-653
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• 1990

Currently numerous methods are in use for myocardial protection from the ravages of ischemia and hypoxia. This study was designed to compare with FDP-GIK[Group II, n=8] and GIK cardioplegic solution[Group I, n=8] in ability of myocardial protection and was examined in the isolated working rat heart subjected to long period[120 min] of hypothermic[10 - 15K] ischemic arrest with multidose[every 30 min] cardioplegic infusion. During postischemic reperfusion period 20 min, hemodynamic functions[aortic flow, coronary flow, peak aortic pressure, cardiac output, heart rate], biochemical enzymatic & electrical activities were evaluated. The time from onset of reperfusion to the return of regular sinus rhythm was significantly reduced from 87$\pm$3 sec to 17$\pm$2 sec[P<0.05]. The postischemic recovery of aortic flow was better in the group II [95.1$\pm$3.3% of its preischemic control level] than in the Group I [75.4$\pm$6.8%] [P<0.05]. Cardiac output and stroke volume was also better in the group[91.3$\pm$1.6%, 89.4$\pm$2.6%, respectively] than in the Group I [79.1$\pm$3.7%, 77.0$\pm$4.8%, respectively] [P<0. 05]. Creatine kinase leakage was also significantly reduced from 33.8$\pm$4.9 IU /10 min / gm * dry weight to 15.4$\pm$3.6 IU /10 min /gm * dry weight[P<0.05]. It is suggested that adding FDP to GIK cardioplegic solution improves its ability to protect the heart against long period of hypoxic ischemia.

• Korean Journal of Veterinary Research
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• v.39 no.1
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• pp.62-69
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• 1999

Although it has been reported that hormones or chemicals, which increase in intracellular cAMP, produced $Mg^{2+}$ release from the heart, it is not well characterized whether a specific $Mg^{2+}$ exchanger is involved in cAMP-induced $Mg^{2+}$ efflux in the mammalian hearts. In this work, we studied the relationship between the increase in intracellular cAMP and ion transport system on $Mg^{2+}$ regulation in the perfused rat heart and isolated myocytes. The $Mg^{2+}$ content in the perfusate and supernatant were measured by atomic absorption spectrophotometer. The addition of membrane permeable cAMP analogue to the perfused hearts and myocytes induced a $Mg^{2+}$ efflux in the dose dependent manners. $Mg^{2+}$ efflux was stimulated by cAMP modulators (forskolin, IBMX and Ro20-1724) in the perfused hearts and myocytes. cAMP-induced $Mg^{2+}$ efflux was inhibited by $H_7$, benzamil or imipramine in the perfused hearts and myocytes, but not by EIPA. We confirmed that a significant $Mg^{2+}$ efflux was induced by an increase in intracellular cAMP in the hearts and myocytes. The cAMP-induced increase of $Mg^{2+}$ efflux in the hearts may be involved in ion transport system ($Na^+-Ca^{2+}$ and $Na^+-Mg^{2+}$ exchanger).

• The Journal of Advanced Prosthodontics
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• v.6 no.6
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• pp.539-546
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• 2014

PURPOSE. Silk fibroin (SF) is a new degradable barrier membrane for guided bone regeneration (GBR) that can reduce the risk of pathogen transmission and the high costs associated with the use of collagen membranes. This study compared the efficacy of SF membranes on GBR with collagen membranes (Bio-$Gide^{(R)}$) using a rat calvarial defect model. MATERIALS AND METHODS. Thirty-six male Sprague Dawley rats with two 5 mm-sized circular defects in the calvarial bone were prepared (n=72). The study groups were divided into a control group (no membrane) and two experimental groups (SF membrane and Bio-$Gide^{(R)}$). Each group of 24 samples was subdivided at 2, 4, and 8 weeks after implantation. New bone formation was evaluated using microcomputerized tomography and histological examination. RESULTS. Bone regeneration was observed in the SF and Bio-$Gide^{(R)}$-treated groups to a greater extent than in the control group (mean volume of new bone was $5.49{\pm}1.48mm^3$ at 8 weeks). There were different patterns of bone regeneration between the SF membrane and the Bio-$Gide^{(R)}$ samples. However, the absolute volume of new bone in the SF membrane-treated group was not significantly different from that in the collagen membrane-treated group at 8 weeks ($8.75{\pm}0.80$ vs. $8.47{\pm}0.75mm^3$, respectively, P=.592). CONCLUSION. SF membranes successfully enhanced comparable volumes of bone regeneration in calvarial bone defects compared with collagen membranes. Considering the lower cost and lesser risk of infectious transmission from animal tissue, SF membranes are a viable alternative to collagen membranes for GBR.

• Environmental Analysis Health and Toxicology
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• v.21 no.1 s.52
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• pp.71-79
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• 2006

Epidemiologic studies have showed a close correlation between arsenic exposure and heart disease such as, cardiovascular problem, ischemic heart disease, infarction, atherosclerosis and hypertension in human. It may increase the mortality of high risk group with heart disease. Regarding the mechanism studies of heart failure, blood vessel, vascular smooth muscle cells and endothelial cells have long been focused as the primary targets in arsenic exposure but there are only a few studies on the cardiomyocytes. In this study, the generation of oxidative stress by low dose of arsenic trioxide was investigated in rat cardiomyocytes. By direct measurement of reactive oxygen species and fluorescent microscopic observation using fluorescent dye 2',7'-dichlorofluorescin diacetate, reactive oxygen species were found to be generated without cell death, where cells are treated with 0.1 ppm arsenic for 24 hours. With the induction of reactive oxygen species, GSH level was decreased by the same treatment. However, DNA damage did not seem to be serious by DAPI staining, while high dose of arsenic (2 ppm for 24 hrs) caused fragmentation of DNA. To identify the molecular biomarkers of low-dose arsenic exposure, gene expression was also investigated with whole genome microarray. As results, 9,022 genes were up-regulated including heme oxygenase-l and glutathione S-transrerase, which are well-known biomarkers of oxidative stress. 9,404 genes were down-regulated including endothelial type gp 91-phox gene by the treatment of 0.1 ppm arsenic for 24 hours. This means that biological responses of cardiomyocytes may be altered by ROS induced by low level arsenic without cell death, and this alteration may be detected clearly by molecular biomarkers such as heme oxygenase-1.

• The Journal of Korean Medicine
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• v.18 no.2
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• pp.340-354
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• 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.