• The Korean Journal of Physiology and Pharmacology
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• v.2 no.6
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• pp.753-761
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• 1998

Preconditioning of a heart with small doses of catecholamines induces a tolerance against the subsequent lethal ischemia. The present study was performed to find a specific receptor pathway involved with the catecholamine preconditioning and to test if adenosine plays a role in this cardioprotective effect. Isolated rat hearts, pretreated with small doses of ${\alpha}-\;or\;{\beta}-adrenergic$ agonists/antagonists, were subjected to 20 minutes ischemia and 20 minutes reperfusion by Langendorff perfusion method. Cardiac mechanical functions, lactate dehydrogenase and adenosine release from the hearts were measured before and after the drug treatments and ischemia. In another series of experiments, adenosine $A_1\;or\;A_2$ receptor blockers were treated prior to administration of adrenergic agonists. Pretreatments of a ${\beta}-agonist,\;isoproterenol(10^{-9}{\sim}10^{-7}\;M)$ markedly improved the post-ischemic mechanical function and reduced the lactate dehydrogenase release. Similar cardioprotective effect was observed with an ?-agonist, phenylephrine pretreatment, but much higher $concentration(10^{-4}\;M)$ was needed to achieve the same degree of cardioprotection. The cardioprotective effects of isoproterenol and phenylephrine pretreatments were blocked by a ${\beta}_1-adrenergic$ receptor antagonist, atenolol, but not by an ${\alpha}_1-antagonist,$ prazosin. Adenosine release from the heart was increased by isoproterenol, and the increase was also blocked by atenolol, but not by prazosin. A selective $A_1-adenosine$ receptor antagonist, 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX) blocked the cardioprotection by isoproterenol pretreatment. These results suggest that catecholamine pretreatment protects rat myocardium against ischemia and reperfusion injury by mediation of ${\beta}_1-adrenergic$ receptor pathway, and that adenosine is involved in this cardioprotective effect.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.4
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• pp.283-289
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• 2013

This study was designed to evaluate the protective effect of Korean red ginseng (KRG) against ischemia/reperfusion (I/R) injury in isolated guinea pig heart. KRG has been shown to possess various ginsenosides, which are the major components of Panax ginseng. These components are known naturally occurring compounds with beneficial effects and free radical scavenging activity. The heart was induced to ischemia for 60 min, followed by 120 min reperfusion. The hearts were randomly allocated into five groups (n=8 for each group): normal control (N/C), KRG control, I/R control, 250 mg/kg KRG group and 500 mg/kg KRG group. KRG significantly increased hemodynamics parameters such as aortic flow, coronary flow and cardiac output. Moreover, KRG significantly increased left ventricular systolic pressure (LVSP), the maximal rate of contraction (+dP/$dt_{max}$) and maximal rate of relaxation (-dP/$dt_{max}$). Also, treatment of KRG ameliorated electrocardiographic index such as the QRS, QT and RR intervals. Moreover, KRG significantly suppressed the lactate dehydrogenase, creatine kinase-MB fraction and cardiac troponin I and ameliorated the oxidative stress markers such as malondialdehyde and glutathione. KRG was standardized through ultra performance liquid chromatograph analysis for its major ginsenosides. Taken together, KRG has been shown to prevent cardiac injury by normalizing the biochemical and oxidative stress.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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• pp.239-249
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• 2021

The present study explored the therapeutic potential of hydrogen sulfide (H2S) in restoring aging-induced loss of cardioprotective effect of remote ischemic preconditioning (RIPC) along with the involvement of signaling pathways. The left hind limb was subjected to four short cycles of ischemia and reperfusion (IR) in young and aged male rats to induce RIPC. The hearts were subjected to IR injury on the Langendorff apparatus after 24 h of RIPC. The measurement of lactate dehydrogenase, creatine kinase and cardiac troponin served to assess the myocardial injury. The levels of H2S, cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), nuclear factor erythroid 2-related factor 2 (Nrf2), and hypoxia-inducible factor (HIF-1α) were also measured. There was a decrease in cardioprotection in RIPC-subjected old rats in comparison to young rats along with a reduction in the myocardial levels of H2S, CBS, CSE, HIF-1α, and nuclear: cytoplasmic Nrf2 ratio. Supplementation with sodium hydrogen sulfide (NaHS, an H2S donor) and l-cysteine (H2S precursor) restored the cardioprotective actions of RIPC in old hearts. It increased the levels of H2S, HIF-1α, and Nrf2 ratio without affecting CBS and CSE. YC-1 (HIF-1α antagonist) abolished the effects of NaHS and l-cysteine in RIPC-subjected old rats by decreasing the Nrf2 ratio and HIF-1α levels, without altering H2S. The late phase of cardioprotection of RIPC involves an increase in the activity of H2S biosynthetic enzymes, which increases the levels of H2S to upregulate HIF-1α and Nrf2. H2S has the potential to restore aging-induced loss of cardioprotective effects of RIPC by upregulating HIF-1α/Nrf2 signaling.

• YAKHAK HOEJI
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• v.59 no.4
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• pp.137-150
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• 2015

Cardiovascular disease is one of the leading cause of death in many developed countries as well as developing countries. Many evidences indicate that natural products have profound beneficial effects for cardioprotection. In addition to the crude extracts, an identified single compound may be used as a lead molecule for the therapeutic interests. In this review, we discuss promising natural products for cardiovascular diseases, their molecular targets, and their mechanisms, which may help the further direction of studies and applications of natural products for cardiovascular diseases.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.4025-4030
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• 2012

Background and Objective: Cardiotoxicity and oxidative stress is a life-threatening side effect of doxorubicin (DOX). We investigate the effects of short-term exercise as therapeutic tool for improvement of cardioprotection against DOX-induced cardiotoxicity in the rat. Methods: Wistar males (weighing $257{\pm}28g$) were divided into six groups: (1) control+placebo (2) control+DOX $10mg.kg^{-1}$ (3) control+DOX $20mg.kg^{-1}$ (4) training+placebo (5) training+ DOX$10mg.kg^{-1}$ (6) training+DOX $20mg.kg^{-1}$. Cardiotoxicity was induced by DOX (10 and $20mg.kg^{-1}$). The rats in groups 4, 5 and 6 experienced treadmill running of 25 to $39min.day^{-1}$ and 15 to $17m.min^{-1}$, 5 days/wk for 3 wk. At the end of the endurance training program, rats in the 1 and 4 groups, in the 2 and 5 groups and in the 3 and 6 groups received saline solution, DOX $10mg.kg^{-1}$ and DOX $20mg.kg^{-1}$, respectively. Result: DOX administration (10 and $20mg.kg^{-1}$) caused significant increase in MDA and Apelin, an insignificant increase in NO and a significant decrease in SOD, as compared to the C+P group. Three weeks of the pretreatment endurance exercise resulted in a significant increase of Apelin and SOD, an insignificant increase of NO and an insignificant decrease of MDA, as compared to the C+P group. Furthermore, after three weeks of endurance training and DOX treatment with $10mg.kg^{-1}$ and $20mg.kg^{-1}$, a significant increase in apelin and SOD, and a significant decrease in MDA were detected in comparison to C+DOX10 and/or C+DOX20 groups. There was a significant difference between DOX$10mg.kg^{-1}$ and DOX$20mg.kg^{-1}$ treatments in MDA levels only. Conclusion: Pretreatment exercise may improve myocardial tolerance to DOX-induced cardiotoxicity by inhibition of oxidative stress and up-regulation of antioxidants in heart tissue.

• Biomedical Science Letters
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• v.24 no.2
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• pp.130-133
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• 2018

The aim of this study was to evaluate the protective function of fisetin, a natural flavonoid in zebrafish heart for the treatment of myocardial infarction in coronary and ischemic heart disease. For this purpose, we induced oxidative stress zebrafish (Danio rerio)-Tg (cmlc2: egfp) by $H_2O_2$ and then administered fisetin, the protective effect of fisetin was determined by measuring the heart rate following fisetin administration. After testing the toxicity of fisetin, we found that the heartt increased in a concentration-dependent manner, however there was no difference between the heart rates of embryos and adults. The improved heart rate demonstrated the cardioprotective effect of fisetin. The result showed that fisetin, at concentration of 3and $5{\mu}M$, significantly increased heart rate compared with the heart with $H_2O_2$ alone. This indicates that fisetin plays an important role in the prevention of heart damage and treatment of cardiovascular diseases caused by oxidative stress due to ischemia / reperfusion.

• Korean Journal of Clinical Pharmacy
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• v.7 no.1
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• pp.33-39
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• 1997

Cardiac and antihypertensive effects of BMS-180448, a cardiac-selective ATP-sensitive potassium channel opener, and its newly synthesized derivatives KR-31281, KR-31282 and KR-31299 were evaluated in isolated perfused rat hearts (25 min global ischemia/30 min reperfusion) and conscious rats. Three new compounds $(10\;{\mu}M)$ induced positive inotropism as evidenced by increased LVDP (left ventricular developed pressure) and RPP (Rate-Pressure Product) in nonischemic rat heart. HR-31299 increased CF (coronary flow) and HR (heart rate) but the other two had no effects. KR-31282, KR-31281 and HR-31299 had a tendency to increase reperfusion LVDP and RPP compared with vehicle, while the latter two significantly reduced reperfusion EDP with a tendency to inclose TTC (time to contracture). All three KR-compounds had very weak effects on MBP and HR in conscious rats. These results indicate that KR-31281 and HR-31299 may have some cardioprotective effects, although weaker than BMS-180448, and their mode of action different from that of BMS-180448, despite the similarity in major structural moeity.

• Korean Journal of Clinical Pharmacy
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• v.20 no.3
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• pp.248-254
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• 2010

본 연구에서는 anthracyclines의 심장 독성을 예방하기 위해 사용되는 dexrazoxane의 가장 적절하고 안전한 용량을 평가하고자 했다. 이 약물은 같은 적응증에도 불구하고 미국과 유럽에서 두 배 차이가 나는 용량으로 허가 받아 사용되고 있다. 그러므로 dexrazoxane의 anthracycline로 인한 심독성의 예방에 관한 논문을 찾아 dexrazoxane : doxorubicin = 20:1의 비율로 사용했을 경우와 10:1로 사용했을 때의 효과와 부작용을 비교하였다. 이 두 가지 용량으로 진행된 모든 임상 연구에서 dexrazoxane이 doxorubicin의 심독성 예방에 통계적으로 유효한 효과가 있다고 결론 내렸다. 또한 dexrazoxane의 추가 요법으로 인해 Tumor effect의 차이를 비교 분석한 결과, 두 가지 용량 모두에서 dexrazoxane이 doxorubicin의 항암 효과에 영향을 미치지 않는 것으로 분석되었다. 대부분의 연구에서 dexrazoxane의 약물 자체의 부작용은 분석하지 않았지만, dexrazoxane:doxorubicin을 20:1의 비율로 사용했던 한 연구에서 dexrazoxane군에서 부작용이 있음이 평가되었다. 반면, dexrazoxane의 용량을 doxorubicin 용량에 비해 10:1로 사용한 모든 연구는, 대상 환자군이 18세 이하의 소아 청소년으로 이 용량을 성인에게도 적용할 수 있는지에 대한 추가 연구가 필요하다. 그러나 항암제의 경우, 대부분 환자의 체표면적(BSA)을 기준으로 약용량을 결정하며, 이는 일반적으로 10세 이상이 되면 어른의 체표면적의 70% 정도가 된다. 그러므로, 본 연구에서는 통계적으로 충분한 수의 10세 이상의 소아, 청소년에게 doxorubicin으로 인한 심독성 예방 효과가 입증되었던 dexrazoxane: doxorubicin을 10:1의 용량으로 사용하여도 임상적인 효과를 기대 할 수 있으며, 이 용량은 dexrazoxane 자체의 유해반응도 감소시킬 수 있을 것이라고 결론 맺는다.

• Korean Circulation Journal
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• v.48 no.12
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• pp.1135-1144
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• 2018

Background and Objectives: Mitochondria play a key role in the pathophysiology of heart failure and mitochondrial permeability transition pore (MPTP) play a critical role in cell death and a critical target for cardioprotection. The aim of this study was to evaluate the protective effects of cyclosporine A (CsA), one of MPTP blockers, and morphological changes of mitochondria and MPTP related proteins in monocrotaline (MCT) induced pulmonary arterial hypertension (PAH). Methods: Eight weeks old Sprague-Dawley rats were randomized to control, MCT (60 mg/kg) and MCT plus CsA (10 mg/kg/day) treatment groups. Four weeks later, right ventricular hypertrophy (RVH) and morphological changes of right ventricle (RV) were done. Western blot and reverse transcription polymerase chain reaction (RT-PCR) for MPTP related protein were performed. Results: In electron microscopy, CsA treatment prevented MCT-induced mitochondrial disruption of RV. RVH was significantly increased in MCT group compared to that of the controls but RVH was more increased with CsA treatment. Thickened medial wall thickness of pulmonary arteriole in PAH was not changed after CsA treatment. In western blot, caspase-3 was significantly increased in MCT group, and was attenuated in CsA treatment. There were no significant differences in voltage-dependent anion channel, adenine nucleotide translocator 1 and cyclophilin D expression in western blot and RT-PCR between the 3 groups. Conclusions: CsA reduces MCT induced RV mitochondrial damage. Although, MPTP blocking does not reverse pulmonary pathology, it may reduce RV dysfunction in PAH. The results suggest that it could serve as an adjunctive therapy to PAH treatment.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.4
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• pp.391-391
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• 2024