• Journal of Chest Surgery
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• 제27권6호
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• pp.427-434
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• 1994

A clinical study was designed to evaluate myocardial metabolism during continuous cold blood cardioplegia [Group A, n=10] in comparison with continuous warm blood cardioplegia [Group B, n=10], in a prospective randomized manner. Myocardial metabolism was assessed in two ways: either by collecting blood from coronary sinus before and after cardiopulmonary bypass or by collecting blood from cardioplegic affluent and effluent simultaneously at the beginning and at the end of cardioplegia. The former samples were assayed for gas analysis, lactic acid and cardiac enzyme [CK, LDH, SGOT] and the latter for gas analysis and lactic acid as a maker of anaerobic metabolism. The results were as follows. 1] Myocardial metabolism was shown to be continued in the state of cardioplegia at lower temperature as evidenced by high oxygen extraction of cardioplegic solution in Group A. 2] Anaerobic metabolism occurring at lower temperature in spite of continuous cold blood cardioplegia can be significantly reduced by continuous perfusion of normothermic blood cardioplegics as evidenced by significant reduction of lactate production in Group B [p〈0.05]. 3] Better myocardial protection can be achieved by employing continuous warm blood cardioplegia as evidenced by less cardiac enzyme release in Group B after cardiopulmonary bypass.

• Journal of Nutrition and Health
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• 제25권7호
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• pp.597-607
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• 1992

The present study examined effects of caffeine on coronary circulation myocardial oxygen me-tabolism and calcium release in isolated perfused guinea pig hearts. Intracoronary caffeine({{{{ {10 }^{-5 } }}}}∼{{{{ { 10}^{-3 } }}}}M) was employed for 10 minutes to measure coronary perfusate flow(CF) and coronary vascular sresistance(CVR) at a constant coronary perfusion pressure of 80 cmH2O Perfusate myocardial oxygen consumption(MVO2) and percent oxygen extraction(%EC2) were calcula-ted. In addition calcium contents in both perfusate samples were measured to calculate calcium release in coronary venous effluent. Caffeine significantly decreased CF and increased CVR during 10 minutes of caffeine perfusion regardless of dose of caffeine perfused exhibiting time-response. While % EO2 was significantly enhanced with caffeine MVO2 was markedly reduced. The coronary venous perfusate pH dcreased during the perfusion with caffeine. These changes were consistent with caffeine-induced metabolic acidosis. Calcium release appeared to be dose-dependent and high dose of caffeine greatly increased venous calcium release even 2 minutes after perfusion with carffeine. These finding in dicate that caffeine produced coronary vasoconst-riction with increased calcium release in isolated perfused guinea pig hearts. Additionaly this vasoconstrictor response mignt be due tin part to the direct actions of caffeine.

• Journal of Nutrition and Health
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• 제28권2호
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• pp.115-126
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• 1995

The effects of energy-yielding substrates on coronary circulation, myocardial oxygen metabolism, and intramyocytic adenylates of perfused Wistar control rat(WC) and spontaneously hypertensive rat(SHR) hearts were examined under basal and $\beta$-adrenergic stimulation conditions. The perfusion medium (1.0mM Ca2+) contained 5mM glucose (+5U/l insulin) in combination with 5mM pyruvate, 5mM lacate, 5mM acetate, or 5mM octanoate as energy substrates. Hearts were perfused with each substrate buffer for 20min under basal conditions. Coronary functinal hyperemia was induced by infusing for 20min isoproterenol (ISO, 1uM), a $\beta$-receptor agonist. Cardiac adenylates, glycolytic intermediates, and coronary venous lactate were measured by using an enzymatic analysis technique. Under basal conditions, acetate and octanoate significantly increased coronary flow(CF) of WC in parallel with myocardial oxygen consumption. However, CF of SHR was partly attenuated by coronary vasoconstriction despite metabolic acidosis. In addition, pyruvate and lactate depressd ISO-induced coronary functional hyperemia in SHR. It should be noted that octanoate exhibited coronary dysfunction under ISO conditions. On the other hand, fat substrates depleted myocardial high energy phosphate pool and accumulated breakdown intermediates. In SHR with coronary vasoconstriction under basal conditions, and with depressed coronary functional hyperemia, high energy phosphates were greatly depleted. These results suggest that energy substrates in the myocardium and coronary smooth muscle alter remarkably coronary circulation, and that coronary circulatory function is associated with a reserve of high energy phosphates and a balance between breakdown and nono synthesis of energy phosphates. These findings could be explained by alterations in the cytosolic redox state manipulated by LDH and hence in the cytosolic phosphorylation potential, which might be involved in hypertension of SHR.

• The Korean Journal of Physiology and Pharmacology
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• 제28권3호
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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.

• Journal of Ginseng Research
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• 제43권4호
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• pp.517-526
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• 2019

Background: The root of Panax ginseng, a member of Araliaceae family, has been used as herbal medicine and functional food in Asia for thousands of years. According to Traditional Chinese medicine, ginseng is the most widely used "Qi-invigorating" herbs, which provides tonic and preventive effects by resisting oxidative stress, influencing energy metabolism, and improving mitochondrial function. Very few reports have systematically measured cell mitochondrial bioenergetics after ginseng treatment. Methods: Here, H9C2 cell line, a rat cardiomyoblast, was treated with ginseng extracts having extracted using solvents of different polarity, i.e., water, 50% ethanol, and 90% ethanol, and subsequently, the oxygen consumption rate in healthy and tert-butyl hydroperoxideetreated live cultures was determined by Seahorse extracellular flux analyzer. Results: The 90% ethanol extracts of ginseng possessed the strongest antioxidative and tonic activities to mitochondrial respiration and therefore provided the best protective effects to H9C2 cardiomyocytes. By increasing the spare respiratory capacity of stressed H9C2 cells up to three-folds of that of healthy cells, the 90% ethanol extracts of ginseng greatly improved the tolerance of myocardial cells to oxidative damage. Conclusion: These results demonstrated that the low polarity extracts of ginseng could be the best extract, as compared with others, in regulating the oxygen consumption rate of cultured cardiomyocytes during mitochondrial respiration.

• 대한약리학회지
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• 제19권1호
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• pp.61-69
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• 1983

Hypothermia is an essential preparatory procedure for cardiac surgery, which lows the metabolic rate and myocardial oxygen demand. However, hypothermia itself is a stress enough to change the tonus of sympathoadrenal system, especially the cardiovascular responses to the catecholamines. It is reported that the positive chronotropic and inotropic response of catecholamines is exaggerated during hypothermia because of decreased norepinephrine uptake at the junctional cleft or decreased catecholamine metabolism. On the other hand, there are evidences of diminished catecholamines responses in low temperature ana further, interconversion of adrenergic receptors is also suggested. Present investigation was planned to observe the cardiovascular changes and its responses to catecholamines during surface hypothermia in cat. Healthy mongrel cats, weighing $2{\sim}3\;kg$, anesthetized with secobarbital(30 mg/kg), were permitted to hypothermia by external cooling technic. Esophageal temperature, ECG (lead II), heart rate, left ventricular pressure with dP/dt, carotid artery pressure and left ventricular contractile force were monitored with Polygragh (Model 7, Grass), and the respiration was maintained with artificial respirator (V 5 KG, Narco). Followings are summarized results. 1) Surface cooling caused progressive decrease of body temperature and reached $l8.8{\pm}0.8^{\circ}C$ and $16.9{\pm}0.6^{\circ}C$ in 120 and 150 min respectively, after immersion into ice water, and ventricular fibrillation was developed at $20.4{\pm}0.65^{\circ}C$. 2) Heart rate, blood pressure and myocardial contractility were decreased after initial increase as the body temperature falls. 3) Systolic and diastolicdd P/dt of left ventricular pressure were decreased and that the decrement of diastolic dP/dt was more marked. 4) On ECG, ST depression, Twave inversion and prolongation of PR interval were prominent in hypothermia, and moreover, the prolongation of PR interval was marked just prior to the development of ventricular fibrillation. 5) The cardiovascular responses to catecholamines, especially to isoproterenol, were suppressed under hypothermia.

• 대한약리학회지
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• 제27권2호
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• pp.109-118
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• 1991

허혈심근의 재관류시 arachidonic acid가 반응성 산소대사물의 발생원으로서 심근 손상에 미치는 영향을 검토하였다. Langendorff 관류장치를 이용하여 흰쥐 적출심장을 0.5ml/min의 저용량으로 관류 (45분)한 후 정상관류 (7 ml/min)로 복귀 시키므로써 실험적인 허혈-재관류 심장을 만들었다. 재관류시 Na arachidonate $(10^{-7}{\sim}10^{-2}{\mu}g/ml)$를 투여한 후 superoxide anion 생성을 관찰하고, 심근 손상의 지표로 lactic dehydrogenase(LDH)유리를 측정 하였으며 이들에 대한 각종 arachidonic acid 대사 억제 약물의 영향을 비교 검토하였다. Superoxide anion 생성은 SOD-억제성 ferricytochrorme C 환원 반응을 이용하였다. 연구성적은 다음과 같다. 1) 저용량 관류후 재관류시 ferricytochrorme C환원은 superoxide dismutase (SOD, 300 U/ml) 및 indomethacin (60 nmole/ml), ibuprofen $(30\;{\mu}g/ml)$에 의하여 억제되었다. 2) Na arachidonate는 용량의존적으로 ferricytochrorme C 환원을 증가 시켰으며 반응성 산소대사물 제거효소인 superoxide dismutase (SOD, 300 U/ml)에 의하여 현저히 억제되었다. 3) Na arachidonate $(10^{-3}\;{\mu}g/ml)$에 의한 superoxide anion 생성은 cyclooxygenase 억제약물인 indomethacin (60 nmol/ml), lipooxygenase 억제약물인 nordihydroguaiaretic acid$(NDGA,\;0.1\;{\mu}mole/ml)$, arachidonic acid의 substrate inhibitor인 eicosatetraynoic acid $(ETYA,\;1\;{\mu}g/ml)$에 의하여 현저히 억제되었다. 4) Na arachidonate는 LDH 유리를 증가시켰으며 SOD에 의하여 유의하게 억제 되었다. 5) Na archidonate에 의한 LDH 유리증가는 indomethacin, NDGA, ETYA에 의하여 유의하게 억제 되었다. 이상의 결과로 흰쥐의 허혈-재관류심근에서 arachidonic acid는 그 대사 과정에서 반응성 산소대사물을 발생하고 이는 심근세포손상에 부분적으로 기여할 수 있을 것으로 여겨졌다.

• 핵의학기술
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• 제22권2호
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• pp.74-78
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• 2018

본 연구는 그리냐르 시약과 $[^{11}C]$$CO_2$ 가스의 반응온도를 최적화하여 $[^{11}C]$아세트산의 방사화학적 수율을 향상시킬 수 있는 방법을 개발하고자 하였다. 본 연구에서는 $TRACERlab^{TM}$ $FX_{C-Pro}$ 자동합성장치에 기체포집 반응법과 고체상 추출 카트리지 분리정제법을 적용하여 $[^{11}C]$아세트산을 합성하였다. 그리냐르 시약으로 3.0 M $CH_3MgCl$를 사용하였으며, 표지반응 시 무수 tetrahydrofuran을 사용하여 0.5 M $CH_3MgCl$로 희석하여 사용하였다. 사이클로트론에서 생산된 $[^{11}C]$$CO_2$ 가스를 포집 후 반응용기에 담겨있는 그리냐르 시약에 불어넣을 때 반응용기를 액체질소로 냉각하여 $0^{\circ}C$, $-10^{\circ}C$, $-55^{\circ}C$가 각각 되게 한 후 표지반응을 진행하였다. 표지 반응 후 1 mM 아세트산 용액을 넣어 반응액을 희석한 후 고체상 추출 카트리지 IC-H와 IC-Ag를 차례로 통과시켜 불순물을 제거하고, 최종산물인 $[^{11}C]$아세트산은 SAX 카트리지에 통과시켜 흡착시킨 후 주사용수를 통과시켜 유기용매 및 불순물을 제거한 후 생리식염수로 용출하였다. 용출된 $[^{11}C]$ 아세트산은 $0.22-{\mu}m$ 멸균필터를 사용하여 멸균 후 HPLC로 방사화학적 순도를 측정하였다. 사이클로트론의 빔 전류를 $50{\mu}A$로 고정하고 빔 조사를 20분간 하여 생산된 $[^{11}C]$$CO_2$ 가스를 그리냐르 시약과 반응시킬 때 온도가 $0^{\circ}C$일 때 $15.2{\pm}1.6GBq$ (n=5)의 $[^{11}C]$아세트산이 합성되었고, 표지반응온도가 $-10^{\circ}C$일 때는 $18.7{\pm}2.1GBq$ (n=19)가 합성되었으며, $-55^{\circ}C$일 때는 $7.7{\pm}1.7GBq$ (n=19)가 합성되었다. 방사화학적 수율이 가장 높았던 $-10^{\circ}C$에서 빔 조사시간에 따른 $[^{11}C]$ 아세트산의 합성수율을 비교하였을 때 10분간 빔을 조사할 때보다 20분간 조사할 경우 약 1.9배 생산량이 증가하는 것을 확인할 수 있었다. 본 연구를 통해 $[^{11}C]$$CO_2$ 가스와 그리냐르 시약을 $-10^{\circ}C$에서 반응 할 경우 방사화학적 수율을 크게 개선할 수 있어 향후 임상에서 통상적으로 생산 시 유용한 표지조건으로 활용될 수 있을 것이라 기대된다.