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In this study, in order to reveal the mechanism in which elevated plasma FFA augments myocardial ischemia, the effect of high plasma FFA on coronary circulation, cardiac function, and myocardial metabolism during cardiac sympathetic nerve stimulation were investigated in dog hearts with moderate coronary-constriction. The left main coronary artery was cannulated with a Griggs-type autoperfusion cannula in 21 anesthetized open chest dogs. Coronary blood flow (CBF) was reduced to the desired level (flow reduction: 32-36%). The anterior ansa of the left stellate ganglion was isolated and stimulated with a bipolar platinum electrode at 10 V, 4 Hz, 2 msec for 5 minutes (SNSt). The hemodynamic and metabolic measurements were performed before and after the coronary constriction, and following SNSt. At the end of protocol, the transmural section of the anterior wall of the left ventricle was removed for determination of the myocardial contents of adenosine triphosphate (ATP), creatine phosphate (CP), lactate and glycolytic intermediates. Dogs were divided into three groups, that is, i) control group (n=8): administered with saline (0.?1ml/kg/min) and heparin (5mg/kg), ii) IL group (n=8): Intralipid (0.1ml/kg/min) and heparin (5mk/kg), iii) IL+CAR group (n=5): Intralipid (0.1ml/kg/min), heparin (5mg/kg) and L-carnitine (200mg/kg). The results were as follows: 1) In the dogs with moderate coronary-constriction, the increment of plasma FFA did not change systemic hemodynamics, coronary circulation, cardiac function, ECG-ST, and myocardial metabolism (oxygen consumption; MVO2, arterio-coronary sinus difference of potassium; ΔK, lactate/pyruvate ratio in coronary sinus blood; L/Pcs), in comparison with those in control group. 2) After SNSt in the control group, a slight increase of CBF and a decrease of coronary vascular resistance (CVR) occurred. An increase of Max dP/dt was observed, while no significant difference was found in systemic hemodynamics, coronary circulation and cardiac function either before or after SNSt. On the other hand, in the IL group, significant decreases of mean blood pressure, CBF, and Max dP/dt, and increases of CVR and left ventricular end-diastolic pressure (LVEDP), were observed. Out of 8 dogs, 4 cases showed an ST elevation like those observed in myocardial infarction, and 2 cases of remarkable ST depression. Following SNSt, release of potassium and lactate from myocardium was apparently augmented in this group. 3) In the IL+ CAR group, the deleterious effects of excess FFA on coronary circulation were observed. Cardiac function, and myocardial metabolism as described above were almost completely prevented with L-carnitine. All cases in the IL+CAR group had only ECG-ST changes. Furthermore, L-carnitine also prevented the decrease of ATP and CP, and remarkable storage of lactate, as well as considerable accumulation of G6P, F6P and GAP due to excess FFA. From these findings, it was clarified that under the condition of moderate coronary-constriction, high FFA did not exacerbate myocardial ischemia, but was apparently aggravated following SNSt. A remarkable decrease of intramyocardial high energy phosphates and an accumulation of lactate were also discovered. 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実験的心筋虚血発症に与える高脂血症の影響とそれに対するL-carnitineの抑制効果
https://doi.org/10.15114/smj.57.355
https://doi.org/10.15114/smj.57.355c8fcda3a-54de-4525-9335-f0f10958d395
名前 / ファイル | ライセンス | アクション |
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n0036472X573355.pdf (1.0 MB)
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Item type | 紀要論文 / Departmental Bulletin Paper(1) | |||||
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公開日 | 2019-08-16 | |||||
タイトル | ||||||
言語 | ja | |||||
タイトル | 実験的心筋虚血発症に与える高脂血症の影響とそれに対するL-carnitineの抑制効果 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | The Effect of the Hyperlipidemia on Experimental Cardiac Ischemia and the Preventive Effect of L-carnitine to Cope with Hyperlipidemia Augmented Ischemia | |||||
言語 | ||||||
言語 | jpn | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Excess free fatty acids | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Myocardial ischemia | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Cardiac sympathetic nerve stimulation | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Cardiac function | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Myocardial metabolism | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | L-carnitine | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | departmental bulletin paper | |||||
ID登録 | ||||||
ID登録 | 10.15114/smj.57.355 | |||||
ID登録タイプ | JaLC | |||||
著者 |
堀田, 大介
× 堀田, 大介× 吉田, 茂夫× 本江, 正臣 |
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著者別名 | ||||||
姓名 | Hotta, Daisuke | |||||
著者別名 | ||||||
姓名 | Yoshida, Shigeo | |||||
著者別名 | ||||||
姓名 | Motoe, Masaomi | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Although it is well known that excess free fatty acids (FFA) have many deleterious effects on the ischemic heart, its mechanism has not been completely clarified. In this study, in order to reveal the mechanism in which elevated plasma FFA augments myocardial ischemia, the effect of high plasma FFA on coronary circulation, cardiac function, and myocardial metabolism during cardiac sympathetic nerve stimulation were investigated in dog hearts with moderate coronary-constriction. The left main coronary artery was cannulated with a Griggs-type autoperfusion cannula in 21 anesthetized open chest dogs. Coronary blood flow (CBF) was reduced to the desired level (flow reduction: 32-36%). The anterior ansa of the left stellate ganglion was isolated and stimulated with a bipolar platinum electrode at 10 V, 4 Hz, 2 msec for 5 minutes (SNSt). The hemodynamic and metabolic measurements were performed before and after the coronary constriction, and following SNSt. At the end of protocol, the transmural section of the anterior wall of the left ventricle was removed for determination of the myocardial contents of adenosine triphosphate (ATP), creatine phosphate (CP), lactate and glycolytic intermediates. Dogs were divided into three groups, that is, i) control group (n=8): administered with saline (0.?1ml/kg/min) and heparin (5mg/kg), ii) IL group (n=8): Intralipid (0.1ml/kg/min) and heparin (5mk/kg), iii) IL+CAR group (n=5): Intralipid (0.1ml/kg/min), heparin (5mg/kg) and L-carnitine (200mg/kg). The results were as follows: 1) In the dogs with moderate coronary-constriction, the increment of plasma FFA did not change systemic hemodynamics, coronary circulation, cardiac function, ECG-ST, and myocardial metabolism (oxygen consumption; MVO2, arterio-coronary sinus difference of potassium; ΔK, lactate/pyruvate ratio in coronary sinus blood; L/Pcs), in comparison with those in control group. 2) After SNSt in the control group, a slight increase of CBF and a decrease of coronary vascular resistance (CVR) occurred. An increase of Max dP/dt was observed, while no significant difference was found in systemic hemodynamics, coronary circulation and cardiac function either before or after SNSt. On the other hand, in the IL group, significant decreases of mean blood pressure, CBF, and Max dP/dt, and increases of CVR and left ventricular end-diastolic pressure (LVEDP), were observed. Out of 8 dogs, 4 cases showed an ST elevation like those observed in myocardial infarction, and 2 cases of remarkable ST depression. Following SNSt, release of potassium and lactate from myocardium was apparently augmented in this group. 3) In the IL+ CAR group, the deleterious effects of excess FFA on coronary circulation were observed. Cardiac function, and myocardial metabolism as described above were almost completely prevented with L-carnitine. All cases in the IL+CAR group had only ECG-ST changes. Furthermore, L-carnitine also prevented the decrease of ATP and CP, and remarkable storage of lactate, as well as considerable accumulation of G6P, F6P and GAP due to excess FFA. From these findings, it was clarified that under the condition of moderate coronary-constriction, high FFA did not exacerbate myocardial ischemia, but was apparently aggravated following SNSt. A remarkable decrease of intramyocardial high energy phosphates and an accumulation of lactate were also discovered. These deleterious effects of excess FFA on myocardial ischemia were almost completely improved by the administration of L-carnitine. Therefore, it was suggested that the harmful effects of excess FFA on myocardial ischemia were mainly related to the inhibition of adenine nucleotide translocase by long chain acyl CoA. | |||||
書誌情報 |
札幌医学雑誌 = The Sapporo medical journal en : The Sapporo medical journal 巻 57, 号 3, p. 355-370, 発行日 1988-06-01 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0036-472X | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
出版者 | ||||||
出版者 | 札幌医科大学医学部 |