WO2023065684A1 - 辛酸钠在制备改善心肺复苏效果以及心肺复苏后多器官功能障碍的药物中的应用 - Google Patents

辛酸钠在制备改善心肺复苏效果以及心肺复苏后多器官功能障碍的药物中的应用 Download PDF

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WO2023065684A1
WO2023065684A1 PCT/CN2022/097056 CN2022097056W WO2023065684A1 WO 2023065684 A1 WO2023065684 A1 WO 2023065684A1 CN 2022097056 W CN2022097056 W CN 2022097056W WO 2023065684 A1 WO2023065684 A1 WO 2023065684A1
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resuscitation
sodium
improving
cardiopulmonary resuscitation
sodium octanoate
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French (fr)
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张茂
徐杰丰
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浙江大学
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
    • A61K31/23—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin of acids having a carboxyl group bound to a chain of seven or more carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure

Definitions

  • the disclosure relates to the technical field of pharmaceutical preparations, in particular to the application of sodium caprylate in the preparation of a drug for improving the effect of cardiopulmonary resuscitation and multiple organ dysfunction after cardiopulmonary resuscitation.
  • Cardiac arrest is a major public health problem with high incidence and low survival rate worldwide.
  • Statistics show that about 350,000 people in developed countries in Europe and the United States experience cardiac arrest every year, and as many as 550,000 in China.
  • the survival rate of patients discharged from hospital is only about 10%, and a large number of surviving patients have severe neurological dysfunction. important cause of poor prognosis.
  • glucose is the most commonly used and easily obtained energy supplement in clinical practice.
  • the body after experiencing the severe blow of a cardiac arrest event, the body usually develops insulin resistance, glucose utilization disorder, and further presents a state of stress hyperglycemia.
  • the present disclosure provides the application of sodium octanoate in the preparation of a medicament for improving the effect of cardiopulmonary resuscitation.
  • the use is administering a pharmaceutically effective dose of sodium caprylate.
  • the pharmaceutically effective dose of sodium caprylate is 14.2-28.5 mg/kg. In some embodiments, the pharmaceutically effective dose of sodium caprylate is 28.5 mg/kg.
  • sodium caprylate improves the effect of cardiopulmonary resuscitation by effectively supplying energy to the body under stress.
  • the drug is an injection.
  • the present disclosure also provides the use of sodium octanoate in the preparation of a medicament for improving multiple organ dysfunction after cardiopulmonary resuscitation.
  • the use is administering a pharmaceutically effective dose of sodium caprylate.
  • the pharmaceutically effective dose of sodium caprylate is 14.2-28.5 mg/kg. In some embodiments, the pharmaceutically effective dose of sodium caprylate is 28.5 mg/kg.
  • the sodium octanoate is used to promote fatty acid oxidation and supply energy during the systemic ischemia-reperfusion injury caused by cardiac arrest resuscitation.
  • the multiple organ dysfunction includes damage to heart function, brain function, and kidney and bowel function.
  • the drug is an injection.
  • the present disclosure also provides the use of sodium octanoate for improving the effect of cardiopulmonary resuscitation.
  • the effect of sodium octanoate on improving cardiopulmonary resuscitation is to effectively supply energy to the body under stress.
  • the present disclosure also provides the use of sodium octanoate for improving multiple organ dysfunction after cardiopulmonary resuscitation.
  • the sodium octanoate is used to promote fatty acid oxidation and supply energy during the systemic ischemia-reperfusion injury caused by cardiac arrest resuscitation.
  • the multiple organ dysfunction includes damage to heart function, brain function, and kidney and bowel function.
  • the use described in any one of the above is administering a pharmaceutically effective dose of sodium caprylate.
  • the above-mentioned pharmaceutically effective dose of sodium caprylate is 14.2 mg/kg-28.5 mg/kg. In some embodiments, the above-mentioned pharmaceutically effective dose of sodium caprylate is 28.5 mg/kg.
  • the present disclosure also provides a method of treating multiple organ dysfunction after cardiopulmonary resuscitation, the method comprising: administering a therapeutically effective amount of sodium caprylate to a subject in need thereof.
  • the method comprises: administering to a subject in need thereof a therapeutically effective amount of sodium caprylate and a pharmaceutically acceptable carrier.
  • FIG. 1 is a graph showing the influence of sodium caprylate provided by Example 3 of the present disclosure on the perfusion level of the heart and brain organs during cardiopulmonary resuscitation;
  • Fig. 2 is a graph showing changes in cardiac function and injury markers of animals in each group provided in Example 4 of the present disclosure
  • Fig. 3 is a graph showing changes in brain function and injury markers of animals in each group provided in Example 4 of the present disclosure
  • Fig. 4 is a graph showing changes in renal and intestinal injury markers of animals in each group provided in Example 4 of the present disclosure
  • FIG. 5 is an analysis diagram of the degree of apoptosis of heart, brain, kidney, and intestinal tissue cells in various groups of animals provided in Example 5 of the present disclosure after resuscitation.
  • Some embodiments of the present disclosure provide an application of sodium octanoate in the preparation of a medicament for improving the effect of cardiopulmonary resuscitation. Some embodiments of the present disclosure also provide the use of sodium caprylate for improving the effect of cardiopulmonary resuscitation.
  • the application of the sodium caprylate provided by the present disclosure in the preparation of a drug for improving the effect of cardiopulmonary resuscitation includes the administration of a pharmaceutically effective dose of sodium caprylate, wherein the method for sodium caprylate to improve the effect of cardiopulmonary resuscitation is to carry out effective Energy Supply.
  • the use of the sodium octanoate provided by the present disclosure for improving the effect of cardiopulmonary resuscitation includes administering a pharmaceutically effective dose of sodium octanoate, wherein the method for improving the effect of cardiopulmonary resuscitation by the sodium octanoate is to effectively supply energy to the body under stress.
  • fatty acids are effective energy-supplying substances that replace glucose in the body under stress
  • sodium octanoate has obtained good research evidence.
  • sodium caprylate is an important energy substrate in the energy supply pathway of fatty acid oxidation, and can be used as an energy source for important organs such as the heart, liver, and skeletal muscle.
  • Sodium octanoate can improve the functional state of myocardial ischemia-reperfusion injury by enhancing fatty acid oxidation energy supply pathway, and its protective mechanism is related to the inhibition of mitochondrial oxidative stress injury.
  • improving cardiopulmonary resuscitation results in increasing the individual's survival rate.
  • the pharmaceutically effective dose of sodium caprylate is 14.2 mg/kg-28.5 mg/kg, such as 15 mg/kg-28 mg/kg, 17 mg/kg-26 mg/kg or 19 mg/kg ⁇ 24 mg/kg.
  • the pharmaceutically effective dose of sodium caprylate is such as 14.2mg/kg, 16mg/kg, 18mg/kg, 20mg/kg, 22mg/kg, 24mg/kg, 26mg/kg, 28mg/kg, 28.5mg/kg kg.
  • the effect of sodium octanoate on improving cardiopulmonary resuscitation is to effectively supply energy to the body in a state of stress.
  • the drug is an injection.
  • Some embodiments of the present disclosure provide an application of sodium caprylate in the preparation of a medicament for improving multiple organ dysfunction after cardiopulmonary resuscitation. Some embodiments of the present disclosure also provide the use of sodium octanoate for improving multiple organ dysfunction after cardiopulmonary resuscitation.
  • the application of the sodium caprylate provided by the present disclosure in the preparation of a drug for improving multiple organ dysfunction after cardiopulmonary resuscitation includes administering a pharmaceutically effective dose of sodium caprylate, wherein the sodium caprylate is used for systemic ischemia caused by cardiac arrest resuscitation Promote fatty acid oxidation for energy during reperfusion injury.
  • the application includes administering a pharmaceutically effective dose of sodium octanoate, wherein sodium octanoate is used for the process of systemic ischemia-reperfusion injury caused by cardiac arrest resuscitation Promotes fatty acid oxidation for energy.
  • the medicament includes sodium caprylate and a pharmaceutically acceptable carrier.
  • the pharmaceutically effective dose of sodium caprylate is 14.2 mg/kg-28.5 mg/kg, such as 15 mg/kg-28 mg/kg, 17 mg/kg-26 mg/kg or 19 mg/kg ⁇ 24 mg/kg.
  • the pharmaceutically effective dose of sodium caprylate is such as 14.2mg/kg, 16mg/kg, 18mg/kg, 20mg/kg, 22mg/kg, 24mg/kg, 26mg/kg, 28mg/kg, 28.5mg/kg kg.
  • sodium octanoate is used to promote fatty acid oxidation and energy supply during the systemic ischemia-reperfusion injury process caused by cardiac arrest resuscitation.
  • multiple organ dysfunction includes heart function damage, brain function damage, and kidney and intestinal function damage.
  • the drug is an injection.
  • Some embodiments of the present disclosure provide a method of treating multiple organ dysfunction after cardiopulmonary resuscitation, comprising: administering a therapeutically effective amount of sodium caprylate to a subject in need thereof.
  • the method comprises: administering to a subject in need thereof a therapeutically effective amount of sodium caprylate and a pharmaceutically acceptable carrier.
  • the application of sodium octanoate provided by the present disclosure in the preparation of medicines for improving the effect of cardiopulmonary resuscitation and the application of sodium octanoate for improving the effect of cardiopulmonary resuscitation includes administering a pharmaceutically effective dose of sodium octanoate, wherein sodium octanoate improves the effect of cardiopulmonary resuscitation
  • the method is to effectively supply energy to the body under stress.
  • the application of sodium octanoate provided by the present disclosure in the preparation of a drug for improving multiple organ dysfunction after cardiopulmonary resuscitation and the application of sodium octanoate for improving multiple organ dysfunction after cardiopulmonary resuscitation includes administering a pharmaceutically effective dose of sodium octanoate, wherein , Sodium octanoate is used to promote fatty acid oxidation and supply energy during systemic ischemia-reperfusion injury caused by cardiac arrest resuscitation.
  • Embodiment 1 animal preparation
  • the experimental animals were first induced anesthesia by intramuscular injection of midazolam 0.4-0.5mg/kg, connected to the ECG monitor, and then injected propofol 2mg/kg through the ear vein for general anesthesia, followed by 4mg/kg/h Intravenous infusion to maintain anesthesia.
  • the ventilation parameters are intermittent positive pressure ventilation (IPPV) mode, oxygen concentration 21%, tidal volume 10ml/kg, positive The pressure is 0mmHg, and the normal physiological range of ETCO 2 is maintained at 35-40mmHg by adjusting the respiratory rate.
  • IPPV intermittent positive pressure ventilation
  • the right femoral artery and vein were exposed during surgery, and Swan-Ganz catheters were inserted into the thoracic aorta and right atrium respectively.
  • the former was used to monitor aortic blood pressure and collect arterial blood samples, and the main lumen of the latter catheter was used to monitor right atrial pressure, Body temperature and venous blood samples were collected, the side lumen of the catheter was used for infusion of therapeutic drugs, and the level of coronary perfusion pressure (CPP) was calculated from the difference between aortic blood pressure and right atrial pressure.
  • CPP coronary perfusion pressure
  • CBF carotid blood flow
  • Model condition setting 8 minutes of cardiac arrest + 8 minutes of cardiopulmonary resuscitation.
  • Cardiac arrest method Induce ventricular fibrillation through right ventricular electrode discharge, and observe for 8 minutes without intervention.
  • Epinephrine give 20 ⁇ g/kg at 2 minutes of cardiopulmonary resuscitation, and repeat every 4 minutes thereafter;
  • Sham group the cardiac arrest resuscitation model was not established, and the same amount of vehicle was administered intravenously as in other groups;
  • CPR group the cardiac arrest resuscitation model was established, and at the same time as the start of CPR, the same amount of vehicle was given intravenously as in other groups;
  • CPR+SO group the cardiac arrest resuscitation model was established, and at the same time as the start of CPR, an equal amount of sodium octanoate dissolved in a vehicle was administered intravenously at 28.5 mg/kg.
  • Sham sham operation
  • CPR cardiopulmonary resuscitation
  • SO sodium octanoate
  • the PiCCO monitor was used to regularly detect changes in cardiac function indicators such as stroke volume (SV) and global ejection fraction (GEF).
  • SV stroke volume
  • GEF global ejection fraction
  • the baseline data of animals in the three groups such as body weight, heart rate, mean arterial pressure, ETCO 2 , CBF, rSO 2 , body temperature and other physiological indicators, had no significant difference among the groups (all P>0.05). See Table 1.
  • ETCO 2 end-tidal partial pressure of carbon dioxide
  • CBF carotid blood flow
  • rSO 2 cerebral oxygen saturation
  • Sham sham operation
  • CPR cardiopulmonary resuscitation
  • SO sodium octanoate.
  • the CPR group and the CPR+SO group experienced cardiac arrest resuscitation.
  • CPP, ETCO 2 , CBF, rSO 2 and other cardio-cerebral perfusion indexes in the CPR+SO group were significantly higher than those in the CPR group at almost all time points, and the differences between groups were statistically significant (all P ⁇ 0.05 ). See Figure 1.
  • Figure 1 is a graph showing the effect of sodium octanoate on the perfusion level of the heart and brain organs during cardiopulmonary resuscitation.
  • A is the level change diagram of coronary perfusion pressure
  • B is the level change diagram of carotid blood flow
  • C is the level change diagram of end-tidal carbon dioxide partial pressure
  • CPP coronary perfusion pressure
  • CBF carotid blood flow
  • ETCO 2 end-tidal partial pressure of carbon dioxide
  • rSO 2 cerebral oxygen saturation
  • CPR cardiopulmonary resuscitation
  • SO sodium octanoate.
  • the CPR+SO group shortened the time of cardiopulmonary resuscitation, the frequency of defibrillation, and the dose of epinephrine, while the return of spontaneous circulation rate, 4h and 24h survival rate increased, and the differences between the groups were statistically significant (all P ⁇ 0.05). See Table 2.
  • animal injury markers were analyzed for the Sham group, the CPR group and the CPR+SO group.
  • Fig. 2 is a graph showing changes in cardiac function and injury markers of animals in each group.
  • a in Fig. 2 is the change diagram of stroke volume;
  • B in Fig. 2 is the change diagram of global ejection fraction;
  • C in Fig. 2 is the change diagram of cardiac troponin;
  • SV stroke volume
  • GEF global ejection fraction
  • cTnI cardiac troponin
  • BL baseline value
  • Sham sham operation
  • CPR cardiopulmonary resuscitation
  • SO sodium octanoate
  • Ratio * P ⁇ 0.05, ** P ⁇ 0.01; compared with CPR group, # P ⁇ 0.05, ## P ⁇ 0.01.
  • Fig. 3 is a graph showing changes in brain function and injury markers of animals in each group.
  • a in Fig. 3 is the change map of neuron-specific enolase
  • B in Fig. 3 is the change map of S100B protein
  • C in Fig. 3 is the score map of neurological deficit
  • NSE neuron-specific enolase
  • S100B S100B protein
  • NDS neurological deficit score
  • BL baseline value
  • Sham sham operation
  • CPR cardiopulmonary resuscitation
  • SO sodium octanoate
  • Fig. 4 is the change diagram of renal and intestinal injury markers of animals in each group; A in Fig. 4 is the change diagram of creatinine; B in Fig. 4 is the change diagram of intestinal fatty acid binding protein; in Fig. 4, Cr is creatinine; BL is baseline value; Sham is sham operation; CPR is cardiopulmonary resuscitation; SO is sodium octanoate; compared with Sham group, * P ⁇ 0.05; compared with CPR group, # P ⁇ 0.05.
  • Example 5 Analysis of the degree of apoptosis of heart, brain, kidney, and intestinal tissue cells in each group of animals after resuscitation
  • Fig. 5 is an analysis diagram of the degree of apoptosis of heart, brain, kidney, and intestinal tissue cells in each group of animals after resuscitation.
  • Heart is the heart; Cortex is the cortex; Hippocampus is the hippocampus; Kidney is the kidney; Bowel is the intestine; TUNEL is in situ end labeling; Sham is the sham operation; CPR is cardiopulmonary resuscitation; SO is sodium octanoate.
  • * P ⁇ 0.05 compared with the CPR group, # P ⁇ 0.05.
  • the above-mentioned drugs for improving the effect of cardiopulmonary resuscitation and multiple organ dysfunction after resuscitation include sodium caprylate and a pharmaceutically acceptable carrier.
  • the drug is administered with a pharmaceutically effective dose of sodium caprylate.
  • Fatty acid oxidation can be promoted to supply energy during the resulting systemic ischemia-reperfusion injury, which can effectively improve the effect of cardiopulmonary resuscitation and multiple organ dysfunction after resuscitation.
  • the disclosure provides an application of sodium octanoate in the preparation of a drug for improving the effect of cardiopulmonary resuscitation and multiple organ dysfunction after cardiopulmonary resuscitation.
  • Fatty acid oxidation provides energy, which can effectively improve the effect of cardiopulmonary resuscitation and multiple organ dysfunction after resuscitation, has excellent industrial practical performance, and can be widely used in the technical field of pharmaceutical preparations.

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Abstract

本公开提供了一种辛酸钠在制备改善心肺复苏效果以及心肺复苏后多器官功能障碍的药物中的应用，涉及药物制剂技术领域。上述用于改善心肺复苏效果及复苏后多器官功能障碍的药物包括施用药学有效剂量的辛酸钠，该药物通过施用药学有效剂量的辛酸钠，所述辛酸钠用于在心脏骤停复苏导致的系统性缺血再灌注损伤过程中促进脂肪酸氧化供能，进而可以有效改善心肺复苏效果及复苏后多器官功能障碍。

Description

辛酸钠在制备改善心肺复苏效果以及心肺复苏后多器官功能障碍的药物中的应用
相关申请的交叉引用
本公开要求于2021年10月22日提交中国专利局的申请号为CN202111232650.5、名称为“辛酸钠在制备改善心肺复苏效果以及心肺复苏后多器官功能障碍的药物中的应用”的中国专利申请的优先权，其全部内容通过引用结合在本公开中。
技术领域
本公开涉及药物制剂技术领域，尤其是涉及一种辛酸钠在制备改善心肺复苏效果以及心肺复苏后多器官功能障碍的药物中的应用。
背景技术
心脏骤停事件是全世界范围内发生率高、存活率低的重大公共卫生问题。数据显示，欧美发达国家每年约35万人经历心脏骤停事件、中国高达55万，然而患者出院存活率仅有10％左右、且大量存活患者存在严重的神经功能障碍，已成为人类死亡及生存预后不良的重要原因。
研究表明，心脏骤停事件发生后，机体能量供应急剧下降至中断，进而启动氧化应激、炎症反应、线粒体功能异常等多种病理损伤途径，造成细胞出现凋亡、坏死、焦亡等多种形式死亡，最终导致多器官功能障碍、甚至机体死亡。因而，在心脏骤停事件发生后的心肺复苏救治过程中，早期及时地补充有效的能量物质，可能遏止上述病理损伤途径的发生发展过程，进而减轻重要器官的损伤程度及改善患者的生存预后结局。
目前，临床上最常用且便于获取的能量补充物质为葡萄糖。然而，机体在经历心脏骤停事件的严重打击后，通常会出现胰岛素抵抗、葡萄糖利用障碍、并进一步呈现应激性高血糖的状态。
因此，研究探寻出一种可以在机体应激状态下替代葡萄糖的有效供能物质，进而有效改善心肺复苏效果及复苏后多器官功能障碍，变得十分必要和迫切。
发明内容
本公开提供辛酸钠在制备改善心肺复苏效果的药物中的应用。
在一些实施方式中，所述应用为施用药学有效剂量的辛酸钠。
在一些实施方式中，所述辛酸钠的药学有效剂量为14.2～28.5mg/kg。在一些实施方式中，所述辛酸钠的药学有效剂量为28.5mg/kg。
在一些实施方式中，辛酸钠改善心肺复苏的效果为在机体应激状态下对机体进行有效供能。
在一些实施方式中，所述药物为注射剂。
本公开还提供辛酸钠在制备改善心肺复苏后多器官功能障碍的药物中的应用。
在一些实施方式中，所述应用为施用药学有效剂量的辛酸钠。
在一些实施方式中，所述辛酸钠的药学有效剂量为14.2～28.5mg/kg。在一些实施方式中，所述辛酸钠的药学有效剂量为28.5mg/kg。
在一些实施方式中，所述辛酸钠用于在心脏骤停复苏导致的系统性缺血再灌注损伤过程中促进脂肪酸氧化供能。
在一些实施方式中，所述多器官功能障碍包括心功能损伤、脑功能损伤以及肾肠功能损伤。
在一些实施方式中，所述药物为注射剂。
本公开还提供了辛酸钠用于改善心肺复苏效果的用途。
在一些实施方式中，所述辛酸钠改善心肺复苏的效果为在机体应激状态下对机体进行有效供能。
本公开还提供了辛酸钠用于改善心肺复苏后多器官功能障碍的用途。
在一些实施方式中，所述辛酸钠用于在心脏骤停复苏导致的系统性缺血再灌注损伤过程中促进脂肪酸氧化供能。
在一些实施方式中，所述多器官功能障碍包括心功能损伤、脑功能损伤以及肾肠功能损伤。
在一些实施方式中，上文任一项所述的用途为施用药学有效剂量的辛酸钠。
在一些实施方式中，上文所述的辛酸钠的药学有效剂量为14.2mg/kg～28.5mg/kg。在一些实施方式中，上文所述辛酸钠的药学有效剂量为28.5mg/kg。
本公开还提供了一种治疗心肺复苏后多器官功能障碍的方法，所述方法包括：向有此需要的受试者给药治疗有效量的辛酸钠。
在一些实施方式中，所述方法包括：向有此需要的受试者给药治疗有效量的辛酸钠和药学上可接受的载体。
附图说明
为了更清楚地说明本公开实施方式或现有技术中的技术方案，下面将对实施方式或现有技术描述中所需要使用的附图作简单地介绍，显而易见地，下面描述中的附图是本公开的一些实施方式，对于本领域普通技术人员来讲，在不付出创造性劳动的前提下，还可以根据这些附图获得其他的附图。
图1为本公开实施例3提供的辛酸钠对心肺复苏期间心脑器官灌注水平的影响图；
图2为本公开实施例4提供的各组动物心功能及损伤标志物的变化图；
图3为本公开实施例4提供的各组动物脑功能及损伤标志物的变化图；
图4为本公开实施例4提供的各组动物肾肠损伤标志物的变化图；
图5为本公开实施例5提供的各组动物复苏后心脑肾肠组织细胞的凋亡程度分析图。
具体实施方式
下面将结合实施例对本公开的技术方案进行清楚、完整地描述，显然，所描述的实施例是本公开一部分实施例，而不是全部的实施例。基于本公开中的实施例，本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例，都属于本公开保护的范围。
本公开的一些实施方式提供了一种辛酸钠在制备改善心肺复苏效果的药物中的应用。本公开的一些实施方式还提供了辛酸钠用于改善心肺复苏效果的用途。
本公开提供的辛酸钠在制备改善心肺复苏效果的药物中的应用，该应用包括施用药学有效剂量的辛酸钠，其中，辛酸钠改善心肺复苏效果的方法为在机体应激状态下对机体进行有效供能。
本公开提供的辛酸钠用于改善心肺复苏效果的用途，该用途包括施用药学有效剂量的辛酸钠，其中，辛酸钠改善心肺复苏效果的方法为在机体应激状态下对机体进行有效供能。
需要说明的是，脂肪酸是机体应激状态下替代葡萄糖的有效供能物质，其代表物质辛酸钠已获得良好的研究证据。最初，研究发现辛酸钠是脂肪酸氧化供能途径的重要能量底物，能作为心、肝、骨骼肌等重要器官的能量来源。辛酸钠能通过增强脂肪酸氧化供能途径而改善局部缺血再灌注损伤心肌的功能状态，其保护机制与抑制线粒体氧化应激损伤有关。然而，在经历心脏骤停复苏导致的系统性缺血再灌注损伤过程中，辛酸钠 能否通过促进脂肪酸氧化供能而改善心肺复苏效果及复苏后多器官功能障碍尚不清楚。因此，通过研究辛酸钠在心脏骤停后心肺复苏救治及复苏后多器官保护中的应用效果、并在此基础上进行该药物的产品研发及临床转化，将为临床心肺复苏救治提供一种新的重要医疗手段，具有很好的研究意义及应用前景。
在一些实施方式中，改善心肺复苏效果在于提高个体的成活率。
在本公开的一种可选的实施方式中，辛酸钠的药学有效剂量为14.2mg/kg～28.5mg/kg，例如15mg/kg～28mg/kg、17mg/kg～26mg/kg或19mg/kg～24mg/kg。在一些实施方式中，辛酸钠的药学有效剂量为诸如14.2mg/kg、16mg/kg、18mg/kg、20mg/kg、22mg/kg、24mg/kg、26mg/kg、28mg/kg、28.5mg/kg。
在本公开的一种可选的实施方式中，辛酸钠改善心肺复苏的效果为在机体应激状态下对机体进行有效供能。
在本公开的一种可选的实施方式中，药物为注射剂。
本公开的一些实施方式提供了一种辛酸钠在制备改善心肺复苏后多器官功能障碍的药物中的应用。本公开的一些实施方式还提供了辛酸钠用于改善心肺复苏后多器官功能障碍的用途。
本公开提供的辛酸钠在制备改善心肺复苏后多器官功能障碍的药物中的应用，该应用包括施用药学有效剂量的辛酸钠，其中，辛酸钠用于在心脏骤停复苏导致的系统性缺血再灌注损伤过程中促进脂肪酸氧化供能。
本公开提供的用于改善心肺复苏后多器官功能障碍的用途中，该用途包括施用药学有效剂量的辛酸钠，其中，辛酸钠用于在心脏骤停复苏导致的系统性缺血再灌注损伤过程中促进脂肪酸氧化供能。
在一些实施方式中，药物包括辛酸钠和药学上可接受的载体。
在本公开的一种可选的实施方式中，辛酸钠的药学有效剂量为14.2mg/kg～28.5mg/kg，例如15mg/kg～28mg/kg、17mg/kg～26mg/kg或19mg/kg～24mg/kg。在一些实施方式中，辛酸钠的药学有效剂量为诸如14.2mg/kg、16mg/kg、18mg/kg、20mg/kg、22mg/kg、24mg/kg、26mg/kg、28mg/kg、28.5mg/kg。
在本公开的一种可选的实施方式中，辛酸钠用于在心脏骤停复苏导致的系统性缺血再灌注损伤过程中促进脂肪酸氧化供能。
在本公开的一种可选的实施方式中，多器官功能障碍包括心功能损伤、脑功能损伤以及肾肠功能损伤。
在本公开的一种可选的实施方式中，药物为注射剂。
本公开的一些实施方式提供了一种治疗心肺复苏后多器官功能障碍的方法，包括：向有此需要的受试者给药治疗有效量的辛酸钠。
在一些实施方式中，该方法包括：向有此需要的受试者给药治疗有效量的辛酸钠和药学上可接受的载体。
本公开提供的辛酸钠在制备改善心肺复苏效果的药物中的应用以及辛酸钠用于改善心肺复苏效果的应用中，该应用包括施用药学有效剂量的辛酸钠，其中，辛酸钠改善心肺复苏效果的方法为在机体应激状态下对机体进行有效供能。
本公开提供的辛酸钠在制备改善心肺复苏后多器官功能障碍的药物中的应用以及辛酸钠用于改善心肺复苏后多器官功能障碍的应用中，该应用包括施用药学有效剂量的辛酸钠，其中，辛酸钠用于在心脏骤停复苏导致的系统性缺血再灌注损伤过程中促进脂肪酸氧化供能。
实施例
下面将结合实施例对本公开的技术方案进行进一步地说明。
实施例1 动物准备
1、所有动物在实验前12h时开始禁食、不禁水。
2、实验动物首先经肌肉注射咪达唑仑0.4-0.5mg/kg诱导麻醉，连接心电监护仪，然后经耳缘静脉注射丙泊酚2mg/kg实施全身麻醉、继以4mg/kg/h静脉泵入维持麻醉状态。
3、迅速进行气管插管、呼气末二氧化碳分压(ETCO 2)监测及机械通气，通气参数为间歇正压通气(IPPV)模式、氧浓度21％、潮气量10ml/kg、呼气末正压0mmHg，通过调节呼吸频率维持ETCO 2在35-40mmHg的正常生理范围。
4、手术暴露右侧股动、静脉，分别置入Swan-Ganz导管至胸主动脉、右心房，前者用于监测大动脉血压与采集动脉血标本，后者导管主腔用于监测右心房压、体温与采集静脉血标本、导管侧腔用于输注治疗药物，以及经大动脉血压与右心房压差值计算冠脉灌注压(CPP)的水平。
5、手术暴露右侧颈外静脉，置入心室颤动的诱导电极至右心室，用于后期诱导心室颤动。
6、手术暴露右侧颈内静脉与左侧股动脉，分别置入中心静脉导管与热稀释动脉导 管，二者连接脉搏指示连续心排血量(PiCCO)监测仪，用于监测心功能指标每搏输出量(SV)和全心射血分数(GEF)的变化。
7、手术暴露右侧颈动脉，剥离表面筋膜，套入颈动脉血流传感器，再连接血流流速超声记录仪，实时监测颈动脉血流(CBF)的变化。
8、剃除动物前额部毛发，暴露前额部皮肤，酒精清洗干净，贴附脑氧监测探头，再连接脑氧监测仪，实时监测脑氧饱和度(rSO 2)的变化。
9、利用控温毯全程维持动物体温在38℃左右的正常温度。
实施例2 模型建立
1、模型条件设置：心脏骤停8min+心肺复苏8min。
2、心脏骤停方法：经右心室电极放电诱导心室颤动，无干预观察8min。
3、心肺复苏方法：
1)连续性人工胸外按压；
2)使用呼吸机进行机械通气(参数为IPPV(间歇正压通气)模式、氧浓度100％、潮气量7ml/kg、呼吸频率10次/min、呼气末正压0mmHg)；
3)肾上腺素：心肺复苏2min时，予以20μg/kg，此后每4min重复1次；
4)除颤：心肺复苏8min时，予以150J电除颤1次；
5)若未恢复自主循环，立即重启心肺复苏2min后除颤1次，重复此循环≤5次，直至复苏成功或宣告失败。
4、复苏后监护4h：
1)重启机械通气(参数为IPPV模式、氧浓度21％、潮气量10ml/kg、呼气末正压3mmHg、呼吸频率恢复至造模前状态)；
2)继续麻醉监护；
3)维持38℃正常体温。
5、猪圈观察20h。
实施例3 动物试验
(一)、实验分组：
国产健康雄性白猪24头，体重35kg左右，随机分为3组：Sham组(n＝6)、CPR组(n＝10)、CPR+SO组(n＝8)，其中Sham表示为假手术；CPR表示为心肺复苏；SO表示为辛酸钠。
(二)、干预措施：
1)Sham组：不建立心脏骤停复苏模型，同其它组经静脉给予等量溶媒；
2)CPR组：建立心脏骤停复苏模型，在CPR开始的同时，同其它组经静脉给予等量溶媒；
3)CPR+SO组：建立心脏骤停复苏模型，在CPR开始的同时，经静脉给予等量溶媒溶解的辛酸钠28.5mg/kg。
注：Sham，假手术；CPR，心肺复苏；SO，辛酸钠。
(三)、观察指标：
1、实验监护期间，全程动态监测心率、血压、ETCO 2、CBF、rSO 2、体温等生理指标的变化，记录动物4h与24h时的存活情况。
2、心肺复苏期间，连续动态监测CPP、ETCO 2、CBF、rSO 2的变化，并记录各组动物的心肺复苏时间、除颤次数、肾上腺素用量、自主循环恢复比例等情况。
3、于造模前及复苏后1h、2h、4h时，使用PiCCO监护仪定期检测每搏输出量(SV)与全心射血分数(GEF)等心功能指标的变化。
4、于造模前及复苏后1h、2h、4h、24h时，采集静脉血标本，离心获取血浆，冻存于-80℃深低温冰箱，择期应用酶联免疫吸附试验法检测心肌损伤标志物心肌肌钙蛋白I(cTnI)、脑损伤标志物神经元特异性烯醇化酶(NSE)与S100B蛋白(S100B)、肾肠损伤标志物肌酐(Cr)与肠型脂肪酸结合蛋白(iFABP)的血清水平。
5、于复苏后24h时，应用神经功能缺损评分(NDS)进行神经功能评估，然后对动物实施安乐死，迅速获取左室心尖部、大脑额叶皮层、右肾上极、回肠末端等部位组织，进行固定、包埋、切片等处理，再采用原位末端标记法(TUNEL)检测心、脑、肾、肠等器官组织的细胞凋亡程度。
(四)、试验结果：
1、各组动物的基本情况：
三组动物的基线数据，如体重、心率、平均动脉压、ETCO 2、CBF、rSO 2、体温等生理指标，组间比较差异均无统计学意义(均P>0.05)。见表1。
表1.各组动物的基本情况
Figure PCTCN2022097056-appb-000001
Figure PCTCN2022097056-appb-000002
Figure PCTCN2022097056-appb-000003
注：ETCO 2，呼气末二氧化碳分压；CBF，颈动脉血流；rSO 2，脑氧饱和度；Sham，假手术；CPR，心肺复苏；SO，辛酸钠。
2、各组动物的心肺复苏结局：
CPR组与CPR+SO组经历心脏骤停复苏过程。然而，心肺复苏期间，CPR+SO组CPP、ETCO 2、CBF、rSO 2等心脑灌注指标在几乎所有时间点均明显高于CPR组，组间比较差异均有统计学意义(均P<0.05)。参见图1。
图1为辛酸钠对心肺复苏期间心脑器官灌注水平的影响图。图1中A为冠脉灌注压的水平变化图；图1中B为颈动脉血流的水平变化图；图1中C为呼气末二氧化碳分压的水平变化图；图1中D为脑氧饱和度的水平变化图。
图1中，CPP为冠脉灌注压；CBF为颈动脉血流；ETCO 2为呼气末二氧化碳分压；rSO 2为脑氧饱和度；CPR为心肺复苏；SO为辛酸钠。与CPR组比较， #P<0.05。
与CPR组相比，CPR+SO组心肺复苏时间缩短、除颤次数减少及肾上腺素用量下降，同时自主循环恢复率、4h与24h存活率增加，组间比较差异均有统计学意义(均P<0.05)。见表2。
表2.各组动物的心肺复苏结局：
Figure PCTCN2022097056-appb-000004
注：CPR，心肺复苏；SO，辛酸钠。与CPR组比较， #P<0.05。
实施例4 各组动物损伤标志物分析
本实施例对Sham组、CPR组和CPR+SO组进行动物损伤标志物分析。
1、各组动物心功能及损伤标志物的变化：
造模前，三组心功能指标SV和GEF值、心肌损伤标志物cTnI血清水平，组间比较差异均无统计学意义(均P>0.05)。复苏后，可见CPR组与CPR+SO组SV和GEF值明显低于Sham组、同时cTnI血清水平显著高于Sham组，组间比较差异均有统计学意义(均P<0.05)。然而，与CPR组相比，CPR+SO组SV和GEF值在复苏1h后均明显高于CPR组、cTnI血清水平在复苏4h后均显著低于CPR组，组间比较差异均有统计学意义(均P<0.05)。参见图2。
图2为各组动物心功能及损伤标志物的变化图。图2中A为每搏输出量的变化图；图2中B为全心射血分数的变化图；图2中C为心肌肌钙蛋白的变化图；
图2中，SV为每搏输出量；GEF为全心射血分数；cTnI为心肌肌钙蛋白；BL为基线值；Sham为假手术；CPR为心肺复苏；SO为辛酸钠；与Sham组相比， *P<0.05， **P<0.01；与CPR组相比， #P<0.05， ##P<0.01。
2、各组动物脑功能及损伤标志物的变化：
造模前，三组脑损伤标志物NSE与S100B的血清水平，组间比较差异均无统计学意义(均P>0.05)。复苏后，可见CPR组在复苏1h后的血清NSE与S100B水平均明显高于Sham组，CPR+SO组在复苏4h后的血清NSE水平、在复苏2h后的血清S100B水平均显著高于Sham组，组间比较差异均有统计学意义(均P<0.05)。然而，与CPR组相比，CPR+SO组NSE在复苏后4h与24h、S100B在复苏后1h、2h与24h的血清水平均显著降低，组间比较差异均有统计学意义(均P<0.05)。另外，CPR组与CPR+SO组在复苏后24h的NDS评分明显高于Sham组，同时CPR+SO组NDS评分显著低于CPR组，组间比较差异均有统计学意义(均P<0.05)。参见图3。
图3为各组动物脑功能及损伤标志物的变化图。其中，图3中A为神经元特异性烯醇化酶的变化图；图3中B为S100B蛋白的变化图；图3中C为神经功能缺损评分图；
图3中，NSE为神经元特异性烯醇化酶；S100B为S100B蛋白；NDS为神经功能缺损评分；BL为基线值；Sham为假手术；CPR为心肺复苏；SO为辛酸钠；与Sham组相比， *P<0.05；与CPR组相比， #P<0.05。
3、各组动物肾肠损伤标志物的变化
造模前，三组肾肠损伤标志物Cr与iFABP的血清水平，组间比较差异均无统计学意义(均P>0.05)。复苏后，可见CPR组与CPR+SO组血清Cr与iFABP水平均明显高于Sham组，组间比较差异均有统计学意义(均P<0.05)。然而，与CPR组相比，CPR+SO 组Cr在复苏后2h与24h、iFABP在复苏后24h的血清水平均显著下降，组间比较差异均有统计学意义(均P<0.05)。参见图4。
图4为各组动物肾肠损伤标志物的变化图；图4中A为肌酐的变化图；图4中B为肠型脂肪酸结合蛋白的变化图；图4中，Cr为肌酐；iFABP为肠型脂肪酸结合蛋白；BL为基线值；Sham为假手术；CPR为心肺复苏；SO为辛酸钠；与Sham组相比， *P<0.05；与CPR组相比， #P<0.05。
实施例5 各组动物复苏后心脑肾肠组织细胞的凋亡程度分析
于复苏后24h时，各组存活动物均实施安乐死，获取心、脑、肾、肠等器官组织进行病理分析结果显示，与Sham组相比，CPR组与CPR+SO组各器官组织的凋亡细胞比例明显增加，组间比较差异均有统计学意义(均P<0.05)。然而，与CPR组相比，CPR+SO组各器官组织细胞的凋亡程度显著减轻，组间比较差异均有统计学意义(均P<0.05)。参见图5。
图5为各组动物复苏后心脑肾肠组织细胞的凋亡程度分析图。图5中，Heart为心脏；Cortex为皮层；Hippocampus为海马；Kidney为肾脏；Bowel为肠；TUNEL为原位末端标记法；Sham为假手术；CPR为心肺复苏；SO为辛酸钠。与Sham组比较， *P<0.05；与CPR组比较， #P<0.05。
综上，上述用于改善心肺复苏效果及复苏后多器官功能障碍的药物包括辛酸钠和药学上可接受的载体，该药物通过施用药学有效剂量的辛酸钠，辛酸钠用于在心脏骤停复苏导致的系统性缺血再灌注损伤过程中促进脂肪酸氧化供能，进而可以有效改善心肺复苏效果及复苏后多器官功能障碍。
最后应说明的是：以上各实施例仅用以说明本公开的技术方案，而非对其限制；尽管参照前述各实施例对本公开进行了详细的说明，本领域的普通技术人员应当理解：其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分或者全部技术特征进行等同替换；而这些修改或者替换，并不使相应技术方案的本质脱离本公开各实施例技术方案的范围。
工业实用性
本公开提供了一种辛酸钠在制备改善心肺复苏效果以及心肺复苏后多器官功能障碍的药物中的应用，该辛酸钠用于在心脏骤停复苏导致的系统性缺血再灌注损伤过程中促进脂肪酸氧化供能，进而可以有效改善心肺复苏效果及复苏后多器官功能障碍，具有 优异的工业实用性能，可广泛地应用于药物制剂技术领域。

Claims (18)

  1. 辛酸钠在制备改善心肺复苏效果的药物中的应用。
  2. 根据权利要求1所述的应用，其特征在于，所述应用为施用药学有效剂量的辛酸钠。
  3. 根据权利要求2所述的应用，其特征在于，所述辛酸钠的药学有效剂量为14.2mg/kg～28.5mg/kg，优选为28.5mg/kg。
  4. 根据权利要求1所述的应用，其特征在于，所述辛酸钠改善心肺复苏的效果为在机体应激状态下对机体进行有效供能。
  5. 根据权利要求1所述的应用，其特征在于，所述药物为注射剂。
  6. 辛酸钠在制备改善心肺复苏后多器官功能障碍的药物中的应用。
  7. 根据权利要求6所述的应用，其特征在于，所述应用为施用药学有效剂量的辛酸钠。
  8. 根据权利要求6所述的应用，其特征在于，所述辛酸钠的药学有效剂量为14.2mg/kg～28.5mg/kg，优选为28.5mg/kg。
  9. 根据权利要求6所述的应用，其特征在于，所述辛酸钠用于在心脏骤停复苏导致的系统性缺血再灌注损伤过程中促进脂肪酸氧化供能。
  10. 根据权利要求6所述的应用，其特征在于，所述多器官功能障碍包括心功能损伤、脑功能损伤以及肾肠功能损伤；
    优选地，所述药物为注射剂。
  11. 辛酸钠用于改善心肺复苏效果的用途。
  12. 辛酸钠用于改善心肺复苏后多器官功能障碍的用途。
  13. 根据权利要求11或12所述的用途，其特征在于，所述用途为施用药学有效剂量的辛酸钠。
  14. 根据权利要求11或12所述的用途，其特征在于，所述辛酸钠的药学有效剂量为14.2mg/kg～28.5mg/kg，优选为28.5mg/kg。
  15. 根据权利要求11所述的用途，其特征在于，所述辛酸钠改善心肺复苏的效果为在机体应激状态下对机体进行有效供能。
  16. 根据权利要求12所述的用途，其特征在于，所述辛酸钠用于在心脏骤停复苏导致的系统性缺血再灌注损伤过程中促进脂肪酸氧化供能。
  17. 根据权利要求12所述的用途，其特征在于，所述多器官功能障碍包括心功能损 伤、脑功能损伤以及肾肠功能损伤。
  18. 一种治疗心肺复苏后多器官功能障碍的方法，其特征在于，所述方法包括：
    向有此需要的受试者给药治疗有效量的辛酸钠；
    优选地，所述方法包括：向有此需要的受试者给药治疗有效量的辛酸钠和药学上可接受的载体。
PCT/CN2022/097056 2021-10-22 2022-06-06 辛酸钠在制备改善心肺复苏效果以及心肺复苏后多器官功能障碍的药物中的应用 WO2023065684A1 (zh)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113730388A (zh) * 2021-10-22 2021-12-03 浙江大学 辛酸钠在制备改善心肺复苏效果以及心肺复苏后多器官功能障碍的药物中的应用

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1545578A4 (en) * 2002-08-28 2010-07-07 Immunex Corp COMPOSITIONS AND METHODS FOR TREATING CARDIOVASCULAR DISEASES
EP1885391A1 (en) * 2005-05-19 2008-02-13 Novo Nordisk A/S Use of glp-2 for the treatment of ischemia-reperfusion injury
CN110506702A (zh) * 2019-08-09 2019-11-29 浙江大学 一种新型的心脏骤停动物模型的建立方法

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113730388A (zh) * 2021-10-22 2021-12-03 浙江大学 辛酸钠在制备改善心肺复苏效果以及心肺复苏后多器官功能障碍的药物中的应用

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
ALVES MARCO G., OLIVEIRA PAULO J., CARVALHO RUI A.: "Substrate selection in hearts subjected to ischemia/reperfusion: role of cardioplegic solutions and gender", NMR IN BIOMEDICINE, vol. 24, no. 9, 1 November 2011 (2011-11-01), GB , pages 1029 - 1037, XP093059395, ISSN: 0952-3480, DOI: 10.1002/nbm.1640 *
HARMANCEY ROMAIN, VASQUEZ HERNAN G., GUTHRIE PATRICK H., TAEGTMEYER HEINRICH: "Decreased long‐chain fatty acid oxidation impairs postischemic recovery of the insulin‐resistant rat heart", THE FASEB JOURNAL, vol. 27, no. 10, 1 October 2013 (2013-10-01), US, pages 3966 - 3978, XP093059403, ISSN: 0892-6638, DOI: 10.1096/fj.13-234914 *
LEI IENGLAM, TIAN SHUO, GAO WENBIN, LIU LIU, GUO YIJING, TANG PAUL, CHEN EUGENE, WANG ZHONG: "Acetyl-CoA production by specific metabolites promotes cardiac repair after myocardial infarction via histone acetylation", ELIFE, vol. 10, 21 December 2021 (2021-12-21), pages 1 - 22, XP093059393, DOI: 10.7554/eLife.60311 *
MONTESSUIT CHRISTOPHE, PAPAGEORGIOU IRÈNE, TARDY-CANTALUPI ISABELLE, ROSENBLATT-VELIN NATHALIE, LERCH RENÉ: "Postischemic recovery of heart metabolism and function: role of mitochondrial fatty acid transfer", JOURNAL OF APPLIED PHYSIOLOGY, vol. 89, no. 1, 1 July 2000 (2000-07-01), US , pages 111 - 119, XP093059400, ISSN: 8750-7587, DOI: 10.1152/jappl.2000.89.1.111 *

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