CN103893205A - Cardioplegic solution containing lidocaine and adenosine and preparation method thereof - Google Patents
Cardioplegic solution containing lidocaine and adenosine and preparation method thereof Download PDFInfo
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- CN103893205A CN103893205A CN201410150766.8A CN201410150766A CN103893205A CN 103893205 A CN103893205 A CN 103893205A CN 201410150766 A CN201410150766 A CN 201410150766A CN 103893205 A CN103893205 A CN 103893205A
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- Prior art keywords
- adenosine
- cardioplegic solution
- lignocaine
- chloride
- distilled water
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- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 title claims abstract description 52
- 239000008148 cardioplegic solution Substances 0.000 title claims abstract description 33
- 239000002126 C01EB10 - Adenosine Substances 0.000 title claims abstract description 26
- 229960005305 adenosine Drugs 0.000 title claims abstract description 26
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 229960004194 lidocaine Drugs 0.000 title claims abstract description 23
- 238000002360 preparation method Methods 0.000 title abstract description 7
- WVTKBKWTSCPRNU-KYJUHHDHSA-N (+)-Tetrandrine Chemical compound C([C@H]1C=2C=C(C(=CC=2CCN1C)OC)O1)C(C=C2)=CC=C2OC(=C2)C(OC)=CC=C2C[C@@H]2N(C)CCC3=CC(OC)=C(OC)C1=C23 WVTKBKWTSCPRNU-KYJUHHDHSA-N 0.000 claims abstract description 26
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims abstract description 26
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims abstract description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims abstract description 26
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 15
- 239000008103 glucose Substances 0.000 claims abstract description 15
- WZRCQWQRFZITDX-UHFFFAOYSA-N (RS)-norcoclaurine Chemical compound C1=CC(O)=CC=C1CC1C2=CC(O)=C(O)C=C2CCN1 WZRCQWQRFZITDX-UHFFFAOYSA-N 0.000 claims abstract description 13
- SMDOOINVMJSDPS-UHFFFAOYSA-N Astragaloside Natural products C1=C(O)C(OC)=CC(C2=C(C(=O)C3=C(O)C=C(O)C=C3O2)OC2C(C(OC3C(C(O)C(O)C(CO)O3)O)C(O)C(CO)O2)O)=C1 SMDOOINVMJSDPS-UHFFFAOYSA-N 0.000 claims abstract description 13
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims abstract description 13
- WZRCQWQRFZITDX-AWEZNQCLSA-N Norcoclaurine Natural products C1=CC(O)=CC=C1C[C@H]1C2=CC(O)=C(O)C=C2CCN1 WZRCQWQRFZITDX-AWEZNQCLSA-N 0.000 claims abstract description 13
- QMNWISYXSJWHRY-XWJCTJPOSA-N astragaloside Chemical compound O1[C@H](C(C)(O)C)CC[C@]1(C)[C@@H]1[C@@]2(C)CC[C@]34C[C@]4(CC[C@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)CO4)O)C4(C)C)C4[C@@H](O[C@H]4[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O4)O)CC3[C@]2(C)C[C@@H]1O QMNWISYXSJWHRY-XWJCTJPOSA-N 0.000 claims abstract description 13
- 239000001110 calcium chloride Substances 0.000 claims abstract description 13
- 229910001628 calcium chloride Inorganic materials 0.000 claims abstract description 13
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims abstract description 13
- 235000019341 magnesium sulphate Nutrition 0.000 claims abstract description 13
- 239000001103 potassium chloride Substances 0.000 claims abstract description 13
- 235000011164 potassium chloride Nutrition 0.000 claims abstract description 13
- WVTKBKWTSCPRNU-UHFFFAOYSA-N rac-Tetrandrin Natural products O1C(C(=CC=2CCN3C)OC)=CC=2C3CC(C=C2)=CC=C2OC(=C2)C(OC)=CC=C2CC2N(C)CCC3=CC(OC)=C(OC)C1=C23 WVTKBKWTSCPRNU-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000011780 sodium chloride Substances 0.000 claims abstract description 13
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 claims abstract description 6
- 235000017471 coenzyme Q10 Nutrition 0.000 claims abstract description 6
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 claims abstract description 6
- 229940110767 coenzyme Q10 Drugs 0.000 claims abstract description 6
- 239000012153 distilled water Substances 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 239000012530 fluid Substances 0.000 claims description 6
- 210000000056 organ Anatomy 0.000 claims description 6
- 239000003755 preservative agent Substances 0.000 claims description 6
- 230000002335 preservative effect Effects 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 3
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 3
- 235000011148 calcium chloride Nutrition 0.000 claims description 3
- 229940019898 coenzyme Q10 60 mg Drugs 0.000 claims description 3
- 229940030840 coenzyme Q10 75 mg Drugs 0.000 claims description 3
- 238000005138 cryopreservation Methods 0.000 claims description 3
- 239000012467 final product Substances 0.000 claims description 3
- 229960001031 glucose Drugs 0.000 claims description 3
- 230000003204 osmotic effect Effects 0.000 claims description 3
- 235000002639 sodium chloride Nutrition 0.000 claims description 3
- 239000000243 solution Substances 0.000 claims description 3
- 239000012154 double-distilled water Substances 0.000 abstract 1
- 239000000162 organ preservation solution Substances 0.000 abstract 1
- 239000007788 liquid Substances 0.000 description 33
- 210000002216 heart Anatomy 0.000 description 27
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- 230000002107 myocardial effect Effects 0.000 description 11
- 230000000052 comparative effect Effects 0.000 description 9
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 8
- 230000028161 membrane depolarization Effects 0.000 description 8
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- 210000004165 myocardium Anatomy 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 230000004087 circulation Effects 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 235000014655 lactic acid Nutrition 0.000 description 4
- 239000004310 lactic acid Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 208000027418 Wounds and injury Diseases 0.000 description 3
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- PTVWPYVOOKLBCG-ZDUSSCGKSA-N levodropropizine Chemical compound C1CN(C[C@H](O)CO)CCN1C1=CC=CC=C1 PTVWPYVOOKLBCG-ZDUSSCGKSA-N 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
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- 230000001681 protective effect Effects 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
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- 239000011734 sodium Substances 0.000 description 2
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- 230000002861 ventricular Effects 0.000 description 2
- IVVNZDGDKPTYHK-JTQLQIEISA-N 1-cyano-2-[(2s)-3,3-dimethylbutan-2-yl]-3-pyridin-4-ylguanidine Chemical compound CC(C)(C)[C@H](C)N=C(NC#N)NC1=CC=NC=C1 IVVNZDGDKPTYHK-JTQLQIEISA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 206010020660 Hyperlactacidaemia Diseases 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 102000016924 KATP Channels Human genes 0.000 description 1
- 108010053914 KATP Channels Proteins 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229940127315 Potassium Channel Openers Drugs 0.000 description 1
- 101100537532 Rattus norvegicus Tnni3 gene Proteins 0.000 description 1
- 206010063837 Reperfusion injury Diseases 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- 101100353477 Solanum tuberosum STH-2 gene Proteins 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 241000053227 Themus Species 0.000 description 1
- VEUACKUBDLVUAC-UHFFFAOYSA-N [Na].[Ca] Chemical compound [Na].[Ca] VEUACKUBDLVUAC-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
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- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
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- 210000005036 nerve Anatomy 0.000 description 1
- LBHIOVVIQHSOQN-UHFFFAOYSA-N nicorandil Chemical compound [O-][N+](=O)OCCNC(=O)C1=CC=CN=C1 LBHIOVVIQHSOQN-UHFFFAOYSA-N 0.000 description 1
- 229960002497 nicorandil Drugs 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000000661 pacemaking effect Effects 0.000 description 1
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- 229960002275 pentobarbital sodium Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229960002310 pinacidil Drugs 0.000 description 1
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- 230000002980 postoperative effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
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Landscapes
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The invention relates to the technical field of cardioplegic solutions, in particular to a cardioplegic solution containing lidocaine and adenosine and a preparation method thereof. Every 1,000ml of organ preservation solution comprises the following components by weight: 5.0-7.0g of sodium chloride, 2.0-3.0g of potassium chloride, 0.3-0.5g of magnesium sulfate, 0.05-0.1g of calcium chloride, 5-8g of glucose, 0.3-0.6g of lidocaine, 0.1-0.2g of adenosine, 0.01-0.02g of astragaloside, 0.05-0.08g of coenzyme Q10, 0.005-0.01g of tetrandrine, 0.005-0.01g of higenamine, 5-8g of histidine and the balance of double distilled water.
Description
Technical field
The present invention relates to cardioplegic solution technical field, be specifically related to a kind of cardioplegic solution that comprises lignocaine and adenosine and preparation method thereof.
Background technology
Since 20th century, started operation on heart the sixties, the pioneers of department of cardiac surgery attempt several modes on the one hand to support patient's circulation, attempt on the other hand protection patient's heart.The protective effect of low temperature is not only local at heart but also obtained accreditation in the application of whole body.Cardiac operation development subsequently has mainly utilized the progressive improvement of extracorporeal circulation parts; the carrying out that can allow to become increasingly complex and perform the operation for more time; but regrettably Myocardial protective effects does not reach perfect condition all the time, the postoperative asystole-multiple perfusion injury that still exists.Therefore, provide a kind of ratio only the better myocardial preservation measure of cooling cardiac muscle be essential.
Cardioplegic solution has been the important guarantee of operation on heart, and it can be divided into following three major types by action principle: depolarization cardioplegic solution, hyperpolarized cardioplegia and polarization cardioplegic solution.Depolarization cardioplegic solution is the maximum class cardioplegic solution of clinical use, and conventional depolarization cardioplegic solution has STH-2 liquid and LA liquid.But some studies show that: the low heart row who occurs after operation on vessels of heart may be not good relevant with the myocardial preservation of High K+ depolarization cardioplegic solution.Its possible reason has: 1. depolarization cardioplegic solution make ground squirrel drop to-below 50mv, but cell membrane potential is between-60 ~-15mv, in existing, to stable state sodium window electric current, can make the overload of myocardial cell generation sodium; 2. transmembrane potential is between-40 ~-15mv, and cell membrane exists interior to calcium current, and under depolarization state, the interior calcium of sarcoplasmic reticulum is easy to outflow, thereby has increased the weight of intracellular calcium overload, and sodium calcium cross-film flows can increase the weight of myocardial damage, is unfavorable for that myocardial function recovers; 3. the high potassium in depolarization cardioplegic solution can coup injury Coronary Arterial Endothelial Cells, causes the autonomous regulatory function of vascular endothelial cell and blood vessel impaired.Hyperpolarized cardioplegia is first to be proposed by Cohn etc. for 1993, adopts KATP channel opener to make ground squirrel generation hyperpolarization (approximately-110mv) and stops fighting in relaxing period.Wherein, the potassium channel openers that bibliographical information is conventional has adenosine, nicorandil, and pinacidil etc., hyperpolarized cardioplegia has carried out the research of long period at laboratory, but because its Myocardial protective effects is imprecise, not yet can be applied to so far clinical.Similar with depolarization cardioplegic solution, also there is cross-film ion and the unbalance problem of energy in hyperpolarized cardioplegia.
Find by research the defect that above-mentioned cardioplegic solution exists, still need further improvement, the time that especially induction stops fighting must shorten as much as possible, and use the cardioplegic solution of minimum available capacity is also suitable to obtain cardiac arrest simultaneously.The method that traditional myocardial preservation adopts chemical asystole to add topical hypothermia has reduced cardiac energy consumption, and adds various additives hypoxic-ischemic degree of injury when making asystole to be down to minimum.The focus of more research in recent years concentrates on ischemic injuries while how reducing asystole and the reperfusion injury after perfusion again.Cardiac muscle is being blocked after circulation in anaerobic metabolism state, when histanoxia, because the acetone acid under oxygen free condition of glucose in cell can be converted into lactic acid, produce a large amount of lactic acid, and in the operation on heart that circulates in vitro, preliminary filling Ringer lactate solution also easily makes them that hyperlactacidemia occurs, and causes serious lactic acidosis.Though low temperature has reduced the metabolism state of cell, sugar utilizes and ATP storage reduces greatly, and negative energy balance appears in myocardial cell in the situation that metabolism does not stop completely.
Lignocaine is clinical common medicine, is usually used in nerve block, treatment arrhythmia, Organoprotective etc.Research finds, lignocaine concentration >=0.6mmol/L can stop the cardiac muscle of fighting fast, and retains its antiinflammatory antioxidation, then rebeating rapidly after perfusion, and fills with rear incidence of arrhythmia and significantly reduce again.
Adenosine is the intermediate product of energy metabolism of myocardial, is bringing into play important pathophysiological role maintaining in the homeostasis of cardiovascular system and various damage mechanism.Adenosine has the effect that regulates coronary circulation.Adenosine, by lasting coronary artery dilating, improves myocardial oxygen, promotes stream in glucose. and supplement energy-rich phosphate bond pond in cell, cardiac function enhancing, and the effect of antagonism catecholamine, recover unbalance oxygen supply and demand and energy metabolism again.In addition, adenosine also have suppress Endothelin release, prevent the function such as gathering and the content of rising myocardial cell Mn-SOD of platelet in microcirculation.
Summary of the invention
The invention provides a kind of cardioplegic solution that comprises lignocaine and adenosine and preparation method thereof, overcome the deficiency of above-mentioned prior art, its can effectively solve traditional cardioplegic solution exist induction stop fighting overlong time, need to pour into again, easily occur after rebeating arrhythmia, easily cause myocardial damage, the easy problem that inflammatory reaction occurs and cannot take oxygen.
A cardioplegic solution that comprises lignocaine and adenosine, in 1000ml organ preservative fluid, component is respectively:
Sodium chloride 5.0-7.0g; Potassium chloride 2.0-3.0g; Magnesium sulfate 0.3-0.5g;
Calcium chloride 0.05-0.1g; Glucose 5-8g; Lignocaine 0.3-0.6g;
Adenosine 100-200mg; Astragaloside 10-20mg; Coenzyme Q10 50-80mg;
Tetrandrine 5-10mg; Demethylcoclaurine 5-10mg; Histidine 5-8g; Distilled water surplus.
In one embodiment of the invention, in 1000ml organ preservative fluid, described component is preferably:
Sodium chloride 6.5g; Potassium chloride 2.3g; Magnesium sulfate 0.35g;
Calcium chloride 0.07g; Glucose 6g; Lignocaine 0.5g;
Adenosine 130mg; Astragaloside 15mg; Coenzyme Q10 75mg;
Tetrandrine 7mg; Demethylcoclaurine 8mg; Histidine 6g; Distilled water surplus.
In another embodiment of the invention, in 1000ml organ preservative fluid, described component is preferably:
Sodium chloride 6g; Potassium chloride 2.5g; Magnesium sulfate 0.4g;
Calcium chloride 0.07g; Glucose 7g; Lignocaine 0.4g;
Adenosine 150mg; Astragaloside 17mg; Coenzyme Q10 60mg;
Tetrandrine 9mg; Demethylcoclaurine 6mg; Histidine 7g; Distilled water surplus.
Another object of the present invention is to provide a kind of method of preparing described cardioplegic solution, and concrete steps are as follows:
(1) 800ml distilled water is added and is greater than in 1000ml container, then add successively sodium chloride, potassium chloride, magnesium sulfate, calcium chloride, be stirred to color and become clear; Add again glucose, lignocaine, adenosine, astragaloside, tetrandrine, histidine and demethylcoclaurine, be stirred to color and become clear; Then add coenzyme Q10, be stirred to color and become clear;
(2) pH of solution is adjusted to 7.65, osmotic pressure is adjusted to 350～385mOsm/L, and distilled water is settled to 1000ml, places 4 DEG C of cryopreservation for subsequent use, to obtain final product.
The present invention has carried out deep research on the consumption of lignocaine and adenosine, and in conjunction with the advantage of motherland's traditional medicine, Chinese medicine extract about Cardioprotective and monomer whose are carried out to the screening test of large amount of complex, determine best Chinese medicine monomer composition and weight proportion thereof, thereby obtain a cardioplegic solution prescription that reaches optimum efficiency, use cardioplegic solution prepared by a small amount of the present invention just can effectively make asystole, avoid because myocardial ischemia-reperfusion is to myocardium damage, incidence of arrhythmia after can improving a rebeating success rate and reducing rebeating, and effectively reduce inflammatory reaction, myocardial cell is played to protection effectively.
Detailed description of the invention
Below by bright the present invention in further example.It is pointed out that following explanation is only illustrating of the technical scheme claimed to the present invention, the not any restriction to these technical schemes.The content that protection scope of the present invention is recorded with appended claims is as the criterion.
embodiment 1
Precision takes following compositions:
Sodium chloride 6.5g; Potassium chloride 2.3g; Magnesium sulfate 0.35g;
Calcium chloride 0.07g; Glucose 6g; Lignocaine 0.5g;
Adenosine 130mg; Astragaloside 15mg; Coenzyme Q10 75mg;
Tetrandrine 9mg; Demethylcoclaurine 6mg; Histidine 7g.
(1) 800ml distilled water is added and is greater than in 1000ml container, then add successively sodium chloride, potassium chloride, magnesium sulfate, calcium chloride, be stirred to color and become clear; Add again glucose, lignocaine, adenosine, astragaloside, tetrandrine, histidine and demethylcoclaurine, be stirred to color and become clear; Then add coenzyme Q10, be stirred to color and become clear;
(2) pH of solution is adjusted to 7.65, osmotic pressure is adjusted to 370mOsm/L, and distilled water is settled to 1000ml, places 4 DEG C of cryopreservation for subsequent use, to obtain final product.
embodiment 2
Precision takes following compositions:
Sodium chloride 6g; Potassium chloride 2.5g; Magnesium sulfate 0.4g;
Calcium chloride 0.07g; Glucose 7g; Lignocaine 0.4g;
Adenosine 150mg; Astragaloside 17mg; Coenzyme Q10 60mg;
Tetrandrine 9mg; Demethylcoclaurine 6mg; Histidine 7g; Other preparation methoies are with embodiment 1.
embodiment 3
Precision takes following compositions:
Sodium chloride 5.0g; Potassium chloride 3.0g; Magnesium sulfate 0.5g;
Calcium chloride 0.05g; Glucose 8g; Lignocaine 0.6g;
Adenosine 200mg; Astragaloside 10mg; Coenzyme Q10 50mg;
Tetrandrine 10mg; Demethylcoclaurine 5mg; Histidine 5g; Other preparation methoies are with embodiment 1.
embodiment 4
Adopt Isolated Rat heart non-circulating type Langendorff perfusion functional test model, by comparing for heart preservation liquid (Thomas liquid, Stanford liquid, UW liquid) with 3 kinds that commonly use, the preservation effect of 4 DEG C of preservation Isolated Rat hearts of research long-time (10 hours).
SD rat, weighs, and 2% pentobarbital sodium 0.5-0.7ml is through lumbar injection.After anesthesia, get dorsal position and fix, inject heparin (3mg/Kg) through left femoral vein, open rapidly breast, in aorta and right subclavian artery intersection from disconnected aorta, excise heart.Immediately heart is put into the plate that contains cold KHB liquid (4 DEG C), wash out and remain in endaortic blood with cold KHB liquid, insert aortic perfusion pipe fixing (end of intrusion pipe should not contact aortic valve), heart is moved to rapidly on Langendorff perfusion device and start perfusion.Perfusion pressure is 90cmH2O (8.32Kpa).Start within 50-70 second, to complete rapidly to perfusion from opening breast, exceed and abandon for 80 seconds.After recovering beat of heart 3 minutes, with electric stimulating instrument pace-making heart, (anode was placed in right auricle, and negative electrode is fixed on right ventricle.Stimulus frequency is 5Hz (300 beats/min), and stimulus waveform is square wave (40mv).Cut right auricle, through right atrium, Bicuspid valve, the sacculus with pressure catheter is sent into left ventricle, another termination pressure transducer of pressure-measuring pipe, the latter is connected with electric physiology polygraph.Be used for measuring cardiac function observation index once, comprise:
1.. LVEDP (LVEDP)
2.. left chamber produces presses (LVDP)
3.. left ventricular pressure differential (+dp/dt)
4.. coronary flow (CF)
The mensuration of coronary flow: collect the liquid flowing out through right atrium, the amount of liquid of collection per minute is coronary flow (ml/min).When perfusion to 30 minute, unable if the Mus heart shrinks, there is the left chamber of ventricular fibrillation to produce and press < 70mmHg, abandon.
In the time of 30 minutes, stop cardiac perfusion, change immediately perfused hearts cardioplegic solution into, pressure is 75cmH
2o (7.36Kpa), 4 DEG C of cardioplegic solution temperature, heart is surface cooling (4 DEG C) simultaneously, pours into after 3 points of kinds, puts heart in corresponding preservation liquid.4 DEG C of constant temperature.Preserve after 10 hours, heart recovers perfusion (method for filling is with the method before stopping fighting), then while filling with 30 minutes, measures cardiac function, cuts left ventricular wall tissue, evenly cuts 2 parts of rapid liquid nitrogen freezings and preserves, and prepares against the mensuration of making energy metabolism index.
Concrete outcome is as follows:
The cardiac function when preservation of SD isolated rat heart is poured into 30 minutes after 10 hours again
| 1. | 2. LVEDP（mmHg） | 3. LVDP（mmHg） | 4. +dp/dt | 5. CF |
| 6. Stanford liquid | 7. 53.2±11.6 | 8. 21.3±5.4 | 9. 478±187 | 10. 5.2±0.7 |
| 11. UW liquid | 12. 59.5±13.3 | 13. 25.8±4.8 | 14. 534±162 | 15. 5.5±0.8 |
| 16. Thomas liquid | 17. 48.2±12.7 | 18. 29.5±5.2 | 19. 567±175 | 20. 5.7±0.8 |
| 21. Embodiment 1 | 22. 21.4±11.3 | 23. 57.8±6.7 | 24. 1772±365 | 25. 7.4±0.9 |
| 26. Embodiment 2 | 27. 22.7±10.5 | 28. 59.4±5.8 | 29. 1838±297 | 30. 7.8±0.7 |
| 31. Embodiment 3 | 32. 24.6±11.5 | 33. 53.4±5.2 | 34. 1674±288 | 35. 7.0±0.4 |
| 36. Comparative example 1 | 37. 39.2±10.1 | 38. 34.5±4.6 | 39. 978±262 | 40. 6.1±0.4 |
| 41. Comparative example 2 | 42. 41.6±12.2 | 43. 31.3±4.8 | 44. 931±224 | 45. 6.3±0.5 |
| 46. Comparative example 3 | 47. 40.9±12.4 | 48. 33.9±4.5 | 49. 953±281 | 50. 6.4±0.6 |
Compared with before preserving, preserve the recovery rate (%) of pouring into again 30 minutes cardiac function for 10 hours
| 51. | 52. LVDP | 53. +dp/dt |
| 54. Stanford liquid | 55. 41.5% | 56. 43.7% |
| 57. UW liquid | 58. 44.2% | 59. 43.8% |
| 60. Thomas liquid | 61. 45.3% | 62. 46.2% |
| 63. Embodiment 1 | 64. 71.1% | 65. 73.6% |
| 66. Embodiment 2 | 67. 75.4% | 68. 76.5% |
| 69. Embodiment 3 | 70. 69.8% | 71. 70.4% |
| 72. Comparative example 1 | 73. 54.7% | 74. 53.5% |
| 75. Comparative example 2 | 76. 51.2% | 77. 52.8% |
| 78. Comparative example 3 | 79. 53.6% | 80. 54.4% |
Preserve the content of cardiac muscle high-energy phosphate while pouring into again 30 minutes in 10 hours
| 81. （μmol/g） | 82. ATP | 83. ADP | 84. AMP |
| 85. Stanford liquid | 86. 1.42±0.11 | 87. 0.73±0.17 | 88. 0.71±0.15 |
| 89. UW liquid | 90. 1.53±0.06 | 91. 0.77±0.15 | 92. 0.65±0.17 |
| 93. Thomas liquid | 94. 1.58±0.08 | 95. 0.81±0.18 | 96. 0.81±0.16 |
| 97. Embodiment 1 | 98. 3.24±0.14 | 99. 1.86±0.22 | 100. 0.93±0.20 |
| 101. Embodiment 2 | 102. 3.42±0.18 | 103. 1.94±0.24 | 104. 0.98±0.24 |
| 105. Embodiment 3 | 106. 2.95±0.15 | 107. 1.79±0.21 | 108. 0.89±0.18 |
| 109. Comparative example 1 | 110. 1.92±0.09 | 111. 0.93±0.12 | 112. 0.63±0.17 |
| 113. Comparative example 2 | 114. 2.05±0.08 | 115. 1.14±0.15 | 116. 0.75±0.18 |
| 117. Comparative example 3 | 118. 1.95±0.08 | 119. 1.06±0.14 | 120. 0.74±0.16 |
embodiment 5
Collect case 100 examples, be equally divided into 6 groups, in operation, apply cardioplegic solution prepared by the present invention (all open-heart surgeries complete intracardiac operation in the 2h that stops fighting), before perfusion cardioplegic solution, patient's heart is carried out to labelling with label, after perfusion cardioplegic solution, after rebeating, measure respectively the index such as myocardial damage biochemical marker burst size, heart blood discharge amount, lactic acid generation of each group.
Concrete outcome is as follows:
CTnI(ng/ml) measurement result
| 121. | 122. Basic value | 123. After recovering beat of heart 2h |
| 124. Stanford liquid | 125. 0.03±0.01 | 126. 11.8±3.8 |
| 127. UW liquid | 128. 0.04±0.01 | 129. 10.5±2.7 |
| 130. Thomas liquid | 131. 0.04±0.01 | 132. 9.9±3.4 |
| 133. Embodiment 1 | 134. 0.03±0.01 | 135. 5.3±1.9 |
| 136. Embodiment 2 | 137. 0.04±0.01 | 138. 4.9±1.6 |
| 139. Embodiment 3 | 140. 0.03±0.01 | 141. 5.4±1.8 |
The variation (L/min) of cardiac output
| 142. | 143. Basic value | 144. Recovering beat of heart | 145. Recovering beat of heart 2h |
| 146. Stanford liquid | 147. 3.4±0.7 | 148. 1.8±0.6 | 149. 2.2±0.5 |
| 150. UW liquid | 151. 3.3±0.5 | 152. 1.9±0.5 | 153. 2.3±0.7 |
| 154. Thomas liquid | 155. 3.4±0.6 | 156. 1.8±0.5 | 157. 2.3±0.6 |
| 158. Embodiment 1 | 159. 3.4±0.7 | 160. 2.3±0.4 | 161. 2.8±0.7 |
| 162. Embodiment 2 | 163. 3.3±0.4 | 164. 2.4±0.5 | 165. 2.9±0.6 |
| 166. Embodiment 3 | 167. 3.4±0.5 | 168. 2.3±0.4 | 169. 2.8±0.6 |
Lactic acid generation (mmol/L)
| 170. | 171. Basic value | 172. Recovering beat of heart 2h |
| 173. Stanford liquid | 174. 0.8±0.3 | 175. 1.9±0.6 |
| 176. UW liquid | 177. 0.7±0.2 | 178. 1.7±0.5 |
| 179. Thomas liquid | 180. 0.8±0.3 | 181. 1.8±0.7 |
| 182. Embodiment 1 | 183. 0.8±0.4 | 184. 1.3±0.5 |
| 185. Embodiment 2 | 186. 0.8±0.2 | 187. 1.2±0.4 |
| 188. Embodiment 3 | 189. 0.8±0.3 | 190. 1.3±0.5 |
In addition, the present invention also respectively detection statistics cardiac induction stop the time of fighting, disposable rebeating success rate, incidence of arrhythmia.
Concrete outcome is as follows:
| 191. | 192. Cardiac induction stops the time of fighting | 193. Disposable rebeating success rate | 194. Incidence of arrhythmia |
| 195. Stanford liquid | 196. 67±23s | 197. 83% | 198. 23% |
| 199. UW liquid | 200. 53±25s | 201. 90% | 202. 31% |
| 203. Thomas liquid | 204. 58±24s | 205. 87% | 206. 28% |
| 207. Embodiment 1 | 208. 42±18s | 209. 100% | 210. 12% |
| 211. Embodiment 2 | 212. 39±14s | 213. 100% | 214. 10% |
| 215. Embodiment 3 | 216. 43±15s | 217. 100% | 218. 13% |
Content of the present invention only for example understands some claimed specific embodiments; the technical characterictic of recording in one of them or more technical scheme can be with one or more technical schemes be combined arbitrarily; these technical schemes that obtain through combination are also in the application's protection domain, just as these technical schemes that obtain through combination have specifically been recorded in the disclosure of invention.
Claims (4)
1. a cardioplegic solution that comprises lignocaine and adenosine, is characterized in that, in 1000ml organ preservative fluid, component is respectively:
Sodium chloride 5.0-7.0g; Potassium chloride 2.0-3.0g; Magnesium sulfate 0.3-0.5g;
Calcium chloride 0.05-0.1g; Glucose 5-8g; Lignocaine 0.3-0.6g;
Adenosine 100-200mg; Astragaloside 10-20mg; Coenzyme Q10 50-80mg;
Tetrandrine 5-10mg; Demethylcoclaurine 5-10mg; Histidine 5-8g; Distilled water surplus.
2. cardioplegic solution according to claim 1, is characterized in that, in 1000ml organ preservative fluid, described component is preferably:
Sodium chloride 6.5g; Potassium chloride 2.3g; Magnesium sulfate 0.35g;
Calcium chloride 0.07g; Glucose 6g; Lignocaine 0.5g;
Adenosine 130mg; Astragaloside 15mg; Coenzyme Q10 75mg;
Tetrandrine 7mg; Demethylcoclaurine 8mg; Histidine 6g; Distilled water surplus.
3. according to the cardioplegic solution described in claim 1-2, it is characterized in that, in 1000ml organ preservative fluid, described component is preferably:
Sodium chloride 6g; Potassium chloride 2.5g; Magnesium sulfate 0.4g;
Calcium chloride 0.07g; Glucose 7g; Lignocaine 0.4g;
Adenosine 150mg; Astragaloside 17mg; Coenzyme Q10 60mg;
Tetrandrine 9mg; Demethylcoclaurine 6mg; Histidine 7g; Distilled water surplus.
4. a method of preparing the cardioplegic solution described in claim 1-3 any one, is characterized in that, step is as follows:
(1) 800ml distilled water is added and is greater than in 1000ml container, then add successively sodium chloride, potassium chloride, magnesium sulfate, calcium chloride, be stirred to color and become clear; Add again glucose, lignocaine, adenosine, astragaloside, tetrandrine, histidine and demethylcoclaurine, be stirred to color and become clear; Then add coenzyme Q10, be stirred to color and become clear;
(2) pH of solution is adjusted to 7.65, osmotic pressure is adjusted to 350～385mOsm/L, and distilled water is settled to 1000ml, places 4 DEG C of cryopreservation for subsequent use, to obtain final product.
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| CN104857021A (en) * | 2015-04-30 | 2015-08-26 | 王涛 | Cold autologous blood cardioplegia solution and preparation method and application thereof |
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| US11844345B2 (en) | 2005-06-28 | 2023-12-19 | Transmedics, Inc. | Systems, methods, compositions and solutions for perfusing an organ |
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