心肌缺氧时慢速心律失常腺苷假说的验证及意义

EXPERIMENTALSTUDYONADENOSINEHYPOTHESISOFBRADYARRHYTHMIASOCCURRINGINMYOCARDIALHYPOXIAANDITSCLINCALSIGNIFICANCE

为研究心肌缺氧时慢速心律失常腺苷假说的意义，在豚鼠和兔的整体及离体心肌缺氧模型上，用酶鉴别分光光度法、相关因素同步定量分析及腺苷拮抗剂作了内生性腺苷的实验研究。结果表明，缺氧心肌的内生性腺苷显著增多（从对照组的每克心肌组织５．８±１．７ｎｍｏｌ增至吸入５％氧组的２７．５ｎｍｏｌ±２．０ｎｍｏｌ，Ｐ＜０．０１）。注射外源性腺苷所致的窦性心动过缓及房室阻滞，与心肌缺氧引起者在表现形式及量效关系上都极为相似。二者的希氏束心电图皆呈Ａ－Ｈ间期延长而Ｈ－Ｖ间期不变，说明传导阻滞的部位相同。从三因素同步定量分析得出内生性腺苷与心律失常间比较，ｒ＝０．９９，Ｐ＜０．０１；用氨茶碱（腹腔内注射５０ｍｇ）能完全阻断豚鼠吸入５％氧组及２％氧组Ⅱ～Ⅲ度房室传导阻滞的发生，提示腺苷与慢速心律失常有因果关系。在临床上应给予腺苷拮抗剂，如甲基黄嘌呤类（氨茶碱）治疗。

Importantroleofendogenousadenosineinthepathogenesisofhypoxicbradyarrhythmiaswasverifiedexperimentalybothinvivoandinvitromodelsofmyocardialhypoxiain180guineapigsand40rabbitsbyusingenzymediferentialspectrophotometry,synchronousquantitativeanalysisofcorelat-edfactorsandadenosineantagonist.Resultsdisclosedthatendogenousadenosineinhypoxicmyocardiumincreasedmarkedlyfromagrammyocardialtissue5.8±1.7nmolofthecontrolgroupto27.5±2.0nmolof5%O2inhalationgroup(P<0.01).SinusbradycardiaandA-VblockinducedbyinjectionofexogenousadenosinewerecloselyakintothosecausedbymyocardialhypoxiabothinECGcharacteristicsanddose-re-sponsecurve.BothoftheirHiselectrogramsshowedprolongationofA-HintervalbutnochangeofH-Vinterval,indicatingthesamelocalityofconductionblock.Synchronousquantitativeanalysisof3relat-edfactorsrevealedacorrelationcoeficientof0.99(P<0.01)betwenendogenousadenosineandbrad-yarhythmias,denotingasubordinateinsteadofcoordinaterelation.Moreover,causeandefectrelationcouldbeshownbetweenthemfromtheresultthataminophyline(50mg,ip)couldabolishcompletelyⅡ°-Ⅲ°A-Vblockwhichwouldotherwisebeboundtooccurafterinhalationof5%O2.Thepresentstudyisthefirstinvivoexperimentalverificationofadenosinehypothesisthroughouttheworldwhichnotonlycanwelexplainthoseatropine-resistantcases,butalsoopensupthewaytoanentirelynewtherapeuticstrate-gyforthesekindsofbradyarrhythmias,i.e.insteadofM-cholinoceptorblocker,adenosineantag-onist(methylxanthines,e.g.aminophyline)shouldbeprescribed.