异体窦房结组织左心室壁移植的实验研究

EXPERIMENTAL STUDY ON XENOGENIC SINO-ATRIAL NODAL TISSUE TRANSPLANTED INTO LEFT VENTRICULAR WALL

目的通过同胞家兔窦房结组织异体移植,观察移植后窦房结组织形态、超微结构改变及是否形成异位起搏功能,旨在为病态窦房结综合征和重度房室阻滞的治疗提供新思路。方法健康家兔70只,雌雄不限,体重1.5～2.0kg。其中42只受体实验动物随机分为假手术组、热缺血移植组和冷缺血移植组(n=14);另28只为热缺血移植组和冷缺血移植组供体实验动物,与受体为同胞兔。各组受体实验动物于左心室游离壁血管稀疏区近心尖部作长6mm、深2mm切口;对照组切口用7-0Prolene线缝合;冷缺血移植组将供体主动脉阻断后经根部灌注4℃冷晶体灌注液至心脏停跳,切取窦房结组织5mm×3mm移植;热缺血移植组供体直接取同等大小窦房结组织移植。术后1、2、3、4周,各组取3只实验动物刺激双侧迷走神经干制作缓慢性心律失常模型,观测心脏电活动;并观察移植窦房结组织学、超微结构变化。结果受体实验动物术后存活36只,每组12只。术后各时间点,刺激双侧迷走神经干后,各组心电活动均明显减慢,呈窦性心动过缓;术后4周假手术组、热缺血移植组、冷缺血移植组心率分别为(81.17±5.67)、(82.42±7.97)、(80.83±6.95)次/分,组间比较差异无统计学意义(P>0.05)。各组未出现心室异位节律起搏。HE染色示热缺血移植组移植窦房结组织存活6只,冷缺血移植组存活8只,两组差异无统计学意义(P>0.05)。透射电镜示热缺血移植组和冷缺血移植组移植窦房结组织均可见相邻的2个窦房结细胞,细胞质内有空泡状结构,少量散乱的肌微丝,相邻细胞间缝隙连接。结论异体窦房结组织移植至心室壁后可以存活,但不能起到异位起搏作用。

Objective To observe the change of sino-atrial nodal tissue structure and ectopic pacing function after xenogenic sino-atrial nodal tissue transplanted into left ventricular wall,so as to provide new ideas for the treatment of sick sinus syndrome and severe atrioventricular block.Methods Seventy healthy rabbits were selected,male or female,and weighing 1.5-2.0 kg.Of them,42 were used as recipient animals and randomly divided into sham operation group,warm ischemia transplantation group,and cold ischemia transplantation group（n=14）,the other 28 were used as donors of warm ischemia and cold ischemia transplantation groups,which were sibling of the recipients.In recipients,a 6-mm-long and about 2-mm-deep incision was made in the vascular sparse area of left ventricular free wall near the apex.In sham operation group,the incision was sutrued directly by 7-0 Prolene suture;in cold ischemia transplantation group,after the aortic roots cross-clamping,4℃cold crystalloid perfusion fluid infusion to cardiac arrest,then sinoatrial node were cut 5 mm×3 mm for transplantation;in warm ischemia transplantation group,the same size of the sinus node tissue was captured for transplantation.After 1,2,3,and 4 weeks,3 rabbits of each group were harvested to make bradycardia by stimulating bilateral vagus nerve and the cardiac electrical activity was observed;the transplanted sinus node histology and ultrastructural changes were observed.Results Thirty-six recipient rabbits survived（12 rabbits each group）.At 1,2,3,and 4 weeks after bilateral vagus nerve stimulation,the cardiac electrical activity in each group was significantly slower,and showed sinus bradycardia.Four weeks after operation the heart rates of sham operation group,warm ischemia,and cold ischemia transplantation group were（81.17±5.67）,（82.42±7.97）,and（80.83±6.95）beats/ minute,respectively;showing no significant difference among groups（P0.05）.And no ectopic rhythm of ventricular pacing occurred.Sino-atrial nodal tissue survived in 6 of warm ischemic transplantation group and in 8 of cold ischemia transplantation group;showing no significant difference between two groups（P0.05）.Two adjacent sinoatrial node cells,vacuole-like structure in the cytoplasm,a few scattered muscle microfilaments,and gap junctions between adjacent cells were found in transplanted sinus node.Conclusion The allograft sinus node can survive,but can not play a role in ectopic pacing.