Dae M W, Lee R J, Ursell P C, Chin M C, Stillson C A, Moise N S
Cardiovascular Research Institute, School of Medicine, University of California at San Francisco, 94143, USA.
Circulation. 1997 Aug 19;96(4):1337-42. doi: 10.1161/01.cir.96.4.1337.
Recently, a colony of German shepherd dogs with inherited spontaneous cardiac arrhythmias and associated sudden death has been developed and characterized. Due to the median age of onset of the arrhythmia (4.5 months), the tendency for the arrhythmia to occur during REM sleep or after exercise, and the absence of structural heart disease, we hypothesized a developmental abnormality of the sympathetic innervation to the heart.
We studied 11 dogs from this colony, ranging in age from 6 months to 6 years, and four 7-month-old German shepherd dogs unrelated to the colony as controls. We imaged the distribution of functional myocardial sympathetic innervation and perfusion with [123I]metaiodobenzylguanidine (MIBG) and 201Tl, respectively. Sympathetic nerve distribution was evaluated morphologically by immunocytochemical localization of tyrosine hydroxylase. All of the hearts showed evidence of a regional decrease in MIBG uptake, ranging from 5.3% to 53.4% of the myocardium, whereas control dogs showed homogeneous MIBG uptake. Immunocytochemical studies on sections from regions with decreased MIBG uptake showed a striking paucity of nerves compared with regions with normal MIBG uptake, confirming denervation. When the dogs were grouped into those with (n=6) and without (n=5) evidence of ventricular tachycardia on ambulatory ECG, the group with ventricular tachycardia showed 35+/-16.5% denervation, whereas the group without ventricular tachycardia showed 12+/-5.6% denervation (P<.02).
Abnormal heterogeneous sympathetic innervation exists in these dogs with inherited ventricular arrhythmia and sudden cardiac death. Mechanisms relating the presence and extent of regional denervation to the incidence of ventricular arrhythmia remain to be defined.
最近，培育并鉴定了一群患有遗传性自发性心律失常及相关猝死的德国牧羊犬。由于心律失常的中位发病年龄为4.5个月，心律失常倾向于在快速眼动睡眠期间或运动后出现，且无结构性心脏病，我们推测心脏交感神经支配存在发育异常。
我们研究了来自该群体的11只年龄在6个月至6岁之间的狗，以及4只与该群体无关的7个月大的德国牧羊犬作为对照。我们分别用[123I]间碘苄胍（MIBG）和201Tl对功能性心肌交感神经支配和灌注分布进行成像。通过酪氨酸羟化酶的免疫细胞化学定位从形态学上评估交感神经分布。所有心脏均显示MIBG摄取有局部降低的证据，范围为心肌的5.3%至53.4%，而对照犬的MIBG摄取均匀。对MIBG摄取降低区域的切片进行免疫细胞化学研究显示，与MIBG摄取正常区域相比，神经明显稀少，证实了去神经支配。当将这些狗分为动态心电图有（n = 6）和无（n = 5）室性心动过速证据的两组时，有室性心动过速的组显示35±16.5%的去神经支配，而无室性心动过速的组显示12±5.6%的去神经支配（P<0.02）。
这些患有遗传性室性心律失常和心源性猝死的狗存在异常的异质性交感神经支配。区域去神经支配的存在和程度与室性心律失常发生率之间的机制仍有待确定。
