Uberfuhr P, Ziegler S, Schwaiblmair M, Reichart B, Schwaiger M
Clinic of Cardiac Surgery, Grosshadern Medical Center, University of Munich, Munich, Germany.
Eur J Cardiothorac Surg. 2000 Feb;17(2):161-8. doi: 10.1016/s1010-7940(99)00367-x.
Heart transplantation (HTx) is associated with autonomic denervation of the donor heart. Sympathetic reinnervation (RI) as defined by the presence of functional nerve terminals occurs only if sympathetic ganglia outside the heart are connected with nerve terminals in the transplanted heart. The purpose of this study was to define the incidence and functional consequences of RI over time after HTx. The activity and distribution of norepinephrine (NE) uptake sites were assessed by positron emission tomography (PET) imaging. Symptom limited exercise testing was performed by bicycle-ergometer.
Forty-seven patients (m:f=42:5, 47.6+/-8. 2 years, age range 27-65 years) were investigated between 2 months and 13.6 years after HTx using PET and the NE analogue C-11-hydroxyephedrine (HED). Tracer uptake was quantified using dynamic imaging protocols yielding regional HED retention fraction. A regional value above 7%/min (+/-2.5 SD above the mean value of denervated hearts) was considered evidence for RI. The functional significance of RI was investigated in 34 patients (m:f=30:4, 49. 3+/-8.4 age range 27-62 years) by symptom limited exercise testing. Cardiac catheterization was performed at the time of PET imaging.
RI could not be assessed in the first year after HTx, in 11% in the second year and in 80% of the patients from the third year on. Retention values plateaued then. In all time intervals, beyond the third year, not reinnervated patients were found. RI remained incomplete and was always restricted to the anterior wall of the left ventricle. Extent of retention of the left ventricle revealed a large individual range up to 66%, averaging of 20%. Recipient age at the time of HTx, reinnervated patients were 5.5 years younger than not reinnervated ones, proved as the only significant influencing factor for RI (P<0.05). Dividing patients into scintigraphically reinnervated (n=20) and not reinnervated (n=14), reinnervated patients displayed during exercise a higher maximal heart rate (137+/-14 vs. 123+/-20/min, P<0.05), heart rate increase (40+/-15 vs. 28+/-13/min, P<0.05), max. oxygen consumption (1674+/-424 vs. 1279+/-308 ml/min, P<0.01) and anaerobic threshold (887+/-170 vs. 717+/-183 mlO(2)/min, P<0.01) than not reinnervated ones. A correlation between transplant vasculopathy and RI could not be demonstrated.
++: RI assessed by PET and the NE analogue HED is time dependent, incomplete, displays a typical pattern and demonstrates a broad individual spread. Furthermore, RI enhances functional parameters of exercise testing.
心脏移植（HTx）与供体心脏的自主神经去神经支配有关。只有当心脏外的交感神经节与移植心脏中的神经末梢相连时，才会出现功能性神经末梢所定义的交感神经再支配（RI）。本研究的目的是确定HTx后随时间推移RI的发生率及其功能后果。通过正电子发射断层扫描（PET）成像评估去甲肾上腺素（NE）摄取位点的活性和分布。通过自行车测力计进行症状限制性运动试验。
47例患者（男∶女 = 42∶5，47.6±8.2岁，年龄范围27 - 65岁）在HTx后2个月至13.6年期间接受了PET和NE类似物C-11-羟基麻黄碱（HED）检查。使用动态成像方案对示踪剂摄取进行定量，得出局部HED保留分数。局部值高于7%/分钟（比去神经心脏的平均值高±2.5标准差）被视为RI的证据。通过症状限制性运动试验对34例患者（男∶女 = 30∶4，49.3±8.4岁，年龄范围27 - 62岁）RI的功能意义进行了研究。在PET成像时进行心脏导管检查。
HTx后第一年无法评估RI，第二年为11%，从第三年起80%的患者可评估到RI。此后保留值趋于平稳。在所有时间间隔内，超过第三年未发现未再支配的患者。RI仍不完全，且始终局限于左心室前壁。左心室的保留程度显示出个体差异很大，高达66%，平均为20%。在HTx时接受者的年龄方面，再支配的患者比未再支配的患者年轻5.5岁，这被证明是RI的唯一显著影响因素（P<0.05）。将患者分为闪烁显像再支配（n = 20）和未再支配（n = 14）两组，再支配的患者在运动时显示出更高的最大心率（137±14对123±20次/分钟，P<0.05）、心率增加幅度（40±15对28±13次/分钟，P<0.05）、最大耗氧量（1674±424对1279±308毫升/分钟，P<0.01）和无氧阈值（887±170对717±183毫升O₂/分钟，P<0.01）。未证明移植血管病变与RI之间存在相关性。
通过PET和NE类似物HED评估的RI是时间依赖性的、不完全的，呈现典型模式且个体差异较大。此外，RI可增强运动试验的功能参数。
