Luisi Andrew J, Suzuki Gen, Dekemp Robert, Haka Michael S, Toorongian Steven A, Canty John M, Fallavollita James A
Department of Medicine, SUNY at Buffalo, VA Western New York Health Care System, NY 14214, USA.
J Nucl Med. 2005 Aug;46(8):1368-74.
We have previously shown that ex vivo counting of (131)I-metaiodobenzylguanidine can identify regional reductions in sympathetic norepinephrine uptake in pigs with hibernating myocardium. However, nonneuronal uptake limited relative differences between regions and would preclude accurate assessment with conventional imaging. We therefore hypothesized that the superior specificity of the positron-emitting isotope (11)C-hydroxyephedrine (HED) would facilitate the imaging of regional differences, and we designed this study to determine whether altered uptake of norepinephrine by sympathetic nerves in viable, dysfunctional myocardium can be imaged in vivo and to determine the temporal progression and stability of sympathetic dysinnervation in hibernating myocardium.
Pigs (n = 15) were chronically instrumented with a 1.5-mm stenosis of the left anterior descending coronary artery, a procedure that we have previously shown to produce viable chronically dysfunctional myocardium with reduced resting flow, or hibernating myocardium, after 3 mo. Physiologic studies and HED PET were performed 1-5 mo later with the animals in the closed-chest sedated state. One animal with a myocardial infarct was analyzed separately.
After 3 mo, anterior hypokinesis developed (wall thickening, 32% +/- 4% vs. 60% +/- 4%, P < 0.001), with reductions in resting flow (subendocardial flow, 0.81 +/- 0.11 vs. 1.20 +/- 0.18 mL/min/g, P < 0.05) and a critical reduction in subendocardial flow reserve (subendocardial adenosine flow, 0.53 +/- 0.20 vs. 3.96 +/- 0.43 mL/min/g, P < 0.001). Extensive defects in HED uptake were found for hibernating myocardium, with regional retention approximately 50% lower than that in normally perfused remote myocardium (0.035 +/- 0.002 vs. 0.066 +/- 0.002 min(-1), P < 0.001). Relative HED uptake (left anterior descending coronary artery/remote) was lower in chronically instrumented animals than in control animals (n = 4, P < 0.001) and animals studied 1 mo after instrumentation (n = 2, P < 0.05). The regional reduction in sympathetic nerve function was persistent and unaltered for at least 2 mo after the development of hibernating myocardium.
Hibernating myocardium is associated with persistent reductions in regional uptake of norepinephrine by sympathetic nerves. The inhomogeneity in sympathetic innervation in viable dysfunctional myocardium is similar to that occurring after myocardial infarction and may contribute to arrhythmic death in patients with ischemic cardiomyopathy.
我们之前已经表明,对(131)I - 间碘苄胍进行体外计数可以识别冬眠心肌猪交感去甲肾上腺素摄取的区域减少。然而,非神经元摄取限制了区域间的相对差异,并且会妨碍用传统成像进行准确评估。因此,我们推测正电子发射同位素(11)C - 羟基麻黄碱(HED)的更高特异性将有助于对区域差异进行成像,并且我们设计了本研究以确定在存活的功能失调心肌中交感神经去甲肾上腺素摄取的改变是否可以在体内成像,并确定冬眠心肌中交感神经去神经支配的时间进程和稳定性。
猪(n = 15)被长期植入左前降支冠状动脉1.5毫米狭窄装置,我们之前已经表明该操作在3个月后会产生具有静息血流减少的存活的慢性功能失调心肌,即冬眠心肌。1 - 5个月后在动物处于闭胸镇静状态下进行生理研究和HED PET。单独分析了一只患有心肌梗死的动物。
3个月后,出现前壁运动减弱(室壁增厚,32%±4%对60%±4%,P < 0.001),静息血流减少(心内膜下血流,0.81±0.11对1.20±0.18 mL/min/g,P < 0.05),心内膜下血流储备显著降低(心内膜下腺苷血流,0.53±0.20对3.96±0.43 mL/min/g,P < 0.001)。发现冬眠心肌的HED摄取存在广泛缺损,区域滞留比正常灌注的远隔心肌低约50%(0.035±0.002对0.066±0.002 min⁻¹,P < 0.001)。长期植入装置的动物中HED的相对摄取(左前降支冠状动脉/远隔)低于对照动物(n = 4,P < 0.001)和植入装置1个月后研究的动物(n = 2,P < 0.05)。冬眠心肌形成后至少2个月,交感神经功能的区域减少持续且未改变。
冬眠心肌与交感神经去甲肾上腺素区域摄取的持续减少有关。存活的功能失调心肌中交感神经支配的不均匀性与心肌梗死后发生的情况相似,可能导致缺血性心肌病患者的心律失常性死亡。