N-13 AMMONIA AS AN INDICATOR OF MYOCARDIAL BLOOD-FLOW
N-13 AMMONIA AS AN INDICATOR OF MYOCARDIAL BLOOD-FLOW
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DOI：
10.1161/01.cir.63.6.1259
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发表时间：
1981-01-01
期刊：
影响因子：
37.8
通讯作者：
KUHL, DE
中科院分区：
文献类型：
--
作者：
SCHELBERT, HR;PHELPS, ME;KUHL, DE
13N氨被描述为适合正电子发射计算机断层扫描的心肌血流显像剂。该药物在心肌中的摄取和保留机制尚不清楚，也没有考虑代谢改变的影响。在开胸狗的各种血流动力学和代谢条件下，研究了心肌中 N13 氨的吸收和保留。 13N 氨在其最初的毛细管传输过程中几乎 100% 被提取，随后是与流量依赖性反向扩散竞争的代谢捕获。在控制流量下，13N 氨的第一毛细管过境萃取分数 (E) 平均为 0.82 .+-。 0.06，并且随着流量的增加而下降。心肌 13N 组织清除半衰期与血流量呈负相关，范围为 110-642 分钟。异丙肾上腺素和普萘洛尔引起的心脏做功和心肌正性肌力状态的变化不影响E或组织清除半衰期。低血浆 pH 值使 E 平均降低 20%，而血浆 pH 值升高则没有影响。低于控制的流量减少与 E 的下降有关。用 L-甲硫氨酸亚磺酰亚胺抑制谷氨酰胺合成酶会损害 13N 氨的代谢捕获，并暗示谷氨酸-谷氨酰胺反应是氨固定的主要机制。 E乘流量的乘积预测心肌13N组织浓度，当流量加倍时，该浓度增加70%。血流和代谢捕获是心肌摄取和保留 13N 氨的主要决定因素。在各种血流动力学和代谢条件下代谢捕获的相对稳定性证明了 13N 氨作为心肌血流显像剂的价值。
13N ammonia was characterized as a myocardial blood flow imaging agent suitable for positron-emission computed tomography. The mechanisms of uptake and retention of this agent in myocardium are not known, and effects of altered metabolism were not considered. The uptake and retention of N13 ammonia were studied in myocardium under various hemodynamic and metabolic conditions in open-chest dogs. 13N ammonia was extracted nearly 100% during its initial capillary transit, followed by metabolic trapping that competed with flow-dependent back diffusion. At control flows the 1st capillary transit extraction fraction (E) of 13N ammonia averaged 0.82 .+-. 0.06 and it fell with higher flows. Myocardial 13N tissue clearance half-times were inversely related to blood flow, and ranged from 110-642 min. Cardiac work and changes in the myocardial inotropic state induced by isoproterenol and propranolol did not affect E or the tissue clearance half-times. Low plasma pH reduced E by an average of 20%, while elevated plasma pH had no effect. Decreases in flow below control were associated with a fall in E. Inhibition of glutamine synthetase with L-methionine sulfoximine impaired metabolic trapping of 13N ammonia and implicates the glutamic acid-glutamine reaction as the primary mechanism for ammonia fixation. The product of E times flow predicts the myocardial 13N tissue concentrations, which increased by 70% when flow was doubled. Blood flow and metabolic trapping are the primary determinants of myocardial uptake and retention of 13N ammonia. The relative constancy of metabolic trapping over a wide range of hemodynamic and metabolic conditions demononstrates the value of 13N ammonia as a myocardial blood flow imaging agent.