Brown M D, Hudlická O
Department of Physiology, University of Birmingham Medical School, England.
Circ Res. 1988 May;62(5):965-74. doi: 10.1161/01.res.62.5.965.
A high intravenous dose of norepinephrine (4 micrograms/kg/min for 60 minutes) to New Zealand Red rabbits produced patchy subendocardial damage (estimated stereologically in frozen sections) of about 5% of the heart volume 2 days after application. The damaged areas showed loss of staining for alkaline phosphatase, an enzyme present in normal capillary endothelium. Heart performance (cardiac output index, cardiac work [i.e., cardiac output X mean blood pressure], and dP/dtmax) were significantly lower than in control hearts. Capillary density distribution estimated in nondamaged areas of the left ventricular free wall was inhomogeneous favoring subepicardial regions, while homogeneous transmural distribution was found in control hearts. Bradycardial pacing (reduction of heart rate to 50% of normal) performed for 3-4 weeks prior to norepinephrine administration showed a protective effect against catecholamine damage manifested in a smaller extent of necrosis, in the maintenance of homogeneous transmural capillary distribution in nondamaged areas, and, most importantly, in the maintenance of normal cardiac pump performance at rest and during maximal work in response to acutely administered norepinephrine.
给新西兰白兔静脉注射高剂量去甲肾上腺素(4微克/千克/分钟,持续60分钟),在用药2天后,产生了约占心脏体积5%的散在性心内膜下损伤(通过对冰冻切片进行体视学估计)。受损区域碱性磷酸酶染色缺失,该酶存在于正常毛细血管内皮中。心脏功能(心输出量指数、心脏做功[即心输出量×平均血压]和最大dp/dt)显著低于对照心脏。在左心室游离壁未受损区域估计的毛细血管密度分布不均匀,心外膜下区域更密集,而对照心脏中则呈均匀的透壁分布。在给予去甲肾上腺素之前进行3 - 4周的缓慢性起搏(将心率降至正常的50%),显示出对儿茶酚胺损伤的保护作用,表现为坏死范围较小、未受损区域维持均匀的透壁毛细血管分布,最重要的是,在急性给予去甲肾上腺素后,静息和最大负荷时维持正常的心脏泵功能。