Hayden J E, Leffler C W
Department of Physiology/Biophysics, University of Tennessee, Memphis 38163, USA.
Pediatr Res. 1997 Jan;41(1):78-82. doi: 10.1203/00006450-199701000-00012.
Substantial physiologic data point to a significant role for dilator prostanoids in the regulation of cerebral vascular tone in newborn pigs. This study begins to address the hypothesis that multiple dilator systems, including prostanoids, can provide for the initiation and maintenance of cerebral vasodilation in response to hypotension. Piglets were anesthetized, and cranial windows were implanted. Hypotension was achieved by hemorrhage to 50% of the control arterial pressure and maintained for 10 min. Each piglet served as its own control by the induction of hypotension and return to normotension before treatment. Pial arterioles dilated (38 +/- 5% increase in diameter) in response to hypotension. Pretreatment with indomethacin (5 mg/kg i.v.) at 20 min and immediately before hypotension did not block this response (28 +/- 7% and 23 +/- 9% increase in diameter, respectively). In contrast, when indomethacin was administered 10 min into the hypotensive period, the dilated arterioles (106 +/- 6 microns) constricted to the normotensive diameter (75 +/- 5 microns) and remained constricted for the duration of the observation. These findings suggest that compensatory mechanisms provide for cerebral vasodilation when prostanoid synthesis and prostacyclin receptors are blocked before hemorrhagic hypotension. However, removal of prostanoids after vasodilation is established in response to hypotension causes constriction without compensation from alternative mechanisms. Awareness of these findings may be important when considering giving indomethacin to sick preterm infants during periods of cardiac instability.
大量生理数据表明，扩张性前列腺素在新生猪脑血管张力调节中起重要作用。本研究开始探讨这样一个假设，即包括前列腺素在内的多种扩张系统可在低血压时启动并维持脑血管舒张。对仔猪进行麻醉，并植入颅骨视窗。通过出血使动脉压降至对照值的50%来诱导低血压，并维持10分钟。每只仔猪在治疗前通过诱导低血压然后恢复至正常血压，以自身作为对照。软脑膜小动脉在低血压时会扩张（直径增加38±5%）。在低血压前20分钟及即将诱导低血压时静脉注射吲哚美辛（5mg/kg）预处理并不能阻断这种反应（直径分别增加28±7%和23±9%）。相比之下，在低血压期开始10分钟时给予吲哚美辛，已扩张的小动脉（106±6微米）会收缩至正常血压时的直径（75±5微米），并在观察期间一直保持收缩状态。这些发现表明，在出血性低血压前前列腺素合成和前列环素受体被阻断时，代偿机制可实现脑血管舒张。然而，在因低血压导致血管舒张建立后去除前列腺素会导致血管收缩，且没有其他机制的代偿。在考虑给心脏不稳定期的患病早产儿使用吲哚美辛时，了解这些发现可能很重要。
