阿片类药物与类前列腺素系统对低血压仔猪脑血流的调控作用

Armstead W M, Mirro R, Busija D W, Leffler C W

Department of Physiology and Biophysics, University of Tennessee, Memphis 38163.

J Cereb Blood Flow Metab. 1991 May;11(3):380-7. doi: 10.1038/jcbfm.1991.78.

The interaction between opioid and prostanoid mechanisms in the control of cerebral hemodynamics was investigated in the conscious hypotensive piglet. Radiomicrospheres were used to determine regional cerebral blood flow (rCBF) in piglets pretreated with the opioid receptor antagonist, naloxone, or its vehicle, saline, during normotension, hypotension, and after the administration of indomethacin, a cyclooxygenase inhibitor, during hypotension. Hemorrhage (30 ml/kg) decreased systemic arterial pressure from 68 +/- 12 to 40 +/- 10 mm Hg but did not decrease blood flow to any brain region. Indomethacin treatment (5 mg/kg) of hypotensive piglets decreased blood flow to all brain regions within 20 min; this decrease in CBF resulted from increases in cerebral vascular resistance of 65 and 281% at 20 and 40 min after treatment, respectively. In hypotensive piglets, cerebral oxygen consumption was reduced from 2.62 +/- 0.71 to 0.53 +/- 0.27 ml 100 g-1 min-1 and to 0.11 +/- 0.04 ml 100 g-1 min-1 at 20 and 40 min following indomethacin, respectively. Treatment with naloxone (1 mg/kg) had no effect on rCBF, calculated cerebral vascular resistance, or cerebral oxygen consumption of normotensive or hypotensive piglets. However, decreases in CBF and oxygen consumption and increases in cerebral vascular resistance upon treatment of hypotensive piglets with indomethacin were attenuated in animals pretreated with naloxone. These data indicate that the removal of prostanoid modulation of an opioid-mediated constrictor influence on the cerebral circulation is a potential mechanism for the increase in cerebral vascular resistance that follows indomethacin treatment of hypotensive piglets.

在清醒的低血压仔猪中研究了阿片类药物与前列腺素机制在控制脑血流动力学中的相互作用。在正常血压、低血压期间以及在低血压期间给予环氧化酶抑制剂吲哚美辛后，使用放射性微球测定用阿片受体拮抗剂纳洛酮或其赋形剂生理盐水预处理的仔猪的局部脑血流量（rCBF）。出血（30 ml/kg）使全身动脉压从68±12 mmHg降至40±10 mmHg，但并未减少流向任何脑区的血流量。对低血压仔猪进行吲哚美辛治疗（5 mg/kg）在20分钟内减少了所有脑区的血流量；这种脑血流量的减少分别是由于治疗后20分钟和40分钟脑血管阻力增加了65%和281%。在低血压仔猪中，脑氧耗量在吲哚美辛治疗后20分钟和40分钟分别从2.62±0.71 ml 100 g-1 min-1降至0.53±0.27 ml 100 g-1 min-1和0.11±0.04 ml 100 g-1 min-1。用纳洛酮（1 mg/kg）治疗对正常血压或低血压仔猪的rCBF、计算出的脑血管阻力或脑氧耗量没有影响。然而，在用纳洛酮预处理的动物中，用吲哚美辛治疗低血压仔猪后，脑血流量和氧耗量的减少以及脑血管阻力的增加有所减弱。这些数据表明，去除前列腺素对阿片介导的脑血管收缩影响的调节是吲哚美辛治疗低血压仔猪后脑血管阻力增加的潜在机制。