Altered release of prostaglandins by opioids contributes to impaired cerebral hemodynamics following brain injury

被引:15
作者
Al-Turki, A
Armstead, WM
机构
[1] Childrens Hosp Philadelphia, Dept Anesthesia, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Anesthesia, Philadelphia, PA 19104 USA
[3] Univ Penn, Dept Crit Care Med, Philadelphia, PA 19104 USA
关键词
pigs; newborn; cerebral circulation; opioids; prostaglandins; brain injury; trauma; radioimmunoassay; cerebrospinal fluid; thromboxane; prostacyclin;
D O I
10.1097/00003246-199805000-00029
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Objectives: After fluid percussion brain injury (FPI) in the newborn pig, pial arteries constrict and responses to dilator stimuli, including opioids, are blunted. This study was designed to determine if altered release of prostaglandins contributes to blunted opioid dilation of cerebral arteries in newborn piglets following brain injury. Design: Prospective, in vivo, cerebral hemodynamic animal study. Setting: University research laboratory. Subjects: Newborn (1- to 5-days old) piglets of either gender. Interventions: In anesthetized, newborn, 1- to 5-day-old pigs, a closed cranial window was used to measure pial artery diameter and to collect cortial periarachnoid cerebrospinal fluid (CSF) for determination of 6-keto-PGF(1 alpha), the stable metabolite of prostaglandin I-2 (PGI(2)) and thromboxane B-2 (TXB2), the stable metabolite of TXA(2), via radioimmunoassay. FPI of moderate severity (1.9 to 2.3 atmospheres) was produced by using a pendulum to strike a piston on a saline-filled cylinder that was fluid coupled to the brain via a hollow screw inserted through the cranium. Measurements and Main Results: Methionine enkephalin (Met) vasodilation was blunted after FPI but was partially restored with indomethacin pretreatment (5 mg/kg iv) (8 +/- 1 [SEM] %, 13 +/- 1%, and 20 +/- 1% vs. 1 +/- 1%, 3 +/- 1%, and 5 +/- 1% vs. 7 +/- 1%, 10 +/- 1%, and 15 +/- 1%, respectively, for 10(-10), 10(-8),and 10(-6) M Met during control conditions, after FPI, and after FPI pretreated with indomethacin, n = 6). Similarly, restoration of Met dilation after FPI was observed with SQ 29,548, a TXA(2) antagonist. Met-induced 6-keto-PGF(1 alpha) release was blunted following FPI (889 +/- 20, 1130 +/- 33, and 1886 +/- 59 vs. 2630 +/- 36, 2775 +/- 30, and 2825 +/- 36 pg/mL for control, 10(-10), and 10(-6) M Met before and after FPI, respectively, n = 6). In contrast, Met-induced TXB2 release was enhanced after FPI (340 +/- 20, 423 +/- 25, and 473 +/- 30 pg/mL vs. 518 +/- 30, 726 +/- 90, and 901 +/- 35 pg/mL for control, 10(-10), and 10(-6) M Met before and after FPI, respectively, n = 6). Leucine enkephalin-and dynorphin-induced dilation and associated prostaglandin release were similarly altered following FPI. beta endorphin-induced constriction was enhanced following FPI, and these potentiated responses were blunted after indomethacin or SQ 29,548 pretreatment. Conclusions: These data show that FPI increases CSF 6-keto-PGF(1 alpha) and TXB2 concentrations. These data suggest that altered release of prostaglandins by opioids contribute to impaired cerebral hemodynamics following FPI in piglets.
引用
收藏
页码:917 / 925
页数:9
相关论文
共 39 条
[1]  
ARMSTEAD WM, 1990, J PHARMACOL EXP THER, V255, P1083
[2]   Role of vasopressin in altered pial artery responses to dynorphin and beta-endorphin following brain injury [J].
Armstead, WM .
JOURNAL OF NEUROTRAUMA, 1996, 13 (03) :115-123
[3]   THE ROLE OF OPIOIDS IN NEWBORN PIG-FLUID PERCUSSION BRAIN INJURY [J].
ARMSTEAD, WM ;
KURTH, CD .
BRAIN RESEARCH, 1994, 660 (01) :19-26
[4]   DIFFERENT CEREBRAL HEMODYNAMIC-RESPONSES FOLLOWING FLUID PERCUSSION BRAIN INJURY IN THE NEWBORN AND JUVENILE PIG [J].
ARMSTEAD, WM ;
KURTH, CD .
JOURNAL OF NEUROTRAUMA, 1994, 11 (05) :487-497
[5]  
ARMSTEAD WM, 1992, P SOC EXP BIOL MED, V199, P149
[6]   POSTISCHEMIC GENERATION OF SUPEROXIDE ANION BY NEWBORN PIG BRAIN [J].
ARMSTEAD, WM ;
MIRRO, R ;
BUSIJA, DW ;
LEFFLER, CW .
AMERICAN JOURNAL OF PHYSIOLOGY, 1988, 255 (02) :H401-H403
[7]  
ARMSTEAD WM, 1989, J PHARMACOL EXP THER, V251, P1012
[8]   RAPID PRODUCTION OF DIACYLGLYCEROLS ENRICHED IN ARACHIDONATE AND STEARATE DURING EARLY BRAIN ISCHEMIA [J].
AVELDANO, MI ;
BAZAN, NG .
JOURNAL OF NEUROCHEMISTRY, 1975, 25 (06) :919-920
[9]   REGIONAL DISTRIBUTION AND RATE OF PRODUCTION OF FREE FATTY ACIDS IN RAT BRAIN [J].
BAZAN, NG ;
BAZAN, HEPD ;
KENNEDY, WG ;
JOEL, CD .
JOURNAL OF NEUROCHEMISTRY, 1971, 18 (08) :1387-&
[10]   THE ROLE OF NITRIC-OXIDE IN OPIOID-INDUCED PIAL ARTERY VASODILATION [J].
DEVINE, JO ;
ARMSTEAD, WM .
BRAIN RESEARCH, 1995, 675 (1-2) :257-263