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Lysophosphatidic acid reduces microregional oxygen supply/consumption balance after cerebral ischemia‐reperfusion
Author(s) -
Weiss Harvey R.,
Mellender Scott J.,
Kiss Geza,
Liu Xia,
Chi Oak
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02448
Subject(s) - ischemia , lysophosphatidic acid , cerebral blood flow , medicine , middle cerebral artery , hemodynamics , anesthesia , cardiology , chemistry , receptor
Lysophosphatidic acid (LPA) is a small phospholipid signaling molecule, whose levels are increased after cerebral ischemia. We hypothesized that exogenous LPA would increase the size of infarct and reduce microregional O 2 supply/consumption balance after cerebral ischemia‐reperfusion. This was tested in isoflurane‐anesthetized rats with middle cerebral artery blockade for 1 hr and reperfusion for 2 hr with or without LPA (1 mg/kg, at 30, 60 and 90 min after reperfusion). Regional cerebral blood flow was determined using a C 14 ‐iodoantipyrine autoradiographic technique. Regional small vessel (20–60 μm diameter) arterial and venous oxygen saturations were determined microspectrophotometrically. There were no significant hemodynamic or arterial blood gas differences between groups. The control ischemic‐reperfused cortex had a similar O 2 consumption to the contralateral cortex. However, microregional O 2 supply/consumption balance was significantly reduced in the ischemic‐reperfused cortex with many areas of low O 2 saturation (43 of 80 veins with O 2 saturation below 50%). LPA did not significantly alter cerebral blood flow, but it did significantly increase O 2 consumption of the ischemic‐reperfused region. It also significantly increased the number of small veins with low O 2 saturations in the reperfused region (76 of 80 veins with O 2 saturation below 50%). This was associated with a significantly increased cortical infarct size after LPA administration (11.4 ± 0.5% control vs 16.4 ± 0.6% LPA). This suggests that LPA reduces cell survival and that it is associated with an increase in the number of small microregions with reduced local oxygen balance after cerebral ischemia‐reperfusion.