Assessment of Cerebral Oxygenation During Acute Ischemia
1Dunn, Jeffrey F.; 1Nwaigwe, Casmiar; 2Grinberg, Oleg Y.; 1Lei, Hao;
1Williams, Heather
1NMR Center, Department of Diagnostic Radiology, Dartmouth Medical School,
Hanover, NH 03755 - USA; 2EPR Center for the Study of Viable Biological
Systems, Dartmouth
Medical School, Hanover, NH 03755 – USA
INTRODUCTION: This study is investigating the relationship between
tissue oxygenation during
ischemia/reperfusion, and outcome from the ischemic insult. Although it is
obvious that oxygen
plays a major role in cell death associated with both hypoxia and ischemia,
it is still unclear
what the dangerous levels are within the brain itself. We will examine the
relationship between
tissue oxygen tension and the cellular energetic status during hypoxia and
ischemia. It is
possible that the triggers for various chains of events, ranging from loss
of metabolic control to
progressive oxidative damage, are intimately involved in the responses of
metabolic processes
to changes in pO2. We propose that there is such a link, and that measuring
tissue pO2 in parallel
with brain energetics and lipid peroxidation (as an assessment of oxidative
damage) will
provide valuable new information on the pathogenesis of stroke induced
injury.
We are studying the time-course of the changes in cerebral oxygenation, and
relating these
to outcome. We know that hypothermia provides significant protection to the
ischemic/hypoxic
brain and so are comparing pO2 with and without hypothermia. We are using
EPR oximetry to
relate interstitial pO2 in ischemia to the outcome of the ischemic event.
METHODS: We are using a 4-vessel rat model of global ischemia. EPR
oximetry material (LiPc) is
implanted in the cortex 3-5 days before the study. The vertebral arteries
are cauterized 2-3 days
before the study. On the study day, the animals are anesthetized with
isoflurane, paralyzed with
pancuronium and artificially ventilated. Temperatures are monitored in the
core and brain with
thermocouples. Temperatures are controlled by placing the rats on a
water-regulated blanket.
The carotid arteries were exposed, and either a surgical tie or inflatable
balloon passed around
them (for reversible occlusion). The animals are positioned in an EPR
machine operating at 1.2
GHz with a loop resonator positioned over the implant.
Three groups of animals were studied, one normothermic with only carotid
occlusion (two
vessel occlusion), one normothermic with 4 vessel occlusion and one
hypothermic with 4 vessel
occlusion. Ischemia was for 10 minutes followed by 30-60 minutes of
recovery.
RESULTS: The two vessel occlusion (data not shown) resulted in a
decline of PtO2 by approximately
30%. These data were used as “controls” to determine if the 4-vessel
occlusion was working.
The logic was that the 4-vessel should have more severe hypoxia than that in
the two vessel and
so the tissue PtO2 should be lower. If this did not occur, we assumed that
the vertebral arteries
were not properly occluded and did not use the animal.
The results indicate that the hypothermic groups have similar values for
PtO2 during
ischemia, but may have a delayed recovery of PtO2 (see figure) This may
relate to the protective
effect of hypothermia, if it reduces the amount of oxidative damage during
reperfusion.
Conversely, the literature on hypothermic coronary bypass surgery indicates
that hypothermia is
associated with increased cerebral damage. A delayed reperfusion of the
brain has been noted
during hypothermic coronary bypass surgery. These data on tissue PtO2 now
need to be
correlated with cell damage and perfusion (studies which we are now
initiating), to determine if
the delay in recovery of PtO2 is protective or damaging to the brain.
EPR oximetry was used to measure interstitial pO2 in an anesthetized rat.
The 4-vessel ischemia model
was used with carotid and vertebral artery occlusion. The data are expressed
as % difference from
the pre-ischemic point. This point is the average of 4 EPR spectra obtained
over 10 minutes before ischemia.
The vertical line indicates the end of ischemia. The hypothermic group
(brain temperature = 32°C)
was compared with a normothermic group (brain temperature = 36-37°C). There
was a significant delay in
re-oxygenation in the hypothermic group (mean±SE, n=5).
Figure Legend.
Cortical oxygenation
during ischemic/reperfusion. EPR oximetry was used to measure interstitial pO2
in an anesthetized rat. The 4-vessel ischemia model was used with carotid and
vertebral artery occlusion. The data are expressed as % difference from the
pre-ischemic point. This point is the average of 4 EPR spectra obtained over 10
minutes before ischemia. The vertical line indicates the end of ischemia. The
hypothermic group (brain temperature = 32°C)
was compared with a normothermic group (brain temperature = 36-37°C). There was a significant delay in
re-oxygenation in the hypothermic group (mean±SE, n=5).