Hemorrhagic infarct conversion in experimental stroke.
OBJECTIVE
This study investigated the relations between hemorrhagic infarction and occlusion, release, levels of glycemia, brain energy state, and lactate content after cerebrovascular occlusion.


METHODS
Prospective, controlled laboratory investigation.


METHODS
One hundred six pentobarbital-anesthetized cats.


METHODS
The middle cerebral artery was occluded with a Yasargil clip transorbitally either temporarily (0.5, four, and eight hours) or permanently. Normoglycemic and hyperglycemic animals were closely monitored for eight hours. Brain pathology was assessed after two weeks' survival or at the time of spontaneous animal death. Topographic brain metabolite studies were carried out after four hours of middle cerebral artery occlusion.


RESULTS
Morphometric quantitation of cerebral hemorrhage and infarction and fluorometric determinations of blood and brain tissue, glucose, glycogen, lactate, adenosine triphosphate, and phosphocreatine from 16 topographic brain sites were carried out. Twenty-one of 82 (25.6%) animals evaluated neuropathologically showed hemorrhagic infarcts. Occluding the artery in hyperglycemic animals caused fivefold more frequent and 25-fold more extensive hemorrhage into infarcts than in normoglycemic animals. Temporary occlusion with clip release after four hours in hyperglycemic animals caused the most extensive hemorrhage into infarcts. Most hemorrhages into infarcts (81%) took place in animals that died within a few hours after they experienced ischemia and that showed infarction and marked edema of the entire middle cerebral artery territory. Linear regression analyses demonstrated a close relation between hemorrhage into infarcts and near-total energy depletion (adenosine triphosphate, less than 0.3 microM/g; phosphocreatine, less than 0.5 microM/g) in brain sites that showed extremely high tissue lactate concentrations (more than 30 microM/g). The biochemical changes that correlated with hemorrhage into infarcts were more marked than those with infarcts without hemorrhage.


CONCLUSIONS
Hyperglycemia and restoration of blood flow to ischemic territories were strong risk factors for hemorrhagic infarct conversion. Concomitant tissue metabolic changes suggest that marked tissue energy depletion accompanied by acidosis damages brain vessels and renders them penetrable for edema fluid and, ultimately, red blood cell extravasation.
de Courten-Myers
G M
GM
Department of Pathology, University of Cincinnati, Ohio.
Kleinholz
M
M
Holm
P
P
DeVoe
G
G
Schmitt
G
G
Wagner
K R
KR
Myers
R E
RE
D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D001923:Brain Chemistry; D002545:Brain Ischemia / Q000150:complications* / Q000209:etiology / Q000378:metabolism; D002415:Cats; D002536:Cerebral Arteries; D002543:Cerebral Hemorrhage / Q000453:epidemiology / Q000209:etiology*; D002544:Cerebral Infarction / Q000150:complications* / Q000209:etiology / Q000378:metabolism; D003250:Constriction; D005947:Glucose / Q000032:analysis; D006943:Hyperglycemia / Q000150:complications; D007773:Lactates / Q000032:analysis; D019344:Lactic Acid; D016014:Linear Models; D010725:Phosphocreatine / Q000032:analysis; D011446:Prospective Studies; D012307:Risk Factors
D007773:Lactates; D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D005947:Glucose