Hemorrhagic Cerebral Infarction by Arterial Occlusion

Recent success with thrombolytic therapy for acute myocardial infarction has stimulated interest in its use for stroke. To determine the hemorrhagic potential of thrombolytic therapy in experimental cerebral infarction, we compared a group of tissue plasminogen activator-treated rabbits (a = 4) with 2 groups of streptokinase-treated rabbits (n = 6 in each), as well as with 3 groups of heparin-treated rabbits (n = 5 in each) and untreated controls (n = 12). Focal cerebral infarction was produced in rabbits by occlusion of the right common carotid and middle cerebral arteries coupled with 2 hours of halothane-induced hypotension. Treatment with heparin or thrombolytic agents began 24 hours after occlusion. One additional group was treated with streptokinase 1 hour after occlusion (n = 6) to determine the hemorrhagic potential of thrombolytic agents in evolving infarction. Rabbits were killed 29-33 hours after occlusion, and brain sections were examined using light microscopy. The results demonstrate that microscopic hemorrhage is frequently present in infarcted tissue irrespective of treatment. Gross cerebral hemorrhage did not occur in untreated rabbits or in rabbits treated with streptokinase 1 hour after occlusion. Only rabbits treated with streptokinase, tissue plasminogen activator, or excessive doses of heparin 24 hours after occlusion, at a time when cerebral infarction was well established, exhibited gross hemorrhage in the area of infarction. These data suggest that treatment of ischemic stroke with thrombolytic agents carries an increased risk of cerebral hemorrhage unless the agents are given early after the onset of symptoms. (Stroke 1987;18:1148-1156)

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 91%

See 1 more Smart Citation

Hemorrhagic complications of thrombolytic therapy in experimental stroke.

Slivka

Pulsinelli

1987

“…Hemorrhagic transformation has been modeled in the dog, cat, primate, rabbit, and rat in which single arterial occlusion generates focal ischemia. 88,89 Canine models subject to hypertension 90,91 and hematomas induced in the maturing infarction in rhesus monkeys by arterial BP elevation 92 consistently produce hemorrhages encapsulated within structural boundaries (eg, putamen, globus pallidus, claustrum). Current thromboembolic models do not resemble these types of lesions.…”

Section: Animal Models Of Hemorrhage-associated Brain Injurymentioning

confidence: 99%

Priorities for Clinical Research in Intracerebral Hemorrhage

Morgenstern

Woodbury-Harris²,

Marler³

2005

118

“…5 The predisposing factor(s) responsible for HT are not well defined, although etiology (thrombotic versus embolic), [5][6][7] collateral circulation, 8,9 reperfusion, 10 hypertension, 6,8,[11][12][13] size of the ischemic lesion, 5,14 -20 and the use of anticoagulants, thrombolytics, [21][22][23][24] or both have been implicated. No precise predictors of HT have been determined, but caution is suggested when thrombolysis is considered in patients with early x-ray CT signs of major stroke such as sulcal effacement, mass effect, edema, or possible hemorrhage 25,26 or National Institutes of Health Stroke Scale score greater than 22.…”

Section: See Editorial Comment Page 151mentioning

confidence: 99%

Prediction of Impending Hemorrhagic Transformation in Ischemic Stroke Using Magnetic Resonance Imaging in Rats

Knight

Barker

Fagan

et al. 1998

100

Background and Purpose-Hemorrhagic transformation (HT) of ischemic brain tissue may occur in stroke patients either spontaneously or after thrombolysis. A method to assess the risk of HT in ischemic tissue after stroke would improve the safety of thrombolytic therapy. As a means of predicting HT, we investigated the role of contrast-enhanced MRI at acute time points in a rat middle cerebral artery occlusion model with reperfusion. Methods-Intraluminal suture occlusion of the middle cerebral artery was used to produce transient ischemia in male Wistar rats (nϭ11). Reperfusion was performed by withdrawal of the occluding filament after 2 (nϭ4), 3 (nϭ6), or 4 (nϭ1) hours. MRI studies were performed before and after reperfusion with the use of conventional T1-weighted imaging, with and without gadolinium (Gd-DTPA) contrast agent, and T2-weighted imaging. Follow-up MRI and histological studies were obtained at 24 hours. Results-Petechial hemorrhage occurred by 24 hours in 9 of 11 animals. All animals showed brain swelling and cellular death throughout the ischemic region at 24 hours. A hyperintense region in the preoptic area became visible after Gd-DTPA injection within minutes after reperfusion in animals with subsequent HT. All animals showing acute Gd-DTPA enhancement subsequently developed petechial hemorrhage (or died) by 24 hours. In these animals, statistically significant differences in signal intensity (Pϭ.0005) between the ipsilateral enhancing region and a homologous contralateral region were detected on post-Gd-DTPA T1-weighted imaging. There was also a statistically significant correlation (Pϭ.01) between the rate of Gd-DTPA uptake and the size of the enhancing area. Two animals did not enhance with Gd-DTPA and did not exhibit hemorrhage on histological examination or MRI at 24 hours. No abnormalities were seen on precontrast T1-weighted images before and shortly after reperfusion or postcontrast T1-weighted images before reperfusion. Conclusions-The primary finding of this study was the detection of early Gd-DTPA parenchymal enhancement in 82% of the animals after reperfusion. Enhancement was seen before any detectable hemorrhage, suggesting that early endothelial ischemic damage occurs before gross brain infarction and hemorrhage. Thus, we suggest that acute Gd-DTPA enhancement may provide an early prediction of petechial hemorrhage. (Stroke. 1998;29:144-151.)