Hemorrhagic infarct induced by arterial hypertension in cat brain following middle cerebral artery occlusion.

Abstract

The purpose of this experiment was to determine whether an acute rise in brain perfusion pressure causes hemorrhagic transformation of an infarct without a reopening of the occluded artery. We raised the blood pressure of 22 cats by aortic obstruction 5-24 hours after transorbital middle cerebral artery clipping; hemorrhagic infarcts were induced in 11. Mean arterial blood pressure increased by 57.2 ±16.9 mm Hg (mean±SD) in the 11 cats with hemorrhagic infarcts and by 40.4 ±16.9 mm Hg in the 11 remaining cats with pale brain infarcts (p<0.05). Induction of hypertension increased regional cerebral blood flow in the ischemic cortical gray matter more in three cats with hemorrhagic infarcts than in seven with pale infarcts. Our results demonstrate that hemorrhagic transformation of an infarct can be induced by a rapid increase in perfusion pressure to brain tissue already exposed to focal ischemia. We also suggest that the restoration of blood flow through Ieptomeningeal collaterals plays an important role in the pathogenesis of hemorrhagic infarction in cases without reopening of occluded arteries. (Stroke 1990^1:589-595) S ince Fisher and Adams 1 first reported autopsy cases of cerebral embolism, hemorrhagic brain infarction has been thought of as a consequence of reperfusion of the damaged vascular bed by a reopening of the occluded artery.2 However, we recently demonstrated in human autopsy cases that hemorrhagic transformation of an infarct in persons with cardioembolic stroke may occur without a reopening of the occluded artery and that restoration of blood flow to the infarcted area through Ieptomeningeal collaterals on the surface of the brain is likely to be responsible for the hemorrhagic transformation in cases with surges of arterial hypertension. The pathogenesis of hemorrhagic infarction has been studied in experimental animals with 4 -6 and without 7 " 9 reopening of the occluded artery. In the latter, hemorrhagic transformation was attributed to underlying pathologic changes of the vasculature, such as hypertensive vascular changes preceding ischemia 8 or degenerative 7 or proliferative 9 vascular changes secondary to ischemia. These factors operate Received August 12, 1988; accepted October 31, 1989. in the presence of sufficient perfusion pressure of the infarcted area through Ieptomeningeal anastomoses. However, no previous study evaluated the mechanisms we proposed based on our observations of human autopsy cases. 3 Also, especially in early reports, 78 physiologic parameters were not adequately monitored. Thus, we designed this experiment to clarify whether a rapid rise in blood pressure causes hemorrhagic transformation of an infarct without a reopening of the occluded artery and to assess the relation between the pathologic distribution of ischemic changes and hemorrhage and the regional cerebral blood flow (rCBF) in cats with induced hypertension after middle cerebral artery (MCA) occlusion. Materials and MethodsWe anesthetized 29 cats weighing 2.4-4.3 kg with 10 mg/kg i.m. ketamine hydro...

Factors influencing acute blood pressure values in stroke subtypes

“…Since the diagnosis of haemorrhagic transformation was made from the CT scan performed 3-5 days after stroke onset in 32 out of 34 cases, a cause-effect relationship between elevated DBP values and haemorrhagic transformation could be assumed. Both experimental 39 and observational 8 studies have stressed the role of high blood pressure in the onset of an infarct, predisposing towards haemorrhagic transformation. Furthermore, excessively high BP values were associated with parenchymal haemorrhage in patients participating in clinical trials of recombinant tissue plasminogen activator.…”

Haemorrhagic transformation in acute ischaemic stroke following thrombolysis therapy: classification, pathogenesis and risk factors

“…This has led to a second theory suggesting the role of collateral circulation reperfusion injury. Ogata et al 25 indicated that HT may occur with persisting occlusion when infarcted areas are exposed to sufficient perfusion pressure from the leptomeningeal collaterals on the surface of the brain, the mechanism of which has also been demonstrated more recently in animal models 26…”

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

“…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.…”