Perfusion pressure breakthrough threshold of cerebral autoregulation in the chronically ischemic brain: an experimental study in cats

Abstract

A study was designed to investigate hyperperfusion syndrome after the restoration of normal cerebral blood flow in a chronically cerebral ischemic state resulting from high-flow arteriovenous malformations or severe carotid stenosis. A fistula between the left distal common carotid artery and the jugular vein was created and the left vertebral artery was simultaneously occluded in 44 cats to produce a chronic cerebral ischemic state. For control experiments, 10 cats underwent occlusion of the left common carotid and vertebral arteries. Six weeks later, pial arterial behavior, disruption of the blood-brain barrier (BBB), and cerebral histological changes were investigated using three experimental methods. In the first, in which a fistula was occluded under normal conditions, pial arteries contracted to some 80% of the resting state; however, no BBB disruption or histological changes were observed. In the second experiment, in which a 20-minute occlusion of the left middle cerebral artery was performed in the cats with a patent fistula, a 30% to 40% dilated state of the pial arteries continued after recirculation, and BBB disruption-induced cerebral edema and infarction were observed. These findings were more prominent in the cats that underwent occlusion of the fistula. On the other hand, in the control group, the pial arteries returned to resting size within 40 minutes, and no BBB disruption or histological changes were observed. In the third experiment, in which moderate hypertension was induced for 1 hour, the pial arteries dilated much more remarkably; BBB disruption and cerebral edema were revealed to be more extensive in the cases of fistula occlusion than within those with a patent fistula. In the control group, however, the pial arteries contracted 10% during hypertension, while BBB disruption and histological changes were not evident. The results indicate that the perfusion pressure breakthrough threshold in the chronically ischemic brain may not be reduced by the restoration of normal blood flow, but may be decreased by the addition of new ischemic insults or hypertension.

Pathophysiology and management of reperfusion injury and hyperperfusion syndrome after carotid endarterectomy and carotid artery stenting

“…Preoperative longstanding hypertension leads to endothelial dysfunction and microangiopathy which can result in a breakdown of the blood brain barrier (BBB). Breakdown of the BBB was observed previously in an animal model of cerebral hyperperfusion [10]. There is evidence of extravasation of serum albumin after BBB breakdown in animal experiments showing that there is activation of the transforming growth factor beta (TGFβ) signaling pathway.…”

Blood–brain barrier breakdown as a novel mechanism underlying cerebral hyperperfusion syndrome

“…Breakdown of the BBB was observed in an animal model of cerebral hyperperfusion [19]. Recent animal experiments have shown that increased permeability of brain blood vessels induces neuronal hyperexcitability [2–4, 7, 21], delayed neuronal degeneration and impairment of cortical function [4, 22].…”

Intracranial hemorrhage and hyperperfusion syndrome following carotid artery stenting

“…Additional efforts to reduce the risk of ICH may include limiting the duration of balloon inflation and employing emboli-prevention devices. These measures help minimize procedural brain ischemia, which potentiates the risk of HPS and ICH (4,24,26). If patients develop clinical symptoms suggestive of HPS or if patients have a documented elevation in MCA velocities to twice their baseline value we typically withhold antiplatelet agents until symptoms have resolved and the blood pressure is optimally controlled.…”

“…This results in increased CBF after recanalization; thus the term "hyperperfusion." This model of HPS is supported by findings of noninvasive testing such as transcranial Doppler ultrasound (TCD), by histopathology on postmortem examinations, and by experimental studies in animal models (9,10,24,26).…”