G. De Ley

Hemispheric blood flow in the rat after unilateral common carotid occlusion: evolution with time.

Acute occlusion of one common carotid artery in the anesthetized normocapnic rat results in a moderate cerebral blood flow (CBF) decrease in both cerebral hemispheres. No asymmetrical perfusion is observed when the overall flow in each hemisphere is considered. The increase in blood flow which normally occurs in hypercapnia is strongly impaired in the cerebral hemisphere on the occluded side resulting in an important asymmetrical hemispheric perfusion. The days (1, 5, 15, 30) following unilateral carotid occlusion normal control CBF values are found in both hemispheres in normocapnic conditions. Hemispheric perfusion asymmetry in hypercapnia also becomes progressively less pronounced with time but a slight asymmetry still persists one month after unilateral carotid occlusion.

Experimental thromboembolic stroke studied by positron emission tomography : immediate versus delayed reperfusion by fibrinolysis

Acute obstruction of the middle cerebral artery (MCA) was obtained by injecting a single autologous blood clot into the internal carotid artery of dogs. The technique induced very reproducible unilateral ischemic lesions in the MCA territory; hemorrhagic transformation of the lesions was often seen. The hemodynamic and metabolic effects of blood clot embolism were studied in 35 dogs with positron emission tomography (PET) and the 15O steady-state technique, and compared with a control group of seven intact animals. In the acute phase, the involved brain tissue still had a nearly normal oxygen consumption (–11%) despite the lowered tissue perfusion (–20%) caused by the vascular obstruction. The lowered oxygen availability was compensated by an increased oxygen extraction ratio (+11%). Twenty-four hours after the insult, the hemodynamic situation had barely changed, and the ischemic event had evolved into a brain infarct in which oxygen consumption was clearly lowered (–25%) and accompanied by a significant lowering (–22%) of the oxygen extraction ratio compared with the acute situation. Therapeutic thrombolysis by local administration of streptokinase (500,000 IU), starting 30 min after the insult, was not able to salvage any brain tissue or to ameliorate tissue perfusion despite angiographically confirmed clot lysis. However, when fibrinolytic therapy was started within the first 5 min after the insult, hemispheric blood flow was normalized, and most of the threatened brain tissue was salvaged, as was indicated by its normalized oxygen consumption and oxygen extraction ratio. Early fibrinolysis was accompanied by definite clinical improvement and substantial reduction in the severity of the morphological lesions that were never hemorrhagic.

PET studies of changes in cerebral blood flow and oxygen metabolism after unilateral microembolization of the brain in anesthetized dogs.

Cerebral blood flow and oxygen metabolism have been measured with the steady—state oxygen‐15 technique and positron emission tomography in anesthetized dogs. Regional microembolization was induced by infusing Sephadex particles (diameter, 40 μm) into one of the common carotid arteries. In the first series of experiments, 2.5 mg Sephadex was infused, and the dogs were examined within 3–4 hours after embolization. In a second series 0.55 mg Sephadex was infused, and the dogs were examined either in the first 3–4 hours or 24–48 hours after embolization. Cerebral blood flow, oxygen extraction ratio, and cerebral oxygen utilization were measured at 3 Pco2 levels. In the acute experiments, cerebral oxygen utilization in the embolized hemisphere was 6 (0.55 mg Sephadex) and 25% (2.5 mg Sephadex) lower than on the contralateral side. While cerebral blood flow was symmetrically distributed in normocapnia and hypocapnia, it was 9 (0.55 mg Sephadex) and 35% (2.5 mg Sephadex) lower in the embolized hemisphere during hypercapnia. In normocapnia and hypocapnia the lower oxygen utilization in the embolized hemisphere was characterized by a lower oxygen extraction ratio, and in hypercapnia by an unchanged (0.55 mg Sephadex) or by a higher (2.5 mg Sephadex) extraction ratio. The different effect on oxygen extraction ratio in the control and embolized hemispheres resulted in images of uncoupling between perfusion and oxygen demand that varied according to the Pco2. The experiments also showed a fall in cerebral blood flow in the embolized hemisphere after 3–4 hours, indicating delayed hypoperfusion. After 24–48 hours, blood flow was about 10% higher in the embolized hemisphere, and this was observed at the 3 Pco2 levels, while the oxygen extraction ratio was systematically lower. Oxygen utilization in the embolized hemisphere was depressed to practically the same extent as in acute experiments. It can be concluded that between 4 and 24 hours after microembolization the cerebral microcirculation shows important changes, with installation of luxury perfusion in the face of an unchanging decreased oxygen metabolism. (Stroke 1987;18:128–137)

Streptokinase treatment versus calcium overload blockade in experimental thromboembolic stroke.

Thromboembolic brain ischemia was produced in dogs using an autologous blood clot model. The effect of postembolic treatment with flunarizine and streptokinase on hemispheric cerebral metabolic rate for oxygen (CMRO2), oxygen extraction ratio (OER), and cerebral blood flow (CBF) was studied by positron emission tomography (oxygen-15 technique) 24 hours after the insult. We studied five groups of experimental dogs and compared them with a control group of nonembolized dogs. Group I received no treatment, Group II was treated locally with 500,000 IU streptokinase starting 30 minutes after the insult, Group III received streptokinase locally 30 minutes after the insult and 0.1 mg/kg i.v. flunarizine immediately after the insult and 2 hours later, Group IV received flunarizine as Group III, and Group V was orally pretreated with 0.5 mg/kg/day flunarizine during 2 weeks preceding embolization. Compared with the contralateral hemisphere, in the embolized hemisphere a significant reduction of CMRO2 (-25% to -40%) and CBF in normocapnia (-35%) and hypercapnia (-50%) was observed in Groups I, II, and V. In Groups III and IV, CMRO2, OER, and CBF of the embolized hemisphere were within the normal range during normocapnia and hypercapnia; the extent of the ischemic lesions was markedly less than in the other groups of experimental dogs. We conclude that flunarizine treatment after experimental thromboembolic stroke had a favorable influence on brain tissue. Chronic preventive flunarizine treatment failed to have a beneficial effect.

Influence of an increased intracranial pressure on cerebral and systemic haemodynamics during endoscopic neurosurgery: an animal model

BACKGROUND During endoscopic neurosurgery, direct mechanical stimulation of the brain by the endoscope and increased intracranial pressure (ICP) caused by the continuous rinsing can induce potentially lethal haemodynamic reflexes, brain ischaemia, and excessive fluid resorption. METHODS In a newly presented rat model of endoscopic neurosurgery, stereotactic access to the cerebrospinal fluid was secured and the ICP was increased by controlled infusion until complete suppression of the cerebral perfusion pressure (CPP). The haematocrit (Hct) level was determined before and after the procedure. During the whole procedure, invasive arterial pressure, ICP, and heart rate were continuously recorded and evaluated in a subsequent offline analysis. After the procedure, the animals were allowed to recover and 7 days later they were killed for histological examination. RESULTS Suppression of the CPP resulted in a severe hypertension combined with tachycardia or mild bradycardia. The Hct decreased from 41 to 35 over the minutes of CPP suppression. After cessation of the infusion, the ICP decreased to 37% of the plateau pressure within 2.5 s. In the first few minutes after restoration of normal ICP, five animals died because of pulmonary oedema. CONCLUSIONS Upon complete suppression of the CPP, an obvious hypertension developed, often together with tachycardia, but no severe bradycardia. At high ICP levels, we observed an important translocation of irrigation fluid to the vascular space. Fatality was not caused by ischaemia or arrhythmia but due to pulmonary oedema.

Hemodynamic and metabolic effects of flunarizine in experimental subarachnoid hemorrhage in dogs.

Cerebral blood flow and oxygen metabolism were measured and a cerebral angiography was performed in dogs with experimental subarachnoid hemorrhage to assess the relation between arterial narrowing (vasospasm) and the fall of blood flow. Cerebral blood volume and the cerebrovascular CO2 reactivity were also measured to estimate the cerebrovascular reserve. Several groups of dogs were treated with flunarizine in different regimens to assess its possible therapeutic effect.The experiments were performed in the three-hemorrhage canine model for subarachnoid hemorrhage. Cerebral blood flow and cerebral oxygen metabolism were measured in anesthetized (nitrous oxide) dogs using positron emission tomography in combination with the 15O steady-state method. Basilar artery diameter was evaluated by digital subtraction angiography.In normal dogs, cerebral blood flow, oxygen consumption, and oxygen extraction ratio were 46.4 +/- 9.0 ml/100 ml per minute, 3.65 +/- 0.76 ml/100 ml per minute, and 39.9 +/- 3.4%, respectiv...

Cerebrovascular reserve in the cat after acute bilateral carotid occlusion

Cerebral blood flow in the cat was studied before and after acute bilateral common carotid occlusion under normocapnic and hypercapnic conditions and after induced hypotension. Regional blood flow to different brain structures was studied with the microsphere method. Local blood flow in the caudate nucleus, the cerebral cortex and medulla oblongata was studied with H2-polarography. Although the blood flow to the anterior brain regions is significantly decreased after bilateral common carotid occlusion, their blood supply is kept above ischaemic levels by re-distribution of the vertebrobasilar flow. Cerebrovascular reserve in anterior brain regions, however, is lost as indicated by the severe impairment of both the flow response to hypercapnia and to blood pressure decrease. After bilateral common carotid occlusion paradoxical CO2-reactions, indicating intracerebral steal, were seen in the caudate nucleus. In posterior brain regions resting blood flow, flow-reaction to hypercapnia and to hypotension are better preserved under these conditions. Measurement of the CBF responses to induced hypercapnia is a dependable test for appreciation of cerebrovascular reserve after cerebrovascular occlusion but may be potentially hazardous where local flow is close to ischaemic levels.

Cerebral histamine in hypoxia

AbstractHistamine in the brain is located in at least two cell types: neurons and mast cells. Neuronal histamine is found in the synaptosomal fraction, has a rapid turn-over rate and is accepted to play a neurotransmitter role. Experimental evidence exists that histamine, is active in the central regulation of blood pressure, arousal, drinking behaviour, mood, reaction to stress and thermoregulation. Mast cell histamine is storedin vesicles and has a slow turnover rate. Its function in the CNS remains obscure(For a review see: Schwartz 1975; Gross, 1982). Stressful situations (platform, airblast, restraint…) are reported to increase or decrease cerebral histamine turnover rate with or without changing endogenous histamine levels (Mazurkiewicz-Kwilecki & Bielkiewicz, 1982).