Jes Olesen

Regional Cerebral Blood Flow in Man Determined by the Initial Slope of the Clearance of Intra-arterially Injected l33Xe

The regional cerebral blood flow can be calculated from the initial slope of the logarithmically displayed clearance curve following intra-arterial injection of 133Xe (rCBFinitial). The relationship between this parameter and the values resulting from stochastic (height over area) and compartmental analyses is extensively discussed. Experimental results demonstrate the theoretically expected close relationship between rCBFinitial and flow of gray substance (rCBFinitial 20% to 30% lower than Fg). It is shown how the cerebral clearance curve (normally biexponential) with low flow values becomes gradually monoexponential. Thus only flow of gray substance changes, whereas flow of white substance is independent of CBF∞. CBF10 was shown to overestimate CBF∞ with about 15% independent of the flow level. Correlation between CBFinitial and CBF10 was linear (r=0.98) at CBF10 values above 20 ml/100 gm/min.nnThe CBFinitial normal value is found to be 64±9 ml/100 gm/min, and the interchannel coefficient of variation is 8.2%. A correction for remaining radioactivity from previous measurements is described. Using this, no significant difference was found between repeated resting state measurements.nnThe CBFinitial-Paco2 relationship was found to be best described as exponential. In a group of patients with various intracranial diseases, 1 mm Hg change in Paco2 resulted in 4% change of CBFinitial quite independent of the CBFinitial level.

Restoration of autoregulation of cerebral blood flow by hypocapnia

DURING RECENT YEARS, a state of cerebral vasomotor paralysis has been demonstrated in foca2Zy diseased brain tissue in patients with apoplexy and intracranial tumors. 14 In these vasoparalytic areas there is a loss of autoregulation normally the cerebral blood flow is independent of the arterial blood pressure within wide limits and a loss of the normal response to changed arterial carbon dioxide tension (PaCOz) vasodilation during increased PaCOz and vasoconstriction during decreased PaCOz. Moreover, in some patients with apoplexy or intracranial tumors it has been observed that the vasomotor function also may be affected in nonfocal parts of the diseased hemisphere. Here, an impaired autoregulation but a preserved reaction to changes ofthe PaCOz was observed. 2-6 This nonfocal loss of autoregulation has been called global, as it was expected that a loss of autoregulation would also be present in the contralateral “nondiseased” hemisphere. It was also predicted that the global loss of autoregulation might be restored by hypocapnia.6 A restoration of autoregulation by hypocapnia might be of essential importance for the possible beneficial effect of the therapeutic use of hyperventilation in patients with intracranial diseases, as will be further commented on in the Discussion. In the present study the autoregulation has been examined in the nondiseased hemisphere of patients with apoplexy or intracranial tumors at different levels of PaCOz to test the abovementioned predictions. patients were studied under general anesthesia induced by 300 mg. of thiopental sodium and 30 mg. of d-tubocurarine chloride and maintained with oxygen and nitrous oxide (1:2). Relaxation was maintained with repeated doses of 5 to 10 mg. d-tubocurarine chloride. Regional c e r e b r a l blood P o w ( r C B F ) measurements were performed in the nondiseased hemisphere (contralateral to the focal lesion) in all patients. After stabilization of PaCOz at about the patient’s own level as recorded during spontaneous respiration before anesthesia, 2 flow measurements were carried out at intervals of fifteen minutes. The first was made during normotension and the second during hypertension induced by infusion of angiotensin (Hypertensin@). Thereafter the patient was hyperventilated, and following stabilization of the PaCOz at about 25 mm. Hg (after forty-five to sixty minutes ) , 2 more measurements were taken during normotension and hypertension. The 133Xe intracarotid injection method was used for the rCBF measurements and the flow was determined in 35 regions of the nondiseased hemisphere. This method has been described in detail p r e v i ~ u s l y ~ ~ ~ ~ * and shall be only briefly summarized here. A small polyethylene catheter was placed into the internal carotid artery by means of the Seldinger technique. Then, 2 to 3 mc. of 133Xe dissolved in 3 ml. of isotonic saline were injected rapidly (one to two seconds) through the catheter into the internal carotid artery. The clear-

The Effect of Intra-arterial Papaverine on the Regional Cerebral Blood Flow in Patients with Stroke or Intracranial Tumor

The effect of intracarotid injection of 10 mg of papaverine on regional cerebral blood flow was measured in 27 patients. Most of the patients had cerebral infarction or intracranial neoplasm. The intra-arterial 133Xenon injection method was used and 16 or 35 regions of the diseased hemisphere were monitored. In patients without focal flow abnormalities an average flow increase of 93% followed the injection. In patients with focal abnormalities of cerebral blood flow the intra-arterial injection of papaverine produced a decrease in focal flow or less increase in flow than normal. It is concluded that vasodilator therapy presumably decreased flow in pathological tissue and that such treatment should not be employed in the therapy of cerebrovascular disease.

Classic migraine: A prospective recording of symptoms.

Systematic prospective records of aura symptoms were obtained from 50 patients, who filled in report forms during the aura phase of two attacks. The pattern of the various aura symptoms was remarkably constant during two attacks. Visual aura was recorded by 94% of the patients, somato‐sensory aura symptoms by 40%, motor disturbances by 18% and speech difficulties by 20%. Visual aura was unilateral in 55%, somato‐sensory aura symptoms were unilateral in 80% and motor aura was unilateral in 100%. Surprisingly, headache was absent in 20% of the aura attacks. When unilateral headache and unilateral aura symptoms occurred in the same attack, headache was most often contralateral to the somato‐sensory and motor aura symptoms. Our observations are in accordance with the hypothesis that the pathophysiological process responsible for the aura symptoms in classic migraine starts at the visual cortex.

Cerebral oxygen extraction, oxygen consumption, and regional cerebral blood flow during the aura phase of migraine.

Background and Purpose The aura phase of migraine is associated with focal blood flow changes, but it has been largely unknown whether these changes are correlated to changes in the cerebral metabolism. Methods Eight patients required carotid angiography for evaluation of transient neurological attacks. Cerebral blood flow (CBF) results, angiography, and clinical observations subsequently suggested the diagnosis: migraine with aura and occasional aura attacks without headache. In the same setting the cerebral angiography was followed by four to six repeated recordings of regional CBF using the intra-arterial 133Xe injection method. Blood samples were drawn from the carotid artery and the internal jugular vein to measure oxygen extraction fraction and cerebral metabolic rate for oxygen. Results The intracarotid regional CBF technique provoked aura symptoms and typical, migraine-related, posterior focal hypoperfusion in four patients, followed by typical unilateral headache in three patients. The remaining four patients had no symptoms or regional CBF changes during the examination. There was a significant increase (mean, 13%) of global oxygen extraction fraction in the four patients during aura symptoms, whereas no significant changes of oxygen extraction fraction were found in the nonsymptomatic group. The increase in global oxygen extraction fraction in the symptomatic group coincided with a drop of hemispheric CBF (mean, 12%). Cerebral metabolic oxygen rate remained essentially unchanged, as did Paco2. Conclusions The data presented suggest that the focal flow reduction during the migraine-aura phase is not a secondary phenomenon of reduced cerebral metabolism. However, arte riolar vasoconstriction might offer a possible explanation for the regional CBF changes observed during the migraine aura.

Cerebral Apoplexy (Stroke) Treated With or Without Prolonged Artificial Hyperventilation: 1. Cerebral Circulation, Clinical Course, and Cause of Death

Fifty patients with severe cerebral apoplexy were treated with artificial hyperventilation of three days duration facilitated by general anesthesia (barbiturates and muscle relaxants) and instituted within the first day after onset of the attack. After a classification according to carotid angiographical findings, degree of consciousness and focal symptoms, a random allocation was performed so that 24 patients were subjected to moderate hypocapnia (PaCO2 about 25 mm Hg) and 26 patients to normocapnia (PaCO2 about 40 mm Hg). Afterward, 21 comparable patients not receiving ventilatory treatment were studied. The clinical course and the mortality rate showed no statistically significant differences between the three groups. All patients studied disclosed a longstanding (12 days) spontaneous hyperventilation. The ventilation treatment was followed by a low cerebral perfusion pressure and a high rate of pulmonary complications. Autopsies from all groups studied typically showed tentorial herniation and pathological lung changes. In 32 of the patients without occlusion of the carotid artery the regional cerebral blood flow was measured before hyperventilation treatment was applied. A low mean flow and focal abnormalities (ischemia, hyperemia, vasoparalysis) typically were found and in good correlation to the autopsy findings. In six of 13 patients tested an “inverse steal syndrome” following aminophylline was disclosed.

Cerebral Apoplexy (Stroke) Treated With or Without Prolonged Artificial Hyperventilation: 2. Cerebrospinal Fluid Acid-Base Balance and Intracranial Pressure

CSF acid-base changes and intracranial pressure (ICP) were studied in 50 patients with cerebral apoplexy (stroke) in the acute phase. Thirty-three of the patients were treated afterward with artificial hyperventilation for 72 hours (15 hypocapnic [PaCO2 25 mm Hg] and 18 normocapnic). The remaining 17 patients were breathing spontaneously throughout. Arterial PCO2, CSF lactate, pyruvate and bicarbonate and ICP were followed during the course. Compared to a control group initial mean values showed significant increases of CSF lactate (2.36 mmol per liter) and pyruvate (0.183 mmol per liter) but with a normal lactate/pyruvate ratio (13.3), a reduced bicarbonate (22.0 mmol per liter), and reduced PaCO2 (34 mm Hg), indicating spontaneous hyperventilation. No correlation between the degree of initial hyperventilation or CSF lactate and the mortality rate was found. ICP averaged initially 15 mm Hg. The untreated patients had almost unchanged CSF values and PaCO2 during the following six days. During induced and sustained hypocapnia and normocapnia, CSF bicarbonate slowly followed changes in PaCO2 with CSF pH tending to return toward normal. The time course of this CSF pH adaptation had an estimated half-time of about six hours, and was complete within 30 hours. A similar time course of changes induced in ICP by ventilation was observed.

TOTAL CO2, LACTATE, AND PYRUVATE IN BRAIN BIOPSIES TAKEN AFTER FREEZING THE TISSUE IN SITU

Severe impairment of cerebral blood flow (CBF) regulation has been demonstrated around brain tumors (Palviilgyi, in press), cerebral infarction (Hsedt-Rasmussen et al. 1967, Fieschi et al. 1969) and intracerebral hematoma (Paulsen e f al. 1969) i.e. in the very same areas where local brain edema is typically seen. Usually a hyperemia (Lassen 1966) and sometimes a decreased flow is found, the normal autoregulation (the mcchanisrn which keeps CBF constant under variations in blood pressurc) is often abolished and frequently the response to increased pC0, is impaired (Lassen & PauIsen 1969, Fieschi et al. 1969). Similar changcs in CBF regulation are often seen during experimental hypoxia (Haggendal 4968), which is known to cause an accumulation of lactate and a decrease of total CO, concentration in brain tissue and CSF in animals (Kaasik et al. 1970a, 1970b). Experimental results thus seem to support the possibility of a metabolic acidosis in various clinical conditions. However, direct measurements of the acid-base conditions in humans suffering from brain lesions have been scarce and all of them deal with the cerebrospinal fluid. For this reason the present study was undertaken in an attempt to determine the acid-base conditions of damaged brain tissue sampled during a neurosurgical intervention. The biochemical parameters used were the total CO, and lactate-pyruvate contents. Because of the high rate of metabolism in brain tissue, it is necessary to freeze the tissue in situ, and a biopsy apparatus for this purpose was constructed. *

Methodology of clinical trials in migraine

Migraine is a condition characterised by recurrent attacks lasting from a few hours to a few days. If attacks are comparatively rare, patients are advised to take symptomatic medication such as ergotamine, aspirin and antinauseants at each attack. If patients suffer two or more severe attacks a month, prophylactic therapy may be indicated.

Effect of histamine on regional cerebral blood flow in man

Regional cerebral blood flow (rCBF) was measured using the intra-arterial 133Xe technique in 35 or 256 areas of a hemisphere. In seven patients rCBF was measured in the resting state and following intracarotid (i.c.) infusion of histamine 10–50 μg/min. In four patients histamine was infused intravenously in a dose of 25–40 μg/min. Histamine caused no significant change in mean arterial blood pressure or arterial PCO2. There was no significant change in mean hemispheric blood flow during i.v. or i.c. histamine infusion. No change in the regional distribution of hemispheric blood flow was observed. Experimental histamine headache is most likely of extracranial origin.