Alessandro Agnoli

Derangement of regional cerebral blood flow and of its regulatory mechanisms in acute cerebrovascular lesions

IT HAS LONG BEEN RECOGNIZED~ that cerebral anoxia produces, in addition to damage to nervous structures, a serious derangement of the mechanisms of regulation of cerebral vasomotility. A more detailed knowledge of the functional aspects of cerebral vascular pathology has been permitted by the availability of reliable methods of exploring quantitatively the circulation in discrete parts of the brain. Studies performed in patients with the radioactive inert gas regional clearance method proposed by Lassen and co-workers in 1963* have demonstrated that [ 11 the autoregulation (constancy of cerebral blood flow at different levels of perfusion pressure) is lost in many patients in the first days after an ischemic insult,”-5 [2] in the same group of patients6 the response to changes in arterial CO, tension may be regionally impaired (loss or delay of cerebral vasodilatation in response to hypercapnia had been previously demonstrated with the N 2 0 method7 and with radioalbumins), and [3] shortly after an acute brain infarction a cerebral reactive hyperemia with marked increase in blood flow (the “luxury perfusion” phenomenon) may occur.5~9,10 Experimental studies have confirmed the above observations,l1-15 whose physiological and possibly practical implications are of considerable importance. The present study further documents the

Metabolism and cerebral energy state: Effect of acute hyperammonemia in beagle dog

Abstract The acute effect of hyperammonemia (NH4+ blood level 0.2 mM) was evaluated in the isolated dog brain in situ. The interference of the transmethylating system of S- adenosyl- L -methionine was also studied by means of infusion with S- adenosyl- L -methionine or adenosine (blood level 0.4 mM). The changes induced by hyperammonemia on the cerebral glutamate-ammonia system (pyruvate, α-oxoglutarate, oxaloacetate, l -alanine, l -glutamate, l -aspartate, l -glutamine, NH4+) were evaluated. Cerebral detoxication of ammonia is connected with the formation of glutamine and. to a lesser extent. of alanine, and is balanced by a decrease in aspartate; glutamate, oxaloacetate, pyruvate and α-oxoglutarate are unmodified or slightly modified. Cerebral intermediate metabolism of glucides was largely activated by acute hyperammonemia. a marked increase in Gibbs free energy being observed. A fraction of this energy not exceeding 10 per cent can be ascribed to the synthesis of glutamine. Hyperammonemia induced a variation of the resting transmembrane potential (as indirectly obtained by applying the Nernst equation), which becomes less negative.

Platelet Aggregation in the Pathogenesis of Cerebrovascular Disorders

Introductory Remarks.- Methodology and Physiology Chairmen: G.V.R. Born and K. Breddin.- The Platelet as an Inflammatory Cell.- Platelet Aggregation in the Pathogenesis of Cerebrovascular Disorders.- The Mathematical Analysis of the Human Platelet Aggregation Mechanism and Its Clinical Application.- Quantitative Valuation of Platelet Aggregation Curves through the Calculation of a Numerical Index.- The Polyunsaturated Fatty Acids in Human Platelets: Effects of Diet and Possible Functional Significance.- Enhanced Platelet Aggregation as a Risk Factor for Progress and Complications of Vascular Disease. New Findings with a Platelet Aggregation Test (PAT III) and on the Dependence of Different Aggregation Tests on Morphologic Platelet Changes.- Pathogenesis Chairmen: M. Anthony, T. Abe, E.J. Acheson, J.S. Meyer, J. Marshall, K.J. Zulch.- Thrombosis and Embolism as a Cause of Ischemic Cerebrovascular Disturbances. Analysis from a Series of 1000 Patients.- Platelet Adhesiveness and Cerebral Vascular Disease Revisited.- The Significance of Platelet Aggregation in Amaurosis Fugax.- Mechanisms of Platelet 5-Hydroxytryptamine Release in Migraine.- Experimental observations on Platelet Emboli in Focal Brain Ischemia.- Observations on Platelet Aggregability in the Acute Phase of Untreated Strokes.- Microembolism in the Nervous System.- Influence of Plasma Components in the Development of Conditions of Increased Platelet Aggregation Found in a Number of Vascular Diseases.- Mechanism Associated with Platelet Adhesiveness in Cerebrovascular Disease.- Regional Intravascular Coagulation and Microthrombosis in Traumatic Brain Lacerations in Man.- Platelet Aggregation in Cerebrovascular Patients.- In Vivo Effect of Cyclic AMP and Related Drugs on Platelet Function.- Platelet Hyperreactivity and Decreased Survival in Chronic Cerebrovascular Patients. Chronic Defibrination Syndrome?.- Arterial Hypertension and Platelet Aggregation in the Patho-Pathogenesis of Cerebrovascular Diseases.- Smoking, Cerebrovascular Diseases and Platelet Functions.- Contribution of Platelet Aggregation and Serotonin Release to Progressive Cerebral Infarction.- Effect of Agents which Modify Platelet Aggregation and/or Coagulation on Experimental Platelet Embolism and Intravascular Coagulation.- Platelet Abnormalities in Cerebrovascular Diseases.- Inhibition of Platelet Aggregation by Synthetic Organic Acids: Quantitative Relationships Between Chemical Structures and Biological Activities.- Some Observations of Platelet Changes in Atherosclerosis and Some Observations in the Platelet Alterations Before and After Antiaggregant Drugs in Normal and Atherosclerotics.- Pharmacology and Clinical Pharmacology Chairmen: C.A. Bouvier, W.S. Fields, O.N. Ulutin, A. Rascol.- Inhibition of Platelet Thrombus Formation by Pharmacological Agents.- A Long-Term Clinical Trial with Antiplatelet Agents in Cerebrovascular Ischemia: Biological and Methodological Aspects.- Effect of Aspirin and Dipyridamole on Platelet Function and on Neurologic Evaluation of Patients Affected by Stroke or Transient Ischemic Attacks.- The Pharmacologic Control of the Enhanced Platelet Aggregation in Preventive Neurology.- Aspirin in Cerebral Ischemia.- The Canadian Cooperative Studies of the Effect of Platelet-Suppressing Drugs in Transient Cerebral Ischemic Attacks.- On the Relationships Between the Activation of the Complement System and the Platelet Aggregation.- Discussion and Concluding Remarks.- Chairmens Considerations.- Concluding Remarks.

Evaluation of vesico-urethral and sweating function in disorders presenting with parkinsonism

Investigation of vesico-urethral and sweating function was performed in twelve patients with classical idiopathic Parkinsons disease and ten patients with parkinsonism associated with features suggestive of more extensive involvement of the nervous system, as in the Shy—Drager syndrome. The urodynamic studies revealed detrusor hyperreflexia with reduction of maximal cystometric capacity in only one patient with Parkinsons disease (8%), but in nine patients with parkinsonism associated with other features (90%). Urethral sphincter electromyography did not indicate denervation in any patient of either group. Delayed or incomplete relaxation of the urethral sphincter during micturition was observed in seven patients with Parkinsons disease (58%) and in two patients of the other group (20%). Decreased sweating responses were found in both groups of patients when compared with control subjects. Hypohidrosis was more pronounced in parkinsonism associated with other features than in Parkinsons disease. Differences in sweating between the two sides of the body were observed in both groups of patients. Although there are differences in vesico-urethral and sweating function, they do not precisely differentiate between patients with classical Parkinsons disease and those with parkinsonism associated with features suggestive of more extensive involvement of the nervous system.

The Vascularisation of the Spinal Cord—Anatomical and Pathophysiological Aspects:

Persisting dearth of knowledge regarding vascular diseases of the spinal cord has recently stimulated a renewed growth of studies within this field. Prior to the fundamental contributions of Adamkievitz and Kady the vascularization of the spinal cord was classically considered to be segmented, consisting of radicular arteries connected in series and anastomosing at the cord surface via the longitudinal arteries, namely the a. spinalis anterior and the aa. spinales posteriores. It was then clearly shown that only a few radicular arteries carried the blood supply of the spinal cord. The other radicular arteries are of vestigial nature in adults, their function being limited to supplying only single spinal

Results and possible developments of the clinical use of S-adenosyl-L-methionine (SAMe) in psychiatry.

Experimental work on the acute, chronic, and fetal toxicity of SAMe was carried out by Stramentinoli and his colleagues (19). The intravenous LD50 in rats is more than 2000 mg/kg, or the equivalent of 140–150 g in a man of 70 kg. In man, on the other hand, clinical trials have revealed a definite action of the substance in the CNS with doses as little as 80/zg/kg; the largest dose so far administered intravenously to humans is 0.5 g daily and has produced no visible side effects.

Direct common carotid injection of radioisotopes for the evaluation of cerebral circulatory disturbances: A study of 116 cases by bilateral radioisotope rheoencephalography

RADIOISOTOPES have been used to study the cerebral circulation in man for several y e a r ~ . l ~ The findings so far published are mainly preliminary and the results of technics which have not yet been widely applied to clinical research. In fact, radioisotopic technics for the study of cerebral circulation in man are a heterogeneous group having as a common denominator only the use of radioactive tracers. Basically, the methods4 described thus far can be divided into 3 groups: 1. Methods to evaluate the cerebral vascular bed,5 the circulating blood volume,6 or the cerebral blood flow f r a ~ t i o n . ~ 2. Methods for the evaluation of the cerebral blood flow (CBF) based on the Fick principle which, like the N 2 0 technic, employ an inert substance freely diffusible from the blood to the cerebral tissue, such as Kr85, Kr79, 1131 antipyrine, and Rb86 C1.1.8-12 3. Methods based on the use of tracers not rapidly diffusible, to determine (a) circulation time and elements of the graphic curves obtained during the first passage of the tracer in cerebral vessels,3, l3-28 and (b) distribution of the blood from an individual extracranial artery to the different parts of the intracranial vascular bed, and its outflow through the 2 main efferent channels (jugular veins).l6Sz6 Some investigators, using these latter methods, have tried to apply the Stewart-Hamilton dilution principle to calculate either absolute cerebral blood flow or an index of cerebral

Effect of some drugs on cerebral energy state during and after hypoxia and complete or incomplete ischemia.

Abstract The effect of caffeine, nicergoline and medibazine was evaluated in the brain of beagle dogs during various experimental conditions of cerebral damage (hypoxia, hypoxia plus incomplete ischemia, hypoxia plus complete ischemia), and during post-hypoxic recovery and restoration of circulation. The behavior of fuels (glycogen, glucose), of glycolytic pathway intermediates (glucose-6-phosphate, pyruvate) and end-product (lactate), as well as the pool of labile phosphates (ATP, ADP, AMP, creatine phosphate) and the energy charge potential were evaluated in the motor area of the cerebral cortex. The drugs tested proved unable to improve the deranged brain metabolism and the energy charge potential under these various hypoxemic conditions. On the contrary, a certain pharmacological effect of nicergoline and medibazine could be observed both in the post-hypoxic recovery and in the recovery following hypoxia plus complete ischemia, caffeine being totally ineffective. As for the recovery subsequent to hypoxia plus incomplete ischemia, none of the drugs tested was able to trigger restoration.

Chairmen’s Considerations

BORN: The subject matter of Methodology and Physiology is furthest away from clinical neurology. I think the important thing there is that the basic investigation of platelets is a very interesting biological thing to spend your time on if you are a biologist and, in my case, the fact that platelets really matter or are thought to matter in clinical conditions of the kind in which you are interested, has come as a rather belated bonus.