Granulocytes, platelet activating factor, and stroke

1116 Stroke Vol 20, No 8, August 1989 Downloaded from http://ahajournals.org by on May 28, 2020 rhagic stroke: A randomized, placebo-controlled doubleblind trial. Stroke 1988;19:716-722 2. Dragunow M, Faull RLM: Neuroprotective effects of adenosine. Trends Pharmacol Sci 1988;9:193-194 3. Bourke RS, Kimelberg HK, Daze MA: Effects of inhibitors and adenosine on (HCO3"/CO2)-stimulated swelling and Cl" uptake in brain slices and cultured astrocytes. Brain Res 1978;154:196-202 4. Bourke RS, Waldman JB, Kimelberg HK, Barron KD, San Filippo CD, Popp AJ, Nelson LR: Adenosine-stimulated astroglial swelling in cat cerebral cortex in vivo with total inhibition by a non-diuretic acylaryloxyacid derivative. J Neurosurg 1981;55:364-370 5. Schrier DJ, Imre KM: The effects of adenosine agonists on human neutrophil function. J Immunol 1986;137:3284-3289 6. Engler R: Consequences of activation and adenosinemediated inhibition of granulocytes during myocardial ischemia. Fed Proc 1987;46:2407-2412 7. Rose FR, Hirschhorn R, Weissmann G, Cronstein BN: Adenosine promotes neutrophil chemotaxis. / Exp Med 1988;167:1186-1194 8. Ward PA, Cunningham TW, McCulloch KK, Johnson KJ: Regulatory effects of adenosine and adenine nucleotides on oxygen radical responses of neutrophils. Lab Invest 1988; 58:438-447 9. Dukta AJ, Kochanek PM, Hallenbeck JM: Influence of granulocytopenia on canine cerebral ischemia induced by air embolism. Stroke 1989;20:390-395 10. Nielson CP, Crowley JJ, Cusack BJ, Vestal RE: Therapeutic concentrations of theophylline and enprofylline potentiate catecholamine effects and inhibit leukocyte activation. / Allergy Clin Immunol 1986;78:660-667 11. Hammerschmidt DE, Kotasek D, McCarthy T, Huh P-W, Freyburger G, Vercellotti GM: Pentoxifylline inhibits granulocyte and platelet function, including granulocyte priming by platelet activating factor. JLab Clin Med 1988; 112:254-263 12. Seida M, Wagner HG, Vass K, Klatzo I: Effect of aminophylline on postischemic edema and brain damage in cats. Stroke 1988;19:1275-1282 13. Fredholm BB, Persson CGA: Xanthine derivatives as adenosine receptor antagonists. EurJPharmacol 1982;81:673-676 Granulocytes, Platelet Activating Factor, and Stroke To the Editor: Saito et al1 report increased leukotriene-like immunoreactivity (G» and D4) in gerbil brain following bilateral common carotid occlusion and reduced leukotriene levels as a result of busulfaninduced granulocytopenia. Their results support the view that granulocytes may be involved in the pathogenesis of cerebral infarction. In addition to being the source of leukotrienes, granulocytes, particularly basophils, produce platelet-activating factor (PAF, l-0-alkyl-2-0-acetyl-sn-glyceryl-3-phosphorylcholine),2 which is a potent inducer of platelet activation, thrombosis, and ischemia.3-4 Apart from the platelet-mediated effects, PAF has also been shown to cause direct neuronal damage,5 cerebral vasoconstriction,6 and cerebral hypoperfusion,7 possibly mediated by specific PAF binding sites in the brain.8-9 In addition, we have reported an increased sensitivity to PAF-induced platelet activation in patients with acute cerebral infarction.10 We therefore suggest that the generation of platelet-activating factor may be another mechanism by which granulocytes participate in the pathogenesis of cerebral infarction. Rajiv Joseph, MD K.M.A. Welch, MD Department of Neurology Henry Ford Hospital Detroit, Michigan References 1. Saito K, Levine L, Moskowitz MA: Blood components contribute to rise in gerbil brain levels of leukotriene-like immunoreactivity after ischemia and reperfusion. Stroke 1988;19:1395-1398 2. Benveniste J, Chignard M: A role for PAF-acether (plateletactivating factor) in platelet-dependent vascular diseases? Circulation 1985;72:713-717 3. Bourgain RH, Maes L, Braquet P, Andries R, Touqui L, Braquet M: The effect of l-0-alkyl-2-acetyl-sn-glycero3-phosphocholine (PAF-acether) on the arterial wall. Prostaglandins 1985;30:185-197 4. Satoh K, Imaizumi T, Kawamura Y, Yoshida H, Takamatsu S, Mizono S: Activity of platelet-activating factor (PAF) acetylhydrolase in plasma from patients with ischemic cerebrovascular disease. Prostaglandins 1988;35:685-697 5. Kornecki E, Ehrlich YH: Neuroregulatory and neuropathological actions of the ether-phospholipid platelet-activating factor. Science 1988;240:1792-1794 6. Armstead WM, Pourcyrous M, Mirro R, Leffler CW, Busija DW: Platelet activating factor: A potent constrictor of cerebral arterioles in newborn pigs. Circ Res 1988;62:l-7 7. Kochanek PM, Nemoto EM, Melick JA, Evans RW, Burke DF: Platelet-activating factor-induced hypotension alters cerebral blood flow and metabolism in rats (abstract). Stroke 1988;19:142 8. Domingo MT, Spinnewyn B, Chabrier PE, Braquet P: Presence of specific binding sites for platelet-activating factor (PAF) in brain. Biochem Biophys Res Commun 1988; 151:730-736 9. Kochanek PM, Dutka AJ, Kumaroo KK, Hallenbeck JM: Platelet activating factor receptor blockade enhances recovery after multifocal brain ischemia. Life Sci 1987; 41:2639-2644 10. Joseph R, Welch KMA, Grunfeld S, Oster SB, D'Andrea G: Baseline and activated platelet cytoplasmic ionized calcium in acute ischemic stroke: Effect of aspirin. Stroke 1988; 19:1234-1238 Pulsed Doppler Assessment of Arterial Obstructive Disease To the Editor: The article by Drs. Rautenberg and Hennerici in Stroke* raised these questions for the authors in my mind: 1. How were the asymptomatic patients selected? 2. What were the features of the symptomatic transient ischemic attacks (TIAs)? 3. Were blood pressures obtained in both arms, and were there significant inequalities? 4. In those patients who received surgery to bypass the innominate obstruction, did the TIAs stop? 5. Finally, is it correct that some of the asymptomatic patients underwent surgery? Reed C. Perron, MD Neurology Group of Bergen County, P. A. Ridgewood, New Jersey Reference 1. Rautenberg W, Hennerici M: Pulsed Doppler assessment of innominate artery obstructive diseases. Stroke 1988; 19:1514-1520 The following is in reply: To the Editor: We appreciate the letter by Dr. Perron. His five questions are answered as follows: 1. The asymptomatic patients were investigated because of carotid bruits, risk factors for atherosclerosis, or coexisting peripheral arterial disease or coronary artery disease (cf. reference 41). Letters to the Editor 1117 2. Two patients had amaurosis fugax attacks of the right eye, and five reported brainstem TIAs. 3. Blood pressure was measured bilaterally, with significant differences found in eight patients. In six patients with bilateral subclavian steal, no differences were seen. 4. After surgery, the TIAs stopped. 5. Among the 10 operated patients, seven were symptomatic. Three asymptomatic patients underwent surgery prior to aortocoronary bypass surgery during the same thoracotomy. W. Rautenberg, MD M. Hennerici, MD Universitdt Diisseldorf Medizinische Einrichtungen Neurologische Klinik Diisseldorf, Federal Republic of Germany Reference 1. Hennerici M, Hulsbomer HB, Hefter H, Lammerts D, Rautenberg W: Natural history of asymptomatic extracranial arterial disease. Brain 1987;110:777-791 Hemorrhagic Transformation of Cardioembolic Stroke Downloaded from http://ahajournals.org by on May 28, 2020 To the Editor: Two recent reports in Stroke provide interesting information and prompt further speculation about hemorrhagic transformation of cardioembolic stroke.1-2 Secondary hemorrhagic transformation of presumed cardioembolic stroke is usually not associated with recognized clinical worsening.3-4 Definition of the temporal window of hemorrhagic transformation has been based on retrospective case series in which computed tomography (CT) data were collected at nonstandard time intervals, perhaps in patients with late hemorrhagic transformation that was undetected and therefore not included.1-5 The single prospective study using serial CTs up to 3 weeks after stroke reported an extraordinarily high prevalence of hemorrhagic infarction (43% of all supratentorial infarcts, 61% of presumed cardioembolic infarcts).6 While initial case collections suggested that the great majority of spontaneous hemorrhagic transformation occurred within 2-4 days of cardioembolic stroke (Figure I),1-2-5 multiple case reports have since documented later occurrence.6-9 In short, the exact limits of the window of spontaneous secondary hemorrhagic transformation remain ill-defined. There is clearly a delay between stroke onset and the development of hemorrhagic transformation detected by CT. In the CT/autopsy series of Lodder et al,1 only 10% (2/21) of the infarcts had definitely transformed before 24 hours, and 43-90% transformed after 24 hours. Among 28 cases of hemorrhagic transformation collected by the Cerebral Embolism Study Group, CTs done before 6 hours (n=7) showed no cases of hemorrhagic transformation while those done between 6 and 18 hours (n=\\) showed hemorrhagic transformation in 45%.5 The potential safety of acute fibrinolytic therapy in cardioembolic stroke may be influenced by this initial delay in hemorrhagic transformation. When Mori et al2 infused intracarotid urokinase into patients with acute middle cerebral artery occlusion, hemorrhagic transformation was linked to presumed cardioembolic sources and the severity of initial deficit rather than to observed recanalization. While Mori et al hypothesized that the volume of the embolus explained the differential recanalization rate of cardioembolic (29%) versus noncardioembolic (75%) middle cerebral artery occlusions (/?=0.048, Fisher's exact test), the age of the embolic fragment may also affect recanalization.2-10 Left atrial thrombi are often many weeks old, firm, and wellorganized and may be less susceptible to lysis than recently formed intracarotid thrombi. These recent reports suggest that 2 3 4 5 6 7 8 Days Interval: Stroke to CT/Autopsy FIGURE 1. Timing of hemorrhagic transformation (HT) defined by computed tomography (n=34) or autopsy (n=14) from two combined case series.1-5 The area indicated as (?)HT reflects the interval between nonhemorrhagic CT l(-)HT] and diagnosis of hemorrhagic infarct [(+)HT] within which the exact time of HT is uncertain. For example, at 24 hours after stroke onset, at least 25% and possibly as many as 77% ofpatients had undergone HT. while very early infusion of fibrinolytic agents (<6 hours) in cardioembolic stroke may safely precede the period of hemorrhagic transformation, recanalization may be less frequently achieved in thrombi of left atrial origin. Robert G. Hart, MD Carla Putnam, PharmD The University of Texas Health Science Center at San Antonio San Antonio, Texas References 1. Lodder J, Kubat-Krijne B, van der Lugt PJM: Timing of autopsy-confirmed hemorrhagic infarction with reference to cardioembolic stroke. Stroke 1988;19:1482-1484 2. Mori E, Tabuchi M, Yoshida T, Yamadori A: Intracarotid urokinase with thromboembolic occlusion of the middle cerebral artery. Stroke 1988;19:802-812 3. Cerebral Embolism Study Group: Immediate anticoagulation of embolic stroke: Brain hemorrhage and management options. Stroke 1984;15:779-789 4. Cerebral Embolism Study Group: Brain hemorrhage in embolic stroke, in Stober T, Shimrigk K, Ganten D, Sherman DG (eds): Central Nervous System Control of the Heart. Boston, Martinus Nijhoff Publishing, 1986, pp 249-253 5. Cerebral Embolism Study Group: Timing of hemorrhagic transformation of cardioembolic stroke, in Stober T, Shimrigk K, Ganten D, Sherman DG (eds): Central Nervous System Control of the Heart. Boston, Martinus Nijhoff Publishing, 1986, pp 229-232 6. Hornig CR, Dorndorf W, Agnoli AL: Hemorrhagic cerebral infarction: A prospective study. Stroke 1986;17:179-185 7. Laureno R, Shields RW, Narayan T: The diagnosis and management of cerebral embolism and haemorrhagic infarction with sequential computerized cranial tomography. Brain 1987;110:93-105 8. Ott BR, Zamani A, Kleefield J, Funkenstein HH: The clinical spectrum of hemorrhagic infarction. Stroke 1986; 17:630-637 9. Sato Y, Mizoguchi K, Sato Y, Ohkita Y, Kaji M: Anticoagulant and thrombolytic therapy for cerebral embolism of cardiac origin. Kurume MedJ 1986;33:89-95 10. Collen D, Stassen JM, Verstraete M: Thrombolysis with human extrinsic plasminogen activator in rabbits with experimental jugular vein thrombosis. / Clin Invest 1983; 71:368-376