RESUMEN
BACKGROUND AND PURPOSE: Treatment of patients with ischemic stroke after endovascular treatment requires in-depth knowledge of complications. The goal of this study was to make endovascular treatment for acute ischemic stroke safer through an in-depth review of the major periprocedural complications observed in the Solitaire FR With Intention for Thrombectomy (SWIFT) trial. MATERIALS AND METHODS: The SWIFT data base was searched for major peri-procedural complications defined as symptomatic intracranial hemorrhage within 36 hours, SAH, air emboli, vessel dissection, major groin complications, and emboli to new vascular territories. RESULTS: Major peri-procedural complications occurred in 18 of 144 patients (12.5%) as follows: symptomatic intracranial hemorrhage, 4.9%; air emboli, 1.4%; vessel dissection, 4.2%; major groin complications, 2.8%; and emboli to new vascular territories, 0.7%. Rates of symptomatic intracranial bleeding by subtype were PH1, 0.7%; PH2, 0.7% (PH1 indicates hematoma within ischemic field with some mild space-occupying effect but involving ≤ 30% of the infarcted area; PH2, hematoma within ischemic field with space-occupying effect involving >30% of the infarcted area); intracranial hemorrhage remote from ischemic zone, 0%; intraventricular hemorrhage, 0.7%; and SAH, 3.5%. We did not observe any statistically significant associations of peri-procedural complications with age; type of treatment center; duration of stroke symptoms; NIHSS score, IV thrombolytics, atrial fibrillation, site of vessel occlusion; rescue therapy administered after endovascular treatment; or device. Comparing the Merci with the Solitaire FR retrieval device, we observed symptomatic cerebral hemorrhage (10.9% versus 1.1%; P = .013); symptomatic SAH (7.3% versus 1.1%; P = .07), air emboli (1.8% versus 1.1%; P = 1.0), emboli to new vascular territories (1.8% versus 0%; P = .38), vessel dissection (1.8% versus 4.5%; P = .65), and major groin complications (3.6% versus 7.9%; P = .48). Angiographic vasospasm was common but without clinical sequelae. CONCLUSIONS: Understanding of procedural complications is important for treatment of patients with stroke after endovascular treatment. We observed fewer endovascular complications with the Solitaire FR device treatment compared with Merci device treatment, particularly symptomatic cerebral hemorrhage.
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Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/instrumentación , Accidente Cerebrovascular/cirugía , Adulto , Anciano , Humanos , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Trombectomía , Adulto JovenRESUMEN
Based on published case series, intra-arterial thrombolysis for basilar artery occlusion reduces mortality and improves outcome even when performed after considerable delays. In contrast, the current use of intravenous thrombolysis is limited to a 3-hour time window. The longer time window for intervention in patients with basilar artery occlusion may vary based on individual clinical features, such as collateral circulation and the site of the occlusion. Clinicopathologic evidence is presented from a patient with a distal basilar artery occlusion treated with local thrombolysis who later expired from a myocardial infarction complicated by cardiac tamponade. Autopsy showed infarction limited to the right pons despite symptom duration of over 72 hours and directly observed neurologic deficits for 27 hours.
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Fibrinolíticos/administración & dosificación , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Terapia Trombolítica , Activador de Tejido Plasminógeno/administración & dosificación , Activador de Plasminógeno de Tipo Uroquinasa/administración & dosificación , Fibrinolíticos/uso terapéutico , Humanos , Infarto de la Arteria Cerebral Media/diagnóstico por imagen , Infusiones Intraarteriales , Infusiones Intravenosas , Radiografía , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Factores de Tiempo , Activador de Tejido Plasminógeno/uso terapéutico , Activador de Plasminógeno de Tipo Uroquinasa/uso terapéuticoRESUMEN
OBJECTIVE: To review the clinical outcomes of stroke patients treated with IV tissue plasminogen activator (tPA; alteplase) in a community setting and to compare outcomes when treatment was initiated by a neurologist or an emergency department (ED) physician in telephone consultation with a neurologist and radiologist. METHODS: Clinical information was prospectively collected for 43 stroke patients treated with IV tPA (alteplase) within a five-hospital network of affiliated community hospitals. Blinded 3-month outcomes were obtained with telephone interview or patient visit. RESULTS: Excellent functional recovery measured by a Modified Rankin score of 0 to 1 (42%), symptomatic intracerebral hemorrhages (7%), and mortality (16.3%) were similar to those reported by National Institute of Neurological Disorders and Stroke (39%, 7.7%, 17.3%). After initial screening by an ED physician, 20 patients were directly examined by a stroke neurologist who then prescribed tPA. Twenty-three patients received tPA prescribed by an ED physician after telephone consultation with a neurologist and review of the head CT by a radiologist. Functional outcome, symptomatic intracerebral bleeding rate, and mortality rate were similar between these groups. Door-to-needle time was similar. Protocol deviations were much higher when ED physicians prescribed the tPA compared to when neurologists did (30% versus 5%). These protocol deviations were reduced with staff education. CONCLUSIONS: The clinical results of the National Institute of Neurological Disorders and Stroke tPA Stroke Trial were replicated in this small series of patients treated in a community setting. Outcomes were similar whether the prescribing physician was a neurologist or an ED physician.
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Isquemia Encefálica/tratamiento farmacológico , Tratamiento de Urgencia/efectos adversos , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Anciano , Isquemia Encefálica/fisiopatología , Femenino , Humanos , Masculino , Pronóstico , Accidente Cerebrovascular/fisiopatologíaRESUMEN
BACKGROUND AND PURPOSE: We sought to determine predictors of acute hospital costs in patients presenting with acute ischemic stroke to an academic center using a stroke management team to coordinate care. METHODS: Demographic and clinical data were prospectively collected on 191 patients consecutively admitted with acute ischemic stroke. Patients were classified by insurance status, premorbid modified Rankin scale, stroke location, stroke severity (National Institutes of Health Stroke Scale score), and presence of comorbidities. Detailed hospital charge data were converted to cost by application of department-specific cost-to-charge ratios. Physician's fees were not included. A stepwise multiple regression analysis was computed to determine the predictors of total hospital cost. RESULTS: Median length of stay was 6 days (range, 1 to 63 days), and mortality was 3%. Median hospital cost per discharge was $4408 (range, $1199 to $59 799). Fifty percent of costs were for room charges, 19% for stroke evaluation, 21% for medical management, and 7% for acute rehabilitation therapies. Sixteen percent were admitted to an intensive care unit. Length of stay accounted for 43% of the variance in total cost. Other independent predictors of cost included stroke severity, heparin treatment, atrial fibrillation, male sex, ischemic cardiac disease, and premorbid functional status. CONCLUSIONS: We conclude that the major predictors of acute hospital costs of stroke in this environment are length of stay, stroke severity, cardiac disease, male sex, and use of heparin. Room charges accounted for the majority of costs, and attempts to reduce the cost of stroke evaluation would be of marginal value. Efforts to reduce acute costs should be monitored for potential cost shifting or a negative impact on quality of care.
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Centros Médicos Académicos/economía , Isquemia Encefálica/economía , Trastornos Cerebrovasculares/economía , Costos de Hospital/estadística & datos numéricos , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/economía , Lechos/economía , Asignación de Costos , Costos y Análisis de Costo , Femenino , Costos de Hospital/clasificación , Humanos , Seguro de Salud , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/economía , Grupo de Atención al Paciente/economía , Estudios Prospectivos , Análisis de Regresión , Índice de Severidad de la Enfermedad , Estados UnidosRESUMEN
BACKGROUND AND PURPOSE: This study was undertaken to examine the relationship between collateral flow and outcome after local intraarterial thrombolytic treatment for basilar artery thrombosis. METHODS: Twenty-four patients with symptomatic basilar thrombosis were treated with intraarterial urokinase. Angiograms at the time of treatment were analyzed to characterize collateral flow. The number of posterior communicating arteries (PCoAs) and the degree of collateral filling of the basilar artery were then compared with symptom duration before treatment, with Glasgow Coma Scale (GCS) score at the time of treatment, with 90-day modified Rankin score, and with 90-day survival status. RESULTS: Of the 20 patients who had carotid artery injections at the time of the thrombolytic procedure, two had no PCoA, eight had one PCoA, and 10 had two PCoAs. Nine had no collateral opacification of the basilar artery, six had collateral opacification of the distal basilar artery, and five had collateral opacification of the distal and proximal basilar artery. Ninety-day survival was 38%; 25% of patients had good neurologic outcomes. No correlation was found between the number of PCoAs and symptom duration, pretreatment GCS score, survival, or neurologic outcome. Duration of symptoms before treatment was longer in patients with collateral flow to the basilar artery. Basilar artery collateral flow did not correlate with survival, but it did correlate with neurologic outcome for the 12 patients with middle or distal basilar artery thrombus in whom collateral flow to the basilar artery was assessed (83% with collateral flow had good neurologic outcomes, but only 17% without collateral flow had good outcomes). All six patients with proximal basilar artery thrombus in whom collateral flow was assessed died, independent of the collateral flow observed. CONCLUSION: In symptomatic acute basilar artery thrombosis, neurologic outcome was better after intraarterial thrombolysis in patients who had collateral filling of the basilar artery, except in cases of proximal basilar thrombosis. Patients with collateral filling of the basilar artery also tolerated longer symptom duration.
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Arteria Basilar , Encéfalo/irrigación sanguínea , Embolia y Trombosis Intracraneal/tratamiento farmacológico , Terapia Trombolítica , Activador de Plasminógeno de Tipo Uroquinasa/administración & dosificación , Arteria Basilar/diagnóstico por imagen , Angiografía Cerebral , Circulación Colateral/efectos de los fármacos , Estudios de Seguimiento , Escala de Coma de Glasgow , Humanos , Infusiones Intraarteriales , Embolia y Trombosis Intracraneal/diagnóstico por imagen , Embolia y Trombosis Intracraneal/mortalidad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Knowledge of the natural history of stenoses due to intracranial atherosclerosis may be useful for evaluating possible treatments such as angioplasty. METHODS: We retrospectively reviewed records over a 7-year period to identify patients with intracranial atherosclerotic stenoses and serial angiograms. Quantitative measurements of stenoses were made in a blinded manner, and clinical outcomes were reviewed. RESULTS: We identified 21 patients with 45 intracranial stenoses who underwent repeat angiography at an average interval of 26.7 months. The average stenosis for all intracranial lesions was 43.9% initially and 51.8% on follow-up (P=.032). The average stenosis in the intracranial internal carotid artery (ICA) was stable (51.2% versus 52.6%). The average stenosis in the anterior cerebral artery (ACA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) progressed from 32.4% to 49.7% (P=.037). Based on a minimum 10% change, 20% of intracranial ICA lesions progressed compared with 61% of ACA, MCA, and PCA lesions. Regression occurred in 14% of the intracranial ICA group and 28% of the ACA-MCA-PCA group. Cerebrovascular events were infrequent during this period, with 4 transient ischemic attacks and 1 intracerebral hemorrhage. CONCLUSIONS: Intracranial atherosclerotic stenoses are dynamic lesions demonstrating both progression and regression.
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Arteriopatías Oclusivas/fisiopatología , Enfermedades Arteriales Cerebrales/fisiopatología , Arteriosclerosis Intracraneal/fisiopatología , Arteriopatías Oclusivas/diagnóstico por imagen , Angiografía Cerebral , Enfermedades Arteriales Cerebrales/diagnóstico por imagen , Arterias Cerebrales/diagnóstico por imagen , Progresión de la Enfermedad , Femenino , Humanos , Arteriosclerosis Intracraneal/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
PURPOSE: To identify factors that predict survival and good neurologic outcome in patients undergoing basilar artery thrombolysis. METHODS: Over a 42-month period, 20 of 22 consecutive patients with angiographic proof of basilar artery thrombosis were treated with local intraarterial urokinase. Brain CT scans, neurologic examinations, symptom duration, clot location, and degree of recanalization were analyzed retrospectively. RESULTS: Overall survival was 35% at 3 months. Survival in patients with only distal basilar clot was 71%, while survival in patients with proximal or midbasilar clot was only 15%. At 3 months, 29% of patients with distal basilar clot and 15% of patients with proximal or midbasilar clot had good neurologic outcomes (modified Rankin score of 0 to 2 and Barthel index of 95 to 100). Complete recanalization was achieved in 50% of patients; 60% of those survived and 30% had good neurologic outcomes. Of patients with less than complete recanalization, only 10% survived. Neither duration of symptoms before treatment (range, 1 to 79 hours), age (range, 12 to 83 years), nor neurologic status at the initiation of treatment (Glasgow Coma Scale score range, 3 to 15) predicted outcome. Pretreatment CT findings (positive or negative for related ischemic changes) did not predict outcome or hemorrhagic transformation. CONCLUSION: The single best predictor of survival after basilar thrombosis and intraarterial thrombolysis was distal clot location. Complete recanalization favored survival. Radiologically evident related infarctions, advanced age, delayed diagnosis, and poor pretreatment neurologic status did not predict poor outcome and therefore should not be considered absolute contraindications for intraarterial thrombolysis in patients with basilar artery thrombosis.
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Arteria Basilar , Embolia y Trombosis Intracraneal/tratamiento farmacológico , Terapia Trombolítica , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Arteria Basilar/diagnóstico por imagen , Arteria Basilar/efectos de los fármacos , Encéfalo/irrigación sanguínea , Niño , Relación Dosis-Respuesta a Droga , Femenino , Estudios de Seguimiento , Humanos , Embolia y Trombosis Intracraneal/diagnóstico por imagen , Embolia y Trombosis Intracraneal/mortalidad , Masculino , Persona de Mediana Edad , Examen Neurológico , Flujo Sanguíneo Regional/efectos de los fármacos , Estudios Retrospectivos , Tasa de Supervivencia , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Activador de Plasminógeno de Tipo Uroquinasa/administración & dosificación , Activador de Plasminógeno de Tipo Uroquinasa/efectos adversosRESUMEN
In a 23-year-old woman, gravida 1, para 1-0-0-1, headaches and seizures developed 1 week after an uncomplicated delivery. Cerebral angiography revealed severe, diffuse cerebral vasospasm. Her symptoms resolved with hyperosmolar, hypervolemic therapy and nimodipine. Magnetic resonance angiography on postpartum day 23 confirmed persistent, severe vasospasm, and repeat magnetic resonance angiography on postpartum day 33 demonstrated interval improvement. This report documents the time course of a case of postpartum vasospasm and its response to hypervolemic, hyperosmolar therapy and nimodipine.
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Ataque Isquémico Transitorio/terapia , Trastornos Puerperales/terapia , Adulto , Femenino , Humanos , Nimodipina/uso terapéutico , EmbarazoRESUMEN
BACKGROUND: Cerebral ischemia is a potent modulator of gene expression. Immediate early genes undergo rapid induction after both global and focal cerebral ischemia. Many immediate early genes code for transcription factors. Additional genes, including those encoding for neurotrophic factors and neurotransmitter systems, are induced in a delayed fashion after cerebral ischemia. The functional significance of early and late gene regulation after cerebral ischemia requires further investigation. These changes may be beneficial (friend) or detrimental (foe). Many of the genes are likely neuroprotective and important for recovery, but others may be involved in ischemic cell death mediated by apoptosis. SUMMARY OF REVIEW: We review evidence that supports the hypothesis that cell death after cerebral ischemia occurs through the dual pathways of ischemic necrosis and apoptosis. CONCLUSIONS: Gene regulation, including immediate early genes, is required for programmed neuronal death after trophic factor deprivation and is predicted to be involved in apoptosis triggered by cerebral ischemia. Novel therapies following cerebral ischemia may be directed at genes mediating either recovery or apoptosis.
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Isquemia Encefálica/genética , Expresión Génica , Genes Inmediatos-Precoces , Animales , Apoptosis , Isquemia Encefálica/patología , HumanosRESUMEN
BACKGROUND: Thrombus within the carotid artery usually occurs in vessels with severe atherosclerotic disease and may embolize to cause transient ischemic attacks and cerebral infarctions. The risk factors for carotid artery thrombus formation in the absence of atherosclerosis are not well characterized. A case series is presented that suggests an association of carotid artery thrombus with severe iron-deficiency anemia and thrombocytosis. CASE DESCRIPTIONS: We describe three women with severe iron-deficiency anemia and thrombocytosis secondary to menorrhagia who developed carotid artery thrombi. Thrombi were detected radiographically. The patients were treated with anticoagulation and antiplatelet therapy. In two patients, follow-up neuroimaging 10 to 14 days later demonstrated resolution of the thrombus and no identifiable vascular disease. CONCLUSIONS: Severe iron-deficiency anemia with thrombocytosis may be a risk factor for carotid artery thrombus formation. Medical management with anticoagulation and antiplatelet therapy is a reasonable approach for these patients while the thrombus resolves.
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Anemia Ferropénica/complicaciones , Trombosis de las Arterias Carótidas/complicaciones , Menorragia/complicaciones , Trombocitosis/complicaciones , Adulto , Anemia Ferropénica/terapia , Trombosis de las Arterias Carótidas/diagnóstico por imagen , Trombosis de las Arterias Carótidas/terapia , Arteria Carótida Común , Arteria Carótida Interna , Angiografía Coronaria , Femenino , Humanos , Leiomioma/cirugía , Tomografía Computarizada por Rayos X , Neoplasias Uterinas/cirugíaRESUMEN
The cases of a father and his son who were diagnosed with pathologically confirmed colloid cysts of the third ventricle are presented. The familial occurrence of this tumor is rare and suggests that genetic factors may play a role in its formation. Consistent with the concept that the cyst originates as a developmental abnormality, it is associated with a variety of congenital defects. The conditions that are associated with these tumors are discussed.
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Ventrículos Cerebrales , Quistes/genética , Adulto , Encefalopatías/diagnóstico por imagen , Encefalopatías/genética , Encefalopatías/patología , Quistes/diagnóstico por imagen , Quistes/patología , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos XRESUMEN
Apoptosis is a rediscovered mechanism of cell death crucial in normal development. Recent exploration of the genetic mechanisms of apoptosis has broadened our insight into the regulation of cell death in development as well as disease states. We present an overview on current understanding of the genetic molecular events in apoptosis in all, or most cell types, with emphasis on events observed in a well-characterized model of neuronal death in vitro. The second part of this article reviews recent studies in in vivo stroke models on the mechanism of cell death relevant to apoptosis after cerebral ischemia. Further delineation of the mechanisms of cell death, especially those that trigger apoptosis, is likely to redirect our approaches in the development of new therapeutic interventions for ischemic stroke.
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Apoptosis , Isquemia Encefálica/patología , Encéfalo/patología , Neuronas/fisiología , Animales , Encéfalo/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , HumanosRESUMEN
Using the whole-cell patch-clamp technique on acutely dissociated and cultured adult rat sensory neurons, we characterized the K+ currents by voltage dependence, kinetics, calcium dependence, and pharmacology. In the presence of Ca channel blockers, the cells heterogeneously expressed transient and sustained outward K+ currents. The transient current was a high-threshold A-current which activated at potentials greater than -30 mV and was blocked by 4-aminopyridine. Some of the sustained current was classified as a delayed rectifier. It demonstrated shallow voltage-dependent inactivation and was blocked by tetraethylammonium. Capsaicin produced large reductions in both transient and sustained currents with an EC50 of 8 microM. Likewise, dendrotoxin partially blocked both currents but with an EC50 of 21 nM. In the absence of Ca channel blockers, a prominent Ca-dependent K+ current was observed. The kinetics of whole-cell potassium currents varied widely among cells, perhaps reflecting the different functional properties of sensory neurons. We also investigated the effects of elevating intracellular cyclic AMP and applying opioids on K+ currents. Membrane-permanent analogs of cyclic AMP and phosphodiesterase inhibitors caused small reductions in voltage-dependent outward current. In contrast, forskolin produced a large reduction in outward current. This response was not solely mediated by cyclic AMP, since large responses were elicited with an inactive congener, 1,9-dideoxyforskolin, but not with the active, water-soluble congener, 7-deacetyl-6-[N-acetylglycyl]-forskolin. Surprisingly, opioids had no effect on resting or voltage-dependent K+ conductances. However, opioid inhibition of Ca2+ currents and Ca-dependent K+ currents was observed. The failure to demonstrate opioid modulation of resting or voltage dependent K+ currents suggests that modulation of Ca2+ currents is the principal mechanism for the inhibitory effect of opioids on sensory neurons.
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AMP Cíclico/farmacología , Narcóticos/farmacología , Neuronas Aferentes/metabolismo , Canales de Potasio/metabolismo , 4-Aminopiridina/farmacología , Animales , Capsaicina/farmacología , Colforsina/farmacología , Venenos Elapídicos/farmacología , Electrofisiología , Técnicas In Vitro , Activación del Canal Iónico/efectos de los fármacos , Cinética , Neuronas Aferentes/efectos de los fármacos , Neurotoxinas/farmacología , Ratas , Ratas Sprague-Dawley , Compuestos de Tetraetilamonio/farmacologíaRESUMEN
Neurons of the neostriatum are richly innervated by cholinergic neurons of intrinsic origin. Both pre- and post-synaptic muscarinic receptors mediate the effects of acetylcholine (ACh). Activation of these receptors is functionally significant, particularly in Parkinson's disease. Current-clamp studies indicate that muscarinic receptors serve to decrease the responsiveness of neostriatal neurons to excitatory inputs. Here we present evidence that this effect is caused, in part, by the muscarinic modulation of the A-current, a transient outward potassium current. The voltage dependence of this current suggests that normally it enhances spike repolarization and slows discharge rate, but does not affect 'synaptic integration'. We find that under the influence of muscarinic agonists, the voltage dependence of A-current activation and inactivation is shifted towards more negative membrane potentials and the peak conductance is increased. Therefore, at relatively hyperpolarized resting potentials, ACh transiently alters the functional role of the A-current, allowing it to suppress excitatory inputs and further slow the discharge rate. But at relatively depolarized resting potentials, ACh increases excitability by removing the A-current through inactivation.
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Cuerpo Estriado/fisiología , Neuronas/fisiología , Canales de Potasio/fisiología , Receptores Muscarínicos/fisiología , Acetilcolina/farmacología , Animales , Atropina/farmacología , Carbacol/farmacología , Células Cultivadas , Cuerpo Estriado/efectos de los fármacos , Conductividad Eléctrica , Potenciales de la Membrana , Muscarina/farmacología , Neuronas/efectos de los fármacos , Ratas , Tetraetilamonio , Compuestos de Tetraetilamonio/farmacologíaRESUMEN
Muscarinic acetylcholine receptor expression and function in cultured rat neostriatal neurons were examined. All experiments were performed on intact neurons grown in vitro for 12-14 days. The muscarinic antagonist N-[3H]methylscopolamine [( 3H]NMS) binds to a single site in cultures with a KD of 89 pM and a Bmax of 187 fmol/mg of protein, or 32,000 sites/neuron. Competition studies using [3H]NMS were performed to determine what receptor subtypes were present. Nonlinear analysis of competition curves was best described with a single binding site for atropine, pirenzepine, and AF-DX 116 (11-[[2-[(diethylamino)-methyl]-1-piperidinyl]acetyl]-5,11-dihydro- 6H-pyrido[2,3-b][1,4]benzodiazepine-6-one), with Ki values of 0.6, 62, and 758 nM, respectively. These results indicate that the muscarinic receptors present in neostriatal cultures are of the M1 subtype, having high affinity for pirenzepine and low affinity for AF-DX 116. In contrast with antagonists, carbachol displaced [3H]NMS from two sites with Ki values of 6.5 and 147 microM, with the higher-affinity form predominant (83% of sites). The M1 receptor subtype was linked to phosphoinositide turnover. Carbachol stimulated the formation of phosphoinositides with an EC50 of 37 microM and was antagonized by atropine. At equimolar doses, pirenzepine was more potent than AF-DX 116 at antagonizing the response.