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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The laboratory rat has been used as an animal model to investigate the effects of cocaine on body temperature and to determine if abuse of the drug is a risk factor in the pathogenesis of exercise-induced heat stroke. Animals were trained to run on a treadmill which was enclosed so that the ambient temperature could be regulated. Exercise at ambient temperatures of 20 and 30 degrees C led to a similar rise in core temperature of approximately 1 degrees C, although the starting core temperature was higher in the rats at 30 degrees C (38.5 +/- 0.10 degrees C compared to 37.9 +/- 0.06 degrees C). Cocaine (20 mg/kg) led to a transient fall in core temperature in the 20 degrees C group; the temperature then rapidly recovered, so that after 60 min exercise there was no significant difference between these and the control animals. At the higher ambient temperature cocaine augmented the rise in core temperature during running, although the animals had regained thermal balance by 30 min and core temperature was maintained at 40.2 +/- 0.13 degrees C until the end of the exercise period. The dopamine D1 receptor antagonist SCH 23390 (0.1, 0.3 or 1.0 mg/kg) led to suppression of spontaneous motor activity so that the rats could be persuaded to exercise for only 30-45 min after treatment. Pretreatment with the antagonist did not affect the rise in core temperature induced by cocaine at 30 degrees C which again stabilized by 30 min at 40.0 +/- 0.12 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cocaine and body temperature: effect of exercise at high ambient temperature. 844 63

Although cocaine abuse has been associated with an increased incidence of cerebrovascular accident, the underlying mechanisms are unknown. In this study we have investigated the effects of cocaine upon the autoregulation of local cortical blood flow (lCBF) during hypertension. Hypertension was induced in conscious rats by intravenous infusion of angiotensin-II (5 micrograms/ml; 0.5-2.5 ml/h), and animals were subsequently injected IV with either cocaine-HCl (5 mg/kg) or saline, prior to the measurement of lCBF of glucose utilization (lCGU) using [14C]-iodoantipyrine or [14C]-2-deoxyglucose quantitative autoradiography, respectively. Hypertension alone (< 155 mmHg) did not significantly alter lCBF in any cortical areas examined. However, at higher mean arterial blood pressure (MABP), lCBF increased focally (+265%) in parietal cortex. Cocaine did not alter lCBF in normotensive animals, but with increasing levels of hypertension (MABP > 145 mmHg), all cocaine-treated rats showed focal increases (200-400%) in lCBF in parietal cortex. Glucose use remained relatively unaffected in all treatment groups. This hyperaemia in cocaine-treated rats at MABP below the normal upper limit of autoregulation may provide a mechanism to explain haemorrhagic stroke in cocaine abusers.
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PMID:Acute cocaine alters cerebrovascular autoregulation in the rat neocortex. 849 81

Cocaethylene is a pharmacologically active cocaine metabolite that is produced in the liver by the transesterification of cocaine only in the presence of ethanol. The acute cardiovascular effects of cocaethylene are not known. We compared the acute cardiovascular effects of cocaethylene with cocaine and with cocaine plus ethanol in 18 dogs. We administered cocaethylene 7.5 mg/kg to 6 dogs, cocaine 7.5 mg/kg to 6 dogs, and cocaine 7.5 mg/kg plus ethanol 1 gm/kg to 6 dogs. The dose of each drug was chosen to produce in dogs the concentrations of cocaethylene or cocaine that have been measured in patients who have experienced cardiotoxic reactions to cocaine or cocaine plus ethanol. Arterial, left ventricular (LV), pulmonary artery wedge pressures (PAWP), the maximum rate of LV pressure rise [(dP/dt)max] and fall [(dP/dt)min], and heart rate (HR) were continuously measured. Stroke volume was determined 3 times during the first hour after drug administration then hourly for four hours. The concentrations of cocaethylene and cocaine peaked in the serum at 3717 +/- 651 ng/ml and 4140 +/- 459 ng/ml, respectively, two minutes after each bolus. The median half-life of cocaethylene was 144.3 minutes whereas the median half-life of cocaine was 96.7 minutes (p < 0.01). Cocaethylene maximally decreased (dP/dt)max by 44%, (dP/dt)min by 29%, and stroke volume by 28% (all p < 0.01) and increased the PAWP by 50% (p < 0.02) and the HR by 13% (p = NS) during the first hour. Cocaine maximally decreased (dP/dt)max by 40%, (dP/dt)min by 31%, and the stroke volume by 26% and increased the PAWP by 100% and the HR by 46% (all p < 0.01) during the first hour. Ethanol plus cocaine maximally decreased (dP/dt)max by 68%, (dP/dt)min by 78% and the stroke volume by 49% and increased the PAWP by 118% and the HR by 74% (all p < 0.01) during the first hour. In this last group, (dP/dt)max and stroke volume remained depressed by approximately 20% (p < 0.01) for five hours. We conclude that cocaethylene is as toxic as cocaine to the myocardium but is less toxic than ethanol plus cocaine.
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PMID:Cocaethylene is as cardiotoxic as cocaine but is less toxic than cocaine plus ethanol. 876 Oct 12

Cocaine use has been associated with vasoconstriction and stroke, and several studies have demonstrated that it decreases relative cerebral blood flow (rCBF) in humans. However, rCBF has not been quantitated. We compared 40 mg IV cocaine hydrochloride to placebo effects on absolute rCBF in four cocaine users using 99mTc-HMPAO SPECT with a modified microsphere model for CBF quantitation. Cocaine produced significant decreases in rCBF in all regions studied with a mean decrease of 30% in absolute whole brain blood flow (P = 0.002) which was 3-fold greater than relative blood flow changes.
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PMID:Acute cocaine effects on absolute cerebral blood flow. 894 1

Several agents have been used to treat cocaine-related cardiovascular complications and toxicity occurring in sensitive individuals, yet the causes of hemodynamic responsiveness and differential sensitivity to cocaine are unknown. In this study, we sought to examine the role of different mediators in a model of variable cardiovascular responses to cocaine. As noted previously in conscious rats, cardiac output (CO) and systemic vascular resistance (SVR) responses to cocaine (5 mg/kg, i.v.) varied widely. Twenty of 34 rats exhibited cocaine-induced decreases in CO of > or =8% and large increases in SVR (designated vascular responders). The remaining rats with little change or an increase in CO and smaller increases in SVR were named mixed responders. Pretreatment with propranolol (1 mg/kg) or metoprolol (1 mg/kg) reduced heart rate. In mixed responders, propranolol or metoprolol reversed the cocaine-induced increase in CO and stroke volume and enhanced the increase in SVR, making these rats respond like vascular responders. Nicardipine (25 microg/kg) reduced the pressor response and selectively reversed the CO responses in vascular responders. N omega-nitro-L-arginine methyl ester (L-NAME; 2.7 mg/kg) increased arterial pressure by increasing SVR. Cocaine induced greater pressor and SVR responses apparently because of a shift in baseline values elicited by L-NAME alone. Therefore, differences in hemodynamic responses patterns may be the result of differences in beta-adrenergic activation or subsequent calcium channel activation or both. We predict that calcium channel antagonists may be useful to treat cocaine-induced cardiovascular complications, whereas beta-adrenergic antagonists are not likely to be beneficial.
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PMID:Mechanisms of hemodynamic responses to cocaine in conscious rats. 951 84

Cocaine is a highly psychoactive substance with numerous effects that readily crosses the placenta, achieving variables levels in the fetus. Determining whether prenatal exposure to cocaine and its metabolites damages the developing human nervous system is hindered by the multiple intervening factors (confounders) that plague clinical settings, which warrant consideration in controlled studies. Prenatal cocaine exposure has been linked to numerous adverse neonatal outcomes, affecting fetal growth (i.e., low birth weight, intrauterine growth retardation, and small head size) and neurobehavior. These neurobehavior effects span the gamut from no abnormalities to impairments in arousal, neurological function, neurophysiological function, and state regulation. Strokes and possibly seizures are also noted. Dose-response effects of fetal cocaine exposure on fetal growth and neonatal neurobehavior are reported using quantitative methods of ascertainment. In early infancy, irritability and hypertonia are also described. Most cocaine associations are transient and resolve in infancy and early childhood. Whether such transient abnormalities place infants at increased risk for later neurodevelopmental impairments is not known. Controlled studies have found no cognitive differences related to prenatal cocaine exposure among toddlers or school age children, except as mediated through effects on head growth. Anecdotally, cocaine-exposed children seem to suffer from neurobehavioral abnormalities, but to date controlled studies have not established an association between cocaine and behavioral disorders, except for inattentiveness. Despite encouraging reports, the question of whether cocaine exerts long-term adverse effects on the developing human nervous system has not yet been resolved, largely because of the limitations of existing studies that rely on inadequate, mostly qualitative ascertainment of cocaine exposure as well as the dearth of studies in older children. Such methodological limitations may have compromised our ability to identify cocaine-exposed children at most risk.
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PMID:Neurological correlates of fetal cocaine exposure. 966 1

Cocaine abuse has been associated with vasculitis and stroke, and is suspected to influence the progression of AIDS dementia. Cocaine may enhance HIV-1 neuroinvasion by actions directed at the blood-brain barrier. HIV-1 appears to penetrate the human brain microvascular endothelial cell barrier by a paracellular route breached by tumor necrosis factor-alpha (TNF-alpha). Cocaine's effects on the blood-brain barrier were investigated using human brain microvascular endothelial cells and peripheral blood monocytes. Cocaine (10(-5) M and 10(-6) M) increased molecular permeability of the barrier and viral invasion by the macrophage-tropic HIV-1(JR-FL) into the brain chamber. Cocaine also augmented apoptosis of brain endothelial cells and monocytes, increased secretion of four chemokines (interleukin-8, interferon-inducible protein-10, macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1) and the cytokine, TNF-alpha, by human monocytes. TNF-alpha enhanced invasion of the brain compartment by macrophage-tropic, lymphotropic, and bitropic HIV-1 strains. These data indicate that HIV-1 neuroinvasion can be increased by (a) cocaine's direct effects on brain microvascular endothelial cells and (b) paracrine effects of cocaine-induced pro-inflammatory cytokines and chemokines on the blood-brain barrier.
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PMID:Cocaine opens the blood-brain barrier to HIV-1 invasion. 1006 3

Cocaine use is associated with adverse events in nearly every organ system. Cardiovascular complications include hemorrhagic and ischemic stroke, aortic dissection, cardiomyopathy, accelerated coronary artery disease, myocardial infarction, and sudden cardiac death. Syncope may be the presenting symptom in these conditions. However, cocaine-induced bradyarrhythmias have been scarcely mentioned. As this case exemplifies, clinicians should be aware of this association when they evaluate syncope, especially in young patients.
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PMID:Cocaine-induced bradyarrhythmia: an unsuspected cause of syncope. 1063 Dec 30

Cocaine-associated stroke (CAS) is an important cause of disability, especially among younger adults. Improved management has increased survival but little has been discussed about rehabilitation, including medication management. Therefore, experience and therapeutic drug management are described during inpatient rehabilitation with three patients with CAS. Case 14 is a 50-year-old male with a history of hypertension who presented with right hemiparesis, aphasia and depression. He was treated with paroxetine for depression and bromocriptine for poor initiation with a good response, improving by 50 FIM points in 44 days. Case 2 is a 44 year-old female with quadriparesis, aphasia, and deficits in attention and initiation. Methylphenidate for attention deficits and bromocriptine for poor initiation was associated with an excellent functional gain (50 FIM points in 37 days). She eventually returned to work. Case 3 is a 46-year-old female with a history of hypertension who presented with right hemiparesis, aphasia and depression. Without neuropharmacologic intervention, she gained 35 FIM points during an uneventful 47 day rehabilitation stay. Acutely, cocaine can induce cerebral vasoconstriction, cerebrovascular spasm, cerebral vasculitis and intracerebral haemorrhage. Chronic use depletes and destroys dopaminergic pathways, which may be a major factor in depression, and attention and initiation deficits-all observed in these cases. Generally, rapid improvements were seen in mood and cognition in two cases where medication was used. Based on the current literature and pathophysiology of CAS, it is suggested that trials of dopaminergic agents for cognition and extremely cautious use of buproprion for depression may be warrented. Details of the above cases and the practical and theoretical issues of neuropharmacologic intervention in CAS are discussed.
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PMID:Cocaine-associated stroke: three cases and rehabilitation considerations. 1081 46

Cocaine may cause stroke, intracranial hemorrhage, seizures, and neurobehavioral abnormalities in fetuses, newborns, and adults, and there could be developmental and/or species differences in mechanisms for these cocaine-induced cerebrovascular effects. To evaluate developmental differences in responses to cocaine, we compared the cerebrovascular and metabolic responses to a 2 mg/kg iv cocaine dose in unanesthetized fetal (n = 8, previously reported, direct fetal injection), newborn (n = 6), and adult (n = 12) sheep. We measured cerebral blood flow, mean arterial blood pressure, and arterial and venous O(2) content, and we calculated cerebral O(2) consumption and cerebral vascular resistance at baseline and at 30 s and at 5, 15, and 60 min after cocaine injection. Cerebral blood flow increased 5 min after injection in the fetus and newborn, but not until 15 min in the adult. In the fetus, cocaine caused a transient cerebral vasoconstriction at 30 s; in all three groups, cocaine caused cerebral vasodilation, which was delayed in the adult. Cerebral metabolic O(2) consumption increased 5 min after injection in the fetus and newborn, but not until 15 min after injection in the adult. Arterial O(2) content decreased 5 min after injection in the fetus and 15 min after injection in the adult. We speculate that clinical differences in response to cocaine injection may be explained, in part, by these developmental differences in the cerebrovascular and metabolic responses to cocaine.
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PMID:Comparison of cerebrovascular effects of intravenous cocaine injection in fetal, newborn, and adult sheep. 1089 35


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