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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pathophysiologic effects of cocaine on neuronal, pulmonary, and cardiovascular tissue are related to the drug's interaction with select catecholamine and neuroendocrine systems. Cocaine has been shown to alter circulating levels of the neurotransmitters, dopamine, norepinephrine, epinephrine, as well as the hypothalamic-pituitary-adrenal axis hormones corticotropin-releasing factor (CRF), adrenocorticotropic hormone (ACTH), and cortisol. Furthermore, brain and lung tissue have been identified as primary sites of cocaine sequestration and metabolism. This paper reviews evidence suggesting that steroid-potentiated actions of catecholamines on vascular tissues contributes to the etiology of cocaine-related medical complications, including ischemic stroke, coronary ischemia, and ischemia-based renal failure.
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PMID:Brain, lung, and cardiovascular interactions with cocaine and cocaine-induced catecholamine effects. 133 74

31P-NMR spectroscopic studies were performed in vivo on brains of rats administered cocaine. Cocaine.HCl (1-5 mg/kg) administered systemically to lightly anesthetized rats resulted in significant and progressive deficits in whole brain intracellular free Mg ([Mg2+]i). Intracellular pH (pHi) also fell in a progressive manner but only after a significant fall in brain [Mg2+]i was noted. Both [Mg2+]i and pHi returned to normal in most rats. Brains of rats that exhibited stroke-like events, however, demonstrated continued intracellular acidosis associated with progressive loss of phosphocreatine and elevation of Pi up until death. These observations are consistent with the tenet that injection of cocaine can result in severe cerebral vasospasm, ischemia and rupture of cerebral blood vessels as a consequence of depletion of brain [Mg2+]i.
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PMID:Cocaine induces intracellular free Mg deficits, ischemia and stroke as observed by in-vivo 31P-NMR of the brain. 142 Feb 62

Although significant morbidity and mortality have been associated with the combined use of cocaine and ethanol, the cardiovascular effects of this combination are unknown. In this study, the effect of ethanol on cocaine-induced cardiovascular alterations was examined in two groups (n = 8 each) of dogs, which were randomized to receive either ethanol (1.68 gm/kg intravenously) or saline solution and cocaine (2 mg/kg intravenously). Ethanol had no effect on heart rate, mean arterial pressure, or rate-pressure product; but it increased ventricular end-diastolic pressure (p < 0.05), reduced coronary diameter (p < 0.02), and decreased ejection fraction by 16% +/- 4% (p < 0.005) from baseline. Cocaine produced increases in mean arterial pressure, rate-pressure product, and left ventricular end-diastolic pressure that were similar in both groups. After administration of cocaine, left ventricular ejection fraction decreased 16% +/- 2% (p < 0.001) from the baseline value in controls and 32% +/- 5% (p < 0.0002 vs baseline; p < 0.01 vs controls) in the ethanol group. Coronary diameter decreased (p < 0.05) in both groups after administration of cocaine; however, there was no difference between groups in the response of coronary circulation to cocaine. Cocaine and ethanol depress myocardial function, and their effects are additive. Failure of ethanol to enhance cocaine-induced coronary vasoconstriction suggests that the additive myocardial depressant effect of this combination is not related to ischemia but rather to a direct toxic effect of these drugs. Individuals who combine ethanol and cocaine may be at increased risk of hemodynamic compromise.
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PMID:Additive myocardial depressant effects of cocaine and ethanol. 144 96

The pathogenesis of acute myocardial ischemia or infarction following cocaine abuse is not known. Cocaine causes an increase in circulating catecholamines. Therefore alpha-adrenergic mediated focal or generalized coronary artery spasm has been presumed to be the likely mechanism to induce ischemia. However, coronary vasospasm in chronic cocaine abusers has not been demonstrated angiographically. Moreover, it has been observed that patients commonly manifest ischemic changes hours up to a week after abusing cocaine. In order to evaluate direct effects of cocaine on coronary vasculature, 6 chronic cocaine abusers admitted with prolonged chest pain and electrocardiographic ST- and T-wave changes were studied. Cocaine administered intravenously (maximum 32 mg) produced subjective sensation of central nervous stimulation (the "high") in all patients. However there was no significant change in coronary artery diameter (assessed by computer-assisted quantitative technique), myocardial perfusion (assessed by contrast echocardiography) or left ventricular wall motion (assessed by two-dimensional echocardiography) as compared with the baseline values. Coronary sinus flow (thermodilution) showed an upward trend, a probable reflection of a significant increase in cardiac output (average 62%, p less than 0.007). Despite a significant elevation in heart rate (average 56%, p less than 0.007), mean systemic arterial pressure (average 12%, p less than 0.05) and rate-pressure product (average 69%, p less than 0.005), no symptomatic or acute electrocardiographic changes were observed. It is concluded that recreational doses of cocaine do not cause focal or generalized coronary vasospasm or reduced myocardial perfusion in patients who present with chest pain temporally related to cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does cocaine cause coronary vasospasm in chronic cocaine abusers? A study of coronary and systemic hemodynamics. 156 28

Cocaine use has increased in recent years, in part as a result of the increased availability of "crack," the inexpensive freebase form. Although it is used medicinally and initially was considered a relatively safe street drug, cocaine clearly has addictive potential as well as adverse health consequences even in low doses. Some of its most serious adverse effects involve the cardiovascular system. Understanding the cellular mechanisms of the action of cocaine on the heart allows insight into the pathophysiology of its adverse effects. Blockade of sodium channels accounts for cocaine's anesthetic effects and acts directly on myocytes to impair action potential generation and conduction, predisposing to dysrhythmias. Blockade of neurotransmitter reuptake has many deleterious effects, including dysrhythmogenesis via increased intracellular calcium, myocardial ischemia via vasospasm and increased myocardial oxygen demand, and contraction band necrosis also via increased intracellular calcium. In addition, alterations in platelet-endothelial cell function predispose to coronary artery thrombosis and ischemia. Alterations in immune function of natural killer cells may, among other effects, predispose to the development of myocarditis, the etiology of which is probably multifactoral. Finally, a direct toxic effect of cocaine on myocytes may, in some cases, produce heart muscle dysfunction. These multiple mechanisms of action combined with the deleterious effects of often-present adulterants give rise to an unpredictable, variable, and potentially life-threatening cardiovascular response to cocaine administration.
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PMID:Cocaine-induced heart disease: mechanisms and pathology. 167 Dec 28

With regard to cardiac findings in cocaine abuse, at autopsy the vast majority of patients dying with cocaine toxicity have either no pathologic change in the heart or only minimal changes that could not account for the patient's death. The second most frequent finding is underlying, mild-to-moderate coronary atherosclerosis, with or without coronary thrombosis. There may be acute or healed myocardial infarction or a sudden cardiac death without myocardial changes of ischemia. A high incidence of contraction band necrosis has been reported in the absence of coronary artery disease and may cause a sudden arrhythmic death. Myocarditis also has been described in a few cases as either lymphocytic or lymphocytic and eosinophilic infiltrate in the presence of myocyte necrosis. Usually, the foci are sparse and not always associated with contraction band necrosis. The underlying mechanisms are thought to be either direct effects of norepinephrine on myocytes or through vasospasm of resistance vessels and secondary myocardial ischemia. Cocaine rarely has been associated with aortic dissection, which is probably a result of cocaine's hypertensive effects.
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PMID:Cocaine-associated cardiovascular disease: clinical and pathological aspects. 174 14

Exposure to cocaine during development has been shown to cause structural and functional alterations in the nervous system. In the current study, the mechanisms underlying these effects were examined in neonatal rats through measurement of ornithine decarboxylase activity, a key regulatory enzyme in the control of neural cell differentiation. Animals were given cocaine (30 mg/kg SC) and ornithine decarboxylase measured 1 and 4 h later in midbrain + brainstem, cerebral cortex and cerebellum. Cocaine caused inhibition of ornithine decarboxylase activity that was not secondary to local anesthesia, as lidocaine was ineffective. The effect of cocaine was independent of direct central actions, as introduction of the drug into the central compartment via intracisternal injection failed to inhibit ornithine decarboxylase. In contrast, prevention of cocaine-induced ischemia by peripheral alpha-adrenergic blockade (phenoxybenzamine) reversed the ornithine decarboxylase inhibition caused by cocaine, and actually unmasked potential stimulatory actions. These data indicate that cocaine-induced ischemia is a major contributor to the net effect of the drug on central nervous system cellular development.
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PMID:Ischemia contributes to adverse effects of cocaine on brain development: suppression of ornithine decarboxylase activity in neonatal rat. 178 62

Spinal cord ischemia and resultant paraplegia are devastating sequelae in up to 40% of patients undergoing repair of thoracoabdominal aneurysms. We investigated the effect of intrathecal tetracaine on the neurological sequelae of spinal cord ischemia and reperfusion with aortic occlusion. Cocaine-derived anesthetics (lidocaine and its analogues) have been shown to decrease neuronal cell metabolism and also have specific neuronal membrane stabilizing effects. New Zealand white rabbits were anesthetized and spinal cord ischemia was then induced by infrarenal aortic occlusion. Animals were divided into six treatment groups. Tetracaine (groups 2 and 4) or normal saline solution (group 5) was administered intrathecally before aortic cross-clamping. Groups 1 and 3 functioned as controls. Group 6 animals received intravenous thiopental. Rabbits were classified as either neurologically normal or injured (paralyzed or paretic). Among controls, 25 minutes of aortic occlusion produced varied neurological sequelae (group 1, 3/6 injured, 50%) whereas 30 minutes resulted in more consistent injury (group 3, 5/6 injured, 83%). All rabbits that received intrathecal saline solution were paralyzed (group 5, 4/4 injured, 100%). Animals treated with intrathecal tetracaine and aortic occlusion of 30 minutes (group 4) showed significantly better preservation of neurological function (6/7 normal, 86%) than controls and saline-treated animals (groups 3 and 5). All animals treated with intrathecal tetracaine and aortic occlusion for 25 minutes (group 2) showed no signs of injury (5/5 normal, 100%), but this was not significant versus controls (group 1). Intravenous thiopental (group 6, 5/5 injured, 100%) had no beneficial effect. Intrathecal tetracaine significantly and dramatically abrogated the neurological injury secondary to spinal cord ischemia and reperfusion after aortic occlusion at 30 minutes in the rabbit model.
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PMID:Spinal cord protection during aortic occlusion: efficacy of intrathecal tetracaine. 203 27

Perinatal exposure to cocaine has been shown to cause morphological and neurobehavioral abnormalities. In the current study, neonatal rats were given an acute injection of cocaine (30 mg/kg s.c.) at 1, 3, 5, 8, 11 or 15 days of age, and [3H]thymidine incorporation into DNA examined over the ensuing 30 min period. Three brain regions were used that differ in their timetables of cell maturation: cerebellum, cerebral cortex and midbrain + brainstem. Cocaine inhibited DNA synthesis in all brain regions, with diminishing impact as the animals matured; by 15 days of age, the effect of cocaine was no longer significant. Inhibition of macromolecule synthesis was selective for DNA, as [3H]leucine incorporation into protein was much less affected by cocaine. Although inhibition of [3H]thymidine incorporation by a single injection of cocaine was short-lived, repeated administration could have cumulative effects: chronic treatment on days 2, 3 and 4 did not desensitize the adverse effect of a subsequent dose administered on day 5. Additionally, with chronic cocaine, the cerebellum displayed a pronounced rebound elevation of DNA synthesis 24 h after the last dose, a characteristic finding in delayed cell maturation. Inhibition of DNA synthesis by cocaine in developing brain was not secondary to ischemia, nor to local anesthesia, as alpha-adrenergic blockade with phenoxybenzamine afforded no protection, and lidocaine could not substitute for cocaine. In contrast, a small amount (15 micrograms) of cocaine injected directly into the central nervous system readily caused inhibition of DNA synthesis; the same dose given systemically had no effect. These data suggest that cocaine damages the developing brain, in part, through direct interference with DNA synthesis.
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PMID:Cocaine acutely inhibits DNA synthesis in developing rat brain regions: evidence for direct actions. 208 73

The chemistry, pharmacology, and pharmacokinetics of cocaine are described, and the medical complications of illicit cocaine use are reviewed. Cocaine is readily absorbed from mucous membranes, the gastrointestinal tract, and the vascular beds of the lungs. Thus there are a number of routes for illicit cocaine administration, with the most popular one being intranasal. The most prevalent problems associated with the use of cocaine appear to be route and dose independent and are cardiovascular in nature; they include myocardial infarction and ischemia, sudden death, cardiac arrhythmias, and hypertension. Seizures, cerebrovascular accidents, hepatotoxicity, rhabdomyolysis, pulmonary complications, and obstetrical complications have also been reported. Gastrointestinal complications and acute toxicity may occur in cocaine smugglers who ingest cocaine-filled packets. Route-dependent complications of cocaine use are also of concern. The mechanism underlying the medical complications has not been fully elucidated but appears to be an extension of the drug's pharmacological properties. The treatment of cocaine-related toxicities is supportive and is based on the organ system affected. Drugs such as propranolol, labetalol, and nitrendipine have been advocated for treating the cardiovascular complications, and measures such as maintaining arterial blood pH, monitoring core body temperature, and diazepam therapy have been used to manage seizures. As the number of case reports of cocaine toxicity increases and the underlying mechanism is conclusively defined, management of the medical complications will improve.
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PMID:Medical complications of illicit cocaine use. 266 29


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