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

It has been suggested that ischemia secondary to coronary vasoconstriction is responsible for adverse cardiovascular effects of cocaine. However, the reported coronary vascular effects of cocaine vary considerably. We sought to determine the effects of cocaine on the coronary vasculature in anesthetized and conscious rats. Rats anesthetized with chloralose were instrumented for estimation of ascending aortic and coronary blood flows using pulsed Doppler velocitometry. Cocaine administration resulted in bradycardia and a biphasic mean arterial pressure response. Cocaine elicited highly variable increases in coronary vascular resistance and decreases in cardiac output. Decreases in coronary blood flow and rate-pressure product were directly correlated. Prazosin significantly attenuated the cardiac output but not the coronary vascular responses to cocaine. Propranolol, on the other hand, significantly shortened the duration of both responses. Conscious rats, instrumented for coronary blood flow determination, also exhibited cocaine-induced increases in coronary vascular resistance, yet the changes in coronary blood flow were not correlated with the rate-pressure product. These results provide the first evidence that cocaine produces equivalent increases in coronary vascular resistance in conscious and anesthetized rats. However, because the relationship between coronary blood flow and rate-pressure is different between the two preparations, as are other cardiovascular responses, we suggest that anesthesia alters the mechanism(s) by which cocaine affects the rat coronary vasculature.
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PMID:Coronary vascular effects of cocaine in rats. 830

It is increasingly apparent that cocaine can provoke lethal cardiac events, including ventricular fibrillation (VF). Cocaine-induced accumulation of intracellular calcium could contribute significantly to the development of these lethal arrhythmias. In order to test this hypothesis, a 2-min coronary occlusion was initiated during the last minute of exercise in instrumented mongrel dogs. Twenty-eight animals were selected in which this test failed to induce ventricular arrhythmias. The test was repeated after cocaine HCl (1.0 mg/kg). Cocaine significantly (P < .01) increased heart rate, left ventricular pressure and d(left ventricular pressure)/dt maximum, and elicited VF in 21 animals. The cocaine exercise+ischemia test was repeated in the animals that developed VF after the pretreatment with the following calcium channel antagonists: diltiazem (n = 8, 1.0 mg/kg), flunarizine (n = 7, 2.5 mg/kg), magnesium sulfate (n = 7, 100 mg/kg), nifedipine (n = 7 100 micrograms/kg), Ro 40-5967 (n = 7, 1.0 mg/kg) and verapamil (n = 6, 250 micrograms/kg). Diltiazem, flunarizine, nifedipine, Ro 40-5967 and verapamil completely suppressed cocaine-induced VF, whereas magnesium prevented VF in five of seven animals. Many of the calcium channel antagonists attenuated the heart rate and systolic pressure increases provoked by cocaine, as well as the heart rate increase induced by the ischemia. Heart rate was therefore matched to the cocaine values by ventricular pacing (verapamil+pace, n = 5), whereas the pressure increases were prevented by nitroprusside (n = 4). Even with heart rate held constant, verapamil prevented VF, whereas nitroprusside failed to protect any animal. Thus, myocardial calcium entry may play a critical role in cocaine-induced VF, whereas calcium antagonists can prevent these malignant arrhythmias independently of their vascular action.
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PMID:Effect of calcium channel antagonists on cocaine-induced malignant arrhythmias: protection against ventricular fibrillation. 833 69

Mesenteric hypoperfusion may be responsible for alterations in gut mucosa leading to necrotizing enterocolitis. Platelet-activating factor (PAF) and cocaine have been implicated in the etiology of necrotizing enterocolitis. We have demonstrated direct toxic effects of these compounds in vitro, but the in vivo mechanism of bowel damage is unknown. Newborn piglets (3.0 +/- 0.3 kg) had physiologic parameters (electrocardiogram, blood pressure, pulse, and central venous pressure) continuously monitored as well as Doppler probe recordings of superior mesenteric artery flow (Qsma). Aortic flow with calculation of cardiac index, and systemic and mesenteric vascular resistances (SVR and MVR) were also determined. Group 1 (N = 8) received PAF (0.5 microgram/kg). Groups 2 (N = 8) and 3 (N = 8) received high (17 mg/kg) and low (9 mg/kg) doses of cocaine, respectively. Each subject served as its own control. Histology demonstrated edema or early mucosal hemorrhage in all groups. PAF caused a third-degree atrioventricular block of short duration and a prolonged decrease of the cardiac index, but only a brief elevation of SVR and MVR. The cocaine groups had a sustained increase of SVR and MVR associated with a decrease of cardiac index. The decrease of Qsma paralleled the changes of MVR in each subject. These data show that both PAF and cocaine induce mesenteric ischemia. The effect of PAF is of short duration and mainly related to its cardiotoxic effects resulting in low Qsma. Cocaine causes an increase in MVR with prolonged depression of mesenteric flow.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Systemic and mesenteric vascular effects of platelet-activating factor and cocaine. In vivo effects on a neonatal swine model. 848 Sep 32

In summary, we report two cases of mesenteric ischemia following cocaine abuse in young women. In such cases it is always difficult to prove a direct causal relationship between the abuse of cocaine and mesenteric ischemia. Both our patients were relatively young (in their thirties) and did not have any history of atherosclerosis, and their urine toxicity screens were positive for the use of cocaine. Cocaine-related hospital visits are on the increase. Mesenteric ischemia should be considered in the differential diagnosis when evaluating a young patient with a history of cocaine abuse presenting with an acute abdomen.
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PMID:Mesenteric ischemia secondary to cocaine abuse: case reports and literature review. 917 33

Nasal insufflation of cocaine injures the nasal mucosa and can perforate the septum. Cocaine-induced vasoconstriction resulting in ischemia is one of the methods that may be responsible for this damage. We are determining whether cocaine also produces a hypercoagulable state that may compound factors which have been previously established to cause damage to the nasal mucosa and septum. This study uses Modified Recalcification Time (MRT), a test developed in our laboratory that has the ability to measure the overall coagulation process. Our study revealed no connection between cocaine and enhanced platelet function or monocyte-released tissue factor. The coagulation process was unaffected by the addition of the drug, so we conclude that cocaine does not cause a hypercoagulable state and cannot assist in the explanation regarding the ischemic changes of the nasal septum.
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PMID:Nasal toxicity of cocaine: a hypercoagulable effect? 1080 Feb 86

Cocaine use can result in various gastrointestinal complications, including gastric ulcerations, retroperitoneal fibrosis, visceral infarction, intestinal ischemia, and gastrointestinal tract perforation. We report cocaine-associated colonic ischemia in three patients and review the literature. Including ours, 28 cases have been reported, with a mean patient age of 32.6 years (range, 23 to 47 years); 53.5% were men and 46.5% were women. The interval between drug ingestion and onset of symptoms varied from 1 hour to 2 days. Cocaine is a potentially life-threatening cause of ischemic colitis and should be included in the differential diagnosis of any young adult or middle-aged patient with abdominal pain and bloody diarrhea, especially in the absence of estrogen use or systemic disorders that can cause thromboembolic events, such as atrial fibrillation.
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PMID:Cocaine-associated ischemic colitis. 1100 54

Cocaine abuse may be associated with a destructive nasal and pharyngeal process felt to be due to ischemia secondary to vasoconstriction. This report is the first to document a necrotizing granulomatous vasculitis associated with nasal destruction and an oronasal fistula in a chronic cocaine user. Cocaine is an environmental insult that may play a role in triggering cerebral and non-cerebral vasculitis including a necrotizing granulomatous vasculitis of the respiratory tract.
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PMID:Necrotizing granulomatous vasculitis associated with cocaine use. 1218 Jul 47

Cocaine has become a popular illicit drug in our society, and pregnant women are not immune from this epidemic. Recently, there have been several references in the literature describing an association between prenatal cocaine exposure and the subsequent development of necrotizing enterocolitis in the neonate, but the mechanism underlying this relationship remains speculative. Because alpha-2 adrenergic receptors are thought to play a role in the autoregulatory mechanism in the newborn intestine that responds to hypoxia and ischemia, we examined the expression of this receptor in the intestine of embryonic rats exposed to low- and high-dose cocaine in utero. Pregnant Sprague Dawley rats were injected daily with either saline, low-dose cocaine, or high-dose cocaine beginning on embryonic d 5 (E 5) and continuing to E 20. Mothers were killed on E 16, E 17, E 18, E 19, and E 20. Embryos were frozen and stored at -80 degrees C. In situ hybridization was performed on 20- micro m sections with 35S-labeled oligonucleotide probes specific for the alpha-2A adrenergic receptor subtype. Densitometric analysis revealed a significant decrease in the alpha-2A receptor expression in the intestine of both the low-dose and high-dose cocaine-exposed animals compared with controls. This down-regulation was demonstrated by E 17, and continued through the remainder of gestation. These changes may limit the normal adaptation to vasoconstriction, thus exacerbating the already insufficient compensatory mechanisms for responding to ischemic injury, and thus may be one of the important factors predisposing cocaine-exposed infants to necrotizing enterocolitis.
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PMID:Alpha-2A adrenergic receptor subtype gene expression in the intestines of cocaine-exposed rat embryos. 1235 43

Over the past 10 years a great deal has been learned about the cardiovascular effects of cocaine. In particular, the acute effects of cocaine have been studied extensively. Upon acute administration cocaine increases blood pressure and heart rate, primarily through an action on the sympathetic nervous system. Cocaine also suppresses the baroreflex response and vagal tone, further contributing to its effects on heart rate. At the same time cocaine is increasing the work-load on the heart it induces coronary artery vasoconstriction, potentially leading to cardiac ischemia. At higher doses cocaine can depress ventricular function and slow electrical conduction in the heart. Both these effects appear to be mediated by cocaine's local anesthetic action. The effects of cocaine mediated by the sympathetic nervous system are greatly reduced in anesthetized animals. Further, when cocaine is administered repeatedly over a short period of time, acute tolerance can develop to the sympathomimetic effects of cocaine. In contrast, the effects of cocaine mediated by its local anesthetic action do not appear blunted by anesthesia or susceptible to acute tolerance. With chronic administration, higher doses appear to induce tolerance while lower doses may induce sensitization to cocaine's sympathomimetic effects. Cocaine also induces a variety of pathological changes in the heart, including myocardial contraction band necrosis and ventricular hypertrophy. These effects of cocaine on the heart can all contribute to potentially lethal cardiovascular events. In addition to the effects of cocaine alone, the metabolites of cocaine may also contribute to cocaine's cardiovascular toxicity, and both licit and illicit drugs used in combination with cocaine might potentially alter its cardiovascular effects.
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PMID:Cocaine and cardiovascular toxicity. 1289 85

Although uncommon, medication-induced colonotoxicity is important to recognize because medication cessation generally leads to prompt clinical improvement, while medication continuation results in disease exacerbation. This review categorizes the association between medications and colonotoxicity as "well-established" or "probable," according to the following criteria: total number of reported cases, number of different research groups reporting an association, experimental and pharmacologic evidence of an association, and validity of an association in each reported case. Cocaine, ergotamine, estrogen, sodium polystyrene, alosetron, amphetamines, pseudoephedrine, and vasopressin are associated with colonic ischemia. The mechanisms include vasospasm, thrombogenesis, and shunting of blood from mesenteric vessels. Narcotics, phenothiazines, vincristine, atropine, nifedipine, and tricyclic antidepressants are associated with colonic pseudo-obstruction. The mechanisms include antagonizing prokinetic neurotransmitters, stimulating antikinetic neurotransmitters, promoting dysmotility, relaxing smooth muscle, and injuring enteric neurons. Numerous antibiotics are associated with pseudomembranous colitis; ampicillin is associated with hemorrhagic colitis; chemotherapy is associated with neutropenic colitis; and deferoxamine is associated with Yersinia enterocolitis. Mechanisms of these toxicities include altering normal bowel flora, weakening immunologic defenses, promoting microorganism virulence, and mucosal injury. Gold compounds, nonsteroidal antiinflammatory drugs, alpha-methyldopa, salicylates, and sulfasalazine are associated with an inflammatory or cytotoxic colitis. The mechanisms include direct mucosal cytotoxicity, antimetabolite effects, or drug allergy. Nonsteroidal antiinflammatory drugs, cyclo 3 fort, flutamide, lansoprazole, and ticlopidine are associated with lymphocytic colitis. The mechanisms include immunologic activation or attenuated immunologic defenses. Chronic cathartic use leads to colonic hypomotility and abdominal distention. Intrarectally administered corrosive compounds can produce a toxic colitis.
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PMID:Colonic toxicity of administered drugs and chemicals. 1518 Jul 42


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