Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activation of an intracellular calcium-calmodulin complex may play an important role in myocardial injury induced by ischemia and reperfusion. Trifluoperazine, a calmodulin antagonist, was used before ischemia to enhance myocardial preservation by preventing intracellular calcium accumulation. The experimental model used an isolated in situ pig heart (19 control animals and 15 trifluoperazine-treated animals) subjected to occlusion of the left anterior descending coronary artery for 60 minutes followed by 60 minutes of hypothermic potassium crystalloid cardioplegic arrest and 60 minutes of reperfusion. Myocardial segmental function measured by ultrasonic crystals showed that active systolic segment shortening was abolished in the distribution of the left anterior descending artery after 60 minutes of occlusion irrespective of the treatment, whereas that not in the distribution of the left anterior descending artery increased by about 15% in both groups of animals. Restoration of systolic segment shortening in the distribution of the left anterior descending artery 60 minutes after reperfusion was 12% and 42% of baseline levels in untreated and trifluoperazine-treated animals, respectively (p less than 0.01). This improvement in segmental function by trifluoperazine was reflected in significantly (p less than 0.05) better global myocardial contractility and compliance and in significantly (p less than 0.01) greater total coronary blood flow and myocardial oxygen consumption. Trifluoperazine also increased myocardial creatine phosphate content in the distribution of the left anterior descending artery (p less than 0.01) during reperfusion, and creatine kinase release was reduced (p less than 0.05). Our results suggest that trifluoperazine improved regional myocardial function after acute occlusion of the left anterior descending artery and reperfusion and that global cardiac performance was thereby improved. The beneficial effects of trifluoperazine may be exerted by prevention of myocardial injury associated with the calcium-calmodulin complex in ischemic and reperfused myocardium.
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PMID:Improvement of myocardial function by trifluoperazine, a calmodulin antagonist, after acute coronary artery occlusion and coronary revascularization. 291 62

An alteration of the blood-brain barrier (BBB) permeability contributes to the development of brain edema after stroke. In this study, we evaluated the effects of 3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate (DY-9760e), a novel calmodulin antagonist, on brain edema formation and BBB integrity in rats subjected to transient focal ischemia. DY-9760e (1 mg/kg/h) was intravenously infused for 6 h, starting immediately after reperfusion of a 1-h middle cerebral artery occlusion. Treatment with DY-9760e significantly suppressed the increase in water content and the extravasation of Evans blue dye after transient focal ischemia. Analysis of a magnetic resonance imaging method revealed that DY-9760e significantly prevented the development of brain edema in the cortical region of the ipsilateral hemisphere. Trifluoperazine, a calmodulin antagonist that is structurally different from DY-9760e, also attenuated brain edema elicited by transient focal ischemia. Furthermore, DY-9760e and trifluoperazine reduced tumor necrosis factor-alpha-induced hyperpermeability of inulin through a cultured brain microvascular endothelial cell monolayer, suggesting an involvement of calmodulin in the regulation of brain microvascular barrier function. The present results demonstrate that DY-9760e ameliorates brain edema formation and suggest that this effect may be mediated in part by the inhibition of enhanced BBB permeability after ischemic insults. Thus, DY-9760e is expected to be a therapeutic drug for treatment of acute stroke patients.
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PMID:3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1H-indazole dihydrochloride 3.5 hydrate (DY-9760e), a novel calmodulin antagonist, reduces brain edema through the inhibition of enhanced blood-brain barrier permeability after transient focal ischemia. 1260 80

Cold preservation results in cell death via iron-dependent formation of reactive oxygen species, leading to apoptosis during rewarming. We aimed to study cold-induced damage (i.e., injury as a consequence of hypothermia itself and not cold ischemia) in proximal tubular cells (PTC) in various preservation solutions presently applied and to clarify the role of mitochondria in this injury. Primary cultures of rat PTC were incubated at 4 degrees C for 24 h in culture medium, UW, Euro-Collins or HTK solution with and without the iron chelator desferal and rewarmed at 37 degrees C in culture medium. Cell damage, morphology, and apoptosis were studied and mitochondrial membrane potential was assessed by fluorescence microscopy. Cold incubation of PTC in culture medium followed by rewarming caused marked cell damage compared to warm incubation alone (LDH release 39+/-10% vs. 1.6+/-0.3%). Cold-induced damage was aggravated in all preservation solutions (LDH release 85+/-2% for UW; similar in Euro-Collins and HTK). After rewarming, cells showed features suggestive for apoptosis. Desferal prevented cell injury in all solutions (e.g., 8+/-2% for UW). Mitochondrial membrane potential was lost during rewarming and this loss could also be inhibited by desferal. Trifluoperazine, which is known to inhibit mitochondrial permeability transition (MPT), was able to prevent cold-induced injury (LDH 85+/-5% vs. 12+/-2%). We conclude that cold-induced injury occurs in PTC and is aggravated by UW, Euro-Collins, and HTK solution. Iron-dependent MPT is suggested to play a role in this damage. Strategies to prevent cold-induced injury should aim at reducing the availability of "free" iron.
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PMID:Hypothermia causes a marked injury to rat proximal tubular cells that is aggravated by all currently used preservation solutions. 1296 15