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)

To investigate cardiac stunning, we recorded intracellular [Ca(2+)], contractions, and electrical activity in isolated guinea pig ventricular myocytes exposed to simulated ischemia and reperfusion. After equilibration, ischemia was simulated by exposing myocytes to hypoxia, acidosis, hyperkalemia, hypercapnia, lactate accumulation, and substrate deprivation for 30 min at 37 degrees C. Reperfusion was simulated by exposure to Tyrode solution. Field-stimulated myocytes exhibited stunning upon reperfusion. By 10 min of reperfusion, contraction amplitude decreased to 43.0 +/- 5.5% of preischemic values (n = 15, P < 0.05), although action potential configuration and sarcoplasmic reticulum Ca(2+) stores, assessed with caffeine, were normal. Diastolic [Ca(2+)] and Ca(2+) transients (fura 2) were also normal in stunned myocytes. In voltage-clamped cells, peak L-type Ca(2+) current was reduced to 47.4 +/- 4.5% of preischemic values at 10 min of reperfusion (n = 21, P < 0.05). Contractions elicited by Ca(2+)-induced Ca(2+) release and the voltage-sensitive release mechanism were both depressed in reperfusion. Our observations suggest that stunning is associated with reduced L-type Ca(2+) current but that alterations in Ca(2+) homeostasis and release are not directly responsible for stunning.
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PMID:Changes in excitation-contraction coupling in an isolated ventricular myocyte model of cardiac stunning. 1212 30

Males exhibit enhanced myocardial ischemia-reperfusion injury versus females under hypercontractile conditions associated with increased sarcoplasmic reticulum (SR) Ca2+. We therefore examined whether there were gender differences in SR Ca2+. We used NMR Ca2+ indicator 1,2-bis(2-amino-5,6-difluorophenoxy)-ethane-N,N,N',N'-tetraacetic acid to measure SR Ca2+ in perfused rabbit hearts. Isoproterenol increased SR Ca2+ in males from a baseline of 1.13 +/- 0.07 to 1.52 +/- 0.24 mM (P < 0.05). Female hearts had basal SR Ca2+ that was not significantly different from males (1.04 +/- 0.03 mM), and addition of isoproterenol to females resulted in a time-averaged SR Ca2+ (0.97 +/- 0.07 mM) that was significantly less than in males. To confirm this difference, we measured caffeine-induced release of SR Ca2+ with fura-2 in isolated ventricular myocytes. Ca2+ release after caffeine in untreated male myocytes was 377 +/- 41 nM and increased to 650 +/- 55 nM in isoproterenol-treated myocytes (P < 0.05). Ca2+ release after caffeine addition in untreated females was 376 +/- 27 nM and increased to 503 +/- 49 nM with isoproterenol, significantly less than in male myocytes treated with isoproterenol (P < 0.05). Treatment of female myocytes with NG-nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase (NOS), resulted in higher SR Ca2+ release than that measured in females treated only with isoproterenol and was not significantly different from that measured in males with isoproterenol. Female myocytes also have significantly higher levels of neuronal NOS. This gender difference in SR Ca2+ handling may contribute to reduced ischemia-reperfusion injury observed in females.
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PMID:Gender differences in sarcoplasmic reticulum calcium loading after isoproterenol. 1294 30

The temporal association of symptoms consistent with ephedrine toxicity after ingestion of ephedrine-containing dietary supplements is heavily relied upon to confirm exposure. Few reports in the literature attempt to associate toxicity with serum levels of these drugs. We report a case of ephedrine-induced cardiac ischemia confirmed by a plasma level. A 22-year-old woman ingesting an ephedrine- and caffeine-containing product for 2 days presented with multiple symptoms, including palpitations, nausea, tremulousness, abdominal pain, and vomiting. The initial electrocardiogram (ECG) revealed a normal sinus rhythm with 1 mm of ST segment depression in leads V3 and V4, along with inverted T waves in leads V1-V4. Her symptoms and ST segment depression resolved over several hours with medical management. The amplitude of her T wave inversions notably diminished with therapy; however, they did not completely resolve. Troponins at presentation and the following morning were negative, and an echocardiogram showed only trace tricuspid regurgitation. A serum ephedrine level, drawn approximately 6 to 7 hr after ingestion, was 150 ng/mL. She was discharged from the hospital after being instructed to avoid ephedrine-containing products.
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PMID:Ephedrine-induced cardiac ischemia: exposure confirmed with a serum level. 1467 95

The adenosine A1/A2 adenosine agonist 5'-(N-ethylcarboxamido) adenosine (NECA) and bradykinin both limit infarction when administered at reperfusion in rabbits. This study compares the signal transduction pathways responsible for their anti-infarct effect. Receptor agonists were administered to isolated rabbit hearts starting 25 min after the onset of a 30-min period of ischemia and continued into the 2-h reperfusion period. Infarct size was measured. Both NECA and bradykinin decreased infarction from 31.5 +/- 2.4% of the risk zone in untreated hearts to 11.8 +/- 2.0% and 15.4 +/- 2.4%, respectively (P<0.05). Protection from both agents was blocked by PD98059, wortmannin, and Nomega-nitro-L-arginine methyl ester (L-NAME), thus demonstrating dependence on activation of extracellular regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K) and stimulation of nitric oxide synthase (NOS). Both wortmannin and PD98059 prevented phosphorylation of ERK 1/2 in NECA-treated hearts, whereas only wortmannin and not PD98059 blocked Akt phosphorylation. These data suggest Akt is upstream of ERK 1/2. In addition, 8-(3-chlorostyryl) caffeine blocked NECA's protection indicating that A2 adenosine receptors trigger NECA's anti-infarct effect. Of note, both bradykinin and acetylcholine (ACh) administered before ischemia to trigger preconditioning's cardioprotection use PI3K and NOS in their signaling pathway. Curiously, however, ACh, unlike bradykinin, was not protective when administered at reperfusion. Hence, both NECA and bradykinin administered at reperfusion protect through a common signaling pathway that includes PI3K, NO, and ERK.
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PMID:NECA and bradykinin at reperfusion reduce infarction in rabbit hearts by signaling through PI3K, ERK, and NO. 1501 Feb 80

The vascular placental pathology (VPP) is associated with many etiologies. Some are the consequence of a maternal genetic or acquired predisposition. Others are associated with a chronic maternal disease (hypertension, lupus, obesity, diabetes, ...). Finally, some others are associated with placental implantation leading to fetal ischemia (multiple pregnancy, chorioangioma, primiparity, feto-placental hydrops) or to environmental (altitude) or nutritional factors (famine and specific alimentary depressions). We classify these factors into three categories according to the risk level (moderate, significant and elevated). While any of these factors can increase the risk of VPP, no one is sufficiently sensitive or specific in predict inevitable onset of VPP. In most cases VPP results from a combination of two (or more) risk factors. The risk factors of VPP classified as moderate include age (> or = 35 years), increased blood pressure during the second trimester of pregnancy, a new paternity, dietetic factors or environmental factors, smoking and controlled diabetes (class B, C), or inactive systemic diseases. Risk is significantly elevated among obese (BMI > or = 25), primiparous women, women with a past familial history (first degree) of preeclampsia or eclampsia, cocaine use or association of tobacco and caffeine use, increased placental mass (associated with twin pregnancy, fetal hydrops or molar pregnancy), uncontrolled diabetes, lupus, active scleroderma. Risk is considered to be high among patients with chronic hypertension, women with a past history of preeclampsia, diabetes (class D, F, R), patients with active systemic disease or with antiphospholipid antibodies or women with lupus or renal lesions and/or proteinuria as well as chronic kidney disease resulting in proteinuria, hypertension and renal insufficiency. Finally, the risk of VPP is considered to be increased in the presence of acquired thrombophilia. It remains moderate in the presence of isolated genetic thrombophilia, except in forms presenting with multiple genetic mutations or associated with an hyperhomocysteinemia. A "high-risk group" is defined among women with past history of deep venous thromboembolic events outside pregnancy, or with a past history of placental vascular pathology (intra-uterine death, placental abruptio, severe and precocious placental, intra-uterine growth retardation, early and repetitive fetal loss) and who, in addition, present with acquired thrombophilia (antiphospholipid antibodies, thrombocytemia), unique homozygous genetic thrombophilia, amultiple genetic thrombophilia or unique heterozygous genetic thrombophilia associated with hyperhomocysteinemia. Prophylactic treatment of acquired thrombophilia and of the multiple genetic forms or associated with hypercysteinemia is a logical rationale, particularly among women with a past history of placental vascular pathology, or with a past history of venous thromboembolic events. On the contrary, prophylaxis using low-molecular-weight heparin in the event of asymptomatic genetic thrombophilic mutations and for women without a past history of deep venous thromboembolism or vascular placental pathology remains controversial.
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PMID:[Vascular placental pathology in high-risk groups: definition and synopsis]. 1502 87

The combination of low-dose ethanol and caffeine (caffeinol) protects cortical areas of the brain from damage produced by distal focal ischemia in rats. There are no data, however, as to whether caffeinol influences injury in subcortical brain regions. Rats were anesthetized with halothane and subjected to 2 h of MCAo by poly-l-lysine-coated intraluminal suture. Caffeinol [a combination of ethanol, 0.33 g/kg, and caffeine, 10 mg/kg (n=5)] or vehicle (0.9% NaCl; n=7) was administered by i.v. infusion over a 2.5-h period beginning 15 min after reperfusion. Neurological status was evaluated daily, and histopathology was quantified at 3 days. Caffeinol therapy significantly improved the neurological score, reduced the total infarct volume (by 52%) and cortical infarct areas at multiple coronal levels, but subcortical infarction and brain swelling were not affected.
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PMID:Caffeinol confers cortical but not subcortical neuroprotection after transient focal cerebral ischemia in rats. 1514 66

This study investigates whether protective effects of an angiotensin II type 1 receptor antagonist (losartan) in ischemia and reperfusion are mediated by actions on Ca(2+) cycling. Effects of exposure to losartan (10 microM) in ischemia were evaluated in isolated guinea pig ventricular myocytes exposed to simulated ischemia and reperfusion at 37 degrees C. Field-stimulated myocytes were exposed to 30 min of simulated ischemia (hypoxia, acidosis, lactate, hyperkalemia, and glucose-free) and reperfusion with Tyrode's solution for 40 min. Cell shortening was measured with a video edge detector, and Ca(2+) concentration was measured with fura-2. Field-stimulated myocytes exhibited stunning in reperfusion, which was abolished in cells exposed to losartan. In microelectrode studies, losartan did not alter the responses of resting potentials or action potentials to ischemia and reperfusion. In the absence of losartan, diastolic Ca(2+) increased in ischemia, and Ca(2+) transients exhibited a rebound overshoot in early reperfusion. Losartan did not affect amplitudes of Ca(2+) transients in ischemia but prevented elevations in diastolic Ca(2+) in ischemia. Furthermore, losartan prevented the overshoot of Ca(2+) transients in early reperfusion and increased the magnitude of Ca(2+) transients in late reperfusion. Sarcoplasmic reticulum (SR) Ca(2+) stores, determined as Ca(2+) released by rapid application of 10 mM caffeine, were not altered in ischemia and reperfusion. However, losartan increased SR Ca(2+) stores in late reperfusion, even in cells that were not exposed to simulated ischemia. We conclude that losartan abolishes stunning in reperfusion by preserving normal diastolic Ca(2+) in ischemia and by increasing Ca(2+) transients through elevation of releasable SR Ca(2+).
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PMID:Attentuation of cardiac stunning by losartan in a cellular model of ischemia and reperfusion is accompanied by increased sarcoplasmic reticulum Ca2+ stores and prevention of cytosolic Ca2+ elevation. 1531 90

Recent studies demonstrated that resveratrol, a grape-derived polyphenolic phytoalexin, provides pharmacological preconditioning (PC) of the heart through a NO-dependent mechanism. Because adenosine receptors play a role in PC, we examined whether they play any role in resveratrol PC. Rats were randomly assigned to groups perfused for 15 min with 1) Krebs-Henseleit bicarbonate buffer (KHB) only; 2) KHB containing 10 microM resveratrol; 3) 10 microM resveratrol + 1 microM 8-cyclopentyl-1,3-dimethylxanthine (CPT; adenosine A(1) receptor blocker); 4) 10 microM resveratrol + 1 microM 8-(3-chlorostyryl)caffeine (CSC; adenosine A(2a) receptor blocker); 5) 10 microM resveratrol + 1 microM 3-ethyl-5-benzyl-2-methyl-4-phenylethynyl-6-phenyl-1,4-(+/-)-dihydropyridine-3,5-dicarboxylate (MRS-1191; adenosine A(3) receptor blocker); or 6) 10 microM resveratrol + 3 microM 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride [LY-294002, phosphatidylinositol (PI)3-kinase inhibitor], and groups perfused with adenosine receptor blockers alone. Hearts were then subjected to 30-min ischemia followed by 2-h reperfusion. The results demonstrated significant cardioprotection with resveratrol evidenced by improved ventricular recovery and reduced infarct size and cardiomyocyte apoptosis. CPT and MRS 1191, but not CSC, abrogated the cardioprotective abilities of resveratrol, suggesting a role of adenosine A(1) and A(3) receptors in resveratrol PC. Resveratrol induced expression of Bcl-2 and caused its phosphorylation along with phosphorylation of cAMP response element-binding protein (CREB), Akt, and Bad. CPT blocked phosphorylation of Akt and Bad without affecting CREB, whereas MRS 1191 blocked phosphorylation of all compounds, including CREB. LY-294002 partially blocked the cardioprotective abilities of resveratrol. The results indicate that resveratrol preconditions the heart through activation of adenosine A(1) and A(3) receptors, the former transmitting a survival signal through PI3-kinase-Akt-Bcl-2 signaling pathway and the latter protecting the heart through a CREB-dependent Bcl-2 pathway in addition to an Akt-Bcl-2 pathway.
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PMID:Pharmacological preconditioning with resveratrol: role of CREB-dependent Bcl-2 signaling via adenosine A3 receptor activation. 1534 77

Although molecular chaperones in the endoplasmic reticulum (ER) are known to be involved in folding and assembly of glycosylated proteins, it is unclear whether preinduced ER chaperones can protect cardiomyocytes from lethal injury. In this study we used tunicamycin, an inhibitor of N-linked glycosylation in the ER, to preinduce ER chaperones in H9c2 cardiomyocytes and we tested the cytoprotective role of preinduced ER chaperones in the cardiomyocytes. Expression of GRP78 at both protein and mRNA levels was markedly increased in cardiomyocytes pretreated with tunicamycin, when compared to non-treatment controls. Following prolonged ATP depletion or oxidative stress, which was used to simulate cardiac ischemia and reperfusion injury, respectively, the release of lactate dehydrogenase (LDH) from tunicamycin-pretreated cardiomyocytes was significantly lower than from non-pretreated cardiomycocytes. Tunicamycin-pretreated cardiomyocytes showed significantly higher Ca2+ release into cytoplasm than controls when treated with both caffeine and thapsigargin, indicating higher storage of Ca2+ in the ER. After oxidative stress, cytosolic Ca2+ levels were maintained relatively stable in tunicamycin-pretreated cardiomyocytes, when compared to control cardiomyocytes. These observations suggest that preinduced ER chaperones protect cardiomyocytes from lethal injury, at least in part, by preventing an increase in cytosolic Ca2+.
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PMID:Preinduced molecular chaperones in the endoplasmic reticulum protect cardiomyocytes from lethal injury. 1564 88

N,N,N',N'-Tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN), a transition-metal chelator, was recently found to protect against myocardial ischemia-reperfusion injury. The goals of this study were to investigate the in vivo antiarrhythmic and antifibrillatory potential of TPEN in rats and guinea pigs and to study the in vitro effects of TPEN on calcium homeostasis in cultured newborn rat cardiac cells in normoxia and hypoxia. We demonstrated on an in vivo rat model of ischemia-reperfusion that TPEN abolishes ventricular fibrillation incidence and mortality and decreases the incidence and duration of ventricular tachycardia. To elucidate the mechanism of cardioprotection by TPEN, contraction, synchronization, and intracellular calcium level were examined in vitro. We have shown for the first time that TPEN prevented the increase in intracellular Ca(2+) levels ([Ca(2+)](i)) caused by hypoxia and abolished [Ca(2+)](i) elevation caused by high extracellular Ca(2+) levels ([Ca(2+)](o)) or by caffeine. Addition of TPEN returned synchronized beating of cardiomyocytes desynchronized by [Ca(2+)](o) elevation. To discover the mechanism by which TPEN reduces [Ca(2+)](i) in cardiomyocytes, the cells were treated with thapsigargin, which inhibits Ca(2+) uptake into the sarcoplasmic reticulum (SR). TPEN successfully reduced [Ca(2+)](i) elevated by thapsigargin, indicating that TPEN did not sequester Ca(2+) in the SR. However, TPEN did not reduce [Ca(2+)](i) in the Na(+)-free medium in which the Na(+)/Ca(2+) exchanger was inhibited. Taken together, the results show that activation of sarcolemmal Na(+)/Ca(2+) exchanger by TPEN increases Ca(2+) extrusion from the cytoplasm of cardiomyocytes, preventing cytosolic Ca(2+) overload, which explains the beneficial effects of TPEN on postischemic cardiac status.
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PMID:N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine improves myocardial protection against ischemia by modulation of intracellular Ca2+ homeostasis. 1568 57


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