Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endogenous glycogen stores are essential to maintain cell functions during myocardial ischemia.. Fasting and L-glutamate improve left ventricular function after an ischemic episode. We studied their effects on myocardial glycogen depletion during ischemia and on left ventricular function and glycogen resynthesis during reperfusion. We allocated 185 Wistar rats to 4 groups: 1) Control, 2) Fasting, 16-20 hours (Fast) 3) L-glutamate supplementation [100 mM] (Glt) or 4) Fasting + L-glutamate supplementation [100 mM]. n = 8-10 in each group. Hearts were mounted in an isolated perfused rat hearts model for 20 min stabilisation, 10/20/30 min ischemia and 60 min reperfusion. At each time point hearts were frozen in liquid nitrogen (-196 degrees C) within 2 seconds and myocardial contents of glycogen, lactate, alanine and glutamate were determined. Left ventricular pressure was measured continuously. Fasting and L-glutamate supplementation improved LV function after ischemia (Fast: p < 0.05, Glt: p < 0.01) and delayed myocardial glycogen depletion (Fast: p < 0.05, Glt: p < 0.01) compared to control. Decreased lactate accumulation and increased alanine content during ischemia were found in fasted (lactate: p < 0.05, alanine: p < 0.05) and L-glutamate supplemented (lactate: p < 0.01, alanine: p < 0.01) hearts compared to control. We did not find any additive effects of fasting and L-glutamate supplementation. In conclusion fasting and L-glutamate supplementation improve left ventricular function during reperfusion and delay myocardial glycogen depletion during ischemia. There were no additive effects of Fasting and L-glutamate supplementation. These finding suggest common metabolic pathways underlying the effects of L-glutamate supplementation and fasting.
 ...
PMID:Effects of L-glutamate supplementation mimic effects of fasting in the ischemic heart. 1287 62

Cardiac ischemia causes beat-to-beat fluctuation in action potential duration (APD) alternans, which leads to T wave alternans and arrhythmias. Occurrence of APD alternans that is out of phase at two sites is especially important, but most APD alternans studies have involved rapid pacing of normal myocardium rather than ischemia. To determine the spatial features of APD alternans during ischemia, blood-perfused rabbit hearts were stained with 4-[beta-[2(di-n-butylamino)-6-napthyl]vinyl]pyridinium (di-4-ANEPPS) and imaged with a high-resolution camera. Hearts were perfused with oxygenated Tyrode solution at 37 degrees C for staining and then switched to a 50:50% blood/Tyrode mixture. Hearts were paced from the right ventricle at 3/s, and made ischemic by stopping flow for 6 min. Images of 10,000 pixels were obtained at 300 frames/s. Motion artifact was controlled by immobilization and by manual selection of undistorted single-pixel records. Upstroke propagation and conduction isochrones were displayed by computerized image processing. APD alternans was demonstrated in six of seven hearts, and was out of phase in different regions of the image in three hearts. The largest spatial variation in the onset of depolarization to 50% repolarization (APD50) was 155%. This caused beat-to-beat reversal of repolarization. An alternans map could be constructed for well-immobilized portions of the image. There were discrete regions of APD alternans separated by a boundary, as occurs with intracellular Ca2+ concentration alternans. Pixels as close together as 1.1 mm showed an APD alternans that was out of phase. The out-of-phase APD alternans was not due to conduction alternans, as shown by upstroke intervals and conduction isochrones. This contrasts with rapid pacing, where a causal relationship appears to exist. These new observations suggest distinct mechanisms for the genesis of arrhythmias during ischemia.
 ...
PMID:Spatial heterogeneity of action potential alternans during global ischemia in the rabbit heart. 1290 20

Erythropoietin is protective against cardiac ischemia, but the underlying mechanisms are unknown. We determined whether erythropoietin (0.5 - 10.0 U/ml) confers acute cardioprotection in infant rabbit hearts and the contribution of protein kinases, nitric oxide synthase and potassium channels to the underlying mechanism. Hearts from normoxic infant New Zealand White rabbits (n=8/group) were isolated and perfused in the Langendorff mode. Biventricular function was recorded under steady-state conditions prior to 30 min global no-flow ischemia and 35 min reperfusion. Administration of erythropoietin for 15 min immediately prior to ischemia resulted in a concentration-dependent increase in recovery of left and right ventricular developed pressure in rabbit hearts following myocardial ischemia and reperfusion. The optimal concentration of erythropoietin that afforded maximum recovery of developed pressure was manifest at 1.0 U/ml. Erythropoietin (1.0 U/ml) treatment resulted in phosphorylation of PKC, p38 MAP kinase and p42/44 MAP kinase. The cardioprotective effects of erythropoietin were abolished by the protein kinase inhibitors SB203580 (p38 MAP kinase), PD98059 (p42/44 MAP kinase) and chelerythrine (PKC) as well as the potassium channel blockers glibenclamide, HMR 1098, 5-HD and Paxilline. Nitrite and nitrate release from hearts before (2.3 +/- 0.9 nmol/min/g) and after (2.4 +/- 1.9 nmol/min/g) 15 min treatment with erythropoietin (1.0 U/ml) were not different. L-NAME and L-NMA did not block the cardioprotective effect of erythropoietin. We conclude the rapid activation of potassium channels and protein kinases by erythropoietin represents an important new mechanism for increasing cardioprotection.
 ...
PMID:Acute cardioprotective effects of erythropoietin in infant rabbits are mediated by activation of protein kinases and potassium channels. 2751 2

The signaling pathways involved in ischemic heart disease are not well characterized. In this study, the roles of Ras-GTPase, tyrosine kinases (TKs) and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in global ischemia and reperfusion (I/R) in a perfused rat heart model were investigated and compared to beneficial effects produced by preconditioning (PC). A 40 min episode of global ischemia followed by a 30 min reperfusion in perfused rat hearts produced significantly impaired cardiac function, measured as left ventricular developed pressure (Pmax) and left ventricular end-diastolic pressure (LVEDP), and impaired coronary hemodynamics, measured as coronary flow (CF) and coronary vascular resistance (CVR). Hearts from male Wistar rats pre-treated with the tyrosine kinase inhibitor, genistein (1 mg/kg/day for 6 days), or the CaMKII inhibitor, KN-93 (578 ng/min for 6 days), produced detrimental effects on recovery of cardiac function and coronary hemodynamics. In contrast, pre-treatment with Ras-GTPase inhibitor FPT III (232 ng/min for 6 days) significantly enhanced cardiac recovery in terms of left ventricular contractility and coronary vascular hemodynamics. Treatment with FPT III also significantly reduced expression of the sodium-hydrogen exchanger-1 (NHE-1) which was elevated during I/R as detected by Western blotting. These data suggest that TKs and CaMKII are involved in signaling pathways leading to recovery from cardiac ischemia, whereas activation of Ras-GTPase signaling pathways are critical in the development of cardiac dysfunction due to I/R.
 ...
PMID:Inhibition of Ras-GTPase, but not tyrosine kinases or Ca2+/calmodulin-dependent protein kinase II, improves recovery of cardiac function in the globally ischemic heart. 1512 5

Aldose reductase (AR), a member of the aldo-keto reductase family, has been implicated in the development of vascular and neurological complications of diabetes. Recently, we demonstrated that aldose reductase is a component of myocardial ischemic injury and that inhibitors of this enzyme protect rat hearts from ischemia-reperfusion injury. To rigorously test the effect of aldose reductase on myocardial ischemia-reperfusion injury, we used transgenic mice broadly overexpressing human aldose reductase (ARTg) driven by the major histocompatibility complex I promoter. Hearts from these ARTg or littermate mice (WT) (n=6 in each group) were isolated, perfused under normoxic conditions, then subjected to 50 min of severe low flow ischemia followed by 60 min of reperfusion. Creatine kinase (CK) release (a marker of ischemic injury) was measured during reperfusion; left ventricular developed pressure (LVDP), end diastolic pressure (EDP), and ATP were measured throughout the protocol. CK release was significantly greater in ARTg mice compared with the WT mice. LVDP recovery was significantly reduced in ARTg mice compared with the WT mice. Furthermore, ATP content was higher in WT mice compared with ARTg mice during ischemia and reperfusion. Infarct size measured by staining techniques and myocardial damage evaluated histologically were also significantly worse in ARTg mice hearts than in controls. Pharmacological inhibition of aldose reductase significantly reduced ischemic injury and improved functional recovery in ARTg mice. These data strongly support key roles for AR in ischemic injury and impairment of functional and metabolic recovery after ischemia. We propose that interventions targeting AR may provide a novel adjunctive approach to protect ischemic myocardium.
 ...
PMID:Central role for aldose reductase pathway in myocardial ischemic injury. 1528 19

Therapeutic angiogenesis is a potential treatment modality for myocardial ischemia. phVEGF-A(165), phPDGF-BB, or a combination of the two were injected into the myocardial infarct border zone in rats 7 days after ligation of the coronary left anterior descending artery. Cardiac function was measured by echocardiography. Hearts were harvested 1 and 4 weeks after plasmid injection. phVEGF-A(165) increased capillary density more than phPDGF-BB, and phPDGF-BB preferentially stimulated arteriolar growth. The combination increased both capillaries and arterioles but did not enhance angiogenesis any more than single plasmid treatments did. VEGF-A(165) and the combination of phVEGF-A(165) and phPDGF-BB counteracted left ventricular dilatation after 1 week but did not counteract further deterioration.
 ...
PMID:Angiogenic and cardiac functional effects of dual gene transfer of VEGF-A165 and PDGF-BB after myocardial infarction. 1531 5

Cardiac ischemia--reperfusion injury results in oxidative stress and poor physiological recovery. This study examined the amount of lipid and protein oxidation during ischemia-reperfusion to assess the degree of oxidative stress. Selenium supplementation was used to alter the antioxidant status of rats and the recovery of myocardial function post ischemia-reperfusion was investigated. Male Wistar rats were fed diets containing 0, 50, and 1000 microg/kg sodium selenite for 5 weeks, whilst controls received normal rat food containing 240 microg/kg selenium. Langendorff-perfused hearts were subjected to 22.5 min global ischemia and 45 min reperfusion, with functional recovery assessed. Heart tissues were assayed for the presence of lipid peroxides and protein carbonyls and correlated to cardiac recovery. Following ischemia and reperfusion there was a significant increase in both protein oxidation and lipid peroxidation. Hearts from selenium-deficient animals demonstrated higher levels of both protein carbonyls and lipid peroxides and were more susceptible to ischemia-reperfusion injury when compared to controls (38% versus 47% recovery of rate pressure product (RPP)). Selenium supplementation lowered the levels of protein carbonyls and lipid peroxides and resulted in improved recovery of cardiac function post ischemia-reperfusion (57% recovery of RPP). These data suggest that selenium supplementation may provide an effective method for reducing oxidative damage post cardiac ischemia-reperfusion.
 ...
PMID:Selenium supplementation and ischemia-reperfusion injury in rats. 1572 Aug 25

Cardiac ischemia reperfusion leads to oxidative stress and poor physiological recovery. Selenium deficiency down-regulates thioredoxin reductase (Txnrd) and glutathione peroxidase (Gpx) activity, impairing recovery from ischemia-reperfusion. Furthermore, selenium supplementation has been shown to be cardioprotective and lessens oxidative stress in reperfused rat hearts. In this study we have investigated the role of selenium in the mRNA expression of these, and related antioxidant proteins, post ischemia-reperfusion. Male rats were fed varying doses of selenium for five weeks. Hearts were isolated and perfused using the Langendorff method with 22.5 min of global ischemia and 45 min reperfusion. RNA was extracted for quantitative real-time PCR analysis of glutathione peroxidase (Gpx)-1 and 4, glutathione reductase (Gsr), thioredoxin peroxidase-2 (Prdx2), thioredoxin (Txn) and thioredoxin reductase (Txnrd)-1 and 2 gene expression. Selenium deficiency produced significant reductions in Gpx-1, Gpx-4, Prdx2, Txnrd-1 and Txnrd-2 expression. Conversely, selenium supplementation of 1000 microg/kg significantly up-regulated Gpx-1, Gpx-4, Txn, Txnrd-1 and Txnrd-2 transcription. Our results show selenium modulates the cardiac mRNA expression of thioredoxin and glutathione related enzymes post ischemia-reperfusion, and impacts on tolerance to ischemia-reperfusion.
 ...
PMID:Effects of dietary selenium on post-ischemic expression of antioxidant mRNA. 1579 62

1. Myocardial ischaemia-reperfusion in humans is associated with increased formation of 15-F(2t)-isoprostane and 5-F(2t)-isoprostane (15-F(2t)-IsoP and 5-F(2t)-IsoP, respectively). Whether this formation is relevant clinically remains controversial. The present study was performed in order to evaluate the ability of the isoprostanes 15-F(2t)-IsoP and 5-F(2t)-IsoP to reduce myocardial ischaemic injury in rat isolated heart. 2. Rats were divided into six groups. Hearts were excised, perfused retrogradely and pretreated with vehicle (ethanol 5.10(-7) and 2.10(-9) mol/L; n = 6), subjected to ischaemic preconditioning (n = 8) or pretreated with the isoprostanes 15-F(2t)-IsoP (3.10(-10) and 3.10(-7) mol/L; n = 8) or 5-F(2t)-IsoP (10(-9) mol/L; n = 8). After a 5 min treatment-5 min washout period, hearts were submitted to 30 min global ischaemia, followed by a 120 min reperfusion period. 3. The infarct-to-ventricle zone ratio was significantly reduced in ischaemic preconditioned (20.6 +/- 2.6%) compared with vehicle groups (44.5 +/- 4.3 and 51.3 +/- 2.5% in groups pretreated with 5.10(-7) or 2.10(-9) mol/L ethanol, respectively). Pretreatment with either isoprostane had no cardioprotective effect; the infarct-to-ventricle ratios were 43.1 +/- 2.2, 49.4 +/- 5.9 and 44.5 +/- 5.0% for groups treated with 3.10(-10) mol/L 15-F(2t)-IsoP, 3.10(-7) mol/L 15-F(2t)-IsoP or 10(-9) mol/L 5-F(2t)-IsoP, respectively. 4. These data provide evidence that the isoprostanes 15-F(2t)-IsoP and 5-F(2t)-IsoP are not implicated in early myocardial preconditioning at concentrations similar to those found in the human coronary sinus following coronary angioplasty.
 ...
PMID:15-F-isoprostane and 5-F-isoprostane are not triggers of myocardial preconditioning. 1585 41

The purpose of this study was to investigate the effects of bosentan, a mixed endothelin receptor A and B subtype antagonist, on myocardial ischemia-reperfusion injury and to explore the influence of the timing of bosentan administration on its cardioprotective effects. Adult rat hearts were perfused by the Langendorff technique with Krebs-Henseleit solution (KH) at a constant flow rate at 10 mL/min. Global myocardial ischemia was induced by stopping KH perfusion for 40 min, and this was followed by 60 min of reperfusion. Hearts were randomized to 1 of 3 experimental groups (n = 7 each): untreated control; treatment with bosentan 1 micromol/L 10 min prior to, during 40 min global ischemia, and for 15 min of reperfusion (BOS); or treatment with bosentan 1 micromol/L after 15 min of reperfusion (BOS-R). We observed that BOS-R, but not the BOS treatment regimen, significantly reduced the release of cardiac-specific creatine kinase and postischemic myocardial infarct size (P < 0.05 vs. control) without affecting myocardial contractility. Left ventricular developed pressure in the BOS group was significantly (P < 0.01) lower than that in the control group throughout reperfusion. It is concluded that pharmacologically delayed antagonism of endothelin-1 during reperfusion attenuates postischemic myocardial injury. Endothelin-1 antagonist application during early reperfusion may exacerbate postischemic myocardial dysfunction.
 ...
PMID:Endothelin A and B receptor antagonist bosentan reduces postischemic myocardial injury in the rat: critical timing of administration. 1587 Aug 40


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>