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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To examine whether basic fibroblast growth factor (bFGF) administered to the heart by perfusion can improve cardiac resistance to injury we employed an isolated rat heart model of ischemia-reperfusion injury and determined the extent of functional recovery in bFGF-treated and control hearts. Global ischemia was simulated by interruption of flow for 60 min. Recovery of developed force of contraction (DF), recorded after reestablishment of flow for 30 min, reached 63.8 +/- 1.5% and 96.5 +/- 3.5% of preischemic levels in control and bFGF-treated hearts (10 micrograms/heart), respectively, indicating that bFGF induced significantly improved recovery of mechanical function. Recoveries of the rates of contraction or relaxation were also significantly improved in bFGF-treated hearts. Extent of myocardial injury, assessed by determination of phosphocreatine kinase in the effluent, was reduced as a result of bFGF treatment. As a first step towards understanding the mechanism and direct cellular target(s) of bFGF-induced cardioprotection, we investigated its fate after perfusion. Perfusion of 10 micrograms bFGF/heart resulted in a 4-fold increase in bFGF associated with the heart compared to control levels, as estimated by biochemical fractionation and immunoblotting. Immunofluorescent staining of the bFGF-perfused hearts revealed intense anti-bFGF staining in association with blood vessels as well as the periphery of cardiomyocytes, suggesting that the latter may be a target for direct bFGF action. In conclusion, our findings of bFGF-induced increases in cardiac resistance to, and improved functional recovery from, ischemia-reperfusion injury indicate that bFGF may have clinical applications in the treatment of ischemic heart disease.
Mol Cell Biochem 1995 Feb 23
PMID:Basic fibroblast growth factor is cardioprotective in ischemia-reperfusion injury. 759 47

In humans high levels of storage iron as well as low iron binding capacity are considered risks for ischemic heart disease development. The aim of this study was to determine whether a diet containing iron to a concentration of the recommended upper limit alters the degree of myocardial ischemic/reperfusion injury on rats and whether simultaneous antioxidant supplementation had any effect. Results indicate that the iron supplemented diet increased the degree of oxidative injury while simultaneous antioxidant supplementation prevented much of this increase. The mechanism for this was probably an elevated hydroxyl radical production due to the enlarged transit iron pool.
Res Commun Mol Pathol Pharmacol 1994 Dec
PMID:Ischemia/reperfusion injury is aggravated by an iron supplemented diet and is partly prevented by simultaneous antioxidant supplementation. 771 4

High energy phosphates [phosphocreatine (PCr) and adenosine triphosphate (ATP)] are maintained in the heart under conditions of altered myocardial contractility and under certain conditions of maintained in the heart under conditions of altered myocardial contractility and under certain conditions of myocardial ischemia (such as hibernating myocardium). However, the metabolic consequences of reduced regional contractility have not been investigated. This study was designed to test the hypotheses that (1) under conditions of normal blood flow, reduction in regional contractility does not result in changes in PCr or ATP and (2) under conditions of reduced blood flow, reduction in regional contractility prevents the expected decline in high energy phosphates usually seen in regional ischemia. An in situ open chest swine preparation was used in which regional contractility was reduced with the administration of intracoronary lidocaine. High energy phosphates were measured using phosphorus-31 magnetic resonance spectroscopy (NMR) under conditions of normal flow and reduced flow. Intracoronary lidocaine infusion in 9 animals did not change blood flow from basal levels, but significantly reduced regional segment shortening from 0.16 +/- 0.02 to 0.02 +/- 0.01. The ratio of PCr/ATP did not change with lidocaine infusion (control: 1.53 +/- 0.09; lidocaine: 1.59 +/- 0.11), but oxygen content in the anterior interventricular vein increased from 8.25 +/- 0.69 to 9.83 +/- 0.91 ml/O2/100 ml blood in parallel studies (P = 0.04). While the lidocaine infusion was maintained, subsequent coronary stenosis significantly reduced subendocardial blood flow from 0.91 +/- 0.06 to 0.41 +/- 0.06 ml/min/g without significantly altering high energy phosphates (PCr/ATP = 1.51 +/- 0.15). In contrast to the 29% decline in PCr previously seen with regional ischemia, PCr was unchanged with this degree of flow reduction in the presence of lidocaine. Thus, PCr and ATP are unchanged under conditions of reduced contractility, consistent with equilibrium of energy synthesis and utilization. In addition, factors which reduce myocardial contractility, either pharmacologically or endogenously, protect against the metabolic consequences of reduced flow by reducing MVO2.
J Mol Cell Cardiol 1994 Dec
PMID:Effects of regional myocardial lidocaine infusion on high energy phosphates. 773 Oct 55

The cardio-protective mechanisms of EGb 761, an extract of Ginkgo biloba leaves, on myocardial ischemia-reperfusion injury were investigated using rabbits subjected to 30 minutes of regional cardiac ischemia and 120 min of reperfusion under anesthesia. Compared to the saline perfused group, EGb 761 treatment (10 mg/kg, injected into the coronary artery) significantly inhibited the increase in lipid peroxidation and maintained total and CuZn-SOD levels in both plasma and tissue during and at the end of reperfusion. Both the decrease in tissue type plasminogen activator (t-PA) and the increase in plasminogen activator inhibitor-1 (PAI-1) caused by ischemia-reperfusion were also significantly suppressed by EGb 761 treatment. Furthermore, the ultrastructure of the myocytes of the EGb 761 treated heart was slightly damaged after ischemia-reperfusion, while the control ischemic-reperfused hearts demonstrated severe histological damages such as swelling and vacuolization of the mitochondria. These results suggest that EGb 761 protects hearts by its antioxidant properties and by its ability to adjust fibrinolytic activity.
Biochem Mol Biol Int 1995 Jan
PMID:Efficiency of Ginkgo biloba extract (EGb 761) in antioxidant protection against myocardial ischemia and reperfusion injury. 773 27

Acute myocardial ischemia leads to a rapid increase of cardiac beta-adrenergic receptors in plasma membranes despite the release of large and desensitizing amounts of endogenous catecholamines. Part of this increase has been shown to occur at the expense of intracellular receptors. To investigate whether an additional expressional regulation of beta-adrenergic receptors due to an increase of mRNA levels is involved, the mRNA levels specific for beta 1- and beta 2-adrenergic receptors were determined after various periods of global ischemia in isolated perfused rat hearts. The subtype-specific quantification of mRNA for beta 1- and beta 2-adrenergic receptors was determined using reverse-transcription followed by PCR (RT-PCR) and RNA protection assays. RT-PCR resulted in single amplification products of the expected sizes (159 bp for beta 1-adrenergic receptors and 240 bp for beta 2-adrenergic receptors). The specificity of these amplification products was confirmed by specific restriction digests. Southern blot hybridizations with internal oligonucleotides and sequencing using the dideoxy chain termination method. For quantification purposes, the mRNAs of housekeeping gene GAPDH and of cardiac alpha-actin were determined as internal standards. Additionally, cRNAs specific for beta 1- and beta 2-adrenergic receptors were used as external standards. Brief periods of global ischemia induced a rapid increase in the steady state level of mRNA for beta 1-adrenergic receptors. There was a statistically significant rise already after 15 min by 57% compared to controls. After 30 min of ischemia the mRNA levels had almost doubled. After 60 min of ischemia, the mRNA levels specific for beta 1-adrenergic receptors tended to decrease, but remained significantly above normoxic controls. In contrast, the mRNA levels specific for beta 2-adrenergic receptors remained constant up to 60 min of global myocardial ischemia. To investigate, whether agonist occupancy of the receptors may contribute to this regulation, the effect of preperfusion with the beta-blocker alprenolol was determined. Contrary to expectation, beta-blockade did not influence the ischemia-induced increase of mRNA levels specific for beta 1-adrenergic receptors. These data demonstrate for the first time, that acute myocardial ischemia induces a rapid, and subtype-selective regulation of mRNA levels for beta 1-adrenergic receptors. However, occupation or activation of beta-adrenergic receptors by an agonist is not involved in this newly characterized regulation of mRNA for beta 1-adrenergic receptors in acute myocardial ischemia.
J Mol Cell Cardiol 1995 Jan
PMID:Regulation of beta-adrenergic receptors in acute myocardial ischemia: subtype-selective increase of mRNA specific for beta 1-adrenergic receptors. 776 Mar 63

Short periods of myocardial ischemia appear to provide protection against subsequent prolonged ischemic episodes in experimental animals and in man. This phenomenon, known as ischemic preconditioning, has not yet been characterized at the cellular or molecular levels; however, tissue hypoxia appears to be required. In this study, we used a previously developed method for hypoxic cardiac myocyte culture in order to establish a model for ischemic (or hypoxic) preconditioning in cell culture. We demonstrate that cultured neonatal rat cardiac myocytes preconditioned by 25 min of exposure to hypoxia followed by reoxygenation were protected against membrane damage for up to 6 h of prolonged severe hypoxia, as determined by arachidonic acid release and contractile recovery. In contrast, non-preconditioned myocytes exhibited significant hypoxic damage after 2-4 h. Pretreatment of cells with PMA, a tumor-promoting phorbol ester, mimicked the protective effects of hypoxic preconditioning; pretreatment with the muscarinic cholinergic agonist carbachol had no effect. Our data suggests that isolated myocytes in culture remain competent to be preconditioned by hypoxia, through a pathway that may involve the activation of protein kinase C.
J Mol Cell Cardiol 1995 Jan
PMID:Cardioprotection in an in vitro model of hypoxic preconditioning. 776 Mar 65

Effects of myocardial ischemia on mitochondrial enzymes and mitochondrial DNA (mtDNA) were examined using the model of Ameroid constriction of canine cardiac vessels. Endocardium supplied by constricted coronary arteries was found to have significantly lower citrate synthase and complex IV activities compared to values obtained from either epicardium supplied by constricted vessels or endocardium supplied by unconstricted coronary arteries. Neither significant differences in mtDNA copy number nor changes in respiratory complexes I, III and V were detected. These results suggest that highly localized, specific mitochondrial enzyme changes result from chronic myocardial ischemia.
Biochem Mol Biol Int 1995 Mar
PMID:Localized mitochondrial dysfunction in canine myocardial ischemia. 777

Insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene has been associated with ischemic heart disease and hypertension. The D allele reportedly correlates with myocardial infarction and it has been suggested that it may serve as the basis of population-based risk assessment. Similarly, determining whether there is an ACE allele pattern associated with hypertension could be useful in developing screening strategies. Previous reports have not shown consistent findings in Caucasian and Japanese population groups, some having a predominance of the I allele. Although African Americans have the highest prevalence of hypertension in the world, their ACE gene polymorphism frequencies have not been clearly defined. We studied the allele and genotype frequencies in this group, consisting of 133 essential hypertensive subjects, and compared their findings with those reported from normotensive African Americans and from other racial groups. The black patients had a different allele distribution than the other populations in that the D was more common than the I allele, occurring at a rate of 59.7%. The most common genotype was DD and it was present in 42.5% of the hypertensive subjects in contrast to the ID genotype which was the most commonly reported genotype in normotensive individuals. The genotype pattern (frequencies of II, ID, DD) was significantly different (p < 0.005, 2 df) from Japanese and Caucasian (Scotland and Australia) populations. There was no common allele or genotype distribution amongst these diverse hypertensive groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Biochem Mol Biol Int 1995 Mar
PMID:Polymorphism of the angiotensin I converting enzyme gene in essential hypertensive patients. 777 1

A potential detrimental role of endothelin-1 in myocardial ischemia/reperfusion injury was studied by use of the endothelin-1 antagonists BQ123 and BQ610. Isolated isovolumetric rat hearts were perfused at constant pressure. BQ123 (7 micrograms/min) and BQ610 (1.75 micrograms/min) did not alter mechanical function or coronary flow and shifted dose-response curves for endothelin-1 significantly to the right. In rats subjected to 30 min of no-flow ischemia, the increase of left ventricular resting pressure was significantly delayed by BQ123 and BQ610 compared to control (BQ123: 20 +/- 2* mmHg, BQ610: 19 +/- 2* mmHg, control: 44 +/- 4 mmHg at 15 min of ischemia, respectively, *P < 0.05 v control). With reperfusion after 30 min of ischemia, recovery of left ventricular developed pressure was not significantly affected but tended to be better with endothelin-1 antagonist pretreatment (BQ123: 20 +/- 3 mmHg; BQ610: 19 +/- 3 mmHg, control 12 +/- 3 mmHg). However, in hearts subjected to 15 min of ischemia followed by reperfusion, recovery of left ventricular developed pressure was improved by BQ610 pretreatment (BQ610: 52 +/- 8* mmHg, control: 24 +/- 6 mmHg). We conclude: BQ123 and BQ610 effectively antagonize the coronary constrictive effect of endothelin-1. BQ123 and BQ610 delay the development of contracture during ischemia and may improve functional recovery during reperfusion. Our findings suggest that endogenous endothelin-1 may contribute to ischemia/reperfusion injury.
J Mol Cell Cardiol 1995 Feb
PMID:Endothelin-1 contributes to ischemia/reperfusion injury in isolated rat heart-attenuation of ischemic injury by the endothelin-1 antagonists BQ123 and BQ610. 777 81

Adaptation to various forms of stress has been found to be associated with increased cellular tolerance to myocardial ischemia. In this study, the effects of myocardial adaptation to oxidative stress was examined by injecting rats with endotoxin (0.5 mg/kg) and its non-toxic derivative, lipid A (0.5 mg/kg). Both compounds exerted oxidative stress within 1 h of treatment as evidenced by enhanced malonaldehyde formation. The oxidative stress disappeared steadily and progressively with time in concert with the appearance of the induction of glutathione and antioxidative enzymes that included superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase. After 24 h of endotoxin or lipid A treatment, the amount of oxidative stress and antioxidant enzyme levels were significantly lower and higher, respectively, compared to those at the baseline levels. Corroborating these results, both endotoxin and lipid A provided protection against myocardial ischemia and reperfusion injury as evidenced by a significantly improved postischemic recovery of left ventricular functions. The data presented here demonstrates that a controlled amount of oxidative stress induces the expression of intracellular antioxidants that can result in enhanced myocardial tolerance to ischemia. This suggests that myocardial adaptation to oxidative stress may be a potential tool for reduction of ischemic/reperfusion injury.
Mol Cell Biochem 1995 Mar 09
PMID:Oxidative stress adaptation improves postischemic ventricular recovery. 779 47


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