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)

It has been previously suggested that alterations in sodium homeostasis, leading to calcium overload may play a part in the mediation of cardiac ischemic injury. It has been demonstrated that the Na+-H+ exchanger plays an important role with regard to the regulation of intracellular sodium during ischemia and reperfusion and that inhibition of the Na+-H+ exchanger during ischemia protects hearts from ischemic injury. Studies using chemically-induced diabetic animals have suggested that the cardiac Na+-H+ exchanger in the diabetic heart is impaired and is responsible for limiting the increase in sodium during ischemia. The extent to which the Na+-H+ exchanger contributes to increases in intracellular sodium during ischemia in diabetic hearts is unclear as direct measurements of exchanger activity have not been made in genetically diabetic hearts. Therefore, this paper aims to address the following issues: (a) is the Na+-H+ exchanger impaired in a genetically diabetic rat heart: (b) does this impairment result in lower [Na]i or [Ca]i during ischemia; and (c) does Na+-H+ exchanger inhibition limit injury and functional impairment in diabetic hearts during ischemia and reperfusion? These issues were examined by inhibiting the Na+-H+ exchanger with ethylisopropylamiloride (EIPA) in isolated perfused hearts from both genetically diabetic (BB/W) and non-diabetic rats. Levels of intracellular sodium, intracellular calcium, intracellular pH and high energy phosphates (using 23Na,19F, 31P NMR spectroscopies, respectively) during global ischemia and reperfusion were also measured. The impact of diabetes on Na+-H+ exchanger activity was assessed by measuring pH recovery of these hearts after an acid load. Creatine kinase release during reperfusion was used as a measure of ischemic injury. This study demonstrated that the Na+-H+ exchanger is impaired in diabetic hearts. Despite this impaired activity, inhibition of Na+-H+ exchanger protected diabetic hearts from ischemic injury and was associated with attenuation of the rise in sodium and calcium, and limitation of acidosis and preservation of ATP during ischemia. The data presented here favor the use of Na+-H+ exchanger inhibitors to protect ischemic myocardium in diabetics. Also, the data provides possible mechanisms for the altered susceptibility of diabetic hearts to ischemic injury.
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PMID:Inhibition of Na+-H+ exchanger protects diabetic and non-diabetic hearts from ischemic injury: insight into altered susceptibility of diabetic hearts to ischemic injury. 1032 6

Patients with acute chest pain are a common problem and a difficult challenge for clinicians. In the United States more than 5 million patients are examined in the emergency department on a yearly basis, at a cost of 6 billion dollars. In the CHEPER registry the prevalence of patients with chest pain in the Emergency Department was 5.3%. Similarly, in 1997 at our institution the prevalence was 4.8%. Only 50% of the patients are subsequently found to have cardiac ischemia as the cause of their symptoms and 50-60% of them showed a non-diagnostic electrocardiogram (ECG). Twenty-five-50% of chest pain patients are not appropriately admitted to the hospital and despite this conservative approach, acute myocardial infarction is misdiagnosed up to 8% of patients with acute chest pain who are released from the emergency department without further evaluation, accounting for approximately 20% of emergency department malpractice in the United States. Important diagnostic information is covered by the patient's medical history, physical examination, and ECG, but often this approach is inadequate for a definitive diagnosis. Creatine kinase (CK) and CK isoenzyme--cardiac muscle subunit (CK-MB)--are traditionally obtained in the emergency department in patients admitted for suspected acute coronary syndrome. Mass measurements of CK-MB have improved sensitivity and specificity, and to date this is the gold standard test for diagnosis of acute myocardial infarction. CK-MB, however, is not a perfect marker because it is not totally cardiac specific and does not identify patients with unstable angina and minimal myocardial damage. There are no controlled clinical impact trials showing that these tests are effective in deciding whether to discharge or to appropriately admit the patient with suspected acute coronary syndrome. Relevant investigative interest has recently been focused on new markers for myocardial injury, including myoglobin, cardiac troponins T and I. Myoglobin, a sensitive but not specific marker for cardiac damage, increases earlier than CK-MB and cardiac troponins. It should be used early after symptom onset and in conjunction with a more specific marker of myocardial damage. Cardiac troponins T and I are highly specific markers for cardiac damage, rise parallel to CK-MB and remain elevated longer, up to 5 to 9 days. They are useful for detection of less severe degrees of myocardial injury, which may occur in several patients with unstable angina who are at higher risk of cardiac events. Recent studies suggest that cardiac troponins have good diagnostic performance and prognostic value in the heterogeneous population of patients seen in the Emergency Department with acute chest pain. Despite these promising data, several analytical and interpretative problems in the routine use of cardiac troponins must be solved. Incremental value of echocardiography in acute chest pain patients is still uncertain. Echocardiography can be recommended as an adjunctive test if readily available during acute chest pain or prolonged pain, especially in patients without previous myocardial infarction. Rest myocardial radionuclide imaging has been studied in the emergency department setting and although the overall diagnostic performance and prognostic value of sestamibi has been found to be promising, it is not suitable, in our country, for extensive clinical use. ECG exercise stress test in the emergency department population has been shown to be safe and it has a good negative predictive value for cardiac events. It should be recommended that any institution identify specific and shared protocol and strategies for management of patients with chest pain. These should include basal clinical evaluation, serial ECG and the use of specific and sensitive myocardial markers. Adjunctive tests, such as echocardiography, nuclear studies and stress tests should be employed when indicated taking into account local facilities.
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PMID:[Is a more efficient operative strategy feasible for the emergency management of the patient with acute chest pain?]. 1073 76

We investigated whether the adenosine triphosphate (ATP)-sensitive K+ (K+ATP) channel that was implicated in the ischemic preconditioning (I-PC) phenomenon, has a role in the cardioprotective effects of fibroblast growth factors (FGFs). For this purpose, we administered glibenclamide, a specific K+ATP channel blocker, before acidic fibroblast growth factor (aFGF, FGF-1) treatment, in rat heart subjected to left ventricular ischemia for 20 minutes followed by reperfusion for 24 hours. Creatine kinase (CK) activity was analyzed in myocardial tissue to assess the degree of cardiac injury. FGF-1 treatment markedly maintains CK activity. This cardioprotective effect of FGF-1 was blocked by glibenclamide. As shown by ultrastructural data, Ca2+ overload and associated cardiomyocyte alterations shown in glibenclamide-treated rats were not observed in specimens from the FGF-1 group. These findings suggest that FGF serves as an effector in I-PC and support a clinical interest of these proteins for increasing myocardial ischemic tolerance.
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PMID:Fibroblast growth factor cardioprotection against ischemia-reperfusion injury may involve K+ ATP channels. 1079 48

Hypoxia and reoxygenation were studied in rat hearts and ischemia and reperfusion in rat hindlimbs. Free radicals are known to be generated through these events and to propagate complications. In order to reduce hypoxic/ischemic and especially reoxygenation/reperfusion injury the (re)perfusion conditions were ameliorated including the treatment with antioxidants (lipoate or dihydrolipoate). In isolated working rat hearts cardiac and mitochondrial parameters are impaired during hypoxia and partially recover in reoxygenation. Dihydrolipoate, if added into the perfusion buffer at 0.3 microM concentration, keeps the pH higher (7. 15) during hypoxia as compared to controls (6.98). The compound accelerates the recovery of the aortic flow and stabilizes it during reoxygenation. With dihydrolipoate, ATPase activity is reduced, ATP synthesis is increased and phosphocreatine contents are higher than in controls. Creatine kinase activity is maintained during reoxygenation in the dihydrolipoate series. Isolated rat hindlimbs were stored for 4 h in a moist chamber at 18 degrees C. Controls were perfused for 30 min with a modified Krebs-Henseleit buffer at 60 mmHg followed by 30 min Krebs-Henseleit perfusion at 100 mmHg. The dihydrolipoate group contained 8.3 microM in the modified reperfusate (controlled reperfusion). With dihydrolipoate, recovery of the contractile function was 49% (vs. 34% in controls) and muscle flexibility was maintained whereas it decreased by 15% in the controls. Release of creatine kinase was significantly lower with dihydrolipoate treatment. Dihydrolipoate effectively reduces reoxygenation injury in isolated working rat hearts. Controlled reperfusion, including lipoate, prevents reperfusion syndrome after extended ischemia in exarticulated rat hindlimbs and in an in vivo pig hindlimbs model.
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PMID:Lipoic acid reduces ischemia-reperfusion injury in animal models. 1096 35

The purpose of this study is to investigate the effects of ischemic preconditioning on myocardial protection and to compare this method to K(+) crystalloid cardioplegia. Langendorff perfused isolated working rat hearts were used in the following groups. After 20 min of stabilisation, 30 hearts were divided into three groups. In group I (control, n=10), hearts were arrested with cold (+4 degrees C) Krebs-Henseleit (K-H) solution, in group II (cardioplegia, n=10) hearts were arrested with cold K(+) cardioplegia solution, and in group III (preconditioning, n=10) hearts were subjected to 5 min normothermic ischemia followed by 5 min reperfusion then arrested with cold K-H solution. All hearts were subjected to 30 min of global ischemia (24 degrees C) and 40 min of reperfusion. Hemodynamic measurements were performed with a left ventricular latex balloon using a data acquisition system. Creatine kinase (CK-MB) washout and Troponin I (cTnI) levels were determined from the coronary effluents. There was no significant difference among the three groups in any of the parameters (hemodynamic and biochemical) measured at the end of stabilisation period. During reperfusion, functional recovery and coronary flow were significantly improved in K(+) cardioplegia and preconditioned groups compared with control group. CK-MB washout and cTnI levels were significantly lower in groups II and III compared with group I at the reperfusion. However no significant difference was observed between K(+) cardioplegia and preconditioned groups among biochemical and hemodynamic parameters and coronary flow at the post-ischemic period. In conclusion, ischemic preconditioning is as effective as K(+) cardioplegia on myocardial protection and recovery of myocardial function during reperfusion.
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PMID:The effectiveness of ischemic preconditioning on myocardial protection and comparison with K(+) cardioplegia. 1099 2

The implications of an elevated Creatine kinase (CK)-MB isoenzyme (MB) in suspected acute coronary syndromes, with a normal total CK, is not well established. Despite many guidelines on managing patients with acute coronary ischemia, none indicates strategies for patients with elevated MB and with a normal CK. The outcome consequence of this result is not firmly established. Our objective was to prospectively evaluate outcomes in patients with suspected acute coronary syndromes, normal initial total CK, and increased MB. All Emergency Department patients with suspected acute coronary syndromes and creatinine < 2.0 mg/dL were eligible for study entry. Serial CK and MB fractions were measured on arrival in the Emergency Department, then 8 and 16 h postpresentation. A composite outcome of death, Q-wave myocardial infarction, or revascularization was defined at the index visit and 6 months later. Outcomes were determined by blinded record review and by telephone contact. In the 698 patients entered, the acute composite outcome rate was 25% (175) and 6.3% (44) at 6 months. Acute and 6 month adverse outcome rates were statistically the same for all patients with an elevated MB fraction, regardless of the total CK level. An elevated MB conferred a higher event rate than did a normal MB. We conclude that the adverse event rate for patients with suspected acute coronary syndromes and an elevated MB is the same whether or not the total CK is elevated. These patients should be considered as having had an acute coronary syndrome.
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PMID:Normal CK, elevated MB predicts complications in acute coronary syndromes. 1134 20

The aim of this work was to compare in the rat the cardioprotective efficacy and the total plasma antioxidant activity of a standardised Ginkgo biloba L. extract (GB) as such (300 mg/kg/day) or complexed with phosphatidylcholine (GB-PC; 1:2 w/w), after a 5 days oral administration. At the end of the treatment, the total plasma antioxidant defence was determined by the TRAP and FRAP assays, and the hearts from all groups of animals subjected to moderate ischemia (flow reduction to 1 ml/min for 20 min) and reperfusion (15 ml/min for 30 min). The recovery of left ventricular developed pressure (LVDP) at the end of reperfusion was 35-40% of the preischemic values in both control and vehicle rats, 50.2% in the GB group and 72.5% in the GB-PC pre-treated animals. Creatine kinase (CK) outflow in the perfusate from the hearts of GB and GB-PC treated animals were restrained to a different extent vs. controls (by 71% GB-PC; by 22% GB); the rate of prostacyclin (6-keto-PGF1 alpha) release was far greater in GB-PC than in GB hearts. In parallel, the GB extract significantly increased the total antioxidant plasma capacity (by 24.5% TRAP; 27.9% FRAP) only when complexed with phospholipids. This indicates an increased bioavailability of phenolic antioxidants when suitably embedded within a lipophilic carrier. The results of this study demonstrate that complexation of Ginkgo biloba with phospholipids induces in the rat, even after a short treatment a greater resistance of the heart to ischemia/reperfusion damage in respect to the native extract, due to an increased plasma antioxidant activity.
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PMID:Complexation of Ginkgo biloba extract with phosphatidylcholine improves cardioprotective activity and increases the plasma antioxidant capacity in the rat. 1145 48

Protein kinase C (PKC) plays a central role in both early and late preconditioning (PC) but its association with inducible nitric oxide synthase (iNOS) is not clear in late PC. This study investigates the PKC signaling pathway in the late PC induced by activation of adenosine A(1) receptor (A(1)R) with adenosine agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) and the effect on iNOS upregulation. Adult male mice were pretreated with saline or CCPA (100 microg/kg iv) or CCPA (100 microg/kg iv) with PKC-delta inhibitor rottlerin (50 microg/kg ip). Twenty-four hours later, the hearts were isolated and perfused in the Langendorff mode. Hearts were subjected to 40 min of ischemia, followed by 30 min reperfusion. After ischemia, the left ventricular end-diastolic pressure (LVEDP) was significantly improved and the rate-pressure product (RPP) was significantly higher in the CCPA group compared with the ischemia-reperfusion (I/R) control group. Creatine kinase release and infarct size were significantly lower in the CCPA group compared with the I/R control group. These salutary effects of CCPA were abolished in hearts pretreated with rottlerin. Immunoblotting of PKC showed that PKC-delta was upregulated (150.0 +/- 11.4% of control group) whereas other PKC isoforms remained unchanged, and iNOS was also significantly increased (146.2 +/- 9.0%, P < 0.05 vs. control group) after 24 h of treatment with CCPA. The data show that PKC is an important component of PC with adenosine agonist. It is concluded that activation of A(1)R induces late PC via PKC-delta and iNOS signaling pathways.
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PMID:Adenosine A(1) receptor mediates late preconditioning via activation of PKC-delta signaling pathway. 1206 2

The effects of fasting and ischemic preconditioning (IP) on heart function of Langendorff-perfused rat hearts exposed to 25 min global ischemia plus 30 min reperfusion (RP), were correlated with lactate release and tissue-levels of long-chain acyl carnitine (LCCa) and CoA (LCCoA). IP was achieved by a 3 min ischemia plus a 5 min reperfusion cycle. Creatine kinase leakage was measured to assess the extent of cardiac injury. Fasting reduced the ischemic-induced contracture, improved RP recovery of mechanical function, reduced lactate release and increased the end-ischemia LCCoA and LCCa levels. Both in the fed and the fasted rat hearts IP delayed the pacemaker depression, reduced the amplitude of ischemic contracture and improved the RP recovery of contraction. However, IP reduced creatine kinase and lactate release only in the fed rat hearts. IP had no effects on tissue LCCa and LCCoA in both groups. These data suggest that: 1) beneficial effects of fasting may be ascribed, at least in part, to a reduced lactate production which may attenuate ischemic myocyte acidification and to the accumulation of fatty acyl esters which would favour citric acid cycle replenishment during RP. 2) beneficial effects of IP could be in part explained by the reduction of lactate production in the fed group although data obtained with the fasted rat heart indicate that another mechanisms must also be involved in the effects of IP. 3) accumulation of LCCoA and LCCa is not involved in the noxious effects of ischemia as well as in the protection effected by IP.
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PMID:Influence of fasting on the effects of ischemic preconditioning in the ischemic-reperfused rat heart. 1222 19

Myocardial function depends on adenosine triphosphate (ATP) supplied by oxidation of several substrates. In the adult heart, this energy is obtained primarily from fatty acid oxidation through oxidative phosphorylation. However, the energy source may change depending on several factors such as substrate availability, energy demands, oxygen supply, and metabolic condition of the individual. Surprisingly, the role of energy metabolism in development of cardiac diseases has not been extensively studied. For instance, alterations in glucose oxidation and transport developed in diabetic heart may compromise myocardial performance under conditions in which ATP provided by glycolysis is relevant, such as in ischemia and reperfusion. In some cardiac diseases such as ischemic cardiomyopathy, heart failure, hypertrophy, and dilated cardiomyopathy, ATP generation is diminished by derangement of fatty acid delivery to mitochondria and by alteration of certain key enzymes of energy metabolism. Shortage of some co-factors such as L-carnitine and creatine also leads to energy depletion. Creatine kinase system and other mitochondrial enzymes are also affected. Initial attempts to modulate cardiac energy metabolism by use of drugs or supplements as a therapeutic approach to heart disease are described.
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PMID:Heart metabolic disturbances in cardiovascular diseases. 1270 3


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