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

The effects of diltiazem, a sarcolemmal Ca2+ channel blocker, and ryanodine, an inhibitor of sarcoplasmic reticulum function, were investigated in isolated newborn rabbit hearts (2 to 5 days old) subjected to ischemia and reperfusion. After cardioplegic arrest with St. Thomas' Hospital solution, global ischemia was induced at 37 degrees C (normothermia) for 45 minutes or at 20 degrees C (hypothermia) for 180 minutes. The hearts were then reperfused at 37 degrees C for 30 minutes. Diltiazem or ryanodine, at concentrations that have minimal to moderately negative inotropic effects under nonischemic conditions, was added to the cardioplegic solution. After normothermic ischemia, reperfusion of untreated hearts resulted in recovery of left ventricular developed pressure to 52.9% +/- 2.5% of the preischemic level. In hearts treated with diltiazem, recovery of left ventricular developed pressure was significantly improved (84.2% +/- 2.9% at 3 x 10(-8) mol/L; p < 0.01). Comparable improvement was achieved with ryanodine (90.5% +/- 4.1% at 10(-9) mol/L; p < 0.01). Creatine kinase leakage and structural derangement of mitochondria were also reduced by both agents. With hypothermic ischemia, left ventricular developed pressure recovered in untreated hearts to 72.7% +/- 3.3% of preischemic values. Treatment with diltiazem improved the recovery of left ventricular developed pressure to 96.9% +/- 3.5% at 3 x 10(-8) mol/L and reduced creatine kinase leakage and mitochondrial damage. Ryanodine also improved the recovery of left ventricular developed pressure and attenuated ultrastructural damage. These findings suggest that Ca2+ handling by the sarcoplasmic reticulum, like transsarcolemmal Ca2+ influx, plays an important role in the pathogenesis of myocardial ischemia-reperfusion injury in the neonatal heart despite the morphologic and functional immaturity of the sarcoplasmic reticulum in the neonate.
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PMID:Protective effects of diltiazem and ryanodine against ischemia-reperfusion injury in neonatal rabbit hearts. 832 Oct 5

Knowledge of the pathophysiology of ischemic heart disease has advanced in parallel with awareness of the significant limitations inherent in clinical assessment. Biochemical assays, long established as the most reliable means of detecting myocardial injury, have improved significantly. Creatine kinase MB, now optimally measured by the newer mass monoclonal antibody assays, and also measurement of the cardiac troponins objectively identify adverse prognosis. Cardiac troponin I appears to have significant advantages over other markers and may become the assay of choice. This is attributable to the confirmation of cardiospecificity claims regarding this marker. These assays permit increased appreciation of the continuous spectrum of ischemic myocardial injury, earlier diagnosis, refinement of the clinical assessment of risk, and evaluation of alternative treatment regimens. Reassessment of the incorporation of biochemical indicators for thrombolytic therapy can be anticipated. This paper integrates the clinical and biochemical literature in reviewing these concepts.
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PMID:Myocardial markers of injury. Evolution and insights. 938 52

Coenzyme Q10 (CoQ10, ubiquinone) has been shown to be protective against myocardial ischemia/reperfusion induced injury. The purpose of this study was to investigate the effect of CoQ10 added to cold cristalloid cardioplegia on hypothermic ischemia and normothermic reperfusion using an isolated working rat heart. Hearts (n = 6-9/group) from male Wistar rats were aerobically (37 degrees C) perfused (20 min) with bicarbonate buffer. This was followed by a 3-min infusion of St. Thomas' Hospital cardioplegic solution containing various concentrations of CoQ10 (0, 1, 3, 6, 12, and 58 mumol/L). Hearts were then subjected to 180 min of hypothermic (20 degrees C) global ischemia and 35 min of normothermic (37 degrees C) reperfusion (15 min Langendorff, 20 min working). Ventricular fibrillation (Vf) upon reperfusion was irreversible in the 12 and 58 mumol/ L CoQ10 groups (4/6 and 3/6, respectively). In the hearts which Vf upon reperfusion was not irreversible, the percent recovery of aortic flow (%AF) was 43.3 +/- 5.4% (n = 9) in the control group versus 31.6 +/- 7.7% (n = 6), 38.0 +/- 12.0% (n = 6), 27.2 +/- 6.9% (n = 6), 31.3% (n = 2), and 30.4 +/- 14.2% (n = 3) in the 1, 3, 6, 12, and 58 mumol/L CoQ10 groups, respectively. Creatine kinase leakage during Langendorff reperfusion tended to be greater in the 12 and 58 mumol/L CoQ10 groups than in the control group. Thus, CoQ10 in the cold cristalloid cardioplegic solution induced irreversible Vf upon reperfusion and failed to improve functional recoveries following hypothermic global ischemia.
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PMID:[The effect of coenzyme Q10 and cold cristalloid cardioplegia on hypothermic global ischemia]. 896 87

In the present study, the contribution of nitric oxide (NO), superoxide, and peroxynitrite to the inflammatory response induced by myocardial ischemia-reperfusion (MI/R) was investigated. Male Sprague-Dawley rats were anesthetized, and the left main coronary artery was ligated for 20 min and reperfused for 5 h. MI/R induced severe arrhythmias, indicated by a significantly elevated arrhythmia score in the MI/R group compared with that in the sham control group. Creatine kinase activity in the left ventricular free wall of the MI/R group was significantly reduced by 38%. In contrast, myeloperoxidase activity in the left ventricular free wall of the MI/R group was increased by 140%. Similarly, superoxide and tissue NO levels in the ischemic region of the heurt were increased by 140 and 90%, respectively. Superoxide and NO values in the nonischemic regions were similar to the sham control group. Total NO synthase (NOS) activity was elevated by 212%; moreover, inducible NOS (iNOS) activity increased 6.7-fold in the ischemic vs. nonischemic regions. MI/R also induced both systemic and remote organ (lung) inflammatory responses. Circulating neutrophils and plasma NO levels were increased by 163 and 138%, respectively, in MI/R rats compared with sham control animals. NO levels and superoxide generation were increased by 90 and 176%, respectively, in the lung tissues. The expression of iNOS and peroxynitrite generation were demonstrated by immunohistochemical staining with polyclonal anti-iNOS and monoclonal anti-nitrotyrosine antibodies, respectively. Sections of both the ischemic area of the ventricular wall and the lung tissue of MI/R animals exhibited a marked immunoreactivity with anti-iNOS and anti-nitrotyrosine antibodies, indicating the presence of iNOS and nitrotyrosine. Our data indicate that NO, superoxide, and peroxynitrite formation are elevated after reperfusion of the ischemic heart, suggesting that these inflammatory mediators may be involved in MI/R injury.
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PMID:Formation of nitric oxide, superoxide, and peroxynitrite in myocardial ischemia-reperfusion injury in rats. 917 2

Reperfusion may prevent or reduce the development and extent of necrosis, but may also lead to an increase in reperfusion damage. Experimental studies performed in various animal models of myocardial ischemia have demonstrated the anti-ischemic properties of trimetazidine (TMZ) and have suggested that TMZ has antioxidant properties, without any direct hemodynamic effects. Our study was aimed at investigating the effects of TMZ before thrombolysis in acute anterior myocardial infarction and included 81 patients, hospitalized within 4 hours of the onset of symptoms. Patients were randomly (double-blind) subdivided in two groups The first group (40 patients, Group A, TMZ-pretreatment), received 40 mg TMZ orally about 15 minute before thrombolysis and, subsequently, 20 mg every 8 hours. The second group (41 patients, Group B) received placebo before thrombolysis. Ventricular arrhythmias (VA) due to reperfusion were evaluated in the first 2 hours. VA occurred in 15 of patients in group A, versus 29 in group B, p<0.05. Creatine kinase (CK) normalization time was achieved after 55.7+/-12.5 hours in group A, versus 61.2+/-12.1 hour in group B, p = 0.048. CK peak was 1772+/-890 in group A vs. 2285+/-910 Ul/l in group B, (p = 0.012). In the follow-up (range 6-22 months), there were 4 deaths, two patients in each group. After 180 days from treatment, the TMZ group showed a smaller end systolic volume than the placebo group (echocardiographic data), 46.2+/-12 and 52.8+/-13 ml/m2, respectively, p = 0.037. Our data suggest that TMZ probably reduces reperfusion damage and/or infarct size in patients with anterior AMI subjected to thrombolysis and affects the post-AMI remodeling. Our data must be interpreted with caution because of the selection of patients. These findings require further extensive trials.
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PMID:Effects of trimetazidine administration before thrombolysis in patients with anterior myocardial infarction: short-term and long-term results. 1054 22

Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have both shown strong angiogenetic effects in ischemic animal models and it has been reported that these growth factors were increased after acute myocardial ischemia. However, there have been few reports on the serum levels of bFGF and VEGF after acute myocardial infarction (AMI), in particular there has not been a comparative study of bFGF and VEGF in human subjects. The time course of circulating levels of bFGF and VEGF was examined in 36 patients with AMI who were within 24h of the onset of the AMI. The serum bFGF and VEGF levels of 50 age- and sex-matched healthy volunteers served as the baseline value. All the patients had undergone coronary angiography on the day of admission (Day 0), but prior to that the serum bFGF and VEGF levels were examined by enzyme-linked immunoassay. The serum bFGF and VEGF levels were also evaluated on Days 7, 14 and 28. Creatine kinase, myosin light chain I and troponin-T were measured subsequently and radionuclide examinations were performed during the early phase of AMI to determine the infarct size. The serum bFGF levels were significantly increased at Day 0 and were maintained until Days 7 and 14. Although serum VEGF levels at Day 0 were similar to the baseline values, they showed a remarkable increase by Days 7 and 14. A high serum level of bFGF was detected in the acute phase of AMI, and a later increase in VEGF was determined in the sub-acute phase, which suggest that these 2 growth factors play an important role at different time points of the reconstructing process of infarcted myocardial tissue.
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PMID:Elevated circulating levels of basic fibroblast growth factor and vascular endothelial growth factor in patients with acute myocardial infarction. 1094 14

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.
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PMID:Central role for aldose reductase pathway in myocardial ischemic injury. 1528 19

Myocardial ischemia-reperfusion injury may complicate coronary artery bypass grafting (CABG) operations. N-Acetylcysteine (NAC) had antioxidant and microcirculatory effects, and inhibits neutrophil aggregation. The aim of this study was to determine the effects of NAC in limiting myocardial ischemia-reperfusion injury in CABG operations. Twenty patients undergoing elective coronary bypass operation with cardiopulmonary bypass were enrolled and randomly assigned to two groups: a control group operated with a routine CABG protocol, and one where NAC was administered intravenously during the operation (NAC group). Blood samples from coronary sinus for tumor necrosis factor-alpha assay, myocardial biopsy specimens for chemiluminescent luminol, and lucigenin measurements of reactive oxygen species were taken. The luminol (specific for (*)OH, H(2)O(2), and HOCl(-) radicals) and lucigenin (specific for O(2) (*-)) levels and the difference ratios after reperfusion were significantly lower in the NAC group. Tumor necrosis factor-alpha levels increased in the control group but, in contrast, a significant decrease was detected in the NAC group (P < 0.01). Creatine kinase-MB levels at 6 and 12 hours were significantly lower in the NAC group (P = 0.02). N-Acetylcysteine has potential effects to limit ischemia reperfusion injury during CABG operations. We believe that its effects on clinical outcome may be more apparent in patients prone to ischemia-reperfusion injury.
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PMID:Effects of N-acetylcysteine on myocardial ischemia-reperfusion injury in bypass surgery. 1644 Jan 48

We have previously found that, following myocardial ischemia/reperfusion injury, isolated hearts from bax gene knockout mice [Bax(-/-)] exhibited higher cardioprotection than the wild-type. We here explore the effect of Bax(-/-), following myocardial infarction (MI) in vivo. Homozygotic Bax(-/-) and matched wild-type were studied. Mice underwent surgical ligation of the left anterior descending coronary artery (LAD). The progressive increase in left-ventricular end diastolic diameter, end systolic diameter, in Bax(-/-) was significantly smaller than in Bax(+/+) at 28 d following MI (p < 0.03) as seen by echocardiography. Concomitantly, fractional shortening was higher (35 +/- 4.1% and 27 +/- 2.5%, p < 0.001) and infarct size was smaller in Bax(-/-) compared to the wild-type at 28 days following MI (24 +/- 3.7 % and 37 +/- 3.3%, p < 0.001). Creatine kinase and lactate dehydrogenase release in serum were lower in Bax(-/-) than in Bax(+/+) 24 h following MI. Caspase 3 activity was elevated at 2 h after MI only in the wild-type, but reduced to baseline values at 1 and 28 d post-MI. Bax knockout mice hearts demonstrated reduced infarct size and improved myocardial function following permanent coronary artery occlusion. The Bax gene appears to play a significant role in the post-MI response that should be further investigated.
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PMID:Bax deficiency reduces infarct size and improves long-term function after myocardial infarction. 1740 56

Any clinical intervention (e.g., coronary angioplasty, thrombolysis) used to reintroduce blood flow to an ischemic region of the myocardium is accompanied by a complex enzymatic cascade of reactions resulting in severe injury to the heart, termed myocardial ischemia/reperfusion (I/R) injury. In this study, we evaluated the ability of H-3010 (1-hydroxy-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrole-3-carboxylic acid (2-(3,4-dimethoxyphenyl)-5-([2-(3,4-dimethoxyphenyl)ethyl]-methylamino)-2-isopropylpentyl)-amide), a pyrroline modification of verapamil (2-(3,4-dimethoxyphenyl)-5-[2-(3,4-dimethoxyphenyl)ethylmethyl-amino]-2-(1-methylethyl)pentanenitrile), to protect the heart against I/R-mediated injury. Isolated perfused rat hearts pretreated with verapamil and H-3010 were subjected to 30 min of global no-flow ischemia followed by 45 min of reperfusion. The recovery (expressed as a percentage of preischemic baseline) in contractile function (left ventricular developed pressure) of hearts subjected to I/R was significantly higher in hearts treated with H-3010 at 5 microM (51.0 +/- 6.4%) as well as at 50 microM (75.1 +/- 7.4%) as compared with verapamil at 5 microM (32.2 +/- 3.7%) or untreated control hearts (18.1 +/- 2.8%). Creatine kinase release was significantly attenuated in hearts treated with H-3010 (45.7 +/- 4.5 U/liter) as compared with untreated controls (131.5 +/- 6.4 U/liter). Similar trends were also observed for lactate dehydrogenase release as well. A marked reduction in percent area of infarction was observed in the H-3010 group (11.7 +/- 1.6%) compared with verapamil (25.1 +/- 2.9%) and control (41.3 +/- 1.9%) groups. Additional in vitro studies showed a marked decrease in reactive oxygen species generation with H-3010. In conclusion, our data clearly demonstrated that the verapamil derivative, H-3010, significantly decreased I/R-induced cardiac dysfunction. This can be attributed to the combined benefits of the pyrroline moiety (antioxidant) and the parent verapamil component (antiarrhythmic) in the protection of the heart from I/R-induced injury.
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PMID:N-hydroxy-pyrroline modification of verapamil exhibits antioxidant protection of the heart against ischemia/reperfusion-induced cardiac dysfunction without compromising its calcium antagonistic activity. 1764 27


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