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)

During acute myocardial ischemia, a combination of increased extracellular K+ concentration and sympathetic nerve activation exists. Using a perfused innervated rat heart model, we studied the influence of increased extracellular K+ concentrations on neural norepinephrine (NE) release, adrenergic stimulation-induced K+ uptake by the heart, and the occurrence of ventricular arrhythmias. Hearts were globally perfused with control (4 mM) or increased concentrations of K+ (7-16 mM). Sympathetic nerve stimulation-induced NE release was analyzed by radioenzymatic assay. Cardiac K+ uptake was assessed by the reduction in K+ concentration in the coronary venous effluent induced by nerve stimulation. Neural NE release was not influenced by increasing K+ from 4 mM to 7, 10, and 13 mM, but was suppressed by 16 mM K+ (-40 +/- 10%). Nerve stimulation induced cardiac uptake of K+, which was blocked by the beta-adrenoceptor antagonist timolol. This stimulated K+ uptake was substantially enhanced by increasing extracellular K+ and was also dependent on the intensity of sympathetic stimulation at 10 mM K+. Sympathetic nerve stimulation, together with a high K+ of 10 mM, was potent in initiating ventricular tachyarrhythmias, and quantitative NE release was well correlated with the frequency of ventricular arrhythmias. Our results demonstrate the synergistic effects of increased extracellular K+ and sympathetic activation, which may be involved in the genesis of ventricular arrhythmias.
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PMID:Sympathetic activation and increased extracellular potassium: synergistic effects on cardiac potassium uptake and arrhythmias. 768 26

Hearts with pressure-overload hypertrophy show an increased intracardiac activation of the renin-angiotensin system (RAS) which may contribute to myocardial ischemia and reperfusion injury. This study investigates whether the hypertrophied myocardium is more vulnerable to ischemia and reperfusion injury and whether the specific inhibition of the cardiac RAS by captopril would modify ischemia and reperfusion injury in the hypertrophied myocardium. By using the isolated working rat heart model, hypertrophied hearts, induced by abdominal aortic banding for 6 weeks, were subjected to 120 min of hypothermic ischemic arrest followed by 30 min of reperfusion. The postischemic cardiac function recovery was measured in both the untreated (n = 10) and the captopril-treated (n = 11) groups and was compared with that of the sham-operated non-hypertrophied control hearts (n = 10). Captopril (23.0 microM) was given to one group with the hypertrophied hearts from the beginning of ischemia to the end of reperfusion. In comparison with the normal control hearts, the cardiac function recovery after 30 min reperfusion was poorer in the hypertrophied hearts, which was associated with a lower recovery of coronary flow (CF), a higher myocardial lactate content and a retarded peak myocardial creatinkinase (CK) release. Captopril significantly improved the cardiac function recovery, which was associated with an increased CF recovery and a lower myocardial lactate content, and a rapid peak CK release. In conclusion, this study shows that the hypertrophied myocardium leads to an increased susceptibility to ischemia and reperfusion injury. Captopril, most likely by its inhibition of the cardiac RAS, is effective in preventing the ischemia and reperfusion injury in the hypertrophied heart.
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PMID:Captopril cardioplegia on myocardial protection in the hypertrophied rat hearts. 772 80

An experimental model of myocardial ischemia/reperfusion injury was used to assess the cardioprotective effects of SC-52608, a low molecular weight superoxide dismutase mimetic. Langendorff perfused rabbit isolated hearts were subjected to 30 min of global ischemia followed by 45 min of reperfusion. Hearts perfused in the presence of 20 microM SC-52608 exhibited a decrease in the release of creatine kinase and intracellular potassium compared to hearts receiving vehicle (control). A progressive increase in left ventricular end-diastolic pressure developed upon reperfusion in all hearts, but was significantly greater in control hearts when compared to hearts treated with SC-52608 (P < 0.05). In addition, results obtained with a radiolabeled monoclonal antibody to the intracellular protein myosin, indicate an increased degree of irreversible damage in vehicle-treated hearts. Myocardial protection was not significant in an additional group of hearts treated with 10 microM SC-52608. The hemodynamic, biochemical, morphological, as well as the antimyosin binding data, demonstrate that pretreatment with SC-52608 protects the myocardium from damage associated with global ischemia and reperfusion. The mechanism by which SC-52608 mediates the observed protective effect is most likely related to its ability to scavenge superoxide.
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PMID:Protective effects of the SOD-mimetic SC-52608 against ischemia/reperfusion damage in the rabbit isolated heart. 779 54

Effect of myocardial ischaemia on the bioantioxidants levels in the cat heart was evaluated. In addition, effect of curcumin, an anti-inflammatory and anti-thrombotic drug, and quinidine, a standard antiarrhythmic drug, was also studied in the cat. Myocardial ischaemia was induced by the ligation of left descending coronary artery. Quinidine (1 mg/kg, iv) was administered 15 min prior to while curcumin (100 mg/kg, ip) was given 30 min before ligation. Hearts were removed 4 h post coronary artery ligation. Levels of glutathione (GSH), malonaldelhyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and lactate dehydrogenase (LDH) were estimated in the ischaemic and non-ischaemic zones. Both the drugs protected the animals against decrease in the heart rate and blood pressure following ischaemia. In the ischaemic zone, after 4 h of ligation, an increase in the level of MDA and activities of MPO and SOD (cytosolic fraction) were observed. Quinidine and curcumin pretreatment prevented the ischaemia-induced elevation in MDA contents and LDH release. Curcumin pretreatment did not prevent the increase in MPO activity while quinidine did. Results obtained indicate alterations in the bioantioxidants following ischaemia and both curcumin and quinidine prevented ischaemia induced changes in the cat heart.
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PMID:Prevention of ischaemia-induced biochemical changes by curcumin & quinidine in the cat heart. 788 81

Stunning (reversible myocardial ischemia without necrosis) occurs with induced global ischemia during cardiac operations and depresses the ability of the heart to utilize oxygen efficiently because less contractile work is developed per unit of oxygen utilized. Interestingly, regional studies have demonstrated dramatic infarct size reduction with stunning episodes before prolonged ischemia, a phenomenon known as myocardial preconditioning. It is postulated that the postischemic contractile dysfunction noted after stunning causes reduced energy demands, which "preconditions" myocardium to withstand a subsequent longer ischemic episode. Some evidence from regional studies suggests that preconditioning may improve functional recovery after ischemia. This study examined the complex relationship between stunning and preconditioning to functional recovery in a surgical setting of global ischemia. To study the effect of stunning, myocardial oxygen consumption, oxygen extraction, and functional indices of contractility were measured before and after isolated rabbit hearts were subjected to 10, 20, or 45 minutes of normothermic 37 degrees C global ischemic stun intervals. This demonstrated that while oxygen consumption and extraction quickly recover to prestun levels, contractility remains depressed well beyond the stun interval. To study the effect of preconditioning using stunning, isolated hearts were then subjected to 120 minutes of 34 degrees C cardioplegic-induced ischemia after preconditioning. Hearts received either modified St. Thomas cardioplegic solution as a control or cardioplegia administered after preconditioning with 37 degrees C ischemic stunning for 5, 10, 15, 20, or 45 minutes or multiple 5- or 10-minute stuns, with reperfusion before cardioplegic-induced ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stunning, preconditioning, and functional recovery after global myocardial ischemia. 794 10

Catecholamines play a major role during initiation and propagation of myocardial ischemia (MI). Therefore their influence on the size of an acute regional MI was investigated in isolated, coronary ligated rabbit hearts during electrical pacing at different rates (Langendorff, constant pressure: 70 cm H2O, Tyrode solution, Ca2+ 1.8 mmol/l). MI was quantified from NADH-surface-fluorescence-photography. After coronary occlusion the stimulation-rate was increased stepwise from 180 beats/min to 300/min. Experiments were performed in hearts of control and reserpinized rabbits (reserpine 7.0 mg/kg i.p. 24 h before preparation). Hearts of control animals were submitted to beta-blockade by propranolol (10(-8) mol/l) or the partial agonists pindolol (10(-6) mol/l) or carteolol (10(-6) mol/l). In untreated control hearts MI was significantly enlarged with increasing heart-rate (p < 0.05). At 300/min MI was doubled as compared to that observed at 180/min. In hearts of reserpinized animals this effect was absent (p > 0.05). Moreover, in control hearts the growth of MI could be prevented by beta-blockade with propranolol, pindolol or carteolol (p > 0.05), however, these hearts became insufficient as indicated by an increase in left ventricular enddiastolic pressure. Therefore we conclude that the pacing-rate dependent growth of MI seems not to be primarily related to myocardial left ventricular pressure nor to the heart rate. Nevertheless the growth of MI is strictly related to the release of catecholamines and might be caused by oxygen free radicals generated from noradrenaline by autoxidation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of propranolol, pindolol and carteolol on acute regional myocardial ischemia in isolated rabbit hearts. 810 27

Calcium release from sarcoplasmic reticulum (SR) may contribute to the intracellular calcium overload observed during myocardial ischemia and reperfusion. We have therefore investigated the ability of ryanodine to enhance myocardial protection when given before ischemia or during reperfusion in the isolated working rat heart. Hearts (n = 6-9/group) from male Wistar rats were aerobically (37 degrees C) perfused (20 min) with bicarbonate buffer (Ca2+ = 2.4 mM). In the first series of studies, this was followed by a 3 min infusion of St Thomas' Hospital cardioplegic solution containing various concentrations of ryanodine. Hearts were then subjected to 38 min of normothermic (37 degrees C) global ischemia and 35 min of reperfusion (15 min Langendorff, 20 min working). The recoveries of aortic flow (%AF) were 50.3 +/- 2.5% in the ryanodine free controls versus 55.2 +/- 5.8, 72.0 +/- 1.3 (p < 0.05), 61.0 +/- 4.3, 51.8 +/- 5.1 and 32.1 +/- 5.0 (p < 0.05)% in the 0.88, 1.75, 2.13, 2.50 and 10.00 nM ryanodine groups, respectively. Creatine kinase (CK) leakage during Langendorff reperfusion was reduced in the 1.75 nM group but was similar to control in all other groups. In the second series of studies, 3 min of cardioplegia without ryanodine and 38 min of ischemia (37 degrees C) were followed by 15 min of Langendorff reperfusion with 0, 0.09, 0.18, 0.88 or 1.75 nM ryanodine, %AF was 59.3 +/- 3.3%, 54.7 +/- 3.3, 53.8 +/- 3.5, 38.4 +/- 8.9 (p < 0.05) and 33.3 +/- 5.8 (p < 0.05)% in the 0, 0.09, 0.18, 0.88 and 1.75 nM ryanodine groups, respectively. CK leakage tended to increase dose-dependently.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Sarcoplasmic reticular calcium release and myocardial protection--effect of ryanodine on myocardial ischemia and reperfusion-induced injury]. 817 88

Age-related differences in the activity of 5'-nucleotidase, an enzyme responsible for conversion of high-energy phosphates to their the diffusible precursors, may help to explain age-related differences in tolerance of global myocardial ischemia. Postischemic function and high-energy phosphate content were measured in the hearts of rabbits 7 to 10 days old (neonate), 30 to 40 days old (1 month), and 6 to 12 months old (adult). Hearts in each age group were subjected to 60 minutes of ischemia at 34 degrees C either with no cardioplegia, with unmodified St. Thomas' Hospital cardioplegic solution, or with St. Thomas' Hospital cardioplegic solution with pentoxifylline, a 5'-nucleotidase inhibitor. These groups were compared with one another and with control hearts that were continuously perfused for 1 hour. In adults, addition of pentoxifylline to St. Thomas' Hospital cardioplegic solution restored adenosine triphosphate and total nondiffusible nucleotide levels to control values and improved recovery of cardiac output and developed pressure compared with results with unmodified St. Thomas' Hospital cardioplegic solution. In contrast, biochemical and functional parameters in neonatal hearts were not affected by either unmodified St. Thomas' Hospital cardioplegic solution cardioplegia or St. Thomas' Hospital cardioplegic solution with pentoxifylline. Functional recovery in neonatal hearts subjected to unprotected ischemia was superior to that in the older age groups. In 1-month-old hearts, St. Thomas' Hospital cardioplegia improved recovery compared with recovery after unprotected ischemia, but no incremental improvement in function or high-energy stores was seen with addition of pentoxifylline. The lack of effect of pentoxifylline on neonatal hearts suggest that there is a relative deficiency of 5'-nucleotidase in this age group. This may contribute to the improved functional recovery observed in unprotected hearts. Furthermore, addition of pentoxifylline to adult hearts appears to confer the benefits of low 5'-nucleotidase activity occurring naturally in the neonate.
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PMID:Developmental differences in myocardial protection in response to 5'-nucleotidase inhibition. 830 72

We studied the effect of halothane on regional myocardial function during acute ischemia and reperfusion in an open-chest pig model. Anesthesia was induced with thiopental and fentanyl and maintained with an intravenous (IV) infusion of pentobarbital and fentanyl. Regional myocardial function was studied with microsonometers placed in the subendocardium supplied by the left anterior descending coronary (LAD) and circumflex coronary artery (LX). Systolic function was evaluated with reference to the end-systolic pressure-length relationship (ESPLR) and regional systolic shortening. Diastolic dysfunction was studied with postsystolic shortening (PSS). Ischemia was induced with 15 min of total occlusion of the LAD artery, and thereafter reperfusion was allowed for 120 min. Five groups were studied: one group received only pentobarbital and fentanyl (n = 10); the other groups received halothane 0.2% (n = 5), 0.4% (n = 7), 0.6% (n = 5), and 0.8% (n = 5). The pentobarbital and fentanyl infusion was adjusted in the halothane groups in an effort to maintain arterial blood pressure and heart rate within specified limits (when possible). Results indicate that regional dysfunction during acute ischemia was equal among all the groups. However, on reperfusion, halothane significantly reduced the incidence of ventricular arrhythmias. Halothane (0.6% and 0.8%) was associated with less regional postischemic systolic dysfunction during reperfusion when compared to the other groups. Hearts subjected to 0.6% and 0.8% halothane also were less stiff at the end of systole (i.e., the extrapolated ventricular volume at zero ventricular pressure was less) after 120 min reperfusion compared to animals receiving less halothane. However, diastolic dysfunction was equal among the groups during reperfusion. We conclude that, in this model, administration of halothane is associated with improved recovery of regional systolic function and potentially beneficial pressure-length relations at the end of systole after acute severe myocardial ischemia and reperfusion. Furthermore, administration of halothane was associated with fewer reperfusion arrhythmias compared to animals not receiving halothane.
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PMID:Halothane and the reperfusion injury in the intact animal model. 846 9

To test the authors' hypothesis that cellular antioxidant enzymes constitute a cellular defense against acute stress, myocardial ischemia reperfusion injury in transgenic mice overexpressing the cellular glutathione peroxidase (GSHPx-1) was studied. Transgenic mice were generated using the entire mouse GSHPx-1 gene including approximately 2.0 kb 5'flanking sequence. A 400% increase of GSHPx activity was found in the hearts of transgenic mice compared with non-transgenic controls. Isolated perfused hearts were prepared from two groups of mice: transgenic overexpressed; non-transgenic controls. Hearts were perfused by Langendorff mode, and after 10 min of stabilization subjected to 30 min of ischemia followed by 20 min of reperfusion. In addition, a group of hearts were perfused for 50 min without subjecting them to ischemia and reperfusion to demonstrate the stability of heart preparation. Transgenic mouse hearts demonstrated significantly improved recovery of contractile force and the rate of contraction, compared to non-transgenic control mouse hearts. The infarct size was also lower in transgenic mouse hearts compared to those of non-transgenic controls. In concert, following ischemia, release of creatine kinase from the transgenic hearts was significantly lower than the control group. The results of this study indicate that increased GSHPx-1 expression renders the heart more resistant to myocardial ischemia reperfusion injury.
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PMID:Transgenic mice overexpressing glutathione peroxidase are resistant to myocardial ischemia reperfusion injury. 887 85


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