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)

Angiotensin-converting enzyme (ACE) activity in the myocardium and angiotensin-II (Ang-II) levels in plasma increase after myocardial ischemia, which lead to exacerbation of myocardial injury and cardiac dysfunction. We examined the protective role of novel antisense-oligodeoxynucleotide (AS-ODN) directed at ACE mRNA in myocardial ischemic injury. Sprague-Dawley rats were treated with ACE-AS-ODN (200 microg per rat, n = 8, i.v.) or inverted-ODN (IN-ODN, 200 microg per rat, n = 8, i.v.), given with 600 microg per rat of liposome DOTAP/DOPE. Hearts from AS-ODN- or IN-ODN-treated rats were excised, perfused in vitro, and subjected to 25 min of global ischemia followed by 30 min of reperfusion. Parallel groups of rats were given ACE inhibitor captopril (5 mg/kg, n = 8) or saline (n = 8) before excising the hearts. Ischemia/reperfusion resulted in myocardial dysfunction (increase in coronary perfusion pressure and LV end-diastolic pressure and a decrease in developed LV pressure) in the saline-treated rats. Myocardial dysfunction was associated with evidence of lipid peroxidation and enzyme leakage (MDA and LDH levels in the myocardium) and up-regulation of ACE protein expression. Administration of AS-ODN or captopril, but not IN-ODN, reduced Ang-II levels in the plasma, decreased ischemia/reperfusion-mediated cardiac functional deterioration and lipid peroxidation, and preserved LDH in the myocardium (all P < 0.05 versus the saline group). AS-ODN and captopril had equipotent effects on cardiac dynamics. ACE protein expression (western blot) was decreased in the hearts of the AS-ODN-treated group, but not in IN-ODN-treated rat hearts. In contrast, ACE protein expression was significantly increased in captopril-treated rat hearts. These observations suggest that AS-ODN directed at ACE mRNA can ameliorate myocardial dysfunction and injury after ischemia/reperfusion, and its use is associated with decreased expression of ACE protein in the ischemic myocardium.
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PMID:Protection against ischemia/reperfusion injury and myocardial dysfunction by antisense-oligodeoxynucleotide directed at angiotensin-converting enzyme mRNA. 1142 Jun 45

Heme oxygenase (HO)-1 degrades the pro-oxidant heme and generates carbon monoxide and antioxidant bilirubin. We have previously shown that in response to hypoxia, HO-1-null mice develop infarcts in the right ventricle of their hearts and that their cardiomyocytes are damaged by oxidative stress. To test whether HO-1 protects against oxidative injury in the heart, we generated cardiac-specific transgenic mice overexpressing different levels of HO-1. By use of a Langendorff preparation, hearts from transgenic mice showed improved recovery of contractile performance during reperfusion after ischemia in an HO-1 dose-dependent manner. In vivo, myocardial ischemia and reperfusion experiments showed that infarct size was only 14.7% of the area at risk in transgenic mice compared with 56.5% in wild-type mice. Hearts from these transgenic animals had reduced inflammatory cell infiltration and oxidative damage. Our data demonstrate that overexpression of HO-1 in the cardiomyocyte protects against ischemia and reperfusion injury, thus improving the recovery of cardiac function.
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PMID:Cardiac-specific expression of heme oxygenase-1 protects against ischemia and reperfusion injury in transgenic mice. 1146 13

We investigated the effects of phytoestrogen on global myocardial ischemia-reperfusion injury in five groups of female rats. A high-phytoestrogen group (HPE) was ovariectomized (Ovx) and fed a diet containing soybean protein and a high-isoflavone soy extract. Another Ovx group of rats was fed the same diet as the HPE group but treated with the estrogen receptor blocker ICI-182,780 (HPE + ICI). A third group of Ovx rats was fed a diet containing soybean protein alone (low-phytoestrogen content; LPE). A fourth Ovx group was fed a diet free of phytoestrogen (Ovx). The fifth group of rats was sham ovariectomized (sham). Hearts from all rats were subjected to 30 min of global, hypothermic (4 degrees C), cardioplegic ischemia and 120 min of normothermic (37 degrees C) reperfusion with oxygenated Krebs-Henseleit buffer. Compared with either the sham or the HPE group, the Ovx and HPE + ICI groups had significantly decreased first derivative of left ventricular pressure (dP/dt), coronary flow rate (CFR), nitrite production and mitochondrial respiratory function and significantly increased Ca2+ accumulation and myocardial histological and ultrastructural injury. The CFR of the LPE group was significantly different from that of either Ovx or HPE + ICI group but the dP/dt, nitrite production, Ca2+ accumulation, and mitochondrial function were not. Our results indicate that diets containing phytoestrogen extract play a cardioprotective role in global myocardial ischemia-reperfusion in female rats.
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PMID:Effects of dietary phytoestrogen on global myocardial ischemia-reperfusion injury in isolated female rat hearts. 1151 91

Left ventricular assist devices (LVAD) may improve cardiac function. The pathogenesis of this phenomenon, called 'reverse remodelling', is not completely elucidated. To examine the hypothesis that LVAD support eliminates tissue stress by reducing local hypoxia, the distribution of heme oxygenase-1 (HO-1), a stress protein inducible by hypoxia, was examined in vivo and in vitro. The immunoreactivity for HO-1 was semi-quantitatively analysed in left ventricular tissue of 23 patients (14 dilated cardiomyopathy (DCM), six ischaemic heart disease (IHD), three myocarditis/congenital heart disease) with end-stage heart failure before and after LVAD support, while two unused donor hearts served as controls. Control hearts stained almost negative for HO-1, while failing hearts showed immunoreactivity mainly in cardiomyocytes, but also in endothelial cells, some smooth muscle cells and fibroblasts. Hearts with IHD showed significantly higher HO-1 immunoreactivity than hearts with DCM or myocarditis/congenital heart disease. After LVAD support, the HO-1 content decreased significantly in the DCM and IHD group and was significantly higher in the subendocardium than in the subepicardium. In vitro, under hypoxic conditions, neonatal rat cardiomyocytes showed an increase of HO-1 protein content up to sixfold above the normal level, which returned to normal values after normoxic cultivation. Mechanical support reduces the HO-1 content of the failing heart and HO-1 is inducible in vitro under hypoxia and is reversible under normoxia. This supports the concept that restoration of cardiac normoxia by mechanical unloading, particularly in the subendocardium, may be in part responsible for the phenomenon of 'reverse remodelling'.
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PMID:Reduction of hypoxia-inducible heme oxygenase-1 in the myocardium after left ventricular mechanical support. 1201 48

Isoflurane mimics the cardioprotective effect of acute ischemic preconditioning with an acute memory phase. We determined whether isoflurane can induce delayed cardioprotection, the involvement of ATP-sensitive potassium (K(ATP)) channels, and cellular location of the channels. Neonatal New Zealand White rabbits at 7-10 days of age (n = 5-16/group) were exposed to 1% isoflurane-100% oxygen for 2 h. Hearts exposed 2 h to 100% oxygen served as untreated controls. Twenty-four hours later resistance to myocardial ischemia was determined using an isolated perfused heart model. Isoflurane significantly reduced infarct size/area at risk (means +/- SD) by 50% (10 +/- 5%) versus untreated controls (20 +/- 6%). Isoflurane increased recovery of preischemic left ventricular developed pressure by 28% (69 +/- 4%) versus untreated controls (54 +/- 6%). The mitochondrial K(ATP) channel blocker 5-hydroxydecanoate (5-HD) completely (55 +/- 3%) and the sarcolemmal K(ATP) channel blocker HMR 1098 partially (62 +/- 3%) attenuated the cardioprotective effects of isoflurane. The combination of 5-HD and HMR-1098 completely abolished the cardioprotective effect of isoflurane (56 +/- 5%). We conclude that both mitochondrial and sarcolemmal K(ATP) channels contribute to isoflurane-induced delayed cardioprotection.
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PMID:Delayed cardioprotection by isoflurane: role of K(ATP) channels. 1206 75

Recently several polyphenolic antioxidants derived from grape seeds and skins have been implicated in cardioprotection. This study was undertaken to determine if the grapes were equally cardioprotective. Sprague Dawley male rats were given (orally) standardized grape extract (SGE) for a period of three weeks. Time-matched control experiments were performed by feeding the animals 45 microg/100 of glucose plus 45 microg/100 g fructose per day for three weeks. After 30 days, rats were sacrificed, hearts excised and perfused via working-mode. Hearts were made ischemic for 30 min followed by two hours of reperfusion. At 100 mg/kg and at 200 mg/kg, SGE provided significant cardioprotection as evidenced by improved post-ischemic ventricular recovery and reduced amount of myocardial infarction. No cardioprotection was apparent when rats were given grape samples at a dose of 50 mg/100 g/day. In vitro studies demonstrated that the SGE could directly scavenge superoxide and hydroxyl radicals which are formed in the ischemic reperfused myocardium. The results demonstrate that the heats of the rats fed SGE reduced myocardial ischemia reperfusion injury by functioning as in vivo antioxidant.
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PMID:Reduction of myocardial ischemia reperfusion injury with regular consumption of grapes. 1207 86

We studied the differences between the functional and bioenergetic effects of antioxidants (AOX) administered before or after myocardial ischemia. Sprague-Dawley rat hearts were perfused with a modified Krebs-Henseleit solution and bubbled with 95% O(2)-5% CO(2). The protocol consisted of 10 min of baseline perfusion, 20 min of global ischemia, and 30 min of reperfusion. An AOX, either 1,2-dihydroxybenzene-3,5-disulfonate (Tiron), a superoxide scavenger, or N-acetyl-L-cysteine, was infused during either baseline or reperfusion. An additional group received deferoxamine as a bolus before ischemia. Hearts were freeze-clamped at baseline, at end of ischemia, and at end of reperfusion for analysis of high-energy phosphates. All AOX, when given before ischemia, inhibited recovery of ATP compared with controls. Both Tiron and deferoxamine also inhibited recovery of phosphocreatine. AOX given before ischemia decreased the efficiency of contraction during reperfusion compared with controls. All of the changes in energetics and efficiency brought on by preischemic AOX treatment could be blocked by a preconditioning stimulus. This suggests that reactive oxygen species, which are generated during ischemia, enhance bioenergetic recovery by increasing the efficiency of contraction.
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PMID:Reactive oxygen species generated during myocardial ischemia enable energetic recovery during reperfusion. 1223 20

Epidemiologic studies suggest that mild-to-moderate wine consumption is associated with a reduced incidence of mortality and morbidity from coronary heart disease. Because wines are produced from grapes, this study was done to determine whether the grapes were equally cardioprotective. Sprague-Dawley male rats were given (orally) standardized grape extract (SGE) (obtained from the California Table Grape Commission, Fresno, CA, U.S.A.) (50, 100, or 200 mg/kg body weight per day) for 3 weeks. Time-matched control experiments were performed by feeding the animals 45 microg/100 g of glucose plus 45 microg/100 g of fructose per day for 3 weeks. After 21 days, rats were killed and the hearts excised and perfused via working mode. Hearts were made ischemic for 30 min followed by 2 h of reperfusion. At 100 mg/kg and at 200 mg/kg, grapes provided significant cardioprotection as evidenced by improved postischemic ventricular recovery (aortic flow, developed pressure, the maximum first derivative of the developed pressure) and reduced amount of myocardial infarction. There were no differences in results between the two groups (100 mg/kg versus 200 mg/kg). No cardioprotection was apparent when rats were given grape samples at a dose of 50 mg/100 g/d. SGE reduced the malonaldehyde content of the heart, indicating reduction of oxidative stress during ischemia and reperfusion. In vitro studies demonstrated that the SGE could directly scavenge superoxide and hydroxyl radicals that are formed in the ischemic reperfused myocardium. The results demonstrate that the hearts of the rats fed SGE are resistant to myocardial ischemia reperfusion injury, suggesting a cardioprotective role of grapes.
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PMID:Cardioprotection with grapes. 1240 85

The effects of chronic alcohol consumption on myocardial ischemia and gas perfusion with 95% O(2)-5% CO(2) were investigated in isolated rat heart. Eighteen adult male Wistar rats were used. Rats were assigned into six groups for each group to contain three rats: normal, alcoholic, normal ischemic, alcoholic ischemic, normal ischemic and 95% O(2)-5% CO(2) perfused, alcoholic ischemic and 95% O(2)-5% CO(2) perfused, respectively. Alcohol (7.2%, v/v) was given to rats by a modified liquid diet for 21 days. Rats were anaesthetized with ketamine (1-2mg kg(-1)). Hearts were quickly isolated. Normal and alcoholic rat hearts were directly sent to the electron microscopic preparation. The other hearts were cut into small pieces and put into Krebs solution. The solution was continuously bubbled using 95% N(2)-5% CO(2) 20 min for ischemia. After removal of normal ischemic and alcoholic ischemic heart specimens for electron microscopic examination, the remaining hearts of the last two groups were bubbled with 95% O(2)-5% CO(2) for another 20 min for the purpose of reperfusion and then were also prepared for electron microscopic examination. The hearts were investigated with a transmission electron microscope (Jeol 100 CXII TEM). Twenty-one days of chronic alcohol consumption was found to have no significant effect on myocardial ischemia determined by transmission electron microscopic examination. Our results suggest that there is no significant relationship between 21 days of alcohol consumption by a liquid diet and myocardial protection.
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PMID:Effects of chronic alcohol consumption on myocardial ischemia in rats. 1259 Oct 11

Recently, rapid and transient cardiac pacing was shown to induce preconditioning in animal models. Whether the electrical stimulation per se or the concomitant myocardial ischemia affords such a protection remains unknown. We tested the hypothesis that chronic pacing of a cardiac preparation maintained in a normoxic condition can induce protection. Hearts of 4-day-old chick embryos were electrically paced in ovo over a 12-h period using asynchronous and intermittent ventricular stimulation (5 min on-10 min off) at 110% of the intrinsic rate. Sham (n = 6) and paced hearts (n = 6) were then excised, mounted in vitro, and subjected successively to 30 min of normoxia (20% O(2)), 30 min of anoxia (0% O(2)), and 60 min of reoxygenation (20% O(2)). Electrocardiogram and atrial and ventricular contractions were simultaneously recorded throughout the experiment. Reoxygenation-induced chrono-, dromo-, and inotropic disturbances, incidence of arrhythmias, and changes in electromechanical delay (EMD) in atria and ventricle were systematically investigated in sham and paced hearts. Under normoxia, the isolated heart beat spontaneously and regularly, and all baseline functional parameters were similar in sham and paced groups (means +/- SD): heart rate (190 +/- 36 beats/min), P-R interval (104 +/- 25 ms), mechanical atrioventricular propagation (20 +/- 4 mm/s), ventricular shortening velocity (1.7 +/- 1 mm/s), atrial EMD (17 +/- 4 ms), and ventricular EMD (16 +/- 2 ms). Under anoxia, cardiac function progressively collapsed, and sinoatrial activity finally stopped after approximately 9 min in both groups. During reoxygenation, paced hearts showed 1) a lower incidence of arrhythmias than sham hearts, 2) an increased rate of recovery of ventricular contractility compared with sham hearts, and 3) a faster return of ventricular EMD to basal value than sham hearts. However, recovery of heart rate, atrioventricular conduction, and atrial EMD was not improved by pacing. Activity of all hearts was fully restored at the end of reoxygenation. These findings suggest that chronic electrical stimulation of the ventricle at a near-physiological rate selectively alters some cellular functions within the heart and constitutes a nonischemic means to increase myocardial tolerance to a subsequent hypoxia-reoxygenation.
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PMID:Ectopic pacing at physiological rate improves postanoxic recovery of the developing heart. 1274 35


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