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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The conducting system was studied in an in situ perfused swine heart preparation with reduced coronary flow (ischemia) using perfusate containing high and low levels of glucose (26.6 versus 8.6mM) with and without insulin. Coronary flow was maintained at normal levels for 60 minutes in control hearts. In ischemic hearts flow was reduced to about 50 percent of control levels for 30 minutes. Ultrastructural studies documented only subtle modifications of Purkinje fibers in ischemic hearts. Glycogen depletion and disruption of cell junctions were observed in some fibers. One consistent finding was the activation of the lysosomal system. The outer membranes of primary lysosomes appeared herniated and in some cases disrupted, and small vesicles containing hydrolytic enzymes were seen in association with the Golgi apparatus and larger primary lysosomes. Specimens prepared for the demonstration of acid phosphatase indicated a redistribution of hydrolytic enzymes in Purkinje fibers with a depostion of acid hydrolases in smaller lysosomal vesicles, the transverse and side-to-side junctions between cells, and occasionally in the sarcoplasmic reticulum. Enriched perfusate containing high levels of glucose with insulin appeared to have no therapeutic effects in terms of the structure of the Purkinje fibers. The results suggest that alterations in the lysosomal system may be one of the earliest structural changes which occur in oxygen-deficient hearts.
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PMID:Ischemic injury to the conducting system of the heart. Involvement of myocardial lysosomes. 43 Oct 98

Sixteen patients with significant two and three vessel coronary artery disease but without clinical congestive heart failure were studied during rapid atrial pacing before and after infusion of 0.015 mg/kg of ouabain. Seven patients with a decreased (less than 50 percent) ejection fraction and nine patients with a normal ejection fraction had a significant (P less than 0.05) increase in resting arterial systolic pressure after the administration of ouabain. However, resting values for coronary sinus flow, coronary vascular resistance, myocardial oxygen consumption and myocardial lactate extraction did not change significantly in either group. During pacing, patients with a decreased ejection fraction demonstrated more ischemia than patients with a normal ejection fraction; however, the administration of ouabain did not significantly alter pacing-related changes in coronary sinus flow, myocardial oxygen consumption, myocardial lactate extraction, ischemic electrocardiographic changes or onset of chest pain in either group. The administration of ouabain has a negligible effect on coronary hemodynamics, myocardial metabolism or clinical signs of ischemia in patients with coronary artery disease with normal or abnormal left ventricular function.
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PMID:Lack of ouabain effect on pacing-induced myocardial ischemia in patients with coronary artery disease. 43 84

The influence of the Valsalva maneuver (VM) on myocardial ischemia was evaluated in 24 patients with coronary heart disease. Clinical and hemodynamic responses to the VM were studied during acute ischemia manifested by angina pectoris with transient left ventricular (LV) dysfunction and compared with responses during nonischemic intervals. In the absence of evidence for acute ischemia (angina and increased LV end-diastolic pressure), six patients had abnormal hemodynamic responses to the VM. Five had lack of systolic pressure overshoot and in one, systolic pressure did not decline during straining. When the VM was performed during an ischemic episode, 14 patients had abnormal responses (12 with lack of overshoot in phase IV and two with lack of systolic pressure decline in phase II). In 18 patients a prompt decline in LV end-diastolic pressure occurred with the disappearance of angina during the VM. These changes uniformly occurred during the latter part of straining (VM phase II) as cardiac size and systolic pressure declined. No adverse effects occurred when a VM was performed during acute ischemia. Our observations suggest that the VM abruptly reduces determinants of cardiac oxygen demand, relieving acute ischemia without harmful effects.
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PMID:Effects of the Valsalva maneuver on myocardial ischemia in patients with coronary artery disease. 43 22

In line with studies on the metabolism of the ischemic myocardium, the effectiveness of diltiazem hydrochloride, a potent calcium antagonist, in reducing the effects of ischemia was evaluated. Nonischemic and ischemic tissue samples were examined in two groups of dogs--Group I, dogs receiving no drug and killed after 60 minutes of regional ischemia, and Group II, dogs given diltiazem after 10 minutes of ischemia and killed 50 minutes later. Administration of diltiazem proved beneficial in several ways: The decrease in adenosine-5'-triphosphate in the ischemic region was halved, inhibition of anaerobic glycolysis was reduced, tissue levels of lactic acid and free fatty acids were lowered and the contractility of glycerinated heart muscle fibers was improved. However, administration of the drug did not influence mitochondrial function. Mitochondrial oxygen consumption and respiratory control were reduced by equal amounts in both groups, as was mitochondrial calcium ion binding. These observations demonstrate that diltiazem is capable of minimizing the consequences of acute ischemic, although the beneficial effects do not extend to all aspects of myocardial metabolism.
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PMID:Effect of diltiazem, a calcium antagonist, on myocardial ischemia. 44 73

Nifedipine, a slow-channel calcium blocker, is thought to provide useful myocardial protection during prolonged total ischemia and reperfusion. An isolated, isovolumic, feline heart model was used to asses the effectiveness of nifedipine in both cardioplegic (100 microgram/10 ml) and noncardioplegic (10 microgram/10 ml) doses for providing myocardial preservation during 90 minutes of hypothermic ischemic arrest and 45 minutes of normothermic reperfusion. Use of nifedipine was compared to hypothermia (27 degrees C) alone and to hypothermia with potassium cardioplegia. Ventricular function was assessed by recovery of isovolumic left ventricular developed pressure and dP/dt. Myocardial carbon dioxide tension (PCO2) and myocardial oxygen tension (PO2) were measured by mass spectrometry. Potassium cardioplegia and the higher dose of nifedipine resulted in immediate asystole. The rates of rise of PCO were greatest in the group receiving 10 microgram nifedipine and in the control group. The rates of rise in the two cardioplegic groups were significantly lower. Recovery of ventricular function was significantly lower with low-dose nifedipine than with potassium cardioplegia. Higher dose nifedipine resulted in a return of function, which was no different than with potassium cardioplegia. Morphologic protection was better with higher dose nifedipine and potassium cardioplegia than with either low-dose cardioplegia or hypothermia alone. These results demonstrate that nifedipine in a cardioplegic dose results in preservation of myocardial structure and function that is similar to that obtained with potassium cardioplegia. In lower noncardioplegic dose, nifedipine does not appear to offer additional protection compared to hypothermia alone. Whether persistent depression of ventricular contractility will limit nifedipine's clinical usefulness as a myocardial protection agent will require further study.
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PMID:Comparison of myocardial protection with nifedipine and potassium. 44 71

There are few data in the literature suggesting that endogenous prostaglandins (PGs) might be involved in the pathomechanism of seizures. Since the mechanism of seizures inducted by exposure to oxygen high pressure (OHP) is not fully elucidated, this study was designed to investigate the effect of exogenous PG s and of indomethacin (a Pg synthesis inhibitor) upon the development and consequences of seizures in rats exposed to OHP (5 ata). In the animals pretreated with PGE2 (1 ng/kg s.c.) pre-seizure time was shortened, lung weight : body weight index increased and symptoms of respiratory failure potentiated, as compared with the control group. Indomethacin (5 mg/kg i.p) prevented the development of seizures and of pulmonary consequences of OHP exposure. Biochemical examination of brains has shown that velocity of free radical oxidation of lipids (reactions manifested by the breakdown of phospholipid fatty acids, mainly unsaturated ones) enhanced by OHP exposure, is further potentiated in rats pretreated with PGE2. Electron microscopic study has shown the alterations similar to those seen in brain ischemia and/or hypoxia, and the magnitude of changes was related to the intensity of symptoms evoked by OHP. The results show that cerebral and pulmonary consequences of OHP exposure are potentiated by exogenous PGE2 and prevented by inhibition of endogenous PG synthesis. This suggests that PGs and/or their active metabolites might be involved in the mechanism of oxygen toxicity during exposure to hyperbaric oxygen.
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PMID:Effect of prostaglandin E2 and of indomethacin upon cerebral and pulmonary consequences of exposure to hyperbaric oxygen in rats. 45 47

The effects of pentobarbital on survival times of mice exposed to oxygen, 5 per cent, were studied over a large dosage range in normal mice and in mice made tolerant to the effect of barbiturates. Tolerance was induced by pretreatment with phenobarbital, 210 mg/kg, for three days, which increased the median anesthetic dose (AD50) for pentobarbital from 34 to 53 mg/kg. In nontolerant mice there was a dose-related increase in mean survival times for doses between 35 and 60 mg/kg, with a maximum increase to 303 per cent above control. At doses of more than 60 mg/kg survival times progressively decreased toward control. For tolerant mice survival time as a function of pentobarbital dosage was shifted to the right, i.e., protection necessitated higher doses. This shift was not explained by lower brain concentrations of pentobarbital in tolerant animals, but rather parallelled the increased tolerance to the anesthetic effect of the barbiturate. The authors conclude that in this model the protective effect of barbiturate is a function of the anesthetic effect rather than the barbiturate concentration in brain per se. Hypothermia (29 C) resulted in an increase in mean survival time comparable to that in barbiturate-treated animals. This supports the hypothesis that protection is ultimately a function of decreased cerebral metabolism, whether produced by anesthesia or by hypothermia. This model measures only the effect on spontaneous respiration during hypoxia. It is possible that other mechanisms are involved if barbiturates protect in other situations, such as during or after periods of complete ischemia.
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PMID:Barbiturate protection in tolerant and nontolerant hypoxic mice: comparison with hypothermic protection. 45 57

FREE FATTY ACIDS (FFA) IN EXCESS FFA: albumin molar ratios have been determined to additionally compromise mechanical performance in ischemic hearts. Carnitine, an intracellular carrier of FFA and an agent which is lost to the heart during ischemia, has been postulated to in part restore function with its replacement. To test whether its benefits are also operative in a setting of excess FFA, these studies were performed. In the main protocol, four groups of perfused swine hearts (n = 45) were compared during 50 min of control flow (179.7 ml/min) and 40 min of global ischemia (106.1 ml/min). Initial base-line serum FFA:albumin molar ratios and carnitine levels in all groups were 1.3:1 and 8.5 nmol/ml, respectively. In two of these groups FFA:albumin ratios were increased to 5.9:1 with constant infusions of Intralipid. In two alternate groups (one with and one without extra FFA supplements) dl-carnitine was supplied, sufficient to increase serum levels nearly 200-fold. Ischemia per se in 14 hearts significantly decreased several parameters of global and regional mechanical function including left ventricular (LV) and mean aortic pressures, LV isovolumetric pressure development (max dp/dt), LV epicardial motion, and LV work, together with concomitant decreases in myocardial oxygen consumption. Elevated FFA in 12 hearts rendered similarly ischemic further decreased mechanical function (LV pressure: -20.8%, P < 0.05; mean aortic pressure -26.9%, P < 0.05; LV max dp/dt: -39%, P < 0.05; regional LV shortening: -51.1%, P < 0.05; and LV work: -50.3%, P < 0.05) as compared with nonsupplemented hearts. dl-Carnitine treatments in nine hearts, not supplemented with extra FFA were without apparent effect in improving overall hemodynamic performance. However, dl-carnitine in 10 high FFA-ischemic hearts effected several improvements as compared with the untreated group: LV pressure was increased 25.6%, P < 0.025; mean aortic pressure: +43.5%, P < 0.05; LV max dp/dt: +41.5%, P < 0.05; regional LV shortening: +241.3%, P < 0.001; and LV work: +76.2%, P < 0.05 at comparable levels of myocardial oxygen consumption. In a separate protocol, the effects of stereospecificity were also studied by comparing l- with dl-carnitine in globally perfused, palmitate-supplemented hearts (five hearts in each treatment group). At similar conditions of flow and serum FFA, changes in mechanical function were comparable, except for a tendency to perform greater LV work at reduced flows in the l-carnitine-treated hearts. Thus, it was demonstrated that carnitine in ischemic hearts is capable of preserving mechanical function under conditions of excess FFA, presumably by modifying the toxic effects of FFA intermediates. The major therapeutic actions appeared to derive from the l-isomer of carnitine.
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PMID:Effects of carnitine in ischemic and fatty acid supplemented swine hearts. 45 63

The effects of 1 and 2 hours of hypothermic anoxic arrest and cardioplegia induced by Mg-lidocaine, K-Mg, or K on left ventricular mitochondrial respiratory function, blood flow, and edema were studied in 41 mongrel dogs. Mitochondrial respiration was assessed by the indices of oxidative phosphorylation. Myocardial temperature recorded in ventricular septum was kept at 20 degrees C during ischemic arrest and 10 minutes of reperfusion. Cardioplegic solutions did not influence noncoronary blood flow during cross-clamping of the aorta. Mitochondrial respiratory function remained at control levels after 1 hour of ischemia induced by hypothermic anoxic arrest or by Mg-lidocaine or K-Mg hypothermic cardioplegia. Mitochondrial state 3 respiration after 2 hours of anoxic arrest was significantly higher in Mg-lidocaine cardioplegia than in anoxic arrest (p less than 0.05), but myocardial edema was equivalent in both groups. Mg in the cardioplegic solution suppressed mitochondrial nonphosphorylating oxygen consumption. These data suggest that mitochondrial function after 1 hour of ischemic arrest at 20 degrees C and 10 minutes of reperfusion is not significantly depressed, but at 2 hours of ischemic arrest, mitochondrial respiration is significantly impaired. However, hypothermic Mg-lidocaine cardioplegia appears to be more effective in sustaining myocardial respiration than does simple hypothermic anoxic arrest when the anoxic period is extended to 2 hours.
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PMID:Myocardial respiration and edema following hypothermic cardioplegia and anoxic arrest. 45 28

The ability of prostacyclin (PGI2) to alter responses to acute myocardial ischemia was studied in open-chest, anesthetized cats. PGI2 was infused intravenously at 0.5 nmoles kg-1 min-1 in cats subjected to 5 h of myocardial ischemia by occlusion of the LAD coronary artery, and in sham-operated controls. GI2 infusion resulted in significantly decreased arterial blood pressure and inhibition of platelet aggregation. Coronary ligation resulted in significant S-T segment elevations lasting 5 h in vehicle-treated animals but only 1 h in cats with myocardial ischemia and receiving PGI2. At 5 h, cats with ischemia and given the vehicle showed S-T segment elevations significantly greater than the other two groups. Ischemic myocardium from vehicle-treated animals exhibited significantly less creatine phosphokinase (CPK) specific activity than normal tissue from the same hearts or myocardial tissue from the other two groups. This loss of CPK from ischemic myocardium of the cats given vehicle was reflected in plasma CPK specific activities which were significantly greater than those of sham-operated cats. The cats with ischemia and treated with PGI2 exhibited lower plasma CPK activities. These changes were moderated by PGI2 infusion during myocardial ischemia. PGI2 infusion may protect the ischemic myocardium by reducing oxygen demand, primarily through reductions in cardiac work, and by perhaps inhibiting platelet aggregation and preserving myocardial cell integrity.
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PMID:Studies on the protective effect of prostacyclin in acute myocardial ischemia. 46 18


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