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)

We studied the role of copper as a potential mediator of postischemic reperfusion injury in the isolated, perfused rat heart. Hearts were equilibrated with Krebs-Henseleit buffer for 10 minutes and then loaded with copper by way of perfusion with buffer containing 20 microM copper(II)-bis-histidial for 30 minutes. Control hearts were perfused with Krebs-Henseleit buffer alone during the loading period. Hearts than were washed with buffer for 10 minutes and subjected to 20 minutes of normothermic global ischemia followed by 30 minutes of reperfusion. Atomic absorption spectroscopy revealed a 67% increase in total copper content in loaded hearts by the end of the wash. By the end of the 30-minute period of reperfusion, control hearts demonstrated a 50-60% recovery of myocardial function as determined by peak systolic pressure, contractility, and heart rate. In contrast, copper-loaded hearts exhibited virtually no functional recovery within the 30-minute time period. Using salicylate as a probe, we determined that peak and duration of .OH formation appears to be increased in copper-loaded hearts during reperfusion. Furthermore, efflux of lactic dehydrogenase was significantly increased in copper-loaded hearts. Our results clearly demonstrate that increasing cardiac content of copper results in enhanced postischemic reperfusion injury associated with increased formation of .OH, thus suggesting an important catalytic role for this transition metal.
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PMID:Copper loading of hearts increases postischemic reperfusion injury. 187 80

Stress echocardiography is a relatively new technique that combines cardiovascular stress with echocardiographic imaging for the diagnosis of coronary artery disease. It is based on the hypothesis that stress-induced ischemia will result in regional wall motion abnormalities that can be detected by two-dimensional echocardiography or abnormalities of global function that can be detected with Doppler ultrasound. Its accuracy for detecting coronary artery disease is high enough to allow for clinical use. In such a role it has added value to the analysis of the routine electrocardiogram and symptoms during exercise. In the patient unable to exercise, pharmacological stress with the use of dobutamine or dipyridamole are realistic alternatives. In addition to the diagnosis of coronary disease, stress echocardiography can be used to demonstrate recovery of function after interventions and to assess prognosis after myocardial infarction.
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PMID:Stress echocardiography for detection of coronary artery disease. 188 3

The cardioprotective effect of calmodulin antagonists, trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) was examined on the isolated rat heart exposed to hypothermic and ischemic conditions by measuring distribution of lysosomal enzymes in myocardial cells, and leakage of creatine kinase (CK) during reperfusion and postischemic recovery in myocardial systolic function. Experimental hearts were infused with 20 degrees C Krebs-Henseleit bicarbonate buffer (KHB) or KHB containing TFP or W-7 for 2min every 30min during hypothermic ischemia. After ischemia for 120min at 20 degrees C, rat hearts were reperfused at 37 degrees C for 30min. TFP and W-7 improved functional recovery and prevented CK release. In TFP treated hearts, leakage of lysosomal enzymes was reduced significantly, whereas stabilization of lysosomes by W-7 did not occur. These results suggest that calcium-calmodulin dependent enzymes may play an important role in the development of cellular damage of the myocardium during hypothermic ischemia, although levels of leakage of lysosomal enzymes may be unreliable predictors of functional recovery after hypothermic ischemia.
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PMID:Protective effects of calmodulin antagonists (trifluoperazine and W-7) on hypothermic ischemic rat hearts. 189 73

Using an isolated working rat heart model, the effects of DL-verapamil, ryanodine, gabexate mesilate (FOY), recombinant human superoxide dismutase (RH-SOD), and coenzyme Q10 upon myocardial protection were evaluated. Under conditions of normothermic ischemia, all these compounds, except RH-SOD, when added to the St. Thomas' cardioplegic solution at an optimal concentration, showed beneficial effects upon functional recovery and enzyme leakage. In contrast, the above compounds, except ryanodine and FOY, failed to improve the protective properties of the St. Thomas' cardioplegic solution under conditions of hypothermic ischemia. Our results indicate that calcium overload via the calcium channel and calcium-induced calcium release from sarcoplasmic reticulum (SR) may contribute to the onset of ischemic-reperfusion injury. However, under conditions of hypothermic ischemia, calcium-induced calcium release from SR plays a dominant role in calcium overload. Furthermore, intracellular calcium overload may activate proteases and result in the acceleration of myocardial injury.
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PMID:The effects of several pharmacologic agents upon postischemic recovery. 190 37

The hypothesis tested is that shifts in pH, induced when a cardioplegic solution is oxygenated, can be detrimental. We added either 100% nitrogen, 95% nitrogen and 5% carbon dioxide, 100% oxygen, or 95% oxygen and 5% carbon dioxide to the cardioplegic solution (St. Thomas' Hospital No. 2 plus glucose 11 mmol/L), and determined postischemic recovery of isolated rat hearts after 3 hours of 10 degrees C cardioplegic protected ischemia. Hearts were arrested and reinfused every 30 minutes throughout the ischemic period with cardioplegic solution. When 5% carbon dioxide was added to nitrogen, the pH of the cardioplegic solution decreased from 9.1 (100% nitrogen) to 7.0 (95% nitrogen: 5% carbon dioxide), a change associated with improved postischemic functional recovery. Aortic output improved from 52.3% +/- 2.7% to 63.9% +/- 2.8%, p less than 0.05, and cardiac output from 60.8% +/- 3.6% to 75.4% +/- 3.3%, p less than 0.01. This improvement was associated with diminished efflux of lactate during ischemia but increased postischemic release of lactate dehydrogenase. When nitrogen was replaced with oxygen, the addition of 5% carbon dioxide resulted in a similar decrease of pH, which again was associated with improved postischemic functional recovery. Aortic output improved from 66.3% +/- 2.8% (100% oxygen) to 88.9% +/- 3.7% (95% oxygen: 5% carbon dioxide), p less than 0.005, and cardiac output from 75.3% +/- 4.1% to 88.9% +/- 2.4%, p less than 0.01. The efflux of lactate during ischemia and the postischemic release of lactate dehydrogenase were similar in both groups. Furthermore, provision of additional oxygen with perfluorocarbons in an electrolyte solution identical to the St. Thomas' Hospital plus glucose solution and oxygenated with 95% oxygen: 5% carbon dioxide conferred no extra protection. In conclusion, the St. Thomas' Hospital No. 2 plus glucose cardioplegic solution should be oxygenated but with 95% oxygen: 5% carbon dioxide and not 100% oxygen because of the additive effect of a relatively "acidotic" pH.
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PMID:Effect of oxygenation and consequent pH changes on the efficacy of St. Thomas' Hospital cardioplegic solution. 844 34

Clinical application of hypothermic pharmacologic cardioplegia in pediatric cardiac surgery is less than satisfactory, despite its well known benefits in adults. Protection of the ischemic immature rabbit heart with hypothermia alone is better than with hypothermic St. Thomas' II cardioplegic solution. Control of cellular calcium is a critical component of cardioplegic protection. We determined whether the existing calcium content of St. Thomas' II solution (1.2 mmol/L) is responsible for suboptimal protection of the ischemic immature rabbit heart. Modified hypothermic St. Thomas' II solutions (calcium content, 0 to 2.4 mmol/L) were compared with hypothermic Krebs bicarbonate buffer in protecting ischemic immature (7- to 10-day-old) hearts. Hearts (n = 6 per group) underwent aerobic "working" perfusion with Krebs buffer, and cardiac function was measured. The hearts were then arrested with a 3-minute infusion of either cold (14 degrees C) Krebs buffer (1.8 mmol calcium/L) as hypothermia alone or cold St. Thomas' II solution before 6 hours of hypothermic (14 degrees C) global ischemia. Hearts were reperfused, and postischemic enzyme leakage and recovery of function were measured. A bell-shaped dose-response profile for calcium was observed for recovery of aortic flow but not for creatine kinase leakage, with improved protection at lower calcium concentrations. Optimal myocardial protection occurred at a calcium content of 0.3 mmol/L, which was better than with hypothermia alone and standard St. Thomas' II solution. We conclude that the existing calcium content of St. Thomas' II solution is responsible, in part, for its damaging effect on the ischemic immature rabbit heart.
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PMID:Calcium content of St. Thomas' II cardioplegic solution damages ischemic immature myocardium. 192 65

In a rat model of volume-controlled hemorrhagic shock causing the death of all saline-treated animals within 30 min of treatment, the intravenous bolus injection of thyrotropin- releasing hormone tartrate (TRH-T) at the dose of 4 mg/kg induced the prompt and sustained disappearance of the ECG and EEG signs of heart and brain ischemia, along with the reversal of hypotension and respiratory depression and with 100% survival rate at the end of the 2 h observation period. These data confirm that, in a pre-terminal condition induced by massive hemorrhage, timely treatment with TRH-T will restore heart and brain perfusion to levels compatible with survival and with functional recovery from ischemia and maintain it at those levels for some hours.
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PMID:TRH reverses the ECG and EEG ischemic changes induced by massive hemorrhage in rats. 194 85

This study examines the effects of brief periods of ischemia on average and cardiac cycle-dependent variation of regional ultrasonic backscatter paralleled with changes in regional myocardial contraction, and to what extent these changes could be reversed by synchronized coronary venous retroperfusion. In five closed-chest dogs, the left anterior descending coronary artery was occluded on four occasions for a 2-minute period and retroperfusion was applied randomly to two of the coronary occlusions. Complete functional recovery was allowed between the occlusions. Two-dimensional echocardiographic images were obtained before and at the peak of the 2-minute occlusion period. Regional myocardial contraction as measured by fractional area change and systolic wall thickening during untreated occlusions decreased from 33.9 +/- 14.0% to -0.15 +/- 6.2%, and from 22.0 +/- 1.8% to -17.9 +/- 2.2%, whereas during retroperfusion-treated occlusions it changed from 37.4 +/- 8.5% to only 23.4 +/- 11.2% (p less than 0.005 versus baseline), and from 24.1 +/- 2.8% to only 12.7 +/- 2.0% (p less than 0.005 versus baseline), corresponding to a preservation of 62% and 52% of baseline regional contraction, respectively. Average regional gray level (arbitrary units) during untreated coronary occlusions exhibited a significant increase in the ischemic regions, from 5.6 +/- 2.7 at baseline to 11.5 +/- 4.4 during occlusion (p less than 0.005); during retroperfusion-treated occlusions, average gray level increased from 4.7 +/- 3.6 to only 6.3 +/- 3.6 (NS). Untreated coronary artery occlusions resulted in a systolic increase in gray level in the ischemic region, followed by a diastolic decrease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Preservation of regional myocardial ultrasonic backscatter and systolic function during brief periods of ischemia by synchronized coronary venous retroperfusion. 195 Sep 92

Isolated Langendorff-perfused rat hearts (n = 6/group) were subjected to 60, 90, 120, or 180 min of ischemia with or without a 2-min preischemic infusion with St. Thomas' Hospital cardioplegic solution that had been modified to contain concentrations of calcium of 0, 0.5, 0.8, 1.0, 1.2, 1.8, or 2.4 mM. In general, irrespective of the calcium concentration, hearts in the cardioplegia group recovered better than those in the noncardioplegia group. There was no consistent relationship between calcium content and postischemic recovery of function or enzyme leakage after any of the durations of ischemia studied. However, as expected, there was a strong inverse relationship between recovery and duration of ischemia. The recovery of function correlated with enzyme leakage but not with the time to onset or magnitude of ischemic contracture. In conclusion, although the neonatal rat heart benefits from cardioplegia the protection is less impressive than that reported for adult hearts. Nonetheless, the neonatal heart appears to be very resistant to ischemia. We propose that many of these differences can be explained on the basis of differences in myocardial calcium handling between neonate and adult.
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PMID:Calcium and cardioplegia in neonates: dose-response and time-response studies in rats. 195 46

Isolated rat hearts were made ischemic for 25 min after an initial recirculating perfusion, followed by 30 min of reperfusion. In some hearts, interventions including administration of ouabain and/or high [K+] in the buffer were performed during the first 10 min of reperfusion. During ischemia, intracellular Na+ (Nai) increased from 15 to 64 mumol/g dry weight (dwt). During reperfusion, Nai declined rapidly (at 10 min of reperfusion: 48 mumol/g dwt, at 30 min: 25 mumol/g dwt) and regular rhythm was recovered within 10 min in hearts without any intervention during reperfusion. 45Ca2+ uptake increased from 0.8 to 7.5 mumol/g dwt after 30 min of reperfusion. Ventricular function recovered by 45%. A 10-min perfusion with 10 or 50 microM of ouabain increased Nai (17 to 21 or 27 mumol/g dwt) with increased left-ventricular (LV) contractile function, but these effects were reversed by combination of high perfusate [K+] (20 mM) in non-ischemic hearts. A 10-min reperfusion with ouabain retarded or stopped the decline in Nai (at 10 min of reperfusion: 54 or 63 mumol/g dwt, at 30 min: 32 or 40 mumol/g dwt). These amounts of ouabain also increased the incidence of ventricular tachyarrhythmias during reperfusion to 30% or 50%, and increased the duration of ventricular fibrillation from 6.5 to 11.5 or 18.0 min. 45Ca2+ uptake reached to 8.8 or 10.0 mumol/g dwt, and function recovered only 35% or 28%. When high perfusate [K+] was combined with ouabain during reperfusion, the retarded decline in Nai, augmented 45Ca2+ uptake, and reduced recovery of function caused by ouabain alone were attenuated. These results suggest that digitalis has toxic effects on reperfused ischemic hearts by inhibition of rapid active outward transport of previously elevated Nai and potentiation of Ca2+ overload.
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PMID:Deleterious effects of digitalis on reperfusion-induced arrhythmias and myocardial injury in ischemic rat hearts: possible involvements of myocardial Na+ and Ca2+ imbalance. 195 72


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