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)

The purpose of the study is to investigate the effects of protease inhibitor (Nafamostat mesilate: NM) upon myocardial protection. Hearts were subjected to 20 min working control perfusion followed by 3 min cardioplegic infusion with the St. Thomas Cardioplegic Solution (ST) contained various concentrations of NM, and global ischemia for 33 min at 37 degrees C (Exp. 1) or 150 min at 20 degrees C (Exp. 2). Hearts were then converted to Langendorff reperfusion (the leakage of Creatine Kinase (CK) and Cathepsin B (Cat-B) ware measured) and 20 min working reperfusion. Various concentrations of NM added during Langendorff reperfusion (Exp. 3). During working perfusion cardiac functions (aortic flow (AoF), coronary flow (CoF), heart rate (HR), aortic pressure (AoP)) were measured, and expressed as the percent recovery of pre-ischemic control value. Post-ischemic recovery of AoF (%AoF) showed the bell-shaped dose-response curve, and the optimal dose was 3 microM (Exp. 1) and 10 microM (Exp. 2) respectively. There was a significant (p < 0.05) increase of %AoF in optimal dose compared with that in controls (64.2 +/- 1.2% vs 52.3 +/- 2.5% in Exp. 1, 68.9 +/- 3.1% vs 54.1 +/- 1.4% in Exp. 2). These increase of functional recovery reflected in the values for CK and Cat-B leakage. The addition of NM in ST reduced CK and Cat-B leakage significantly in the concentration of 5 microM (in Exp. 1) and 10 microM (in Exp. 2) respectively. But the addition of NM in reperfusate did not reduced CK leakage significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effects of protease inhibitor upon the ischemia-reperfusion injury]. 143 2

Oxidative metabolism in reperfused neonatal myocardium has not been characterized. A blood-perfused isovolumic heart preparation was used to quantify metabolic and mechanical responses of the neonatal left ventricle to global normothermic ischemia and reperfusion. Hearts from piglets aged 2-7 days were subjected to either 2 hrs of total ischemia at 37 degrees C followed by 1 hr of reperfusion or 3 hrs of perfusion alone; glucose and palmitate oxidation were measured in separate experiments by incorporation of the appropriate [14C]-labeled substrate into the perfusate. In the pre-ischemic period, glucose, palmitate, and lactate contributed 10%, 41%, and 36%, respectively, to oxidative metabolism. After 2 hrs of total normothermic ischemia, oxidation of exogenous glucose was 165% and 229% of control values at 30 and 60 minutes of reperfusion, respectively; palmitate oxidation was 110% and 143% of control values at these times. Despite increased glucose oxidation, palmitate oxidation accounted for 69% of myocardial oxygen consumption after 1 hr of reperfusion, with glucose responsible for 25%. Lactate use was minimal during reperfusion. Reperfusion was accompanied by rapid and parallel recovery of oxygen utilization, mechanical function, and high-energy phosphates. The neonatal piglet heart demonstrates significant metabolic and mechanical tolerance to prolonged ischemia. Although glucose utilization increased markedly, palmitate was the primary substrate for energy production in the post-ischemic neonatal heart.
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PMID:Oxidative metabolism and mechanical function in reperfused neonatal pig heart. 143 13

The effects of adenosine in the nonischemic heart have been shown to be mediated via its binding to extracellular adenosine A1 and A2 receptors located predominantly on myocytes and endothelial cells, respectively. We tested the hypothesis that the beneficial effect of adenosine on postischemic myocardial function is mediated via an adenosine A1 receptor mechanism. Isolated rat hearts perfused at constant pressure (85 cmH2O) were subjected to 30 min of global no-flow ischemia (37 degrees C) and 45 min of reperfusion. Hearts treated with adenosine (100 microM) and the adenosine A1 receptor agonist N6-cyclohexyladenosine (CHA; 0.25 microM) recovered 72 +/- 4 and 70 +/- 4% of preischemic left ventricular developed pressures (LVDP), respectively, after 45 min of reperfusion compared with untreated hearts (54 +/- 3% of preischemic LVDP). Adenosine and CHA hearts exhibited greater myocardial ATP contents than control hearts after 10 min of ischemia, but there were no differences in tissue ATP levels after 30 min of ischemia. In contrast, hearts treated with the adenosine A2 receptor agonist phenylaminoadenosine (0.25 microM) failed to demonstrate improved postischemic function (52 +/- 5%). The addition of the A1-selective antagonist 8-cyclopentyl-1,3-dipropylxanthine blocked the cardioprotective effect of adenosine (57 +/- 4%). These results suggest that adenosine enhances postischemic myocardial function via an A1 receptor mechanism.
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PMID:Adenosine improves recovery of postischemic myocardial function via an adenosine A1 receptor mechanism. 144 99

Antioxidant properties of thioctic and dihydrolipoic acid have been demonstrated in membranes and low density lipoproteins (LDL) in vitro. In vivo studies with dietary supplementation of thioctic acid to rats showed that it can also protect tissues against oxidative damage. Presumably, this action is due to a thioctic acid dihydrolipoic acid (TA/DHLA) coupled antioxidant mechanism, which enhances the activity of other antioxidants (i.e. ascorbate, alpha-tocopherol) by regenerating them from their radical form. In the present study, thioctic acid proved to protect against ischemia/reperfusion injury to Langendorff perfused hearts. Hearts isolated from rats fed thioctic acid and subjected to ischemia exhibited better mechanical recovery (left ventricular developed pressure) after reperfusion and lower lactate dehydrogenase leakage. Thioctic acid supplementation also decreased the appearance of fluorescent lipid peroxidation products after ischemia/reperfusion, lowered the rate of 2,2'-azobis-(2,4-dimethylvaleronitrile) (AMVN) induced lipid peroxidation in heart homogenates, and prevented the loss of alpha-tocopherol. The total sulfhydryl group content in thioctic acid fed animals was higher and the decrease due to ischemia-reperfusion was not as marked in this group as observed in the control. These results show that dietary supplementation with thioctic acid in vivo provides protection against ischemia/reperfusion injury in the Langendorff heart model.
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PMID:Thioctic acid protects against ischemia-reperfusion injury in the isolated perfused Langendorff heart. 144 47

Diabetics suffer from an increased incidence of myocardial infarction and are less likely to survive an ischemic insult. Since L-propionylcarnitine (LPC) has been shown to protect against ischemic/reperfusion injury, we hypothesized that LPC may be of even greater benefit to the diabetic heart. Diabetes was induced by i.v. streptozotocin, 60 mg/kg; duration: 12 wks. The chronic effect of LPC was determined by daily i.p. injections (100 mg/kg) for 8 wks. The acute effects of LPC were determined by adding it to the perfusion medium (5 mM) of control and diabetic hearts. Initial cardiac contractile performance of isolated perfused working hearts was assessed by varying left atrial filling pressure. Hearts were then subjected to 90 min of low flow global ischemia followed by 30 min reperfusion. Chronic LPC treatment had no effect on initial cardiac performance in either control or diabetic hearts. Acute addition of LPC to the perfusion medium enhanced pump performance of control hearts, but had no effect in diabetic hearts. Both acute and chronic LPC significantly improved the ability of control and diabetic hearts to recover cardiac contractile performance after ischemia and reperfusion, however, chronic treatment was more effective in diabetic hearts.
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PMID:Protection of the ischemic diabetic heart by L-propionylcarnitine therapy. 148 Jan 41

Depletion of high-energy phosphates, accumulation of inorganic phosphate and intracellular acidosis have each been proposed as important events in the transition from reversible to irreversible ischemic injury. To assess whether each variable is predictive of functional recovery on reperfusion, these were measured in the isolated isovolumic rat heart using 31P NMR. Perfused hearts were subjected to either 10, 12 or 40 min of normothermic ischemia followed by 40 min of reperfusion. Hearts were then freeze-clamped for further analysis of phosphate metabolites by NMR and ion chromatography. High-energy phosphates, Pi, phosphomonoesters and pH were measured by 31P NMR spectroscopy at 2 minute intervals. Heart rate and developed pressure were monitored simultaneously. All hearts undergoing 10 min of ischemia and 40% of hearts subjected to 12 min of ischemia demonstrated good functional recovery. The remainder of hearts ischemic for 12 min went into contracture on reperfusion with little return of function. Hearts subject to 40 min of ischemia went into ischemic contracture and showed no recovery on reperfusion. Intracellular pH, [ATP], and [Pi] measured prior to reperfusion did not predict the extent of recovery. However, phosphomonoesters were detected prior to reperfusion in all hearts that did not recover well, but were not observed in hearts that showed good mechanical recovery. Analysis of tissue extracts by 31P NMR and ion chromatography indicated that the most prominent components of the phosphomonoesters were glucose 6-phosphate, alpha-glycerol phosphate and AMP. In conclusion, of the various phosphorus metabolites that can be measured by 31P NMR, only one group, the phosphomonoesters, was predictive of functional recovery.
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PMID:Predicting functional recovery from ischemia in the rat myocardium. 148 87

The experiments in the present study were designed to address two issues: Is it possible to manipulate intramyocardial pH in neonatal hearts with different buffers in cardioplegic solution and, if so, do differences in intramyocardial pH during ischemia influence functional recovery? Isolated working hearts from 7- to 10-day-old rabbits underwent 60 minutes of cardioplegic arrest at 37 degrees C with cardioplegic washouts at the onset of ischemia and at 30 minutes. Hearts were reperfused with oxygenated physiologic saline solution (pH = 7.4), returned to the working mode for 30 minutes, and hemodynamic measurements were obtained to compare with baseline values. Intramyocardial pH was held constant during the ischemic interval by infusing cardioplegic solution containing different buffers: histidine (pK 6.0 at 37 degrees C), bicarbonate (pK 6.4), or tromethamine (pK 8.1). The intramyocardial pH was measured continuously with a Khuri glass electrode system (Vascular Technology, Inc., North Chelmsford, Mass.). Cardioplegic solutions buffered to pH values of 6.0 (histidine), 7.4 (bicarbonate), and 8.0 (tromethamine) were associated with ischemic intramyocardial pH values of 6.3 +/- 0.03, 7.02 +/- 0.05, and 7.88 +/- 0.06, respectively. Functional recovery was best in the acidic (histidine) and worst in the basic (tromethamine) groups. Recoveries of developed pressure, the rate of rise of pressure over time, and aortic flow were significantly better for each parameter in the bicarbonate-treated compared with the tromethamine-treated hearts (p less than 0.005). Recovery in the histidine group, however, was superior to that in both the bicarbonate-treated and the tromethamine-treated hearts (p less than 0.005). Regression analysis demonstrated that a significant inverse relationship existed between functional recovery and intramyocardial pH, supporting the conclusions that intramyocardial pH is an important determinant of functional recovery in the neonatal heart and that acidic conditions during normothermic ischemia optimize preservation of myocardial function.
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PMID:The effect of intramyocardial pH on functional recovery in neonatal hearts receiving St. Thomas' Hospital cardioplegic solution during global ischemia. 149 95

We used the isolated perfused working rat heart to investigate the effects of transient hypocalcemic reperfusion after cardioplegic arrest with the St. Thomas' Hospital cardioplegic solution and 25 minutes of global normothermic (37 degrees C) ischemia. Hearts were reperfused (Langendorff mode) transiently (20 minutes) with solutions containing various concentrations of calcium; this was followed by 30 minutes of reperfusion with standard (1.4 mmol/L, the physiologic concentration) calcium buffer (10 minutes in the Langendorff mode and 20 minutes in the working mode). Recovery of cardiac output in control hearts (calcium concentration 1.4 mmol/L throughout) was 51.7% +/- 4.6%; in hearts transiently reperfused with hypocalcemic buffer (0.25, 0.5, 0.75, or 1.0 mmol/L) the recoveries of cardiac output were 49.3% +/- 6.4%, 52.2% +/- 7.2%, 58.7% +/- 3.2%, and 47.2 +/- 4.7%, respectively (all not significant), whereas recovery was only 14.7% +/- 2.8% (p less than 0.05) in hearts transiently reperfused with calcium 0.1 mmol/L. Creatine kinase leakage was significantly (p less than 0.05) greater in the group reperfused with calcium 0.1 mmol/L, but it did not vary significantly between the other groups. Tissue high-energy phosphate content was similar and in the normal range in all groups except for the group reperfused with calcium 0.1 mmol/L. In further experiments, the duration of hypocalcemic (0.5 mmol/L) reperfusion was varied (0, 5, 10, 15, 20, or 30 minutes). No significant differences in recovery of cardiac output were observed (58.2% +/- 5.0%, 52.3% +/- 5.7%, 52.0% +/- 8.2%, 61.2% +/- 5.0%, 62.2% +/- 4.3%, and 66.2% +/- 3.2%, respectively). In additional studies, the standard calcium concentration (1.4 mmol/L) used before and after ischemia was replaced by hypercalcemic solution (2.5 mmol/L). Despite this, transient (10 minutes) hypocalcemic (0.5 mmol/L) reperfusion did not improve recovery. Finally, studies were undertaken with a longer duration of ischemia (40 minutes), and although recovery of cardiac output in the hypocalcemic group (0.5 mmol/L for 10 minutes) tended to be higher than in the control group (29.7% +/- 4.8% versus 18.5% +/- 4.9%, respectively), statistical significance was not achieved. We conclude that in these studies transient hypocalcemic reperfusion did not afford any additional protection over and above that afforded by cardioplegia alone.
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PMID:Transient hypocalcemic reperfusion does not improve postischemic recovery in the rat heart after preservation with St. Thomas' Hospital cardioplegic solution. 149 96

Continuous hypothermic low-flow infusion of cardioplegic or other preservation solutions has been advocated for extending the maximum duration of storage of donor hearts for transplantation. We report the effect of varying the pressure during continuous infusion of St. Thomas' Hospital cardioplegic solution on functional recovery after long-term storage. Isolated working rat hearts (six per group) were aerobically perfused (20 minutes), and control indexes of cardiac function were measured; hypothermic ischemic arrest was then induced by a 3-minute infusion (60 cm H2O) of cold (7.5 degrees C) St. Thomas' Hospital cardioplegic solution. Hearts were then stored for 8 hours at 7.5 degrees C, either immersed in St. Thomas' Hospital cardioplegic solution (noninfused control) or continuously infused at varying infusion pressures with St. Thomas' Hospital cardioplegic solution, which had been both oxygenated and supplemented by the addition of glucose (11.1 mmol/L). After 8 hours of hypothermic ischemia, the rate of cardioplegic infusion was measured as an index of vascular resistance. The hearts were then reperfused (Langendorff) for 30 minutes during which creatine kinase leakage was measured. The hearts were then converted to working preparations for 20 minutes, and the recovery of contractile function was measured and expressed as a percentage of the preischemic control value. In hearts that had been subjected to continuous infusion at 6, 10, 20, 30, 40, and 60 cm H2O, the recoveries of aortic flow were 0% (p less than 0.05), 38.6% +/- 5.1% (p less than 0.05), 36.2% +/- 3.6% (p less than 0.05), 14.0% +/- 8.0%, 5.8% +/- 2.9%, and 9.9% +/- 4.7%, respectively, and the postischemic leakage of creatine kinase was 98.7 +/- 19.5 (p less than 0.05), 26.2 +/- 4.2, 15.5 +/- 3.4, 30.4 +/- 11.1, 109.8 +/- 21.8 (p less than 0.05), and 136.0 +/- 14.1 (p less than 0.05) IU/30 min/gm dry weight, respectively. In contrast, in noninfused control hearts the recovery of aortic flow was 11.1% +/- 7.5%, and creatine kinase leakage was 58.9 +/- 8.7 IU/30 min/gm dry weight. In conclusion, maximum myocardial preservation was obtained with continuous low-flow hypothermic cardioplegic infusion at pressures between 10 and 20 cm H2O.
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PMID:Long-term preservation of the heart: the effect of infusion pressure during continuous hypothermic cardioplegia. 149 29

The possibility that unloading the heart during regional ischemia and/or reperfusion may limit infarct size was investigated by inducing regional ischemia in both a heterotopically transplanted heart (unloaded) and the recipient's heart (loaded control). In this way, the extent of myocardial infarction was compared in paired hearts in the same animal under similar experimental conditions. Hearts excised from donor rabbits, were arrested with St. Thomas' Hospital cardioplegic solution and maintained at 15 degrees C for 1 hour during which time they were transplanted into the necks of recipient rabbits. 24 hours later, rabbits were reanesthetized and the left circumflex coronary artery ligated in both the transplanted and the recipient's hearts. After 1 hour of regional ischemia hearts were reperfused for 3 hours. The transplanted heart was paced at 205 beats per minute (bpm) throughout the experiment. Similar values for infarct size were obtained in both the loaded and unloaded hearts (73 +/- 4% vs 75 +/- 6%, respectively). No significant differences were seen in any other parameters. In conclusion, our results suggest that during regional ischemia the amount of work performed by the heart does not appear to be a major factor in determining the ultimate size of an infarct.
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PMID:Mechanical unloading and infarct size: studies with the heterotopically transplanted rabbit heart. 152 97


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