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

The introduction of positron emission tomography (PET) as a powerful imaging modality has played a major role in the understanding of the pathophysiological bases for cerebrovascular disorders. PET is the only technique that allows measurement of regional cerebral blood flow, blood volume, oxygen extraction fraction, and oxygen and glucose metabolism with detail and accuracy. Using PET, these physiological parameters can be measured to determine the extent of the disease from the early stages of cerebrovascular disorders to acute cerebral infarction. Significant hemodynamic and metabolic abnormalities are noted in chronic ischemia, but no structural changes are noted on anatomic images. PET studies have shown that in many patients in the early phases (10 to 12 hours) of clinically diagnosed acute stroke, a substantial area of ischemia exists, which, if untreated, will become irreversibly damaged. Similar to the results achieved in patients with acute myocardial infarction, appropriate intervention in patients with cerebrovascular disorders may significantly reduce the extent of injury to the brain. PET also has been useful in predicting functional recovery and monitoring the effects of various therapeutic approaches. Although functional imaging of the brain with single photon emission computed tomography can successfully be used in the investigation of several disorders of the brain, its role in cerebrovascular disorders is quite limited. PET is a unique modality that studies ischemic diseases of the brain, and it potentially could play a significant role in the management of patients with cerebrovascular disease. This will be further realized when aggressive approaches are used routinely in the future.
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PMID:Positron emission tomography in cerebrovascular disorders. 143 68

A high adrenergic strain during reperfusion after ischemia impedes functional recovery. Conversely, adrenergic blockade may be beneficial during reperfusion. This study was undertaken to find out if early postoperative high-dose infusion of the selective beta 1-blocking agent metoprolol tartrate has additional effects on metabolic variables related to myocardial energy supply/demand balance compared with those obtained with a late preoperative oral dose. The study included 21 male patients undergoing coronary bypass grafting. All patients received an oral dose of metoprolol before the operation. After the operation, patients were randomized to a control group or a group receiving intravenous infusion of metoprolol. Myocardial uptake of oxygen and substrates was determined before and during atrial pacing. Metoprolol reduced arterial concentrations of free fatty acids, reduced myocardial uptake of free fatty acids, and enhanced myocardial uptake of lactate. During paced tachycardia, the metoprolol concentration correlated negatively with myocardial uptake of free fatty acids (r = -0.80; p < 0.001) and positively with myocardial uptake of lactate (r = 0.53; p < 0.05). It is concluded that postoperative infusion of metoprolol induces myocardial metabolic changes compatible with an improved energy supply/demand balance.
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PMID:Influence of beta 1-blockade on myocardial substrates early after a coronary operation. 144 2

We evaluated the viability and energy metabolism of ischemically damaged pancreas during preservation by the two-layer (University of Wisconsin solution (UW)/perfluorochemical (PFC)) cold storage method. The pancreas grafts subjected to 60-120 min warm ischemia were preserved by the two-layer (UW/PFC) cold storage method for 24 hours (group 3), a simple cold storage in UW for 24 hours (group 2) or without preservation (control) (group 1). The tissue concentration of adenine nucleotides (ANs) were determined using high performance liquid chromatography (HPLC) and the viability of the pancreas graft was tested in the canine model of segmental pancreas autotransplantation. The functional success rates of pancreas grafts of groups 1, 2 and 3 after 60 min of warm ischemia were 5/5 (100%), 4/5 (80%) and 5/5 (100%). After 90 min warm ischemia, the success rates of groups 1, 2 and 3 were 0/5 (0%), 0/5 (0%) and 5/5 (100%) respectively. Only the two-layer method (group 3) was effective for functional recovery of the pancreas suffered 90 min warm ischemia. However, after more than 105 min, the result was 0/5 (0%) in group 3. In groups 1 and 2, there was no correlation between the posttransplant viability and tissue concentration of ANs and energy charge potential (ECP) at the end of preservation. However, in group 3, there was an excellent correlation between the posttransplant viability and tissue concentration of adenosine triphosphate (ATP) and total adenine nucleotides (TAN) at the end of preservation. We conclude that tissue concentration of ATP and TAN at the end of 24 hour preservation by the two-layer (UW/PFC) method will predict the posttransplant outcome of pancreas graft subjected to significant warm ischemia.
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PMID:Evaluation of the viability and energy metabolism of ischemically damaged canine pancreas during preservation by the two-layer (University of Wisconsin solution/perfluorochemical) cold storage method. 145 89

Covalent linkage of polyethylene glycol to superoxide dismutase prolongs the serum half-life of the enzyme and may facilitate intracellular access. We tested the myocardial protective effect of polyethylene glycol superoxide dismutase administered once, 24 hours before ischemia. Because hearts were studied ex vivo in a crystalloid perfused system, cardioprotection could be ascribed to intramyocardial or membrane-bound polyethylene glycol superoxide dismutase accumulation. Thirty isolated rabbit hearts from the four following groups were studied: (1) control: untreated rabbits (n = 7); (2) PEG-control: 24-hour intravenous preinfusion of methoxypolyethylene glycol 5000 (5 mg/kg) to examine the effect of polyethylene glycol alone, without conjugation to superoxide dismutase (n = 8); (3) PEG-SOD 10,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (10,000 U/kg) (n = 8); (4) PEG-SOD 30,000: 24-hour preinfusion of polyethylene glycol superoxide dismutase (30,000 U/kg) (n = 7). After measurement of baseline function with use of an intraventricular balloon, hearts were subjected to normothermic ischemia until a 4 mm Hg rise in intracavitary pressure was observed. Function was assessed at 15-minute intervals throughout reperfusion and expressed as percent return of developed pressure. After 60 minutes of reperfusion, recovery of function was greater for the PEG-SOD 30,000 group (85.6% +/- 2.6%) when compared with either the untreated or PEG-control group (68.9% +/- 2.3% and 71.4% +/- 2.0%, respectively). A similar difference was seen throughout reperfusion. Although an improved return of function was shown in the lower dose PEG-SOD 10,000 group, the margin of difference when compared with any of the control groups was determined to be insignificant at all times of reperfusion and at 60 minutes (75.9% +/- 3.2%). These data demonstrate that high, but not low, doses of polyethylene glycol superoxide dismutase significantly reduce reperfusion injury when administered 24 hours before initiation of global ischemia. Moreover, since the perfusate was superoxide dismutase free, this effect was most likely intramyocardial or membrane bound and therefore might be added to protection afforded by circulating superoxide dismutase.
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PMID:Polyethylene glycol-conjugated superoxide dismutase attenuates reperfusion injury when administered twenty-four hours before ischemia. 145 23

The effects of pretreatment with the nucleoside transport inhibitor lidoflazine on repeated ischemia-reperfusion injury induced by normothermic intermittent aortic crossclamping were studied in canine hearts. Eighteen mongrel dogs were allocated to three groups: placebo (n = 6), lidoflazine (1 mg/kg) (n = 6), and lidoflazine (1 mg/kg) plus the adenosine receptor blocker aminophylline (7 mg/kg) (n = 6). Pretreatment was performed intravenously during 15 minutes before extracorporeal circulation. All hearts were subjected to four intervals of 15 minutes of global ischemia each followed by 10 minutes of reperfusion. After weaning from extracorporeal circulation, functional recovery was followed for 1 hour. In the lidoflazine group, myocardial adenosine content (0.25 +/- 0.06 mumol/gm dry weight) was 3.5 times higher than that in the control group (0.07 +/- 0.03 mumol/gm dry weight; p < 0.05) at the end of the last aortic crossclamping. The release of adenosine from the myocardium during each reperfusion period was significantly higher than that in the control group (p < 0.05). Myocardial extraction of lactate was normalized at every reperfusion interval in the lidoflazine group but not in the control group (p < 0.05). In the lidoflazine group functional recovery was significantly better than that in the control group. Positive rate of rise of pressure, negative rate of rise of pressure, and cardiac output recovered to, respectively, 150% +/- 19%, 82% +/- 8%, and 131% +/- 15% in the lidoflazine group versus, respectively, 37% +/- 9%, 23% +/- 7%, and 29% +/- 8% in the control group (p < 0.001) at 1 hour after extracorporeal circulation. When the adenosine receptor blocker aminophylline was administered in association with lidoflazine, protection dropped significantly: positive and negative rate of rise of pressure and cardiac output were, respectively, 58% +/- 8%, 46% +/- 9%, and 67% +/- 16% at 1 hour after extracorporeal circulation (p < 0.05 versus lidoflazine alone). These results suggest that the cardioprotective effects of lidoflazine are at least in part mediated by adenosine receptor stimulation via nucleoside transport inhibition-induced accumulation of endogenous adenosine in the myocardium.
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PMID:Nucleoside transport inhibition mediates lidoflazine-induced cardioprotection during intermittent aortic crossclamping. 145 24

A high adrenergic strain during reperfusion after ischemia impedes functional recovery. Conversely, adrenergic blockade may be beneficial during reperfusion. Negative inotropic effects may outweigh the expected benefit, however. Against this background hemodynamic and metabolic effects of early postoperative infusion with the beta 1-selective agent metoprolol were studied in 22 patients after coronary operations. During basal postoperative conditions, intravenous metoprolol reduced cardiac index and stroke volume index compared with control patients, while other variables were unaffected. During the higher adrenergic level of a dopamine infusion (7 micrograms/kg per minute), the heart rate, rate pressure product, and myocardial oxygen uptake were attenuated in proportion to the plasma level of metoprolol. Intravenous beta 1-blockade did not affect the cardiac output or stroke volume responses to dopamine (the cardiac output was still, however, 19% lower than in control patients). A release of myocardial creatinine kinase isoenzyme myocardial band was observed during dopamine infusion, suggesting that myocardial ischemia was induced. The release was not influenced by metoprolol, but it correlated with heart rate (r = 0.60; p < 0.01). It is concluded that infusion of metoprolol early after coronary operations depresses myocardial contractility with some 19%, which was without clinical significance in straightforward patients; the increased myocardial metabolic demand during a period of increased adrenergic stress was attenuated by metoprolol. This may be of importance for myocardial recovery.
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PMID:High-dose intravenous beta 1-blockade in patients early after cardiac operations. Negative inotropism versus myocardial oxygen economy. 145 32

In this study we determined the effects of high levels of fatty acids on recovery of heart function when present either during or after ischemia. Isolated working hearts from 6-wk streptozotocin diabetic and control rats perfused with 11 mM glucose were subjected to 25 min of global ischemia followed by 30 min of aerobic reperfusion. Four groups were studied: 1) 1.2 mM palmitate present before, during, and after ischemia; 2) 1.2 mM palmitate present before and during ischemia, followed by reperfusion in the absence of palmitate; 3) no palmitate before and during ischemia, followed by 1.2 mM palmitate during reperfusion; and 4) no palmitate before and during ischemia or during reperfusion. In control hearts, palmitate during reperfusion depressed recovery of function regardless of whether palmitate was present or absent during ischemia. In contrast, palmitate present during reperfusion did not depress recovery of mechanical function in the diabetic rat hearts. However, the presence of palmitate during ischemia itself in diabetic rat hearts was detrimental to recovery of mechanical function. The presence of palmitate during ischemia resulted in an accelerated rate of ATP loss and a decreased rate of lactate accumulation during ischemia, although this effect was similar in control and diabetic rat hearts. Our results demonstrate that high concentrations of fatty acids depress functional recovery of control rat hearts during the reperfusion period but depress recovery of function in diabetic rat hearts when present during ischemia itself.
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PMID:Effects of high levels of fatty acids on functional recovery of ischemic hearts from diabetic rats. 147 76

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

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


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