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

The influence of temperature and pressure during early reperfusion after 2 h of hypothermic, cardioplegic ischemia was investigated. Adenosine triphosphate (ATP) and creatine-phosphate (CP) were measured after 45-min reperfusion. The experiments were carried out in normal and previously infarcted rat hearts (the left coronary artery having been ligated 3 weeks earlier). Four groups, each containing six hearts, were studied. Group 1 consisted of normal hearts reperfused with an abrupt rise in temperature and pressure, group 2 of normal hearts exposed to slowly rising temperature and pressure, and group 3 and 4 of previously infarcted hearts. Reperfusion procedures in groups 3 and 4 were the same as in group 1 and 2, respectively. The study showed that previously infarcted hearts have a lowered tolerance to ischemia and that the reperfusion technique may influence the preservation of myocardial energetics, although this influence was not statistically significant in normal hearts following only 2 h of ischemia. The gently reperfused infarcted hearts had energy stores equal to the normal hearts after 2 h of ischemia and 45 min of reperfusion, whereas the infarcted hearts reperfused in a rougher mode had significantly lowered values (P less than 0.05 for ATP and P less than 0.01 for CP).
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PMID:Improved energy preservation following gentle reperfusion after hypothermic, ischemic cardioplegia in infarcted rat hearts. 327 3

This study was designed to determine whether multidose St. Thomas' Hospital cardioplegic solution is as effective for preservation of the immature myocardium during ischemia as it is for the mature myocardium. An isolated working heart model was used. Sets of six hearts from immature (3 to 4 weeks, 500 gm) and mature (24 weeks, 2 kg) rabbits were subjected to 60, 90, or 120 minutes of ischemia. Myocardial protection consisted of infusion of cardioplegic solution every 30 minutes at 4 degrees C in a dose of 10 ml/kg of animal weight and maintenance of hypothermia at 10 degrees C by immersion in a cold saline bath. The percent recovery of preischemic aortic flow was lower in the immature than the mature hearts after 90 minutes (60.3% +/- 7.4% versus 101.8% +/- 4.3%) and after 120 minutes (57.4% +/- 10.6% versus 91.1% +/- 13.6%) of ischemia (results expressed as mean value +/- standard error of the mean, p less than 0.05). There were no differences between the mature and the immature hearts in the recovery of heart rate, left atrial pressure, mean aortic pressure, or glycogen stores. Adenosine triphosphate levels measured at the end of the experiment were not different from control in the immature hearts subjected to 60 or 90 minutes of ischemia, but did decline after 120 minutes of ischemia (18.5 +/- 0.8, 16.9 +/- 1.3, 16.6 +/- 0.6 versus 12.3 +/- 1.8 mumol/gm dry weight, p less than 0.05). Adenosine triphosphate levels in the mature hearts were lower than control in hearts subjected to 60, 90, and 120 minutes of ischemia (18.0 +/- 1.2 versus 13.6 +/- 1.1, 12.8 +/- 0.9, 13.7 +/- 1.5 mumol/gm dry weight, p less than 0.05). Multidose St. Thomas' Hospital cardioplegia does not provide adequate preservation of hemodynamic function in the immature rabbit heart, even though myocardial high-energy stores are well preserved. Additional work is necessary to clarify the mechanism of this finding and to develop appropriate methods for protection of the immature myocardium.
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PMID:The immature and the mature myocardium. Responses to multidose crystalloid cardioplegia. 335 95

The cardioprotective effect of the addition of the slow calcium-channel blocker nifedipine to cardioplegic solution was tested in two double-blind placebo controlled randomized studies. The first study included 24 patients undergoing aortic-coronary bypass grafting, and the second included 24 patients undergoing aortic valve replacement. Nifedipine at a dose of 200 micrograms/L or placebo was added to St. Thomas' Hospital cardioplegic solution. The following markers of ischemia were used: adenosine triphosphate and its catabolites, creatine phosphate and inorganic phosphate, determined in transmural left ventricular biopsy specimens taken before, at the end of, and after aortic cross-clamping; hemodynamic recovery 15 minutes after cessation of cardiopulmonary bypass; clinical outcome in terms of the incidence of arrhythmias, low cardiac output, positive inotropic support immediately after operation, and follow-up at 15 months. The main difference between the two studies was that myocardial temperature during cross-clamping remained constant at 14 degrees C in coronary bypass grafting but increased to 25 degrees C in valve operations despite the application of the same amounts of cardioplegic solutions. This lower temperature resulted in better preservation of high-energy phosphates in coronary bypass operations as compared to the placebo group having valve replacement operations. According to analysis of variance, a drug effect could be demonstrated only in the aortic valve replacement study: Accumulation of breakdown products of the adenine nucleotide pool was less in the nifedipine group than in the placebo group (p less than 0.05). Adenosine triphosphate decreased only to 84% in the nifedipine group and to 72% in the placebo group. Despite this adenosine triphosphate-sparing effect, weaning from cardiopulmonary bypass was more difficult in the nifedipine group. Left ventricular stroke work index 15 minutes after bypass was decreased to 72% of the prebypass value in the nifedipine group (t test, p less than 0.01) and only to 86% in the placebo group (p = NS). In contrast, after the patients were admitted to the intensive care unit, the incidence of low cardiac output tended to be lower in the nifedipine group than in the placebo group: 33% versus 58% (p = NS). In conclusion, ischemia-induced degradation of nucleotides as it occurs when myocardial cooling is inadequate can be prevented by the addition of nifedipine to the St. Thomas' Hospital cardioplegic solution. This effect, however, is not associated with an improved clinical outcome.
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PMID:Nifedipine as an adjunct to St. Thomas' Hospital cardioplegia. A double-blind, placebo-controlled, randomized clinical trial. 351 8

Previously, we have demonstrated that hearts preserved ex vivo for 12 hours maintain normal hemodynamic performance after orthotopic transplantation. To complete our studies of these preserved hearts, we evaluated myocardial metabolism by determining high energy phosphate levels and catecholamine concentrations in 22 canine hearts. Group I was the control group in which six hearts were given cold cardioplegic solution; full thickness biopsies were taken from the myocardium in two areas of the right and left ventricles and septum; and adenosine triphosphate, adenosine diphosphate, adenosine monophosphate, creatine phosphate, and catecholamines were determined. Group II, in which the hearts were preserved 12 hours, had eight hearts that were stopped with cold cardioplegic solution, excised, and then preserved in an ex vivo state with a 32 degrees C modified blood perfusate. After a 12-hour perfusion period, the hearts were stopped and biopsies taken. Group III involved cold ischemia and had six hearts that were stopped with cardioplegic solution, excised, opened, flushed, and stored for 2.5 hours at 2 degrees to 4 degrees C. Biopsies were obtained as in groups I and II. Adenosine triphosphate levels were slightly reduced in the 12 hour preserved heart when compared with the control group and the heart in the cold ischemia group preserved for 2.5 hours (p less than 0.01). Creatine phosphate levels were significantly elevated after 12 hour preservation when compared with groups I and III (p less than 0.01). Hearts preserved by cold ischemia also had a reduction (p = 0.03) of creatine phosphate when compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High energy phosphates and catecholamine stores after prolonged ex vivo heart preservation. 361 57

Clinical experience indicates that the risk of reparative cardiac operations is increased in the neonatal period relative to that in older infants and children. Age-related differences in the susceptibility to myocardial ischemic dysfunction were evaluated by comparison of left ventricular function and metabolism in neonatal (mean age = 7 days) and weanling (mean age = 96 days) piglets. Six animals in each group supported on cardiopulmonary bypass were subjected to (1) 120 minutes of hypothermic crystalloid cardioplegic arrest (CP-120) and (2) 15 minutes of normothermic ischemic arrest (NA-15) after a 60 minute interval of reperfusion. Left ventricular systolic and diastolic function was measured after each intervention via endocardially implanted ultrasonic dimension crystals in a septolateral minor-axis position. In both groups, systolic dysfunction was evidenced by an increase in the dimension-axis intercept (p = 0.001), but not the slope of the end-systolic pressure-dimension relation. Left ventricular end-diastolic stiffness, expressed as left ventricular end-diastolic pressure versus Lagrangian strain, increased to a similar degree in both groups (p = 0.001). Adenosine triphosphate levels declined significantly (p = 0.001) in both groups in response to the ischemic interventions with no evident intergroup differences. Lactate levels increased significantly during the course of the experiment (p = 0.04); however, the increases were greater (p = 0.009) at all intervals in the neonatal group. This study demonstrates age-related metabolic differences in response to ischemia consistent with a greater dependence on glycolysis in neonatal myocardia. However, the fact that discriminating age-related differences in left ventricular function were not evident suggests that factors other than young age per se account for the increased surgical mortality in the neonatal period.
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PMID:Age-related differences in the response to myocardial ischemic stress. 365 56

Prolonged normothermic ischemia in the canine model is generally fatal with standard resuscitative techniques. To determine whether such myocardial injury is recoverable with biventricular support, we subjected 10 dogs to 45 minutes of ischemia at 37 degrees C. After ischemia, the animals were supported for 24 hours with biventricular assist with the centrifugal pump. During early reperfusion, none of the hearts could sustain a stable rhythm or blood pressure. Myocardial adenosine triphosphate concentration, expressed as micromoles per gram of heart protein, was dramatically reduced from a control of 31.5 +/- 2.4 to 14.6 +/- 2.9 (p less than 0.01 versus control), a 54% reduction. Ultrastructural analysis did not reveal the explosive cell swelling of irreversible cell injury. After 12 hours of biventricular assist, developed pressure partially recovered to 60.0 +/- 10 mm Hg (p less than 0.01 versus control) and maximal positive dP/dt measured 2,649 +/- 412 mm Hg/sec (p less than 0.01 versus control). Adenosine triphosphate concentration increased to 25.2 +/- 5.5 (p less than 0.01 versus control). Electron microscopic examination showed less chromatin clumping, no further mitochondrial distortion, and more abundant glycogen. After 24 hours of biventricular assist, cardiac output in the seven dogs successfully weaned from biventricular assist measured 3.6 +/- 0.6 L/min, developed pressure recovered to 76.3 +/- 8.9 mm Hg, and its first derivative recovered to 4,282 +/- 585 mm Hg/sec (all measurements not significant compared with control). Examination by an electron microscope revealed no severe mitochondrial injury.
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PMID:Recovery of the failing canine heart with biventricular support in a previously fatal experimental model. 366 94

Phosphorus-31 nuclear magnetic resonance spectroscopy (31P NMR) was used to assess the temporal changes of high-energy phosphate metabolites in the region of acute myocardial ischemia of open-chest cats. Eight anesthetized cats were studied following ligation of the left anterior descending coronary artery. Creatine phosphate showed a 79 +/- 16% (mean +/- SD) reduction by 4 min after the onset of ischemia. Prominent qualitative reductions of the spectral peak of creatine phosphate occurred by 40 s after ischemia. Adenosine triphosphate measured under the beta spectral peak (beta-ATP) decreased 37 +/- 9% by 20-25 min after ligation of the left anterior descending coronary artery. These reductions developed more slowly and were of smaller magnitude than those of creatine phosphate. Intracellular pH decreased from 7.39 +/- 0.07 to 7.13 +/- 0.09 units by 40 s after ischemia. By 30 min, pH decreased to 6.07 +/- 0.40 units. The study shows, therefore, the temporal changes of high-energy phosphate metabolites during ischemia in localized regions of the myocardium of open-chest animals.
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PMID:In vivo evaluation of intracellular pH and high-energy phosphate metabolites during regional myocardial ischemia in cats using 31P nuclear magnetic resonance. 371 90

The potential for improving myocardial protection with the high-energy phosphates adenosine triphosphate and creatine phosphate was evaluated by adding them to the St. Thomas' Hospital cardioplegic solution in the isolated, working rat heart model of cardiopulmonary bypass and ischemic arrest. Dose-response studies with an adenosine triphosphate range of 0.05 to 10.0 mmol/L showed 0.1 mmol/L to be the optimal concentration for recovery of aortic flow and cardiac output after 40 minutes of normothermic (37 degrees C) ischemic arrest (from 24.1% +/- 4.4% and 35.9% +/- 4.1% in the unmodified cardioplegia group to 62.6% +/- 4.7% and 71.0% +/- 3.0%, respectively, p less than 0.001). Adenosine triphosphate at its optimal concentration (0.1 mmol/L) also reduced creatine kinase leakage by 39% (p less than 0.001). Postischemic arrhythmias were also significantly reduced, which obviated the need for electrical defibrillation and reduced the time to return of regular rhythm from 7.9 +/- 2.0 minutes in the control group to 3.5 +/- 0.4 minutes in the adenosine triphosphate group. Under more clinically relevant conditions of hypothermic ischemia (20 degrees C, 270 minutes) with multidose (every 30 minutes) cardioplegia, adenosine triphosphate addition improved postischemic recovery of aortic flow and cardiac output from control values of 26.8% +/- 8.4% and 35.4% +/- 6.3% to 58.0% +/- 4.7% and 64.4% +/- 3.7% (p less than 0.01), respectively, and creatine kinase leakage was significantly reduced. Parallel hypothermic ischemia studies (270 minutes, 20 degrees C) using the previously demonstrated optimal creatinine phosphate concentration (10.0 mmol/L) gave nearly identical improvements in recovery and enzyme leakage. The combination of the optimal concentrations of adenosine triphosphate and creatine phosphate resulted in even greater myocardial protection; aortic flow and cardiac output improved from their control values of 26.8% +/- 8.4% and 35.4% +/- 6.3% to 79.7% +/- 1.1 and 80.7% +/- 1.0% (p less than 0.001), respectively. In conclusion, both extracellular adenosine triphosphate and creatine phosphate alone markedly improve the cardioprotective properties of the St. Thomas' Hospital cardioplegic solution during prolonged hypothermic ischemic arrest, but together they act additively to provide even greater protection.
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PMID:Enhanced myocardial protection with high-energy phosphates in St. Thomas' Hospital cardioplegic solution. Synergism of adenosine triphosphate and creatine phosphate. 382 Nov 50

The purpose of this study was to determine noninvasively some critical level of high-energy phosphate stores that relates to the recovery of ventricular contractile function after graded cardiac ischemia. Rabbit hearts (n = 30) were equipped with an intraventricular balloon to monitor developed pressure and +/- dp/dt and placed in a nuclear magnetic resonance magnet (Bruker, 4.7 Tesla). Each heart underwent 10, 20, 40, or 60 minutes of global ischemia followed by 1 hour of reperfusion. The pH as determined by nuclear magnetic resonance dropped from 7.14 +/- 0.04 to 7.07 +/- 0.07 (p less than 0.02) at 1 minute and to 6.19 +/- 0.08 at 30 minutes of ischemia; pH ceased to fall thereafter. Phosphocreatine was depleted to 10% +/- 7% of its preischemic control in 10 minutes. Adenosine triphosphate (ATP) concentrations were 71% +/- 14% and 1% +/- 2% at 10 and 60 minutes. Regression analysis of recovered developed pressure on end-ischemic ATP (EIATP) revealed: developed pressure = 0.93 (EIATP) + 23 (r2 = 0.99). We conclude that: anaerobic metabolism as evidenced by a fall in pH appears to be active for 30 minutes after normothermic ischemia and then ceases; phosphocreatine buffers the fall in ATP during early ischemia; there is a tight correlation between EIATP and recovery of left ventricular contractile function with a threshold content of approximately 80% below which recovery of function will not be complete.
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PMID:Recovery of left ventricular function after graded cardiac ischemia as predicted by myocardial P-31 nuclear magnetic resonance. 398 18

Adenosine triphosphate (ATP) has been reported to be a hypotensive agent similar in effect to sodium nitroprusside (SNP). The purpose of this study was to examine and compare the effects of both SNP and ATP on general coronary hemodynamics, myocardial O2 consumption, and circulating catecholamines. Twelve dogs were anesthetized with 1.0% halothane and given either SNP or ATP by controlled infusion to reduce their systemic blood pressure by 50% for a 2-h period followed by a (blood pressure) recovery period. The ATP-induced hypotension was rapid, easily controlled, not accompanied by tachyphylaxis over the 120 min studied, and resulted in an increase in coronary sinus blood flow (CSBF), which plateaued at 260% above control. The increase in CSBF was almost immediate and remained at this elevated level for the duration of the induced hypotension. During the ATP-induced hypotension, there was no change in heart rate or circulating catecholamines. A 60% reduction in myocardial O2 uptake was observed, presumably from the cardiac unloading. In contrast, SNP-induced hypotension required a marked increase in dose over time, did not significantly increase CSBF, did increase heart rate, and resulted in large increases in circulating plasma catecholamines. Neither agent affected cardiac output. ATP-induced hypotension resulted in no change in cardiac lactic acid uptake, while SNP caused lactic acid production, indicating possible cardiac ischemia or cyanide toxicity.
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PMID:Myocardial hemodynamics during induced hypotension: a comparison between sodium nitroprusside and adenosine triphosphate. 405 Dec 12


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