Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to investigate the relationship between myocardial oxygen consumption and oxygen-induced myocardial injury. Dog hearts were exposed to 40 min normothermic ischemia and then reperfused for 10 min with three oxygenated perfusates containing different hemoglobin concentrations and with moderate hemodilution. The experimental groups consist of a moderate hemodilution group (Group M) receiving 8 g/dl of hemoglobin, an extreme hemodilution group (Group E) given 4 g/dl of hemoglobin, and a hemoglobin-free autologous plasma group (Group F). Hearts in the non-ischemic control group (Group C) were also perfused with moderate hemodilution throughout. In Group C, Group M and Group E, the O2 tension of perfusates was maintained at about 100 mmHg and in Group F, at over 300 mmHg. Oxygen extraction at 5 min after reperfusion in Group C was 14%, in Group M and Group E less than 10%, but in Group F 70%. Oxygen consumption in Group F was more than twice that in Group E and surpassed that in Group C. Group M also showed a significant increase in oxygen consumption compared with Group E at 5 min after reperfusion. Among the ischemic groups, Group E showed improvement of left ventricular function almost comparable to Group C accompanied by a rapid decrease in myocardial lactate, improved preservation of myocardial adenine nucleotides and prevention of myocardial lipid peroxidation. In contrast, Group F showed persistently higher values of lipid peroxides and lactate, the poorest recovery of adenine nucleotides, and impairment of left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1985 May
PMID:Reperfusion injury induced by augumented oxygen uptake in the initial reperfusion period. Possible efficacy of extreme hemodilution. 403 84

Long-chain acyl-CoA and acylcarnitine hydrolase activities were determined in fresh and perfused rabbit heart and correlated with tissue levels of their respective substrates, long-chain acyl-CoA and acylcarnitine. In fresh heart homogenate acyl-CoA hydrolase activity was 3-fold greater than acylcarnitine hydrolase activity; sonication of homogenate doubled acyl-CoA hydrolase activity but did not significantly change acylcarnitine hydrolase activity. Hearts perfused with 10 mM glucose by the nonrecirculating Langendorff method had depressed levels of acyl-CoA hydrolase activity under both aerobic and ischemic conditions. Extract from buffer-perfused heart showed increased acylcarnitine hydrolase activity and elevated levels of acylcarnitine. Homogenate acyl-CoA hydrolase activity was not sedimented by centrifugal forces up to 50,000 X g; however, less than 25% of homogenate acylcarnitine hydrolase activity remained in the 50,000 X g supernatant. The hypolipidemic drug clofibrate was an effective in vitro inhibitor of acylcarnitine hydrolase activity but not of acyl-CoA hydrolase activity. The fatty acid analog tetradecylglycidic acid inhibited only acyl-CoA hydrolase activity. These results suggest that acyl-CoA hydrolase and acylcarnitine hydrolase activities are differentially affected in the perfused heart by substrate levels and oxygen availability. In addition, the diverse response of these two hydrolase activities to a variety of biochemical parameters implies that the observed hydrolyses of palmitoyl-CoA and palmitoylcarnitine are catalyzed by at least two separate hydrolase enzymes.
J Mol Cell Cardiol 1984 Oct
PMID:Long-chain acyl-CoA and acylcarnitine hydrolase activities in normal and ischemic rabbit heart. 615 Oct 1

Enhanced phosphorylase activation in hearts from hyperthyroid animals has been well documented. To elucidate the mechanisms responsible for the enhanced phosphorylase a formation, hearts from euthyroid and hyperthyroid rats were perfused by the Langendorff method with calcium (3.75 mM), isoproterenol, dibutryl cAMP and trifluoperazine, an inhibitor of calcium-calmodulin dependent enzymes. Comparative biochemical analyses revealed increased phosphorylase a formation in hearts from both euthyroid and hyperthyroid animals following exposure to calcium, dibutryl cAMP and isoproterenol. Hearts from hyperthyroid rats had an increased sensitivity to threshold concentrations of isoproterenol for both cAMP formation and phosphorylase b to a conversion. At higher concentrations of isoproterenol (10(-8) M and 3 x 10(-8) M), no significant differences in cAMP formation were noted between euthyroid and hyperthyroid animals in spite of persistently increased phosphorylase a levels in the hyperthyroid state. Trifluroperazine had no effect on basal phosphorylase a levels but significantly inhibited phosphorylase a formation in both groups following calcium or isoproterenol stimulation. However, enhanced phosphorylase a formation was still present in the hearts from hyperthyroid rats following trifluoperazine preperfusion. Determinations of phosphorylase kinase activity revealed a specific activity in the hyperthyroid animals twice that of the euthyroid controls. At least two mechanisms, an increased sensitivity to beta-adrenergic agents and increased cardiac phosphorylase kinase activity, may mediate the enhanced phosphorylase a formation found in hearts from hyperthyroid rats.
J Mol Cell Cardiol 1983 Mar
PMID:Mechanisms of enhanced phosphorylase activation in the hyperthyroid rat heart. 630 61

Verapamil may protect ischemic myocardium by several mechanisms: prevention of Ca overload as a direct effect of blocking Ca influx through slow channels, coronary vasodilatation, decreased contractility, or cardioplegia produced by high doses. We manipulated the experimental situation to ask whether the first mechanism alone could be protective. We studied isovolumically contracting rabbit hearts perfused at 37 degrees C, paced at 150/min, and maximally vasodilated by dipyridamole. Hearts were subjected to 60 min of low flow ischemia followed by 60 min reperfusion. Two groups were exposed to verapamil 0.5 microM beginning either 2 to 4 min before ischemia or 10 min after the onset of ischemia (when pressure development had ceased) and continuing until reperfusion. Developed pressure recovered during reperfusion to 70 +/- 4% of its initial value in hearts treated with verapamil before ischemia compared to 40 +/- 5% for control hearts and 35 +/- 11% for hearts treated with verapamil 10 min after the onset of ischemia. There was significant preservation of phosphocreatine at 10 min of ischemia and of ATP at 60 min in the early verapamil group compared to the other two. When verapamil was present before ischemia, pressure development during early ischemia was reduced to about 50% of control. Consequently there was substantial sparing of high energy phosphates and enhanced recovery of mechanical function. If verapamil was added 10 min after the onset of ischemia, when it no longer could affect cardiac work, there was no protection. Therefore, in the isolated rabbit heart, verapamil had an important protective effect only by reducing contractility of ischemic myocardium.
J Mol Cell Cardiol 1983 Oct
PMID:Verapamil protection of ischemic isolated rabbit heart: dependence on pretreatment. 631 59

Metabolic and functional recovery following 60 minutes of low flow (0.1 ml/min) ischemia were compared in rabbit hearts perfused with normal sodium and potassium, low sodium (120 mM NaCl replaced by 120 mM LiCl), or zero potassium perfusate during ischemia. During the control, pre-ischemic, and reperfusion periods, all hearts were perfused identically with normal sodium and potassium. 31P NMR was used to monitor intracellular pH (pHi), ATP, and phosphocreatine (PGr). Developed pressure, end diastolic pressure, pHi, and the integrated areas of ATP and PCr were equivalent in the three groups in the pre-ischemic period. The fall in pHi, PCr, ATP, and developed pressure and the rise in end diastolic pressure during 60 min ischemia also did not differ among the three groups. In contrast to the lack of an effect of perfusate sodium and potassium on the decline in parameters of metabolism and function during ischemia, there was a marked difference in the recovery of these indices during reperfusion. Hearts perfused with low sodium during ischemia exhibited the best recovery (expressed as percent of control) of developed pressure (95 +/- 4%), PCr (106 +/- 6%), and ATP (51 +/- 2%) and the smallest rise in end diastolic pressure (229 +/- 50%); hearts perfused with normal sodium and potassium during ischemia had intermediate recovery values for developed pressure (53 +/- 10%), PCr (78 +/- 9%), ATP (45 +/- 4%) and end diastolic pressure (487 +/- 73%) and the hearts perfused with zero potassium solution during ischemia exhibited the poorest recovery of developed pressure (23 +/- 6%), PCr (49 +/- 6%), ATP (39 +/- 5%) and end diastolic pressure (968 +/- 185%).(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1984 Sep
PMID:Perfusate sodium during ischemia modifies post-ischemic functional and metabolic recovery in the rabbit heart. 649 72

Eighty isolated rat heart preparations were used to study relationships among creatine kinase (CK) release, the loss of vascular competence (no-reflow), and the distribution of morphological changes across the left ventricular wall which occur during 60 min global ischaemia or anoxia and following subsequent oxygenated reperfusion. Hearts were either fixed with glutaraldehyde for light and electron microscopy or were injected with 1% fluorescein to define the distribution of perfusable vessels. The extent of no-reflow in half of the hearts was reduced experimentally by maintaining the diastolic volume of the left ventricular lumen during ischaemia and anoxia with a water-filled balloon. The amount of CK released during 20 min of reoxygenation or reperfusion was inversely proportional to the extent of the no-reflow area observed just prior to reoxygeneration, and also reflected the transmural extent and the severity of myocardial cell damage. Extensive contraction band necrosis was only observed in reperfused regions of anoxic hearts. In isovolumic hearts reoxygenation caused no-reflow to develop in the ventricular myocardium, and this appeared to be associated with hypercontraction. Thus the no-reflow phenomenon has a profound effect on the transmural distribution of myocardial cell damage and enzyme release which follows post ischaemic reperfusion and post anoxic reoxygenation.
J Mol Cell Cardiol 1984 Oct
PMID:The influence of the no-reflow phenomenon on reperfusion and reoxygenation damage and enzyme release from anoxic and ischaemic isolated rat hearts. 651 64

The effects of physical stresses produced by transient distension of a left ventricular balloon, on myocardial creatine kinase (CK) release and cellular morphology, were studied in Langendorff perfused rat hearts at 37 degrees C. Hearts subjected to 15 or 30 min anoxia, developed anoxic contracture, but only small amounts of CK were released following ventricular distension. In contrast, when anoxic hearts in contracture were perfused with calcium-free medium for 5 min, prior to distension, there occurred a large peak of CK release immediately following inflation of the intraventricular balloon. Oxygenated hearts or hearts made anoxic, but which had not developed contracture, release little CK activity, although they were subjected to ventricular distension after a calcium-free perfusion period. Large myocardial enzyme releases were associated with morphological lesions of widely separated cells, dehiscence of intercalated disc cell junctions, and sarcolemmal membrane damage. Hearts subjected to calcium-free perfusion were abnormally susceptible to physical stress-induced myocardial enzyme release.
J Mol Cell Cardiol 1983 Jul
PMID:Physical stress-mediated enzyme release from calcium-deficient hearts. 662 Mar 94

We have investigated whether Ca2+ antagonists reduce the amount of noradrenaline lost from the myocardium during periods of ischaemia and reperfusion. Hearts obtained from adult, male normotensive Sprague Dawley, Wistar Kyoto and spontaneously hypertensive rats were perfused in the Langendorff mode at 37 degrees C before being made globally ischaemic for either 15, 30 or 60 min. Some of the hearts were reperfused, and in some ECG records were made. 90-min normothermic aerobic perfusion failed to cause a significant change in left ventricular noradrenaline content. In Sprague Dawley and spontaneously hypertensive, but not Wistar Kyoto rats, 15 min ischaemia followed by 1 min reperfusion caused a significant (P less than 0.05) loss of noradrenaline. Extending the ischemic episode to 60 min resulted in a further loss of noradrenaline (P less than 0.005) in the Sprague Dawley, Wistar Kyoto and spontaneously hypertensive hearts and this loss was exacerbated upon reperfusion. Neither dl verapamil (2.5 X 10(-8) to 1.2 X 10(-6) mol/l) nor diltiazem (0.25 to 1.25 X 10(-6) mol/l) caused any change in the noradrenaline content of the aerobically perfused hearts. (1.25 X 10(-1) to 1.2 X 10(-1) mol/l) verapamil abolished the release of noradrenaline caused by 15 min ischaemia and reduced the release caused by 60 min ischaemia and 15 min reperfusion. The dose-response curve for verapamil was bell-shaped and the activity resided in the l form. Diltiazem (1.25 X 10(-6) mol/l but not 2.5 X 10(-1) mol/l) also abolished the loss of noradrenaline caused by short periods of ischaemia and reperfusion.
J Mol Cell Cardiol 1984 Apr
PMID:An inhibitory effect of verapamil and diltiazem on the release of noradrenaline from ischaemic and reperfused hearts. 672 22

Rat hearts were perfused on a Langendorff apparatus at 37 degrees C with oxygenated Krebs-Henseleit medium with 2.5 mM Ca2+ or Ca2+-free medium for 5 min prior to addition of 0.04 or 1 mM DNP. Effluent was analyzed for creatine kinase (CK) activity and tissue was sampled at 0, 1.5 and 3 min for ATP and CP analysis. Hearts were perfusion-fixed for light and electron microscopy. Contractile function was monitored by intraventricular balloon or a force displacement transducer. In control hearts, 1 mM (but not 0.04 mM) DNP caused a rapid contracture, without CK release. In Ca2+-free hearts, 1 mM (but not 0.04 mM) DNP produced a rapid, massive release of CK. Tissue CP and ATP fell to low levels coincident with contracture and CK release. Morphology of injured hearts showed cellular contracture with uniform sarcomere shortening and widely separated cells with dehiscence of opposing intercalated disc membrane faces. Separated cells had bleb-like protrusions of cytoplasm surrounded by fragmented sarcolemmal membranes. The results demonstrate that following Ca2+-free perfusion, irreversible damage can occur in the absence of extracellular Ca2+ and in hearts with uncoupled mitochondria which were depleted of ATP. It is postulated that Ca2+-free perfusion weakens intercalated discs and that DNP-stimulated mitochondrial calcium release produces contracture, which tears cells apart at weakened cell junctions, causing sarcolemmal membrane damage and CK release.
J Mol Cell Cardiol 1984 Jun
PMID:2,4-Dinitrophenol (DNP)-induced injury in calcium-free hearts. 674 89

An isolated rat heart preparation was used to characterize the temperature dependence of the calcium paradox and also to assess the validity of various indices of hypothermic protection. Hearts were subjected to 10-min periods of calcium depletion at various degrees of hypothermia followed by 20 min of normothermic calcium repletion. Using enzyme or protein leakage during calcium repletion as an index of hypothermic protection during calcium depletion, paradox injury was reduced extensively by relatively moderate hypothermia. Thus, depletion at 29 degrees C reduced total creatine kinase leakage by 57 +/- 4% from 1585 +/- 24 IU/g dry wt to 677 +/- 63 IU/g dry wt and at 25 degrees C leakage was reduced by 85 +/- 4% from 1585 +/- 24 IU/g dry wt to 237 +/- 71 IU/g dry wt. However, upon calcium repletion there was no recovery of contractile function. It was not until the myocardial depletion temperature was reduced to 20 degrees C that some functional recovery occurred. Under these circumstances cumulative creatine kinase leakage was reduced to below 88 IU/g dry wt, 6% of its normothermic value and protein leakage was undetectable. Functional recovery was not complete until the temperature was reduced to 15 degrees C or below. Correlation of cumulative enzyme leakage with functional recovery suggested a narrow release threshold (50 to 100 IU/g dry wt) above which no recovery occurred and below which a full recovery could be confidently predicted. Morphological assessments an all-or-none phenomenon; thus although increasingly severe hypothermia progressively reduced the percent of cells that sustained damage (as opposed to the degree of damage in all cells), it was not until 100% of cells appeared ultrastructurally undamaged that functional recovery was observed. Calcium-free perfusion at 4 degrees C protected the intercalated discs from gross lesions and prevented the separation of the external lamina from the surface coat. Our results also stress the heterogeneity of tissue injury and hypothermic protection and in addition shed further light upon the component mechanisms contributing to calcium injury.
J Mol Cell Cardiol 1983 Jun
PMID:The temperature dependence of the calcium paradox: enzymatic, functional and morphological correlates of cellular injury. 687 88


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>