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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polymorphonuclear granulocytes PMN) are suggested mediators of myocardial ischemia-reperfusion injury. We have previously shown that activated PMN producing oxygen free radicals (OFR) in the coronary circulation are cardiodepressive. OFR may induce lipid peroxidation and production of eicosanoids. We have investigated the influence of cyclo-oxygenase and lipoxygenase inhibitors on the effects of activated, OFR producing PMN in the Langedorff rat heart model. Left ventricular developed pressure (LVDP) was measured by a balloon in the left ventricle. Human PMN and drugs were given into the aortic cannula for 10 min and the hearts were observed for 30 min thereafter. After infusion for 5 min OFR production in the cellular infusate was measured at the level of the aortic cannula by a chemiluminescence (CL) technique. Phorbol 12-myristate 13-acetate (PMA)-activated PMN (n = 8), produced a CL response of 27649 +/- 11048 counts (mean +/- S.E.M.), and reduced coronary flow (CF) to 53 +/- 6% (mean +/- S.E.M.) and LVDP to 38 +/- 9% of baseline values at the end of the observation period. Ibuprofen (n = 6), a cyclooxygenase (CO) inhibitor, neither influenced the CL response (31915 +/- 7563) of activated PMN, nor the reduction of CF and LVDP at this time. Although both BW 755C (n = 7), a dual inhibitor of CO and lipoxygenase (LO) (CF:90 +/- 4%, LVDP:99 +/- 6%) and diethylcarbamazine (DCM) (n = 8), a LO inhibitor (CF:88 +/- 11%, LVDP:87 +/- 4%), significantly inhibited the cardiodepressive effects of activated PMN. BW 755C alone abolished the CL response (431 +/- 158 counts), whereas DCM had no effect on CL (30105 +/- 1698 counts).(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1990 May
PMID:Oxygen free radical producing leukocytes cause functional depression of isolated rat hearts: role of leukotrienes. 211 68

The precise mechanism responsible for the early contractile failure after the onset of myocardial ischemia remains unclear. Physiological studies have reported that intracellular accumulation of inorganic phosphate and intracellular acidosis are the main factors of contractile failure. In contrast, biochemical experiments have shown that the Ca2+ sensitivity of myofibrillar ATPase became less as incubation pH reduces, but the maximal myofibrillar ATPase activity did not change.
J Mol Cell Cardiol 1990 Feb
PMID:Waste of ATP for tension development in myocardial acidosis: chemomechanical uncoupling at myofibrillar level. 213 35

Isolated adult rat myocytes were used to develop an in vitro model of myocardial ischemia. Freshly isolated myocytes were spun into a cell pellet to limit extracellular volume. Excess supernatant was removed and the pellet was covered with mineral oil and incubated in a temperature controlled water bath. After various periods of incubation, cells were analyzed for adenine nucleotide levels, lactate accumulation, rate of cell death, and cell morphology. Adenine nucleotide profiles after 60 min incubation at 37 degrees C showed marked depletion of adenosine triphosphate (ATP) and large increases in adenosine monophosphate (AMP), adenosine, inosine, and lactate and no significant difference in levels of inosine monophosphate. These results are consistent with ischemic conditions. Reduction of the incubation temperature to 34 and 30 degrees C slowed the rate of cell squaring and the onset of cell death. Resuspension of ischemic cells after 30, 45, 60 and 90 min incubation in hypotonic buffer (170 mosmol) to induce acute cell swelling caused an increase in the number of non-viable cells at each time point. Control cells and ischemic cells incubated less than 30 min did not show increases in non-viable cells when subjected to hypotonic swelling. Morphological analysis revealed that isolated myocytes respond to ischemia in a heterogeneous fashion and exhibit changes at both light and electron microscopic levels similar to those seen in other ischemic models. These results indicate that pelleted isolated adult rat myocytes may be a useful in vitro model to study myocardial ischemic cells injury.
J Mol Cell Cardiol 1990 Feb
PMID:An in vitro model of myocardial ischemia utilizing isolated adult rat myocytes. 232 36

In isolated heart preparations, dl-verapamil inhibits the increased vulnerability to ventricular fibrillation and reduces myocardial tissue levels of cyclic 3'5'-adenosine monophosphate (cyclic AMP), a proposed arrhythmogenic agent. The ventricular antiarrhythmic effect of dl-verapamil may not be mediated by selective slow channel inhibition since both d(+) and l(-) isomers display equipotent activity. Three different mechanisms may contribute to the antiarrhythmic properties of dl-verapamil: calcium channel antagonism (l(-) isomer), sodium channel inhibition (d(+) isomer) and reduced cyclic AMP accumulation. In the intact animal model, coronary artery ligation is associated with increased levels of circulating catecholamines and sympathetic neural overactivity. In isolated heart preparations, it is therefore appropriate to evaluate the influence of dl-verapamil and isomers on vulnerability to ventricular fibrillation and cyclic AMP accumulation during acute myocardial ischemia with added adrenergic stimulation. We found that dl and l(-) but not d(+)-verapamil (all 1.5 X 10(-7) M) inhibited the fall in ventricular fibrillation threshold through a mechanism not involving cyclic AMP. L(-) but not d(+) verapamil inhibited Ca2+ dependent slow responses and decreased action potential duration at 90% repolarization. We propose that the ventricular antiarrhythmic property of dl and l(-) verapamil during acute regional myocardial ischemia with added adrenergic stimulation is due to inhibition of transsarcolemmal calcium influx.
J Mol Cell Cardiol 1986 Jun
PMID:The influence of verapamil and its isomers on vulnerability to ventricular fibrillation during acute myocardial ischemia and adrenergic stimulation in isolated rat heart. 242 59

Myocardial ischemia leads to the damage of cellular membranes and release of intracellular enzymes. We studied the influence of the prostacyclin analog, iloprost, on alterations in membrane phospholipid content and composition in rat myocardium during ischemia. Infusion of iloprost (100 ng/kg/min) or its vehicle started 20 min after coronary artery ligation, and the hearts were analyzed after 6 h. Myocardial creatine kinase activity was significantly reduced by approximately 25% in the ischemic areas of hearts from rats receiving vehicle. This reduction in myocardial creatine kinase activity was totally abolished by infusion of iloprost. Total phospholipid content was significantly reduced by 10% in ischemic areas of hearts obtained from vehicle infused animals. Iloprost infusion also prevented the loss of total phospholipids in the ischemic areas. The data show that coronary artery ligation is associated with a significant loss of total membrane phospholipids in ischemic regions of rat myocardium, characterized by significant decreases in phosphatidylcholine, phosphatidylethanolamine and cardiolipin. The decrease in cardiac phosphatidylcholine and phosphatidylethanolamine content was prevented by iloprost, whereas the decrease in cardiolipin content was unaltered. Infusion of the prostacyclin analog iloprost almost totally inhibited the ischemia induced loss of phospholipids, suggesting that this may be an important component of its cytoprotective mechanism of action.
J Mol Cell Cardiol 1987 Mar
PMID:Protective actions of a stable prostacyclin analog in ischemia induced membrane damage in rat myocardium. 243 96

Heart and skeletal muscle cells rapidly lose potassium ions after withdrawal of oxygen. In myocardial ischemia, cellular release of potassium and interruption of extracellular washout produce a rapid and marked increase of extracellular K+ concentration. Harris et al. were the first to observe the coincidence of the K+ shift and the frequent occurrence of ventricular arrhythmias. They ascribed a major role to K+ in the genesis of the electrophysiological changes in early ischemia. The purpose of this article is to outline briefly in the first part the relationship between potassium accumulation and the electrical changes in ischemia with emphasis on reviewing the role of K+ in the slowing of impulse propagation and production of conduction block. In the second part, the possible mechanisms leading to potassium imbalance will be discussed and experimental data will be presented which suggest that an important component of net potassium loss is related to the development of acidosis.
J Mol Cell Cardiol 1987 Oct
PMID:Extracellular K+ and H+ shifts in early ischemia: mechanisms and relation to changes in impulse propagation. 244 90

During ischemia in so-called slow heart-rate hearts, there is a marked inhibition of the mitochondrial ATPase mediated by inhibitor protein binding to the enzyme (Rouslin, W., and Pullman, M. E. (1987) J. Mol. Cell. Cardiol. 19, 661-668). This ischemia-induced ATPase inhibition is triggered by a drop in mitochondrial matrix pH (Rouslin, W. (1987) J. Biol. Chem. 262, 3472-3476) which occurs as a result of the cell acidification which develops rapidly during the ischemic process. One effect of the ATPase inhibition is a marked slowing of the net rate of tissue ATP hydrolysis and, thus, a prolongation of cell viability during ischemia. In the present study, we demonstrate that matrix acidification in intact mitochondria from slow heart-rate hearts appears to be mediated by the Pi transporter. Pi/H+ symport appears to be the primary process which mediates matrix acidification and thus ATPase inhibition in intact slow heart-rate heart mitochondria made acidotic in vitro and, presumably, also in mitochondria in situ during the ischemic process. In contrast, intact mitochondria from a so-called fast heart-rate species, which exhibited only a low level of ischemia-induced ATPase inhibition in situ (Rouslin, W. (1987) Am. J. Physiol. 252, H622-H627), failed to exhibit a Pi- and pH-dependent mitochondrial ATPase inhibition mechanism in vitro. The Pi-dependent mitochondrial ATPase inhibition mechanism reported here for slow heart-rate hearts is consistent with a role for Pi as a coordinating signal promoting the conservation of cell ATP during myocardial ischemia.
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PMID:Regulation of mitochondrial matrix pH and adenosine 5'-triphosphatase activity during ischemia in slow heart-rate hearts. Role of Pi/H+ symport. 252 49

The effect of regional myocardial ischemia complicated by ventricular fibrillation (VF) on the ultrastructure of subendocardial (SE) and false tendon (FT) Purkinje cells (PC) was studied in anesthetized dogs. In all cases of early ischemia with spontaneous VF, many PC exhibited ultrastructural damage as early as 2 min after the onset of ischemia. The changes noted were: intercalated disk dissociation, sarcoplasmic reticulum vacuolization (SRV), supercontraction, mitochondrial swelling, and sarcolemmal defects (rigor cells). The appearance of at least some rigor PC seemed to precede spontaneous VF, since these cells were absent from the conduction systems in control hearts in which VF was induced by electric shock or reperfusion, from hearts from sham-operated dogs, or from hearts subjected to longer periods of uncomplicated myocardial infarction. These observations indicate that alterations in SE and FTPC may play a role in the pathogenesis of sudden death due to early myocardial ischemia. The mechanism of this rapid damage of PC remains obscure.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Ultrastructure of Purkinje cells in the subendocardium and false tendons in early experimental myocardial infarction complicated by fibrillation in the dog. 256 51

A new sampling method of cross-sectioning the canine heart in situ was developed. A mechanical device, driven by spring power, enabled cross-sectioning of a short-axis plane of the beating canine heart (4 mm thick) with high speed rotating blades, at a pre-determined phase of the cardiac cycle, and instantaneous freeze-clamping (2.4 mm thick) with pre-cooled aluminum blocks, all within 120 ms. By this method, the anatomical structures of the sample were well preserved. Transmural metabolism and flow distribution were instantaneously fixed and high resolution of the two-dimensional redox state was obtained by application of NADH fluorescence photography. Micro-samplings from the desired portion of the cross-sectional slice were possible at -190 degrees C. NADH fluorescence of the samples did not increase from the surface to 1.2 mm in depth, confirming that there was no ischemic artifact. With the present technique, a heart sample in which transmural metabolism, and the redox state, are fixed and visualized is attainable, thus providing a new tool for the study of myocardial ischemia.
J Mol Cell Cardiol 1989 Feb
PMID:A rapid cross-sectioning and freeze-clamping device for the beating canine heart. 266 89

We have previously observed a long-lasting antiischemic and antiarrhythmic effect induced by prostacyclin (PgI2) or its stable analogue, 7-oxo-PgI2-ephedrine salt in dogs subject to local myocardial ischemia. This protection appeared when the vasodilating and platelet aggregation inhibiting effect of PgI2 or its analogue was over and persisted even 72 h after treatment. We have also found that short incubation with 7-oxo-PgI2 may induce a long-lasting prolongation of the action potential duration and of the effective refractory period in the isolated rabbit papillary muscle preparation without affecting the membrane potential or the rate of rise of the action potential. Our present experiments have shown a 7-oxo-PgI2 induced, dose-dependent prolongation of the ventricular functional refractory period in conscious rabbits and anesthetized dogs, as well as an increase of the QT interval in the ECG in both species and also in conscious guinea-pigs. In all three species 50 micrograms/kg i.m. dose proved to be optimal, evoking maximal effect 48 h after treatment. In conscious rabbits this pre-treatment prevented the train of non-stimulated extra beats induced by premature stimuli. Furthermore it also prevented widening of the QRS complex appearing in non-treated controls after programmed stimulation. Pre-treatment significantly increased electrical fibrillo-flutter thresholds in the auricles and ventricles of anesthetized cats. These electrophysiological changes seem to be closely related to the 7-oxo-PgI2 induced, late appearing and long-lasting protection from ischemic and reperfusion arrhythmias.
J Mol Cell Cardiol 1989 Jun
PMID:7-oxo-PgI2 induced late appearing and long-lasting electrophysiological changes in the heart in situ of the rabbit, guinea-pig, dog and cat. 267 53


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