Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During induced myocardial ischemia for cardiac surgery, myocardial stunning occurs and aerobic metabolism of glucose, fatty acids, and lactate is inhibited as anaerobic pathways predominate. Even following reperfusion, stunned myocardium uses oxygen and substrate inefficiently leading to poor functional recovery as less mechanical work is developed per oxygen utilized. Amino acids potentially can act as cardiac metabolic substrates during and after ischemia, utilizing the transamination of amino acids by the malate-aspartate shuttle to form high energy phosphates via the tricarboxylic acid cycle. We investigated if "preloading" hearts with a physiologic spectrum of amino acids could increase postischemic myocardial recovery. Isolated perfused rabbit hearts were subjected to 120 min of 34 degrees C cardioplegic ischemia. Hearts received cardioplegia alone as controls or were "preloaded" with a 0.05% amino acid perfusion for 30 min prior to cardioplegic ischemia. Following reperfusion, analysis of functional recovery revealed that contractility and cardiac efficiency were improved with amino acids substrate preloading. The mechanism of this may be due to uptake of amino acids prior to ischemia, which are later utilized for internal reparative work during ischemia and external contractile work after ischemia.
 ...
PMID:Amino acid substrate preloading and postischemic myocardial recovery. 140 15

Pharmacological modulation of [K+]o accumulation and action potential changes during acute myocardial ischemia is under evaluation as a promising new antiarrhythmic and cardioprotective strategy during myocardial ischemia and reperfusion. We studied the effects of cromakalim, a K+ channel opener that activates ATP-sensitive K+ channels, in isolated arterially perfused rabbit interventricular septa subjected to ischemia and reperfusion and, through use of the patch clamp technique, in inside-out membrane patches excised from guinea pig ventricular myocytes. During aerobic perfusion, 5 microM cromakalim shortened action potential duration (APD) from 217 +/- 7 to 201 +/- 10 msec, had no effect on [K+]o, and reduced tension by 17 +/- 3% (n = 11). During ischemia, pretreatment with 5 microM cromakalim resulted in 1) more rapid APD shortening (71 +/- 9 versus 166 +/- 7 msec at 10 minutes and 63 +/- 12 versus 122 +/- 8 msec at 30 minutes), 2) similar [K+]o accumulation after 10 minutes (8.9 +/- 0.3 versus 9.6 +/- 0.5 mM) but a trend toward increased [K+]o accumulation after 30 minutes (11.0 +/- 1.7 versus 9.6 +/- 1.0 mM), and 3) similar times for tension to decline to 50% of control (2.14 +/- 0.16 versus 2.14 +/- 0.19 minutes) but shorter time to fall to 20% of control (4.34 +/- 0.33 versus 4.90 +/- 0.22 minutes; p = 0.003). After 60 minutes of reperfusion following 30 minutes of ischemia, recovery of function was similar, with a trend toward better recovery of developed tension (to 58 +/- 9% versus 39 +/- 10% of control; p = 0.18) and tissue ATP levels in cromakalim-treated hearts but no differences in APD or rest tension. Thus, 5 microM cromakalim had mild effects in normal heart but greatly accelerated APD shortening during ischemia without markedly increasing [K+]o accumulation, possibly because the more rapid APD shortening reduced the time-averaged driving force for K+ efflux through ATP-sensitive K+ channels. A significant cardioprotective effect during 30 minutes of ischemia plus 60 minutes of reperfusion could not be demonstrated in this model. In excised membrane patches studied at room temperature, the ability of cromakalim to activate ATP-sensitive K+ channels was significantly potentiated by 100 microM but not 15 microM cytosolic ADP, suggesting that in addition to the modest fall in cytosolic ATP during early ischemia, the rapid increases in cytosolic ADP may further sensitize cardiac ATP-sensitive K+ channels to activation by cromakalim.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Activation of ATP-sensitive K+ channels by cromakalim. Effects on cellular K+ loss and cardiac function in ischemic and reperfused mammalian ventricle. 142 30

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.
 ...
PMID:High-dose intravenous beta 1-blockade in patients early after cardiac operations. Negative inotropism versus myocardial oxygen economy. 145 32

The effectiveness of University of Wisconsin solution (UWS) and oxygenated St. Thomas' Hospital solution (STS) for prolonged myocardial protection was evaluated in isolated working rat hearts preserved for 12 h at 4 degrees C using three different preservation techniques: induction of cardiac arrest and subsequent hypothermic storage with STS (group 1, n = 9) or UWS (group 4, n = 9), intermittent coronary flush (every 90 min) with STS (group 2, n = 9) or UWS (group 5, n = 9), or continuous coronary perfusion with STS (group 2, n = 7) or UWS (group 6, n = 7) before 60 min of reperfusion. In the UWS preserved hearts, recovery of aortic flow was greater when the simple storage technique was employed compared to intermittent or continuous coronary perfusion (groups 5 and 6). In the STS preserved hearts, aortic flow recovery was superior when the intermittent perfusion technique was applied. The same pattern was observed with regard to recovery of left ventricular pressure. Lactate dehydrogenase release during reperfusion was significantly less pronounced in group 4 (UWS, single flush, simple storage) as compared to group 1 (STS, single flush and simple storage), whereas best preservation of myocardial high energy phosphates was observed when hearts were preserved with multiple dose cardioplegia using STS. Simple hypothermic storage with UWS affords the best functional recovery after prolonged myocardial ischemia in all groups. Repetitive or continuous application of this solution is detrimental, possibly due to potassium overloading. In STS treated groups, multiple dose application of oxygenated STS enhances functional and metabolic recovery compared to its single dose application.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Prolonged myocardial protection with St. Thomas' Hospital solution and University of Wisconsin solution. The importance of preservation techniques. 161 May 95

Phospholipase D (PLD) activity was found to be present in the membrane fraction of rat myocardial cells by in vitro assays (36.7 +/- 4.1 nmol/mg protein per h against 1-palmitoyl-2-arachidonoyl- phosphatidylcholine) and demonstrated in intact cells by the specific transphosphatidylation reaction (in the presence of 0.02% ethanol) quantitated using n-[1-14C]butanol (201.16 +/- 7.1 pmol/min per g dry weight in the whole heart). Both methods showed a significant increase in PLD activity (by 62 and 44%, respectively) in hearts subjected to reversible (30 min) global normothermic ischemia followed by reperfusion (30 min). In hearts prelabeled with [1-14C]arachidonic acid, ischemia/reperfusion induced a significant increase in the amount of radiolabel incorporated into phosphatidic acid (PtdOH) (by 49.6%) and diacylglycerol (DG) (by 259%). DG kinase inhibition by 100 microM dioctanoylethylene glycol did not affect the ischemia/reperfusion DG and PtdOH levels while PtdOH phosphohydrolase inhibition with 40 microM propranolol produced a further increase in PtdOH (to 2.36-fold the baseline level) and a reduction in DG (to only 145% over the baseline levels). Put together, all these results suggest an activation of PLD during myocardial ischemia/reperfusion generating intracellular PtdOH, part of which is converted by PtdOH phosphohydrolase to DG. We further investigated the possible pathophysiological significance of the observed PLD activation. Stimulation of PLD with sodium oleate (20 microM) induced a significant improvement of functional recovery of ischemic hearts during reperfusion (as monitored by coronary flow and left intraventricular pressure measurements) and an attenuation of cellular injury as expressed by lactate dehydrogenase and creatine kinase release in the coronary effluent during reperfusion. These results suggest a PLD-mediated signaling in the ischemic heart which may benefit functional recovery during reperfusion.
 ...
PMID:Phospholipase D signaling in ischemic heart. 161 Sep 13

Echocardiography has revealed evidence of "subnormal" regional contraction patterns that result from myocardial ischemia and are often accompanied by nonadjacent "hyperkinetic" regions. Whether these regions of hyperkinetic wall motion persist unchanged or revert to normal after coronary artery bypass graft (CABG) surgery has not been studied in humans. Using echocardiography, we evaluated both dysfunctional and normal myocardial regions for changes in segmental wall motion and percent of systolic wall thickening that occurred immediately after CABG surgery in 32 patients. Segmental wall motion analysis before CABG surgery in these patients revealed that 170 (66%) of 256 myocardial segments were subnormal, of which 115 (67%) improved and 102 (60%) returned to normal immediately after CABG surgery. Eleven myocardial segments that were hyperkinetic before CABG surgery returned to normal after CABG surgery. Preoperatively, 162 (63%) of 256 myocardial segments had systolic wall thickening less than 30%, which increased from 11.8% +/- 8.9% to 24.3% +/- 14.3% (mean +/- SD) (P less than 0.01) postoperatively. Conversely, a reverse trend was found when systolic wall thickening was greater than 30% before CABG surgery: thickening decreased from 46.2% +/- 13.8% to 33.4% +/- 14.8% after CABG surgery (P less than 0.01). Thus, we conclude that immediately after CABG surgery, there is a recovery of function in some myocardial segments and a reduction in function in others. Furthermore, we conclude that the semiquantitative assessment of percent of systolic wall thickening is a more reliable (consistent) echocardiographic index of myocardial function compared with the qualitative assessment of segmental wall motion immediately after CABG surgery.
 ...
PMID:Echocardiographic analysis of dysfunctional and normal myocardial segments before and immediately after coronary artery bypass graft surgery. 163 35

Dopamine frequently is used to improve cardiac performance after acute myocardial ischemia. Inotropic agents, however, increase myocardial oxygen demand and could potentially delay recovery from ischemic injury. To evaluate this problem, we studied eight chronically instrumented dogs in the conscious state and performed two 15-minute coronary occlusions 48 hours apart. After one of the occlusions, either dopamine (15 micrograms/kg/min) or saline placebo was administered intravenously from 1.0 to 1.5 hours of reperfusion. The alternative infusion was given during the second study. Preload recruitable work area, the area beneath the stroke work versus end-diastolic length relationship, was used to assess intrinsic myocardial performance. Ischemia decreased preload recruitable work area to 13% of control after both occlusions. After reperfusion, a 30-minute dopamine infusion acutely increased myocardial function nearly threefold as compared with placebo. Myocardial performance after dopamine administration, however, was significantly depressed compared with placebo throughout the remaining 24 hours of reperfusion (p less than 0.01). These data indicate that dopamine may impair functional recovery after ischemic myocardial injury and suggest that inotropic interventions should be used in this setting only when absolutely indicated.
 ...
PMID:The effects of dopamine on myocardial functional recovery after reversible ischemic injury. 223 34

The effect of myocardial preservation with perfluorochemical as cardioplegic solution was studied with isolated canine hearts which was compared between intermittent coronary perfusion and continuous coronary perfusion. Intermittent perfusion group (group I) was infused every 30 minutes during 5 hours ischemia with oxygenated perfluorochemical at the amount of 10 ml/kg. Continuous perfusion group (group II) was infused continuously at the amount of 10 ml/kg/30 minutes. After 5 hours of ischemic time, total perfusion volume of both group were same 100 ml/kg. The comparison of myocardial preservation effect between group I and group II was examined with biochemical study, hemodynamic study and histological study. As a result, biochemical study such as GOT, CPK, and Lactate showed higher in group II than in group I, and value of catecholamine and adenylate levels in myocardial tissue showed higher in group I than in group II. In hemodynamic study, LVSW and LVEDP showed excellent value in group I, but never showed adequate function in group II at late working phase. On the other hand, LVmax dp/dt was recovered excellently in group I but in group II was not recovered at early working phase. In histological findings with electronic microscopy, there were some limited ischemic lesion in group II, which was suggested disturbance of micro circulation. It may be attributable to low perfusion pressure of continuous perfusion method. Finally, with regard to SOD (Super oxide dismutase) consumption, group I took higher than group II, and also oxygen consumption. It shows that in group I there is an effective activity of aerobic metabolism during ischemia, which explain not only the improved functional recovery but also generation of free radical, caused by super oxide etc. It is concluded from these results that intermittent perfusion has provided excellent preservation against myocardial ischemia, and also has possibility of danger to set up reperfusion injury.
 ...
PMID:[Experimental study on myocardial preservation by perfluorochemical "comparison of myocardial preservation effect between continuous perfusion and intermittent perfusion"]. 239 94

The majority of deaths associated with ischemic heart disease occur suddenly because of disturbances in cardiac rhythm culminating in ventricular fibrillation. Past research has focused on elucidating the biochemical membrane mechanisms responsible for the adverse electrophysiologic alterations in the ischemic heart, with major emphasis on the influence of adrenergic neural factors. It has been demonstrated that both alpha 1-and beta-adrenergic mechanisms contribute to arrhythmogenesis in the ischemic heart. In the normal heart, alpha 1-adrenergic input has very little effect on electrophysiologic indices. However, during early ischemia and reperfusion, enhanced alpha 1-adrenergic responsivity associated with a twofold reversible increase in alpha 1-adrenergic receptors in vivo has been demonstrated. Likewise, in a variety of species, alpha 1-adrenergic inhibition with prazosin markedly decreases the incidence of malignant ventricular arrhythmias associated with either myocardial ischemia or subsequent reperfusion. One major manifestation of alpha 1-adrenergic receptor activation during reperfusion of ischemic myocardium is an increase in intracellular calcium ion (Ca2+). It has been demonstrated that reperfusion of ischemic myocardium increases intracellular Ca2+ in reversibly injured tissue, and that the gain in intracellular Ca2+ is prevented by alpha 1-adrenergic inhibition with hydroxyphenylethyl aminomethyl tetralone, even when administered just prior to reperfusion. Subsequently, it was demonstrated that the alpha 1-adrenergic-induced increase in mitochondrial Ca2+ contributes to the decline in mitochondrial function. These findings suggest that even single-dose intervention with alpha 1-adrenergic inhibitors may improve markedly the functional recovery and extent of ultimate necrosis in humans after coronary thrombolysis. To investigate the mechanisms responsible for the increase in alpha 1-adrenergic receptors during ischemia, we used isolated adult canine ventricular myocytes exposed to hypoxia. Thirty minutes of hypoxia at 25 degrees C or 10 minutes of hypoxia at 37 degrees C resulted in a threefold reversible increase in the density of surface alpha 1-adrenergic receptors and a threefold increase in the cellular content of long-chain acylcarnitines. Inhibition of carnitine acyltransferase I abolished not only the accumulation of long-chain acylcarnitines during hypoxia but also the increase in alpha 1-adrenergic receptors. Exposure of normoxic myocytes to exogenous long-chain acylcarnitines (1 mumol/liter) for 10 minutes also increased alpha 1-adrenergic receptor number. These findings indicate that the sarcolemmal accumulation of long-cha
 ...
PMID:Mechanisms contributing to the arrhythmogenic influences of alpha 1-adrenergic stimulation in the ischemic heart. 254 81

Persistence of regional contractile dysfunction after restoration of blood flow to transiently ischemic myocardium has been well described. To date, most studies have been performed in anesthetized animals. The present investigation compared the time course of recovery of regional segment shortening (percentage of segment shortening) in anesthetized versus conscious dogs subjected to a brief period of total occlusion of the left anterior descending coronary artery. Periods of occlusion lasting 5, 10, and 15 minutes were followed by 3 hours of reperfusion. Dogs anesthetized with sodium pentobarbital (30 mg/kg intravenously) had a significantly higher heart rate and blood pressure and lower dP/dt than conscious dogs. Coronary artery occlusion resulted in similar degrees of regional dyskinesis or akinesis, indicative of severe myocardial ischemia, in all experiments. During reperfusion, a gradual return of contractile function toward baseline was observed. At the end of the first 15 minutes of reflow, dogs subjected to 5 minutes of coronary occlusion demonstrated approximately 70% of control segment shortening in the previously ischemic zone. Animals subjected to 10- and 15-minute periods of coronary artery occlusion showed approximately 60% and 40% of control segment shortening at the same time point, respectively. The remainder of the 3-hour reperfusion period was characterized by a more gradual recovery of regional segment function. No differences were observed between anesthetized and conscious animals. It is concluded that the time course of functional recovery of postischemic reperfused myocardium is directly related to the duration of coronary occlusion and is similar in conscious and anesthetized dogs.
 ...
PMID:Time course of recovery of "stunned" myocardium following variable periods of ischemia in conscious and anesthetized dogs. 295 32


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