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)

The phrase "heart failure" encompasses many clinical entities. The therapeutic principles determining the treatment of these entities vary according to the etiology of congestive heart failure (CHF), the existing hemodynamics, and the mode of action of different drugs. In acute CHF due to myocardial ischemia, intracellular acidosis and the accumulation of phosphate may be the initial underlying causes of contractile failure while, minutes later, lack of high-energy compounds may be an important contributory factor. The cause of contractile failure in chronic syndromes is less well understood. There is evidence for the desensitization of beta receptors on the cell surface but the precise location of the defect is unclear. The receptors may be down-regulated but, in addition, abnormalities have been reported in several other parts of the contractile pathway including the contractile proteins and the sarcoplasmic reticulum. Deficiency of cyclic adenosine monophosphate has also been suggested as a mechanism of contractile failure. In both acute and chronic CHF, there is a redistribution of blood flow to the body organs. Of particular significance is the reduction of blood flow to the kidneys, and a reversal of this defect is one of the major therapeutic objectives. Positive inotropic drugs, vasodilators and drugs altering relaxation of the heart, have been evaluated in the treatment of CHF. Pure inotropic drugs can cause tachycardia, ischemia and "metabolic exhaustion" of the myocardium. The most advantageous profile for an "inotropic" drug in many patients with CHF would be a drug combining systemic vasodilatation, renal vasodilatation, increased relaxation of the myocardium only a mild positive inotropic effect and no chronotropic effect.
 ...
PMID:Current therapeutic principles in the acute management of severe congestive heart failure. 304 59

Complete global myocardial ischemia or zero coronary arterial flow in dogs results in a series of well-defined changes which begin when the myocardium converts from aerobic to anaerobic metabolism. These processes continue until the myocardium dies. The products of anaerobic metabolism, chiefly glycolytic intermediates, inorganic phosphate, H+, and creatine, are produced intracellularly and accumulate in the tissue. Because the demand for high-energy phosphates (HEP) in the tissue exceeds the supply available from anaerobic glycolysis and HEP reserves, net ATP level declines, approaching zero after 100 min of ischemia at 37 degrees C. At this time, the changes in totally ischemic tissue in vitro are equivalent to those seen in myocytes irreversibly injured by severe ischemia in vivo. During reoxygenation after total ischemia, the resumption of effective contractile activity depends partly on the metabolic changes and degree of myocyte injury sustained during ischemia.
 ...
PMID:Complete global myocardial ischemia in dogs. 304 98

We investigated the influence of the thromboxane (TX) synthetase inhibitor HOE 944 (6-(5-Methylimidazol-1-yl)methyl-2-naphthoic acid-Hydrochloride), prostacyclin (PGI2) and indomethacin on reperfusion arrhythmias in isolated perfused ischemic rat hearts. HOE 944, PGI2 and indomethacin were perfused in a concentration of 1 x 10(-6), 5 x 10(-8) and 1 x 10 (-6) mol/l respectively (in vitro). In another set up rats were pretreated p.o. with a daily dose of 30 mg/kg for 7 days (ex vivo). Acute regional myocardial ischemia was induced in isolated working rat hearts by occlusion of the left coronary artery. Reperfusion commenced upon release of this occlusion which was invariably associated with ventricular fibrillations (VF). Perfusion with 1 x 10(-6) mol/l HOE 944 did not affect these arrhythmias. In contrast hearts from HOE 944 pretreated rats were protected against fibrillations (p less than 0.01). PGI2 perfusion was also protective against VF (p less than 0.01) whereas indomethacin perfusion aggravated VF. In the ischemic period cardiodynamics like left ventricular pressure (LVP), dp/dt max and coronary flow (CF) were improved in HOE 944 pretreated rat hearts. In the venous effluent the enzyme activities of lactate dehydrogenase (LDH) and creatine kinase (CK) as well as lactate production were decreased in the ischemic and reperfusion period. Myocardial tissue levels of ATP were distinctly increased and lactate levels decreased in HOE 944 pretreated rats, whereas glycogen and creatine phosphate did not change.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Influence of the thromboxane synthetase inhibitor HOE 944, prostacyclin and indomethacin on reperfusion arrhythmias, cardiodynamics and metabolism in isolated ischemic rat hearts. 307 62

Changes in cytosolic free calcium concentration during myocardial ischemia were measured by 19F NMR in 5FBAPTA-loaded perfused rat hearts. The hearts were perfused with Krebs-Henseleit buffer containing 5 microM of the acetoxymethyl ester of 5FBAPTA, which was hydrolyzed by cytosolic esterases to achieve cytosolic concentrations of 5FBAPTA of 0.12 to 0.65 mM. Cytosolic free calcium concentrations were calculated as the product of the ratio of peak areas for bound and free 5FBAPTA in the NMR spectra and the dissociation constant (708 nM). The basal cytosolic calcium concentration, measured in potassium or magnesium arrested hearts, was 252 nM, and the time-average calcium concentration in beating hearts was 630 nM. Following the onset of total ischemia, there was no immediate substantial change in cytosolic calcium despite a rapid decline in creatine phosphate and ATP and a marked increase in inorganic phosphate as monitored by 31P NMR, but by 10 minutes, there was a substantial increase in free calcium concentration. The ratio of peak areas of bound and free 5FBAPTA returned to the preischemic value during reperfusion, and there was no detectable loss of 5FBAPTA from the heart. Creatine phosphate was also restored to its preischemic level during reperfusion. These results indicate that cytosolic free calcium increases during ischemia and is not immediately associated with lethal injury. This increase in cytosolic calcium may activate degradative enzymes that eventually could compromise myocyte viability.
 ...
PMID:Elevation in cytosolic free calcium concentration early in myocardial ischemia in perfused rat heart. 310 61

Cardiopulmonary bypass is associated with a reduction in plasma free triiodothyronine in patients undergoing cardiac operations. A previous experimental study in pigs demonstrated a marked inotropic effect when triiodothyronine was administered after a period of myocardial ischemia and cardiopulmonary bypass; this was associated with a significant reduction in mortality compared with the mortality in control pigs. To clarify the effect of triiodothyronine on myocardial high energy phosphate stores and lactate, a series of experiments was done in baboons undergoing 3 hours of myocardial ischemia while supported by cardiopulmonary bypass. Seven baboons received no triiodothyronine and six received 6 micrograms of triiodothyronine at the end of the ischemic period. Seventy minutes after cardiopulmonary bypass, the myocardial adenosine triphosphate level was significantly higher (p less than 0.01) in the treated animals. In untreated animals, a steady increase in myocardial lactate occurred after cardiopulmonary bypass; by 120 minutes after ischemia (70 minutes after cardiopulmonary bypass) there was a significant difference in lactate levels between the two groups (p less than 0.01). We postulate that a combination of global ischemia and depletion of triiodothyronine results in reduced mitochondrial function, inhibition of the tricarboxylic acid cycle, and increased anaerobic metabolism and depletion of myocardial phosphates. Triiodothyronine replacement therapy leads to improved mitochondrial function and increased aerobic metabolism, which results in increased synthesis of myocardial phosphates. We suggest that there may be a place for the administration of triiodothyronine in patients undergoing cardiac operations with a prolonged myocardial ischemic period or in whom there is any evidence of low cardiac output after discontinuation of cardiopulmonary bypass.
 ...
PMID:Effect of triiodothyronine (T3) on myocardial high energy phosphates and lactate after ischemia and cardiopulmonary bypass. An experimental study in baboons. 239 86

Missing the moment for application of ventricular assist devices (VAD) may be one of the major causes of multiple organ failure in patients who are to be weaned from cardiopulmonary bypass (CPB) with the aid of VAD. To determine the optimal timing for application of VAD in such patients, we examined the effect of a CPB assist on cardiac functional recovery from severe global ischemia using an experimental canine system. In the present study we created myocardial ischemia by clamping the aorta for 20 minutes (Group I; N = 7) or 45 minutes (Group II; N = 11) under normothermic CPB. The reliability of the method in creating severe cardiac failure was confirmed by testing the levels of adenosine triphosphate (ATP), creatine phosphate (CP), and lactate. After reperfusion of the myocardium, the heart was assisted by a totally vented CPB. The left ventricular end-systolic pressure-volume relationship (Emax), which is a load-independent index of contractility, was obtained every 15 minutes for up to 120 minutes of reperfusion. The Emax revealed that the function of the damaged heart recovers exponentially with time after reperfusion. From curves of the functional recovery of the heart, CPB support appeared to be beneficial for the first 60 minutes after reperfusion, and aided in the recovery of cardiac function in hearts damaged by global myocardial ischemia. However, CPB assist thereafter may not be effective in further improving cardiac function. We therefore concluded that the decision to use VAD should be determined by cardiac function by 60 minutes of reperfusion to avoid prolonging CPB time.
 ...
PMID:Optimal timing for application of ventricular assist devices in patients who cannot be weaned from cardiopulmonary bypass. An experimental study. 319 47

Proton NMR imaging of myocardial ischemia without infarction requires the use of paramagnetic contrast agents. Even during the first few hours of infarction, imaging without contrast enhancement reveals only slight natural image contrast. Myocardial infarction, however, is much more readily detected during the first few days and weeks post coronary occlusion; this is due to a marked elevation in T2 during this time period. Chronic infarction, several months after the acute event, does not demonstrate altered signal intensity, but can be detected by visualizing myocardial wall thinning and aneurysm formation. Information regarding high energy phosphate metabolism can be acquired in vivo in ischemic animal preparations; preliminary data has demonstrated that it is possible to acquire similar information noninvasively in man. Development of this technique will eventually permit the study of pharmacological and mechanical interventions aimed at preserving myocardium in the ischemic heart. Exogenous labelling of myocardial tissue with carbon-13 permits the study of the effects of substrates on cellular metabolism. Ultimately, the technique of chemical shift imaging will provide a method of spatially resolving valuable metabolic information in the form of an NMR image. Eventually, with the gradual development of NMR technology, imaging and spectroscopy will become truly important clinical tools in the investigation of ischemic heart disease in man.
 ...
PMID:Evaluation of myocardial ischemia and infarction by nuclear magnetic resonance techniques. 328 14

The present work is divided into two parts: clinical observations and experimental investigations. The endogenic formation of nicotinic acid was decreased in all patients with ischaemic heart disease, and we have found an increased accumulation of kynurenine in blood serum after tryptophan loading in many cases - a clear indication of pyridoxal-5-phosphate (P-5-P) deficiency in the organism. The results of experimental investigations showed that L-kynurenine sulphate initiates cardiac dysrhythmias as well as dystrophic changes in cardiomyocytes. Both the clinical observations and experimental investigations point out a previously unknown pathogenetic mechanism for the ischaemic heart disease, and for bradyarrhythmia as well as myocardial cell failure, caused by P-5-P deficiency in the organism.
 ...
PMID:[Peculiarities of nicotinic acid formation in coronary heart disease with special reference to heart arrhythmias]. 336 17

Myocardial ischemia causes both systolic and diastolic dysfunction. A variety of positive inotropic agents with different subcellular mechanisms may be used clinically in an attempt to reverse ischemic contractile failure. We tested the hypothesis that two inotropic agents, isoproterenol (a beta-adrenergic agonist) and ouabain (a sodium pump inhibitor), might have different effects on left ventricular (LV) diastolic function during ischemic failure despite an equivalent inotropic effect. Isolated isovolumic (balloon-in-LV) blood perfused rabbit hearts were paced at constant physiological heart rate (4 Hz), given either no drug (controls, n = 7), isoproterenol (n = 7), or ouabain (n = 7), and then subjected to 6 minutes of low flow ischemia (75% reduction of baseline coronary flow). The doses of isoproterenol and ouabain were selected to produce equivalent modest inotropic effects (15% increase in LV + dP/dt) in each heart during baseline perfusion conditions. During the ischemic period, there was a marked decrease in contractility, and neither isoproterenol nor ouabain demonstrated a positive inotropic effect relative to the control group. However, these agents had markedly different effects on diastolic chamber distensibility (assessed by end-diastolic pressure at constant LV volume) during ischemia. In the control and isoproterenol groups, diastolic chamber distensibility did not change during the ischemic period. In contrast, ouabain treatment resulted in a marked decrease in diastolic chamber distensibility during ischemia; this change was not completely reversible during the 10-minute reperfusion period. The mechanism by which ouabain decreased diastolic chamber distensibility relative to isoproterenol was assessed indirectly. The ouabain and isoproterenol groups were subjected to equivalent degrees of ischemia as assessed by oxygen supply/demand imbalance; during ischemia, each drug group did not differ with regard to myocardial perfusion rates, determinants of myocardial oxygen demand (heart rate, LV developed pressure, LV + dP/dt), myocardial oxygen consumption, lactate production, and ATP and creatine phosphate content. We therefore inferred that the greater decrease in diastolic distensibility in the ouabain group was not due to a greater metabolic severity of ischemia. These observations are consistent with a mechanism of cytosolic calcium overload induced by ouabain, resulting in persistent active myofilament tension development throughout diastole, to cause the observed decrease in diastolic chamber distensibility during ischemia in the ouabain group.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Effects of ouabain and isoproterenol on left ventricular diastolic function during low-flow ischemia in isolated, blood-perfused rabbit hearts. 339 61

We compared the effects of repeated short periods of myocardial ischemia with those of permanent occlusion (canine open-chest) with regard to tissue content of adenine nucleotides, nucleosides, creatine phosphate, and ultrastructure. Coronary occlusion for 3 min followed by a reperfusion period of 7 min was repeated up to a cumulative occlusion time of either 45 or 90 min. After cumulative occlusions of 15, 30, 45, and 90 min, transmural needle biopsies were taken from the ischemic area to be analyzed for adenine nucleotides, nucleosides, creatine phosphate, and ultrastructural changes. At the end of each experiment, tetrazolium salt staining was used for macroscopic detection of myocardial necrosis. These data were obtained with those obtained from dogs with a permanent coronary occlusion of 45 and 90 min, respectively. After repeated coronary occlusions at a cumulative occlusion time of 45 min, macroscopic detection of necrosis was negative, and after 90 min of cumulative coronary occlusion, patchy subendocardial tissue necrosis was found in only one out of 13 dogs, whereas in the group with permanent coronary occlusion, small patchy subendocardial necrosis was found in 95% after 45 min, and after 90 min permanent coronary occlusion, large subendocardial necrotic areas spreading towards the epicardial layers were found in 90% of the hearts. Ultrastructural investigations showed only slight to moderate ischemic injury after 45 and 90 min intermittent coronary occlusion, whereas permanent coronary occlusion produced moderate to severe ischemic injury after 45 min; and 90 min permanent coronary occlusion produced irreversible ischemic injury in all subendocardial tissue samples and in 80% of the subepicardial tissue samples.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Influence of repetitive coronary occlusions on myocardial adenine nucleosides, high energy phosphates and ultrastructure. 343 1


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