Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The long term impact of pre-hospital thrombolysis in acute myocardial infarction on the subsequent development of heart failure symptoms was investigated in 362 consecutive patients. The pre hospital strategy, used in 61 patients, allowed for very early administration of streptokinase, within 1.2+/-0.6 (mean+/-S.D.) hours from pain onset. In contrast, 294 patients treated in hospital received lytic treatment within 2.0+/-0.9 hours. The pre hospital group showed faster reperfusion, as measured by the time to peak creatine kinase and to ST segment recovery, but only a slightly better ventricular function, as compared to hospital treated patients. Heart failure symptoms were significantly reduced in the pre hospital group during hospitalization and at long term follow up: there were less dyspnea, fatigue, orthopnea, nocturnal dyspnea, nocturia, peripheral edema and episodes of pulmonary edema. Angina was reduced as well. We conclude that the initial benefit of prehospital thrombolysis translates into long term reduction of heart failure symptoms, thus improving quality of life.
 ...
PMID:Prevention of congestive heart failure by early, prehospital thrombolysis in acute myocardial infarction: a long-term follow-up study. 970 26

This review describes the effects of changes in left ventricular pressures and heart rate on myocardial high-energy phosphate metabolism. When cardiac workload is substantially increased, creatine kinase flux will increase markedly, phosphocreatine will show a small but detectable decrease, and ATP will not change. In this context, heart rate is a much weaker acute metabolic stimulus than left ventricular developed pressure. However, in heart failure, chronic reduction of heart rate has beneficial effects on alterations of high-energy phosphate metabolism.
 ...
PMID:Influence of left ventricular pressures and heart rate on myocardial high-energy phosphate metabolism. 983 37

Differential diagnosis of patients who present with chest pain remains problematical. It has been shown that 11.8-7% of patients with acute myocardial infarction (AMI) are sent home from the emergency department (ED). Audit of our own ED has shown the incidence of missed prognostically significant myocardial damage to be 6.7%. Diagnostic criteria for AMI have classically been based on the triad of history, ECG and measurement of cardiac enzymes. The choice of 'cardiac enzymes' has been dictated by the evolution of laboratory techniques, commencing with measurement of aspartate transaminase and progressing to measurement of creatine kinase (CK) and its MB isoenzyme (CK-MB). Measurement of CK-MB has been shown by both clinical studies and rigorous statistical analysis to represent the best test for the diagnosis of AMI. The advent of real time immunoassay together with advances in therapeutic options for management of acute coronary syndromes (ACS) has resulted in a paradigm shift in the approach to laboratory testing. Immunoassay for CK-MB (CK-MB mass measurement) is diagnostically superior to CK-MB activity measurement and is the test of choice for 'classical' AMI. Development of immunoassays for the cardiac troponins, i.e. cardiac troponin T (cTnT) and cardiac troponin I (cTnI), has enhanced diagnostic specificity. These measurements are completely specific for cardiac damage, allow quantitation of the extent of infarction and are diagnostically superior to CK-MB measurement. Applications of this specificity have included the differential diagnosis of CK elevation in arduous physical training, detection of myocardial damage after DC cardioversion and prediction of ejection fraction. Of more interest is the utility of these markers in management of patients presenting without clear electrocardiographic changes. Diagnosis and management of patients presenting with ST segment elevation has been clarified by large clinical trials of thrombolytic agents. In such patients, thrombolysis is the treatment of choice. Patients presenting with ST segment elevation represents the minority of patients with probable ACS 9.6% of all patients presenting to our hospital. The majority require risk stratification into high- and low-risk groups. It is here that cardiac troponins have a major role. The measurement of cTnT has been shown in a large number of studies to enable risk stratification of patients with unstable angina. The combination of cTnT, admission ECG and stress ECG can be used for a comprehensive risk stratification of patients with unstable angina. The combination of cTnT, admission ECG and stress ECG can be used for a comprehensive risk stratification which can be completed by 24 h from admission, as well as allowing a safe discharge policy from the ED. Measurements of cardiac troponins can also be used to predict prognosis in patients with other diagnostic categories. Patients with cardiac failure can be risk stratified according to cTnT status. cTnT status on admission allows subdivision into high- and low-risk groups in patients presenting with ST segment elevation. Certainly, cTnT measurement can be incorporated into a clinical decision-making strategy to assign patients to investigation and management pathways. There is evidence that cTnT may be useful to guide therapeutic options. The major issue is one of cost. In the U.K. model of managed care with undemanding diagnostic standards, the role of cTnT will be to enhance clinical decision-making strategies, to provide accurate diagnosis and to reduce lengths of stay. This can be shown to have potential for major improvements in cost efficiency. Improvements in diagnostic accuracy can reduce inappropriate long-term drug therapy. In systems with a more aggressive laboratory investigation strategy, rationalization of test numbers will provide an immediate cost reduction while improving quality. Finally, use of point-of-care testing (POCT) means that biochemical testing can be pe
 ...
PMID:Troponin T or troponin I or CK-MB (or none?). 985 34

Excessive right heart hypertrophy was investigated under additional acute hypoxic stress to find out a possible contribution of mitochondrial dysfunction to sudden heart failure. Severe right heart hypertrophy in rats was induced by exposure to hypobaric pressure (46,663 Pa) for 4 weeks. Heart rate, isovolumic pressure and coronary flow were determined in the Langendorff mode of perfusion. After normoxia, the hearts were subdued to acute hypoxia/reoxygenation. Mitochondrial membrane potential was measured at the heart surface by fluorometry using 2-(dimethylaminostyryl)-l-ethylpyridinium iodide (DASPEI). At the end of each experiment mitochondria were isolated and ATP synthesis, ATPase, as well as creatine kinase activity were determined. Compared to normal hearts the heart rate is decreased in the hypertrophied group whereas right ventricular systolic and (end)diastolic pressure (adjusted to isovolumetric maxima) are increased. Coronary flow is decreased. Cytosolic creatine phosphate ATP levels and ATP/ADP ratios are significantly (p < 0.01) decreased. Furthermore, ATP synthesis and creatine kinase activities are diminished. At high ADP, respiration is loosely coupled or partially uncoupled. Acute hypoxia is particularly deleterious to hypertrophied hearts: Mitochondrial membrane potential as measured by heart surface fluorometry decreases extensively and is only very incompletely restored during reoxygenation. Rate-pressure product decreases precipitously and is restored during reoxygenation only to a very low extent. The results indicate an insufficient energy metabolism of mitochondria during acute hypoxia/reoxygenation which adds to the earlier described shifted isozyme pattern of myosin and decreased activities of myosin and sarcoreticular Ca2+ ATPase, leading to myocardial failure in right heart hypertrophy.
 ...
PMID:Hemodynamics and mitochondrial energy metabolism in right heart hypertrophy after acute hypoxic stress. 1021 64

Broad-breasted white turkey poults fed furazolidone developed dilated cardiomyopathy (DCM) characterized by ventricular dilatation, decreased ejection fraction, beta1-receptor density, sarcoplasmic reticulum (SR) Ca2+-ATPase, myofibrillar ATPase activity, and reduced metabolism markers. We investigated the effects of carteolol, a beta-adrenergic blocking agent, by administrating two different dosages (0.01 and 10.0 mg/kg) twice a day for 4 wk to control and DCM turkey poults. At completion of the study there was 59% mortality in the nontreated DCM group, 55% mortality in the group treated with the low dose of carteolol, and 22% mortality in the group treated with the high dose of carteolol. Both treated groups showed a significant decrease in left ventricle size and significant restoration of ejection fraction and left ventricular peak systolic pressure. Carteolol treatment increased beta-adrenergic receptor density, and the high carteolol dose restored SR Ca2+-ATPase and myofibrillar ATPase activities, along with creatine kinase, lactate dehydrogenase, aspartate transaminase, and ATP synthase activities, to normal. These results show that beta-blockade with carteolol improves survival, reverses contractile abnormalities, and induces cellular remodeling in this model of heart failure.
 ...
PMID:Cellular and molecular remodeling in a heart failure model treated with the beta-blocker carteolol. 1033 Feb 54

Although the downregulation of creatine kinase activity has been associated with heart failure, creatine kinase-deficient transgenic hearts have a preserved contractile function. This suggests the existence of alternative phosphotransfer pathways in the myocardium, the identity of which is still unknown. In this study, we examined the contribution of adenylate kinase-catalyzed phosphotransfer to myocardial energetics. In the isolated mitochondria/actomyosin system, which possesses endogenous adenylate kinase activity in both compartments, substrates for adenylate kinase promoted the rate and amplitude of actomyosin contraction that was further enhanced by purified adenylate kinase. Inhibition of adenylate kinase activity diminished both actomyosin contraction and mitochondrial respiration, which indicated reduced energy flow between mitochondria and myofibrils. In intact myocardium, the net adenylate kinase-catalyzed phosphotransfer rate was 10% of the total ATP turnover rate as measured by 18O-phosphoryl labeling in conjunction with gas chromatography and mass spectrometry. In pacing-induced failing heart, adenylate kinase-catalyzed phosphotransfer increased by 134% and contributed 21% to the total ATP turnover. Concomitantly, the contribution by creatine kinase dropped from 89% in normal hearts to 40% in failing hearts. These phosphotransfer changes were associated with reduced levels of metabolically active ATP but maintained overall ATP turnover rate. Thus, this study provides evidence that adenylate kinase facilitates the transfer of high-energy phosphoryls and signal communication between mitochondria and actomyosin in cardiac muscle, with an increased contribution to cellular phosphotransfer in heart failure. This phosphotransfer function renders adenylate kinase an important component for optimal myocardial bioenergetics and a compensatory mechanism in response to impaired intracellular energy flux in the failing heart.
 ...
PMID:Adenylate kinase-catalyzed phosphotransfer in the myocardium : increased contribution in heart failure. 1034 88

The elimination of caffeine was investigated in a 1860 g, 31 week gestation neonate, following the accidental administration of a 160 mg.kg-1 dose. The first serum concentration measured was 217.5 mg.l-1 at 36.5 h after dosing. Fitting of time-concentration data was performed using non-linear regression with MKMODEL. A first order elimination model was superior to a mixed order model. Parameter estimates were: clearance 0.01 l.h-1, volume of distribution 1.17 litres, elimination half-life 81 h. Toxic manifestations included hypertonia, sweating, tachycardia, cardiac failure, pulmonary oedema and metabolic disturbances (metabolic acidosis, hyperglycaemia and creatine kinase elevation). An unusual feature of this infant's illness course was gastric dilatation. These signs resolved by day 7 at a serum concentration of 60-70 mg.l-1. Caffeine clearance has traditionally been reported as either an absolute value or as directly proportional to body weight. The per kilogram model gives an erroneous impression that clearance is greatest in early childhood and then decreases with age until adult rates are reached in late adolescence. Age-related clearance values reported in the literature were reviewed using an allometric 3/4 power model. This size model demonstrates that clearance increases in infancy and reaches adult rates within the first three months of life.
 ...
PMID:Caffeine overdose in a premature infant: clinical course and pharmacokinetics. 1038 69

We have tested the hypothesis that decreased functioning of creatine kinase (CK) at sites of energy production and utilization may contribute to alterations in energy fluxes and calcium homeostasis in congestive heart failure (CHF). Heart failure was induced by aortic banding in 3-week-old rats. Myofilaments, sarcoplasmic reticulum (SR), mitochondrial functions, and CK compartmentation were studied in situ using selective membrane permeabilization of left ventricular fibers with detergents (saponin for mitochondria and SR and Triton X-100 for myofibrils). Seven months after surgery, animals were in CHF. A decrease in total CK activity could be accounted for by a 4-fold decrease in activity and content (Western blots) of mitochondrial CK and a 30% decrease in M isoform of CK (MM-CK) activity. In myofibrils, maximal force, crossbridge kinetics, and alpha-myosin heavy-chain expression decreased, whereas calcium sensitivity of tension development remained unaltered. Myofibrillar CK efficacy was unchanged. Calcium uptake capacities of SR were estimated from the surface of caffeine-induced tension transient (SCa) after loading with different substrates. In CHF, SCa decreased by 23%, and phosphocreatine was 2 times less efficient in enhancing calcium uptake. Oxidative capacities of the failing myocardium measured as oxygen consumption per gram of fiber dry weight decreased by 28%. Moreover, the control of respiration by creatine, ADP, and AMP was severely impaired. Our observations provide evidence that alterations in CK compartmentation may contribute to alterations of energy fluxes and calcium homeostasis in CHF.
 ...
PMID:Subcellular creatine kinase alterations. Implications in heart failure. 1040 Sep 12

Cardiac troponin I (cTnI) and creatine kinase MB isoenzyme (CK-MB) were measured in the plasma of 37 patients with acute heart failure. Elevated plasma cTnI concentrations were found in 89% of acute heart failure patients (P < 0.001 compared with a normal population), while plasma CK-MB showed no significant difference (P = 0.09). During follow-up, serial measurements of cTnI and CK-MB were performed. In acute heart failure patients, improvement of the clinical profile was associated with declining cTnI concentrations, while deterioration of heart function was closely related to increasing cTnI. Plasma CK-MB activities remained within the normal range throughout the observation period. This preliminary study provides evidence of cardiac damage to functionally overloaded myocytes. cTnI may be a sensitive marker both for early detection of myocyte damage and for monitoring of function in patients with acute heart failure.
 ...
PMID:Monitoring of cardiac troponin I in patients with acute heart failure. 1045 4

Oral feeding with the creatine analogue beta-guanidinopropionate (beta-GP) reduces myocardial phosphocreatine and creatine concentrations by about 80%in vitro, this is accompanied by reduced contractile performance. We hypothesized, thus, that beta-GP feeding leads to hemodynamic changes in vivo characteristic of heart failure. beta-GP was fed to Wistar rats for up to 8 weeks. In isolated hearts, function was measured isovolumically, myocardial energetics were followed with (31)P-NMR spectroscopy. In vivo hemodynamics were measured with Millar-Tip-catheters and an electromagnetic flow probe. Beta-GP feeding did not alter heart weight. In vitro, diastolic pressure-volume curves indicated structural left ventricular dilatation, and a 36% reduction of left ventricular developed pressure was found; phosphocreatine was reduced by approximately 80%, ATP unchanged and creatine kinase reaction velocity ((31)P-MR saturation transfer) decreased by approximately 90%. The total creatine pool (high-pressure liquid chromatography) was reduced by up to approximately 70%. In contrast to in vitro findings, in vivo cardiac hemodynamics (including left ventricular developed pressure, d P/d t(max), cardiac output and peripheral vascular resistance) at rest and during acute volume loading showed no alterations after beta-GP feeding. The only functional impairment observed in vivo was a 14% reduction of maximum left ventricular developed pressure during brief aortic occlusion. In the intact rat, cardiac and/or humoral compensatory mechanisms are sufficient to maintain normal hemodynamics in spite of a 90% reduction of creatine kinase reaction velocity. However, chronic beta-GP feeding leads to structural left ventricular dilatation.
 ...
PMID:Functional and energetic consequences of chronic myocardial creatine depletion by beta-guanidinopropionate in perfused hearts and in intact rats. 1052 22


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