Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetate is used during regular hemodialysis to replace the bicarbonate lost during dialysis. The temporal changes of plasma bicarbonate and acetate concentrations and the critical role of acetate metabolism for the maintenance of plasma bicarbonate are described. We point out that the maximal rate of acetate oxidation in man is usually reached during dialysis, and we identify physiologic and pathologic factors that may modify this Vmax. A syndrome of 'intolerance to acetate' has been described. This syndrome is analyzed in the light of the metabolic consequences of a rapid flux of acetate oxidation in liver and muscle cells. More specifically, the effects of rapid acetate metabolism on tissue ATP, CoA, adenosine and other ATP degradation products are presented. The possible impact of dialysis-induced depletion of carnitine on optimal acetate metabolism is discussed. The potential clinical consequences produced by these changes are presented in relation to the symptoms sometimes observed during dialysis against acetate: vasodilation, hypotension and angina pectoris. The hypoxemia induced by acetate is also briefly reviewed. Different directions are proposed for future research.
 ...
PMID:Acetate metabolism during hemodialysis: metabolic considerations. 332 61

Earlier we have shown in the dog model mimicking angina on effort a delayed antiischaemic effect of PgI2 and its stable analogue 7-oxo-PgI2-Na, appearing only when the drug induced marked vasodilatation was over [1]. In the present experiments we could show that the protective effect appears at a time when the blood pressure returned to normal and in addition the marked platelet aggregation inhibitory effect has also faded away. In the rat 7-oxo-PgI2 could substantially diminish vasopressine induced T-wave elevation in the ECG if given 2 hours before administration of vasopressin. In addition it could moderate the vasopressin induced metabolic changes appearing as diminution of the myocardial CP and ATP-level and increase of the myocardial lactate content. A similar metabolic protection was found in the heart of rats pretreated with 7-oxo-PgI2 2 hours before taking myocardial samples and exposing them for 1 minute to ischaemia by incubation in Ringer solution. It is concluded that a direct metabolic and hemodynamic effect could be at least partly responsible for the late antiischaemic effect of 7-oxo-PgI2. This effect was also present in the early phase of experimental myocardial infarction in conscious rats if animals were pretreated with 7-oxo-PgI2 2 hours before occlusion. However treatment did not increase survival rate and failed to reduce the incidence and severity of arrhythmias.
 ...
PMID:On the late antiischaemic action of the stable PgI2 analogue: 7-oxo-PgI2-Na and its possible mode of action. 639 60

Nicorandil is a balanced arterial and venodilator that may also possess cardioprotective properties via its activation of ATP-sensitive potassium channels. It has a number of beneficial hemodynamic effects and has been shown to be effective in treating angina with similar efficacy as the currently available antianginal agents. In addition, it may have useful effects in unstable and variant angina. In this review we examine the hemodynamic effects of nicorandil and discuss the currently available data on its clinical efficacy, both in isolation and in comparison with other agents.
 ...
PMID:Potassium channel openers: clinical applications in ischemic heart disease--overview of clinical efficacy of nicorandil. 764 27

The authors propose a new method of treating coronary patients with angina pectoris of effort and at rest. It involves combination of transesophageal pacing with simultaneous intravenous administration of phosphobion. The treatment given to 10 coronary patients produced positive antiischemic and hemodynamic effect against its absence in control subjects treated conventionally with ATP.
 ...
PMID:[Therapeutic effect of intravascular phosphobion during transesophageal electric cardiostimulation in patients with ischemic heart disease]. 804 16

In vitro and in vivo studies suggest that opening of ATP-sensitive potassium channels following ischaemia enhances recovery of myocardial contraction, dilates blood vessels and has an antiarrhythmic effect. Different sulphonylurea compounds that block the ATP-sensitive potassium channels exert different effects on cardiac functions. Glibenclamide decrease, arrhythmogenesis during acute myocardial infarction in rats and reduces strophanthin cardiotoxicity in rabbits. Other sulphonylurea compounds, but not glibenclamide, increase arterial blood pressure and myocardial contractility. These effects may be partly secondary to blockade of ATP-sensitive potassium channels and partly due to independent cardiac and extracardiac actions. Glimepiride may have a more advantageous cardiovascular effect than glibenclamide. The studies suggest the hypothesis that deleterious cardiovascular effects of some hypoglycaemic sulphonylurea drugs may contribute to the high cardiovascular mortality rate in diabetes mellitus. An observational study suggested glibenclamide decreased the incidence of fatal myocardial infarction and development of ventricular fibrillation in patients suffering from acute myocardial infarction. Glibenclamide may also decrease the incidence of ventricular ectopic beats in digitalized patients compared with other sulphonylurea compounds. The studies suggested the survival of subjects treated with glibenclamide, insulin, or diet alone after the first attack of angina pectoris or after first acute myocardial infarction may be longer compared with those on other sulphonylurea therapies. Further large scale prospective, randomised studies are needed to determine whether the reported effects can be verified and are sufficiently large to affect clinical prescribing.
 ...
PMID:Potassium channels in the cardiovascular system. 852 23

Many cells are equipped with so-called potassium (K+) channels which have an important role in maintaining transmembrane potential. Closure of these channels leads to membrane depolarization, which can be followed by cell-specific activity such as contraction of vascular smooth muscle, or secretion of insulin from pancreatic beta-cells. Therefore, it is not surprising that a number of drugs have been introduced which influence K+ channels by either blocking or opening them. The treatment of type 2 (non-insulin-dependent) diabetes mellitus with sulphonylurea derivatives (SU), which exert their insulinotropic effect by closing the K+[ATP] channels of the pancreatic beta-cell, is customary. Slight differences are described in the insulinotropic action of the various SU. Claims in the past that treatment with SU increases cardiovascular mortality are not supported by sound evidence. SU may even reduce cardiovascular mortality by protecting against ventricular arrhythmias during cardiac ischaemia. K+[ATP]-channel-opening drugs are under investigation for the treatment of essential hypertension and angina pectoris. They are at least as effective in achieving adequate blood pressure control as calcium channel blockers. The recently introduced coronary vasodilating drug, nicorandil, exerts its effect by two mechanisms of action: opening K+[ATP] channels in vascular smooth muscle cells of coronary arteries and activation of guanidyl cyclase by its nitro-group in these cells. A proarrhythmic effect of K+[ATP] channel openers has only been observed at very high doses, but not in the low doses used in angina pectoris and hypertension. In vivo no negative effect of K+[ATP]-channel-opening drugs on insulin secretion is found.
 ...
PMID:Clinical relevance of ATP-dependent potassium channels. 854 97

There have been hints over the years about the involvement of purines in pain, and we now have direct evidence with the cloning and characterisation of extracellular receptors for ATP (P2X-purinoceptors) on nociceptive sensory neurons. In this article, a hypothesis is put forward about the sources of ATP released to activate these receptors in three different pain conditions--as a cotransmitter from sympathetic nerves in causalgia and reflex sympathetic dystrophy; from endothelial cells in vascular pain, including migraine and angina; and from tumour cells in cancer. These findings are leading to an active search for selective P2-purinoceptor antagonists to alleviate pain.
 ...
PMID:A unifying purinergic hypothesis for the initiation of pain. 866 73

Ischemic preconditioning has been shown to be one of the most powerful means of protecting the myocardium from ischemic injury in experimental animal models, although the mechanism is incompletely understood. In this review we discuss the evidence for preconditioning occurring in ischemic syndromes in humans, whether the human myocardium can be preconditioned, and whether preconditioning would have a place as a therapeutic tool in clinical practice. Some studies evaluating patients after acute myocardial infarction have shown a better outcome in patients reporting angina before the onset of the infarction, but this is not a universal finding, and it is difficult to exclude other confounding factors, such as collateral flow, from influencing the results. More controlled prospective studies have evaluated patients undergoing percutaneous transluminal coronary angioplasty and have found less ST-segment change and less reported angina during the second balloon inflation when compared with the first. Again, it is impossible to completely exclude other causes for this effect, but the dependence on mechanisms that are known to be important for preconditioning in animal models does suggest the phenomena are the same. Further experiments using isolated human atrial muscle have shown that human myocardium can be preconditioned and that the mechanisms involved are similar to those elucidated in animal models (adenosine, protein kinase C, and ATP-dependent potassium channels). In clinical medicine preconditioning is most likely to benefit patients when it is used to protect against the ischemia induced by cardiac surgery. In this respect, a study has shown that in patients undergoing coronary artery bypass grafts, the reduction in ATP occurring during the first ischemic period is attenuated in those given an ischemic preconditioning protocol beforehand. Despite these advances, it is likely that the full potential of preconditioning in clinical practice will not be realized until the whole mechanism of protection is understood and a safe pharmacological "preconditioning" agent becomes available.
 ...
PMID:Preconditioning the human myocardium: recent advances and aspirations for the development of a new means of cardioprotection in clinical practice. 885 Mar 77

Cardiac L-carnitine content, essential for mitochondrial fatty acid transport and ATP-ADP exchange, decreases during ischemia. In animal models, administration of the natural derivative, L-propionylcarnitine, may reduce ischemia and improve cardiac function. To evaluate possible antiischemic effects of L-propionylcarnitine was compared with placebo in a randomized, double-blind, parallel design, in addition to preexisting therapy. Patients with > or = 2 anginal attacks per week and objective signs of ischemia with angina during bicycle exercise testing were included. After an initial 2-week, single-blind placebo phase, 37 patients received 500 mg L-propionylcarnitine tid, and 37 patients received placebo for 6 weeks. Both groups were comparable at baseline. Three patients discontinued the study while on placebo (two because of noncompliance, one because of palpitations) and one while on L-propionylcarnitine (noncompliance). Although heart rate, blood pressure at rest, and maximal exercise were not affected, L-propionylcarnitine increased the time to 0.1 mV ST-segment depression [44 +/- 3 vs. 8 +/- 2 seconds (mean +/- SEM) in the placebo group; p = 0.05], and exercise duration improved by 5% compared with placebo. Anginal attacks and the consumption of nitroglycerin were not affected in either group. Thus, following a 6 week treatment period, L-propionylcarnitine induced additional, albeit marginal, antiischemic effects in anginal patients who were still symptomatic despite maximal conventional antianginal therapy. It is questionable whether in these patients this form of metabolic treatment will achieve great benefit, although in some improvement can be expected.
 ...
PMID:Additional antiischemic effects of long-term L-propionylcarnitine in anginal patients treated with conventional antianginal therapy. 885 Mar 78

Within a few seconds after a sudden reduction of coronary blood flow regional contractile dysfunction ensues. The mechanisms responsible for the rapid reduction in contractile function during acute myocardial ischemia remain unclear, but may involve a rise in inorganic phosphate. When severe ischemia, such as resulting from a sudden and complete coronary artery occlusion, is prolonged for more than 20-40 min, myocardial infarction develops, and there is irreversible loss of contractile function. When myocardial ischemia is less severe but nevertheless prolonged, the myocardium is dysfunctional but can remain viable. In such ischemic and dysfunctional myocardium, contractile function is reduced in proportion to the reduction in regional myocardial blood flow; i.e. a state of "perfusion-contraction matching" exists. The metabolic status of such myocardium improves over the first few hours, as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns towards control values. Ischemic myocardium, characterized by perfusion-contraction matching, metabolic recovery and lack of necrosis, has been termed "short-term hibernating myocardium". Short-term hibernating myocardium can respond to an inotropic stimulation with increased contractile function, however, at the expense of a renewed worsening of the metabolic status. This situation of an increased regional contractile function at the expense of metabolic recovery during inotropic stimulation can be used to identify short-term hibernating myocardium. When inotropic stimulation is prolonged, the development of short-term hibernation is impaired and myocardial infarction develops. The mechanisms responsible for the development of short-term myocardial hibernation remain unclear at present; a significant involvement of adenosine and of activation of ATP-dependent potassium channels has been excluded. Whereas short-term hibernation is well characterized in animal experiments, the existence of hibernation over weeks or months (long-term hibernation) can only be inferred from clinical studies. Hibernation, as defined by Rahimtoola, is a state of chronic contractile dysfunction which is fully reversible upon reperfusion. Clinical syndromes consistent with the existence of myocardial hibernation include unstable and stable angina, acute myocardial infarction and left ventricular dysfunction and/or congestive heart failure. In long-term hibernating myocardium morphological alterations occur; the myofibrils are reduced in number and disorganized and myocardial glycogen content as well as the extracellular collagen network are increased. Thus, despite the fact that the myocardium remains viable during persistent ischemia and contractile dysfunction is reversible upon reperfusion, there are severe morphological alterations. Understandably, full functional recovery following reperfusion might therefore require weeks or even months.
 ...
PMID:Hibernating myocardium: a review. 900 53


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