Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vivo determination of the density of dihydropyridine (DHP) binding sites will allow the assessment of pathophysiological changes associated with heart disease. The calcium channel antagonist S 11568: (+/-)(amino-7 dioxa-2,5 heptyl)-2(dichloro -2,3 phenyl) -4 methyl-6dihydro -1,4 pyridine has an in vitro profile of high potency and of high selectivity for the L-type Ca2+ channel. S 11568 was labelled by a reaction between 11C-diazomethane and the precursor 6-(7-amino-2,5-dioxa heptyl)-4-(2,3-dichloro phenyl)-5-(ethoxycarbonyl)-2 methyl-1,4 dihydro nicotinic acid. (+)-PN 200 110, a DHP with in vitro high affinity for the L-type Ca2+ channel, was also radiolabeled. Positron emission tomographic (PET) studies of both 11C-DHP myocardial uptake were performed in Beagle dogs. 11C-(+)-PN 200 110 had a rapid wash-out from myocardium. In contrary, after a bolus injection, 11C-S 11568 myocardial concentration increased to reach a maximum in 1-2 minutes and then remained in a plateau with a slight downslope while the blood concentration fell rapidly. Myocardial uptake was 2 to 4 fold higher than lung uptake, leading to a good contrast on PET images. Pre-treatment with unlabeled S 11568 (2 mumol/kg or 6 mumol/kg over 15 minutes) reduced myocardial uptake by 60% and 80%, respectively. Specific binding was estimated during a displacement experiment: bolus of unlabeled S 11568: 1 mumol/kg followed by a continuous infusion of 3 mumol/kg over 2 hours. It was found to represent 80% of the total binding. To assess influence of S 11568 on coronary blood flow and therefore on the myocardial tracer delivery, coronary blood flow was measured using 15O-H2O and PET at baseline and following bolus injections of 0.4, 0.8, 2 mumol/kg of S 11568. Only the higher dose increased coronary blood flow. This is the in vivo demonstration of the binding characteristics to myocardial tissue of a DHP ligand. Such properties make S 11568 suitable for PET experiments. The studies of DHP binding sites will provided new insights concerning physiological situations as well as heart disease.
 ...
PMID:Canine myocardial dihydropyridine binding sites: a positron emission tomographic study with the calcium channel inhibitor 11C-S11568. 796 14

Propafenone hydrochloride, a class 1C antiarrhythmic agent, combines sodium channel-blocking effects with beta-blocking capacities and a weak calcium antagonism. The drug exerts marked electrophysiologic effects on accessory atrioventricular pathways. In patients with atrioventricular nodal reentry tachycardia, propafenone is able to block conduction in the fast conducting pathway. In addition, propafenone is very effective in young patients with supraventricular tachycardia based on enhanced abnormal automaticity. In pediatric patients, left ventricular performance remains unimpaired. Proarrhythmic events have been noted in children only occasionally. In accordance with the electrophysiologic profile, intravenous and oral propafenone is an effective agent for treatment of supraventricular tachycardia based on a reentry mechanism and due to abnormal automaticity (i.e., supraventricular tachycardia based on an accessory atrioventricular pathway, atrioventricular nodal reentry tachycardia, junctional ectopic tachycardia, and atrial ectopic tachycardia). In children with ventricular dysrhythmias, efficacy seems to be related to the underlying cardiac diagnosis. Propafenone is well tolerated in the majority of young patients. Incidence of proarrhythmic events seems to be lower with propafenone than with other class 1C agents. However, the risk of these serious adverse events should be taken into account when therapy with propafenone is considered, particularly in patients with structural heart disease.
 ...
PMID:New antiarrhythmic drugs in pediatric use: propafenone. 799 37

After heart disease, cancer and stroke, Alzheimer's disease (AD) is the fourth major cause of death in the developed countries. Due to demographic changes, this situation will further worsen in the future. With the use of molecular biology techniques, important progress has recently been made in the understanding of the molecular changes leading to some forms of this disabling illness. The first step was the partial sequencing of the amyloid protein accumulating in the senile plaques and vascular deposits characteristic of AD. This allowed the cloning of a cDNA coding for a long amyloid precursor protein (APP). During the last few years, independent reports have described the presence of several reproducible point mutations in specific codons of APP in early onset familial Alzheimer patients. These mutations are responsible for an abnormal processing of APP, leading to the formation of pathological beta/A4 amyloid deposits. beta/A4 has been shown to possess neurotrophic properties in embryonic neurones and to be a potent neurotoxic agent in differentiated hippocampal neurones. More recently, modifications of intracellular calcium, activation of kinases, free radical generation and anomalies in potassium channels have been described as possible mechanisms of beta/A4 toxicity. Some forms of Apo-E lipoprotein may be an additional risk factor. Hence, it now seems possible to elaborate a coherent theory to explain the cascade of events leading to the development of AD. Genetically induced point mutations or environmental factors may produce a modification of the APP metabolism and processing. As a consequence, abnormal deposits of beta/A4 are formed. They may exert direct or indirect neurotoxic actions. A degeneration of cholinergic, catecholaminergic and other neurones follows, leading to the well known cognitive and behavioural changes of AD.
 ...
PMID:Towards a pharmacological approach of Alzheimer's disease based on the molecular biology of the amyloid precursor protein (APP). 799 77

The purpose of this review is to examine current research on the iron status of the elderly and factors that influence the body burden of iron. Studies of noninstitutionalized elderly individuals report mean iron intakes that meet current Recommended Dietary Allowances for iron. Dietary practices that may decrease iron bioavailability, and hence iron stores in the body, include low intakes of ascorbic acid or high intakes of calcium, and decreased consumption of highly available iron from meat, fish, and poultry. Although not well documented, the effect of age on iron absorption and iron excretion appears to be small, and body stores of iron increase with age. It is difficult to estimate the prevalence of iron deficiency in elderly persons, because impaired iron status can be the result of iron deficiency or chronic disease. Further study is necessary to determine whether red blood cell ferritin and serum transferrin receptors may be useful biochemical markers to differentiate the anemia of chronic disease from iron deficiency anemia. Hereditary hemochromatosis is a genetic disease that greatly increases the body burden of iron and the risk of hepatic disease among homozygotes. Because iron deficiency or iron excess may impair health, the role of iron in diseases associated with aging such as depressed immune response, neurological dysfunction, cancer, and heart disease is discussed.
 ...
PMID:Iron nutriture in elderly individuals. 800 89

Heart disease still pervades all socioeconomic classes within the United States. Understanding the effects of environmentally-related pathogenesis (e.g., heavy metal accumulation) may aid in developing novel treatments for the prevention of heart dysfunction. The aim of this report was to use experimental investigation in an attempt to expand upon the multivariate importance of divalent cation interactions in the development of heart disease. Calcium and cadmium levels were measured by flame atomic absorption spectrophotometry in various tissues derived from two types of hypertensive rabbit models. Both models of hypertension developed mean arterial pressures of at least 50 mm mercury greater than those of controls over a 5 week period. Interrelationships between calcium and cadmium levels were found to exist for both hypertensive groups in the left ventricle, aorta, and renal medulla. The renal cortex showed no such interrelationship for the renal hypertensive group. Multiple interrelationships between calcium and cadmium levels and hypertrophy were also observed. These studies related the importance of endogenous or exogenous (viz, environmental) factors governing cadmium and calcium accumulation in hypertensive rabbits. The resulting relationships between divalent cations and hypertrophy were presented to draw attention to areas which remain unexplored with perspective to cardiovascular disease.
 ...
PMID:Divalent cations in hypertension with implications to heart disease: calcium, cadmium interactions. 800 48

We present three patients without significant coronary or other structural heart disease who were resuscitated after ventricular fibrillation attributed to coronary spasm. Angina pectoris was present in two of the cases and silent myocardial ischemia in the third. All patients were given calcium antagonists at discharge. A defibrillator was also implanted in the patient with silent myocardial ischemia because further episodes of ischemia would probably have occurred without premonitory symptoms. Coronary spasm might be a mechanism of ventricular fibrillation in patients without significant structural heart disease. Diagnostic tests should therefore be performed to confirm or exclude coronary spasm in such cases. The implantation of an automatic defibrillator seems justified in selected patients with documented coronary spasm, silent myocardial ischemia, and associated sustained ventricular tachyarrhythmia, although prospective studies are not yet available.
 ...
PMID:Ventricular fibrillation related to coronary spasm in patients without significant coronary or other structural heart disease. 804 79

Substantial evidence indicates that T wave alternans is an intrinsic property of ischemic myocardium. The electrophysiologic basis appears to be spatial and temporal heterogeneity of repolarization resulting from changes in action potential morphology rather than in activation sequence. Ischemia-induced changes in postrepolarization refractoriness and depressed electrical restitution of action potential duration have also been implicated. The main underlying ionic basis for T wave alternans during coronary occlusion appears to be derangements in intracellular cycling of calcium. Accumulation of potassium in the extracellular space adjoining ischemic cells and disruption in electrogenic sodium-calcium exchange may also be involved. In humans, T wave alternans has been observed in Prinzmetal's and classical angina, angioplasty, and bypass graft occlusion. Under these conditions associated with acute myocardial ischemia, alternans is restricted to the ischemic zone, and alternation in action potential morphology is an underlying factor. Recently, repolarization alternans has been shown to be a statistically significant predictor of the results of electrophysiologic testing and arrhythmia-free survival in individuals with and without organic heart disease. Collectively, these observations provide a rationale for quantitation of T wave alternans magnitude for assessment of vulnerability to life-threatening ventricular arrhythmias both in response to and independent of the effects of myocardial ischemia.
 ...
PMID:Electrophysiologic basis for T wave alternans as an index of vulnerability to ventricular fibrillation. 805 49

The safety of autologous blood donation by "high-risk" patients (those with some preexisting medical conditions) has been questioned. The authors reviewed 1393 consecutive blood donation records (207 high-risk autologous [HRA], 665 non-high-risk autologous [NHRA], and 521 directed donors [DD]) to determine the safety and outcome of blood donation by HRA patients as compared with other donors at their center. The HRA group included patients with a history of significant coronary artery on cerebral vascular disease, recent seizures, cardiac arrhythmia, chronic heart failure, valvular or congenital heart disease, symptomatic dyspnea, insulin-dependent diabetes and/or current therapy with two or more antihypertensive medications. Those designated NHRA were all other autologous donors; DD met all criteria for homologous donation. Donor characteristics including predonation hematocrit, pre- and postdonation mean arterial pressure and heart rates were similar in all groups. Eight HRA donors (3.9%) had reactions, compared with 21 NHRA (3.2%) and 23 DD (4.4%), a difference that was without statistical significance. The reaction rate in all autologous donors (HRA and NHRA) was 3.4%. No differences in symptoms reported, hemodynamics or reaction severity were observed among the three groups (P > .05). A multiple logistic regression was performed within and among the groups with the risk factor categories listed above and medication classes including beta blockers, cardiac glycosides, calcium-channel blockers, antihypertensive agents, nitrates, and antiarrhythmic agents (chi 2 = 14.9; P = .0006). Only first-time donation (P = .0001) and cardiac glycoside usage (P = .04) were positively associated with an untoward reaction. The authors conclude that donation by HRA donors is at least as safe as that by donors who meet homologous donation criteria in their population and setting.
 ...
PMID:Comparable safety of blood collection in "high-risk" autologous donors versus non-high-risk autologous and directed donors in a hospital setting. 787 63

Practical feasibility and clinical tolerability of low dose heparin given subcutaneously for the prevention of reinfarction were evaluated in this open, multicentric trial of post-marketing surveillance. 309 investigators participated. 2830 evaluable patients (2090 M, 709 F, mean age 63 years) who had in the previous 2 years a myocardial infarction were treated subcutaneously with calcium heparin (Calciparina Italfarmaco, 0.5 ml prefilled syringe) at the daily dosage of 12.500 U. The foreseen treatment length was of 1 year; after 6 months of daily injections, calcium heparin could be taken for cycles of 30 days, with 10 day intervals. The enrolled patients resulted to be representative of the population affected with ischemic cardiopathy. One year treatment with calcium heparin was completed by 2040 patients (72.1%); about 1/4 of the patients did not complete the protocol. Patient's subjective decision to withdraw accounted for 46.3% of withdrawals; poor tolerability accounted for 15% of withdrawals (3.8% of total patients). Overall, 237 patients (8.4%) suffered from adverse reactions (353 complaints). Local reactions at the injection site accounted for 60% of total adverse reactions, involving 7.5% of total cases. To follow, allergic reactions (2.5%) and other different types of adverse reaction (incidence less than 0.5%). By analyzing the reactions that provoked drug withdrawal, no organ or function (e.g.: haemostasis) were found to be at risk during the heparin treatment. 64 patients died during the trial. These deaths were in prevalence due to cardiovascular diseases: ventricular fibrillation, cardiac failure, arterial thromboembolism (cardiac reinfarction, stroke).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[The feasibility and tolerability of prolonged treatment with low doses of heparin-calcium administered subcutaneously in infarct patients. A multicenter clinical study]. 810 97

The QT interval is the period from onset of the QRS complex to the end of the T wave. The QT interval is useful for monitoring drug (eg, quinidine) and electrolyte (eg, calcium) effects on the heart. It depends principally on heart rate (HR), and the relationship between QT interval and HR has been expressed for human beings and for dogs. The purpose of the study reported here was to quantify that relationship for dogs and to assess whether body weight also influenced QT interval. The ECG was recorded from 17 dogs, ranging in weight between 7 and 25 kg. Dogs were anesthetized with fentanyl/droperidol/ketamine, and HR was accelerated by administration of graded doses of atropine. A significant relationship was not found between QT interval and body weight. Despite changes in HR during sinus arrhythmia, a significant relationship was not found between QT and RR intervals. The QT interval vs HR accelerated by atropine was analyzed for all dogs and for small (7 to 10 kg, n = 5), medium (10 to 20 kg, n = 7), and large dogs (20 to 25 kg, n = 5). Equations relating QT interval to mean HR were calculated for each group. Our data may serve as a baseline with which to compare QT intervals from dogs with heart disease and/or electrolyte imbalance.
 ...
PMID:Duration of QT interval in clinically normal dogs. 811 51


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