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

Enzymatic hydrolysis with beta-glucuronidase/sulfatase was used for the enantioselective determination of N-hydroxymexiletine glucuronide in plasma for pharmacokinetic studies. N-Hydroxymexiletine glucuronide was determined as the quantity of mexiletine released by hydrolysis (difference between the enantiomeric concentrations of mexiletine obtained with and without hydrolysis). Plasma samples (100 microliters) were treated at pH 5.0 with 10 mg of the enzyme (Limpet Acetone Powder type I) for 16 hr at 37 degrees C and extracted at pH 10.4 with diisopropyl ether. Chiral mexiletine discrimination was obtained by reaction with o-phthalaldehyde/N-acetyl-L-cysteine, separation of the resulting diastereomers on a C-18 reversed-phase column with a mobile phase of methanol-0.05 N acetate buffer, pH 5.5 (6.5:3.5, v/v), and fluorescence detection (lambda ex 350 nm, lambda em 455 nm). The performance characteristics for the enantioselective analysis of mexiletine preceded by enzymatic hydrolysis were recovery approximately 90%, quantification limit 1 ng/ml, and linearity up to 1000 ng/ml plasma for both enantiomers. The coefficients of variation obtained in the study of intra- and inter-day precision were respectively 5% and 7% for both enantiomers. The assay was shown to be suitable for a pharmacokinetic study performed in a patient with the arrhythmic form of chronic Chagas' heart disease treated with 200 mg t.i.d. of racemic mexiletine hydrochloride. The high sensitivity of the method allows analysis of only 100 microliters plasma.
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PMID:Enantioselective analysis of N-hydroxymexiletine glucuronide in human plasma for pharmacokinetic studies. 995

Cardiovascular risk associated with hormone replacement therapy (HRT) has been analysed by large epidemiological studies. This treatment has different effects depending on the type of vessel (venous or arterial) or site (heart or brain). The several meta-analyses which have been published conclude that there is a significant decrease of about 30 to 50 per cent in ischaemic heart disease associated with HRT. In addition, oestrogen replacement therapy is associated with a 25 per cent decrease in cardiovascular mortality. A recent meta-analysis has analysed the effect of HRT on cerebrovascular risk. A significant 20 per cent increase in ischaemic stroke associated with the use of HRT has been shown. However, a protective association of about 30 per cent has been observed in haemorrhagic stroke with HRT use. Recent epidemiological studies have suggested an increased risk of thromboembolic disease associated with HRT. The results of a randomized blind placebo-controlled secondary prevention trial have recently been published. In this clinical trial, women who receive oestrogen (0.625 mg conjugated equine oestrogen daily) plus progestin (2.5 mg medroxyprogesterone acetate daily) therapy did not experience a reduction in overall risk of non-fatal myocardial infarction and cardiovascular heart disease death. This treatment also significantly increases the rate of thromboembolic events. Other randomized trials of HRT for primary prevention are scheduled to yield results by 2000 or 2005. All these studies have been conducted essentially in Anglo-Saxon countries and have analysed the effects of conjugated equine oestrogens alone or combined with medroxyprogesterone acetate. This treatment is not currently used in France. But no randomized trials are under way with the HRT common in France (transdermic oestrogen combined with natural progesterone). The effects of this treatment on cardiovascular disease remain unknown.
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PMID:[Cardiovascular risk and hormone replacement therapy in menopause]. 1050 Apr 54

A general health survey was conducted in nonpregnant and noncontracepting women aged 15-44 years to determine the presence of any health problems that might affect the use of depot-medroxyprogesterone acetate (DMPA) as a contraceptive method in rural district in Nepal. The survey included a general assessment interview by nonphysicians, followed by formal medical histories and physical exams by female gynecologists. Findings revealed that a possible pregnancy (9 cases) and abnormal uterine bleeding (1 case) were the only conditions identified in which DMPA should not be used based on the WHO Medical Eligibility Criteria for Contraceptive Use. 5 additional cases of cardiovascular problems, in which DMPA initiation was not usually recommended, were also detected. The reports included heart disease (2 cases), past history of hypertension (1 case), current hypertension (1 case), and headache and hypertension (1 case).
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PMID:Conditions in rural Nepal for which depot-medroxyprogesterone acetate initiation is not recommended: implications for community-based service delivery. 1054 50

In the premenopausal period, the risk of heart disease is considerably lower in women than in men; however, in the postmenopausal period, when estrogen levels are considerably lower, women's risk of heart disease increases dramatically and approaches that of men. Numerous animal studies, using a variety of models, also confirm estrogen's cardioprotective effect. Although the results of numerous population-based, observational studies have demonstrated a lower risk of heart disease in women who receive estrogen replacement therapy, evidence from prospective, randomized clinical trials is scant. The Postmenopausal Estrogen/Progestin Intervention (PEPI) trial evaluated cardiovascular risk factors, not events, in a large, prospective, randomized trial and found that estrogen improved lipid profiles and other known risk factors. In addition, the PEPI trial compared several estrogen/progestogen treatment regimens, including both medroxyprogesterone acetate (MPA) and micronized progesterone (MP), and found that combined hormone replacement therapy regimens including MP attenuated the beneficial effects of estrogen less than those containing MPA. In the Heart and Estrogen/Progestin Replacement Study (HERS), however, which prospectively evaluated whether estrogen and MPA use reduced the number of nonfatal myocardial infarctions and cardiovascular events, no effect was seen. Although HERS was a null trial, the vast literature base showing a cardioprotective effect should not be discounted. Further research will be required before blanket recommendations on the cardioprotective effects of hormone therapy can be made.
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PMID:Preserving cardiovascular benefits of hormone replacement therapy. 1075 7

Congestive heart failure is a growing public health problem and continues to be characterized by a poor prognosis. Its prevalence may be estimated at 0.4-2% of the general population with an incidence varying from 1-10% in elderly patients. This may be in part explained by the progressive aging of the population and the more effective therapeutic strategies for coronary heart disease and hypertension: since they increase the life-expectancy of patients, they favor the onset of this clinical syndrome at a more advanced age. The number of hospital admissions has also increased; mortality is 50% within 4 years of diagnosis, although patients with very severe cardiac decompensation die within 1 year. Despite the fact that with the use of the most advanced molecules created by pharmacological research (ACE inhibitors, beta-blockers, angiotensin-II-receptor antagonists) a significant reduction in morbidity and mortality as well as clear improvement of symptoms and quality of life have been obtained in diverse clinical trials, there is still no certain evidence that in the general population, mortality due to chronic heart disease has been reduced. In our opinion, several factors explain the gap between the favorable results of clinical trials and the lack of significant reduction in morbidity and mortality in clinical practice: A) the selection criteria utilized in clinical studies exclude, for the most part, patients present in general population; B) the average age of the patients included (60 years) is not representative of the overall population; C) patients with associated co-morbidity are generally excluded; D) the number of women enrolled in the trials is quite low; E) compliance is certainly better in the trials than in clinical practice; F) higher drug dosages are used in the trials than in clinical practice. To intervene in these areas and thus make the positive results obtained in the trials available to the general population is, in our opinion, the principal challenge of the future. For this task, the close collaboration and commitment of the internist, the geriatrist, the cardiologist and the family doctors is necessary so that the results reported in clinical trials may be translated into general medical practice.
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PMID:[The difficulties of translating into daily clinical practice the favorable results of clinical trials in chronic heart failure]. 1084 89

Thyroid hormones influence cardiac performance directly and indirectly via changes in peripheral circulation. Little, however, is known about the effect on myocardial oxidative metabolism and its relation to cardiac function and geometry. Patients with a history of thyroidectomy for thyroid cancer present a unique model to investigate the cardiac effects of hypothyroidism. Ten patients without heart disease were investigated in the hypothyroid state and again 4-6 weeks later under euthyroid conditions. Myocardial oxidative metabolism was measured by positron emission tomography with [11C]acetate and the clearance constant k(mono). Cine magnetic resonance imaging was applied to determine left ventricular geometry. A stroke work index (SWI = stroke volume x systolic blood pressure/ventricular mass) was calculated. Then, to estimate myocardial efficiency, a work metabolic index [WMI = SWI x heart rate/k(mono)] was obtained. Compared to hormone replacement, systemic vascular resistance and left ventricular mass were significantly higher in hypothyroidism. Ejection fraction and SWI were significantly lower. Despite an additional reduction of k(mono), the WMI was significantly lower, too. In summary, cardiac oxygen consumption is reduced in hypothyroidism. This reduction is associated with increased peripheral resistance and reduced contractility. Estimates of cardiac work are more severely suppressed than those of oxidative metabolism, suggesting decreased efficiency. These findings may provide an explanation for development or worsening of heart failure in hypothyroid patients with preexisting heart disease.
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PMID:Effect of thyroid hormones on cardiac function, geometry, and oxidative metabolism assessed noninvasively by positron emission tomography and magnetic resonance imaging. 1084 59

Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy. The ARBs specifically block the interaction of angiotensin II at the AT1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development. The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect. The variation in the molecular structure of the ARBs results in differences in the binding affinity to the receptor and pharmacokinetic profiles. The differences observed in lipid solubility, absorption/distribution, plasma protein binding, bioavailability, biotransformation, plasma half-life, and systemic elimination influence the time of onset, duration of action, and efficacy of the ARBs. On the basis of the daily mg dose, the antihypertensive potency of the ARBs follows the sequence: candesartan cilexetil > telmisartan approximately = losartan > irbesartan approximately = valsartan > eprosartan. After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels = 0.5-4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60-80% for irbesartan); food does not influence the bioavailability, except for valsartan (a reduction of 40-50%) and eprosartan (increase). A limited dose-peak plasma levels/areas under the plasma level-time curve proportionality is observed for some of the ARBs. Most of these drugs have high plasma protein binding (95-100%); irbesartan has the lowest binding among the group (90%). The steady-state volumes of distribution vary from a low of 9 L (candesartan) to a high of 500 L (telmisartan). (ABSTRACT TRUNCATE
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PMID:Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. 1085 85

Heart disease is the major cause of mortality in the developed world. Despite recent advances in the therapy of heart failure due to ACE inhibitors and beta-blockers, the prognosis of this syndrome is still poor. In the past few years, the effects of growth hormone (GH) and insulin-like growth factor-I (IGF-I) on heart morphology and function were extensively studied. Some studies dealing with experimental heart failure of animals and one controversial study dealing with human heart failure suggest positive hemodynamic effects of GH and/or IGF-I treatment. This review summarizes the physiological effects of GH/IGF-I on the myocardium, their signal transduction mechanisms, and the data currently available on the therapeutic use of these agents.
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PMID:[Hormone therapy in heart failure: growth hormone and insulin-like growth factor I]. 1102 Dec 70

Diabetes mellitus as a disease of epidemiological impact leads to diabetic cardiopathy by modulation of myocardial, vascular and metabolic components. This includes the development of a coronary microangiopathy and a decrease of diastolic and systolic function of the left ventricle as well as the development of an autonomic diabetic neuropathy. Patients with diabetes show an increased mortality concerning cardiovascular events. They more often suffer from myocardial infarction as non-diabetics mostly with a more serious course. Moreover, the post-infarction course is affected with a worse prognosis as in non-diabetics. For diagnosis of cardial involvement in diabetes electrocardiographic and echocardiographic procedures are of use. Special tests of the autonomic function complete the diagnostic ensemble. An early therapy with ACE-inhibitors and beta blocking agents as well as a strong diabetes therapy, in particular with insulin, can influence the mortality favorably. Moreover, the diagnosis and therapy of additional cardiovascular risk factors (arterial hypertension, dyslipidemia) are very important, because these are correlated with a for diabetic patients markedly increased risk of mortality. The clinical relevance of the term diabetic cardiopathy is justified by the 6 factors: macroangiopathy, microangiopathy, disturbances of the myocardial metabolism, myocardial fibrosis, autonomic diabetic neuropathy and disturbances of the coagulability. Diagnostic and therapeutic goals are discussed.
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PMID:[Cardiac complications in diabetes mellitus]. 1102 65

We tested the hypothesis that treatment of mdx mouse muscular dystrophy with the glucocorticoid deflazacort prevents cardiomyopathic lesions and is accompanied by changes in metabolism and gene expression that reflect the improved tissue integrity. Cardiac muscle pathology, expression of alpha-cardiac myosin heavy chain, DNA synthesis, laminin, and basic fibroblast growth factor (bFGF) were examined to characterize dystrophy and changes with treatment. The potential of proton magnetic resonance spectroscopy (H-NMRS) to track cardiac dystrophy and deflazacort effects was also studied. Deflazacort (but not equipotent prednisone) reproducibly decreased lesion prevalence and severity. Treatment also produced cardiomyocyte hypertrophy and a 5.4-fold increase in alpha-cardiac myosin content. Expression of bFGF messenger RNA (mRNA), notable around lesions, rose 3.3-fold, and laminin expression rose 2.1-fold after deflazacort. Studies using H-NMRS showed a cardiac "signature" with less glycine and taurine than limb muscle or diaphragm and shifts with progression of dystrophy (distinct from normal aging) in many metabolites. Increased taurine, acetate, and succinate were present after 2 weeks of deflazacort treatment but were not present after 4 weeks. Although paired kinetic and functional studies of myocardium will be needed to determine the origin of such changes, these results demonstrate the potential application of H-NMRS to monitor clinical heart disease and treatment. In addition, the metabolic effects of deflazacort were substantial in preventing the progression of cardiomyopathy in mdx mice and included increased expression of protectant and stabilizing factors and hypertrophy of cardiac myocytes.
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PMID:Metabolic shifts and myocyte hypertrophy in deflazacort treatment of mdx mouse cardiomyopathy. 1118 Feb 2


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