Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nitric oxide (NO), produced by either constitutive or inducible isoforms of NO synthase (cNOS or iNOS), influences myocardial inotropic and chronotropic responses. This pathway has been studied using NO donors or NOS inhibitors or by immune-mediated stimulation of iNOS. Although inhibition of constitutive NO activity in the heart does not influence indices of myocardial contractility, NO donors, in some species and preparations, may exert a negative inotropic effect as well as an enhancement of diastolic relaxation. The best documented cardiac action of NO is inhibition of the positive inotropic and chronotropic responses to beta-adrenergic receptor stimulation. Basal NO production, presumable via cNOS, appears to exert a mild tonic inhibition of beta-adrenergic responses. On the other hand, excessive NO production mediated by iNOS may contribute to the myocardial depression and beta-adrenergic hyporesponsiveness associated with conditions such as sepsis, myocarditis, cardiac transplant rejection, and dilated cardiomyopathy. Muscarinic cholinergic stimulation of the heart appears to stimulate NO production that mediates, at least partially, parasympathetic slowing of heart rate and inhibition of beta-adrenergic contractility. NO-stimulated production of 3',5'-cyclic guanosine monophosphate via guanylyl cyclase accounts for many of the observed physiological actions of NO. 3',5'-Cyclic guanosine monophosphate inhibits the beta-adrenergic-stimulated increase in the slow-inward calcium current and reduces the calcium affinity of the contractile apparatus, actions that could contribute to a negative inotropic effect, an abbreviation of contraction, and an enhancement of diastolic relaxation. Biochemical, immunocytochemical, and molecular biological techniques have been used to show the presence of both cNOS and iNOS within the myocardium. cNOS is expressed in myocytes, endothelial cells, and neurons in the myocardium, and there is evidence for iNOS in myocytes, small vessel endothelium, vascular smooth muscle cells, and immune cells that infiltrate the heart. Taken together, these observations suggest that NO influences normal cardiac physiology and may play an important role in the pathophysiology of certain disease states associated with cardiac dysfunction.
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PMID:Role of nitric oxide in the regulation of myocardial function. 756 4

Using methods of cytochemical investigation of the blood polymorphonuclear leucocytes (PMNL), parameters have been studied, characterizing the systems of biological defence and bioenergetics in patients with dilated cardiomyopathy (DCMP), infectious allergic myocarditis (IAM) and myocarditic cardiosclerosis (MCS). DCMP patients showed depression of NBT--test against the background of the increase in the cationic proteins (CP) level in the blood PMNLs, which was a major cytochemical feature. G-6-PhDG activity was increased in IAM patients against the background of high values of NBT-test. Increased values for G-6-PhDG, CP, phosphatases in the presence of low levels of myeloperoxidase in the blood PMNL suggest chronic inflammatory process in the myocardium. Investigation into the cytochemical parameters of bioenergetic and biological defence of the blood PMNL in patients with DCMP, IAM and MCS permits optimization of the diagnosis and treatment policy in the aforementioned nosological entities.
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PMID:[The cytochemical characteristics of the blood polymorphonuclear leukocytes in dilated cardiomyopathy and an inflammatory myocardial lesion]. 790 Mar 29

The efficacy of beta-blocking drugs in the treatment of chronic heart failure remains controversial. A major obstacle to their acceptance in this pharmacotherapeutic role has been their reputed negative inotropic effects and the resulting depression of cardiac function when given acutely to patients in heart failure. However, in a number of uncontrolled studies in patients in mild or moderate heart failure due to dilated cardiomyopathy, these drugs, when titrated from a low-dose starting point, have been shown to improve the surrogate endpoints of symptoms and certain haemodynamic parameters. It is presumed that this benefit is related to the improvement in myocardial contractile activity secondary to the gradual up-regulation of the depressed myocardial beta-receptors in patients with chronic heart failure. At present, the data regarding the improvement in exercise tolerance are conflicting and there are no published data on the influence of beta-adrenoceptor-blocking drugs on survival. The potential of beta-blocking drugs to improve the clinical state in some patients with heart failure is, however, being further explored in two prospective randomized trials.
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PMID:Beta blockers in heart failure. 810 58

The prognostic value of thallium-201 imaging in patients with unstable angina is not well established. Forty consecutive patients with unstable angina who had responded to medical therapy underwent predischarge symptom-limited exercise testing and 39 of them underwent exercise thallium-201 imaging, on average 3 days after the exercise test. Exercise echocardiography was performed in 36 of these patients in conjunction with the predischarge exercise test. Patients with previous myocardial infarction, coronary revascularization, left bundle branch block and dilated cardiomyopathy were not included in the study. An echocardiographic wall-motion score index was derived by analyzing left ventricular regional wall motion. During a follow-up period of 30 +/- 6.4 months, 3 patients had a non-fatal myocardial infarction and 20 required revascularization because of a recurrence of severe medically refractory angina. Univariate predictors of cardiac events (non-fatal myocardial infarction or a need for revascularization) during follow-up included ST-depression during exercise, positive exercise echocardiography, a low exercise wall-motion score index, the presence of thallium-201 redistribution and the number of myocardial segments with thallium-201 redistribution. However, stepwise logistic regression analysis revealed that the presence of thallium-201 redistribution was the only significant non-invasive predictor (P < 0.005) of a cardiac event among patients who underwent predischarge exercise testing and exercise thallium-201 imaging. Among patients undergoing exercise echocardiography and exercise thallium-201 imaging, the number of segments with thallium-201 redistribution was the only significant predictor (P < 0.0005) of future cardiac events.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prognostic significance of exercise thallium-201 myocardial perfusion imaging compared to stress echocardiography and clinical variables in patients with unstable angina who respond to medical treatment. 840 10

We undertook a prospective study of the symptoms of hypertrophic cardiomyopathy with the aim of profiling symptomatic morbidity in detail, determining the prevalence of anxiety and depression, and describing the prevalence and associations of syncope and postprandial symptom exacerbation. A questionnaire was administered to consecutive outpatients; 70 with hypertrophic cardiomyopathy, 43 with coronary artery disease, 32 with idiopathic dilated cardiomyopathy, and to 40 normal subjects. Hypertrophic cardiomyopathy patients underwent exercise testing, echocardiography, and Holter monitoring. Hypertrophic cardiomyopathy patients had a high frequency of cardiac symptoms and, on average, had a level of symptomatic morbidity equivalent to that of chronic stable angina and dilated cardiomyopathy. There was no evidence for an excess of anxiety (14%) or depression (6%) in patients with hypertrophic cardiomyopathy. Syncope and presyncope, especially provoked by exertion or posture change, were characteristic and common symptoms in hypertrophic cardiomyopathy. A history of syncope was associated with an abnormal blood pressure response to exercise in over 50% of cases that may be the mechanism of syncope in some. Postprandial exacerbation of symptoms occurred in over one-third of hypertrophic cardiomyopathy patients, half of coronary disease patients, and infrequently in dilated cardiomyopathy. Hypertrophic cardiomyopathy patients with postprandial symptoms had a greater frequency of angina, were more symptomatic, and had a reduced exercise capacity, suggesting that postprandial symptoms are a marker for more severe disease.
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PMID:Symptoms of hypertrophic cardiomyopathy, with special emphasis on syncope and postprandial exacerbation of symptoms. 872 95

Bisoprolol was administered orally at doses of 1.25-5 (mean 3.2 +/- 1.1)mg/day for 3-10 (mean 4.1 +/- 1.6) months in 19 patients with congestive heart failure secondary to dilated cardiomyopathy. All patients heart rate and blood pressure were sensitive to the first dose 1.25 mg bisoprolol and when the dose was titrated to 2.5 mg, it was effective and led to a smooth course during a 10-hour period of observation. After treatment, the patients heart function, including fractional shortening, ejection fraction and exercise ability increased significantly and both the severity and the incidence of ventricular arrhythmias decreased significantly. The response of heart rate to exercise and isoproterenol infusion tended to be normal lymphocyte beta-adrenergic receptor density was increased. It is shown that bisoprolol is a promising beta-blocking agent in treating congestive heart failure. The mechanisms of its effects may be related to depression of excessive sympathetic activity, decrease of heart rate and up-regulation of beta-adrenergic receptor.
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PMID:[Clinical effects of bisoprolol in congestive heart failure due to dilated cardiomyopathy]. 873 31

Myofibrillar but not actomyosin ATPase is depressed in failing myocardium from patients with dilated cardiomyopathy. Since there is a similar depression of myofibrillar ATPase in mitral regurgitation myocardium, we investigated whether or not the hydrolytic and mechanical performances of myosin are altered by comparing the maximal actomyosin ATPase activity and the in vitro myosin motility of myocardial myosin from patients with mitral regurgitation heart failure with that of patients with normal ventricular function. The results show that there is no significant difference (P > .05) between nonfailing and failing values for either the maximal actomyosin ATPase activity (0.3 s-1.head-1) or the myosin motility (1 micron/s). These observations suggest that changes, other than in the myosin heavy chain, contribute to the altered myocardial performance in mitral regurgitation myocardium.
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PMID:Maximal actomyosin ATPase activity and in vitro myosin motility are unaltered in human mitral regurgitation heart failure. 875 98

We found recently autoantibodies against the adenine nucleotide translocator (ANT), a carrier in the inner mitochondrial membrane, in sera of patients with myocarditis and dilated cardiomyopathy. To elucidate whether these antibodies are of pathophysiological importance, we investigated the function and expression of the adenine nucleotide translocator (ANT) in the heart muscle tissue of patients suffering from myocarditis and DCM. We found a markedly lowered transport capacity of the translocator accompanied by an elevation in total ANT protein content. The alteration in ANT protein amount is caused by an ANT isoform shift characterized by an increase in ANT 1 isoform protein associated with a decrease in ANT 2 isoform and an unchanged ANT 3 content. It could be shown that the isoform shift is not a progressive process during the disease period but an event in the early period of illness which becomes permanent. Simulating the effect of pathogenetic factors of autoimmunological diseases, we infected A/J mice with the enterovirus Coxsackie B3 and immunized guinea pigs with myocardial ANT protein. Both treatments led to autoimmunological responds and to a lowered myocardial transport capacity of ANT, to a disturbed energy metabolism and consequently to a depression of heart function.
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PMID:Significance of the adenine nucleotide translocator in the pathogenesis of viral heart disease. 897 71

The electrocardiographic features indicating left ventricular dysfunction were studied in 32 consecutive patients having left bundle branch block including 10 with idiopathic genesis without significant underlying disease, 6 with dilated cardiomyopathy, 8 with old myocardial infarction, and 8 with hypertensive heart disease. The patients were divided into two groups; those with favorable left ventricular systolic function and those with poor left ventricular systolic function evaluated by using non-invasive methods. Electrocardiographic findings were compared between these two groups. Ten patients had favorable and 22 poor left ventricular systolic function. One or more of the following electrocardiographic findings were observed in the poor group, but none in the favorable group: low voltage in the limb leads, prolonged intraventricular conduction (QRS duration wider than 0.17 sec), transitional zone between V5 and V6, depression of the ST-J point by more than 0.2 mV in V6, reverse progression of the R wave in V1-V5, marked left axis deviation (axis beyond: 30 degrees), left atrial overload (positive Morris index), PQ prolongation, and abnormal Q waves in I, aVL, V6. No significant differences in the distribution of these findings was observed in any of the underlying diseases. The clinical background of patients with left bundle branch block who had no significant underlying disease showed favorable left ventricular systolic function except the patients above 80 years of age, who showed poor left ventricular systolic function. In contrast, patients with underlying mild hypertensive heart disease may have a favorable left ventricular systolic function. Thus, left ventricular systolic function in patients with left bundle branch block may be suspected by observing these electrocardiographic findings.
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PMID:[Estimation of left ventricular systolic function based on the electrocardiograms in cases with left bundle branch block]. 948 48

A considerable effort has been made in the last 15 years to evaluate the safety and efficacy of calcium channel blockers (CCBs) in the treatment of patients with chronic congestive heart failure (CHF). Available studies have provided strong evidence for a potential detrimental effect of the first-generation calcium antagonists in patients with CHF, indicating the need for great caution when these drugs are used in patients with significant depression of left ventricular systolic function. A number of second-generation CCB have demonstrated a strong vasodilatory effect and favorable hemodynamic action but failed to show a similar improvement in exercise capacity, morbidity and mortality. Moreover, drugs such as nicardipine and nisoldipine have resulted in a detrimental effect in some patients and, therefore, cannot be considered safe when used in patients with moderate-to-severe heart failure. Available information from the V-HeFT III study demonstrate a lack of an unfavorable effect of felodipine on exercise tolerance in patients with chronic heart failure. Although mortality rate was similar in both the felodipine and the placebo group, because of the relatively small number of patients in this study, no clear conclusion can be drawn regarding the effect of felodipine on mortality in patients with CHF. An encouraging signal regarding a potential role of CCB in the treatment of chronic heart failure has been provided by the recently completed PRAISE study. This prospective large-scale study demonstrated the safety of amlodipine, a long-acting dihydropyridine derivative, when used in patients with heart failure due to coronary artery disease. Furthermore, this study demonstrated a substantial reduction in mortality in patients with CHF due to nonischemic cardiomyopathy and provided a strong indication for a potential therapeutic benefit of amlodipine when added to standard CHF therapy in this patient population. No clear explanation is available at the present time regarding the reason for the deleterious effect demonstrated with some of the dihydropyridines and the contrasting benefit seen with amlodipine. Finally, more information regarding the safety and efficacy of dihydropyridines should become available in the next year. The PRAISE II study is ongoing and will provide further information regarding the therapeutic role of amlodipine in patients with nonischemic dilated cardiomyopathy. The MACH-1 study is evaluating the effect of mibefradil, a predominant T-type channel blocker with an ideal activity profile, on morbidity and mortality in patients with chronic CHF.
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PMID:Calcium channel blockers in heart failure. 957 Apr 28


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