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)

Current heart failure therapy has included both stimulation and inhibition of beta-adrenergic receptors. Full beta-agonists have not been clinically effective because of side effects or loss of efficacy over the long term. Full beta-antagonists are effective in selected patients but are not tolerated in others because of cardiac depression. Partial beta-antagonists (beta-blockers with weak intrinsic sympathomimetic activity) do not possess sufficient agonist activity to counteract their own cardiac depressant action. Partial beta-agonists produce mild beta-antagonism, but not enough to offset their overall cardiac stimulating property. The partial beta-agonists have been clinically effective in some patients with heart failure and appear to be a potentially useful and unique class of agents because of their ability to modulate cardiac beta-receptors in such a way as to avoid an excessive response to endogenous or exogenous stimuli.
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PMID:Beta-receptor-active agents: role of partial agonists in patients with heart failure. 247 9

Cardiac failure is treated with increasing success by phosphodiesterase-III (PDE-III) inhibitors such as amrinone, milrinone, and enoximone. While relatively pure positive inotropic substances (e.g., dopamine and dobutamine) are limited by tolerance development and MVO2 increase, the efficacy of PDE inhibitors is maintained by avoiding catecholamine and beta-receptors. They have positive inotropic, positive lusitropic, and vasodilatatory properties; myocardial oxygen consumption remains unaltered. PDE-III inhibitors act by selectively inhibiting PDE-III, leading to an increased cAMP concentration in myocardial and smooth muscle cells. In contrast, forskolin increases intracellular cAMP by activation of adenylate cyclase. It could be shown that parenteral administration of the PDE inhibitors sulmazole, amrinone, and enoximone resulted in preload and afterload reduction due to vasodilation with concomitant decrease of peripheral and pulmonary vascular resistance; they also led to elevated cardiac output and ejection fraction as well as a significant increase in dp/dtmax, while left ventricular filling pressures were markedly lowered. Pulmonary pressure values fell significantly, whereas heart rate and myocardial oxygen consumption showed no clinically relevant alterations. In patients with angiographically documented coronary artery disease, the anti-ischemic efficacy of enoximone could be proven both during exercise and stress pacing. The decrease of the pathologically elevated pulmonary pressures during ischemia was accompanied by reduced ST-segment depression following enoximone without changing MVO2 significantly. First tests after intracoronary application of enoximone confirmed its direct myocardial efficacy, indicating its positive inotropic and lusitropic properties. Thus, patients in cardiac failure have useful therapeutic alternatives at their disposal when taking PDE inhibitors. The anti-ischemic properties of these drugs need further evaluation.
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PMID:Present use of positive inotropic drugs in heart failure. 248 Apr 92

Elevated systemic vascular resistance in heart failure causes further depression of cardiac function. Decreased systemic vascular resistance, on the other hand, is associated with an improvement in cardiac performance. Thus, peripheral vasodilators, irrespective of their mechanism of action, have the potential to improve cardiac function in heart failure. Increased peripheral vascular tone appears to result from a number of interrelated neuroendocrine dysfunctions--an activated renin-angiotensin-aldosterone system, inappropriate release of arginine vasopressin, and enhanced systemic and cardiac sympathetic activity (indicated by increased levels of circulating norepinephrine and markedly increased cardiac norepinephrine release). Augmented sympathetic activity may not only increase systemic vascular resistance but can also induce myocardial cellular dysfunction. Furthermore, downregulation of cardiac beta-adrenoceptors may contribute to inadequate cardiac performance. Reduction of sympathetic tone and upregulation of the beta-adrenoceptors is the rationale for beta-blocker therapy in heart failure and, indeed, cardioselective beta-blockers improve cardiac function in some patients with dilated cardiomyopathy. Third-generation beta-blockers, such as celiprolol, possess both cardioselective and peripheral vasodilatory properties and are therefore potentially beneficial in heart failure.
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PMID:Potential use of third-generation beta-blockers in heart failure. 248 86

The terminal phases of volume-overload heart failure are characterised by eccentric ventricular hypertrophy. Relatively little attention has been directed to exploring the mechanisms involved in this development. The increase in diastolic wall stress leads to replication of the sarcomeres in series. The hypertrophied myocytes has a defective contractile ability that is due to an intrinsic depression of contractility; this is restored when failure is reversed. The development of appropriate hypertrophy is dependent upon adequacy of the coronary blood supply to the failing myocytes. Reduction of preload and afterload can be expected to be more effective in reducing systolic wall stress, and hence myocardial oxygen demands, in eccentric hypertrophy than in the nonfailing heart with concentric hypertrophy. However, there is no information available on the influence of anti-heart-failure drugs on the myocardial hypertrophy associated with severe volume-overload failure. The presence of such hypertrophy carries an ominous prognosis and may be associated with the high incidence of arrhythmic sudden deaths. The detection of myocardial hypertrophy in the patient with failure emphasises the urgency of adequate reduction of the elevated preload and afterload without impairment of the coronary perfusion gradient.
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PMID:Influence of drug therapy on myocardial hypertrophy in left ventricular failure. 248 20

The renin-angiotensin system has a wide range of physiological actions, and thus interference with the system has attractive therapeutic potential. The orally active angiotensin converting enzyme (ACE) inhibitors have so far been the most successful drugs in this area. They lower arterial pressure both in renovascular and essential hypertension, and their effects are enhanced by concomitant diuretic therapy or dietary salt restriction. Since, in renovascular hypertension, the affected kidney depends on enhanced local generation of angiotensin II to help preserve its function, the circulation and excretory capacity of this kidney may be compromised with ACE inhibition. ACE inhibitors can improve exercise tolerance and diminish cardiac ventricular arrhythmias in patients with heart failure. Because these drugs lower plasma aldosterone, they tend to correct potassium deficiency and hypokalemia, which may have been induced by diuretic treatment. Hypotension can occur with the first dose of ACE inhibitor, especially in sodium-depleted subjects; in patients on prior antihypertensive therapy, particularly if this includes a diuretic; and in the elderly. Not all of the actions of ACE inhibitors are necessarily due to lowering of plasma angiotensin II: accumulation of kinins may be responsible for some of the effects and side effects. Common to all ACE inhibitors are occasional rashes, cough, and, more rarely, angioedema. Apparently peculiar to captopril, and less often seen with the lower doses now employed, are taste disturbance, proteinuria, and marrow depression. ACE inhibitors, should not be used in pregnant women.
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PMID:Converting enzyme inhibitors in the treatment of hypertension. 248 62

To evaluate cordiodepressive risks of antiarrhythmic treatment with diprafenone, we monitored, in addition to conventional hemodynamic parameters, end-systolic pressure-volume relations to assess potential negative inotropic effects. Thirteen patients underwent hemodynamic analysis with and without the influence of diprafenone 1.5 mg/kg, both a) at rest (paced heart rate of 90 beats/min and b) during tachycardia (paced tachycardia of 160 beats/min). Left ventricular volumes increased under the influence of diprafenone, both at rest (end-diastolic volume by an average of 12%, end-systolic volume by 21%) and during tachycardia (by 15% and by 47%, respectively). Diprafenone induced a depression of left ventricular function during tachycardia only: Ejection fraction fell by an average of 25% and stroke work by 19%, while end-diastolic pressure increased by an average of 28% and systemic vascular resistance by 34%. Diprafenone caused the loops of the end-systolic pressure-volume relationship to move rightward and decreased the slope k, indicating negative entropy, both at rest and during tachycardia. Thus, since under the influence of diprafenone negative inotropic effects and depressed left ventricular function were found (while determinants of preload and afterload increased), diprafenone should not be used as an antiarrhythmic agent in patients with advanced cardiac failure.
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PMID:Influence of the new class I antiarrhythmic agent diprafenone on the end-systolic pressure-volume relationship (conductance technique). 248 30

The prognostic value of exercise testing was studied in 118 patients with angiographically proven chronic coronary disease, positive ET and/or a history of myocardial infarction (MI) who were followed up for 698 years (mean 5.9 years). Medical treatment was instituted step by step and controlled by repeated ET's. ET remained positive (ST depression 1 mm) in 58 cases (group I), was alternately positive and negative in 22 cases (group II) and became normal in 38 cases (group III). The mean duration of follow-up in these three groups was 5.0, 7.6 and 6.4 years respectively. Eight patients were lost sight of. Ergometric data and outcome were similar in groups II and III, but there were differences between group I (58 patients) and groups II + III (60 patients) as regards: (a) ergometric data: total workload (22,077 +/- 9,860 vs 34,856 +/- 15,552 joules), workload causing a 1 mm ST depression (13,892 +/- 9,253 vs 31,555 +/- 15,811 joules) and maximal ST depression (2.5 +/- 0.9 vs 0.9 +/- 0.8 mm); (b) outcome: cardiac deaths (12 vs 3), myocardial revascularization (19 vs 6); but there was no significant difference as regards MI (4 vs 5), heart failure (11 vs 5) and extracardiac deaths (3 vs 4). It is concluded that the persistence of a positive ET under optimal medical treatment is a major argument in favour of myocardial revascularization.
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PMID:[Prognostic value of the normalization of the exercise test under medical treatment in coronary insufficiency]. 251 71

Transdermal nitroglycerin becomes more and more common mode of pharmacotherapy as this form of nitroglycerin ensures permanent therapeutic level of the drug in the blood serum for a long time. The largest clinical experience with transdermal nitroglycerin has been gathered in effort angina although it is used in all forms of ischemic heart disease. It has been documented that transdermal nitroglycerin improves exercise tolerance, increases pain threshold, delays the onset of ST segment depression in the ECG and decreases the incidence of anginal attacks. Beneficial effects of transdermal nitroglycerin on hemodynamic parameters have been shown also in patients with myocardial infarction, especially complicated by heart failure. First results obtained in the treatment of silent myocardial ischemia are very promising. The development of tolerance requires 12-hour intervals in the use of nitroglycerin patches.
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PMID:[Transdermal use of nitroglycerin]. 251 62

The course of experimental myocardial infarction was accompanied by the growth response of the right ventricle (RV) in some rats. Rats with RV hypertrophy unlike ones without RV hypertrophy had depressed cardiac contraction force and velocity at rest as well as a minimal capacity to respond to functional stress. Dibunol (butylhydroxytoluene, 30 mg/kg) prevented the depression of cardiac contractility and RV growth. RV hypertrophy in the rats following left coronary artery ligation is the consequence of the left ventricle pump failure and resultant pulmonary hypertension. RV hypertrophy may be proposed as an index of postinfarct heart failure and its reduction as an index of the cardioprotective effect of various pharmacological interventions.
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PMID:[Myocardial infarct in rats: right ventricular hypertrophy as a criterion of postinfarct left ventricular heart failure]. 252 1

The effect of angiotensin converting enzyme inhibition on myocardial ischaemia was studied in 12 normotensive patients with chronic stable angina and exercise induced ST segment depression. The study was randomised, double blind, placebo controlled, and crossover with treatment periods of two weeks. Enalapril was used to inhibit angiotensin converting enzyme. Assessment was by angina diaries and maximum symptom limited treadmill exercise tests. The results for the whole group showed a significant reduction in systolic blood pressure at rest and at peak exercise. Mean total exercise duration was 466 s (95% confidence interval 406 to 525) when the patients were taking placebo and 509 s (436 to 583) when they were taking enalapril. Four patients prolonged their total exercise time (mean 450 to mean 591 s) by more than 20%. Two patients, however, developed ischaemia earlier on exercise and reduced their total exercise duration (mean 490 to mean 390 s). Although angiotensin converting enzyme inhibition tended to reduce myocardial ischaemia in the group as a whole, some patients improved while others deteriorated. Thus the effects of enalapril are variable and this may have important implications when enalapril is used to treat heart failure in patients with underlying severe ischaemic heart disease.
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PMID:The variable effects of angiotensin converting enzyme inhibition on myocardial ischaemia in chronic stable angina. 254 48


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