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)

Depressed cardiac pump function is the hallmark of congestive heart failure, and it is suspected that decreased influx of Ca2+ into the cardiac cell is responsible for depressed contractile function. Since Ca2+ channels in the sarcolemmal membrane are considered to be an important route for the entry of Ca2+, we examined the status of Ca2+ receptors/channels in failing rat hearts after myocardial infarction of the left ventricular free wall. For this purpose, the left coronary artery was ligated and hearts were examined 4, 8, and 16 weeks later; sham-operated animals served as controls. Hemodynamic assessment revealed decreased total mechanical energy (left ventricular systolic pressure x heart rate), increased left ventricular diastolic pressure, and decreased positive and negative dP/dt in experimental animals at 4, 8, and 16 weeks. Although accumulation of ascites in the abdominal cavity was evident at 4 weeks, other clinical signs of congestive heart failure in experimental rats were evident from the presence of lung congestion and cardiac dilatation at 8 and 16 weeks after induction of myocardial infarction. The density of Ca2+ receptors/channels in crude membranes, as assessed by [3H]nitrendipine binding assay, was found to be decreased in the uninfarcted experimental left ventricle at 8 and 16 weeks; however, no change in the affinity of nitrendipine was evident. A similar depression in the specific binding of another dihydropyridine compound, [3H]PN200-110, was also evident in failing hearts. Brain and skeletal muscle crude membrane preparations, unlike those of the right ventricle and liver, revealed a decrease in Ca2+ receptors/channels density in experimental animals at 16 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Nitrendipine binding in congestive heart failure due to myocardial infarction. 215 68

Follow-up data for 515 survivors of acute non-Q wave myocardial infarction were categorized according to mortality: 1) between hospital discharge and 3 months after infarction (early), and 2) between 3 and 12 months after infarction (late). The mortality rate decreased steadily for the first 3 months and was constant thereafter. There were 25 early and 32 late deaths. After adjustment for the longer time associated with the 3 to 12 month period, the relative risk per unit time of early as compared with late mortality was 2.64. Risk factors for early mortality were different from those that predicted late mortality. Independent predictors of mortality between hospital discharge to 3 months after infarction were ST segment depression that persisted during hospitalization (p less than 0.0001), in-hospital reinfarction (p = 0.0006) and a history of congestive heart failure (p = 0.0255). Persistent ST depression and in-hospital reinfarction had neither a univariate nor an independent association with 3 to 12 month mortality. Age (p less than 0.0001), reinfarction between discharge and 3 months (p = 0.0147) and diabetes (p = 0.0404) were independently associated with late mortality. Early mortality was only 0.5% (1 of 199) in patients with no ST depression at either baseline or discharge (group 1); 4.8% (8 of 168) in those with ST depression at exactly one time point (group 2) and 13.7% (16 of 117) in those who had ST depression present at both time points (group 3). All pairwise differences were significant (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential risk patterns associated with 3 month as compared with 3 to 12 month mortality and reinfarction after non-Q wave myocardial infarction. The Diltiazem Reinfarction Study Group. 217 63

Timely administration of thrombolytic therapy decreases myocardial infarct size, lessens the incidence of congestive heart failure and improves survival. However, available data suggest that only 10% of patients with acute infarction in the United States receive thrombolytic drugs. Given the benefits of thrombolytic therapy, all patients with myocardial infarction would likely be treated were it not for associated risks. Several groups exist in which the risk/benefit ratio of thrombolytic therapy continues to be controversial, including those with inferior infarction, absence of ST segment elevation or presentation greater than 6 h from symptom onset, elderly patients and those with hypertension. Three recent thrombolytic trials reported a reduction in mortality that was entirely independent of infarct location. Pooled data from trials involving 12,000 patients with inferior infarction have demonstrated a reduction in mortality rate (6.8% versus 8.7%, p less than 0.0001). Furthermore, improvement in regional and global left ventricular function occurred after reperfusion therapy of inferior infarction. Pooled data indicate that patients treated between 6 and 24 h after symptom onset have a lower mortality rate than do those who receive placebo (11.1% versus 13.1%, p less than 0.001). Improved survival occurs after thrombolytic therapy in patients with ST segment elevation or left bundle branch block, but not in those with isolated ST depression or a normal electrocardiogram. Age should not be considered an absolute contraindication because the lifesaving potential of thrombolytic therapy in the elderly may be two to three times that of the overall group of patients with myocardial infarction. Finally, recent studies demonstrated that patients who present with hypotension or hypertension or who have undergone cardiopulmonary resuscitation may also benefit.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Optimal utilization of thrombolytic therapy for acute myocardial infarction: concepts and controversies. 219 50

Congestive heart failure is a complex clinical syndrome that has its basis in an abnormality of myocardial cell function resulting in impaired ventricular performance, exercise intolerance, and ventricular arrhythmias. The functional defect in myocardial performance may be related to alterations in receptor function, in regulatory proteins, or in biochemical mechanisms. Remodeling of the left ventricle has been observed to play an important role in the natural course of heart failure. The complex interplay between cellular elongation, reactive hypertrophy, and the influence of the change from ellipsoid to spheroidal shape of the left ventricle after acute myocardial infarction are just beginning to be understood. Prevention of this remodeling effect by pharmacologic intervention is being widely explored, although the mechanisms are poorly defined. Impedance to left ventricular ejection is also an important determinant of cardiac performance in heart failure. Constriction of arteriolar resistance vessels and reduction in compliance of arterial conductance vessels is a common manifestation of heart failure and may be under the influence of neural, hormonal, endothelial, and local regulatory factors. Increased tone of venous capacitance vessels contributes to a shift of blood centrally and to an increase in ventricular preload. Vasodilator drugs by relaxing the arterial, arteriolar, and venous vasculature result in a reduction in impedance and left ventricular afterload and a decrease in cardiac filling pressure and preload. Structural changes of hypertrophy and remodeling apparently contribute to the changes in resistance, compliance, and capacitance in the vasculature. Treatment of heart failure is aimed at relieving symptoms and prolonging life. Interventions to improve left ventricular function are critical to symptom relief. Vasodilators have been most effective for this purpose, and new positive inotropic drugs are being tested for efficacy. Long-term benefit may require interference with the myocardial and peripheral vascular remodeling processes that lead to progressive depression of ventricular performance. New insights into the cellular and subcellular mechanisms of this progression are critical to the development of innovative therapeutic strategies.
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PMID:Heart failure: mechanisms of cardiac and vascular dysfunction and the rationale for pharmacologic intervention. 221 Jan 53

Out of 432 patients with coronary heart disease, 106 (24.5%) were found to have transient myocardial infarction during ECG monitoring of ST segment for 10 hours of daily activity. High-grade ventricular arrhythmias were revealed in 74.6% of mainly male and middle-aged subjects. 63.4% of the patients exhibited congestive heart failure, 48.1% had postinfarct cardiosclerosis, and 25.5% presented with diabetes mellitus. Transient myocardial ischemia was more frequently detected during exercise and more rarely during emotional stress (21.7%), meal (19.8%), and smoking (7.8%). Asymptomatic episodes of ST segment elevation were recorded in 36.8%, while asymptomatic episodes of ST segment depression, in 29.2%. The duration of asymptomatic episodes of ST segment elevation and depression was twice and 1.5 times, respectively, less than that of symptomatic ones. Substantial myocardial perfusion and metabolic impairments were revealed with an asymptomatic ST segment depression frequency of at least one an hour, an amplitude of more than 2 mm, and a duration of no less than 40 min.
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PMID:[Clinical evaluation of transient myocardial ischemia]. 223 60

The programmed onset of myocardial dysfunction and its progression to congestive heart failure in the cardiomyopathic Syrian hamster is hallmarked by alterations in myocellular calcium regulation. To determine whether calcium channel blockade is effective in halting the progressive depression of myocardial contractile performance in this animal model of congestive heart failure, oral verapamil therapy was instituted at 50 days of age, and treatment continued for various durations until the time of study at either 150 or 250 days of age. Left ventricular papillary muscle isometric and isotonic performance, as well as transmembrane electrical characteristics, was depressed in diseased hamsters at 150 days of age and deteriorated further by 250 days of age. These changes were evidenced by prolongation of contraction duration, a marked depression in the load-velocity relation, and a significant prolongation in the repolarization phase of the transmembrane action potential. Myocardial functional and electrical alterations associated with the progression of life in myopathic hamsters were completely halted by verapamil therapy that was continuous from 50 days after birth until death by diastolic arrest, at 150 or 250 days of age. However, premature termination of verapamil treatment before death resulted in a progressive renewal of the functional and electrical alterations for the duration of drug termination. It is concluded that the pathological changes seen during the lifetime of the cardiomyopathic hamster can be prevented by continuous calcium channel blockade and that intermediate prevention can be attained by protracted verapamil therapy. Thus, chronic verapamil therapy may be a useful adjunct in the prevention of human congestive heart failure of similar etiology.
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PMID:Chronic calcium channel blockade prevents the progression of myocardial contractile and electrical dysfunction in the cardiomyopathic Syrian hamster. 224

Antiarrhythmic drugs may induce congestive heart failure in patients with malignant ventricular arrhythmias and depressed left ventricular (LV) function. Whether Doppler echocardiography can detect drug-induced depression in LV function was assessed. Continuous-wave Doppler measurements of ascending aortic blood flow velocity were obtained in 16 patients while not receiving antiarrhythmic drugs on 2 consecutive days to assess day-to-day variability, as well as while receiving maximally tolerated oral doses of mexiletine (11 patients) and propafenone (9 patients). While receiving propafenone, a drug with moderate negative inotropic activity, peak flow velocity declined by 9 +/- 8% (p less than 0.05), the flow velocity integral (termed stroke distance, representing stroke volume) declined by 8 +/- 11% (p less than 0.10), the rate-corrected stroke distance declined by 9 +/- 8% (p less than 0.02) and the minute distance, representing cardiac output, declined by 10 +/- 12% (p less than 0.05). In contrast, while receiving mexiletine, a drug with minimal negative inotropic activity, none of these parameters changed significantly. Five of 9 patients (56%) treated with propafenone showed a decline in rate-corrected stroke distance exceeding the 95% confidence limit of day-to-day variability, which was +/- 13 percent. Two of these 5 patients developed clinical signs of congestive heart failure. Continuous-wave Doppler echocardiography can detect antiarrhythmic drug-induced LV dysfunction and may be used to anticipate the development of significant clinically overt congestive heart failure.
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PMID:Changes in cardiac output determined by continuous-wave Doppler echocardiography during propafenone or mexiletine drug testing. 230 84

Corwin is a new, long-acting beta 1-adrenergic partial agonist for oral and intravenous (i.v.) use. The effects of corwin were compared with those of dobutamine in acute ischemic left ventricular failure in dogs. Failure was produced by embolization of the left main coronary artery with 50 micron plastic microspheres. This induced severe depression in left ventricular function, as evidenced by a marked increase in left ventricular end-diastolic pressure, reduction in left ventricular dP/dtmax, and cardiac output. After 45 min was allowed for stabilization, the 27 dogs were randomly assigned to three groups: control (n = 9), dobutamine-treated (5-10 micrograms/kg/min i.v., n = 9), and corwin-treated (0.025-0.10 mg/kg i.v., n = 9). The doses of dobutamine and corwin were adjusted to give an increase in left ventricular dP/dtmax of 50%. Both drugs similarly increased cardiac output (p less than 0.01), lowered left ventricular end-diastolic pressure (p less than 0.01) and total peripheral vascular resistance (p less than 0.01), but did not affect the heart rate. Only dobutamine increased the mean arterial pressure (p less than 0.01). Both drugs also increased the arterial concentrations and myocardial uptake of fatty acids (p less than 0.05) but caused only a small and nonsignificant increase in myocardial oxygen consumption. Our findings indicate that the hemodynamic and metabolic profiles of corwin and dobutamine are similar, and both drugs should be of special value in the treatment of congestive heart failure. Since corwin can be given orally and has a longer duration of action, it is potentially useful in the long-term treatment of heart failure.
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PMID:Comparative effects of dobutamine and corwin, a beta 1-adrenergic partial agonist, in experimental left ventricular failure. 241 Jul 22

Twenty-four hour ambulatory electrocardiography was performed on 3,290 survivors of acute myocardial infarction participating in the Beta-Blocker Heart Attack Trial (BHAT). History of myocardial infarction before the qualifying event, congestive heart failure and age were independently associated with the frequency and complexity of ventricular premature beats. Of the 1,640 patients randomized to placebo therapy, 163 died (76 suffered sudden death) during a 25 month average follow-up period. Ventricular ectopic activity was an independent predictor of total mortality after taking into consideration 16 other prognostic factors describing past history, risk factors, physical examination and laboratory investigations. Seven categoric definitions of ventricular ectopic activity predicted mortality, with similar odds ratios ranging from 2.27 to 2.69. A reciprocal relation of the sensitivity and specificity of each definition in predicting mortality was observed. Three clinical criteria (ST depression, cardiomegaly and prior infarction) allowed stratification of patients into four subsets with respective mortality rates of 35.5% (three criteria present), 19.0% (two criteria), 11.5% (one criterion) and 4.7% (none). Presence of ventricular ectopic activity (greater than or equal to 10 ventricular premature beats/h or pairs, ventricular tachycardia or multiform complexes) was associated with higher mortality rates in all four risk strata. The relative risk was higher (3.86) in the lowest risk stratum (mortality 2.4% without and 9.1% with ventricular ectopic activity). Thus, in survivors of acute myocardial infarction, ventricular ectopic activity was more pronounced in patients with prior myocardial infarction and congestive heart failure. It predicted mortality independently of other factors. Although mortality ratios were similar for all seven arrhythmia definitions, a reciprocal relation between sensitivity and specificity of the definitions in predicting mortality existed; ventricular ectopic activity was associated with increased mortality in all risk strata, but with a higher risk ratio in the numerically larger, low risk subset.
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PMID:Prognostic significance of ventricular ectopic activity in survivors of acute myocardial infarction. 243 59

MDL 72567 (2,6 dimethyl,3 methoxycarbonyl,4-(2-nitrophenyl), 5-(2-furoyl)1,4 dihydropyridine) was a potent antagonist of Ca2+-induced contractions in K+-depolarized taenia preparations from the guinea pig caecum (pA2 8.8 +/- 0.1). MDL 72567 was a potent displacer of [3H]nitrendipine binding from rat cortical membrane preparations (Ki 3.99 nM), indicating an effect at the dihydropyridine binding site, which is consistent with the finding that the inhibitory effects of MDL 72567 in smooth muscle were prevented by the dihydropyridine Ca2+ channel activator Bay K 8644. MDL 72567 slowed spontaneously beating rat atria preparations to a greater extent than did nifedipine, however, for a given negative inotropic effect. Furthermore, in pithed rat preparations infused with angiotensin II to elevate blood pressure, the hypotensive effects of MDL 72567 (3 nmol/kg-3 mumol/kg, intravenously, i.v.) were accompanied by bradycardia, whereas nifedipine, PY 108-068, and nicardipine lowered blood pressure without affecting heart rate. When compared with nifedipine, MDL 72567 caused less reflex tachycardia for a given fall in blood pressure, in anesthetized beagles and in conscious renal hypertensive dogs. In anesthetized dogs, MDL 72567 increased cardiac contractility at all hypotensive doses tested (30-3,000 nmol/kg, i.v.), whereas nifedipine caused profound myocardial depression at higher doses (1,000-3,000 nmol/kg, i.v.) even though the compounds had equivalent vasodilator effects. Thus, although MDL 72567 appears to cause a direct myocardial slowing that can partially offset reflex tachycardia, the compound has negligible negative inotropic effects and may therefore be useful in angina pectoris or even in congestive heart failure.
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PMID:MDL 72567, a dihydropyridine calcium-antagonist, that causes vasodilation and direct sinus bradycardia. 244 Nov 55


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