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

1. As a local anaesthetic on frog nerve, LB46 had 0.4 times the activity of procaine and 2 times that of INPEA.2. In reducing the maximum rate of depolarization (MRD) of intracellularly recorded cardiac action potentials, LB46 was 20 times more potent than INPEA.3. As an antagonist of the chronotropic effect on atrial muscle and of the inotropic effects on ventricular muscle of isoprenaline the pA(2) values for LB46 were 9.05+/-0.15 and 9.30+/-0.06 respectively, and for INPEA 6.00+/-0.16 and 6.10+/-0.12.4. LB46 was 8 times more active than racemic propranolol in blocking the effects of isoprenaline on isolated cardiac muscle, and since its direct action on the cardiac membrane was only 0.1 times that of propranolol, there was a net gain of 80 times in the specificity of LB46 for class 2 (antisympathetic) over class 1 (depression of MRD) antidysrhythmic actions.5. INPEA was 2.5 times less active as a beta-adrenoceptor blocking drug on cardiac muscle than (+)-propranolol, and 1,300 times less active than LB46.6. INPEA, but not LB46, prolonged the duration of both atrial and ventricular intracellular action potentials.
 ...
PMID:Effects on cardiac muscle of the -adrenoceptor blocking drugs INPEA and LB46 in relation to their local anaesthetic action on nerve. 440 Jan 81

1. The action of piperazine on mammalian smooth, cardiac and skeletal muscles has been studied.2. Piperazine increased tone and produced a dose dependent contraction of isolated smooth muscle, which was antagonized by atropine.3. With cardiac muscle, piperazine depressed both the rate and force of contraction and was antagonized by atropine. At higher concentrations, a non-specific depression of cardiac muscle was found. The intravenous injection of piperazine produced a transient decrease in both heart rate and blood pressure and this was followed by an increase.4. In about half of the mammalian skeletal muscle preparations, piperazine potentiated the twitch of the muscle evoked by electrical stimulation.5. On the frog neuromuscular preparation, piperazine produced potentiation of the twitch but this was followed first by blockade of the effects of nerve stimulation and then by depression of the effects of direct muscle stimulation.
 ...
PMID:Some pharmacological properties of piperazine. 466 88

We have further defined the binding characteristics of [3H]nitrendipine to myocardial microsomal membranes of cats, dogs, rats, and rabbits and to canine coronary vasculature (1.5-3.0 mm OD), and we have studied nitrendipine's effect on contractile responses in isolated feline cardiac muscle and canine coronary arteries. [3H]nitrendipine binding is rapid, saturable, and reversible in all four species and in all of these tissues. Feline myocardium has a single binding site with a dissociation constant (KD) of 1.94 nM. Canine myocardium may have two classes of binding sites, with the high-affinity site having a KD of 0.17 nM. Nitrendipine depresses contractility in isolated feline cardiac muscle and canine coronary arteries in a dose-dependent manner [half-maximal dose (ED50) 0.20 microM in isolated feline cardiac muscle and 1.6-6.3 nM for potential dependent contractile responses in isolated canine coronary arteries] and severely blunts the contractile response to increases in extracellular calcium concentration in isolated feline papillary muscles. In contrast to verapamil and D 600, nitrendipine does not prevent the treppe phenomenon. In isolated feline cardiac muscle and large canine coronary arteries, the minimal nitrendipine concentration required for specific binding and for depression of contractile responses is similar. However, only in large canine coronary arteries is the ED50 for nifedipine's depression of contractility similar to the KD for [3H]nitrendipine binding in the respective tissue.
 ...
PMID:Nitrendipine: effects on vascular responses and myocardial binding. 609 95

The importance of prostacyclin (PGI2) and thromboxane (Tx) medication of depressed cardiac performance during abdominal aortic aneurysm operative surgery was studied by contrasting the effects of 650 mg aspirin administered 12 hours before operation to that of a placebo. In 11 patients who received a placebo, the stable metabolite of PGI2, 6-keto-PGF1 alpha rose from 0.050 +/- 0.032 eta grams/ml to 0.419 +/- 0.257 eta grams/ml (p less than 0.01) 30 minutes after the skin incision. The stable metabolite of TxA2, TxB2 did not increase until the aorta was clamped when TxB2 rose from 0.089 +/- 0.054 eta grams/ml to 0.193 +/- 0.138 eta grams/ml (p less than 0.05); this was prior to blood transfusion. During aortic clamping cardiac output decreased 27% (p less than 0.001). In vitro testing of patient plasma showed: 1) depressed developed tension (Tpd) of a rat papillary muscle by 16% (p less than 0.05); 3) reduction of Ca++-ATPase and Mg++-ATPase activity in a rat myocardial subfraction of sarcoplasmic reticulum (p less than 0.05); 3) reduction of Ca++-ATPase in a rat myocardial subfraction of myofibrils (p less than 0.01). Aspirin administered to 11 patients produced no measurable changes in blood loss or fluid requirements. Aspirin lowered preoperative 6-keto-PGF1 alpha and TxB2 levels (p less than 0.01) and prevented an increase of either agent during operation. The low Tx levels were associated with a stable cardiac output during aortic clamping. Further, plasma obtained from aspirin-treated patients did not depress papillary muscle contractility nor decrease ATPase activity of either myocardial subfraction. The observation that TxB2 when added to a papillary muscle or myocardial subfractions, did not decrease Tpd or ATPase suggests that TxB2 plays an indirect role in altering cardiac muscle activity. The results indicate that Txs modulate cardiac depression, which can be prevented with 650 mg aspirin before operation.
 ...
PMID:Maintenance of cardiodynamics with aspirin during abdominal aortic aneurysmectomy (AAA). 611 60

Ro 03-7894 (0.6 mM) produced a non-parallel shift to the right of dose-response curves to (-)-isoprenaline in K+ depolarized uterine preparations from the guinea-pig. The displacement of the curves was readily reversed by washing. A rightward shift of similar magnitude was also produced by Ro 03-7894 in transmurally stimulated ileal preparations. The relaxant effects of fenoterol in carbachol-contracted guinea-pig tracheal preparations (in the presence of 2 microM atenolol) were not altered by 0.6 mM Ro 03-7894. In the three tissues there was no evidence of a reduction in the maximal inhibitory response to the agonists. In uterine and tracheal preparations, Ro 03-7894 (0.6 mM) depressed contractile responses to exogenous calcium. The depression of responses was enhanced after washout of Ro 03-7894 for 80 min. Contractile responses of ileal preparations to transmural stimulation were also depressed by Ro 03-7894. Concentration-effect curves for the positive inotropic effects of (-)-isoprenaline in guinea-pig left atrial preparations were markedly shifted to the right and the maximum response depressed by 0.6 mM Ro 03-7894. Although the rightward shift of the curves was fully reversed during the 120 min washout period, the maximal responses remained depressed. In similar experiments, Ro 03-7894 produced a washout-resistant depression of inotropic responses to histamine and calcium. The results of radioligand binding studies in left atria using (-)-[125I]-iodocyanopindolol indicated that, when compared to the untreated atria, there was no reduction in the maximal density of binding sites 120 min after washout of 0.6 mM Ro 03-7894. 5 On the basis of the present results it is concluded that Ro 03-7894 induces a non-specific depressant effect on smooth and cardiac muscle preparations during exposure to the drug. This depressant effect persists following washout of the drug. There is no evidence for an irreversible effect of Ro 03-7894 at beta-adrenoceptor sites.
 ...
PMID:Is Ro 03-7894 an irreversible antagonist at beta-adrenoceptor sites? 614 74

Studies on the rats with genetically-controlled hypertension (spontaneously hypertensive rats, SHR) in which myocardiopathy had been produced by isoproterenol (ISP) administration (2 X 80 mg/kg sc daily for two days) have shown that the myocardiopathy results in a fall of the activity of adenylate cyclase (AC) lasting from the second to the fourth day after administration of ISP, while the activity of phosphodiesterase (PDE) remained unchanged. In vitro, ISP (10(-7)-10(-4)M), Mg2+ (4-25nM), GTP (10(-6)-10(-5)M) and GTP (10(-5)M) given in combination with ISP (10(-6)-10(-5)M) elevated the AC activity in the cardiac muscle of SHR similarly in controls and the rats with ISP-induced myocardiopathy. The results indicate that the depression of AC activity in the cardiac muscle of SHR following ISP-induced myocardiopathy is a result of reduction of the number of AC molecules rather than a consequence of the structural damage of AC.
 ...
PMID:The activity of adenylate cyclase and phosphodiesterase in the isoproterenol-damaged cardiac muscle of spontaneously hypertensive rats. 631 39

An alteration in calcium metabolism in cardiac muscle was observed in diabetic rats 3 mo after streptozotocin treatment. Depression of cardiac output and left ventricular pressure development were more sensitive to decreased extra-cellular calcium in hearts from diabetic than from control animals and occurred within the normal physiological range of freely ionized serum calcium. This decrease in calcium sensitivity was not present after 2 wk of diabetes. In vivo treatment with insulin for 1 mo completely reversed the effect. Addition of octanoate (0.3 mM) to the perfusate of isolated hearts completely reversed the defect, whereas epinephrine (25 nM) only partially reversed it. When the glucose concentration of the perfusate was decreased, the function of diabetic hearts declined and was further diminished at decreasing calcium levels. Hearts from normal rats were unaffected. These results suggest that there is a defect in calcium metabolism or flux in the chronic diabetic rat heart.
 ...
PMID:Altered sensitivity of chronic diabetic rat heart to calcium. 636 27

Congestive heart failure is associated with ventricular hypertrophy and dilatation, increased circulating catecholamines, and peripheral vasoconstriction. The extent to which these changes occur, whether they are a favorable "compensatory mechanism" or contribute to cardiocirculatory dysfunction, depends on the cause and severity of the heart failure. The addition of new sarcomeres through ventricular hypertrophy distributes the excess workload of the failing ventricle over more contractile units. In ventricular pressure overload, hypertrophy primarily increases wall thickness and ventricular volume is not usually increased; the converse is true with ventricular volume overload. Hypertrophy can result in enhanced or depressed contractile performance, depending on the stimulus for hypertrophy and method by which contractility is evaluated. The "ventricular function curve," which relates stroke volume to ventricular filling pressure or volume, overestimates the role played by the "Starling principle" as a compensatory mechanism and underestimates how well contractile performance is preserved. The evaluation of end systolic pressure-volume relationships under conditions of variable afterload closely reflects the isometric length-tension relationship and is therefore a more accurate way to quantitate cardiac muscle performance. Pressure overload hypertrophy usually leads to a depression in contractility whereas volume overload may not. An exaggerated sympathoadrenal response is another hallmark of severe heart failure that enhances contractility, helps initiate hypertrophy, and maintains arterial perfusion pressure. A generalized increase in peripheral vascular resistance occurs and is most prominent in those circulations most susceptible to neurohumoral control (renal, splanchnic, cutaneous). This favors perfusion of the cerebral and coronary circulations. Vasoconstriction is further enhanced by the activation of the renin-angiotensin-aldosterone system and secretion of ADH. This results in sodium retention and plasma volume expansion. In early mild heart failure, vasomotor tone may be normal at rest; however, the sympathoadrenal response to exercise may be intense. Moderate alpha receptor stimulation reduces skeletal muscle blood supply and favors the intramuscular redistribution of blood flow from inactive to active muscle fibers, thereby maintaining a normal oxygen consumption. During the later stages of heart failure, increased vascular stiffness due to increased sodium content and excessive norepinephrine appears to restrict nutritional blood flow to exercising muscle at the conductance-vessel level. Vasodilator drugs may reduce aortic impedance and improve cardiac output, may lower ventricular filling pressure, and relieve congestive symptoms, and may result in complex but favorable changes in the distribution of blood flow to the regional circulations.
 ...
PMID:Cardiocirculatory dynamics in the normal and failing heart. 645 90

Monensin toxicosis was induced in lambs by either a single oral dose of 12 mg/kg or six daily doses of 8 mg/kg. Clinical signs of toxicosis consisted of depression, dyspnea, stiffness of gait, reluctance to move, and recumbency. Serum creatine phosphokinase activity was increased. Samples of skeletal and cardiac muscle were obtained over a six-day period and examined by light and electron microscopy. Light microscopic changes in cardiac and skeletal muscles consisted initially of vacuolation and intracellular edema of muscle cells followed by segmental necrosis. Interstitial fibrosis was present on days 5 and 6 postexposure. Muscle fiber necrosis was more severe in skeletal than cardiac muscles and most severe in sheep given 8 mg/kg of monensin daily. Macrophages were seen only in areas of severe necrosis. The earliest ultrastructural change was severe swelling of mitochondria. Secondary changes consisted of lipid accumulation and myofibrillar alterations. Myoblast proliferation was present as early as four days after initial exposure to monensin.
 ...
PMID:Light and electron microscopic changes in cardiac and skeletal muscle of sheep with experimental monensin toxicosis. 663 66

The calcium channel blocking agent, nifedipine, has been shown to improve indexes of left ventricular relaxation, diastolic filling and compliance in patients with hypertrophic cardiomyopathy. The mechanism of action of nifedipine on diastolic properties in patients with hypertrophic cardiomyopathy is unclear and could result from an improvement in myocardial inactivation or from systemic vasodilation and left ventricular unloading. To distinguish between these mechanisms, the effects of nifedipine and the vasodilator nitroprusside on left ventricular diastolic properties were compared in 10 patients with nonobstructive hypertrophic cardiomyopathy using simultaneous micromanometer left ventricular pressure and echocardiographic measurements. Left ventricular peak systolic pressure was comparable during nitroprusside infusion (132 +/- 38 mm Hg) and after nifedipine (132 +/- 32 mm Hg). During nitroprusside infusion, the decrease in left ventricular end-diastolic pressure (22 +/- 11 to 17 +/- 11 mm Hg, p less than 0.05) was associated with a decrease in left ventricular end-diastolic dimension. In contrast, the decrease in left ventricular end-diastolic pressure after nifedipine (22 +/- 11 to 18 +/- 10 mm Hg, p less than 0.05) was associated with no reduction of left ventricular end-diastolic dimensions, suggesting an increase in left ventricular distensibility. Compared with nitroprusside, nifedipine was associated with less prolongation of the left ventricular isovolumic relaxation time and less depression of the peak left ventricular posterior wall thinning rate and peak left ventricular internal dimension filling rate. These data suggest that the effects of the calcium channel blocker, nifedipine, on diastolic mechanics in hypertrophic cardiomyopathy result not only from systemic vasodilation but also from improved cardiac muscle inactivation.
 ...
PMID:Comparison of the effects of nitroprusside and nifedipine on diastolic properties in patients with hypertrophic cardiomyopathy: altered left ventricular loading or improved muscle inactivation? 668 50


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