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)

The purpose of the study was to compare the actions of propofol and thiopental on myocardial contractility and cellular electrophysiologic behavior. Isometric tension of isolated guinea pig right ventricular papillary muscle was studied in normal and 26 mM potassium Tyrode's solutions at various stimulation rates (after rest up to 3 Hz). Normal and slow action potentials were also recorded by conventional microelectrodes. Propofol (30, 100, and 300 microM) applied in the commercial 10% Intralipid emulsion caused dose-dependent depression of contractions at all stimulation rates, whereas Intralipid alone had no effect. Thiopental (10, 30, and 100 microM) caused depression similar to the threefold greater concentrations of propofol. Although neither drug altered the normal action potential (AP) amplitude or dV/dt max, thiopental (30 microM) increased AP duration. In the partially depolarized (26 mM potassium) beta-adrenergically stimulated myocardium, propofol and thiopental caused dose-dependent contractile depression similar to that in normal Tyrode's solution. Whereas propofol did not alter slow AP characteristics, 30-100 microM thiopental increased slow AP duration (consistent with decreased potassium conductance), and 100 microM thiopental depressed dV/dt max (consistent with decreased calcium channel ionic influx). Comparing the clinical plasma concentration ranges required for an equivalent anesthetic effect, propofol depresses myocardial contractility less than thiopental.
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PMID:Propofol and thiopental depression of myocardial contractility. A comparative study of mechanical and electrophysiologic effects in isolated guinea pig ventricular muscle. 153 21

The diagnostic and prognostic value of ST recordings in unstable coronary artery disease were evaluated in 198 men below 70 years of age admitted to the coronary care unit because of chest pain due to myocardial ischaemia but without the development of Q-wave infarction. The ST recordings were performed for 24 h in bed in the CCU (n = 75) between 6 and 66 hours after the last episode of pain, before discharge during ambulation in hospital 4-6 days after admission (n = 198), and ambulatory out of hospital 1 month later (n = 109). The long-term ECG was registered from bipolar leads corresponding to V2 and V5 using two-channel FM-recorders. Significant ST episodes were defined as ST segment deviation greater than or equal to 0.1 mV from baseline and lasting for at least 1 min. During the recordings 85-90% of the patients were treated with betablockers and 27-41% also with calcium channel blockers. In the CCU recordings, ST depression occurred in 23% of the patients, 21% had asymptomatic and 7% symptomatic episodes. Before discharge the ST recordings showed ST depression in 18% of the patients, 16% asymptomatic and 7% symptomatic. Ambulatory monitoring after 1 month showed a higher occurrence of ST depressions--33% (P less than 0.01 compared to day 5), 26% had episodes without pain and 13% painful episodes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Diagnostic and prognostic importance of ST recording after an episode of unstable angina or non-Q-wave myocardial infarction. 155 18

The response to nimodipine as an inhibitor of cocaine toxicity was investigated in pentobarbital-anesthetized dogs and in isolated dog heart preparations at constant heart rates. Nimodipine (10 micrograms/kg) markedly decreased peripheral and coronary vascular resistance and increased cardiac output, cardiac work, and coronary blood flow. When corrected for the change in afterload, nimodipine had a positive inotropic response, as measured by +/- maximal dP/dt, in the cocaine-depressed animal. Thus, cocaine toxicity was partially reversed by nimodipine. In the isolated heart preparation, nimodipine resulted in further cardiac depression similar to that seen with other calcium channel antagonists.
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PMID:The effects of nimodipine on cocaine toxicity. 160 65

1. The effects of endothelin were studied, in vitro, on neurones contained in the rabbit vesical pelvic ganglion by use of intracellular and single-electrode voltage clamp techniques under conditions where sodium and potassium channels were blocked. 2. In the current-clamp experiments, endothelin (1 microM) caused a depolarization followed by a hyperpolarization of the membrane potential. In the voltage-clamp experiments, endothelin (0.01-1 microM) caused an inward current followed by an outward current in a concentration-dependent manner. 3. Membrane conductance was increased during the endothelin-induced depolarization and inward current. Membrane conductance was decreased during the endothelin-induced hyperpolarization and outward current. 4. The endothelin-induced inward and outward currents were not altered by lowering external sodium concentration or raising external potassium concentration. 5. The endothelin-induced inward current was depressed (mean 72%) in a Krebs solution containing nominally zero calcium and high magnesium. These results suggest that a predominent component of the endothelin-induced inward current is mediated by calcium ions. 6. The calcium-insensitive component of the inward current was abolished by a chloride channel blocker, 4-acetamide-4'-isothiocyanostilbene-2,2'-disulphonic acid. The mean reversal potential for the calcium-insensitive component of the inward current was -18 mV. This value is near the equilibrium potential for chloride. Thus, it is presumed that the calcium-insensitive component of the inward current is carried by chloride ions. 7. Endothelin caused an initial depression followed by a long lasting facilitation of both rapidly and slowly decaying components of high-threshold calcium channel currents (N- and L-type). 8. In summary, the data show that for neurones in the vesical pelvic ganglia, endothelin causes membrane depolarization and activates an inward current. The ionic mechanisms involve receptor-operated calcium and chloride currents. Also, endothelin causes an initial depression followed by a long-lasting facilitation of the voltage-dependent calcium current.
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PMID:Endothelin modulates calcium channel current in neurones of rabbit pelvic parasympathetic ganglia. 165 45

Although often not considered, the heart is one of the targets of multiple organ failure in sepsis and septic shock, with myocardial depression being a prominent component of this "acute septic cardiomyopathy". Hypotheses concerning the etiology of this depression are increasingly elucidated on a cellular level, including dysfunction of the beta-adrenoceptor/G protein/adenylate cyclase system, calcium channel blockade by cardiodepressant factor, contractile impairment by activated leucocytes, as well as inhibition of protein synthesis by Pseudomonas exotoxin A. In the search for "mechanisms of myocardial depression in sepsis", isolated cardiomyocytes may play a role as research tools with respect to: a) discrimination between direct and indirect cardiodepressant effects; b) identifying not only the acute, but also chronic toxin- and mediator-induced cardiodepression; c) clarification of the mechanism of action of cardiodepressant bacterial toxins and sepsis mediators; d) establishment of in vitro models of leucocyte-mediated cardiodepression in sepsis.
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PMID:Mechanisms in acute septic cardiomyopathy: evidence from isolated myocytes. 166 46

Dimethindene maleate (DM) (= Fenistil) is a potent antihistamine with a prolonged duration of action. On the histamine-stimulated guinea-pig ileum DM has a pA2 of 9.3 but produces a very marked depression of the maximum response at 10(-8) M. DM has no effect on H2 receptors nor on H3 receptors, and is not a calcium channel blocker. Muscarinic receptors (carbachol-stimulated ileum) were only influenced (competitively) at 10(-7) M or above, suggesting that the non-competitive effects described above could be due to a specific reaction with the histamine H1 receptor. As non-specific effects, such as membrane-stabilisation, would normally be seen with both isomers equally, we studied the effects of the optical isomers of DM. The (-) isomer had a profile identical to that of DM, but was slightly more potent. The (+) isomer was some 30 times less potent (results confirmed by binding studies). However in contrast to DM and the (-) isomer, the (+) isomer showed a "classical" antagonism, pA2 = 7.7, with no evidence of non-competitive effects. Thus the more active (-) isomer of DM has a potent, non-competitive H1 histamine antagonist effect. The relevance of these findings to DM's clinical profile is discussed.
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PMID:Investigation of the antihistaminic action of dimethindene maleate (Fenistil) and its optical isomers. 167 35

The predominant consequences of mu-opioid-receptor activation are depression of both neuronal activity and transmitter release. Mu-Opioid agonists have previously been observed to increase a potassium conductance and to inhibit adenylate cyclase. We now report that activation of mu-opioid receptors directly decreases the N-type calcium-channel current in a differentiated, human neuroblastoma cell line (SH-SY5Y). The coupling between the mu-opioid receptor and the calcium channel involves a pertussis toxin-sensitive G protein and is independent of changes in adenylate cyclase activity. The inhibition of the calcium-channel current is voltage dependent because it is largely overcome by strong membrane depolarization. It is not associated with changes in the kinetics of current inactivation. Therefore, the mu-receptor belongs to the superfamily of G-protein-coupled, inhibitory neurotransmitter receptors which modulate the activity of calcium and potassium channels and adenylate cyclase.
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PMID:Mu-opioid-receptor-mediated inhibition of the N-type calcium-channel current. 167 47

The effects of the calcium channel antagonist nifedipine and the protein kinase C (PKC) inhibitor, staurosporine were examined on the pressor actions of a full, cirazoline, and a partial, St587, alpha 1-adrenoceptor agonist as well as the alpha 2-adrenoceptor agonist B-HT 920 in the pithed rat preparation. Administration of nifedipine or staurosporine significantly reduced the diastolic blood pressure of pithed rats. Staurosporine displaced the dose-diastolic pressure response curves for B-HT 920 and St587 to the right in a dose-dependent manner. The ED50 value for the dose-response curves to B-HT 920 and St587 were found to be significantly increased after the administration of staurosporine. Staurosporine also caused a depression of the maximum response to B-HT 920 and St587. The presence of nifedipine resulted in an increase in the ED50 value of the dose-response curve to B-HT 920 and St587, and this was accompanied by significant reductions of the maximum response, whereas the administration of either staurosporine or nifedipine did not significantly affect the calculated ED50 value of the dose-response curve to cirazoline. In the presence of the calcium channel antagonist but not the PKC inhibitor the maximum response to cirazoline was significantly depressed. As judged from the slope function of the dose-response curves the nature of the inhibition produced by nifedipine compared to staurosporine also appeared to differ. Thus, with nifedipine as the antagonist, the slope function of the dose-response curve for alpha-agonists was significantly reduced. Moreover, in contrast to the actions of staurosporine, nifedipine reduced the maximum response to cirazoline in a dose-independent manner. This study supports the hypothesis that activation of alpha-adrenoceptors that have a substantial dependence on extracellular calcium for vasoconstriction are susceptible not only to the action of calcium channel antagonists but also to the actions of the PKC inhibitor staurosporine, thus suggesting that PKC may modulate directly/indirectly calcium channel activity in vascular smooth muscle.
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PMID:Effects of staurosporine on the pressor responses to alpha-adrenoceptor agonists in pithed rats: a comparison with nifedipine. 168 70

Amiodarone and its pharmacologically active metabolite desethylamiodarone have a sodium channel blocking action that explains some of their antiarrhythmic efficacy. However, the well-documented depression of the calcium channel-dependent sinus node and atrioventricular node function that occurs with amiodarone therapy suggests that amiodarone also blocks calcium influx through voltage-dependent calcium channels. Recent electrophysiologic data support the notion that amiodarone, but not desethylamiodarone, acts as a calcium channel antagonist. In this study, the effects of amiodarone and desethylamiodarone on calcium antagonist receptors associated with the voltage-dependent calcium channels were characterized. Amiodarone, but not its active metabolite desethylamiodarone, was a potent competitor at dihydropyridine and phenylalkylamine (verapamil-like) calcium antagonist binding sites in rat heart, brain, and skeletal and smooth muscles. Substantial inhibition of calcium antagonist binding was retained even after extensive washing of membranes and 2 days after in vivo treatment of rats with amiodarone. The pattern of inhibition of calcium antagonist binding suggests that amiodarone acts at phenylalkylamine binding sites. It is suggested that the acute effects of amiodarone--sinus and atrioventricular node inhibition, vasodilatation, and negative inotropic actions--may reflect calcium antagonist influences of amiodarone itself. Chronic effects of drug therapy, such as inhibition of ventricular conduction by sodium channel blockade, may selectively involve desethylamiodarone.
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PMID:Differential effects of amiodarone and desethylamiodarone on calcium antagonist receptors. 169 76

The effects of verapamil and nifedipine on cellular mechanisms of arrhythmia were examined in isolated canine Purkinje fiber-papillary muscles. Microelectrode recordings were made simultaneously from both tissues. Preparations were superfused with Tyrode's solution modified to mimic specific conditions of ischemia for 40 min with or without calcium channel blockers. Verapamil or nifedipine resulted in significantly greater depolarization of Purkinje tissue in response to ischemic conditions and increased the incidence of inexcitability or conduction block in Purkinje and muscle tissues. These calcium channel blockers caused only minor changes in ischemia-induced depolarization of muscle. In Purkinje tissue, return to nonischemic conditions in the absence of drugs caused, in sequence, oscillatory afterpotentials, temporary depolarization to inexcitability, and a phase of automaticity at low membrane potential. These events did not occur in muscle. Verapamil or nifedipine abolished oscillatory afterpotentials and low membrane potential automaticity in Purkinje tissue. However, reperfusion-induced depolarization and inexcitability of Purkinje tissue was delayed but not attenuated. This study demonstrates that verapamil or nifedipine exacerbate depolarization and depression of conduction in Purkinje tissue exposed to ischemic conditions. However, verapamil and nifedipine suppress some but not all potential mechanisms of arrhythmia induced by reperfusion.
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PMID:Effects of verapamil and nifedipine on mechanisms of arrhythmia in an in vitro model of ischemia and reperfusion. 170 59


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