Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0042510 (ventricular fibrillation)
10,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanism of action of 2-nicotinamidoethyl nitrate (SG-75), was investigated by the use of arterially blood-perfused papillary muscle preparations of the dog. All drugs were administered intra-arterially. SG-75 shortened the effective refractory period (ERP) and decreased the rate of automaticity and developed tension of the papillary muscle, whereas verapamil failed to change the ERP despite a decrease in the developed tension. SG-75 in extremely high doses induced ventricular fibrillation. Methacholine produced decreases in the rate of automaticity and developed tension, and the actions were abolished by atropine. The SG-75-induced decreases in two parameters were not modified by atropine. These results indicate that the cardiac action of SG-75 differs from that of calcium-antagonistic vasodilators and it is suggested that the basic mechanism of action of SG-75 involves an increase in potassium conductance in the membrane of cardiac muscle, without mediation through muscarinic receptors.
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PMID:Circumstantial evidence for increased potassium conductance of membrane of cardiac muscle by 2-nicotinamidoethyl nitrate (SG-75). 16 36

Although consideral information is available concerning the structural and biochemical changes in the skeletal muscles of patients with malignant hyperthermia, little is known of the cardiac changes in this disease. However, ventricular fibrillation and cardiac arrest are frequent in these patients. In 3 patients with malignant hyperthermia, contraction bands and foci of myofiberlysis were found in the heart at necropsy. Ultrastructurally, areas of myofiber overstretching adjacent to contraction bands and foci of extensive myofiberlysis were associated with disruptions of the sarcolemma. Similar ultrastructural findings have been reported in the skeletal muscles of these patients and are thought responsible for the hyperkalemia which is a constant feature of malignant hyperthermia. Our findings suggest that the ventricular arrhythmias, frequent in this disease, are the result of direct damage to cardiac muscle rather then secondary to elevated plasma levels of potassium.
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PMID:Myocardial changes in malignant hyperthermia. 33 38

Pinacidil is a member of the new antihypertensive drug family possessing an action that involves an increased potassium efflux in vascular and cardiac muscle. We investigated the contribution of opening of ATP-sensitive potassium channel to the development of reperfusion-induced arrhythmias and myocardial ion shifts, particularly that of Na+, K+, Ca2+, and Mg2+ in isolated rat hearts. After 30 min of normothermic global ischemia, pinacidil with 1 to 60 mumol/l failed to reduce the incidence of reperfusion-induced arrhythmias, even on the postischemic/reperfused myocardium in a subset of hearts unresponsive to reperfusion-induced arrhythmias (the duration of ischemia was reduced to 25 min), pinacidil treatment was associated with a greater incidence of reperfusion-induced arrhythmias (100%) as compared to the control value (50%). These proarrhythmic effects of pinacidil were also reflected in a maldistribution of myocardial ion contents both in nonischemic and ischemic/reperfused hearts. Cicletanine, a furopyridine antihypertensive agent that has no effect on coronary resistance, reduced the incidence of reperfusion arrhythmias, and its antiarrhythmic effect was antagonized by pinacidil. The same observation was made in relation to myocardial ion content, e.g., pinacidil-induced K+ loss and Ca2+ gain were antagonized by cicletanine, both in nonischemic and ischemic/reperfused hearts. It is hypothesized that the increased tendency to develop reperfusion-induced ventricular fibrillation is associated with the pinacidil-induced K+ efflux. The present study does not attempt to address the question of specific ionic currents; however, it has been suggested that proarrhythmic and antiarrhythmic effects of pinacidil and cicletanine, respectively, may relate to same receptor sites in which the latter may reflect a specific blockade of the outward K+ ion current via ATP-sensitive K+ channels. If this is so, the use of K+ channel openers as antihypertensive agents may be of particular concern in that population of postinfarction patients who are known to be at high risk of sudden coronary death.
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PMID:Reperfusion-induced arrhythmias and myocardial ion shifts: a pharmacologic interaction between pinacidil and cicletanine in isolated rat hearts. 141 6

The newly developed antihypertensive agent naftopidil blocks alpha 1-adrenoceptors and inhibits Ca2+ entry via potential-dependent channels in vascular and cardiac muscle. It is extensively metabolized in vivo. Since it is of interest whether its metabolites are still pharmacologically active, we have characterized the effects of (naphthyl)hydroxy-naftopidil (NHN), (phenyl)hydroxy-naftopidil (PHN), and O-desmethyl-naftopidil (DMN) in various isolated preparations of the guinea pig heart. In constant-flow Langendorff hearts, the compounds decreased force of contraction by 66-81% and slowed spontaneous heart rate by 28-48%. DMN reduced perfusion pressure by 33%. The fibrillation threshold, which was measured as the strength of alternating current required to induce ventricular fibrillation, increased more than 10-fold. In papillary muscles, 3 x 10(-5) M of all compounds reduced force of contraction (pD2 values approximately 5.5) and shortened the action potential duration in the plateau phase. The maximum depolarization velocity (dV/dtmax) was slightly reduced (10-21%) by NHN, PHN, and DMN. In voltage-clamped ventricular cardiomyocytes, the calcium current ICa was depressed by the three compounds (10(-6)-10(-4) M) in a concentration-dependent manner. In conclusion, the three naftopidil metabolites investigated have pharmacological activities similar to those of their parent compound and hence could contribute to the in vivo effects of naftopidil.
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PMID:Characterization of Ca(2+)-antagonistic effects of three metabolites of the new antihypertensive agent naftopidil, (naphthyl)hydroxy-naftopidil, (phenyl)hydroxy-naftopidil, and O-desmethyl-naftopidil. 172 7

Based on the therory of promoting flow of qi and dispersing blood stasis, the KUO GUAN QU YU LING coronary--dilating and stagnation--dispersing) powder in capsules were prepared for the treatment of 60 cases of coronary heart disease. After a 30 day course of treatment, cardiac ischemia was improved in 64.7% and the symptom of angina pectoris was relieved in 61.7% of the patients. This drug also acted to reduce blood lipids and to improve left cardiac function. Pharmacological study indicated that this preparation improved the tolerance of cardiac muscle against anoxia and prevented ventricular fibrillation and cardiac damage from ischemia.
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PMID:Observations on the treatment of coronary heart disease by kuo guan qu yu ling. 236 65

The effects of the 5-hydroxytryptamine2 (5-HT2) antagonists ketanserin and ritanserin on ischaemia- and reperfusion-induced arrhythmias were investigated in pentobarbitone-anaesthetised rats. Both ketanserin (3 mg kg-1) and ritanserin (1 mg kg-1) significantly reduced the incidence of ventricular fibrillation (from 60 to 25% and 88 to 12%, respectively) and the mortality induced by reperfusion after 5 min of myocardial ischaemia. Neither drug significantly altered the number of ventricular ectopic beats, the incidence of ventricular tachycardia, ventricular fibrillation, or mortality during the first 25 min of coronary artery occlusion. Significant dose-dependent reductions in heart rate and arterial blood pressure were observed with all doses of ketanserin (0.1-3 mg kg-1) and ritanserin (0.3 and 1 mg kg-1), but neither drug had any major effect on arterial blood gases or pH. In isolated guinea pig and rat atria and ventricular muscle preparations, ketanserin (10(-5) M) and ritanserin (3 X 10(-5) M) reduced the maximal driving frequency, whereas 5-HT itself was without effect. The results suggest that the antiarrhythmic activity of ketanserin and ritanserin observed in this study was probably not due to 5-HT2 receptor or alpha 1-adrenoceptor blockade, but may have been due to a direct action on cardiac muscle.
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PMID:Ketanserin and ritanserin can reduce reperfusion-induced but not ischaemia-induced arrhythmias in anaesthetised rats. 244 3

This study evaluates the capacity of regional substrate-enriched blood cardioplegic reperfusion (without bypass) to salvage cardiac muscle subjected to 40 minutes of regional ischemia. Results are compared with those obtained by normal blood reperfusion at either systemic or reduced perfusion pressure (i.e., simulating acute angioplasty or streptokinase thrombolysis). All studies were carried out in beating, working hearts when the conditions of reperfusion were not controlled. The results show that regional cardioplegic reperfusion without cardiopulmonary bypass reduces the incidence of perfusion ventricular fibrillation (15% versus 55%, p less than 0.05), increases recovery of subendocardial creatine phosphate (35.3 versus 14.0 mumol/gm, p less than 0.05) and adenosine triphosphate (6.0 versus 3.1 mumol/gm, p less than 0.05), reduces histochemical damage evaluated by triphenyltetrazolium chloride (0% versus 43% transmural nonstaining, p less than 0.05), and improves myocardial contractile reserve capacity (91% versus 41%, p less than 0.05). Normal blood reperfusion restored immediate systolic shortening in only 3 of 18 hearts (17%), and regional cardioplegic reperfusion without bypass produced early recovery of regional systolic shortening in only 10 of 16 hearts (63%, p greater than 0.05). Thus the value of controlling reperfusate composition without simultaneous control of reperfusion conditions is limited.
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PMID:Metabolic and histochemical benefits of regional blood cardioplegic reperfusion without cardiopulmonary bypass. 374 81

The course of recovery of heart activity [assessed by heart rate, atrioventricular (AV) conduction time, monophasic action potentials, contractile force, and perfusion rate] from hypothermic ischemic arrest was studied on isolated perfused rat hearts. The effect of control ischemic arrest was compared with various cardioplegic protective formulations based on high K+ content. During control hypothermic ischemia (20 degrees C), the heart activity extinguished only gradually, action potentials were biphasic, AV conduction was extremely prolonged, and contractions were slow and relatively strong. On reperfusion (37 degrees C), the recovery of electrical activity was almost instantaneous and normalized within 2 min, whereas the contractile force remained substantially depressed. In contrast, K+-containing cardioplegic solutions stopped the heart within several cycles. Postarrest recovery was delayed and transitorily associated with severe arrhythmias (AV block, repetitive afterdepolarizations and oscillations during elevated plateau, and ventricular fibrillation). Nevertheless, the action potentials as well as the contractile force virtually normalized in 10-15 min. Procaine-containing cardioplegic solutions were ineffective in preventing the onset of postarrest reperfusion arrhythmias, whereas addition of nifedipine to the K+-containing cardioplegic solutions largely prevented these arrhythmias, and contractile force was further improved by high concentrations of glucose. The data indicate that postarrest electrical and mechanical recovery do not recover in parallel. Furthermore, high concentrations of calcium antagonist and glucose preserve the electrical and mechanical properties of the cardiac muscle during periods of cardiac arrest.
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PMID:Differences in electrical and mechanical recovery from ischemic heart arrest and cardioplegia. 399 47

1. Alprenolol, a beta-adrenoceptor blocking drug reported to have the same potency as propranolol in vitro and in vivo, was found to be four times more active than procaine as a local anaesthetic on frog sciatic nerve.2. At doses of 0.125 mg/kg and above alprenolol protected anaesthetized guinea-pigs against ouabain-induced ventricular fibrillation.3. In isolated rabbit atria, resting potentials were unchanged, and the duration of the action potential was not prolonged, by concentrations of alprenolol up to 10.5 x 10(-6)M. The maximum rate of depolarization (MRD), however, was reduced by 30% at a concentration of 0.525 x 10(-6)M. This was 214 times less than the concentration which reduced the frog action potential height by 25%.4. The concentration of alprenolol required to produce more than 15% decrease in contraction or maximum driven frequency was 3.5 x 10(-6)M.5. As a test of the direct action of alprenolol on isolated cardiac muscle, MRD was also a more sensitive test than the measurement of electrical threshold or conduction velocity.
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PMID:Local anaesthetic and anti-arrhythmic actions of alprenolol relative to its effect on intracellular potentials and other properties of isolated cardiac muscle. 439 60

1 The intravenous administration, to anaesthetized rats, of meptazinol (1 and 2 mg kg-1), a partial agonist at opiate receptors, greatly reduced the incidence of ventricular extrasystoles that resulted from acute coronary artery occlusion. The incidence of ventricular fibrillation (VF) was reduced from 50% (in the controls) to 10% and the mortality from 30% to zero. 2 In similar doses, pretreatment with meptazinol also reduced ventricular arrhythmias, including fibrillation, in conscious rats subjected to coronary artery occlusion. In this model, survival at 16 h was increased from 27% in the controls to 50% and 83% respectively in rats pretreated with 1 and 2 mg kg-1 of the drug. 3 In antiarrhythmic doses, meptazinol had little effect on either heart rate or systemic arterial blood pressure. 4 Intracellular action potential recordings from papillary muscle removed from rats given meptazinol (2 mg kg-1) 15 min previously showed an increase in APD50 and APD90 of more than 40%. There was no effect on dV/dtmax. When superfused with meptazinol in vitro normal rat papillary muscle stimulated at 1 or 3 Hz showed an increase in APD90 and a decrease in dV/dtmax. 5 The antiarrhythmic effect of meptazinol in these models can probably be explained by direct actions on the cardiac muscle action potential (increase in APD) although effects on opiate receptors cannot be ruled out. It is suggested that meptazinol might be useful in relieving pain, and in reducing the severity of arrhythmias in the early stages of acute myocardial infarction.
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PMID:Antiarrhythmic actions of meptazinol, a partial agonist at opiate receptors, in acute myocardial ischaemia. 630 99


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