Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of Bunaphtine on right atrial and ventricular monophasic action potentials were investigated in 6 patients using the technique of endocavitary recording with a suction electrode. The authors found that the drug, given intravenously in the usual therapeutic dosages, increases the total duration of MAP both atrial and ventricular, together with quite a proportional ERP prolongation. At ventricular level MAP's increase in correlated to a prevailing and strong increase of phase 3. However, the variations of the MAP's amplitude, its O dv/dt phase and the cardiac specific conduction's alterations (noted only at higher dosages) have been inconstant and poor on the whole. On the basis of these results, the mechanism of the action of the drug is discussed.
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PMID:[Effects of Bunaphtine on right atrial and ventricular monophasic action potentials in man. Preliminary note (author's transl)]. 101 Jan 95

In this paper the authors conclude their study of the mechanism of the action of Bunaphtine. Both atrial and ventricular MAP were recorded by a suction electrode in 13 patients before and after Bunaphtine (1.5-2 and 2.5 mg/Kg i.v.). With the lower dosages, the drug acts specifically on repolarization: it greatly increases the duration of MAP, together with a proportional ERP prolongation; the ERP/MAP ratio is not changed. With the higher dosages, there is a greater effect on the depolarization velocity (decrease of the O dv/dt phase of MAP) and on the conduction, this last being less evident. At the atrial level there is a conspicous ERP prolongation, with a remarkable increase of ERP/MAP ratio. There is full agreement between these results and those obtained experimentally on the dog and in vitro. Bunaphtine has therefore unquestionable antiarrhythmic properties and it can have a double action mechanism; with higher dosages its action-quinidine-like-is predominant at the atrial level.
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PMID:[A study of the mechanism of the action of Bunaphtine recording the myocardial monophasic action potentials in man. Conclusive report (author's transl)]. 101 Feb 48

The use of MAP recording techniques has been said to have bridged the gap between basic in vitro investigation of the transmembrane action potential and observations made in situ from the beating heart. With regard to antiarrhythmic agents, MAP recordings are particularly useful in evaluating drugs which prolong repolarization. The simultaneous measurement of MAP and ERP at the same site permits the comparison of drug effects on repolarization and refractoriness. The ability to safely and reliably record the MAP contributes importantly to the evaluation and classification of antiarrhythmic drug effects in vivo and may ultimately lead to more rational selection of drug therapy for individual patients. Antiarrhythmic drug effects demonstrated with MAP recordings have generally shown good agreement with the Vaughan Williams classification of electrophysiological actions. An important key to drug efficacy may be that some drugs prolong refractoriness beyond their effect on repolarization. Conversely, a potential explanation for proarrhythmia may lie in slowing of conduction without the concomitant protective effect of postrepolarization refractoriness. The phenomenon of use dependence, which has been demonstrated for many drugs, suggests why an agent that prevents induction of arrhythmia during programmed stimulation in the electrophysiology laboratory may not prevent spontaneous arrhythmia initiation at slower heart rates. The paramount task of clinical electrophysiology is the successful treatment of rhythm disturbances. The more detailed and quantitative evaluation of drug effects afforded by MAP recordings may ultimately result in the more effective use of antiarrhythmic drugs in general and to more precise tailoring of therapy for individual patients.
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PMID:Monophasic action potential recordings: evaluation of antiarrhythmic drugs. 206 9

The contribution of the sympathetic nervous system in the definition of various electrophysiological variables was studied in chemically sympathectomised dogs. Chemical sympathectomy was obtained following intravenous injection of 50 mg X kg-1 of 6-hydroxydopamine. Sympathectomised dogs presented significant increases in: basic sinus period, sino-atrial conduction time (SACT), AH and HV intervals of the His bundle electrogram, atrial functional (AFRP) and effective (AERP) refractory periods, atrio-ventricular node functional (AVNFRP) and effective (AVNERP) refractory periods, ventricular functional (VFRP) and effective (EVRP) refractory periods and atrial (AMAP) and ventricular (VMAP) monophasic action potential durations. Corrected sinus recovery time (CSRT) was not affected by chemical sympathectomy. Neither was the atrial ERP/MAP duration ratio. This new form of sympathectomy affects all the levels of the cardiac conduction system. Such results are in accordance with those obtained with surgical sympathectomy or the use of beta-blocking agents.
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PMID:Electrophysiology of the chemically sympathectomised dog. 681 69

The cardiovascular effects of the K-ATP channel blocker U-37883A and 5 related morpholinoguanidines were determined in 6 experimental preparations. In anesthetized dogs, U-37883A (0.5-8.0 mg/kg i.v.) increased mean arterial pressure (MAP; +18%) and left ventricular (LV) effective refractory period (ERP; +35%), and decreased LV contractility (-41%). Higher doses of U-37883A (16-32 mg/kg) fatally reduced MAP (-84%), heart rate (HR; -57%) and LV contractility (-72%). In anesthetized rats, U-37883A (1.0-50 mg/kg i.v.) also maximally reduced MAP, HR and LV contractility by 68, 77 and 48%, respectively. U-37883A and its analogs were diuretic in conscious rats (1.5-15 mg/kg i.v.) and blocked pinacidil in rabbit mesenteric artery (EC50 = 0.5-50 microM). In rabbit papillary muscle, 50 microM U-37883A significantly reduced force of contraction (-33%) and prolonged conduction time (+244%). Milder papillary effects were seen with the N'-OH analog U-45194A, which did not depress LV contractility in intact rats. In conscious dogs, oral U-45194A (50 mg/kg) was diuretic but reduced LV stroke volume and increased peripheral vascular resistance. These studies characterize U-37883A's systemic cardiovascular and direct myocardial effects, and identify U-45194A as a less cardiac depressant analog having U-37883A-like diuretic and functional K-ATP channel blocking activities.
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PMID:Cardiovascular effects of the K-ATP channel blocker U-37883A and structurally related morpholinoguanidines. 880 57

Externally regulated phosphatase (ERP or MKP-1) is a dual specificity phosphatase that has been implicated in the dephosphorylation of mitogen activated protein kinases (MAP kinases). MAP kinase is activated in response to external signals and in turn phosphorylates proteins essential to the regulation of cell growth. To study the role of ERP/MKP-1 protein in mammalian development and its function in signal transduction we have generated mice, embryonic stem (ES), cells and mouse embryo fibroblasts (MEFs) that are deficient in the ERP/MKP-1 protein. ERP/MKP-1-deficient mice are born at normal frequency, are fertile and present no phenotypic or histologic abnormalities. MAP kinase activity and the induction of c-fos mRNA is unaltered in MEFs lacking the ERP/MKP-1 protein, indicating no alteration of the MAP kinase pathway. In addition, ERP/MKP-1 deficient MEFs grow and enter DNA synthesis at the same rate as control cells. Our results demonstrate that the activity of ERP/MKP-1 is not essential for embryo development and indicate that the lack of ERP/MKP-1 activity can be compensated by other phosphatases in vivo.
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PMID:Disruption of the erp/mkp-1 gene does not affect mouse development: normal MAP kinase activity in ERP/MKP-1-deficient fibroblasts. 880 81