Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The antiarrhythmic effect of magnesium sulfate (Mg) as well as the hemodynamics were studied using the coronary ligation and reperfusion models in rats. In the study on coronary ligation arrhythmia, i.v. administration of Mg (0.6, 2, 6, 20 and 60 micromol) was conducted at 5 min after coronary ligation. Mg had an action to decrease the total number of premature ventricular contraction (PVC), the duration of ventricular tachycardia (VT), the frequency of VT and ventricular fibrillation (Vf) and the mortality ratio for 30 min after coronary ligation. In the 6-60 micromol groups, significant antiarrhythmic action (p < 0.01 vs. control) was attained. In the study on reperfusion arrhythmia, i.v. administration of Mg (20, 60 and 200 micromol) was conducted at 4 min after coronary ligation, and at 1 min after ligation, the coronary artery was reperfused. Mg had an action to decrease the frequency of Vf, the mortality ratio and the duration of VT and Vf and to extend the interval between the initiation of reperfusion and the occurrence of VT and Vf for 10 min after reperfusion. In the 200 micromol group, significant antiarrhythmic action (p < 0.05 vs. control) was attained. Administration of Mg decreased the heart rate and blood pressure. We concluded that Mg can control myocardial ischemia-induced and reperfusion-induced arrhythmia and that sudden cardiac death which occurs as a result of arrhythmia can be prevented.
Mol Cell Biochem 1999 Sep
PMID:Antiarrhythmic effect of magnesium sulfate against occlusion-induced arrhythmias and reperfusion-induced arrhythmias in anesthetized rats. 1054 68

Cocaine use poses a major health problem not only because of the dependence it causes but also because of the generation of life-threatening cardiac arrhythmias following overdose. Elucidating the molecular mechanisms of action of cocaine, therefore, remains a critical step in developing treatment for cocaine addiction and preventing cardiac complications. Although the neurotransmitter transporters are suggested to be primary targets for cocaine, the continued drug-seeking behavior of transporter knock-out mice suggests the involvement of additional mechanisms. Several studies have shown that voltage-gated calcium channel blockers can prevent the behavioral and reinforcing effects of the drug and also cocaine-induced cardiac events, including lethal ventricular fibrillation. However, the role of voltage-gated calcium channels in cocaine-induced responses is not clear. Herein, I show that cocaine, in pharmacological doses, selectively and potently enhances L-type calcium channel currents in isolated rat ventricular myocytes. This potentiation by cocaine is due to an increase and decrease, respectively, in the calcium channel opening and closing rates, with no apparent effects on voltage-dependence or single-channel conductance. The effects of cocaine are rapidly reversible and unaffected by prior ATPgammaS-induced channel phosphorylation. These results suggest that cocaine directly binds and facilitates the opening of L-type calcium channels. Importantly, elevated intracellular calcium levels via this mechanism triggering second messenger pathways and gene activation may contribute to many of the cardiovascular and central nervous system effects of cocaine.
Mol Pharmacol 1999 Dec
PMID:Selective potentiation of L-type calcium channel currents by cocaine in cardiac myocytes. 1057 40

The aim of the study was to use the isolated blood-perfused rat heart to: (i) determine whether brief intermittent rapid pacing and ventricular fibrillation are able to mimic preconditioning by ischemia and thereby protect the isolated blood-perfused heart against ischemia-induced injury and (ii) characterize the effects of these interventions on cardiac metabolism. To this end, isolated, blood-perfused (2.4 ml/min), paced (360 beats/min) rat hearts (n = 6/group), were aerobically perfused for 20 min. Hearts were then randomized to four groups: (i) a further 16 min aerobic perfusion (UC, untreated controls), (ii) ischemic preconditioning (IP, 3 min ischemia + 3 min reperfusion followed by 5 min ischemia + 5 min reperfusion), (iii) electrically induced ventricular fibrillation (VF, 3 min fibrillation + 3 min sinus rhythm followed by 5 min fibrillation + 5 min sinus rhythm) and (iv) rapid pacing at > or = 600 beats/min (RP, 3 min rapid pacing + 3 min normal heart rate followed by 5 min rapid pacing + 5 min normal heart rate). Hearts were then subjected to 35 min of zero-flow, global ischemia (37 degrees C) and 40 min reperfusion. In parallel studies, blood samples were collected during the first 3 min of treatment and plasma taken for the analysis of noradrenaline. The hearts were then immediately frozen and assayed for high energy phosphates and noradrenaline content. Time-to-50% contracture during ischemia was 13.2 +/- 0.8 min in controls; this was reduced to 6.3 +/- 1.1 min by IP but was unaffected by VF or RP (12.4 +/- 1.1 and 12.8 +/- 1.2 min respectively). Post-ischemic left ventricular developed pressure (LVDP) in untreated controls recovered to only 19.9 +/- 8.4% of its pre-ischemic value whereas with IP, VF and RP substantial and similar improvements were observed (60.3 +/- 7.4, 56.2 +/- 5.7 and 45.3 +/- 10.3%, respectively, P < 0.01). This protection was achieved without any significant depletion of high energy phosphates during VF or RP. Noradrenaline was essentially unchanged in controls and with RP, but VF caused a loss from tissue and a large elevation in the plasma. Our results suggest that both RP and VF are as effective as brief ischemia in protecting the heart against injury during ischemia and reperfusion. In contrast to IP, this protection can be achieved without the exacerbation of ischemic contracture and without inducing ischemia during the preconditioning period.
J Mol Cell Cardiol 1999 Nov
PMID:Cardioprotection: intermittent ventricular fibrillation and rapid pacing can induce preconditioning in the blood-perfused rat heart. 1059 Oct 23

HNS-32 (N1,N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3, 8-dimethylazulene-1-carboxamidine: CAS 186086-10-2) is a newly synthesized compound, and possesses antiarrhythmic properties with vasodilator action in dog hearts. The aim of this study was to investigate the dose-dependent effects of HNS-32 on ischemia- and/or reperfusion-induced ventricular arrhythmias in anesthetized rats in vivo and compared with those of mexiletine. Saline or drugs were administered intravenously 5 min prior to coronary artery occlusion. On the ischemia-induced ventricular arrhythmias, HNS-32 showed dose-dependent reduction of total number of premature ventricular complexes (PVC) from 2091+/-225 to 656+/-116 and 286+/-69 beats/30 min (p < 0.05), the ventricular tachycardia (VT) duration from 183+/-33 to 28+/-9 and 4+/-2 sec (p < 0.05), the incidence of VT from 100 to 90 (n.s.) and 40% (p < 0.05), and the incidence of ventricular fibrillation (VF) from 50 to 0 and 0% (p < 0.05) with 3 and 5 mg/kg, respectively. Mexiletine also reduced these parameters to 936+/-159 beats/30 min (p < 0.05), 39+/-22 sec (p < 0.05), 90% (n.s.) and 10% (n.s.), respectively. HNS-32 completely suppressed the late reperfusion-induced arrhythmias, however mexiletine did not affect them. On the early reperfusion-induced ventricular arrhythmias, HNS-32 showed dose-dependent reduction of VT duration from 126+/-34 to 37+/-12 and 3+/-2 sec (p < 0.05), incidence of VT from 100 to 90 (n.s.) and 40% (p < 0.05), incidence of VF from 100 to 10 and 0% (p < 0.05), and mortality rate from 90 to 0 and 0% (p < 0.05), with 3 and 5 mg/kg, respectively. Mexiletine also reduced these parameters to 16+/-9 sec (p < 0.05), 80 (n.s.), 50 (p < 0.05), and 10% (p < 0.05), respectively. HNS-32 significantly reduced the heart rate in a dose-dependent manner, from 399+/-14 to 350+/-8 and 299+/-10 beats/min (p < 0.05) with 3 and 5 mg/kg, respectively. The antiarrhythmic effects of HNS-32 were more potent than that of the similar dose of mexiletine against occlusion-induced and reperfusion-induced arrhythmias in in vivo rats.
Mol Cell Biochem 2000 Feb
PMID:Effects of HNS-32, a novel antiarrhythmic drug, on ventricular arrhythmias induced by coronary artery occlusion and reperfusion in anesthetized rats. 1082 31

A protective effect of the n-3 polyunsaturated fatty acids (PUFAs) in preventing ventricular fibrillation in experimental animals and cultured cardiomyocytes has been demonstrated in a number of studies. In this study, a possible role for the n-3 PUFAs in the treatment of atrial fibrillation (AF) was investigated at the cellular level using atrial myocytes isolated from young adult rats as the experimental model. Electrically-stimulated, synchronously-contracting myocytes were induced to contract asynchronously by the addition of 10 microM isoproterenol. Asynchronous contractile activity was reduced following acute addition of the n-3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) at 10 microM, compared with no fatty acid addition (from 99.0+/-1.0% to 30.7+/-5.2% (p < 0.05) for DHA and 23.8+/-2.8% (p < 0.01) for EPA), while the saturated fatty acid, docosanoic acid (DA) and the methyl ester of DHA (DHA m.e.) did not exert a significant effect on asynchronous contractile activity. Asynchronous contractile activity was also reduced to 1.7+/-1.7% in the presence of the membrane fluidising agent, benzyl alcohol (p < 0.001 vs no fatty acid addition). Cell membrane fluidity was determined by steady state fluorescence anisotropy using the fluorescent probe, TMAP-DPH. Addition of DHA, EPA or benzyl alcohol significantly increased sarcolemmal membrane fluidity (decreased anisotropy, r(ss)) of atrial myocytes compared with no addition of fatty acid (control) (from r(ss) = 0.203+/-0.004 to 0.159+/-0.004 (p < 0.01) for DHA, 0.166+/-0.001 (p < 0.01) for EPA and 0.186+/-0.003 (p < 0.05) for benzyl alcohol, while DA and DHA m.e. were without effect. It is concluded that the n-3 PUFAs exert anti-asynchronous effects in rat atrial myocytes by a mechanism which may involve changes in membrane fluidity.
Mol Cell Biochem 2000 Mar
PMID:Termination of asynchronous contractile activity in rat atrial myocytes by n-3 polyunsaturated fatty acids. 1083 92

The effects of high-dose epinephrine (HDE) combined with isoprenaline (Iso) on myocardial hemodynamics of isolated rabbit heart were studied. The electrophysiology and L-type Ca2+ channel of single ventricular myocyte after cardioversion of ventricular fibrillation were determined. The results suggest that parameters of hemodynamics were significantly enhanced by HDE+Iso than that of HDE (p < 0.01). The OS and Vmax of HDE+Iso increased 83.7 and 10.15% respectively compared to HDE alone. The APF of HDE+Iso is much more rapid than that of HDE (138.38 +/- 9.96 vs. 55.58 +/- 8.63 min(-1), p < 0.001). The APD50 and APD90 of HDE+Iso were significantly decreased; HR was increased (134.16 +/- 1.48 vs 62.20 +/- 6.25 min(-1)); and the amplitude current of through L-type Ca2+ channel was reduced but was significantly higher than the control. We conclude that HDE+Iso can improve the hemodynamics and improve electrophysiology of cardiomyocytes after cardioversion of ventricular fibrillation which is likely interrelated with I(Ca). The combined use of epinephrine and isoprenaline for cardiopulmonary resuscitation of primary ventricular fibrillation may be beneficial when employed in clinical situations.
Mol Cell Biochem 2000 Apr
PMID:The effects of high-dose epinephrine combined with isoprenaline on isolated rabbit heart and cardiomyocytes after cardioversion of ventricular fibrillation. 1088 29

Diabetic hearts are suggested to exhibit either increased or lower sensitivity to ischemia. Detrimental effects of prolonged ischemia can be attenuated by preconditioning, however, relatively little is known about its effects in the diseased myocardium. This study was designed to test the susceptibility to ischemia-induced arrhythmias and the effect of preconditioning in the diabetic heart. Rats were made diabetic with streptozotocin (45 mg/kg, i.v.). After 1 week, isolated Langendorff-perfused hearts were subjected to 30 min occlusion of LAD coronary artery without or with preceding preconditioning induced by one cycle of 5 min ischemia and 10 min reperfusion. Glycogen and lactate contents were estimated in the preconditioned and non-preconditioned hearts before and after ischemia. Diabetic hearts were more resistant to ischemia-induced arrhythmias: incidence of ventricular tachycardia (VT) decreased to 42% and only transient ventricular fibrillation (VF) occurred in 17% of the hearts as compared to the non-diabetic controls (VT 100% and VF 70% including sustained VF 36%; p < 0.05). Preconditioning effectively suppressed the incidence and severity of arrhythmias (VT 33%, VF 0%) in the normal hearts. However, this intervention did not confer any additional protection in the diabetic hearts. Despite higher glycogen content in the diabetic myocardium and greater glycogenolysis during ischemia, production of lactate in these hearts was significantly lower than in the controls. Preconditioning caused a substantial decrease in the accumulation of lactate in the normal hearts, whereby in the diabetic hearts, this intervention did not cause any further reduction in the level of lactate. In conclusion, diabetic rat hearts exhibit lower susceptibility to ischemic injury and show no additional response to preconditioning. Reduced production of glycolytic metabolites during ischemia can account for the enhanced resistance of diabetic hearts to ischemia as well as for the lack of further protection by preconditioning.
Mol Cell Biochem 2000 Jul
PMID:Acute diabetes modulates response to ischemia in isolated rat heart. 1097 67

Ventricular fibrillation leading to sudden cardiac death can occur even in the absence of structural heart disease. One form of this so-called idiopathic ventricular fibrillation (IVF) is characterized by ST segment elevation (STE) in the electrocardiogram. Recently we found that IVF with STE is linked to mutations of SCN5A, the gene encoding the cardiac sodium channel alpha -subunit. Two types of defects were identified: loss-of-function mutations that severely truncate channel proteins and missense mutations (e.g. a double mutation, R1232W and T1620M) that cause only minor changes in channel gating. Here we show that co-expression of the R1232W+T1620M missense mutant alpha -subunits in a mammalian cell line stably transfected with human sodium channel beta(1)-subunits results in a phenotype similar to that of the truncation mutants. In the presence of beta(1)subunits the expression of both ionic currents and alpha -subunit-specific, immunoreactive protein was markedly suppressed after transfection of mutant, but not wild-type alpha -subunits when cells were incubated at physiological temperature. Expression was partially restored by incubation at reduced temperatures. Our results reconcile two classes of IVF mutations and support the notion that a reduction in the amplitude of voltage-gated sodium conductance is the primary cause of IVF.
J Mol Cell Cardiol 2000 Oct
PMID:Functional suppression of sodium channels by beta(1)-subunits as a molecular mechanism of idiopathic ventricular fibrillation. 1101 31

Protein kinase C (PKC) has been known to play an important role in ischemic preconditioning (IP). This study was designed to examine whether the translocation of PKC is associated with the cardioprotective effects of IP in vivo on infarct size and ventricular arrhythmias in a rat model. Using anesthetized rats, heart rate, systolic blood pressure, infarct size and ventricular arrhythmias during 45 min of coronary occlusion were measured. PKC activity was assayed in both the cytosolic and cell membrane fraction. Brief 3-min periods ofischemia followed by 10 min ofreperfusion were used to precondition the myocardium. Calphostin C was used to inhibit PKC. Infarct size was significantly reduced by IP (68.1 (2.5)%, mean (S.E.) vs. 45.2 (3.4)%, p < 0.01). The reduction in infarct size by IP was abolished by pretreatment with calphostin C. The total number of ventricular premature complex (VPC) during 45 min of coronary occlusion was reduced by IP (1474 (169) beats/45 min vs. 256 (82) beats/45 min, p < 0.05). The reduction the total number of VPC induced by IP was abolished by the administration of calphostin C before the episode of brief ischemia. The same tendency was observed in the duration of ventricular tachycardia and the incidence of ventricular fibrillation. PKC activity in the cell membrane fraction transiently increased immediately after IP (100 vs. 142%, p < 0.01) and returned to baseline 15 min after IP. Pretreatment with calphostin C prevented the translocation of PKC. The translocation of PKC plays an important role in the cardioprotective effect of IP on infarct size and ventricular arrhythmias in anesthetized rats.
Mol Cell Biochem 2000 Nov
PMID:Protein kinase C is involved in cardioprotective effects of ischemic preconditioning on infarct size and ventricular arrhythmia in rats in vivo. 1119 88

The objective of this study was to investigate if a variation in extracellular-K+ concentrations alters the effects of global pre-conditioning on ischemia-induced arrhythmias. Rat hearts were Langendorff-perfused with Krebs-Henseleit solution and randomised in 8 groups (n = 12/group): four control groups (K+: 2, 4, 6, or 8 mmol/L) which underwent 30-min coronary artery occlusion and four preconditioned groups (K+: 2, 4, 6, or 8 mmol/L) in which the 30-min regional ischemia was preceded by 2 cycles of 3 min global ischemia. In the presence of low K+ (2 mmol/L), there were no differences between control and preconditioning groups in the number of ventricular premature beats (VPBs): 194 +/- 64 vs. 217 +/- 81, the incidence of ventricular tachycardia (VT): 100% vs. 100% and of ventricular fibrillation (VF): 100% vs. 100%. In the presence of normal K+ concentration (4 mmol/L), ischemic preconditioning reduced the number of VPBs from 88 +/- 26 to 25 +/- 10, (p < 0.05), the incidence of VT from 100 to 50% (p < 0.05), and of VF from 67 to 16% (p < 0.05). In the condition of higher K+ concentration (6 mmol/ L), VPBs (34 +/- 8 vs. 11 +/- 4), the incidence of VT (100% vs. 25%; p < 0.05 ) and VF (25% vs. 8%) were further reduced in preconditioned hearts. In the condition of K+ concentration (8 mmol/L), there were no differences in VPBs (11 +/- 3 vs. 7 +/- 2), the incidence of VT (8% vs. 0%) and VF (8% vs. 0%) between control and preconditioned hearts. Our data show that ischemic preconditioning affords protection against arrhythmias during coronary artery occlusion in the isolated rat heart and that hypokalemia abolishes the antiarrhythmic effects of global preconditioning.
Mol Cell Biochem 2000 Nov
PMID:Influence of extracellular potassium on the antiarrhythmic effect of global preconditioning in isolated perfused rat hearts. 1119 93


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