UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Short periods of coronary artery occlusion protect the heart against the effects of a subsequent prolonged period of ischaemia. This phenomenon is known as preconditioning of the ischaemic myocardium. 2. In mongrel, chloralose-urethane anaesthetized open-chest dogs, within a restricted body weight range, two 5 min periods of occlusion of the anterior descending branch of the left coronary artery markedly reduced the severity of the early ischaemic arrhythmias resulting from a prolonged (25 min) occlusion of the same coronary artery starting 20 min later. Thus, the number of ventricular premature beats (VPBs) was reduced from 528 +/- 140 in controls to 78 +/- 27 in preconditioned dogs, the incidence of ventricular fibrillation (VF) was reduced from 47% to 0% and the incidence of ventricular tachycardia (VT) from 100% to 20%. ST-segment elevation recorded from electrodes within the ischaemic area, and the degree of inhomogeneity of conduction within the ischaemic area were markedly reduced in these preconditioned dogs. 3. The incidence of VF following reperfusion of the ischaemic myocardium at the end of the 25 min occlusion period was reduced in the preconditioned dogs from 100% to 60%; there was thus a 40% survival from the combined ischaemia-reperfusion insult compared with 0% in the controls. 4. NG-nitro-L-arginine methyl ester (L-NAME) an inhibitor of the L-arginine nitric oxide pathway, given in a dose of 10 mg kg-1 intravenously on two occasions, both before the initial preconditioning occlusion and then again before the prolonged occlusion, partially attenuated the protective effects of preconditioning.There were more VPBs (220 +/- 75), a higher incidence of VT (60%) and more episodes of VT (11.5 +/- 6.0 compared to 0.7 +/- 0.3 episodes in the preconditioned dogs not given L-NAME); none of the animals survived reperfusion (incidence of VF 100%). The improvement in the severity of the degree of in homogeneity which resulted from preconditioning was abolished by L-NAME administration.5. L-NAME itself elevated blood pressure (from 96 +/- 5 mmHg diastolic to 119 +/- 7 mmHg), reduced heart rate (from 155 +/- 7 to 144 +/- 4 beats min-') but did not change LVEDP, LVdP/dt,,,,, coronary blood flow, ST-segment elevation or the degree of inhomogeneity of conduction. When given 10 min before the prolonged coronary artery occlusion in dogs not subjected to preconditioning, L-NAME had no significant effect on the severity of arrhythmias except for more periods of VT (a mean of 11.7 +/- 4.7episodes per dog).6. It is concluded from these studies that the generation of nitric oxide contributes to the marked antiarrhythmic effects of preconditioning in the canine myocardium, probably through elevation of cyclic GMP.
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PMID:Preconditioning of the ischaemic myocardium; involvement of the L-arginine nitric oxide pathway. 147 63

The effects of endothelin-1 (ET-1), an ET(A)/ETB-receptor agonist, and IRL 1620, a potent and selective ETB-receptor agonist, were assessed on left circumflex coronary artery diameter (sonomicrometry) and flow (electromagnetic flow probe) in pentobarbital-anesthetized dogs. Intracoronary (i.c.) bolus injections of ET-1 (80 pmol/dose) caused large, sustained coronary diameter decreases (281 +/- 39 microns) and transient flow increases (5.6 +/- 2.6 ml/min), followed by transient (10.0 +/- 1.9 ml/min) and then sustained flow reductions (6.6 +/- 2.5 ml/min) before terminating in ventricular fibrillation after two to five doses (max delta s; n = 4 dogs). IRL 1620 boluses (5-2,000 pmol/dose i.c.; max delta s; n = 3) also dose-dependently and transiently increased (16.8 +/- 1.4 ml/min; 200 pmol), then transiently decreased (12.8 +/- 1.5 ml/min; 1,600 pmol) flow but had minimal effects on diameter (delta = -23 +/- 4 microns; 2,000 pmol). Doses of IRL 1620 beyond 400 pmol were accompanied by a slowly responding, sustained decrease in baseline flow (-9.2 +/- 2.7 ml/min) and baseline diameter (232 +/- 150 microns). In a separate group of dogs (n = 5), IRL 1620 (400 pmol i.c.) was evaluated before and after sequential inhibition of cyclooxygenase (indomethacin; 10 mg/kg i.v.) and then nitric oxide synthase (N omega-nitro-L-arginine methyl ester, L-NAME; 50 mg/kg i.v.). Indomethacin alone did not affect the flow increase to IRL 1620 (11.0 +/- 2.0 versus 11.8 +/- 1.8 ml/min) but blunted the flow decrease by 30 +/- 6% (10.6 +/- 1.4 versus 7.1 +/- 0.7 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential responsiveness of conduit and resistance coronary arteries to endothelin A and B receptor stimulation in anesthetized dogs. 750 56

Inhibition of the angiotensin converting enzyme (ACE) with ramipril was studied in male Wistar rats during long-term inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME). Chronic treatment with L-NAME in a dose of 25 mg/kg per day over 6 weeks caused myocardial hypertrophy and a significant increase in systolic blood pressure (245 +/- 16 mmHg) as compared to controls (155 +/- 4 mmHg). Animals receiving simultaneously L-NAME and ramipril were protected against blood pressure increase and partially against myocardial hypertrophy. L-NAME caused a significant reduction in glomerular filtration rate (GFR: 2.56 +/- 0.73 ml.kg-1.min-1) and renal plasma flow (RPF: 6.93 +/- 1.70 ml.kg-1.min-1) as compared to control (GFR: 7.29 +/- 0.69, RPF: 21.36 +/- 2.33 ml.kg-1.min-1). Addition of ramipril prevented L-NAME-induced reduction in GFR and renal plasma flow. L-NAME produced an elevation in urinary protein excretion and serum creatinine and a decrease in potassium excretion which was antagonised by ramipril. L-NAME-induced increase in plasma renin activity (PRA) was further elevated with ramipril treatment. Isolated hearts from rats treated with L-NAME showed increased post-ischaemic reperfusion injuries. Compared to controls duration of ventricular fibrillation was increased and coronary flow reduced. During ischemia the cytosolic enzymes lactate dehydrogenase and creatine kinase, as well as lactate in the venous effluent were increased. Myocardial tissue values of glycogen, ATP, and creatine phosphate were decreased, whereas lactate was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ramipril prevents the detrimental sequels of chronic NO synthase inhibition in rats: hypertension, cardiac hypertrophy and renal insufficiency. 753 99

It has been proposed that NO may function as an endogenous cardioprotectant. We have investigated whether modulation of NO levels (detected in coronary effluent by chemiluminescence) by a blocker of its synthesis, by supplementation of its precursor, and by administration of an NO donor can influence reperfusion arrhythmias in the isolated rat heart. Rat hearts were perfused with modified Krebs' solution and subjected to 5, 35, or 60 minutes of left regional ischemia followed by 10 minutes of reperfusion. NG-Nitro-L-arginine methyl ester (L-NAME), which blocks NO synthase, increased the incidence of reperfusion-induced ventricular fibrillation (VF) from 5% in the control condition to 35% after 60 minutes of ischemia (n = 20, P < .05). The profibrillatory effect of L-NAME was prevented in hearts coperfused with 1 or 10 mmol/L L-arginine (an NO precursor) but persisted in hearts coperfused with D-arginine (1 mmol/L). L-NAME did not increase VF susceptibility in hearts reperfused after 5 or 35 minutes of ischemia. L-NAME caused sinus bradycardia (264 +/- 10 versus 309 +/- 5 bpm in control groups, P < .05) and reduced coronary flow before ischemia (6.2 +/- 0.6 versus 9.2 +/- 0.6 mL.min-1.g-1 tissue in controls, P < .05). L-NAME reduced coronary effluent NO levels after 60 minutes of ischemia; during the first minute of reperfusion, values were reduced from 1457 +/- 422 to 812 +/- 228 pmol.min-1.g-1 (P < .05). This effect was prevented by coperfusion with L-arginine (10,344 +/- 1730 pmol.min-1.g-1, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of NO modulation on cardiac arrhythmias in the rat isolated heart. 755 53

Ischemic preconditioning (PC) has been shown to limit ischemia- and reperfusion-induced arrhythmias. We wished to determine whether the antiarrhythmic effect of PC would be affected by inhibition of the L-arginine nitric oxide (NO) pathway in anesthetized rats. Ischemia and reperfusion were produced by occlusion and release of a snare around the left coronary artery in all rats. The effect of PC (three cycles of 2-min coronary artery occlusion and 5-min reperfusion) on development of reperfusion-induced arrhythmias after 5-min coronary artery occlusion was studied in 12 rats. In 24 other rats, the specific NO synthesis inhibitor NG-monomethyl-L-arginine (L-NMMA 10 mg/kg, n = 12) or the muscarinic receptor antagonist-NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME 10 mg/kg, n = 12), was administered intravenously (i.v.) before PC. In control groups, solvent (n = 15), L-NAME (10 mg/kg i.v., n = 12), L-NMMA (10 mg/kg i.v., n = 12), or L-arginine (L-Arg 100 mg/kg i.v., n = 12) was administered to rats 5 min before coronary artery occlusion without PC. PC significantly reduced the incidence of ventricular premature beats (VPBs) from 100% in the non-PC solvent group to 17%, decreased the incidence of ventricular tachycardia (VT) from 93 to 8%, and abolished the incidence of reversible and irreversible ventricular fibrillation (RVF and IVF: 87 and 47% in the non-PC solvent group, respectively). L-NAME and L-NMMA did not significantly affect the protective effect of PC on reperfusion-induced arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does the antiarrhythmic effect of ischemic preconditioning in rats involve the L-arginine nitric oxide pathway? 759 18

Endothelin-1 (ET-1) has been demonstrated to produce numerous cardiac effects and increased production of the peptide has been shown in cardiac disease states. Although the cardiac effects of ET-1 have been examined extensively on its own, few studies have reported potential cross-talk between ET-1 with other endothelium-derived factors. We examined whether nitric oxide (NO) can modulate the effects of ET-1 on isolated rat hearts or ventricular myocytes. At 0.05 nM, ET-1 produced no effects on either systolic or diastolic function although a two-fold increase in left ventricular end-diastolic pressure (LVEDP) was observed in hearts pretreated with 10 microM of the NO synthase inhibitor L-NAME. Higher concentrations of ET-1 (0.5 and 5 nM) produced a direct elevation in LVEDP which was enhanced by L-NAME and totally blocked by the NO donor S-nitrosoacetylpenicillamine (SNAP, 10 microM) although responses to 5 nM ET-1 were highly variable with no significant differences between treatment groups. SNAP totally prevented ventricular fibrillation produced by either 0.05 or 0.5 nM ET-1 whereas the pro-fibrillatory actions of 5 nM ET-1 were unaffected. In cardiac myocytes, SNAP significantly attenuated the elevation in intracellular Ca2+ produced by ET-1 (5 nM). The positive inotropic actions of ET-1 on either hearts or myocytes were unaffected by any treatment. The protective effect of SNAP against ET-1 in both isolated hearts (reduction in LVEDP and incidence of fibrillation) as well as ventricular myocytes (attenuation of the elevation in intracellular Ca2+) was mimicked by 8-bromo-cyclic GMP (50 microM). Our study suggests that NO protects against the cardiotoxic effects of ET-1, possibly via inhibition of intracellular Ca2+ elevations, a property shared by cGMP, the likely mediator of the biological effects of NO.
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PMID:Modulation of endothelin-1 effects on rat hearts and cardiomyocytes by nitric oxide and 8-bromo cyclic GMP. 872 59

To assess the role of reactive oxygen species and nitric oxide (NO) in the genesis of reperfusion-induced arrhythmias, the effects of reactive oxygen species scavengers and NO synthase inhibitors on the incidence of ventricular fibrillation and irreversible ventricular fibrillation (mortality) were examined. Hearts of anesthetized rats were subjected to 4 min regional ischemia followed by 4 min reperfusion. The animals were treated i.v. with superoxide dismutase, a O2- scavenger, catalase, a H2O2 scavenger, dimethylthiourea, a .OH scavenger, or NG-nitro-L-arginine methyl ester (L-NAME) and NG-nitro-L-arginine (L-NNA), NO synthase inhibitors. Superoxide dismutase (430 and 4300 U/kg/min) reduced the mortality from 93% to 43% and 57%, respectively, whereas treatment with catalase or dimethylthiourea did not affect these arrhythmias. L-NAME (0.1 and 0.3 mg/kg/min) reduced the mortality from 93% to 50% and 43%, respectively. L-NNA (0.3 mg/kg/min) reduced the mortality from 93% to 50%. This reduction by the NO synthase inhibitors was abolished by administration of L-Arg. However, L-Arg blocked neither a small increase in systolic blood pressure nor a decrease in heart rate elicited by the NO synthase inhibitors. The combinated treatment of superoxide dismutase (4300 U/kg/min) with L-NAME (0.3 mg/kg/min) reduced the mortality from 93% to 7%. These results suggest that the genesis of reperfusion-induced arrhythmias observed in this model may be in part due to O2- and NO.
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PMID:Involvement of superoxide and nitric oxide in the genesis of reperfusion arrhythmias in rats. 881 24

The severity and incidences of arrhythmias induced by left coronary artery occlusion (7 min) and reperfusion (7 min) were compared in two groups of rats anaesthetized by using urethane (1.25 g kg-1, i.p.) or sodium pentobarbitone (60 mg kg-1, i.p.). A possible modification by nitric oxide synthesis blocker NG-nitro-L-arginine methyl ester (L-NAME; 20 mg kg-1, slow i.v. bolus) was also investigated. The ectopic activity observed in urethane-anaesthetized rats was less in number when compared to that of sodium pentobarbitone. The duration of ventricular tachycardia (VT) was significantly less in urethane group during the occlusion and reperfusion periods but incidence of ventricular fibrillation (VF) during the reperfusion was significantly higher. The administration of L-NAME caused a significant increase in the arterial blood pressure which disappeared after coronary artery occlusion in either anaesthesia groups. However, L-NAME had no significant effect on the difference observed between the two groups except the significant difference between total number of ectopic beats in both anaesthesia groups during occlusion was abolished by L-NAME treatment. These results suggest that, in this experimental model, the anaesthetic agent used can affect the severity of ischaemia-reperfusion arrhythmias and basal nitric oxide release does not have a major influence on them.
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PMID:Comparison of sodium pentobarbitone and urethane anaesthesia in a rat model of coronary artery occlusion and reperfusion arrhythmias: interaction with L-NAME. 881 41

Nitric oxide (NO) is an endogenous protectant against reperfusion-induced ventricular fibrillation (VF) in the rat isolated heart. Here, the following were investigated: (1) the tissue source of cardioprotective NO using a novel inhibitor (7-nitro indazole; 7-NI) of the neuronal form of NO synthase (NOS) and direct detection of coronary effluent NO by chemiluminescence; and (2) the species dependence by comparing rat and rabbit hearts. Perfusion with modified Krebs solution was followed by 60 min left regional ischemia and 10 min reperfusion. 7-NI (1 microM) increased the incidence of VF from 0% to 60% in rat hearts (n = 10; P < 0.05). Co-perfusion with L-arginine (1 mM) reduced VF incidence to 20% (P:N.S. v controls). The inactive analog of 7-NI (6-amino indazole: 6-AI) had no pro-fibrillatory activity. Neither 7-NI nor 6-AI affected coronary flow or recovery of flow during reperfusion. 7-NI reduced basal coronary effluent NO levels to below the limit of detection (< 1 pmol), but a massive increase in NO levels occurred when L-arginine was co-perfused with 7-NI. Although 7-NI had no effect on basal coronary flow and, by implication, resting NO release, it was found, in separate studies, to antagonise substance P-induced vasodilatation and NO release, suggesting that its neuronal selectivity is lost in the presence of an exogenously administered activator of endothelial NOS in rat hearts. In rabbit hearts, in contrast, 7-NI had no effect on VF or NO levels. However, in rabbit hearts the isozyme non-selective NO synthase blocker, NG-nitro-L-arginine methyl ester (L-NAME; 100 microM), increased VF incidence from 0 to 50% (P < 0.05) and, during the first minute of reperfusion, reduced NO levels from 4929 +/- 893 to 2505 +/- 483 pmol/min/g (P < 0.05) and recovery of coronary flow by 22% (P < 0.05). Each of these effects were prevented by L-arginine co-perfusion. These data indicate a role for basally released NO as an endogenous antifibrillatory cardioprotectant in rat and rabbit isolated heart and indicate that the tissue source (neuronal in rat but not in rabbit heart) is species-dependent.
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PMID:Endogenous protection against reperfusion-induced ventricular fibrillation: role of neuronal versus non-neuronal sources of nitric oxide and species dependence in the rat versus rabbit isolated heart. 893 Aug 5

The effect of a nitric oxide (NO) donor and the influence of endogenous NO in modulating ischaemia-induced arrhythmias was assessed in anaesthetised rats. The nitric oxide donor C87-3754 (1 mg/kg) caused a significant reduction in arterial blood pressure before coronary artery ligation but did not influence the incidence or severity of ventricular arrhythmias during a 30-min period of myocardial ischaemia [60 and 58% incidence of ventricular fibrillation (VF) in control and treated rats, respectively]. When the hearts were preconditioned by a short (3 min) coronary artery occlusion before the 30-min period of ischaemia, there was a marked reduction in both the number of ventricular ectopic beats (260 +/- 65 vs. 812 +/- 256 beats/min in controls; p < 0.05) and the incidence of ventricular fibrillation (9 vs. 67% in controls; p < 0.05). Neither NG-nitro-L-arginine methyl ester (L-NAME; 10-100 mg/kg) nor methylene blue (1-50 mg/kg) attenuated this marked antiarrhythmic effect of preconditioning. L-NAME caused a significant increase in blood pressure with all doses used, whereas methylene blue did not increase blood pressure. Both L-NAME and methylene blue attenuated ventricular arrhythmias in non-preconditioned hearts. L-NAME reduced the number of ventricular ectopic beats (from 812 +/- 256 to 318 +/- 81 beats/min at 10 mg/kg; p < 0.05), whereas methylene blue decreased the incidence of VF from 67 to 20% at a dose of 50 mg/kg (p < 0.05). These findings suggest that neither endogenous nor exogenously administered NO reduces ischaemic arrhythmias in anaesthetised rats. Furthermore, the antiarrhythmic effect of preconditioning in this species appears to be independent of NO. The antiarrhythmic effects seen with both methylene blue and L-NAME may be the result of actions other than inhibition of the production or actions of NO.
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PMID:The role of nitric oxide in modulating ischaemia-induced arrhythmias in rats. 915 67

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