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  • 1
    ISSN: 1435-1803
    Keywords: ATP ; myocardial stunning ; rabbit ; verapamil ; xanthine oxidase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The role of free radicals and the protective action of calcium antagonists have been established in myocardial stunning in canine hearts, which contain a considerable level of xanthine oxidase, a free radical producing enzyme. However, myocardial stunning in hearts which lack xanthine oxidase and its modification by calcium antagonistsin vivo remain uncharacterized. The present study examined this issue using open-chest anesthetized rabbits. Myocardial stunning was induced by a 10-min coronary occlusion and reperfusion. Regional systolic thickening fraction (TF) was determined using an epicardial Doppler sensor, together with other hemodynamic parameters. In untreated control rabbits, recovery of TF from the 10 min transient ischemia was 43±3% of the baseline at 30 min after reperfusion. Administration of verapamil (200 μg/kg bolus plus 40 μg/kg/min), which was started before the onset of ischemia and continued until 20 min after reperfusion, significantly improved the recovery of TF to 74±6% (p〈0.05). A similar improvement in post-ischemic contractile function (TF=77±10%) was observed when verapamil was injected at the same rate, but the infusion was discontinued 1 min after the coronary occlusion. Myocardial ATP depletion after the 10 min ischemia was significantly less in the verapamil-pretreated rabbits compared with untreated controls (10.1±1.0 vs 6.2±0.7 μmol/g dry wt., p〈0.05). The difference in TF between the rabbits with and without verapamil treatment could not be explained by afterload reduction. When verapamil (100 μg/kg bolus plus 20 μg/kg/min) was given during the reperfusion period alone, TF recovery was poorer (TF=22±8%) than the control value. Thus, it was concluded that verapamil attenuates myocardial stunning in the hearts with trace levels of xanthine oxidase, and that the beneficial effect is achieved only by pretreatment, not by post-ischemic treatment with verapamil.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-1803
    Keywords: Preconditioning ; reperfusion arrhythmia ; adenosine receptor ; prostaglandin ; bradykinin ; rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The mechanism for the suppression of reperfusion arrhythmia by preconditioning (PC) remains unknown. This study aimed to examine the roles of the adenosine receptor, prostaglandin (PG), and bradykinin (BK) receptor in PC. Under pentobarbital anesthesia, the coronary artery of the rat was occluded for 5 min and then reperfused. In untreated controls, this protocol induced ventricular tachycardia (VT) in 100% of the rats and ventricular fibrillation (VF) in 60%. PC with 2 min ischemia/5 min reperfusion prior to the 5 min coronary occlusion significantly reduced the incidence of reperfusion VT and VF to 30% and 0%, respectively. This antiarrhythmic effect of the PC was not blocked when rats were pretreated with 8-phenyltheophylline (8-PT, 10 mg/kg), aspirin-DL-lysin (18 mg/kg), or a specific BK receptor antagonist, Hoe 140 (20 nmol/kg). None of these agents alone significantly modified the incidence of reperfusion VT or VF. These results suggest that neither the adenosine receptor, endogenous PG, nor BK receptor play a major role in the mechanism of suppression of perfusion arrhythmias by PC in the rat heart.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-1803
    Keywords: Adenosine ; bradykinin ; microdialysis ; myocardial infarction ; rabbit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Preconditioning is known to decelerate degradation of the tissue adenine nucleotides during ischemia and to delay ischemic myocardial necrosis. However, it is not known whether these two phenomena are related. To obtain an insight into this question, the present study examined whether adenosine and B2 receptor antagonists, which block the infarct size-limiting effect of preconditioning, modify the interstitial purine levels during preconditioning and subsequent sustained ischemia. In pentobarbital anesthetized open-chest rabbits, a microdialysis probe was placed in the territory of a branch of the left coronary artery, and perfused with Ringer solution. Preconditioning was performed with 5 min ischemia/5 min reperfusion. Dialysate adenosine and inosine were elevated from the baseline values of 0.064±0.011 and 0.329±0.044μM to 0.189±0.069 and 4.106±1.451 μM, respectively during preconditioning, but their elevation during a subsequent 20 min of ischemia was significantly lower compared with that in the non-preconditioned myocardium. This suppression of the purine accumulation during ischemia by preconditioning was not abolished by 2 μg/kg of Hoe 140, a specific B2 receptor antagonist, or by 10 mg/kg of 8-phenyltheophylline, a non-selective adenosine receptor antagonist. Since the doses of Hoe 140 and 8-phenyltheophylline are sufficient to block the infarct size-limiting effect of preconditioning, the present results suggest that there is a dissociation between the suppression of adenine nucleotide degradation during ischemia by preconditioning and the enhancement of myocardial resistance against infarction. Thus, it is unlikely that a reduction of adenine nucleotide utilization by preconditioning is sufficient to protect the myocardium against ischemic necrosis.
    Type of Medium: Electronic Resource
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