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Heart Rate Reduction (heart + rate_reduction)

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Medical Sciences100%

Selected Abstracts

Studies on the Acute Toxicity, Pharmacokinetics and Pharmacodynamics of Paliperidone Derivatives , Comparison to Paliperidone and Risperidone in Mice and Rats

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 2 2010
Fengying Sun
The i.g. LD50 and i.v. maximum tolerated doses of PD1, PD5 and PD6 were greater than those of paliperidone and risperidone in mice. Pharmacokinetic study showed that PDs were quickly metabolized to paliperidone to take effect in the treatment of schizophrenia in rats after i.g. administration. Only traces of the parent substances were found. Pharmacodynamic study showed that PDs significantly reduced MK-801-induced hyperlocomotion in mice. The electrocardiogram (ECG) was recorded at 0, 5, 10, 15, 20, 25, 30, 45 and 60 min. in anaesthetized rats after i.v. injection of 0.21, 0.59, 1.69 ,mol/kg drugs. Heart rate reduction had a linear relation with dose after i.v. injection of PDs, paliperidone and risperidone. No significant change in the ECG parameters was found in all groups after administration of the low dose. Although the reductions in heart rate and the corrected QT interval (QTc) were observed in all drugs at the high dose, PD5 and PD6 were associated with smaller effects on the ECG parameters than other compounds, including paliperidone and risperidone. Therefore, PD5 and PD6 could be potential candidates for the treatment of schizophrenia. [source]

Heart rate reduction by inhibition of If or by ,-blockade has different effects on postsystolic wall thickening

BRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2007
L Lucats
Background and purpose: Postsystolic wall thickening (PSWT) is part of thickening that occurs after end-systole and represents wasted effort as it does not contribute to ejection. The effects of antianginal drugs on PSWT remain to be established. We compared the effects on PSWT of two agents that reduce heart rate, the ,-blocker atenolol and the selective inhibitor of If current, ivabradine. Experimental approach: Six dogs were prepared to measure wall thickening by sonomicrometry in the conscious state, at rest and during exercise, after administration of saline, atenolol (1mg.kg -1) or ivabradine (1mg.kg -1). Key results: Atenolol and ivabradine similarly reduced heart rate vs saline at rest (about 10-20%) and during exercise (about 30%). Atenolol but not ivabradine decreased dP/dtmax. Concomitantly, PSWT increased with atenolol vs saline at rest (0.35±0.07 vs 0.21±0.03mm, respectively) and during exercise (0.30±0.04 vs 0.15±0.04mm, respectively). In contrast, ivabradine did not alter PSWT. Importantly, atenolol but not ivabradine increased the ratio of postsystolic to systolic wall thickening by 80±23%. This enhanced thickening during diastole with atenolol was accompanied by impeded isovolumic relaxation of the left ventricle, as illustrated by the significant correlation between the isovolumic relaxation time constant , and the postsystolic to systolic wall thickening ratio. None of these effects of atenolol were abolished when heart rate was controlled with atrial pacing. Conclusion and implications: For a similar heart rate reduction at rest and during exercise, ivabradine, but not atenolol, did not alter PSWT and preserved the part of thickening contributing to ejection. British Journal of Pharmacology (2007) 150, 335,341. doi:10.1038/sj.bjp.0706996 [source]

Cooling Device for Bradycardia Based on Peltier Element for Accurate Anastomosis of Off-Pump Coronary Artery Bypass Grafting

ARTIFICIAL ORGANS, Issue 10 2002
Yukio Kuniyoshi
Abstract: Upon introducing off-pump coronary artery bypass grafting (CABG), the indications for CABG were expanded to include patients who previously had no operative indications. For accurate anastomosis, various devices and methods have been developed. Bradycardia is easily induced by drug administration. However, this method of achieving bradycardia also has adverse effects on cardiac function. We have developed a new device to decrease the heart rate by regional cooling of the sino-atrial node. The new device is incorporated with Peltier's element, which uses an electric charge to create a temperature gradient on both of its surfaces. In terms of the cooling ability of this device, its cooling surface is chilled from 25°C to 0°C within 30 s. During in vivo animal experiments, this device has been shown to decrease the myocardial temperature around the sino-atrial node to 15°C and suppress sino-atrial node activity, resulting in bradycardia to 60 beats/min level. In summary, the simple and easily applicable device for local cooling in combination with the application of diltiazem for effective heart rate reduction may be very helpful for the surgeon and may avoid disadvantages for critically ill patients. [source]

Heart rate reduction by inhibition of If or by ,-blockade has different effects on postsystolic wall thickening

BRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2007
L Lucats
Background and purpose: Postsystolic wall thickening (PSWT) is part of thickening that occurs after end-systole and represents wasted effort as it does not contribute to ejection. The effects of antianginal drugs on PSWT remain to be established. We compared the effects on PSWT of two agents that reduce heart rate, the ,-blocker atenolol and the selective inhibitor of If current, ivabradine. Experimental approach: Six dogs were prepared to measure wall thickening by sonomicrometry in the conscious state, at rest and during exercise, after administration of saline, atenolol (1mg.kg -1) or ivabradine (1mg.kg -1). Key results: Atenolol and ivabradine similarly reduced heart rate vs saline at rest (about 10-20%) and during exercise (about 30%). Atenolol but not ivabradine decreased dP/dtmax. Concomitantly, PSWT increased with atenolol vs saline at rest (0.35±0.07 vs 0.21±0.03mm, respectively) and during exercise (0.30±0.04 vs 0.15±0.04mm, respectively). In contrast, ivabradine did not alter PSWT. Importantly, atenolol but not ivabradine increased the ratio of postsystolic to systolic wall thickening by 80±23%. This enhanced thickening during diastole with atenolol was accompanied by impeded isovolumic relaxation of the left ventricle, as illustrated by the significant correlation between the isovolumic relaxation time constant , and the postsystolic to systolic wall thickening ratio. None of these effects of atenolol were abolished when heart rate was controlled with atrial pacing. Conclusion and implications: For a similar heart rate reduction at rest and during exercise, ivabradine, but not atenolol, did not alter PSWT and preserved the part of thickening contributing to ejection. British Journal of Pharmacology (2007) 150, 335,341. doi:10.1038/sj.bjp.0706996 [source]