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. 1995 Jun;115(4):579–586. doi: 10.1111/j.1476-5381.1995.tb14971.x

Acute and chronic cardiac and regional haemodynamic effects of the novel bradycardic agent, S16257, in conscious rats.

S M Gardiner 1, P A Kemp 1, J E March 1, T Bennett 1
PMCID: PMC1908496  PMID: 7582475

Abstract

1. We carried out experiments to assess the cardiac and regional haemodynamic effects of single or repeated injections of the novel bradycardic agent. S16257, (7,8-dimethoxy 3-[3-([(IS)-(4,5-dimethoxybenzocyclobutan-1- yl)methyl]methylamino)propyl] 1,3,4,5-tetrahydro-2H-benzapin 2-one), in conscious rats. 2. In the first experiment, male Long Evans rats were chronically instrumented for the measurement of cardiac or regional haemodynamics (n = 9 in each group), and, on separate experimental days, were randomized to receive i.v. bolus injections of vehicle (5% dextrose) or S16257 at a dose of 1 mg kg-1. 3. In animals instrumented for the measurement of cardiac haemodynamics (n = 9), following injection of vehicle, there were no immediate changes, and 7-8 h later there were slight reductions in heart rate and mean arterial blood pressure only. Injection of S16257 caused an immediate, transient, pressor effect but thereafter there were reductions in heart rate, mean arterial blood pressure, cardiac index and total peripheral conductance, together with increases in stroke index and peak aortic flow. The integrated decreases in heart rate, mean arterial blood pressure, cardiac index and total peripheral conductance and increases in stroke index, peak aortic flow, dF/dtmax and central venous pressure following S16257 were all significantly greater than the changes after vehicle injection. After injection of S16257, the fall in heart rate and fall in cardiac index were not linearly related. 4. In animals instrumented for the measurement of regional haemodynamics (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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