Chronic effects of .BETA.1-adrenoceptor partial agonist xamoterol on resting and exercise hemodynamics in patients with heart failure.

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A β1-partialagonist, xamoterol, has a dual β1-agonist-antagonist action according to thelevels of sympathetic activity and has been shown to improve effort tolerance and cardiacfunction in patients with chronic heart failure (CHF). To investigate which action ofagonism or antagonism is responsible for the beneficial effect, we observed chronic effectsof xamoterol on resting and exercise (EX) hemodynamics, and assessed consequent changesin EX duration, left ventricular function, and subjective symptoms in 19 patients with CHF (NYHA II and III). The study consisted of a placebo run-in period of 2 wk, axamoterol period (200 mg bid) of 8 wk, and a placebo wash-out period of 2 wk. The threegraded (mild, intermediate, and high levels) supine bicycle EX test was performed at theend of each period with the same workload . Heart rate (HR) and systolic blood pressure (SBP) were measured at rest and at each EX level and then the EX was continued untilpatients were exhausted. Xamoterol did not alter HR at rest but decreased it significantlyat the intermediate and high EX levels (P<0.05). Similar effects were also observed on SBP but not significantly. Although xamoterol increased EX duration and improved symptoms in some patients (6 and 5 patients, respectively), the differences were not statistically significant. Xamoterol did not change the left ventricular dimensions and fractionalshortening measured by echocardiography . It is indicated that when xamoterol was chronically administered to patients with CHF, its β1-antagonist action during EX was morepredominant than the agonist action at rest, and that xamoterol did not produce a clinicalimprovement in CHF after 8 wk of administration. However, xamoterol's β1-antagonistaction at high levels of sympathetic tone may protect the failing heart against excessivesympathetic stimulation and then prolong survival in patients with heart failure . Furtherlong-term studies are needed to assess the clinical efficacy of xamoterol in CHF .
一般社団法人日本臨床薬理学会の論文

Chronic effects of .BETA.1-adrenoceptor partial agonist xamoterol on resting and exercise hemodynamics in patients with heart failure.

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