Predominantβ-adrenoceptor blocking effect of xamoterol averaged over the day in patients with mild to moderate heart failure: insight into the mechanism of its long-term clinical efficacy

Journal of Applied Physiology

et al. 2002

Leg venous pressure markedly falls during upright exercise via a muscle pump effect, creating de novo perfusion pressure. We examined physiological roles of this mechanism in increasing femoral artery blood flow (FABF) and its alterations in chronic heart failure (CHF). In 10 normal subjects and 10 patients with CHF, standard hemodynamic variables, mean ankle vein pressure (MAVP), and FABF with Doppler techniques were obtained during graded upright bicycle exercise. To evaluate a nonspecific blood flow response, normal subjects also performed supine exercise. In normal subjects, MAVP rapidly declined by 45 mmHg and FABF correspondingly increased 5.3-fold without a systemic pressor response during 10 s of light upright exercise at 5 W. Approximately 67% of the blood flow response was attributed to the venous pressure drop-dependent mechanism. In CHF patients, MAVP declined by only 36 mmHg and FABF increased only 1.7-fold during the same upright exercise. The muscle venous pump has an ability to increase FABF at least threefold via the venous pressure drop-dependent mechanism. This mechanism is impaired in CHF patients.

Section: Discussionmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 93%

Muscle pump-dependent self-perfusion mechanism in legs in normal subjects and patients with heart failure

Shiotani

Journal of Applied Physiology

et al. 2002

“…They do not directly controvert the beneficial effects of physical exercise in patients with chronic heart failure because most rehabilitation programmes use a less intense exercise protocol than that used in our study. However, sympathetic activation that may account for exercise induced diastolic dysfunction is inevitable even during submaximal exercise in patients with chronic heart failure 37. Although further studies are needed to assess the optimal amount of exercise in patients with chronic heart failure, our results imply that an adequate interval between exercise episodes is essential to reduce the risk of progression of heart failure during long term exercise training.…”

Section: Discussionmentioning

confidence: 77%

Sustained left ventricular diastolic dysfunction after exercise in patients with dilated cardiomyopathy

Morikawa

Koretsune

et al. 1998

Heart

Objective-To investigate the recovery process of exercise induced diastolic dysfunction in heart failure, using Doppler echocardiographic techniques. Design and patients-Transmitral flow velocity profiles and standard noninvasive haemodynamic indices were obtained serially over seven days after symptom limited bicycle exercise tests in 18 patients with dilated cardiomyopathy and eight normal subjects. In three patients with cardiomyopathy we also measured the pulmonary capillary wedge pressure for 24 hours after exercise. Results-The intensity of exercise, as assessed by respiratory gas analysis, was lower in patients with dilated cardiomyopathy than in normal subjects. Despite the higher exercise level, all haemodynamic variables returned to baseline within one hour after exercise in normal subjects. In contrast, patients with dilated cardiomyopathy showed a sustained decrease in the peak early diastolic filling velocity and a sustained increase in the deceleration time of early filling for 24 hours or more after exercise. Because other haemodynamic variables recovered within one hour after exercise even in patients with dilated cardiomyopathy, the postexercise changes in ventricular filling were not explained by changes in loading conditions. Conclusions-Exercise induced diastolic left ventricular dysfunction of the failing heart persists for 24 hours or more after exercise. The eYcacy of exercise training on a daily basis in dilated cardiomyopathy requires further evaluation.

“…It is of note that, although the long-term clinical efficacy of xamoterol has been reported in patients with mild to moderate heart failure [20][21][22], the drug has been demonstrated to worsen the prognosis of patients with severe heart failure [23]. In patients with severe heart failure, xamoterol acts as an antagonist, even at rest, because of increased sympathetic activity [24]. Hence, cardiac decompensation may occur during xamoterol administration to patients with severe heart failure.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological effects of concomitant administration of ?-adrenoceptor blocker and agonist in normal subjects: characterization by heart rate response to exercise

Karita

Koretsune

et al. 1995

Eur J Clin Pharmacol

Self Cite

The effects of a combination regimen of metoprolol and beta 1-adrenoceptor agonist denopamine on resting and exercise heart rate have been studied in 10 normal volunteers. Maximal ramp upright bicycle exercise was performed three times at 1-week intervals. Two hours before each exercise test, 5 mg metoprolol plus 20 mg denopamine, 5 mg metoprolol plus a denopamine placebo, or two placebos were orally administered in a double-blind fashion. During exercise after placebo administration, heart rate increased in parallel with the exercise intensity. Compared to the placebo values, resting heart rate was significantly decreased by an average of 10 beats.min-1 by 5 mg metoprolol, whereas it was not altered by the combination regimen. During exercise, however, both the combination regimen and metoprolol alone showed a significant negative chronotropic effect, decreasing peak exercise heart rate by an average of 14 and 21 beats.min-1, respectively. Peak oxygen uptake was also significantly decreased by both regimens. We conclude that concomitant administration of 5 mg metoprolol and 20 mg denopamine exerts an effective beta-adrenoceptor blocking action during exercise but a minimal effect at rest in normal subjects. The combination regimen appears to have a favourable pharmacological profile for beta-adrenoceptor blocker therapy in patients with chronic heart failure.