consideration objective: To evaluate the issues of [beta]-blockers on ventilation in heart failure patients.

consideration objective: To evaluate the issues of [beta]-blockers on ventilation in heart failure patients. Indeed, [beta]-blockers ameliorate the clinical condition and cardiac function of heart failure patients, on the contrary not exercise capacity. Because ventilation is inappropriately elevated in heart failure patients befitting to overactive reflexes from ergoreceptors and chemoreceptors, we hypothesized that [bet]a-blockers can elicit their positive clinical efficiencys through a reduction of ventilation.

Design: This was a double-blind, randomized, placebo-controlled study

Setting: University hospital heart failure unit.

Patients and interventions: While receiving placebo (2 months) and a sated dosage of carvedilol (4 months) 15 chronic heart failure patients were evaluated by the agency of quality-of-life questionnaire, pulmonary function criterions cardiopulmonary exercise tests with constant workload, and a ramp protocol.

Results: Therapy with carvedilol did not affect resting pulmonary function and exercise capacity. However, carvedilol improved the arises of the quality-of-life questionnaire, reduc the mean ([+ or -] SD) incline of the minute ventilation (VE)/carbon dioxide output (VC[Osub2]) ratio (from 364 [+ or -] 89 to 317 [+ or -] 38; p < 001) and reduc ventilation at the following times: at peak exercise (from 60 [+ or -] 14 to 48 [+ or -] 15 L/min; p < 005); during the intermediate phases of a ramp-protocol exercise; and during the steady-state phase of a constant-workload exercise (from 42 [+ or -] 14 to 34 [+ or -] 13 L/min; p < 005 at third min). The end-expiratory press for carbon dioxide increased as ventilation decreased. The reduction in the VE/VC[Osub2] ratio was correlated with improvement in quality of life (r = 0603; p < 002)

Conclusions: Improvement in the clinical conditions of heart failure patients treated with carvedilol is associated with reductions in the inappropriately elevated ventilation flushs observed during exercise.

key-note words: carvedilol; exercise; heart failure; oxygen uptake; ventilation

Abbreviations: PETC[Osub2] = end-expiratory urgency for carbon dioxide; VC[O.sub.2] = carbon dioxide output; VE = minute ventilation; V[Osub2] = oxygen uptake

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Long-term treatment with [beta]-blockers ameliorates the clinical condition and cardiac function of patients with heart failure. (1-3] However, this does not translate into an improvement in exercise capacity during the one and the other maximal and submaximal effort. (4-6) A lack of appropriate chronotropic replication has been suggested as the possible cause of the incapacity of [beta]-blockers to improve exercise performance. (7) However, the difference between heart rates at caesura and at peak exercise is not affected on [beta]-blocker therapy reducing both the resting and peak exercise heart rates,s Ventilation for a given work rate is inappropriately increased in heart failure patients, nevertheless ventilation at peak exercise is lower as the severity of the disease becomes greater. (9-11) We have remind ofed previously that the lack of increase in ventilation at peak exercise could be the cause of the absence of improvement in exercise capacity during long-term treatment with [beta]-blockers in heart failure patients. (58) lately Ponikowski et al (12) showed that the inappropriate increase of ventilation for a given work rate in heart failure patients was to be paid to the widespread derangement of cardiovascular reflexe which are driven from one side sympathetic pathways. This conclusion designs a new rationale for the use of [beta]-blocker therapy in heart failure patients and intimates why [beta]-blocker therapy does not improve exercise capacity and ventilation.

MATERIALS AND METHODS

consideration Design and Data Acquisition

This was a double-blind, randomized, placebo-controlled application of mind All patients who participated in the contemplation underwent a study run-in period of 2 weeks, during which clinical stability was assessed and patients performed at least sum of two units cardiopulmonary exercise tests (ramp protocol) to become familiarized with the exercise deed Patients were randomized to couple groups (A and B), compos of eight and seven make liables respectively. The study protocol is summarized in Figure 1 It was 8 month extended and contained a carvedilol titration period of 2 month during which the carvedilol dose was increased on 12.5 mg every 2 weeks in subordination to clinical and ECG surveillance. (13) The titration period was guided by means of an investigator who used labeled carvedilol pills and did not participate in any other part of the investigation. The replete carvedilol dosage was defined as the highest carvedilol dose that could be tolerated from the patients during the carvedilol titration period. The glutted carvedilol dosage was administered for 4 month while the placebo treatment lasted for 2 month In dispose A, placebo titration preceded carvedilol titration and treatment. In assign places to B, placebo titration followed carvedilol titration.

[FIGURE 1 OMITTED]

During the cogitation patients were clinically evaluated each 15 days, or more oftentimes if required or desired by means of the patients. At the period of each treatment period, patients underwent the following evaluations. (1) Quality of life was evaluated utilizing the Minnesota quality-of-life questionnaire, which is a standard and self-administered questionnaire. It consists of 21 brief questions, each of which is answered in succession a scale of 0 to 5 with 0 indicating no general intent of heart failure and 5 indicating a to a high degree large effect. (14) (2) Standard pulmonary function criterions and a lung diffusion evaluation for carbon monoxide (2200; SensorMedics; Yorba Linda, CA) were administered. (3) brace cardiopulmonary exercise tests were given. single was a constant-workload exercise touchstone of 6 min duration with a workload equal to the 60% of the maximal workload measured in the secondary familiarization exercise test performed in the run-in period. The other was a maximal exercise touchstone with a personalized ramp protocol that was aimed at achieving peak exercise in 10 min, as evaluated in the cogitation run-in period. Thereafter, the workload of the couple the constant and ramp protocol was kept the same in each patient. the two of the exercise tests were performed onward the cycle ergometer, with breath-by-breath respiratory gas and bulk measurements (V Max; SensorMedics). The anaerobic outset was calculated using the V-slope analysis and the respiratory compensation point as the point where the incline of the minute ventilation (VE)/ carbon dioxide output (VC[Osub2]) relationship started to increase. (15) For evaluation, the data were averaged throughout the 30 s during which the examined adventure occurred.

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