Chronic effects of labetalol, pindolol, and propranolol on calf blood flow in intermittent claudication. beta blockade and intermittent claudication: placebo controlled trial of atenolol and nifedipine and their combination. Chronic effects of metoprolol and methyldopa on calf blood flow in intermittent claudication. Effect of beta-adrenergic blockers on the peripheral circulation in patients with peripheral vascular disease.
To evaluate the role of beta-adrenoceptor blockade on lower limb circulation in patients with peripheral arterial disease, heart rate, blood pressure, calf blood flow and vascular resistance were measured at rest and during reactive hyperemia in seven patients with hypertension and intermittent claudication. The study was performed as a placebo-controlled, double-blind, crossover trial of 10 days with doses of propranolol, 80 mg twice a day, pindolol, 5 mg twice a day, labetalol, 200 mg twice a day, and labetalol, 400 mg twice a day as active drug. Heart rate was lowest during propranolol dosing and blood pressure was lowest during labetalol dosing irrespective of the labetalol dose used. The degree of peripheral arterial disease modulated the effect of beta-blockade on limb circulation. In the less symptomatic limbs, reactive hyperemic flow was greater after pindolol than after the other drugs and did not differ from the level recorded after placebo. These differences were inconsistent and small in the more symptomatic limbs. Thus as the peripheral arterial disease became more severe and extensive, beta-blockade, irrespective of its type, lost its hemodynamic effect on lower limb circulation. To determine the effects of the beta 1 selective adrenoceptor blocker atenolol, the dihydropyridine calcium antagonist nifedipine, and the combination of atenolol plus nifedipine on objective and subjective measures of walking performance and foot temperature in patients with intermittent claudication.
                Randomised controlled double blind four way crossover trial.
                Royal Hallamshire Hospital, Sheffield.
                49 patients (40 men) aged 39-70 with chronic stable intermittent claudication.
                Atenolol 50 mg twice daily; slow release nifedipine 20 mg twice daily; atenolol 50 mg plus slow release nifedipine 20 mg twice daily; placebo. Each treatment was given for four weeks with no washout interval between treatments.
                Claudication and walking distances on treadmill; skin temperature of feet as measured by thermistor and probe; blood pressure before and after exercise; subjective assessments of walking difficulty and foot coldness with visual analogue scales.
                Atenolol did not significantly alter claudication distance (mean change -6%; 95% confidence interval 1% to -13%), walking distance (-2%; 4% to -8%), or foot temperature. Nifedipine did not alter claudication distance (-4%; 3% to -11%), walking distance (-4%; 3% to -10%), or foot temperature. Atenolol plus nifedipine did not alter claudication distance but significantly reduced walking distance (-9%; -3% to -15% (p less than 0.003)) and skin temperature of the more affected foot (-1.1 degrees C; 0 to -2.2 degrees C (p = 0.05)). These effects on walking distance and foot temperature seemed unrelated to blood pressure changes.
                There was no evidence of adverse or beneficial effects of atenolol or nifedipine, when given singly, on peripheral vascular disease. The combined treatment, however, affected walking ability and foot temperature adversely. This may have been due to beta blockade plus reduced vascular resistance, which might also explain the reported adverse effects of pindolol and labetalol on claudication. In a placebo-controlled double-blind study 14 hypertensive patients with intermittent claudication were treated with metoprolol (100-200 mg daily) and methyldopa (500-1000 mg daily) for 3 weeks and their effects on heart rate, blood pressure as well as on resting and hyperaemic calf blood flow and vascular resistance were compared. In their antihypertensive effect metoprolol and methyldopa did not differ significantly. In 23 diseased limbs the calf blood flow and vascular resistance remained unchanged at rest during the trial. The active drugs reduced hyperaemic flow (P less than 0.05). The peak flow was reduced by 20% (P greater than 0.01) with metoprolol and by 15% with methyldopa below the initial level and by 17% and by 12% below the level recorded on placebo, respectively. Neither of the drugs influenced vascular resistance during reactive hyperaemia. Thus, in patients with intermittent claudication antihypertensives should be used with care. Beta-Adrenergic blockers have not been widely used in patients with peripheral vascular disease because these drugs have been reported to worsen the symptoms of intermittent claudication. To test this assumption we studied the effects of a beta 1-selective and a nonselective beta-adrenergic blocker on postexercise calf blood flow and symptoms of claudication in 19 patients with mild-to-moderate peripheral vascular disease. Subjects received placebo for 3 weeks, and then were randomized to 120 mg/day propranolol or 150 mg/day metoprolol with the use of a crossover design. Blood flow in the calf was measured by strain-gauge plethysmography at rest and immediately after exercise on a bicycle ergometer at a low and a high workload. The symptoms of claudication were monitored during bicycle exercise and by patient diaries maintained between visits. Maximal exercise heart rate was reduced an equivalent amount by metoprolol (19 beats/min) and propranolol (16 beats/min). Mean arterial pressure was reduced by propranolol at rest and by both drugs with exercise. Calf blood flow was not affected by either drug compared with placebo at rest or at either workload. In addition, the symptoms of claudication were not worsened by either drug. We conclude that despite evidence of beta 1-adrenergic blockade and a lowering of arterial pressure, neither beta-adrenergic blocker adversely affected the peripheral circulation.