Non-selective beta-adrenergic blockade prevents reduction of the cerebral metabolic ratio during exhaustive exercise in humans

Abstract

Intense exercise decreases the cerebral metabolic ratio of oxygen to carbohydrates [O(2)/(glucose + (1/2)lactate)], but whether this ratio is influenced by adrenergic stimulation is not known. In eight males, incremental cycle ergometry increased arterial lactate to 15.3 +/- 4.2 mm (mean +/- s.d.) and the arterial-jugular venous (a-v) difference from -0.02 +/- 0.03 mm at rest to 1.0 +/- 0.5 mm (P < 0.05). The a-v difference for glucose increased from 0.7 +/- 0.3 to 0.9 +/- 0.1 mm (P < 0.05) at exhaustion and the cerebral metabolic ratio decreased from 5.5 +/- 1.4 to 3.0 +/- 0.3 (P < 0.01). Administration of a non-selective beta-adrenergic (beta(1) + beta(2)) receptor antagonist (propranolol) reduced heart rate (69 +/- 8 to 58 +/- 6 beats min(-1)) and exercise capacity (239 +/- 42 to 209 +/- 31 W; P < 0.05) with arterial lactate reaching 9.4 +/- 3.6 mm. During exercise with propranolol, the increase in a-v lactate difference (to 0.5 +/- 0.5 mm; P < 0.05) was attenuated and the a-v glucose difference and the cerebral metabolic ratio remained at levels similar to those at rest. Together with the previous finding that the cerebral metabolic ratio is unaffected during exercise with administration of the beta(1)-receptor antagonist metropolol, the present results suggest that the cerebral metabolic ratio decreases in response to a beta(2)-receptor mechanism.

Figure 1. Arterial–internal jugular venous differences of O₂, glucose, lactate and (glucose + ½lactate) across the brain in response to incremental exercise with (•) and without (○) administration of propranolol

During control exercise the subjects became exhausted at a work load of 239 W, but administration of propranolol reduced exercise capacity, with exhaustion appearing at 209 W. Values are mean ± s.e.m.*Different from rest (P < 0.05); †different from control exercise (P < 0.05).

Figure 2. The arterial–internal jugular venous difference for O₂/glucose (O₂-to-glucose index) and for [O₂/(glucose + ½lactate)] (cerebral metabolic ratio) during control exercise (○) and during exercise with propranolol (•)

Values are mean ± s.e.m.*Different from rest (P < 0.05); †different from control exercise (P < 0.05).

Figure 3. The ratio between the arterial–internal jugular venous difference for O₂ and the arterial–internal jugular venous difference for glucose + ½lactate

The theoretical ratio of 6: 1 is illustrated. Control exercise (○) causes the ratio to deviate from the expected ratio of 6: 1 as the uptake of carbohydrates increases more than that of O₂. During exercise with β-blockade (•), the curve is shifted parallel but upward (P < 0.05) demonstrating that for a given a–v diff for glucose + ½lactate, the a–v diff for O₂ is higher during exercise with β-blockade. Values are mean ± s.e.m.*Different from rest (P < 0.05); †different from control exercise (P < 0.05).