The actions of the beta-adrenoceptor blocking agents propranolol and metoprolol in the maximally exercised horse [proceedings].

This study tested how two beta-blockers, propranolol and metoprolol, change heart, performance, and metabolic responses to maximal gallops in horses. Both drugs blunted post-exercise heart rate and some metabolic surges but slowed running performance, and metoprolol raised exercise noradrenaline levels.

What the researchers asked and why it matters

• Question: How do the beta-adrenoceptor antagonists propranolol and metoprolol affect cardiovascular and metabolic responses to maximal exercise in horses?
• Rationale: Beta-blockers reduce sympathetic drive to the heart and tissues. Understanding their effects during extreme exertion informs equine sports medicine, exercise physiology, and clinical use (e.g., arrhythmias) where performance and safety are concerns.
• Drug profiles for context:
  • Propranolol: nonselective beta1/beta2 antagonist.
  • Metoprolol: beta1-selective antagonist at usual doses.

How the study was done (from the abstract)

• Subjects: Horses performing maximal gallops.
• Interventions: Single doses of propranolol 0.2 mg/kg or metoprolol 0.2 mg/kg.
• Comparisons: Resting versus post-exercise responses, with and without drug.
• Measurements: Heart rate immediately after exercise; performance time for each gallop; plasma glucose, glycerol, lactate; blood pH; plasma free fatty acids (FFA); plasma noradrenaline (norepinephrine).
• Design details (e.g., sample size, randomization, timing) are not specified in the abstract.

Key findings

• Cardiovascular:
  • Both propranolol and metoprolol reduced the immediate post-exercise elevation in heart rate.
  • Both drugs reduced performance, evidenced by increased time to complete each gallop.
• Metabolic and acid–base:
  • The usual exercise-induced rises in plasma glucose, glycerol, and lactate were attenuated by both drugs.
  • The exercise-associated fall in blood pH (acidosis) was also blunted with both drugs.
  • Despite the above, plasma free fatty acids increased to a greater extent with beta-blockade.
• Catecholamines:
  • Maximal exercise caused a nine- to twelve-fold increase in plasma noradrenaline.
  • Neither drug changed resting noradrenaline.
  • During exercise, metoprolol further increased noradrenaline levels compared with no drug; this effect was not reported for propranolol.

Interpreting the results

• Reduced heart rate and slower gallop times:
  • Beta1 blockade lowers cardiac chronotropy and inotropy, reducing peak cardiac output and limiting maximal speed.
  • Performance decrement aligns with diminished sympathetic support during maximal exertion.
• Blunted lactate rise and smaller pH drop:
  • Lower lactate and less acidosis likely reflect reduced exercise intensity achieved under beta-blockade and diminished catecholamine-driven glycogenolysis.
  • Reduced glycolytic flux is consistent with attenuated rises in plasma glucose.
• Lower glycerol but higher free fatty acids:
  • Attenuated glycerol suggests reduced whole-body lipolysis (glycerol is a direct index of triglyceride breakdown).
  • Paradoxically higher plasma FFA may reflect decreased clearance/uptake by working muscle (due to reduced perfusion or altered beta-mediated transport/oxidation) rather than increased lipolysis.
  • The dissociation between glycerol and FFA points to altered FFA trafficking and utilization with beta-blockade during intense exercise.
• Noradrenaline responses:
  • The large exercise-induced rise is typical of maximal sympathetic activation.
  • Metoprolol’s further increase during exercise likely represents reflex sympathetic augmentation to overcome cardiac beta1 blockade.
  • Why propranolol did not show the same reported increase could relate to its beta2 blockade, which may reduce presynaptic facilitation of noradrenaline release or alter peripheral feedback, partially offsetting reflex rises.

Implications for equine practice and sport

• Beta-blockers impair maximal performance in horses by limiting heart rate and cardiac output.
• They blunt extreme metabolic perturbations (lactate and acidosis), but this reflects lower achieved intensity rather than improved fitness.
• Altered fatty acid handling under beta-blockade suggests caution in interpreting post-exercise lipid markers and in managing horses with metabolic or perfusion concerns.
• In competitive settings, beta-blockers are generally prohibited due to performance and safety considerations; the findings reinforce their performance-impairing effects.

Limitations and what’s missing

• Abstract does not disclose sample size, study design (e.g., crossover, blinding), timing of dosing relative to exercise, or route of administration.
• No direct measurements of cardiac output, stroke volume, muscle oxygenation, or substrate oxidation to confirm mechanistic inferences.
• Only noradrenaline was reported; epinephrine and other hormones (insulin, cortisol) were not presented.
• Acute, single-dose findings may not extrapolate to chronic beta-blocker administration or submaximal exercise.

Future directions

• Compare dose–response effects and different timing of administration for both drugs.
• Directly measure substrate uptake/oxidation (e.g., stable isotope tracers) to clarify why FFA rise while glycerol is blunted.
• Assess epinephrine and insulin dynamics, muscle perfusion, and mitochondrial function during exercise with beta-blockade.
• Evaluate effects across exercise intensities, training states, and in horses with cardiac conditions.

Bottom line

• Both propranolol and metoprolol blunt heart rate and some metabolic disturbances after maximal gallops but slow horses down.
• Metoprolol uniquely raises exercise noradrenaline further, and both drugs shift lipid handling in a way that increases circulating free fatty acids, likely via reduced clearance rather than increased lipolysis.