Metabolic Consequences of Beta-Adrenergic Receptor Blockade for the Acutely Ischemic Dog Myocardium^[*]

Summary

In an experimental study in 50 dogs the myocardial uptake of free fatty acids (FFAs) after beta-blockade was determined using radioiodinated heptadecanoic acid as a metabolic tracer. All 4 beta-blockers used (metoprolol, timolol, propranolol and pindolol) lowered the uptake of FFAs in the normal canine heart. Uptake of FFAs was also diminished after coronary artery occlusion per se, but administration of beta-blockers exerted little additional influence on the uptake of FFAs. This observation was qualitatively parallelled by the uptake of ²⁰¹T1 in concomitant experiments. Plasma FFA levels were increased by pindolol (non-selective with intrinsic sympathomimetic activity), not changed by metoprolol (a cardioselective betablocking agent) and lowered by timolol and propranolol (both nonselective compounds). The extent of ischemic tissue, as reflected by uptake of iodoheptadecanoic acid and ²⁰¹T1, was diminished by metoprolol but not by other beta-blockers. Regional distribution of both tracers, as shown in the endo-epicardial uptake ratios, was hardly influenced by beta-blockade, except for a small increase of ²⁰¹T1 uptake in non-occluded endocardium. Uptake of ²⁰¹T1 as well as of iodoheptadecanoic acid in the ischemic area was increased by metoprolol, timolol and propranolol and decreased by pindolol. We conclude that beta-blocking agents confer different effects on myocardial uptake and metabolism of FFAs which might possibly be related to their different inherent properties.

Zusammenfassung

Bei 50 Hunden wurde die Myokardspeicherung freier Fettsäuren nach Beta-Blockade mit Hilfe der radiojodierten Heptadekansäure als Stoffwechsel-Tracer bestimmt. Alle 4 Beta-Blocker (Metoprolol, Timolol, Propranolol und Pindolol) setzten die Speicherung freier Fettsäuren in normalen Hundeherzen herab. Die Speicherung freier Fettsäuren wurde auch durch Verschluß einer Koronararterie an sich verringert, jedoch übte die Verabreichung von Beta-Blockern nur einen geringen zusätzlichen Einfluß auf die Speicherung freier Fettsäuren aus. Diese Beobachtung wurde in begleitenden Versuchen über die Speicherung von ²⁰¹T1 qualitativ bestätigt. Die Konzentration freier Fettsäuren im Plasma wurden durch Pindolol (nicht-selektiv mit eigener sympathomimetischer Aktivität) erhöht, durch Metoprolol (ein herzspezifischer Beta-Blocker) nicht vermindert und durch Timolol und Propranolol (beide nichtselektive Verbindungen) herabgesetzt. Das Ausmaß des ischämischen Gewebes wiedergegeben durch die Speicherung der Jodheptadekansäure und des ²⁰¹T1 wurde durch Metoprolol, jedoch nicht durch die anderen Beta-Blocker vermindert. Die durch das endo-/epikardiale Speicherungsverhältnis nachgewiesene regionale Verteilung der beiden Tracer wurde auch die Beta-Blockade kaum beeinflußt, mit Ausnahme eines geringen Anstiegs der ²⁰¹T1 Speicherung im nicht betroffenen Endokard. Die Speicherung sowohl des ²⁰¹T1 als auch der Jodheptadekansäure im ischämischen Gebiet wurde durch Metoprolol, Timolol und Propranolol erhöht und durch Pindolol herabgesetzt. Wir schließen daraus, daß Beta-Blocker verschiedene Wirkungen auf die myokardiale Speicherung und den Stoffwechsel freier Fettsäuren ausüben und daß diese möglicherweise mit deren verschiedenen Ausgangseigenschaften in Zusammenhang stehen.

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