Chronotropic effects of carnitine derivatives in isolated rabbit atria at defined transmural pressures

: Acetylcarnitine isomers and gamma-betaine methylesters are closely structure-related to cholinergic agonists. With continuous perfusion at defined transmural pressures of 0.1 and 0.5 kPa their effects on the chronotropic autoregulation of isolated spontaneously beating atria were examined in comparison with acetylcholine. Independent of the transmural pressure, the two isomers of acetylcarnitine had no effects on the heart rate up to a concentration of 10(-3) mol/l. Among the carboxylesters of gamma-betaines, the crotonobetaine methylester was up to 100 fold more effective than acetylcholine. Hydrogenation of the double bond decreased the negative chronotropic response 10 times. The L(-)-carnitine-methylester did not influence the spontaneous heart rate up to 3 X 10(-3) mol/l, but the D-isomer inhibited it significantly. Increase of the transmural pressure caused the same level of heart rate in both controls and atria under free betaines. At transmural pressure of 0.5 kPa, in comparison with 0.1 kPa, a significantly greater impairment of heart rate, released by crotonobetaine-methylester, was observed. Atropine blocked the interactions of the gamma-betaine-methylesters with the muscarinic cholinergic receptors of the pacemaker cells.