Effect of vasoactive intestinal peptide on pacemaker location and heart rate in the dog atrium

Abstract

Vasoactive intestinal polypeptide (VIP) was either injectedintravenously (300 pmol·kg–1) or perfused (1 nmol in 1 min) into the sinusnode artery (SNA) in anesthetized dogs to study its effect on subsidiary atrial pacemakers.Isochronal maps were obtained from 128 unipolar electrograms recorded on the epicardialsurface of both atria in nine animals. When VIP was perfused into the SNA or injectedintravenously, heart rate increased by 29 ± 16% and 12 ± 12%, and blood pressure decreased by16 ± 15 mmHg (1 mmHg = 133.3 Pa) and 24 ± 18 mmHg, respectively. Nosignificant change in heart rate (3 ± 6% decrease) accompanied a similar decrease in bloodpressure after an intravenous sodium nitroprusside perfusion. The perfusion of VIP into the SNAas well as the intravenous injection of VIP induced a shift of the pacemaker site to the region ofBachmann’s bundle in a third of the preparations, while the pacemaker remained in the sinusnode area in two thirds. A perfusion of isoproterenol into the SNA produced a similar heart rateincrease (32 ± 14%, NS vs. VIP), and shifted the pacemaker site rostrally within the sinus node inthree of five preparations, or to the region of Bachmann’s bundle in two of five preparations.The response to VIP in the location of the pacemaker was significantly different from theresponse to isoproterenol. Repeated perfusions of VIP into the SNA after 10-, 25-, 40-, and60-min intervals produced 2 ± 13% (p < 0.005 vs. the effect of first VIP administration),14 ± 12% (p < 0.05), 10 ± 12% (p < 0.05) and 30 ± 13% (NS) heart rateincreases, respectively, thereby demonstrating a tachyphylactic effect. In conclusion, VIP seemsto exert its positive chronotropic effect directly (probably via specific VIP receptors), althoughthe phenomenon of tachyphylaxis may suggest an indirect sympathomimetic mechanism.Key words: vasoactive intestinal peptide,subsidiary atrial pacemakers, sinus node artery, atrial mapping.