title: Adenosine as adjunct to potassium cardioplegia: effect on function, energy metabolism, and electrophysiology.
abstract: Adenosine is known to induce rapid cardioplegic arrest and to improve postischemic recovery in the isolated rat heart. Long exposures to high doses of adenosine impair postischemic recovery, however. In this paper we tested the combination of low-dose adenosine (1 mmol/L) with potassium (26 mmol/L), with the aim of achieving rapid arrest (as with high-dose adenosine) but eliminating the need for postarrest washout of adenosine. Cardioplegic solutions studied were (1) Krebs-Henseleit potassium (26 mmol/L) (K); (2) K plus adenosine (1 mmol/L) (KA); (3) K plus an adenosine deaminase inhibitor [erythro-9-(2-hydroxy-3-nonyl)adenine] (0.1 mmol/L) (KE); and as control (4) Krebs-Henseleit potassium (6 mmol/L) (C). We induced cardiac arrest in Langendorff-perfused rat hearts by infusing the cardioplegic solution for 3 minutes at 3 ml/min. Total ischemia lasted 20 minutes at 37 degrees C, followed by reperfusion for 30 minutes. High potassium decreased the arrest time from 260 +/- 16 seconds (group C, mean values +/- standard error of the mean) to 22 +/- 4 seconds (group K). A further decrease to 10 +/- 2 seconds was observed with KA (p = 0.016 versus K). KE, which increased endogenous adenosine, gave intermediate effects. All hearts recovered during reperfusion; the product of developed tension and heart rate (grams per minute) was superior in KA hearts (6250 +/- 740 versus K hearts 4380 +/- 390; p = 0.050). KE gave an intermediate result (5290 +/- 900), while C showed the worst recovery (3180 +/- 830). Our electrophysiologic studies with sinus node and atrial tissue suggest that adenosine induced hyperpolarization and an increase in potassium permeability, thereby arresting the sinus node before depolarization of the membrane by potassium (26 mmol/L). We conclude that low-dose adenosine as an adjunct to potassium shortens the arrest time in this model and improves postischemic recovery.
authors.affiliation: Cardiochemical Laboratory, Erasmus University, Rotterdam, The Netherlands.
authors.forename: J W
authors.initials: JW
authors.lastname: de Jong
authors.forename: P
authors.initials: P
authors.lastname: van der Meer
authors.forename: H
authors.initials: H
authors.lastname: van Loon
authors.forename: P
authors.initials: P
authors.lastname: Owen
authors.forename: L H
authors.initials: LH
authors.lastname: Opie
mesh_terms: D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000008:administration & dosage*; D000818:Animals; D004338:Drug Combinations; D004594:Electrophysiology; D004734:Energy Metabolism / Q000187:drug effects; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006324:Heart Arrest, Induced; D011188:Potassium / Q000008:administration & dosage; D017680:Potassium Compounds; D051381:Rats
chemical_list: D000227:Adenine Nucleotides; D004338:Drug Combinations; D017680:Potassium Compounds; C018369:potassium cardioplegic solution; C010192:9-(2-hydroxy-3-nonyl)adenine; D000225:Adenine; D000241:Adenosine; D011188:Potassium