THERAPEUTIC ANTIDYSRHYTHMIC AND FUNCTIONAL PROTECTION IN HUMAN ATRIA

Approximately 30% of patients suffer supraventricular dysrhythmias aft er cardiac bypass. While the heart can be constructively preconditione d to maintain function against subsequent ischemic insult using a vari ety of stimuli across many species, preconditioning in experimental an imals is associated with decreased postischemic reperfusion cardiac dy srhythmias. This mode of therapeutic preconditioning has not been prev iously examined in human atrial myocardium, We therefore hypothesized that preconditioning provides both antidysrhythmic and functional prot ection to human atria. To study this, human atrial trabeculae were sus pended in organ baths, paced at 1 Hz, while force development and ecto py were recorded before and after simulated ischemia. The study consis ted of five groups: (1) control trabeculae (n = 12), (2) trabeculae ex posed to dysrhythmogenic stimuli (phenylephrine 50 mu M and isoprotere nol 25 mu M (n = 8)), (3) trabeculae exposed to ischemia-reperfusion ( IIR) injury and then drug stimulated (n = 10), (4) trabeculae precondi tioned with adenosine (ADO 125 mu M) then drug stimulated (n = 10), an d (5) trabeculae preconditioned with ischemic preconditioning (TPC) th en drug stimulated (n = 6) each at end reoxygenation. Differences betw een groups were assessed using chi(2) analysis and ANOVA (Bonferroni/D unn), Results demonstrated that human atrial trabeculae did not exhibi t dysrhythmia at baseline or when stimulated with alpha and beta agoni sts.,After I/R, control trabeculae exhibited stimulated reperfusion dy srhythmia, while trabeculae preconditioned with either ADO or transien t ischemia exhibited decreased stimulated dysrhythmia (each P < 0.05 v s, I/R). Functionally, I/R decreased developed force (DF) to 16 +/- 2% of baseline (%BDF) while ADO pretreatment increased postischemic DF t o 41 +/- 3% BDF (P < 0.05 vs. IIR) while IPC increased DF to 49 +/- 3% BDF (P < 0.05 vs. I/R), We conclude that (1) human atrial trabeculae can be functionally preconditioned with either ADO or IPC, and (2) pro tective preconditioning/cardioprotection does extend to dysrhythmia co ntrol and is therapeutically accessible in human atrial myocardium. (C ) 1998 Academic Press.