Therapeutic Antidysrhythmic and Functional Protection in Human Atria

• Published in: The Journal of surgical research Vol. 76; no. 2; pp. 143 - 148
• Main Authors: Cain, Brian S., Meldrum, Daniel R., Meng, Xianzhong, Pulido, Edward J., Banerjee, Anirban, Harken, Alden H.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.05.1998; Elsevier
• Subjects: adenosine; Adenosine - therapeutic use; Adrenergic alpha-Agonists - pharmacology; Adrenergic beta-Agonists - pharmacology; Antiarythmic agents; arrhythmia; Arrhythmias, Cardiac - etiology; Arrhythmias, Cardiac - prevention & control; Biological and medical sciences; Cardiovascular system; Coronary Artery Bypass - adverse effects; Electric Stimulation; Heart Atria - drug effects; Humans; ischemia-reperfusion; ischemic preconditioning; Ischemic Preconditioning, Myocardial; Isoproterenol - pharmacology; Medical sciences; Myocardial Contraction - drug effects; Myocardial Reperfusion Injury - prevention & control; Pharmacology. Drug treatments; Phenylephrine - pharmacology; trabeculae; adenosine; trabeculae; ischemic preconditioning; ischemia-reperfusion; arrhythmia; Human; Postoperative; Arrhythmia; Cardiovascular disease; Antiarrhythmic agent; Coronary heart disease; Myocardial disease; Vascular disease; Chemotherapy; Reperfusion; Treatment; Ischemia; Bypass; Heart disease; Surgery; Myocardium; Complication; Influence; Pretreatment
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1006/jsre.1998.5309

Approximately 30% of patients suffer supraventricular dysrhythmias after cardiac bypass. While the heart can be constructively preconditioned to maintain function against subsequent ischemic insult using a variety of stimuli across many species, preconditioning in experimental animals is associated with decreased postischemic reperfusion cardiac dysrhythmias. This mode of therapeutic preconditioning has not been previously examined in human atrial myocardium. We therefore hypothesized that preconditioning provides both antidysrhythmic and functional protection to human atria. To study this, human atrial trabeculae were suspended in organ baths, paced at 1 Hz, while force development and ectopy were recorded before and after simulated ischemia. The study consisted of five groups: (1) control trabeculae (n= 12), (2) trabeculae exposed to dysrhythmogenic stimuli (phenylephrine 50 μM and isoproterenol 25 μM (n= 8)), (3) trabeculae exposed to ischemia-reperfusion (I/R) injury and then drug stimulated (n= 10), (4) trabeculae preconditioned with adenosine (ADO 125 μM) then drug stimulated (n= 10), and (5) trabeculae preconditioned with ischemic preconditioning (IPC) then drug stimulated (n= 6) each at end reoxygenation. Differences between groups were assessed using χ2analysis and ANOVA (Bonferroni/Dunn). Results demonstrated that human atrial trabeculae did not exhibit dysrhythmia at baseline or when stimulated with α and β agonists. After I/R, control trabeculae exhibited stimulated reperfusion dysrhythmia, while trabeculae preconditioned with either ADO or transient ischemia exhibited decreased stimulated dysrhythmia (eachP< 0.05 vs. I/R). Functionally, I/R decreased developed force (DF) to 16 ± 2% of baseline (%BDF) while ADO pretreatment increased postischemic DF to 41 ± 3% BDF (P< 0.05 vs. I/R) 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) protective preconditioning/cardioprotection does extend to dysrhythmia control and is therapeutically accessible in human atrial myocardium.