Left atrium (LA) physiology is influenced by changes in left ventricular (LV) performance and load.
Objectives
The purpose of this study was to define the effect of acute changes in LV loading conditions on LA physiology in subacute myocardial infarction (MI).
Methods
MI was percutaneously induced in 19 Yorkshire pigs. One to 2 weeks after MI, 14 pigs underwent acute LV unloading using a percutaneous LV assist device, Impella. The remaining 5 pigs underwent acute LV loading by percutaneous induction of aortic regurgitation. A pressure-volume catheter was inserted into the LA using a percutaneous transseptal approach, and LA pressure-volume loops were continuously monitored. Atrial arrhythmia inducibility was examined by burst-pacing of the right atrium. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) levels and ryanodine receptor phosphorylation were examined in LA tissues to study the potential effect of stretch-dependent oxidative stress.
Results
MI resulted in reduced LV ejection fraction and increased LV end-diastolic pressure with concomitant increase in LA pressure and volumes. Acute LV unloading resulted in a reduction of LV end-diastolic pressure, which led to proportional decreases in mean LA pressure and maximum LA volume. LA pressure-volume loops exhibited a pump flow-dependent, left-downward shift. This was associated with reduced LA passive stiffness, suggesting the alleviation of the LA stretch that was present after MI. Prior to acute unloading of the LV, 71% of the pigs were arrhythmia-inducible; LV unloading reduced this to 29% (p = 0.02). Time to spontaneous termination of atrial arrhythmias was decreased from median 55 s (range 5 to 300 s) to 3 s (range 0 to 59 s). In contrast, acute LV loading with aortic regurgitation increased LA pressure without a significant effect on arrhythmogenicity. Molecular analysis of LA tissue revealed that NOX2 expression was increased after MI, whereas acute LV unloading reduced NOX2 levels and diminished ryanodine receptor phosphorylation.
Conclusions
Acute LV unloading relieves LA stretch and reduces atrial arrhythmogenicity in subacute MI.
This study was supported by American Heart Association grant 17SDG33410873 and National Institutes of Health (NIH) grant R01 HL139963 (to Dr. Ishikawa); NIH grants R01 HL119046, R01 HL117505, R01HL128099, R01 HL129814, R01HL131404, and R43HL108581 (to Dr. Hajjar); NIH grant R00 HL116645 (to Dr. Kho); and a Transatlantic Leducq Foundation grant (to Dr. Hajjar). The Impella device and console were supplied by Abiomed. Dr. Ishikawa has received a research grant from Abiomed. Dr. Bikou was supported by the Deutsche Herzstiftung. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
