Abstract
Recent studies revealed that relatively small changes in perfusate sodium ([Na+]o) composition significantly affect cardiac electrical conduction and stability in contraction arrested ex vivo Langendorff heart preparations before and during simulated ischemia. Additionally, [Na+]o modulates cardiomyocyte contractility via a sodium-calcium exchanger (NCX) mediated pathway. It remains unknown, however, whether modest changes to [Na+]o that promote electrophysiologic stability similarly improve mechanical function during baseline and ischemia–reperfusion conditions. The purpose of this study was to quantify cardiac mechanical function during ischemia–reperfusion with perfusates containing 145 or 155 mM Na+ in Langendorff perfused isolated rat heart preparations. Relative to 145 mM Na+, perfusion with 155 mM [Na+]o decreased the amplitude of left-ventricular developed pressure (LVDP) at baseline and accelerated the onset of ischemic contracture. Inhibiting NCX with SEA0400 abolished LVDP depression caused by increasing [Na+]o at baseline and reduced the time to peak ischemic contracture. Ischemia–reperfusion decreased LVDP in all hearts with return of intrinsic activity, and reperfusion with 155 mM [Na+]o further depressed mechanical function. In summary, elevating [Na+]o by as little as 10 mM can significantly modulate mechanical function under baseline conditions, as well as during ischemia and reperfusion. Importantly, clinical use of Normal Saline, which contains 155 mM [Na+]o, with cardiac ischemia may require further investigation.
Highlights
In recent years, our laboratory published several manuscripts demonstrating that relatively small changes in perfusate ionic composition, sodium, have profound effects on cardiac electrical conduction and stability, especially when these changes occur in conjunction with a cardiac insult such as ischemia or reduced gap junctional c oupling[1,2,3]
Studies have demonstrated that ventricular arrhythmias and myofibrillar hypercontracture associated with ischemia–reperfusion injury are, at least in part, due to intracellular C a2+ overload and increased calcium-calmodulin dependent protein kinase II (CaMKII) a ctivity[10,11]
It stands to reason that increasing [Na+]o should decrease Ca2+ influx through NCX, which leads to the specific hypothesis that elevating [Na+]o reduces ischemia–reperfusion injury in ex vivo Langendorff-perfused hearts
Summary
Our laboratory published several manuscripts demonstrating that relatively small changes in perfusate ionic composition, sodium, have profound effects on cardiac electrical conduction and stability, especially when these changes occur in conjunction with a cardiac insult such as ischemia or reduced gap junctional c oupling[1,2,3]. Isolated myocyte studies demonstrated that reducing [ Na+]o increased C a2+ influx through N CX8,9. Studies have demonstrated that ventricular arrhythmias and myofibrillar hypercontracture associated with ischemia–reperfusion injury are, at least in part, due to intracellular C a2+ overload and increased calcium-calmodulin dependent protein kinase II (CaMKII) a ctivity[10,11]. It stands to reason that increasing [Na+]o should decrease Ca2+ influx through NCX, which leads to the specific hypothesis that elevating [Na+]o reduces ischemia–reperfusion injury in ex vivo Langendorff-perfused hearts. [Na+]o management may differentially affect electrical and mechanical function of the heart
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