Ventricular performance and Na+-K+ ATPase activity are reduced early and late after myocardial infarction in rats

I Stefanon,D.V Vassallo,A.A Fernandes,J.R Cade,R.F Ribeiro Junior,G.P Targueta,J.G Mill

doi:10.1590/s0100-879x2009005000015

I Stefanon, D.V Vassallo + Show 5 more

Open Access

https://doi.org/10.1590/s0100-879x2009005000015

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Abstract

Myocardial infarction leads to compensatory ventricular remodeling. Disturbances in myocardial contractility depend on the active transport of Ca2+ and Na+, which are regulated by Na+-K+ ATPase. Inappropriate regulation of Na+-K+ ATPase activity leads to excessive loss of K+ and gain of Na+ by the cell. We determined the participation of Na+-K+ ATPase in ventricular performance early and late after myocardial infarction. Wistar rats (8-10 per group) underwent left coronary artery ligation (infarcted, Inf) or sham-operation (Sham). Ventricular performance was measured at 3 and 30 days after surgery using the Langendorff technique. Left ventricular systolic pressure was obtained under different ventricular diastolic pressures and increased extracellular Ca2+ concentrations (Ca2+e) and after low and high ouabain concentrations. The baseline coronary perfusion pressure increased 3 days after myocardial infarction and normalized by 30 days (Sham 3 = 88 +/- 6; Inf 3 = 130 +/- 9; Inf 30 = 92 +/- 7 mmHg; P < 0.05). The inotropic response to Ca2+e and ouabain was reduced at 3 and 30 days after myocardial infarction (Ca2+ = 1.25 mM; Sham 3 = 70 +/- 3; Inf 3 = 45 +/- 2; Inf 30 = 29 +/- 3 mmHg; P < 0.05), while the Frank-Starling mechanism was preserved. At 3 and 30 days after myocardial infarction, ventricular Na+-K+ ATPase activity and contractility were reduced. This Na+-K+ ATPase hypoactivity may modify the Na+, K+ and Ca2+ transport across the sarcolemma resulting in ventricular dysfunction.

Highlights

Myocardial infarction induces a progressive geometric, structural, and functional remodeling of both ventricles [1,2,3,4]
Several adaptive changes resulting from the myocardium infarction, including myocyte hypertrophy [5], increased deposition of extracellular matrix components [6], and chamber enlargement [7,8], seem to depend either on hemodynamic disturbances determined by the loss of contractile tissue [9] or on the neurohumoral activation triggered by myocardial ischemia [10,11,12]
While the α subunit contains the amino acids involved in catalytic function, ion transport and cardiac glycoside binding, the function of the β subunit is not yet fully understood, it is essential for the normal activity of the enzyme and is involved in the transport of the functional Na+-K+ ATPase in the plasma membrane [16]

Summary

Introduction

Myocardial infarction induces a progressive geometric, structural, and functional remodeling of both ventricles [1,2,3,4]. Several adaptive changes resulting from the myocardium infarction, including myocyte hypertrophy [5], increased deposition of extracellular matrix components [6], and chamber enlargement [7,8], seem to depend either on hemodynamic disturbances determined by the loss of contractile tissue [9] or on the neurohumoral activation triggered by myocardial ischemia [10,11,12]. The best described disturbances in myocardial contractility are intimately dependent on the active transport of ions, namely Ca2+ and Na+, which are regulated by SERCA and Na+-K+ ATPase. While the α subunit contains the amino acids involved in catalytic function, ion transport and cardiac glycoside binding, the function of the β subunit is not yet fully understood, it is essential for the normal activity of the enzyme and is involved in the transport of the functional Na+-K+ ATPase in the plasma membrane [16].

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