Changes in [Na(+)](i), compartmental [Ca(2+)], and NADH with dysfunction after global ischemia in intact hearts. Am J Physiol Heart Circ Physiol 2001 Jan;280(1):H280-93
Date
12/21/2000Pubmed ID
11123243DOI
10.1152/ajpheart.2001.280.1.H280Scopus ID
2-s2.0-0035001033 (requires institutional sign-in at Scopus site) 93 CitationsAbstract
We measured the effects of global ischemia and reperfusion on intracellular Na(+), NADH, cytosolic and mitochondrial (subscript mito) Ca(2+), relaxation, metabolism, contractility, and Ca(2+) sensitivity in the intact heart. Langendorff-prepared guinea pig hearts were crystalloid perfused, and the left ventricular (LV) pressure (LVP), first derivative of LVP (LV dP/dt), coronary flow, and O(2) extraction and consumption were measured before, during, and after 30-min global ischemia and 60-min reperfusion. Ca(2+), Na(+), and NADH were measured by luminescence spectrophotometry at the LV free wall using indo 1 and sodium benzofuran isophthalate, respectively, after subtracting changes in tissue autofluorescence (NADH). Mitochondrial Ca(2+) was assessed by quenching cytosolic indo 1 with MnCl(2). Mechanical responses to changes in cytosolic-systolic (subscript sys), diastolic (subscript dia), and mitochondrial Ca(2+) were tested over a range of extracellular [Ca(2+)] before and after ischemia-reperfusion. Both [Ca(2+)](sys) and [Ca(2+)](dia) doubled at 1-min reperfusion but returned to preischemia values within 10 min, whereas [Ca(2+)](mito) was elevated over 60-min reperfusion. Reperfusion dissociated [Ca(2+)](dia) and [Ca(2+)](sys) from contractile function as LVP(sys-dia) and the rise in LV dP/dt (LV dP/dt(max)) were depressed by one-third and the fall in LV dP/dt (LV dP/dt(min)) was depressed by one-half at 30-min reperfusion, whereas LVP(dia) remained markedly elevated. [Ca(2+)](sys-dia) sensitivity at 100% LV dP/dt(max) was not altered after reperfusion, but [Ca(2+)](dia) at 100% LV dP/dt(min) and [Ca(2+)](mito) at 100% LV dP/dt(max) were markedly shifted right on reperfusion (ED(50) +36 and +125 nM [Ca(2+)], respectively) with no change in slope. NADH doubled during ischemia but returned to normal on initial reperfusion. The intracellular [Na(+)] ([Na(+)](i)) increased minimally during ischemia but doubled on reperfusion and remained elevated at 60-min reperfusion. Thus Na(+) and Ca(2+) temporally accumulate during initial reperfusion, and cytosolic Ca(2+) returns toward normal, whereas [Na(+)](i) and [Ca(2+)](mito) remain elevated on later reperfusion. Na(+) loading likely contributes to Ca(2+) overload and contractile dysfunction during reperfusion.
Author List
Varadarajan SG, An J, Novalija E, Smart SC, Stowe DFMESH terms used to index this publication - Major topics in bold
AnimalsBlood Pressure
Calcium
Coronary Circulation
Cytosol
Fluorescent Dyes
Guinea Pigs
Homeostasis
In Vitro Techniques
Indoles
Kinetics
Mitochondria, Heart
Myocardial Contraction
Myocardial Ischemia
Myocardial Reperfusion
Myocardium
NAD
Oxygen Consumption
Sodium Channels
Ventricular Function, Left
