Abstract 3887: Pressure Overload Heart Failure Affects Interfibrillar but Not Subsarcolemmal Mitochondrial Function
Years ago a debate arose whether two functionally different mitochondrial subpopulations (subsarcolemmal - SSM and interfibrillar - IFM) exist in heart muscle. This debate has never been resolved and nowadays potential differences are often ignored. Presumably, SSM are providing ATP for basic cell function while IFM provide energy for the contractile apparatus. We speculated that two distinguishable subpopulations exist that are differentially affected by pressure overload. Male Sprague-Dawley rats were subjected to transverse aortic constriction (TAC) for 20 weeks or sham operation. Contractile function was assessed by echocardiography. Heart tissue was analysed by electron microscopy. Mitochondria were isolated by differential centrifugation and respiratory capacity was analyzed using a Clark electrode. Pressure overload (PO) induced left ventricular hypertrophy with increased posterior wall diameter (LVPWD: 1,4±0,2 vs. 2,6±0,2 mm; p<0,05) and impaired contractile function (EF: 75±6 vs. 53±8 %; p<0,05). State 3 respiration (all in nAO/min/gdry) in sham were 50% higher in IFM than in SSM (IFM vs. SSM glutamate: 503±91 vs. 331±62; palmitoyl-carnitine 521±83 vs. 308±50 and pyruvate 615±107 vs. 344±69; p<0,05). Pressure overload significantly impaired respiratory rates in IFM (sham vs. PO: glutamate 503±91 vs. 239±64, palmitoyl-carnitine 521±83 vs. 241±27 and pyruvate 615±107 vs. 198±14; p<0,05), but only mildly reduced state 3 in SSM (glutamate 331±62 vs. 174±19, palmitoyl-carnitine 308±50 vs. 237±42 and pyruvate 344±69 vs. 185±14; n.s.). As a result, there were no differences between SSM and IFM after 20 weeks of pressure overload (IFM vs. SSM glutamate: 239±64 vs. 174±19, palmitoyl-carnitine 241±27 vs. 237±42, pyruvate 198±14 vs. 185±14). Electron microscopy revealed normal morphology but reduced volume density (38±1 vs. 33±1%) suggesting reduced ATP producing capacity. SSM and IFM differ in their respiratory capacity under control conditions. These differences are masked by the effects of pressure overload. Differential effects on respiratory capacity in the subpopulations together with normal mitochondrial morphology support the notion of SSM maintaining basic cell function and IFM producing ATP for contractile function.