Reduced inotropic reserve and increased susceptibility to cardiac ischemia/reperfusion injury in phosphocreatine-deficient guanidinoacetate-N-methyltransferase-knockout mice.
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Reduced inotropic reserve and increased susceptibility to cardiac ischemia/reperfusion injury in phosphocreatine-deficient guanidinoacetate-N-methyltransferase-knockout mice. / Michiel, Ten Hove; Lygate, Craig A; Fischer, Alexandra; Schneider, Jürgen E; Sang, A Elisabeth; Hulbert, Karen; Sebag-Montefiore, Liam; Watkins, Hugh; Clarke, Kieran; Isbrandt, Dirk; Wallis, Julie; Neubauer, Stefan.
In: CIRCULATION, Vol. 111, No. 19, 19, 2005, p. 2477-2485.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Reduced inotropic reserve and increased susceptibility to cardiac ischemia/reperfusion injury in phosphocreatine-deficient guanidinoacetate-N-methyltransferase-knockout mice.
AU - Michiel, Ten Hove
AU - Lygate, Craig A
AU - Fischer, Alexandra
AU - Schneider, Jürgen E
AU - Sang, A Elisabeth
AU - Hulbert, Karen
AU - Sebag-Montefiore, Liam
AU - Watkins, Hugh
AU - Clarke, Kieran
AU - Isbrandt, Dirk
AU - Wallis, Julie
AU - Neubauer, Stefan
PY - 2005
Y1 - 2005
N2 - BACKGROUND: The role of the creatine kinase (CK)/phosphocreatine (PCr) energy buffer and transport system in heart remains unclear. Guanidinoacetate-N-methyltransferase-knockout (GAMT-/-) mice represent a new model of profoundly altered cardiac energetics, showing undetectable levels of PCr and creatine and accumulation of the precursor (phospho-)guanidinoacetate (P-GA). To characterize the role of a substantially impaired CK/PCr system in heart, we studied the cardiac phenotype of wild-type (WT) and GAMT-/- mice. METHODS AND RESULTS: GAMT-/- mice did not show cardiac hypertrophy (myocyte cross-sectional areas, hypertrophy markers atrial natriuretic factor and beta-myosin heavy chain). Systolic and diastolic function, measured invasively (left ventricular conductance catheter) and noninvasively (MRI), were similar for WT and GAMT-/- mice. However, during inotropic stimulation with dobutamine, preload-recruitable stroke work failed to reach maximal levels of performance in GAMT-/- hearts (101+/-8 mm Hg in WT versus 59+/-7 mm Hg in GAMT-/-; P
AB - BACKGROUND: The role of the creatine kinase (CK)/phosphocreatine (PCr) energy buffer and transport system in heart remains unclear. Guanidinoacetate-N-methyltransferase-knockout (GAMT-/-) mice represent a new model of profoundly altered cardiac energetics, showing undetectable levels of PCr and creatine and accumulation of the precursor (phospho-)guanidinoacetate (P-GA). To characterize the role of a substantially impaired CK/PCr system in heart, we studied the cardiac phenotype of wild-type (WT) and GAMT-/- mice. METHODS AND RESULTS: GAMT-/- mice did not show cardiac hypertrophy (myocyte cross-sectional areas, hypertrophy markers atrial natriuretic factor and beta-myosin heavy chain). Systolic and diastolic function, measured invasively (left ventricular conductance catheter) and noninvasively (MRI), were similar for WT and GAMT-/- mice. However, during inotropic stimulation with dobutamine, preload-recruitable stroke work failed to reach maximal levels of performance in GAMT-/- hearts (101+/-8 mm Hg in WT versus 59+/-7 mm Hg in GAMT-/-; P
M3 - SCORING: Zeitschriftenaufsatz
VL - 111
SP - 2477
EP - 2485
JO - CIRCULATION
JF - CIRCULATION
SN - 0009-7322
IS - 19
M1 - 19
ER -