TY - JOUR
T1 - Norepinephrine-induced acute heart failure in transgenic mice overexpressing erythropoietin
AU - Deten, Alexander
AU - Shibata, Junpei
AU - Scholz, Dimitri
AU - Briest, Wilfried
AU - Wagner, Klaus F.
AU - Wenger, Roland H.
AU - Zimmer, Heinz Gerd
N1 - Funding Information:
This work was supported by the Deutsche Forschungs-gemeinschaft (ZI 199/10-3, 4), the formel.1 program of the medical faculty of the Leipzig University (formel.1–19) and by grants of BMBF (NBL-3-Förderung; Kennzeichen 01ZZ0106).
PY - 2004/1/1
Y1 - 2004/1/1
N2 - Objective: Overexpression of erythropoietin (Epo) in mice (Epo-tg6) leads to an increase in hematocrit and blood volume, and strongly reduces endurance upon exercise. It was the aim of this study to characterize the mechanisms underlying the reduced cardiac performance. Methods: Left (LV) and right (RV) ventricular function was measured with and without norepinephrine (NE) stimulation in 12 anaesthetized Epo-tg6 and in 13 wild-type (WT) control mice. Results: There were no differences in heart function under baseline resting conditions. Stimulation with NE (10 μl bolus injections of 1-100 ng per mouse) in WT mice led to a dose-dependent increase in heart rate (HR), LV developed pressure (LVDP) and rate of rise in LV pressure (LV dP/dt max), while LV end-diastolic pressure (LVEDP) was unchanged. Except for HR, these parameters increased to a lesser extent in EPO-tg6 mice. Strikingly, LVEDP strongly increased in Epo-tg6 mice after NE (up to >20 mmHg). Eleven out of 13 Epo-tg6, but none of the WT mice died or required resuscitation after high-doses of NE. In these cases severe diastolic dysfunction became overt since the relative myocardial relaxation time was significantly prolonged and the duration of diastole was shortened. Moreover, the ECG showed a marked ST segment depression as well as deep negative T-waves. The NE-induced reduction in myocardial adenosin-triphosphate (ATP) content was more pronounced in Epo-tg6 mice after 10 min of continuous NE infusion (50 ng/min per mouse). Conclusion: NE-induced stress in Epo-tg6 mice led to acute heart failure associated with diastolic dysfunction and myocardial ischemia.
AB - Objective: Overexpression of erythropoietin (Epo) in mice (Epo-tg6) leads to an increase in hematocrit and blood volume, and strongly reduces endurance upon exercise. It was the aim of this study to characterize the mechanisms underlying the reduced cardiac performance. Methods: Left (LV) and right (RV) ventricular function was measured with and without norepinephrine (NE) stimulation in 12 anaesthetized Epo-tg6 and in 13 wild-type (WT) control mice. Results: There were no differences in heart function under baseline resting conditions. Stimulation with NE (10 μl bolus injections of 1-100 ng per mouse) in WT mice led to a dose-dependent increase in heart rate (HR), LV developed pressure (LVDP) and rate of rise in LV pressure (LV dP/dt max), while LV end-diastolic pressure (LVEDP) was unchanged. Except for HR, these parameters increased to a lesser extent in EPO-tg6 mice. Strikingly, LVEDP strongly increased in Epo-tg6 mice after NE (up to >20 mmHg). Eleven out of 13 Epo-tg6, but none of the WT mice died or required resuscitation after high-doses of NE. In these cases severe diastolic dysfunction became overt since the relative myocardial relaxation time was significantly prolonged and the duration of diastole was shortened. Moreover, the ECG showed a marked ST segment depression as well as deep negative T-waves. The NE-induced reduction in myocardial adenosin-triphosphate (ATP) content was more pronounced in Epo-tg6 mice after 10 min of continuous NE infusion (50 ng/min per mouse). Conclusion: NE-induced stress in Epo-tg6 mice led to acute heart failure associated with diastolic dysfunction and myocardial ischemia.
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U2 - 10.1016/j.cardiores.2003.10.026
DO - 10.1016/j.cardiores.2003.10.026
M3 - Article
C2 - 14732207
AN - SCOPUS:0346096546
VL - 61
SP - 105
EP - 114
JO - Cardiovascular Research
JF - Cardiovascular Research
SN - 0008-6363
IS - 1
ER -