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Title (Primary) Worsening of long-term myocardial function after successful pharmacological pretreatment with cyclosporine
Author Laudi, S.; Weimann, J.; Haschke, M.; Trump, S.; Schmitz, V.; Christians, U.; Kaisers, U.; Steudel, W.
Source Titel Journal of Physiology and Pharmacology
Year 2007
Department IMMU
Volume 58
Issue 1
Page From 19
Page To 32
Language englisch
Keywords myocardial infarction; ischemia/reperfusion; cyclosporine; preconditioning; outcome
Abstract Pretreatment with cyclosporine (CsA) decreases infarct size 24h after myocardial ischemia/reperfusion (I/R). The goal of this study was to determine effects of CsA pretreatment on long-term cardiac function after I/R-injury. Rats were randomly assigned to group1: vehicle-only, group2: CsA-5mg/kg/day, and group3: CsA-12.5mg/kg/day given orally for three days prior to I/R-injury (30 min of left anterior descending coronary artery occlusion). Post-I/R survival and cardiac function were evaluated 14 days after I/R-injury by echocardiography and invasive hemodynamic measurements. Rats with I/R-injury showed increased left ventricular pressure (LVEDP) compared to rats without I/R-injury (p<0.005). Although CsA initially decreased infarct size, no differences of LVEDP were seen 14 days after I/R-injury (vehicle: 21.2±8.9 mmHg, CsA-5mg/kg/day: 21.5±0.7 mmHg, CsA-12.5mg/kg/day: 20.5±9.4 mmHg). Ejection fraction and fractional shortening were decreased compared to baseline, but showed no differences between groups. On day 14, a dose-dependent increase in left ventricular end diastolic diameter was seen (p<0.001). CsA pretreatment was associated with a dose-dependent decrease in post-I/R-survival (vehicle: 56%, CsA-5mg/kg/day: 32%, CsA-12.5mg/kg/day: 16%; p=0.017). CsA pretreatment did not improve long-term cardiac function despite decreased infarct size 24h after I/R-injury, but increased post-I/R mortality significantly. Poor cardiac function after CsA pretreatment might be caused by left ventricular dilation.
Persistent UFZ Identifier
Laudi, S., Weimann, J., Haschke, M., Trump, S., Schmitz, V., Christians, U., Kaisers, U., Steudel, W. (2007):
Worsening of long-term myocardial function after successful pharmacological pretreatment with cyclosporine
J. Physiol. Pharmacol. 58 (1), 19 - 32