Worsening of long-term myocardial function after successful pharmacological pretreatment with cyclosporine
Laudi, S.; Weimann, J.; Haschke, M.; Trump, S.; Schmitz, V.; Christians, U.; Kaisers, U.; Steudel, W.
Journal of Physiology and Pharmacology An Official Journal of the Polish Physiological Society 58(1): 19-32
2007
ISSN/ISBN: 0867-5910 PMID: 17440223 Document Number: 610458
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.