Thorac Cardiovasc Surg 2013; 61 - OP241
DOI: 10.1055/s-0032-1332480

Effects of cyclosporine pretreatment on tissue oxygen levels and cytochrome oxidase activity. A study in the skeletal muscle- model for ischemia and reperfusion impact

D Troitzsch 1, JM Hasenkam 1, H Nygaard 1, RG Moosdorf 2, S Vogt 2, 3
  • 1Aarhus University and Aarhus University Hospital, Cardiovascular Program, Faculty of Health Sciences, Aahrus, Denmark
  • 2Universitätsklinikum Gießen und Marburg GmbH, Herzchirurgie, Marburg, Germany
  • 3Biomedizinisches Forschungszentrum der Philipps-Universität Marburg, Kardiovaskuläres Forschungslabor/Herzchirurgie, Marburg, Germany

Objectives: We hypothesized that pretreatment with single dose cyclosporine (CsA) prevents alterations and improves tissue oxygen and mitochondrial redox state (CytOx) in ischemia and reperfusion-reoxygenation (I/R).

Methods: In a model of Latissimus dorsi (LD), the muscle was prepared and mobilized in New Zealand White rabbits. Warm ischemia was induced for 4 hours, followed by 2 hours of reperfusion. The animals were randomized to receive a 60 mg/kg intravenous bolus of cyclosporine (CsA group, n = 10) or physiologic saline (control, n = 10) at 10 min before ischemia onset. Muscle tissue oxygen tension (PO2) and mitochondrial CytOx were measured during I/R simultaneously. High-energy phosphate (HEP) levels were determined using high-field 31P magnetic resonance spectroscopy (MRS). Mitochondrial viability index and wet-to-dry ratio were used to assess the tissue viability between groups.

Results: Decreases of tissue oxygen levels (PO2) and CytOx were faster during ischemia in the control group in comparison to CsA group, also the loss of PCr and ATP depletion. After ischemia, recovery of tissue oxygen, mitochondrial CytOx and HEP was slower in controls. Tissue PO2 in the CsA group (p < 0.05 vs. control) was significantly higher compared with control group after I/R. Mitochondrial CytOx was also improved in the CsA group (p < 0.01) compared with the control group. Muscle phosphocreatine (PCr) and adenosine triphosphate (ATP) levels were significantly preserved and higher in CsA group versus control (P < 0.01, P < 0.05). Mitochondrial viability index and wet-to-dry ratio confirmed significantly preserved tissue and lower edema formation in the CsA group.

Conclusion: The pretreatment with single dose CsA prevents alterations and improves tissue oxygenation and mitochondrial oxidation in skeletal muscle ischemia and reperfusion-reoxygenation.