P229 Changes in Myocardial Gene Expression During Cardioplegic Arrest Depends on Cardioplegic Solution Type.
1U.Fischer, 2C.Cox, 2A.Steven, 3G.Laine, 1A.Antonyan, 4W.Bloch, 1U.Mehlhorn
1Klinik und Poliklinik für Herz- und Thoraxchirurgie, Universität zu Köln, Köln; 2University of Texas-Houston, Houston, US; 3Michael E. DeBakey Institue, Texas A&M University, College Station, US; 4Institut I für Anatomie, Universität zu Köln, Köln.

Objectives: For evaluation and improvement of myocardial protection during cardioplegic arrest (CA) it is crucial to understand intracellular changes. As only little is known about altered gene expression during CA, we investigated gene expression in rat myocardium subjected to CA with two different cardioplegic solutions using the new microarray-technique.

Methods: Twelve adult rats (300-350g) were anesthetized, intubated and mechanically ventilated. CA was initiated by infusion of ice-cold crystalloid solution (either Bretschneider solution (Custodiolâ) or St. Thomas solution (Plegisolâ), 10ml/kg) into the aortic root. The hearts were stored for 120 min (n=6 each) in 0.9% sodium chloride solution (28°C). Six additional rats with no CA served as controls. Fluorescent-labeled cDNA probes were generated by reverse transcription of mRNA prepared from control and 120 min CA tissue. The probe pairs were applied to microarrays that contained about 14000 rat heart cDNA clones.

Results: After 120 min of CA with Custodiol more than 900 genes were differently expressed, either significantly up or down regulated, whereas with Plegisol expression of only 80 genes was changed. The pattern of gene expression changes as well as the degree of change was different between the two groups. Furthermore, whereas CA with Plegisol resulted in a maximal 2fold change, Custodiol led to a gene expression increase up to 15fold. Interestingly, while expression of the atrial natriuretic factor (ANF) was 80% decreased with Plegsiol, ANF-expression was 6fold increased with Custodiol.

Conclusions: Myocardium not only reacts to CA with multiple changes in gene expression during ischemia; these changes also depend on cardioplegic solution type. The new microarray technology is a powerful tool to investigate molecular changes during CA and the effect of both clinically used as well as future strategies in myocardial protection.