Effects of A ngiotensin II T ype 1 R eceptor A ntagonist and T emperature on P rolonged C ardioplegic A rrest in N eonatal R at M yocytes

Cardioplegic arrest is a model of ischemia/reperfusion injury and results in the death of irreplaceable cardiac myocytes by a programmed cell death or apoptosis. Signal transducers and activators of transcription ( STAT ) signaling pathways play an important role in the modulation of apoptosis after ischemia and reperfusion. Angiotensin II type 1 ( AT 1) receptor antagonist added to cardioplegia could represent an additional modality for enhancing myocardial protection during cardioplegic arrest. To test that hypothesis, we studied the effect of AT 1 receptor antagonism and cardioplegia temperature perfusion on STATs modulation during cardioplegic arrest in neonatal rat hearts. Isolated, nonworking hearts ( n = 4 per group) from neonatal rats were perfused aerobically in the Langendorff mode according to the following scheme: D ulbecco's M odified E agle's M edium solution ( G roup 1); cold (4°C) modified S t. T homas' Hospital no. 2 ( MSTH 2) cardioplegic solution ( G roup 2); cold (4°C) MSTH 2 cardioplegic solution plus AT 1 antagonist ( V alsartan) ( G roup 3); and warm (34°C) MSTH 2 cardioplegic solution ( G roup 4). Thus, myocytes were isolated by enzymatic digestion, and STAT 1, STAT 2, STAT 3, and STAT 5 were investigated in W estern blot studies. Times to arrest after cardioplegia were 6–10 s for all groups with the exception of G roup 1 (spontaneous arrest after 12–16 s). Total cardioplegia delivery volume was about 300 mL in 15 min. Perfusion with cold MSTH 2 supplemented with AT 1 receptor antagonist ( G roup 3) induced a significant reduction in STAT 1, STAT 2, and STAT 5 tyrosine phosphorylation versus other groups ( P