Custodiol-N (Tm) Cardioplegia Lowers Cerebral Inflammation And Activation Of Hypoxia-Inducible Factor-1 Alpha

OBJECTIVES: Cardioplegic solutions induce cardiac arrest and protect cardiac tissue from ischaemia-reperfusion injury. However, the effects on the brain, which is vulnerable to cardiopulmonary bypass (CPB) surgery and ischaemia-reperfusion injury, mostly remain unknown. We investigated if cardioplegic solutions differ in their effects in altered oxygen conditions and in their ability to induce cerebral inflammation.METHODS: Thirty pigs were subjected to a midline sternotomy and CPB at 34 degrees C with 90 min cardiac arrest followed by 120 min reperfusion. Following randomization on a 1:1:1 basis, they received either a single shot of histidine-tryptophan-alpha-ketoglutarate (HTK)-Bretschneider solution (n = 10), histidine-tryptophan-alpha-ketoglutarate-N (HTK-N; n = 10) or HTK plus 1.2 mg/l cyclosporine A (HTK/CsA; n = 10). Brain regions of interest (frontal cortex, cerebellum, brain stem, diencephalon, colliculus superior) were analysed by real time quantitative reverse transcriptase polymerase chain reaction for hypoxia-inducible factor-1 alpha (HIF-1 alpha), tumour necrosis factor-alpha, interleukin (IL)-10, IL-1 beta and IL-1 receptor as well as by immunohistochemical analysis for HIF-1 alpha. Blood gas and electrolyte analyses were performed.RESULTS: Comparisons between baseline and reperfusion period levels revealed that HTK-N cardioplegia induced a smaller reduction of the haemoglobin content and blood calcium concentrations (hb(baseline): 5.97 +/- 0.63 mmol/l; hb(reperfusion): 6.16 +/- 0.66 mmol/l; P= 0.428; Ca-baseline(2+): 1.36 +/- 0.05 mmol/l; Ca-reperfusion(2+): 1.28 +/- 0.05 mmol/l; P < 0.001) compared to HTK (hb(baseline): 5.93 +/- 0.45 mmol/l; hb(reperfusion): 4.72 +/- 0.79 mmol/l; P= 0.001; Ca-baseline(2+): 1.34 +/- 0.07 mmol/l; Ca-reperfusion(2+): 1.24 +/- 0.06 mmol/l; P = 0.004) and HTK/CsA cardioplegia (hb(baseline): 5.88 +/- 0.44 mmol/l; hb(reperfusion): 5.14 +/- 0.87 mmol/l; P= 0.040; Ca-baseline(2+): 1.38 +/- 0.04 mmol/l; Ca-reperfusion(2+): 1.20 +/- 0.14 mmol/l; P= 0.001). Brain region-specific regulation of the HIF-1 alpha expression, no general HIF-1 alpha activation and a lower tumour necrosis factor-alpha expression (p(to) (HTK) = 0.050, P-to (HTK/CsA)= 0.013) were documented for HTK-N cardioplegia.CONCLUSIONS: HTK-N (Custodiol-N) induced fewer cerebral effects and less inflammation during CPB surgery than HTK and HTK/CsA cardioplegia. These data suggest that HTK-N exerts brain protective effects during and after CPB surgery.