Factors associated with nadir hematocrit were identified by linear regression.

Results: Median nadir hematocrit was 30% (25th to 75th percentile, 27%-33%). Lower nadir hematocrit was associated with higher maximum intraoperative lactic acid (intrasubject correlation, -0.44). After risk adjustment, nadir hematocrit was associated with worse renal function (lower estimated glomerular filtration rate; P = .012), more myocardial injury (higher troponin level; P = .004), longer PRI-724 postoperative ventilator support (P < .001), longer hospital stay (P < .001), and higher mortality (P = .042). Female

gender, older age, lower body mass index, higher New York Heart Association class, and combined valve procedure and coronary artery bypass were associated with lower nadir hematocrit; however, the strongest correlate was preoperative hematocrit (correlation coefficient, 0.74).

Conclusions: Although red blood cell transfusion has associated morbidity risk, there must be a tradeoff between adverse effects of low hematocrit during cardiac surgery and those Batimastat cost of transfusion. The strong association of nadir hematocrit with preoperative hematocrit suggests the need for investigation and optimization before elective cardiac surgery. (J Thorac Cardiovasc Surg 2012;144:654-62)”
“The cloning of K(ca)2 channels revealed three subtypes, with each displaying distinct but partially overlapping expression distributions in the

mammalian I-BET151 CNS and periphery. Activation

of K(ca)2 channels leads to membrane hyperpolarization and inhibition of action potential firing. Block of K(ca)2 channels has been suggested as a novel target for cognitive enhancement, depression, myotonic muscular dystrophy and heart arrhythmias. It is clear however, that blockers selective for individual K(ca)2 channel subtypes would be required to be therapeutically useful. K(ca)2 channel current is blocked by apamin, with the bee venom toxin being unusual in displaying some selectivity between K(ca)2 channel subtypes. This suboptimal selectivity is not sufficient to be therapeutically useful and the toxin has been shown in vivo to have a very narrow therapeutic window. Mutational and molecular modelling studies of the K(ca)2 channels are beginning to determine how selective block might be achieved. Mutagenesis has indicated the importance of the outer pore region and the extracellular loop between transmembrane domains S3 and S4 for block of K(ca)2 current by apamin. Mapping the sequence of transmembrane domains S5, pore helix and S6 onto the crystal structures of KcsA, MthK and Kv1.2 has provided an approximation of the pore structure. This approach has allowed structural modelling of the interactions between toxins and channel, demonstrating that the toxins that show little discrimination between K(ca)2 channel subtypes interact with the outer pore and around the K(+) selectivity filter.