Next generation of cardiovascular studies: transcriptional responses of the human myocardium during cardiac surgery.

486 March 2015 A RGUABLY, one of the most significant directions for research in anesthesiology is finding new approaches to make surgical interventions safer. Interesting is the fact that despite a surgical procedure being performed for the correct indication and in a technically superb manner, patients may frequently be threatened by perioperative organ injury.1 For example, myocardial injury is one of the leading causes of morbidity and mortality in surgical patients, including patients undergoing noncardiac surgery. As such, a recent study in over 15,000 patients undergoing inpatient noncardiac surgery demonstrated that elevated troponin— irrespective of the presence of an ischemic feature—independently predicts 30-day mortality, suggesting that myocardial injury occurs frequently in the perioperative period and is associated with dramatic increases of mortality.2 Consistent with the notion that perioperative organ injury is one of the leading causes of morbidity and mortality of surgical patients, numerous experimental studies have tried to find novel therapeutic targets that would allow rendering a specific organ more resistant to the detrimental effects of limited supply with oxygen and nutrients, such as occurs during ischemia and reperfusion injury. Many of these studies have taken an approach to examine transcriptional changes as an indicator to find potentially important therapeutic targets. Frequently, such studies would set out with the notion that endogenous protective pathways could be activated during injurious conditions, thereby resulting in the enhanced transcription of protective genes that could be targeted to help adopt a specific organ to tolerate injurious conditions more efficiently. Subsequently, pharmacologic approaches that would directly target such pathways could be applied as novel organ-protective approaches. One of the main limitations of many of these studies is related to the model system that is being used. Indeed, such studies would most frequently expose mice to injurious conditions to elicit organ injury (e.g., myocardial ischemia, acute kidney injury, and acute lung injury) and subsequently examine adaptive responses that could be important in perioperative organ protection. As published in the current edition of AneStheSIOLOGY, Muehlschlegel et al.3 took a different approach to identify transcriptional changes that could be targeted for perioperative organ protection.3 Focusing on myocardial injury, they performed next-generation RnA sequencing to examine transcriptional changes that occur within the left ventricle of patients undergoing cardiac surgery. This innovative approach allows for the first time to identify in an unbiased fashion the transcriptional changes within the left ventricular wall occurring in patients undergoing open heart surgery. Importantly, the authors can be congratulated on studying transcriptional responses during cardiac surgery in a translationally relevant model system. They were able to obtain left ventricular biopsies from 45 patients undergoing aortic valve replacement surgery at baseline and after an average of 79 min of cold cardioplegic arrest. This was achieved by utilizing left ventricular punch biopsies from the site of a routinely placed surgical vent in the anterolateral Next Generation of Cardiovascular Studies