Patients undergoing cardio-pulmonary bypass (CPB) surgery exhibits endothelial dysfunction and vascular damage, often leading to post-operative vasoplegia. Endothelial progenitor cells (EPCs) and Hematopoietic stem cells (HSCs) are known to routinely home into the site of damaged endothelium and vessel wall for repair (re-endothelialisation and neo-vascularisation). The objectives of the study are to enumerate number of circulating progenitor cells, to determine Nitric Oxide (NO) index and to establish a correlation between number of circulating progenitor cells and various biochemical parameters during different stages of on-pump and off-pump cardiac surgery. Finally, we elucidated the role of arginase in mitigating hypoxia induced stress responses in in vitro endothelial cell culture system. For the study, 31 elective cardiac surgery patients (19 on-pump and 12 off-pump) were recruited and on-pump individuals were further categorized into two groups: clinically insignificant vasoplegic Group 1 (G1) or mild vasoplegia and a clinically significant vasoplegic Group 2 (G2) or severe vasoplegia based on severity of post-operative vasoplegia. Flow cytometry analysis revealed a significant increase in CD34+ followed by CD133+, CD34+CD133+ (HSCs) and VEGFR2+ cells in on-pump patients. Upon categorisation, G1 individuals exhibited a significant early increase in the number of CD34+ and CD34+CD133+ (HSCs) from 1 hour onwards, which was however blunted in G2 subjects. Plasma arginase activity measured through biochemical assays was also found to be higher in G1 subjects at 6 hours which was blunted in G2 subjects. Further, Spearman’s correlation analyses demonstrated a significant negative correlation of number of days spent in ICU and duration of ventilation with the counts of CD133+ and CD34+CD133+ cells respectively. In vitro experiments replicated the observed phenomenon of increased arginase activity, where arginase in response to hypoxia plays a protective role by promoting autophagy and inhibiting apoptosis. Lack of early response of CD34+, CD34+CD133+ cells combined with low plasma arginase activity in G2 individuals could be responsible for severity of vasoplegia.
List of publicaton:
1) Nandi S, Potunuru UR, Kumari C, Nathan AA, Gopal J, et al. (2020) Altered kinetics of circulating progenitor cells in cardiopulmonary bypass (CPB) associated vasoplegic patients: A pilot study. PLOS ONE 15(11): e0242375. https://doi.org/10.1371/journal.pone.0242375