The effects of preconditioning coronary artery disease patients with hyperbaric oxygen prior to coronary artery bypass graft surgery & cardiopulmonary bypass

IntroductionCoronary artery bypass graft (CABG) is associated with periods of ischaemia and reperfusion, which may lead to myocardial dysfunction. In clinical studies, hyperbaric oxygen (HBO2) treatment following an acute myocardial infarction (AMI), has been shown to limit myocardial injury and improve myocardial function. The primary efficacy objective of this study was to determine if systemically preconditioning coronary artery disease (CAD) patients with HBO2, prior to first time elective on cardiopulmonary bypass (CPB) CABG surgery, leads to a remote preconditioning like effect that is capable of improving myocardial function following CABG. The main secondary objectives of this study were to assess the safety of HBO2 preconditioning and, its effects on myocardial injury and post operative intensive care unit (ICU) length of stay. The exploratory secondary objectives were to assess the effects of HBO2 preconditioning on surrogate serum biomarkers of endothelial and neutrophilic adhesiveness and, myocardial biomarkers of cardioprotection. Methods In this single centre, randomised control study, 81 patients, who were having first time elective on CPB CABG surgery, were recruited. 40 were randomised to the Control Group and 41 to the HBO2 Group. Treatment with HBO2 preconditioning was completed approximately 2 hours prior to CPB and consisted of two 30 minute sessions of 100% oxygen at 2.4 atmospheres (ATA) separated 5 minutes apart. Efficacy was measured by determining peri-operative haemodynamic measurements using a pulmonary artery (PA) catheter. Safety was measured by collecting peri-operative data on myocardial injury and adverse events (AEs) and, post operative days spent in ICU. Using collected peri-operative venous blood, myocardial injury was determined by measuring the concentration of serum Troponin-T. In these same venous blood samples, endothelial and neutrophilic adhesiveness was indirectly assessed by measuring the concentrations of sE-selectin, sP-Selectin and sICAM-1 and, sPSGL-1, respectively. Using intra-operative right atrial biopsies, the degree of cardioprotection provided by HBO2 preconditioning was determined by measuring the quantity of myocardial eNOS and Hsp72. Analysis of the serum and myocardial biomarkers were done by ELISA.Results Compared to the Control Group, the HBO2 Group demonstrated a significant improvement in left venticular stroke work (LVSW) 24 hours post CPB (p=0.005). While there were no significant safety findings, there were fewer cardiovascular, pulmonary, renal and neurological AEs in the HBO2 Group. This group also had a significantly shorter post operative ICU length of stay. 1 hour post HBO2 preconditioning, the concentration of sPSGL-1 increased significantly in the HBO2 Group. At all time points, the peri-oprative concentration of sPSGL-1 was higher in the HBO2 Group but none of the changes were significant. The latter was also the case for the peri-operative concentration of sP-Selectin, apart from following the period of ischaemic and reperfusion, when it was lower in the HBO2 Group. Intra-operatively, the concentration of sE-Selectin increased significantly in the HBO2 Group and was higher in this group throughout the peri-operative period. During this intra-operative period also, the concentration of sICAM-1 was higher in the HBO2 Group and the increase was particularly significant following the period of ischaemia and reperfusion. 24 hours post CPB, the concentrations of all the serum soluble adhesion molecules were higher in the HBO2 Group. No significant differences were observed between the groups with respect to the concentrations of serum Troponin-T and, the quantity of myocardial eNOS and Hsp72. However, in the HBO2 Group, the peri-operative concentrations of serum Tropinin-T, eNOS and Hsp72 were lower. Furthermore, while there was a pre-CPB reduction of both eNOS and Hsp72, following ischaemia and reperfusion, the quantity of both these myocardial biomarkers were increased. Conclusion From this study, it can be concluded that HBO2 preconditioning of patients with CAD prior to on CPB CABG, is capable of improving myocardial function 24 hours post CABG. Additionally, the data suggest that this may also be a safe modality of treatment as it did not lead to significant post operative AEs, limited peri-operative myocardial injury and reduced post operative ICU length of stay. It also led to increased post operative concentrations of the measured surrogate biomarkers of endothelial and neutrophilic adhesiveness, with a number of significant peri-operative changes. Finally, while HBO2 treatment did not lead to significant changes in the myocardial biomarkers of cardioprotection, the quantities of these increased in the HBO2 Group following ischaemia and reperfusion, suggesting that it may be capable of inducing endogenous cardioprotection following ischaemia and reperfusion

The effects of preconditioning coronary artery disease patients with hyperbaric oxygen prior to coronary artery bypass graft surgery & cardiopulmonary bypass

IntroductionCoronary artery bypass graft (CABG) is associated with periods of ischaemia and reperfusion, which may lead to myocardial dysfunction. In clinical studies, hyperbaric oxygen (HBO2) treatment following an acute myocardial infarction (AMI), has been shown to limit myocardial injury and improve myocardial function. The primary efficacy objective of this study was to determine if systemically preconditioning coronary artery disease (CAD) patients with HBO2, prior to first time elective on cardiopulmonary bypass (CPB) CABG surgery, leads to a remote preconditioning like effect that is capable of improving myocardial function following CABG. The main secondary objectives of this study were to assess the safety of HBO2 preconditioning and, its effects on myocardial injury and post operative intensive care unit (ICU) length of stay. The exploratory secondary objectives were to assess the effects of HBO2 preconditioning on surrogate serum biomarkers of endothelial and neutrophilic adhesiveness and, myocardial biomarkers of cardioprotection. Methods In this single centre, randomised control study, 81 patients, who were having first time elective on CPB CABG surgery, were recruited. 40 were randomised to the Control Group and 41 to the HBO2 Group. Treatment with HBO2 preconditioning was completed approximately 2 hours prior to CPB and consisted of two 30 minute sessions of 100% oxygen at 2.4 atmospheres (ATA) separated 5 minutes apart. Efficacy was measured by determining peri-operative haemodynamic measurements using a pulmonary artery (PA) catheter. Safety was measured by collecting peri-operative data on myocardial injury and adverse events (AEs) and, post operative days spent in ICU. Using collected peri-operative venous blood, myocardial injury was determined by measuring the concentration of serum Troponin-T. In these same venous blood samples, endothelial and neutrophilic adhesiveness was indirectly assessed by measuring the concentrations of sE-selectin, sP-Selectin and sICAM-1 and, sPSGL-1, respectively. Using intra-operative right atrial biopsies, the degree of cardioprotection provided by HBO2 preconditioning was determined by measuring the quantity of myocardial eNOS and Hsp72. Analysis of the serum and myocardial biomarkers were done by ELISA.Results Compared to the Control Group, the HBO2 Group demonstrated a significant improvement in left venticular stroke work (LVSW) 24 hours post CPB (p=0.005). While there were no significant safety findings, there were fewer cardiovascular, pulmonary, renal and neurological AEs in the HBO2 Group. This group also had a significantly shorter post operative ICU length of stay. 1 hour post HBO2 preconditioning, the concentration of sPSGL-1 increased significantly in the HBO2 Group. At all time points, the peri-oprative concentration of sPSGL-1 was higher in the HBO2 Group but none of the changes were significant. The latter was also the case for the peri-operative concentration of sP-Selectin, apart from following the period of ischaemic and reperfusion, when it was lower in the HBO2 Group. Intra-operatively, the concentration of sE-Selectin increased significantly in the HBO2 Group and was higher in this group throughout the peri-operative period. During this intra-operative period also, the concentration of sICAM-1 was higher in the HBO2 Group and the increase was particularly significant following the period of ischaemia and reperfusion. 24 hours post CPB, the concentrations of all the serum soluble adhesion molecules were higher in the HBO2 Group. No significant differences were observed between the groups with respect to the concentrations of serum Troponin-T and, the quantity of myocardial eNOS and Hsp72. However, in the HBO2 Group, the peri-operative concentrations of serum Tropinin-T, eNOS and Hsp72 were lower. Furthermore, while there was a pre-CPB reduction of both eNOS and Hsp72, following ischaemia and reperfusion, the quantity of both these myocardial biomarkers were increased. Conclusion From this study, it can be concluded that HBO2 preconditioning of patients with CAD prior to on CPB CABG, is capable of improving myocardial function 24 hours post CABG. Additionally, the data suggest that this may also be a safe modality of treatment as it did not lead to significant post operative AEs, limited peri-operative myocardial injury and reduced post operative ICU length of stay. It also led to increased post operative concentrations of the measured surrogate biomarkers of endothelial and neutrophilic adhesiveness, with a number of significant peri-operative changes. Finally, while HBO2 treatment did not lead to significant changes in the myocardial biomarkers of cardioprotection, the quantities of these increased in the HBO2 Group following ischaemia and reperfusion, suggesting that it may be capable of inducing endogenous cardioprotection following ischaemia and reperfusion