Lethal ventricular arrhythmias (VT/VF) is serious complications in severe hemorrhagic shock (HS). Cardiac autonomic imbalance and dysfunction are well known unfavorable conditions. However, the effect of oxygenation including artificial oxygen carrier is not fully understood. To investigate the role of oxygenation in lethal HS, cardiac autonomic activity measures, cardiac function test, optical mapping analysis (OMP), and electrophysiological study (EPS) were performed in rats lethal HS.
Methods and Results:
1) Over the course of 150 min, rats were subjected to blood withdrawal (0.2 mL/min; total 85% bleeding) and simultaneously transfused with washed rat red blood cells (wRBC), liposome-encapsulated hemoglobin (LHb) or 5% albumin (5%ALB). Temporal changes in cardiac function by 2-D Echocardiography, heart-type fatty acid-binding protein (hFAB) levels, plasma levels of catecholamines, heart rate variability (HRV), and hypoxia-inducible factor 1α expression (HIF1) were measured. As results, > 85% of the rats transfused with either LHb or wRBC survived for 8 days. LHb transfusion suppressed HIF1 expression in the heart, maintained low levels of hFAB, and attenuated sympathetic nerve activity as reflected by changes in HRV and catecholamines. 2) After cannulating 22G catheter into the abdominal aorta, acute HS was induced by withdrawing 30% of total blood for 25 min. After HS, the rats were immediately resuscitated by transfusing the same amount of wRBC, LHb, or 5%ALB. After excising the heart, OMP and EPS were performed in Langendorff-perfused hearts. OMP revealed abnormal ventricular conduction delay in conjunction with impaired action potential duration (APD) dispersion in 5%ALB. In contrast, myocardial conduction velocity and APD dispersion were substantially attenuated in wRBC or LHb. Sustained VT/VF was easily provoked by burst pacing stimulus to the LV in 5%ALB whereas no VT/VF was induced with wRBC or LHb.
Conclusions:
The results indicate that wRBC and LHb attenuates cardiac dysfunction and sympathetic overactivity during lethal HS. Oxygenated hemoglobin transfusion by using either wRBC or LHb prevents VT/VF by preserving myocardial electrical structures caused by ischemia-reperfusion injury in HS.
THE EFFICACY OF HEMOGLOBIN-VESICLE, AN ARTIFICIAL OXYGEN CARRIER, IN HEMORRHAGIC SHOCK RESUSCITATION, AND CARDIOPULMONARY BYPASS
