Cardiopulmonary Bypass with Low- Versus High-Priming Volume: Comparison of Inflammatory Responses in a Rat Model

Abstract

A cardiopulmonary bypass (CPB) can preserve life. However, interactions between blood and large artificial surfaces might help to provoke a series of chain reactions during CPB that result in the formation and release of numerous powerful inflammatory mediators including hormones and autacoids. We postulated that small CPB circuits with reduced priming volumes and less surface areas that come into contact with blood would attenuate systemic inflammatory responses by reducing the levels of cytokines and organ tissue damage during CPB. Rats were assigned to groups that underwent CPB with a high priming volume (PV) of 15 ml and a surface area of 0.044 m or a low PV of 7 ml and a surface area of 0.034 m. We measured serum levels of cytokines and biochemical markers during CPB. Levels of proinflammatory cytokines and biochemical markers were significantly elevated in the group with a high PV, than low PV at 60 min, whereas none of these factors significantly differed between the groups at 120 min. These data suggested that in addition to blood being in contact with surfaces, the duration of CPB exposure is also an important factor for nonlinear time variances in damage caused by the systemic inflammatory response.

A Rat Model of Clinically Relevant Extracorporeal Circulation Develops Early Organ Dysfunctions

“…As described recently, limiting the circuit volume also prevented the appearance of an excessive and early inflammatory response, thanks to a limited contact area between blood and the circuit components [ 19 ]. This strategy allowed us to achieve normo-volemic hemodilution with a hematocrit value of >20% for ECC maintenance, which is consistent with clinical observations and contributes to limited mortality and potential acute renal failure [ 20 , 21 , 22 ].…”

Ghrelin Pre-treatment Attenuates Local Oxidative Stress and End Organ Damage During Cardiopulmonary Bypass in Anesthetized Rats

“…Further, although the level of another clinical index of end organ damage, LDH, increased over the course of CPB in protocol 1, and was not reduced by ghrelin in that experiment (Figure 1B ) we showed that an additional post-CPB dose of ghrelin after CPB greatly reduced LDH in protocol 3, to nearly sham group level. CPB has been shown many times, to induce inflammation that in turn leads to dysfunction in multiple organ systems, including the cardiovascular, pulmonary, hepatic, renal and central nervous systems (Chello et al, 2006 ; Gottesman and Wityk, 2006 ; Gottesman et al, 2008 ; Heusch et al, 2012 ; Fujii et al, 2015 , 2016 ). This increase in LDH with time is most likely attributable to haemolysis resulting from the shear forces associated with the action of the roller pump used in this study, as previously reported (Möhnle et al, 2005 ).…”

“…Animals were housed 3 per cage under controlled conditions (12:12 h-light dark cycles) and were fed ad libitum with water and standard food pellets (Oriental Yeast Co., Ltd, Tokyo, Japan). The rat CPB was applied via venoarterial bypass and performed following Fujii et al ( 2015 , 2016 ).…”

“…The CPB model used in this study is considered to be equivalent to the established human CPB procedure, which is often associated with systemic inflammation and organ damage (Boyle et al, 1997 ; Fujii et al, 2015 , 2016 ). We used a blood flow rate comparable to clinical reports, about 2.4 l/min/m 2 of body surface area, with a cardiac index sufficient to adequately perfuse an adult patient during mild hypothermia and with 24% haematocrit levels (Alston et al, 2006 ; Santambrogio et al, 2009 ).…”