A novel small animal extracorporeal circulation model for studying pathophysiology of cardiopulmonary bypass

Abstract

Extracorporeal circulation (ECC) is indispensable for cardiac surgery. Despite the fact that ECCcauses damage to blood components and is non-physiologic, its pathophysiology has not been fully elucidated. This is because difficulty in clinical research and animal experiments keeps the knowledge insufficient. Therefore, it is desirable to have a miniature ECC model for small animals, which enables repetitive experiments, to study the mechanism of pathophysiological changes during ECC. We developed a miniature ECC system and applied it to the rat. We measured changes in hemodynamics, blood gases and hemoglobin (Hb) concentration, serum cytokines (TNF-α, IL-6, IL-10), biochemical markers (LDH, AST, ALT), and the wet-to-dry weight (W/D) ratio of the lung for assessing whether the rat ECC model is comparable to the human ECC. The ECC system consisted of a membranous oxygenator (polypropylene, 0.03 m(2)), tubing line (polyvinyl chloride), and roller pump. Priming volume of this system is only 8 ml. Rats (400-450 g) were divided into the SHAM group (n = 7) and the ECC group (n = 7). Blood samples were collected before, 60 and 120 min after initiation of ECC. During ECC, blood pressure and Hb were maintained around 80 mmHg and 10 g/dL, respectively. The levels of the inflammatory and biochemical markers and the W/D ratio were significantly elevated in the ECC group, indicating some organ damages and systemic inflammatory responses during ECC. We successfully established the ECC for the rat. This miniature ECC model could be a useful approach for studying the mechanism of pathophysiology during ECC and basic assessment of the ECC devices.

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

“…These findings were similar to those of our previous studies. [5][6][7] Levels of the proinflammatory cytokines TNF-α, IL-6, and the biochemical markers LDH, AST, and ALT were significantly more elevated in the high PV CPB group than in the low PV CPB group at 60 min, whereas none of the markers significantly differed between them at 120 min. The W/D ratio in the lungs at the end of CPB was higher in the high PV group than in the low PV group, indicating more water accumulation in the high PV group.…”

“…4 The current study compares inflammatory responses in a rat model of CPB using a new small circuit and a relatively conventional large circuit. [5][6][7] We tested the hypothesis that the small CPB circuit with reduced PV and blood contact with surfaces would attenuate the systemic inflammatory response and reduce levels of inflammatory cytokines as well as organ tissue damage. We therefore compared levels of serum CD11b, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) and the biochemical markers lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) between groups of rats given CPB with the new small or the conventional large circuit.…”

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 ).…”