Extracorporeal circulation (ECC) is indispensable for cardiac surgery. Since difficulty in clinical research keeps the knowledge insufficient, it is desirable to have a miniature ECC system for small animals. We aimed to establish a miniature ECC system and apply the system to the rat for investigating biochemical changes. The ECC system consisted of a membranous oxygenator (polypropylene, 0.03 m²), tubing line (polyvinyl chloride) and roller pump. Priming volume of this system is only 15 ml. Rats were divided into the SHAM group and the ECC group. ECC pump flow was initiated and maintained at 70 ml/kg/min. We measured the serum cytokine levels of tumor necrosis factor-a, interleukin (IL)-6, and IL-10, and biochemical markers (lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase) before, 60, and 120 min after the initiation of ECC. In addition, we measured the wet-to-dry weight (W/D) ratio of the left lung tissues. During ECC, blood pressure and Hb were maintained around 80 mmHg and 10g/dl, the serum cytokine levels and biochemical markers were significantly elevated in the ECC group compared with the SHAM group. The W/D ratio increased significantly more in the ECC group compared with that in the SHAM group. These data suggest that ECC promotes organ damages and systemic inflammatory response. This rat ECC model is considered to be equivalent to the already established human ECC and useful for studying the mechanism of pathophysiological changes during artificial perfusion.

Extracorporeal circulation (ECC) methods are being increasingly used for mechanical support of respiratory and cardio-circulatory failure. Especially, cardiopulmonary bypass (CPB) during cardiovascular surgery, sustenance of the patient’s life by providing an appropriate blood flow and oxygen supply to principal organs. On the other hand, systemic inflammatory responses in patients undergoing cardiovascular surgery supported by CPB contribute significantly to CPB-associated mortality and morbidity. Our previous research showed that CPB causes a systemic inflammatory response and organ damage in a small animal CPB model. We have been studying the effects of hyperoxia and blood plasma substitute on CPB. In this review, we present a study focusing on the systemic inflammatory response during CPB, along with our findings.

Background: Extracorporeal membrane oxygenation (ECMO) is being increasingly used for mechanical support of respiratory and cardio-circulatory failure. An excessive systemic inflammatory response is observed during sepsis and after cardiopulmonary bypass (CPB) with similar clinical features. We hypothesized that hyperoxia condition encourages the systemic inflammatory response and organ disorder during ECMO. To prove this hypothesis correct, we investigated the systemic inflammatory responses at normal and high levels of arterial oxygen pressure (PaO₂) in the rat ECMO model. Methods: Rats were randomly assigned to one of the following groups depending on the value of PaO₂ during ECMO: A group (n=11, PaO₂ 100–199 mmHg), B group (n=10, PaO₂ 200–299 mmHg), C group (n=8, PaO₂ 300–399 mmHg), and D group (n=11, PaO₂ >400 mmHg). Serum cytokine levels [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10)] were measured before, 60, and 120 min after the initiation of ECMO. The wet-to-dry weight (W/D) ratio of the left lung was also measured, and dihydroethidium (DHE) staining, reflecting superoxide generation, of lung and liver tissues was performed 120 min after ECMO initiation. Results: In the C and D groups, the pro-inflammatory cytokines (TNF-α and IL-6) significantly increased during ECMO compared with the other groups. On the other hand, the increase in anti-inflammatory cytokines (IL-10) was more suppressed in the C and D groups than in the other groups. The W/D ratio increased significantly more in the C and D groups than in the other groups. In addition, DHE fluorescence had a tendency to increase as the PaO₂ rose. Conclusions: These data demonstrate that it is better to avoid administration of too much oxygen during ECMO to attenuate lung injury linked to generation of superoxide and the systemic inflammatory response.

Currently, nonpulsatile selective cerebral perfusion for cerebroprotection against thoracic aortic aneurysm is used in clinical settings. We performed synchrotron radiation microangiography to determine the effects on selective cerebral perfusion modulation by pulsatile flow. We established cerebral perfusion at normothermia and severe hypothermia in anesthetized rats, during which cerebral angiography was performed. NG-nitro-L-arginine-methyl ester hydrochloride (L-NAME) was administered to determine the effect of pulsatile flow with nitric oxide synthesis. In comparison with nonpulsatile flow, the relative diameters of small internal carotid artery were 132.11 ± 5.49% and 114.96 ± 4.60% during pulsatile flow at normothermia and severe hypothermia (p < 0.05). The angiographic scores, an indicator of vessel count, for nonpulsatile and pulsatile flow at normothermia were 0.198 ± 0.013 vs. 0.258 ± 0.010 (p < 0.001) and those at severe hypothermia were 0.158 ± 0.017 vs. 0.214 ± 0.015 (p < 0.01), respectively. In comparison with nonpulsatile flow, the relative internal carotid artery diameters during pulsatile flow with and without L-NAME were 98.50 ± 1.7% vs. 114.96 ± 4.6%, respectively, during severe hypothermia. These results show that pulsatile flow is effective in increasing blood vessel diameter, number of vessels, and perfusion distribution range in the rat model and that it was more effective at normothermia during nitric oxide production.