Sviluppo di un nuovo micro-ossigenatore in un modello di circolazione extracorporea nell'animale di piccola taglia

Objective: Cardiopulmonary bypass (CPB) is an essential component of conventional cardiac surgery. Although the morbidity and mortality rate has decreased during the last few years, CPB continues to be associated with significant mortality, with still unknown device/patient interactions. CPB is known to induce systemic inflammation and myocardial dysfunction, which is associated with a significant morbidity. Contact of blood with the artificial surface of the bypass circuit, cardioplegic arrest, and operative trauma result in a postperfusion syndrome, including pulmonary and renal dysfunction, neurological and gastrointestinal injury, coagulation disorders, increased interstitial fluid, and susceptibility to infections. It has been increasingly recognized that this generalized inflammation and organ dysfunction is implicated in the pathogenesis of post-CPB cardiovascular dysfunction, including myocardial stunning. In order to clarify the patophysiological processes, numerous experimental studies have been developed, but most of them have been performed in larger animal models, such as dogs, sheep, and pigs. These models have substantial limitations because they are expensive and require laboratory staff and resources. A rat model of CPB can reduce the cost of animals and equipments, is more accessible and allows a large availability of assay also with transgenic, knock-out and syngenic species. Indeed cardiovascular research has mainly focused on rat models and, therefore, much more information about its physiological and pathophysiological responses are available and comparable. The present study outlines the development and validation of a complex small animal model of CPB with a new miniaturized hollow fibre oxygenator mimicking current clinical standards. This model is reproducible and it is the starting point to study various pathophysiologic effects related to CPB, myocardial protection and systemic inflammation in vivo. Methods: A hollow-fibre small priming volume (6.3ml) oxygenator was manufactured according to specifications resulting from engineering, heart surgery and perfusionist expertise (Dideco-Sorin Group, Italy) with the following characteristics: Gas Exchange Surface-450cm2, Heat Exchange Surface-16cm2. The oxygenator was tested in vitro and in vivo in 5 anaesthetised, ventilated, open-chest rats using a miniaturized roller pump and heat exchanger. Pressures were monitored in the animal, before and after the oxygenator. Central venous cannulation through the right atrium, and aortic cannulation, through the carotid artery, were used. Results: In vitro: blood oxygenation was 8-fold (room air to 100% FIO2) and PCO2 removal was 2.5-fold. In vivo: ECC was performed without blood prime for 90 minutes (60 minutes without ventilation) maintaining stable haemodynamics. A maximal blood flow rate of 124ml/min/kg was obtained. Arterio-venous PO2 gradients were 10-fold (FIO2@100%) with only small variations when changing blood flow rates. Conclusions: In conclusion, we have developed an in vivo model of rat CPB with a new miniaturized hollow fibre oxygenator with industrial standards characteristics. The results obtained with this oxygenator, cannulation and ECC circuit, achieves optimal gas transfer with small asanguinous priming volumes. This preliminary study shows that this rodent model provides reproducible data and is suitable to study clinically relevant problems related to CPB, myocardial protection and systemic inflammation.