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Summary: Similarities between humans and swine have been established on the basis of anatomic and physiologic characteristics. Consequently, the use of swine in biomedical research has increased over the last few decades. Most cardiopulmonary bypass (CPB) techniques in swine are only partial CPBs without cardiac arrest or aortic clamping. In addition, the post-operative period is often limited to a few hours. We decided to establish a swine model of total CPB with cardiac arrest and aortic clamping while allowing a post-operative period of 24 h. The purpose of this article is to describe our swine model that closely simulates the human situation in CPB surgery. Cardiac arrest with cardioplegia and aortic clamping was undertaken for 75 min. CPB was well-tolerated, and all pigs were weaned from it. Post-operative care was continued for 24 h. Hemodynamic and respiratory changes, characterized by reduced cardiac function, arrhythmias, and decreased oxygenation associated with ischemia-reperfusion and the inflammatory process under CPB, were recorded and compared to the same parameters in control pigs. [Copyright &y& Elsevier]