Despite the urgent need for experimental research in the field of acute heart failure and, particularly cardiogenic shock, currently there are only limited options in large animal models enabling research using devices applied to human subjects. The majority of available models are either associated with an unacceptably high rate of acute mortality or are incapable of developing sufficient severity of acute heart failure. The objective of our research was to develop a novel large animal model of acute severe cardiogenic shock. Advanced left ventricular dysfunction was induced by global myocardial hypoxia by perfusing the upper body (including coronary arteries) with deoxygenated venous blood. The model was tested in 12 pigs: cardiogenic shock with signs of tissue hypoxia developed in all animals with no acute mortality. Cardiac output decreased from a mean (+/- SD) of 6.61+/-1.14 l/min to 2.75+/-0.63 l/min, stroke volume from 79.7+/-9.8 ml to 25.3+/-7.8 ml and left ventricular ejection fraction from 61.2+/-4.3 % to 17.7+/-4.8 % (P</=0.001 for all comparisons). In conclusion, the porcine model of acute cardiogenic shock developed in the present study may provide a basis for studying severe left ventricular dysfunction, low cardiac output and hypotension in large animals. The global myocardial hypoxia responsible for the decrease in cardiac contractility was not associated with acute death in this model.