To investigate central and pulmonary hemodynamics in a standardized normovolemic experimental muscle injury model, 8 anesthetized and mechanically ventilated test pigs were intracavally infused with 100 ml of autologous muscle extract over a period of 100 min; 8 control pigs received Ringer’s solution. The cardiac index decreased 20% and the heart rate decreased 10% within 30 min of starting the infusion in the muscle extract group and remained depressed. Mean arterial pressure increased significantly in both groups. The pulmonary capillary wedge pressure and central venous pressure remained relatively unchanged during the 5-hour study. A 2-fold increase in mean pulmonary arterial pressure and a nearly 4-fold increase in the pulmonary vascular resistance index was seen in the muscle extract infusion group, which however returned to normal. Arterial hemoglobin concentration and systemic vascular resistance index remained fairly stationary in both groups. Immediate significant decreases in both arterial oxygen saturation and arterial oxygen tension were observed in the muscle extract group, however both variables recovered towards the end of the experiment. A slight increase in arterial blood pH value was noted during the experiment. In conclusion, autologous muscle extract infusion causes decreases in heart rate and cardiac index, as well as a significant increase in pulmonary vascular tone and systemic hypoxemia, emphasizing the detrimental effects of skeletal muscle injury following severe trauma.