Background: The study was conducted to determine the effects of isolated acute intracranial hypertension (AICH) on extracerebral organs.Design: A total of 14 mechanically ventilated pigs were randomized to two groups of seven each: (1) control and (2) AICH.Methods: AICH was induced by inflating an intracranial balloon catheter. The inflation volume was adjusted to keep intracranial pressure between 30 and 40 cm H2O. Hemodynamics, gas-exchange, and global oxygen delivery parameters were observed over a 4-hour period. At the end of the 4-hour period, tissue samples of heart, lungs, liver, and kidneys were collected and histologically graded for inflammation, edema, and cell damage (necrosis) using semiquantitative scores.Results: Animals with AICH had increased heart rate and cardiac output, and higher scores for inflammation, edema, and necrosis in heart, lung, kidney, and liver tissues (all p < 0.05). Peripheral and mixed-venous oxygen saturations were unaffected.Conclusions: Isolated AICH induces injury to multiple extracerebral organs, even in the absence of hypoperfusion or hypoxemia.