Effects of Acute Intracranial Hypertension on Extracerebral Organs: A Randomized Experimental Study in Pigs

Abstract

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.

Keywords

acute intracranial hypertension - multiple organ dysfunction - organ cross-talk

• References

• 1 Kalsotra A, Zhao J, Anakk S, Dash PK, Strobel HW. Brain trauma leads to enhanced lung inflammation and injury: evidence for role of P4504Fs in resolution. J Cereb Blood Flow Metab 2007; 27 (5) 963-974
• 2 López-Aguilar J, Villagrá A, Bernabé F , et al. Massive brain injury enhances lung damage in an isolated lung model of ventilator-induced lung injury. Crit Care Med 2005; 33 (5) 1077-1083
• 3 Lu J, Goh SJ, Tng PY, Deng YY, Ling EA, Moochhala S. Systemic inflammatory response following acute traumatic brain injury. Front Biosci 2009; 14: 3795-3813
• 4 Bratton SL, Davis RL. Acute lung injury in isolated traumatic brain injury. Neurosurgery 1997; 40 (4) 707-712 , discussion 712
• 5 Zygun DA, Kortbeek JB, Fick GH, Laupland KB, Doig CJ. Non-neurologic organ dysfunction in severe traumatic brain injury. Crit Care Med 2005; 33 (3) 654-660
• 6 Solenski NJ, Haley Jr EC, Kassell NF , et al. Medical complications of aneurysmal subarachnoid hemorrhage: a report of the multicenter, cooperative aneurysm study. Participants of the Multicenter Cooperative Aneurysm Study. Crit Care Med 1995; 23 (6) 1007-1017
• 7 Gruber A, Reinprecht A, Illievich UM , et al. Extracerebral organ dysfunction and neurologic outcome after aneurysmal subarachnoid hemorrhage. Crit Care Med 1999; 27 (3) 505-514
• 8 Fisher AJ, Donnelly SC, Hirani N , et al. Enhanced pulmonary inflammation in organ donors following fatal non-traumatic brain injury. Lancet 1999; 353 (9162) 1412-1413
• 9 Fu YC, Chi CS, Chiu YT , et al. Cardiac complications of enterovirus rhombencephalitis. Arch Dis Child 2004; 89 (4) 368-373
• 10 Hacke W, Schwab S, Horn M, Spranger M, De Georgia M, von Kummer R. ‘Malignant’ middle cerebral artery territory infarction: clinical course and prognostic signs. Arch Neurol 1996; 53 (4) 309-315
• 11 Pratschke J, Wilhelm MJ, Kusaka M , et al. Accelerated rejection of renal allografts from brain-dead donors. Ann Surg 2000; 232 (2) 263-271
• 12 Terasaki PI, Cecka JM, Gjertson DW, Takemoto S. High survival rates of kidney transplants from spousal and living unrelated donors. N Engl J Med 1995; 333 (6) 333-336
• 13 Busson M, Benoit G, N'Doye P, Hors J. Analysis of cadaver donor criteria on the kidney transplant survival rate in 5,129 transplantations. J Urol 1995; 154 (2 Pt 1) 356-360
• 14 Mascia L. Acute lung injury in patients with severe brain injury: a double hit model. Neurocrit Care 2009; 11 (3) 417-426
• 15 Mirzayan MJ, Probst C, Krettek C , et al. Systemic effects of isolated brain injury: an experimental animal study. Neurol Res 2008; 30 (5) 457-460
• 16 Silverberg J, Ginsburg D, Orman R, Amassian V, Durkin HG, Stewart M. Lymphocyte infiltration of neocortex and hippocampus after a single brief seizure in mice. Brain Behav Immun 2010; 24 (2) 263-272
• 17 Heuer JF, Pelosi P, Hermann P , et al. Acute effects of intracranial hypertension and ARDS on pulmonary and neuronal damage: a randomized experimental study in pigs. Intensive Care Med 2011; 37 (7) 1182-1191
• 18 Rohde V, Rohde I, Thiex R , et al. Fibrinolysis therapy achieved with tissue plasminogen activator and aspiration of the liquefied clot after experimental intracerebral hemorrhage: rapid reduction in hematoma volume but intensification of delayed edema formation. J Neurosurg 2002; 97 (4) 954-962
• 19 Wu S, Fang CX, Kim J, Ren J. Enhanced pulmonary inflammation following experimental intracerebral hemorrhage. Exp Neurol 2006; 200 (1) 245-249
• 20 Yildirim E, Kaptanoglu E, Ozisik K , et al. Ultrastructural changes in pneumocyte type II cells following traumatic brain injury in rats. Eur J Cardiothorac Surg 2004; 25 (4) 523-529
• 21 Cobelens PM, Tiebosch IA, Dijkhuizen RM , et al. Interferon-β attenuates lung inflammation following experimental subarachnoid hemorrhage. Crit Care 2010; 14 (4) R157
• 22 Whalen MJ, Carlos TM, Kochanek PM , et al. Interleukin-8 is increased in cerebrospinal fluid of children with severe head injury. Crit Care Med 2000; 28 (4) 929-934
• 23 Ott L, McClain CJ, Gillespie M, Young B. Cytokines and metabolic dysfunction after severe head injury. J Neurotrauma 1994; 11 (5) 447-472
• 24 Czura CJ, Tracey KJ. Autonomic neural regulation of immunity. J Intern Med 2005; 257 (2) 156-166
• 25 Takada M, Nadeau KC, Hancock WW , et al. Effects of explosive brain death on cytokine activation of peripheral organs in the rat. Transplantation 1998; 65 (12) 1533-1542
• 26 Arand M, Melzner H, Kinzl L, Brückner UB, Gebhard F. Early inflammatory mediator response following isolated traumatic brain injury and other major trauma in humans. Langenbecks Arch Surg 2001; 386 (4) 241-248
• 27 Sen S, Stober T, Burger L, Anstätt T, Rettig G, Schieffer H. [Incidence of ventricular arrhythmia relative to the QT interval in spontaneous intracranial hemorrhages]. Dtsch Med Wochenschr 1984; 109 (21) 817-820
• 28 Bourdages M, Bigras JL, Farrell CA, Hutchison JS, Lacroix J ; Canadian Critical Care Trials Group. Cardiac arrhythmias associated with severe traumatic brain injury and hypothermia therapy. Pediatr Crit Care Med 2010; 11 (3) 408-414
• 29 Grosse-Wortmann L, Bindl L, Seghaye MC. Multiple types of cardiac arrhythmias in a child with head injury and raised intracranial pressure. Pediatr Cardiol 2006; 27 (2) 286-288
• 30 Daniele O, Caravaglios G, Fierro B, Natalè E. Stroke and cardiac arrhythmias. J Stroke Cerebrovasc Dis 2002; 11 (1) 28-33
• 31 Quilez ME, Fuster G, Villar J , et al. Injurious mechanical ventilation affects neuronal activation in ventilated rats. Crit Care 2011; 15 (3) R124
• 32 Pelosi P, Ferguson ND, Frutos-Vivar F , et al; Ventila Study Group. Management and outcome of mechanically ventilated neurologic patients. Crit Care Med 2011; 39 (6) 1482-1492
• 33 Calzia E, Asfar P, Hauser B , et al. Hyperoxia may be beneficial. Crit Care Med 2010; 38 (10, Suppl) S559-S568
• 34 Nathan C. Immunology: oxygen and the inflammatory cell. Nature 2003; 422 (6933) 675-676
• 35 Bitterman H. Bench-to-bedside review: oxygen as a drug. Crit Care 2009; 13 (1) 205
• 36 Lefer AM, Lefer DJ. Pharmacology of the endothelium in ischemia-reperfusion and circulatory shock. Annu Rev Pharmacol Toxicol 1993; 33: 71-90
• 37 Pelosi P, Rocco PR. The lung and the brain: a dangerous cross-talk. Crit Care 2011; 15 (3) 168