Luis Ignacio González-Granado
Wilson P. Daugherty, Joseph E. Levasseur, Dong Sun, Gaylan L. Rockswold and M. Ross Bullock
Object. In the current study, the authors examined the effects of hyperbaric O2 (HBO) following fluid-percussion brain injury and its implications on brain tissue oxygenation (PO2) and O2 consumption (VO2) and mitochondrial function (redox potential).
Methods. Cerebral tissue PO2 was measured following induction of a lateral fluid-percussion brain injury in rats. Hyperbaric O2 treatment (100% O2 at 1.5 ata) significantly increased brain tissue PO2 in both injured and sham-injured animals. For VO2 and redox potential experiments, animals were treated using 30% O2 or HBO therapy for 1 or 4 hours (that is, 4 hours 30% O2 or 1 hour HBO and 3 hours 100% O2). Microrespirometer measurements of VO2 demonstrated significant increases following HBO treatment in both injured and sham-injured animals when compared with animals that underwent 30% O2 treatment. Mitochondrial redox potential, as measured by Alamar blue fluorescence, demonstrated injury-induced reductions at 1 hour postinjury. These reductions were partially reversed at 4 hours postinjury in animals treated with 30% O2 and completely reversed at 4 hours postinjury in animals on HBO therapy when compared with animals treated for only 1 hour.
Conclusions. Analysis of data in the current study demonstrates that HBO significantly increases brain tissue PO2 after injury. Nonetheless, treatment with HBO was insufficient to overcome injury-induced reductions in mitochondrial redox potential at 1 hour postinjury but was able to restore redox potential by 4 hours postinjury. Furthermore, HBO induced an increase in VO2 in both injured and sham-injured animals. Taken together, these data demonstrate that mitochondrial function is depressed by injury and that the recovery of aerobic metabolic function may be enhanced by treatment with HBO.
Wilson P. Daugherty, Michelle J. Clarke, Harry J. Cloft and Giuseppe L. Lanzino
Intracranial aneurysms in the pediatric population are relatively rare entities. Immunocompromised patients (often from HIV/AIDS or pharmacological immunosuppression) represent a significant fraction of children with cerebral aneurysms. One proposed mechanism of aneurysm formation in these patients is from direct infection of the affected arteries. In this study, the authors report on a case of a 14-year-old girl with common variable immunodeficiency with T-cell dysfunction and a CSF polymerase chain reaction test positive for varicella-zoster virus who underwent evaluation for carotid and basilar artery fusiform aneurysms.
Taek Hyun Kwon, Dong Sun, Wilson P. Daugherty, Bruce D. Spiess and M. Ross Bullock
Object. This study was conducted to determine whether perfluorocarbons (PFCs) improve brain oxygenation and reduce ischemic brain damage in an acute subdural hematoma (SDH) model in rats.
Methods. Forty adult male Sprague—Dawley rats were allocated to four groups: 1) controls, acute SDH treated with saline and 30% O2; 2) 30-PFC group, acute SDH treated with PFC infusion in 30% O2; 3) 100-O2 group, acute SDH treated with 100% O2; and 4) 100-PFC group, acute SDH treated with PFC plus 100% O2. Ten minutes after the induction of acute SDH, a single dose of PFC was infused and 30% or 100% O2 was administered simultaneously. Four hours later, half of the rats were killed by perfusion for histological study to assess the extent of ischemic brain damage. The other half were used to measure brain tissue oxygen tension (PO2). The volume of ischemic brain damage was 162.4 ± 7.6 mm3 in controls, 165.3 ± 11.3 mm3 in the 30-PFC group, 153.4 ± 17.3 mm3 in the 100-O2 group, and 95.9 ± 12.8 mm3 in the 100-PFC group (41% reduction compared with controls, p = 0.002). Baseline brain tissue PO2 values were approximately 20 mm Hg, and after induction of acute SDH, PO2 rapidly decreased and remained at 1 to 2 mm Hg. Treatment with either PFC or 100% O2 improved brain tissue PO2, with final values of 5.14 and 7.02 mm Hg, respectively. Infusion of PFC with 100% O2 improved brain tissue PO2 the most, with a final value of 15.16 mm Hg.
Conclusions. Data from the current study demonstrated that PFC infusion along with 100% O2 can significantly improve brain oxygenation and reduce ischemic brain damage in acute SDH.
Philipp Taussky, Brandon O'Neal, Wilson P. Daugherty, Sothear Luke, Dallas Thorpe, Robert A. Pooley, Clay Evans, Ricardo A. Hanel and William D. Freeman
Near-infrared spectroscopy (NIRS) offers noninvasive bedside measurement of direct regional cerebral arteriovenous (mixed) brain oxygenation. To validate the accuracy of this monitoring technique, the authors analyzed the statistical correlation of NIRS and CT perfusion with respect to regional cerebral blood flow (CBF) measurements.
The authors retrospectively reviewed all cases in which NIRS measurements were obtained at a single, academic neurointensive care unit from February 2008 to June 2011 in which CT perfusion was performed at the same time as NIRS data was collected. Regions of interest were obtained 2.5 cm below the NIRS bifrontal scalp probe on CT perfusion with an average volume between 2 and 4 ml, with mean CBF values used for purposes of analysis. Linear regression analysis was performed for NIRS and CBF values.
The study included 8 patients (2 men, 6 women), 6 of whom suffered subarachnoid hemorrhage, 1 ischemic stroke, and 1 intracerebral hemorrhage and brain edema. Mean CBF measured by CT perfusion was 61 ml/100 g/min for the left side and 60 ml/100 g/min for the right side, while mean NIRS values were 75 on the right and 74 on the left. Linear regression analysis demonstrated a statistically significant probability value (p < 0.0001) comparing NIRS frontal oximetry and CT perfusion–obtained CBF values.
The authors demonstrated a linear correlation for frontal NIRS cerebral oxygenation measurements compared with regional CBF on CT perfusion imaging. Thus, frontal NIRS cerebral oxygenation measurement may serve as a useful, noninvasive, bedside intensive care unit monitoring tool to assess brain oxygenation in a direct manner.
Zhengwen Zhou, Wilson P. Daugherty, Dong Sun, Joseph E. Levasseur, Nabil Altememi, Robert J. Hamm, Gaylan L. Rockswold and M. Ross Bullock
Hyperbaric oxygen (HBO2) has been shown to improve outcome after severe traumatic brain injury, but its underlying mechanisms are unknown. Following lateral fluid-percussion injury (FPI), the authors tested the effects of HBO2 treatment as well as enhanced normobaric oxygenation on mitochondrial function, as measured by both cognitive recovery and cellular adenosine triphosphate (ATP) levels.
Adult male Sprague–Dawley rats were subjected to moderate lateral FPI or sham injury and were allocated to one of four treatment groups: 1) FPI treated with 4 hours of normobaric 30% O2; 2) FPI treated with 4 hours of normobaric 100% O2; 3) FPI treated with 1 hour of HBO2 plus 3 hours of normobaric 100% O2; and 4) sham-injured treated with normobaric 30% O2. Cognitive outcome was assessed using the Morris water maze (MWM) on Days 11 to 15 after injury. Animals were then killed 21 days postinjury to assess hippocampal neuronal loss. Adenosine triphosphate was extracted from the neocortex and measured using high-performance liquid chromatography. The results showed that injured animals treated with HBO2 or normobaric 100% O2 alone had significantly higher levels of cerebral ATP as compared with animals treated using normobaric 30% O2 (p ≤ 0.05). The injured animals treated with HBO2 had significant improvements in cognitive recovery, as characterized by a shorter latency in MWM performance (p ≤ 0.05), and decreased neuronal loss in the CA2/3 and hilar regions as compared with those treated with 30% or 100% O2 (p ≤ 0.05).
Both hyperbaric and normobaric hyperoxia increased cerebral ATP levels after lateral FPI. In addition, HBO2 treatment improved cognitive recovery and reduced hippocampal neuronal cell loss after brain injury in the rat.
Sahar S. Abdelmoneim, Eelco F. M. Wijdicks, Vivien H. Lee, Wilson P. Daugherty, Mathieu Bernier, Jae K. Oh, Patricia A. Pellikka and Sharon L. Mulvagh
The pathophysiology of myocardial dysfunction after subarachnoid hemorrhage (SAH) remains unclear. Using myocardial real-time perfusion contrast echocardiography (RTP-CE), the authors evaluated microvascular function in patients with acute SAH.
Over a 15-month period, 10 patients with acute SAH and evidence of cardiac dysfunction were prospectively enrolled. The authors performed RTP-CE within 48 hours of SAH diagnosis. Wall motion and myocardial perfusion were evaluated in 16 left ventricle segments. Qualitative and quantitative RTP-CE analyses were conducted to compare patients with and without regional wall motion abnormalities (RWMAs). Follow-up RTP-CE at a mean of 53.7 ± 43 days was undertaken in patients with baseline RWMAs.
Ten patients with SAH and evidence of cardiac dysfunction were prospectively enrolled. There were 3 men and 7 women whose mean age was 63.5 ± 10.1 years. The authors documented evidence of RWMAs in 6 patients. Normal perfusion was demonstrated by RTP-CE in all patients at baseline and follow-up, despite the presence of RWMAs. Compared with patients presenting with normal wall motion, in patients with RWMAs there was a trend for higher quantitative RTP-CE parameters, suggesting hyperemia with mean myocardial blood flow velocity (β, s−1) of 1.08 ± 0.61 (95% CI 0–2.61) compared with 1.62 ± 0.64 (95% CI 0.94–2.29) and myocardial blood flow (A × β, dB/s) of 0.99 ± 0.41 (95% CI 0–2.0) versus 1.63 ± 0.86 (95% CI 0.72–2.53). Follow-up RTP-CE was feasible in 3 patients with RWMAs. Regional systolic function was restored in those who completed follow-up.
The authors found that RTP-CE readily evaluates microvascular function in patients with SAH. Wall motion and perfusion dissociation were observed. Quantitative RTP-CE showed a trend for microvascular hyperemia in patients with RWMAs, suggesting that post-SAH myocardial dysfunction could occur in the absence of microvascular dysfunction.