Robert P. Weenink

Animal models of cerebral arterial gas embolism

Cerebral arterial gas embolism is a dreaded complication of diving and invasive medical procedures. Many different animal models have been used in research on cerebral arterial gas embolism. This review provides an overview of the most important characteristics of these animal models. The properties discussed are species, cerebrovascular anatomy, method of air embolization, amount of air, bubble size, outcome parameters, anesthesia, blood glucose, body temperature and blood pressure.

Hyperbaric oxygen does not improve cerebral function when started 2 or 4 hours after cerebral arterial gas embolism in swine

Objective:Hyperbaric oxygenation is the accepted treatment for cerebral arterial gas embolism. Although earlier start of hyperbaric oxygenation is associated with better outcome, it is unknown how much delay can be tolerated before start of hyperbaric oxygenation. This study investigates the effect of hyperbaric oxygenation on cerebral function in swine when initiated 2 or 4 hours after cerebral arterial gas embolism. Design:Prospective interventional animal study. Setting:Surgical laboratory and hyperbaric chamber. Subjects:Twenty-two Landrace pigs. Interventions:Under general anesthesia, probes to measure intracranial pressure, brain oxygen tension (PbtO2), and brain microdialysis, and electrodes for electroencephalography were placed. The electroencephalogram (quantified using temporal brain symmetry index) was suppressed during 1 hour by repeated injection of air boluses through a catheter placed in the right ascending pharyngeal artery. Hyperbaric oxygenation was administered using U.S. Navy Treatment Table 6 after 2- or 4-hour delay. Control animals were maintained on an inspiratory oxygen fraction of 0.4. Measurements and Main Results:Intracranial pressure increased to a mean maximum of 19 mm Hg (SD, 4.5 mm Hg) due to the embolization procedure. Hyperbaric oxygenation significantly increased PbtO2 in both groups treated with hyperbaric oxygenation (mean maximum PbtO2, 390 torr; SD, 177 torr). There were no significant differences between groups with regard to temporal brain symmetry index (control vs 2-hr delay, p = 0.078; control vs 4-hr delay, p = 0.150), intracranial pressure, and microdialysis values. Conclusions:We did not observe an effect of hyperbaric oxygenation on cerebral function after a delay of 2 or 4 hours. The injury caused in our model could be too severe for a single session of hyperbaric oxygenation to be effective. Our study should not change current hyperbaric oxygenation strategies for cerebral arterial gas embolism, but further research is necessary to elucidate our results. Whether less severe injury benefits from hyperbaric oxygenation should be investigated in models using smaller amounts of air and clinical outcome measures.

Quantitative electroencephalography in a swine model of cerebral arterial gas embolism.

OBJECTIVE Cerebral arterial gas embolism (CAGE) is a serious hazard in cardiovascular surgery and other invasive procedures. We used a swine model of CAGE to determine if quantitative electroencephalography (qEEG) is a useful tool in diagnosis and prognostication of CAGE. METHODS 0.05 ml/kg of air was injected into the ascending pharyngeal artery in 16 pigs. Intracranial pressure, lactate in brain microdialysate and brain oxygen tension were measured during 4h after embolization. The qEEG parameters mean amplitude (MAMP), alpha-delta ratio (ADR), spectral edge frequency (SEF(90)), spatial brain symmetry index (sBSI) and temporal brain symmetry index (tBSI) were calculated. RESULTS MAMP and tBSI but not ADR, SEF(90) and sBSI correlate with intracranial pressure, brain lactate and brain oxygen tension after 4h. Early levels of MAMP and tBSI can predict intracranial pressure, brain lactate and brain oxygen tension after 4h. CONCLUSIONS MAMP and tBSI are sensitive for cerebral injury and can predict outcome in a swine model of CAGE. SIGNIFICANCE This study provides evidence for the utility of qEEG for diagnosis and prognosis in CAGE. Further studies are necessary to investigate the use of this method in patients.

Cerebral arterial gas embolism in swine. Comparison of two sites for air injection

Cerebral arterial gas embolism is a risk in diving and occurs as a complication in surgery and interventional radiology. Swine models for cerebral arterial gas embolism have been used in the past. However, injection of air into the main artery feeding the pig brain - the ascending pharyngeal artery - might be complicated by the presence of the carotid rete, an arteriolar network at the base of the brain. On the other hand, anastomoses between external and internal carotid territories are present in the pig. In order to determine the most appropriate vessel for air injection, we performed experiments in which air was injected into either the ascending pharyngeal artery or the external carotid artery. We injected 0.25 ml/kg of room air selectively into the ascending pharyngeal artery or the external carotid artery of 35-40 kg Landrace pigs (n=8). We assessed the effect on cerebral metabolism by measuring intracranial pressure, brain oxygen tension and brain glucose and lactate concentrations using cerebral microdialysis. Intracranial pressure and brain oxygen tension changed significantly in both groups, but did not differ between groups. Brain lactate increased significantly more in pigs in which air was injected into the ascending pharyngeal artery. Intracranial pressure, brain oxygen tension and brain lactate correlated after injection of air into the ascending pharyngeal artery, but not after injection into the external carotid artery. Our model is suitable for investigation of cerebral arterial gas embolism. The ascending pharyngeal artery is the most appropriate vessel for air injection.

Detection of cerebral arterial gas embolism using regional cerebral oxygen saturation, quantitative electroencephalography, and brain oxygen tension in the swine

BACKGROUND Cerebral air emboli occur as a complication of invasive medical procedures. The sensitivity of cerebral monitoring methods for the detection of air emboli is not known. This study investigates the utility of electroencephalography and non-invasively measured cerebral oxygen saturation in the detection of intracerebrovascular air. NEW METHOD In 12 pigs oxygen saturation was continuously measured using transcranial near-infrared spectroscopy and oxygen tension was continuously measured using intraparenchymal probes. Additionally, quantitative electroencephalography and microdialysis were performed. Doses of 0.2, 0.4, 0.8, and 1.6 ml of air were injected into the cerebral arterial vasculature through a catheter. RESULTS Oxygen saturation and electroencephalography both reacted almost instantaneously on the air emboli, but were less sensitive than the intraparenchymal oxygen tension. There was reasonable correlation (ρ ranging from 0.417 to 0.898) between oxygen saturation, oxygen tension, electroencephalography and microdialysis values. COMPARISON WITH EXISTING METHODS Our study is the first to demonstrate the effects of cerebral air emboli using multimodal monitoring, specifically on oxygen saturation as measured using near-infrared spectroscopy. CONCLUSIONS Our results show that non-invasively measured oxygen saturation and quantitative electroencephalography can detect the local effects of air emboli on cerebral oxygenation, but with reduced sensitivity as compared to intraparenchymal oxygen tension. Prospective human studies using multimodal monitoring incorporating electroencephalography and oxygen saturation should be performed.

Characterization and quantification of porcine circulating endothelial cells

Endothelial damage is a critical step in the development of (xeno) transplantation‐related and cardiovascular pathology. In humans, the amount of circulating endothelial cells (CEC) correlates to disease intensity and functions as a valuable damage marker. While (xeno) transplantation and cardiovascular research is regularly performed in porcine models, the paucity of antibodies against porcine endothelium epitopes hinders the use of CEC as damage marker.

Acute Neurological Symptoms During Hypobaric Exposure: Consider Cerebral Air Embolism

Cerebral arterial gas embolism (CAGE) is well known as a complication of invasive medical procedures and as a risk in diving and submarine escape. In the underwater environment, CAGE is caused by trapped air, which expands and leads to lung vessel rupture when ambient pressure decreases during ascent. Pressure decrease also occurs during hypobaric activities such as flying and, therefore, CAGE may theoretically be a risk in hypobaric exposure. We reviewed the available literature on this subject. Identified were 12 cases of CAGE due to hypobaric exposure. Based on these cases, we discuss pathophysiology, diagnosis, and treatment of CAGE due to hypobaric exposure. The low and slow pressure decrease during most hypobaric activities (as opposed to diving) account for the low incidence of CAGE during these exposures and suggest that severe air trapping must be present to cause barotrauma. This is also suggested by the large prevalence of air filled cysts in the case reports reviewed. We recommend considering CAGE in all patients presenting with acute central neurological injury during or shortly after pressure decrease such as flying. A CT scan of head and chest should be performed in these patients. Treatment with hyperbaric oxygen therapy should be initiated as soon as possible in cases of proven or probable CAGE.