IschemiaFocal epidural cooling reduces the infarction volume of permanent middle cerebral artery occlusion in swine
Introduction
Mortality and morbidity from ischemic stroke are high. The treatment of acute ischemic stroke has been the topic of much research. Neuroprotective agents, including glutamate receptor antagonists, calcium channel blockers, and free-radical scavengers, have shown encouraging results in animal models, but they have not yet been proven to be beneficial clinically [20]. As such, many clinicians and researchers redirected their interest and attention toward hypothermia as a method of cerebral protection.
Artificial hypothermia is widely used in different areas of medicine, and the protective effects of hypothermia against cerebral injury or ischemia have long been recognized in animal models. At present, mild or moderate systemic hypothermia by surface cooling is the most common method of hypothermia used in surgical procedures. However, many studies have reported that it carries the risk of causing complications [32], [34], [36], and a recently published study showed that treatment with mild systemic hypothermia in clinical trials has shown no effect in improving outcomes in severe brain injury [6], [7], [21].
These investigations have emphasized the need for a safer, more effective means of achieving cerebral hypothermia; therefore, SBH was attempted to avoid the complications of systemic cooling. In this study, we have developed a novel method in a porcine model by which selective reduction of brain hypothermia could achieve moderate or deep brain hypothermia. We have investigated the effects of hypothermia with the epidural cooling method on cerebral infarction size and histology in a swine model of PMCAO.
Section snippets
Animal preparation
The experiments were performed on 12 adult male domestic swine, weighing 30 to 35 kg (mean mass, 32.3 ± 1.6 kg), and conducted in accordance with Institutional Policies and Guidelines for the Care and Use of Laboratory Animals. All pigs were denied food overnight but allowed free access to water. Room temperature was maintained by an air conditioner at approximately 18 °C throughout all experiments. After an intraperitoneal injection of atropine sulfate (0.5 mg/kg), anesthesia was mechanically
Results
All animals survived until the end of the experiment. No significant differences in MABP were noted between the groups during the experiment.
Discussion
Time of initiation, duration, and depth of hypothermia are important factors in reducing ischemic infarction volume [9], [16]. Deeper and more rapid hypothermia can achieve better protective effects against ischemic stroke. However, deeper systemic hypothermia (<32°C) through the use of surface cooling with external cooling blankets has not been achieved in clinical practice because of severe side effects, including cardiac arrhythmias, coagulopathy, and immunosuppression [5], [10], [12], [18],
Conclusion
The present study has demonstrated, with histologic confirmation, that epidural cooling may be a useful strategy for reducing infarct volume after the onset of ischemia.
References (41)
- et al.
Efficacy of intraoperative heat administration by ventilation with warm humidified gases and oesophageal warming system
Br J Anaesth
(1996) - et al.
Isolated profound cerebral cooling with a bi-carotid heat exchanger shunt in dogs
Resuscitation
(1983) - et al.
Immediate or delayed mild hypothermia prevents focal cerebral infarction
Brain Res
(1992) - et al.
Quantification of infarct size on focal cerebral ischemia model of rats using a simple and economical method
J Neurosci Methods
(1998) - et al.
Changes in coagulation and fibrinolysis occurring in dogs during hypothermia
Thromb Res
(1985) - et al.
Reduction by delayed hypothermia of cerebral infarction following middle cerebral artery occlusion in the rat: a time-course study
J Neurosurg
(1992) - et al.
The importance of brain temperature in cerebral ischemic injury
Stroke
(1989) - et al.
Epidural cooling for selective brain hypothermia in porcine model
Acta Neurochir (Wien)
(2006) - et al.
Hypothermia in the sepsis syndrome and clinical outcome: the Methylprednisolone Severe Sepsis Study Group
Crit Care Med
(1992) - et al.
Systemic hypothermia in treatment of brain injury
J Neurotrauma
(1992)
Lack of effect of induction of hypothermia after acute brain injury
N Engl J Med
Bloodless surgery by means of profound hypothermia and circulatory arrest: effect on brain and heart
Ann Surg
Combination of decompressive craniectomy and mild hypothermia ameliorates infarction volume after permanent focal ischemia in rats
Stroke
Some physiologic effects of short and long term hypothermia upon the liver
Surgery
Effects of intraischemic hypothermia on cerebral damage in a model of reversible focal ischemia
Neurosurgery
Reflections on circulatory control
Lancet
Safety and performance of a novel intravascular catheter for induction and reversal of hypothermia in a porcine model
Neurosurgery
The effect of mild hypothermia on permanent focal ischemia in rat
Neurosurgery
Mild intraischemic hypothermia reduces postischemic hyperperfusion, delayed postischemic hypoperfusion, blood-brain barrier disruption, brain edema, and neuronal damage volume after temporary focal cerebral ischemia in rats
J Cereb Blood Flow Metab
Therapeutic hypothermia for acute ischemic stroke: what do laboratory studies teach us?
Stroke
Cited by (19)
Postcooling But Not Precooling Benefits Motor Recovery by Suppressing Cell Death After Surgical Spinal Cord Injury in Rats
2022, World NeurosurgeryCitation Excerpt :As such, the concept of regional hypothermia (RH) was introduced. Interests in neurologic applications of RH ensued with promising results; it was shown to reduce infarction in a middle cerebral artery occlusion model,5 improve motor recovery after traumatic spinal cord injury,6 favor neurologic outcome in adult brain injury,7 and reduce perihematomal edema after intracranial hemorrhage.8 Hypothermic interventions have also been widely adopted in cardiothoracic surgeries, with protective benefits in ameliorating cerebral and spinal cord ischemia demonstrated in both laboratory and clinical settings.9
Protective effect against focal cerebral ischemia injury in acute phase of a novel invasive device for regional hypothermia
2015, Journal of the Chinese Medical AssociationCitation Excerpt :Accordingly, methods and devices that provide regional hypothermia have been developed to cool through blood vessels,9–12 nasal cavity,13–18 meninges19–21 and the head.22–27 Unfortunately, the cooling efficiency through brain parenchyma has not been measured in most of those devices, and only a few studies have explored the neuroprotective effects of regional hypothermia.21,28–31 In addition, the optimal temperature range for regional hypothermia is still controversial.28,29,32
Neuroprotective effects of focal brain cooling on photochemically-induced cerebral infarction in rats: Analysis from a neurophysiological perspective
2013, Brain ResearchCitation Excerpt :Despite these favorable outcomes, systemic hypothermia can also lead to fatal complications, such as infection, cardiac arrhythmia, and disruption of blood coagulation (Clifton et al., 1993; Marion et al., 1993; Schubert, 1995). To resolve these issues, focal brain cooling (FBC) has recently drawn attention as a minimally invasive treatment for brain injuries (Oku et al., 2009; Wagner et al., 2005; Zhang et al., 2007; Clark et al., 2009). Compared with systemic hypothermia, FBC has the advantage of reducing the cooling temperature below 30 °C, without producing permanent brain damage or systemic complications (Yang et al., 2006).
Mild hypothermia reduces spreading depolarizations and infarct size in a swine model
2023, Journal of Cerebral Blood Flow and Metabolism