scholarly journals Intracranial Pressure Elevation after Ischemic Stroke in Rats: Cerebral Edema is Not the Only Cause, and Short-Duration Mild Hypothermia is a Highly Effective Preventive Therapy

2014 ◽  
Vol 35 (4) ◽  
pp. 592-600 ◽  
Author(s):  
Lucy A Murtha ◽  
Damian D McLeod ◽  
Debbie Pepperall ◽  
Sarah K McCann ◽  
Daniel J Beard ◽  
...  
Keyword(s):  
Intracranial Pressure ◽  
Short Duration ◽  
Cerebral Edema ◽  
Mild Hypothermia ◽  
Dry Weight ◽  
Preventive Therapy ◽  
Stroke Onset ◽  
Experimental Stroke ◽  
Moderate Hypothermia ◽  
Intracranial Pressure Elevation

In both the human and animal literature, it has largely been assumed that edema is the primary cause of intracranial pressure (ICP) elevation after stroke and that more edema equates to higher ICP. We recently demonstrated a dramatic ICP elevation 24 hours after small ischemic strokes in rats, with minimal edema. This ICP elevation was completely prevented by short-duration moderate hypothermia soon after stroke. Here, our aims were to determine the importance of edema in ICP elevation after stroke and whether mild hypothermia could prevent the ICP rise. Experimental stroke was performed in rats. ICP was monitored and short-duration mild (35 °C) or moderate (32.5 °C) hypothermia, or normothermia (37 °C) was induced after stroke onset. Edema was measured in three studies, using wet—dry weight calculations, T2-weighted magnetic resonance imaging, or histology. ICP increased 24 hours after stroke onset in all normothermic animals. Short-duration mild or moderate hypothermia prevented this rise. No correlation was seen between ΔICP and edema or infarct volumes. Calculated rates of edema growth were orders of magnitude less than normal cerebrospinal fluid production rates. These data challenge current concepts and suggest that factors other than cerebral edema are the primary cause of the ICP elevation 24 hours after stroke onset.

scholarly journals Intracranial Pressure Elevation Reduces Flow through Collateral Vessels and the Penetrating Arterioles they Supply. a Possible Explanation for ‘Collateral Failure’ and Infarct Expansion after Ischemic Stroke

2015 ◽  
Vol 35 (5) ◽  
pp. 861-872 ◽  
Author(s):  
Daniel J Beard ◽  
Damian D McLeod ◽  
Caitlin L Logan ◽  
Lucy A Murtha ◽  
Mohammad S Imtiaz ◽  
...  
Keyword(s):  
Blood Flow ◽  
Intracranial Pressure ◽  
Arterial Occlusion ◽  
Vessel Diameter ◽  
Experimental Stroke ◽  
Collateral Flow ◽  
Intracranial Pressure Elevation ◽  
Infarct Expansion ◽  
Flow Through ◽  
Collateral Vessels

Recent human imaging studies indicate that reduced blood flow through pial collateral vessels (‘collateral failure’) is associated with late infarct expansion despite stable arterial occlusion. The cause for ‘collateral failure’ is unknown. We recently showed that intracranial pressure (ICP) rises dramatically but transiently 24 hours after even minor experimental stroke. We hypothesized that ICP elevation would reduce collateral blood flow. First, we investigated the regulation of flow through collateral vessels and the penetrating arterioles arising from them during stroke reperfusion. Wistar rats were subjected to intraluminal middle cerebral artery (MCA) occlusion (MCAo). Individual pial collateral and associated penetrating arteriole blood flow was quantified using fluorescent microspheres. Baseline bidirectional flow changed to MCA-directed flow and increased by 4450% immediately after MCAo. Collateral diameter changed minimally. Second, we determined the effect of ICP elevation on collateral and watershed penetrating arteriole flow. Intracranial pressure was artificially raised in stepwise increments during MCAo. The ICP increase was strongly correlated with collateral and penetrating arteriole flow reductions. Changes in collateral flow post-stroke appear to be primarily driven by the pressure drop across the collateral vessel, not vessel diameter. The ICP elevation reduces cerebral perfusion pressure and collateral flow, and is the possible explanation for ‘collateral failure’ in stroke-in-progression.

scholarly journals Short-duration hypothermia completed prior to reperfusion prevents intracranial pressure elevation following ischaemic stroke in rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniel Omileke ◽  
Sara Azarpeykan ◽  
Steven W. Bothwell ◽  
Debbie Pepperall ◽  
Daniel J. Beard ◽  
...  
Keyword(s):  
Intracranial Pressure ◽  
Ischaemic Stroke ◽  
Short Duration ◽  
Infarct Volume ◽  
Arterial Occlusion ◽  
Reperfusion Therapy ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Stroke Patients ◽  
Post Stroke

AbstractReperfusion therapies re-establish blood flow after arterial occlusion and improve outcome for ischaemic stroke patients. Intracranial pressure (ICP) elevation occurs 18–24 h after experimental stroke. This elevation is prevented by short-duration hypothermia spanning the time of reperfusion. We aimed to determine whether hypothermia-rewarming completed prior to reperfusion, also prevents ICP elevation 24 h post-stroke. Transient middle cerebral artery occlusion was performed on male outbred Wistar rats. Sixty-minute hypothermia to 33 °C, followed by rewarming was induced prior to reperfusion in one group, and after reperfusion in another group. Normothermia controls received identical anaesthesia protocols. ΔICP from pre-stroke to 24 h post-stroke was measured, and infarct volumes were calculated. Rewarming pre-reperfusion prevented ICP elevation (ΔICP = 0.3 ± 3.9 mmHg vs. normothermia ΔICP = 5.2 ± 2.1 mmHg, p = 0.02) and reduced infarct volume (pre-reperfusion = 78.6 ± 23.7 mm3 vs. normothermia = 125.1 ± 44.3 mm3, p = 0.04) 24 h post-stroke. There were no significant differences in ΔICP or infarct volumes between hypothermia groups rewarmed pre- or post-reperfusion. Hypothermia during reperfusion is not necessary for prevention of ICP rise or infarct volume reduction. Short-duration hypothermia may be an applicable early treatment strategy for stroke patients prior to- during-, and after reperfusion therapy.

scholarly journals Hypothermia and rewarming prior to reperfusion, prevents intracranial pressure elevation after ischaemic stroke in rats: an investigation to define the importance of cooling during reperfusion

2021 ◽  
Author(s):  
Daniel Omileke ◽  
Sara Azarpeykan ◽  
Steven W Bothwell ◽  
Debbie Pepperall ◽  
Daniel J Beard ◽  
...  
Keyword(s):  
Intracranial Pressure ◽  
Ischaemic Stroke ◽  
Short Duration ◽  
Infarct Volume ◽  
Arterial Occlusion ◽  
Reperfusion Therapy ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Stroke Patients ◽  
Post Stroke

Abstract Reperfusion therapies re-establish blood flow after arterial occlusion and improve outcome for ischaemic stroke patients. Intracranial pressure (ICP) elevation occurs 18–24 h after experimental stroke. This elevation is prevented by short-duration hypothermia spanning the time of reperfusion. We aimed to determine whether hypothermia-rewarming completed prior to reperfusion, also prevents ICP elevation 24 h post-stroke. Transient middle cerebral artery occlusion was performed on male outbred Wistar rats. Sixty-minute hypothermia to 33℃, followed by rewarming was induced prior to reperfusion in one group, and after reperfusion in another group. Normothermia controls received identical anaesthesia protocols. ΔICP from pre-stroke to 24 h post-stroke was measured, and infarct volumes were calculated. Rewarming pre-reperfusion prevented ICP elevation (ΔICP = 0.3 ± 3.9 mmHg vs. normothermia ΔICP = 5.2 ± 2.1 mmHg, p = 0.02) and reduced infarct volume (pre-reperfusion = 78.6 ± 23.7 mm3 vs. normothermia = 125.1 ± 44.3 mm3, p = 0.04) 24 h post-stroke. There were no significant differences in ΔICP or infarct volumes between hypothermia groups rewarmed pre-or post-reperfusion. Hypothermia during reperfusion is not necessary for prevention of ICP rise or infarct volume reduction. Short-duration hypothermia is a broadly applicable potential early treatment strategy for stroke patients prior to- during-, and after reperfusion therapy.

scholarly journals Decreased Intracranial Pressure Elevation and Cerebrospinal Fluid Outflow Resistance: A Potential Mechanism of Hypothermia Cerebroprotection Following Experimental Stroke

2021 ◽  
Vol 11 (12) ◽  
pp. 1589
Author(s):  
Daniel Omileke ◽  
Steven W. Bothwell ◽  
Debbie Pepperall ◽  
Daniel J. Beard ◽  
Kirsten Coupland ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Intracranial Pressure ◽  
Ischaemic Stroke ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Experimental Stroke ◽  
Outflow Resistance ◽  
Hypothermia Treatment ◽  
Post Stroke ◽  
Intracranial Pressure Elevation

Background: Elevated intracranial pressure (ICP) occurs 18–24 h after ischaemic stroke and is implicated as a potential cause of early neurological deterioration. Increased resistance to cerebrospinal fluid (CSF) outflow after ischaemic stroke is a proposed mechanism for ICP elevation. Ultra-short duration hypothermia prevents ICP elevation 24 h post-stroke in rats. We aimed to determine whether hypothermia would reduce CSF outflow resistance post-stroke. Methods: Transient middle cerebral artery occlusion was performed, followed by gradual cooling to 33 °C. At 18 h post-stroke, CSF outflow resistance was measured using a steady-state infusion method. Results: Hypothermia to 33 °C prevented ICP elevation 18 h post-stroke (hypothermia ∆ICP = 0.8 ± 3.6 mmHg vs. normothermia ∆ICP = 4.4 ± 2.0 mmHg, p = 0.04) and reduced infarct volume 24 h post-stroke (hypothermia = 78.6 ± 21.3 mm3 vs. normothermia = 108.1 ± 17.8 mm3; p = 0.01). Hypothermia to 33 °C did not result in a significant reduction in CSF outflow resistance compared with normothermia controls (0.32 ± 0.36 mmHg/µL/min vs. 1.07 ± 0.99 mmHg/µL/min, p = 0.06). Conclusions: Hypothermia treatment was protective in terms of ICP rise prevention, infarct volume reduction, and may be implicated in CSF outflow resistance post-stroke. Further investigations are warranted to elucidate the mechanisms of ICP elevation and hypothermia treatment.

scholarly journals Ultra-Short Duration Hypothermia Prevents Intracranial Pressure Elevation Following Ischaemic Stroke in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniel Omileke ◽  
Debbie Pepperall ◽  
Steven W. Bothwell ◽  
Nikolce Mackovski ◽  
Sara Azarpeykan ◽  
...  
Keyword(s):  
Intracranial Pressure ◽  
Ischaemic Stroke ◽  
Short Duration ◽  
Animal Studies ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Rapid Cooling ◽  
Long Duration ◽  
Intracranial Pressure Elevation ◽  
Cooling Methods

There is a transient increase in intracranial pressure (ICP) 18–24 h after ischaemic stroke in rats, which is prevented by short-duration hypothermia using rapid cooling methods. Clinical trials of long-duration hypothermia have been limited by feasibility and associated complications, which may be avoided by short-duration cooling. Animal studies have cooled faster than is achievable in patients. We aimed to determine whether gradual cooling at a rate of 2°C/h to 33°C or 1°C/h to 34.5°C, with a 30 min duration at target temperatures, prevented ICP elevation and reduced infarct volume in rats. Transient middle cerebral artery occlusion was performed, followed by gradual cooling to target temperature. Hypothermia to 33°C prevented significant ICP elevation (hypothermia ΔICP = 1.56 ± 2.26 mmHg vs normothermia ΔICP = 8.93 ± 4.82 mmHg; p = 0.02) and reduced infarct volume (hypothermia = 46.4 ± 12.3 mm3 vs normothermia = 85.0 ± 17.5 mm3; p = 0.01). Hypothermia to 34.5°C did not significantly prevent ICP elevation or reduce infarct volume. We showed that gradual cooling to 33°C, at cooling rates achievable in patients, had the same ICP preventative effect as traditional rapid cooling methods. This suggests that this paradigm could be translated to prevent delayed ICP rise in stroke patients.

scholarly journals Evaluation of Hypothermia in Sick Neonates as Predictor of Fatality at a Tertiary Care Center of Eastern Nepal

2018 ◽  
Vol 14 (2) ◽  
pp. 8-11
Author(s):  
Piush Kanodia ◽  
R Bhandari ◽  
N Bhatta ◽  
S Yadav
Keyword(s):  
Respiratory Distress ◽  
Neonatal Sepsis ◽  
Prospective Observational Study ◽  
Mild Hypothermia ◽  
Care Center ◽  
Tertiary Care ◽  
Birth Asphyxia ◽  
Moderate Hypothermia ◽  
Time Of Admission ◽  
Frequent Problem

Introduction: Hypothermia is a common and frequent problem in newborns. It has larger impact in outcome related to management of sick infants.Objective: To correlate the severity of hypothermia in sick extramural neonates with fatality and physiological derangements.Materials and Methods: This prospective observational study was carried out at Neonatology unit of Pediatric department of B. P. Koirala Institute of Health Sciences (BPKIHS) Dharan. Total 200 extramural hypothermic neonates were transferred to BPKIHS from June 2015 to June 2016. Neonates weighing more than 1000 g, with abdominal skin temperature less than 36.5°C at admission were included in the study.. Clinical features and associated features were recorded at the time of admission. Oxygen saturation was recorded by a pulse oximeter.Results: Fatality was observed to be 39.3% in mildly hypothermic babies, 51.6% in moderately hypothermic babies and 80% in severely hypothermic babies. However, the presence of associated illness (birth asphyxia, neonatal sepsis and respiratory distress), physiological derangements (hypoxia, hypoglycemia and shock) and weight less than 2000 g were associated with more than 50% fatality even in mildly hypothermic babies. When moderate hypothermia was associated with hypoxia or shock, the fatality was 83.3% and 90.9%, respectively. Similarly, mild hypothermia with hypoglycemia was associated with 71.4% fatality.Conclusion: The presence of associated illness (birth asphyxia, neonatal sepsis and respiratory distress), physiological derangements (hypoxia, hypoglycemia and shock) and weight less than 2000 g should be considered adverse factors in hypothermic neonates. Their presence should classify hypothermia in the next higher category of severity in WHO classification. JNGMC Vol. 14 No. 2 December 2016,   page: 8-11  

Early Effects of Acid-Base Management during Hypothermia on Cerebral Infarct Volume, Edema, and Cerebral Blood Flow in Acute Focal Cerebral Ischemia in Rats

2002 ◽  
Vol 97 (4) ◽  
pp. 868-874 ◽  
Author(s):  
Rainer Kollmar ◽  
Thomas Frietsch ◽  
Dimitrios Georgiadis ◽  
Wolf-Rüdiger Schäbitz ◽  
Klaus F. Waschke ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cerebral Edema ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Cerebral Infarct ◽  
Moderate Hypothermia ◽  
Acid Base ◽  
Base Management ◽  
Ph Stat

Background Although the frequency for the use of moderate hypothermia in acute ischemic stroke is increasing, the optimal acid-base management during hypothermia remains unclear. This study investigates the effect of pH- and alpha-stat acid-base management on cerebral blood flow (CBF), infarct volume, and cerebral edema in a model of transient focal cerebral ischemia in rats. Methods Twenty Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2 h during normothermic conditions followed by 5 h of reperfusion during hypothermia (33 degrees C). Animals were artificially ventilated with either alpha- (n = 10) or pH-stat management (n = 10). CBF was analyzed 7 h after induction of MCAO by iodo[(14)C]antipyrine autoradiography. Cerebral infarct volume and cerebral edema were measured by high-contrast silver infarct staining (SIS). Results Compared with the alpha-stat regimen, pH-stat management reduced cerebral infarct volume (98.3 +/- 33.2 mm(3) vs. 53.6 +/- 21.6 mm(3); P > or = 0.05 mean +/- SD) and cerebral edema (10.6 +/- 4.0% vs. 3.1 +/- 2.4%; P > or = 0.05). Global CBF during pH-stat management exceeded that of alpha-stat animals (69.5 +/- 12.3 ml x 100 g(-1) x min(-1) vs. 54.7 +/- 13.3 ml x 100 g(-1) x min; P > or = 0.05). The regional CBF of the ischemic hemisphere was 62.1 +/- 11.2 ml x 100 g(-1) x min(-1) in the pH-stat group versus 48.2 +/- 7.2 ml x 100 g(-1) x min(-1) in the alpha-stat group ( P> or = 0.05). Conclusions In the very early reperfusion period (5 h), pH-stat management significantly decreases cerebral infarct volume and edema as compared with alpha-stat during moderate hypothermia, probably by increasing CBF.

Controlled Evaluation of Muscle Relaxation in the Ventilated Neonate

PEDIATRICS ◽  
1981 ◽  
Vol 67 (5) ◽  
pp. 641-646
Author(s):  
N. N. Finer ◽  
P. M. Tomney
Keyword(s):  
Birth Weight ◽  
Intracranial Pressure ◽  
Low Birth Weight ◽  
Muscle Relaxation ◽  
Control Period ◽  
Pancuronium Bromide ◽  
Intracranial Pressure Elevation ◽  
Controlled Evaluation ◽  
And Control ◽  
Inspiratory Oxygen

To assess the effects of muscle relaxation on the critically ill ventilated neonate, pancuronium bromide was administered for a 12-hour period to ten low-birth-weight neonates (960 to 2,000 gm) of 26 to 34 weeks gestation, all of whom required mechanical ventilation and were studied within 48 hours of birth (six to 39 hours). The infants were also studied for a 12-hour period during which no pancuronium bromide was administered. During both study periods, the order of which was randomized, heart rate, blood pressure, Po2, and intracranial pressure were continuously measured. The amounts of handling during the pancuronium and control periods were similar. The results revealed a significantly greater duration of hypoxia (P02 < 50 torr) (56.1 vs 23.6 minutes, P < .001) and hyperoxia (Po2 > 70 torr) during the control period (92.5 vs 13 minutes, P < .001). Durations of intracranial pressure elevation 10 cm H2O above the infant's baseline were significantly less during paralysis (6.7 vs 58.8 minutes, P < .001) as were spikes of intracranial pressure to greater than 25 cm H2O (1.6 vs 24.4, P < .05). There was no significant improvement in blood gas values, fractional inspiratory oxygen, or ventilator settings during muscle relaxation. Pancuronium reduced periods of nonoptimal oxygenation and elevated intracranial pressure and may therefore help to decrease adverse sequelae for the low-birth-weight, ventilated neonate.

Abstract W P211: Investigating the Cause for “Collateral Failure” in Stroke-in-Progression: Intracranial Pressure Elevation Reduces Flow Through Collateral Vessels

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Daniel Beard ◽  
Damian McLeod ◽  
Neil J Spratt
Keyword(s):  
Intracranial Pressure ◽  
Flow Velocity ◽  
Cerebral Perfusion ◽  
Perfusion Pressure ◽  
Minor Stroke ◽  
Collateral Flow ◽  
Mca Occlusion ◽  
Intracranial Pressure Elevation ◽  
Flow Through ◽  
Collateral Vessels

Background: Adequacy of the collateral circulation is a major determinant of outcome in stroke patients. Recent human imaging data indicates that collateral failure, rather than reperfusion-reocclusion is the most common cause for early progression in minor stroke. Our previous experimental data shows that intracranial pressure (ICP) rises transiently 24 h after even minor stroke. Herein, we investigated the effect of ICP manipulation on blood flow through collateral vessels during MCA occlusion. Methods: We developed and validated a method to quantify flow velocity and vessel diameter of anterior-middle cerebral artery (ACA-MCA) leptomeningeal collaterals in rats during stroke, using fluorescent microspheres. BIood flow velocity and diameter was quantified in individual collateral vessels and used to calculate absolute flow during MCA occlusion and reperfusion (n = 6). In separate experiments, ICP was increased after MCA occlusion by fluid infusion into the lateral ventricles and effects on relative collateral flow were determined (n = 4). Results: In vitro validation indicated accurate flow quantification (R 2 = 0.99, P<0.0001). Collateral flow was seen to switch from bidirectional to unidirectional flow (toward occluded vessel) and increase by 595 ± 134 % within 10 min of vessel occlusion. Direction and flow changes were variable after MCA reperfusion, however there was a mean flow reduction of 52 ± 15 % by 5 mins. Artificially elevating ICP during MCA occlusion caused a reduction of cerebral perfusion pressure which was strongly correlated with collateral flow reduction (R 2 = 0.90, p<0.0001). Discussion: Our method permits real time quantification of flow through individual collateral vessels during stroke and reperfusion. Intracranial pressure elevation reduced collateral flow, proportional to its effect on cerebral perfusion pressure. Coupled with our previous data indicating significant ICP elevation after even minor stroke, this suggests that transient ICP elevation is the possible cause of the collateral failure recently described in patients with stroke-in-progression.

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