Oximetry-Guided Reoxygenation Improves Neurological Outcome After Experimental Cardiac Arrest
Current guidelines suggest that cardiac arrest (CA) survivors should be ventilated with 100% O(2) after resuscitation. Breathing 100% O(2) may worsen neurological outcome after experimental CA. This study tested the hypothesis that graded reoxygenation, with oximetry guidance, can safely reduce FiO(2) after resuscitation, avoiding hypoxia while promoting neurological recovery. Mature dogs underwent 10 minutes of CA and restoration of spontaneous circulation with 100% O(2.) Animals were randomized to 1-hour additional ventilation on 100% FiO(2) or to rapid lowering of arterial O(2) saturation to <96% but >94% with pulse oximeter guidance. Animals were awakened at hour 23, and the neurological deficit score (0=normal; 100=brain-dead) was measured. Reanesthetized animals were perfusion-fixed and the brains removed for histopathology. The neurological deficit score was significantly better in oximetry (O) dogs. O dogs appeared aware of their surroundings, whereas most hyperoxic (H) animals were stuporous (neurological deficit score=43.0+/-5.9 [O] versus 61.0+/-4.2 [H]; n=8, P<0.05). Stereological analysis revealed fewer injured CA1 neurons in O animals (cresyl violet: 35.5+/-4.3% [O] versus 60.5+/-3.3% [H]; P<0.05). There were also fewer fluoro-Jade B-stained degenerating CA1 neurons in O animals (3320+/-267 [O] versus 6633+/-356 [H] per 0.1 mm(3); P<0.001). A clinically applicable protocol designed to reduce postresuscitative hyperoxia after CA results in significant neuroprotection. Clinical trials of controlled normoxia after CA/restoration of spontaneous circulation should strongly be considered.
[Show abstract] [Hide abstract] ABSTRACT: Exercise training offers cardioprotection against ischemia and reperfusion (I/R) injury. However, few essential signals have been identified to underscore the protection from injury. In the present study, we hypothesized that exercise-induced acceleration of myocardial tissue oxygenation recovery contributes to this protection. C57BL/6 mice (4 weeks old) were trained on treadmills for 45 min/day at a treading rate of 15 m/min for 8 weeks. At the end of 8-week exercise training, mice underwent 30-min left anterior descending coronary artery occlusion followed by 60-min or 24-h reperfusion. Electron paramagnetic resonance oximetry was performed to measure myocardial tissue oxygenation. Western immunoblotting analyses, gene transfection, and myography were examined. The oximetry study demonstrated that exercise markedly shortened myocardial tissue oxygenation recovery time following reperfusion. Exercise training up-regulated Kir6.1 protein expression (a subunit of ATP-sensitive K+ channel on vascular smooth muscle cells, VSMC sarc-KATP) and protected the heart from I/R injury. In vivo gene transfer of dominant negative Kir6.1AAA prolonged the recovery time and enlarged infarct size. In addition, transfection of Kir6.1AAA increased the stiffness and reduced the relaxation capacity in the vasculature. Together, our study demonstrated that exercise training up-regulated Kir6.1, improved tissue oxygenation recovery, and protected the heart against I/R injury. This exercise-induced cardioprotective mechanism may provide a potential therapeutic intervention targeting VSMC sarc-KATP channels and reperfusion recovery.0Comments 1Citation
- "Since myocyte necrosis occurs only hours after the ischemic event, we speculate that slower oxygenation recovery following ischemia may cause a delay in the delivery of oxygen and nutrients to the already stressed myocytes and contribute to I/R injury. Finally, as previously reported333435 , graded re-oxygenation upon reperfusion with less hyperoxic blood oxygen content but normal blood flow has protective effects on the reperfused tissue against reperfusion injury. Further, post-conditioning with short bouts of ischemia upon reperfusion also protects the reperfused myocardium . "
[Show abstract] [Hide abstract] ABSTRACT: RECOVER was created to optimize survival of small animal patients from cardiopulmonary arrest. Several findings from this study are applicable to cardiopulmonary resuscitation in the neonatal foal. In particular, chest compressions should be a priority with no pauses and a "push hard, push fast" approach. The importance of ventilation is minimized with short, infrequent breaths at a rate of 10 to 20 per minute recommended.0Comments 1Citation
- "(continued on next page) Q11 Please note that the reference style has been changed from a NameeDate style to a Numbered style, and the references have been renumbered both in text and in reference list so that they appear in sequential order. Q12 Originally references " Balan et al, 2006; Brodbelt et al, 2008; Brücken et al, 2010; Fletcher et al, 2012; Hopper et al, 2012; Kilgannon et al, 2008; McMichael et al, 2012; Reynolds et al, 2007; Rozanski et al, 2012; Smarick et al, 2012 " were not cited in the text. Hence they have been combined with the citation of corresponding previous references. "
[Show abstract] [Hide abstract] ABSTRACT: The objective of this study was to study the effect of diabetic hyperglycemia on astrocytes after forebrain ischemia. Streptozotocin (STZ)-injected hyperglycemic and vehicle-injected normoglycemic rats were subjected to 15 minutes of forebrain ischemia. The brains were harvested in sham-operated controls and in animals with 1 and 6 h of recirculation following ischemia. Brain damage was accessed by haematoxylin and eosin (H&E) staining, cleaved caspase-3 immunohistochemistry and TdT-mediated-dUTP nick end labeling (TUNEL). Anti-GFAP antibody was employed to study astrocytes. The results showed that the 15-minute ischemia caused neuronal death after 1 and 6 h of reperfusion as revealed by increased numbers of karyopyknotic cells, edema, TUNEL-positive and active caspase-3-positive cells. Ischemia also activated astrocytes in the cingulated cortex as reflected by astrocyte stomata hypertrophy, elongated dendrites and increases in the number of dendrites, and immunoreactivity of GFAP. Diabetic hyperglycemia further enhanced neuronal death and suppressed ischemia-induced astrocyte activation. Further, diabetes-damaged astrocytes have increased withdrawal of the astrocyte end-foot from the cerebral blood vessel wall. It is concluded that diabetes-induced suppression and damages to astrocytes may contribute to its detrimental effects on recovery from cerebral ischemia.0Comments 4Citations
- "It is reported that hyperglycemia presented in 28% of stroke patients without a previous known history of DM . Several studies have demonstrated that hyperglycemic ischemia induces more production of oxidative stress markers, cerebral energy metabolism disturbance, neuronal death, and neurologic behavioral impairment than those observed following normoglycemic ischemia and reperfusion345678. While injury to, and death of, neurons has been the focus of ischemic brain injury research, evidence suggests that astrocytes also undergo dysfunction and delayed death after global cerebral ischemia91011. "