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Background and Purpose: Monitoring for hypotension, hyperglycemia, hypoxia, and dehydration is key to reducing early death in stroke patients. Evaluation of physiological predictors of infarct volume and mortality may provide opportunities for effective interventions to improve outcomes. The purpose of this study is: 1) to describe and compare the predictive effects of venous blood gas (VBG) on infarct volume and mortality in acute stroke in rats; 2) and we have begun to collect arterial blood gas (ABG) to compare differences obtained proximal and distal to the occluded intracranial thrombi in acute ischemic stroke patients.Methods: 3-month old Sprague-Dawey rats (n = 9) underwent permanent or transient middle cerebral artery occlusion (MCAO). Pre- and post-MCAO venous samples provided pH, pCO2, pO2, and electrolyte values (iCa2+, K+, and Na+). Linear regression determined predictors of infarct volume from these values, and Cox regression analyzed VBG changes between tMCAO (n = 28) and pMCAO (n = 29) to determine predictors of mortality. We compared mean proximal and distal pH, pCO2, pO2, and electrolytes (iCa2+, K+, and Na+) in stroke patients (n = 7) arterial samples using Wilcoxon Signed Ranks test.Results: Animal studies demonstrated pH and iCa2+ are predictors of infarct volume, but not mortality. After pMCAO (n = 9), change in pH or iCa2+ significantly predicted infarct volume [F(1,7) = 7.351, β = -0.716, p = 0.03] and [F(1, 7) = 6.782, β = -0.701, p = 0.035]; as pH and calcium decreased, infarct volume increased. These variables explained 44% and 42% of the total variance in these models. In human patients (n = 7), there were significant differences in blood samples proximal and distal to the intracranial thrombus for pCO2(p = 0.018), HCO3- (p = 0.028), iCa2+ (p = 0.043), K+ (p = 0.028), and Na+ (p = 0.044).Conclusions: In conclusion, there are acute changes in acid/base balance and electrolytes during stroke in rodent models and humans. In cross-species comparison ionized calcium changes were significant in both, with iCa2+ changes predicting stroke volume in the rat model. These preliminary findings are novel, and warrant further exploration in human patients.