Adenosine impacts cerebral ischemia reperfusion (IR) through the inhibitory A1 and the excitatory A2 receptors. The present study aimed at investigating the contrasting role of pERK1/2 in mediating adenosine A1R (protective) versus A2AR (deleterious) effects in IR. Male Wistar rats subjected to bilateral carotid occlusion (45 min) followed by reperfusion (24 h) exhibited increased pERK1/2 activity, downstream from DAG pathway, along with increases in hippocampal glutamate, c-Fos, NF-κB, TNF-α, iNOS, TBARS, cytochrome c, caspase-3, BDNF, Nrf2, and IL-10 contents. Further, hippocampal microglial reactivity, glial TNF-α, and BDNF expression were observed. Although unilateral intrahippocampal injection of either the A1R agonist CHA or the A2AR agonist CGS21680 increased pERK1/2, only CHA mitigated histopathological and behavioral deficits along with reducing glutamate, microglial activation, c-Fos, TNF-α, iNOS, TBARS, cytochrome c and caspase-3 and elevating Nrf2 and IL-10 levels in IR rats. These results yield insight into the double-faceted nature of pERK1/2 in mediating protective and deleterious effects of A1R and A2AR signaling, respectively, against IR injury.

OBJECTIVES: Total annual costs for syncope-related hospitalizations were $2.4 billion in 2000. The aim of this study was to examine the type and number of tests ordered for patients admitted with syncope and whether these tests helped establish the cause.

METHODS: We studied the records of 1038 patients coded as "syncope" in billing records, and 167 fulfilled the eligibility criteria. The main outcome measures were the diagnostic yield of the ordered tests, the incremental cost/incremental benefit, and the number of admissions that can be averted if risk stratification were used in the evaluation.

RESULTS: The etiology of the syncope was identified in 48.3% of the patients. Postural blood pressure measurement has the highest diagnostic yield at 58.7%, whereas history taking diagnosed 19.7% of cases. The diagnostic yields of telemetry, electrocardiogram, radionuclide stress test, echocardiography, and troponin measurement were 4.76%, 4.24%, 3.44%, 0.94%, and 0.62%, respectively. Chest x-ray, carotid ultrasonography, 24-hour Holter monitoring, brain computed tomography, and brain magnetic resonance imaging did not yield the diagnosis in any of the patients. Only 1.9% of the money spent in the evaluation of syncope was effective in leading to a definitive diagnosis. The orthostatic blood pressure measurement was ranked first in the incremental cost/incremental benefit ratio and the radionuclide stress test was ranked last (17.03 vs 42,369.0, respectively). Approximately 6% of the patients did not meet the admission criteria.

CONCLUSIONS: Physicians ordered unnecessary tests that have a low yield and are not cost-effective. A standardized algorithmic approach should be the cornerstone in the evaluation of syncope.