Abstract
Object: Several previous studies reported metabolic derangements and an accumulation of metabolic products in the early phase of experimental subarachnoid hemorrhage (SAH), which may contribute to secondary brain damage. This may be a result of deranged oxygen utilization due to enzymatic dysfunction in aerobic glucose metabolism. This study was performed to investigate, if pyruvate dehydrogenase enzyme (PDH) is affected in its activity giving further hints for a derangement of oxidative metabolism.Methods: Eighteen male Sprague-Dawley rats were randomly assigned to one of two experimental groups (n = 9): (1) SAH induced by the endovascular filament model and (2) sham-operated controls. Mean arterial blood pressure (MABP), intracranial pressure (ICP), and local cerebral blood flow (LCBF; laser-Doppler flowmetry) were continuously monitored from 30 min before until 3 h after SAH. Thereafter, the animals were sacrificed and PDH activity was measured by ELISA.Results: PDH activity was significantly reduced in animals subjected to SAH compared to controls.Conclusion: The results of this study demonstrate for the first time a reduction of PDH activity following SAH, independent of supply of substrates and may be an independent factor contributing to a derangement of oxidative metabolism, failure of oxygen utilization, and secondary brain damage.
Highlights
Subarachnoid hemorrhage (SAH) is a disease with very poor prognosis
Carpenter et al showed by positron emission tomography (PET) in SAH patients on days 2–5 after aneurysm rupture a significant reduction of the cerebral metabolic rate of oxygen (CMRO2) of 25%, suggesting primary metabolic alterations and an uncoupling of cerebral blood flow (CBF) and metabolism after SAH (Carpenter et al, 1991)
The physiological changes in this present series were rather moderate compared to previous reports using the same experimental model (Prunell et al, 2004; Westermaier et al, 2009b, 2011) this study shows a clear depression of pyruvate dehydrogenase enzyme (PDH) activity in rats subjected to SAH
Summary
Subarachnoid hemorrhage (SAH) is a disease with very poor prognosis. Approximately 15% of patients die before they are admitted to hospital, the overall mortality is as high as 50%. A variety of harmful events like intracerebral hemorrhage, occlusive hydrocephalus, and a steep increase of ICP and decrease of cerebral perfusion pressure (CPP) cannot be prevented, because their onset is before hospital admission. These events are in the focus of emergency management when SAH is diagnosed. A persistent increase of lactate and a secondary increasing level of pyruvate concentration after SAH was monitored (Westermaier et al, 2011) These observations suggest a persistent failure of aerobic glycolysis after SAH. The purpose of this study was to investigate, if the activity of pyruvate dehydrogenase enzyme (PDH)—as a key enzyme to the TCA cycle—is deranged in the early phase of experimental SAH
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