title: Cerebrospinal fluid from subarachnoid haemorrhage patients causes excessive oxidative metabolism compared to vascular smooth muscle force generation.
abstract: Cerebrospinal fluid (CSF) from subarachnoid haemorrhage (SAH) patients can stimulate vascular smooth muscle to generate force in vitro. CSF from SAH patients suffering from delayed ischaemic neurological deficits due to cerebral vasospasm can generate near maximal force in vitro and previous experiments have ascribed this generation of force to be a calcium mediated event. The intracellular calcium concentration has been demonstrated to rise during the vasospastic process. Calcium also stimulates oxidative metabolism as does adenosine diphosphate (ADP), the product of adenosine triphosphate (ATP) hydrolysis. Significant alteration in high energy metabolites such as ATP, ADP and phosphocreatine have also been demonstrated in various models of SAH mediated vasospasm. Vascular smooth muscle predominantly uses oxidative metabolism for force generation and reserves glycolytic metabolism for ion homeostasis. A decrease in oxidative metabolism during force generation would imply failing mitochondria and increased glycolytic high-energy phosphate supply. Increased oxidative metabolism would imply a decreased efficiency of the contractile apparatus or mitochondria. The aim of this study was to see if SAH CSF stimulation of porcine carotid artery oxidative metabolism was altered during force generation when compared with incremental calcium stimulation with potassium chloride depolarisation. CSF from patients (n = 10) who had subarachnoid haemorrhage stimulated force generation but with a significant 'right shift' in oxygen consumption. This 'right shift' is indicative of an increased energy cost for contractile work. These results suggest that vascular smooth muscle contractile apparatus, when stimulated by subarachnoid cerebrospinal fluid, is consuming excess adenosine triphosphate during force generation.
authors.affiliation: Department of Biochemistry, South Parks Rd., University of Oxford, MRC Biochemical and Clinical Magnetic Resonance Spectroscopy Unit, John Radcliffe Hospital, Headington, Oxford, UK.
authors.forename: G J
authors.initials: GJ
authors.lastname: Pyne
authors.forename: T A
authors.initials: TA
authors.lastname: Cadoux-Hudson
authors.forename: J F
authors.initials: JF
authors.lastname: Clark
mesh_terms: D000328:Adult; D000818:Animals; D002118:Calcium / Q000502:physiology; D002122:Calcium Chloride / Q000494:pharmacology; D002555:Cerebrospinal Fluid / Q000502:physiology*; D046508:Culture Techniques; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D010085:Oxidative Phosphorylation; D010101:Oxygen Consumption / Q000502:physiology; D013345:Subarachnoid Hemorrhage / Q000503:physiopathology*; D013552:Swine; D014661:Vasoconstriction / Q000502:physiology*; D020301:Vasospasm, Intracranial / Q000503:physiopathology*
chemical_list: D002122:Calcium Chloride; D002118:Calcium