ABSTRACT
The sensitivity of several neurophysiological and cognitive tests to different levels of hypoxia was investigated. Cerebral hypoxia in healthy volunteers may be a disease model for dementia or other forms of brain dysfunction. Twelve healthy subjects were included in a randomized, single-blind, placebo-controlled, three-period cross-over trial. They received three air/N2 gas mixtures via mask breathing [aimed at peripheral oxygen saturation (SPO2) values of > 97% (placebo), 90% and 80%, with normal end-tidal CO2]. Central nervous system effects were tested regularly for 130 min by saccadic and smooth pursuit eye movements, electro-encephalogram, visual analogue scales and cognitive tests. Treatments were well tolerated. Compared to SPO2 90%, SPO2 80% reduced saccadic peak velocity by 16.4 degrees/s [confidence interval (CI) -26.3, -6.4], increased occipital delta power by 14.3% (CI 3.6, 25.1), and significantly increased most cognitive reaction times. SPO2 80% also decreased correct responses for the binary choice task and serial word recognition [-1.3 (-2.2, -0.3) and -3.5 (-6.2, -0.8), respectively] compared to SPO2 90%. Cognitive performance was decreased by SPO2 80% and increased by SPO2 90% compared to placebo. Sensitive effect measurements can be identified for these interventions. The applicability as a model for cognitive impairment should be investigated further.
Subject(s)
Cognition Disorders/psychology , Hypoxia/psychology , Psychomotor Performance/physiology , Adult , Affect/physiology , Attention/physiology , Carbon Dioxide/blood , Choice Behavior/physiology , Cross-Over Studies , Double-Blind Method , Electroencephalography , Female , Heart Rate/physiology , Humans , Hypoxia/complications , Male , Memory/physiology , Mental Recall/physiology , Models, Biological , Neuropsychological Tests , Oxygen/blood , Reaction Time/physiology , Reading , Saccades/physiology , Visual Perception/physiologyABSTRACT
To investigate how mechanical stress is sensed by cardiomyocytes and translated to cardiac hypertrophy, cardiomyocytes were subjected to stretch while measuring phospholipase C (PLC) and phospholipase D (PLD) activities and levels of intracellular calcium ions ([Ca2+]i) and pH. In stretched cardiomyocytes, PLC activity increased 2-fold after 30 min, whereas PLD activity hardly increased at all. Mechanical stress induced by prodding or by cell stretch increased [Ca2+](i)by a factor 5.2 and 4, respectively. Gadolinium chloride (stretch-activated channel blocker) attenuated the prodding-induced and stretch-induced [Ca2+](i)rise by about 50%. Blockade of ryanodine receptors by a combination of Ruthenium Red and procaine reduced the [Ca2+](i)rise only partially. Diltiazem (L-type Ca2+ channel antagonist) blocked the prodding-induced [Ca2+](i)rise completely, and reduced the stretch-induced [Ca2+](i)rise by about 50%. The stretch-induced [Ca2+](i)rise was unaffected by U73122, an inhibitor of PLC activity. Stretch did not cause cellular alkalinization. In conclusion, in cardiomyocytes, PLC and [Ca2+](i)levels are involved in the stretch-induced signal transduction, whereas PLD plays apparently no role. The stretch-induced rise in [Ca2+](i)in cardiomyocytes is most probably caused by [Ca2+](i)influx through L-type Ca2+ channels and stretch-activated channels, leading to Ca2+-induced Ca2+ -release from the SR via the ryanodine receptor.
