Browsing by Subject "Arterial Pressure"
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Item Characterization of Arterial Pressure and Cerebral Blood Flow Responses To Repeated Thigh Cuff Inflation In Three Experimental Models (Humans, Pigs, Rats)(2022-05) Bhuiyan, Nasrul A.; Rickards, Caroline A.; Tune, Johnathan D.; Cunningham, J. ThomasIn a human model of simulated blood loss, oscillatory patterns of arterial pressure and blood flow, or "pulsatile perfusion", can protect cerebral and peripheral tissue oxygenation, and prolong tolerance to this stress. In this pilot study, we characterize the hemodynamic responses to pulsatile perfusion therapy induced via repeated thigh cuff inflations in humans at rest, and in pig and rat models of actual blood loss. In 2 human participants, 0.1 Hz (10-second cycle) thigh cuff oscillations induced robust 0.1 Hz oscillations in arterial pressure and cerebral blood flow. In the two animal models, all subjects underwent a baseline period, hemorrhage of 55% of total blood volume, then a 30-min period with or without thigh cuff oscillations (0.1 Hz for pigs, and 0.5 Hz for rats). Decreases in mean arterial pressure (MAP) and carotid artery blood flow were observed in response to hemorrhage (P≤0.002) in both pigs and rats. At the end of the PPT period, however, no differences were observed between the oscillation or no oscillation groups for absolute MAP (rats, P=0.44; pigs, P=0.90) or common carotid artery (CCA) peak blood flow (rats, P=0.92; pigs, P=0.93). When examining the frequency power spectrums, there was not a robust increase in 0.5 Hz oscillations for MAP (P=0.23) or CCA flow (P=0.82), but 0.1 Hz oscillations were detected in CCA flow for pigs (P=0.09). While in the human model, large increases in oscillatory power were observed for both arterial pressure and cerebral blood flow, the responses in the two animal models were inconclusive due to high inter-individual variability. These findings indicate the need for further studies and refinement of the thigh cuff approach in the animal models to reliably induce hemodynamic oscillations.Item Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice(Springer Nature, 2017-06-23) Li, Weizu; Ding, Yanfeng; Smedley, Crystal; Wang, Yanxia; Chaudhari, Sarika; Birnbaumer, Lutz; Ma, RongThe present study was conducted to determine if TRPC6 regulates glomerular filtration rate (GFR) and the contractile function of glomerular mesangial cells (MCs). GFR was assessed in conscious TRPC6 wild type and knockout mice, and in anesthetized rats with and without in vivo knockdown of TRPC6 in kidneys. We found that GFR was significantly greater, and serum creatinine level was significantly lower in TRPC6 deficient mice. Consistently, local knockdown of TRPC6 in kidney using TRPC6 specific shRNA construct significantly attenuated Ang II-induced GFR decline in rats. Furthermore, Ang II-stimulated contraction and Ca(2+) entry were significantly suppressed in primary MCs isolated from TRPC6 deficient mice, and the Ca(2+) response could be rescued by re-introducing TRPC6. Moreover, inhibition of reverse mode of Na(+)-Ca(2+) exchange by KB-R7943 significantly reduced Ca(2+) entry response in TRPC6-expressing, but not in TRPC6-knocked down MCs. Ca(2+) entry response was also significantly attenuated in Na(+) free solution. Single knockdown of TRPC6 and TRPC1 resulted in a comparable suppression on Ca(2+) entry with double knockdown of both. These results suggest that TRPC6 may regulate GFR by modulating MC contractile function through multiple Ca(2+) signaling pathways.Item Pulsatile Perfusion Therapy: A Novel Approach for Improving Cerebral Blood Flow and Oxygenation Under Simulated Hemorrhagic Stress(2018-05) Anderson, Garen K.; Rickards, Caroline A.; Goulopoulou, Styliani; Mallet, Robert T.; Jones, Harlan P.Introduction: Tolerance to both actual and simulated hemorrhage varies between individuals. Low frequency (~0.1 Hz) oscillations in mean arterial pressure (MAP) and brain blood flow (indexed via middle cerebral artery velocity, MCAv), may play a role in tolerance to reduced central blood volume; subjects with high tolerance to simulated hemorrhage induced via application of lower body negative pressure (LBNP) exhibit greater low frequency power in MAP and MCAv compared to low tolerant subjects. The mechanism for this association has not been explored. We hypothesized that inducing low frequency oscillations in arterial pressure and cerebral blood flow would attenuate reductions in cerebral blood flow and oxygenation during simulated hemorrhage. Methods: 14 subjects (11M/3F) were exposed to oscillatory (0.1 Hz, 0.05 Hz) and non-oscillatory (0 Hz) LBNP profiles with an average chamber pressure of -60 mmHg. Each profile was separated by a 5-min recovery. Measurements included arterial pressure and stroke volume via finger photoplethysmography, MCAv via transcranial Doppler ultrasound, and cerebral oxygenation of the frontal lobe (ScO2) via near infrared spectroscopy. Results: No differences were observed between profiles for reductions in MAP (P=0.60) and MCAv (P=0.90). The reduction in ScO2, however, was attenuated (P=0.04) during the oscillatory profiles compared to the 0 Hz profile. A similar attenuation was observed in stroke volume (P [less than] 0.001). Importantly, tolerance was higher during the oscillatory profiles (P=0.03). Discussion: In partial support of our hypothesis, cerebral oxygenation was protected during the oscillatory profiles. While MCAv was similar between conditions, the oscillatory pattern of cerebral blood flow may elicit a shear-stress induced vasodilation, so assessment of velocity may mask an increase in flow. Importantly, more subjects were able to tolerate the oscillatory profiles compared to the static 0 Hz profile, despite similar arterial pressure responses. These findings emphasize the potential importance of hemodynamic oscillations in maintaining perfusion and oxygenation of cerebral tissue during hemorrhagic stress.