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2-Vessel Occlusion/Hypotension: A Rat Model of Global Brain Ischemia
Published on: June 22, 2013
Two-cytochrome metabolic model for carotid body PtiO2 and chemosensitivity changes after hemorrhage
D G Buerk1, P K Nair, W J Whalen
1Biomedical Engineering and Science Institute, Drexel University, Philadelphia, Pennsylvania 19104.
Insights
Hemorrhage significantly reduced oxygen levels in the cat carotid body (CB), impacting tissue PO2 and nerve activity. Computer simulations suggest altered blood flow and metabolism during hypotension.
Area of Science:
- Physiology
- Biophysics
Background:
- The carotid body (CB) is a critical chemoreceptor involved in regulating respiration and cardiovascular function.
- Understanding oxygen (O2) dynamics within the CB is essential for comprehending its physiological responses to altered blood pressure.
Purpose of the Study:
- To investigate the effects of hemorrhage-induced hypotension on tissue oxygen levels (PtiO2) and oxygen disappearance curves (DCs) in the cat carotid body.
- To correlate these physiological changes with sinus nerve discharge (ND) and to model the underlying metabolic processes.
Main Methods:
- Microelectrode measurements of PtiO2 in cat carotid bodies under normal and hemorraged conditions.
- Assessment of O2 disappearance rates and sinus nerve discharge following transient occlusion of blood supply.
- Computer simulation using a two-cytochrome metabolic model, incorporating physiological parameters like oxyhemoglobin and blood pH.
Main Results:
- Hemorrhage significantly reduced mean PtiO2 and slowed O2 disappearance rates, correlating with decreased blood pressure.
- Resting sinus nerve discharge increased during hypotension and was inversely correlated with PtiO2.
- The two-cytochrome metabolic model simulation aligned with experimental data, predicting changes in blood flow and O2 metabolism.
Conclusions:
- Hypotension induced by hemorrhage alters oxygen homeostasis within the carotid body.
- These alterations in PtiO2 and O2 metabolism are reflected in changes in neural activity.
- The study provides insights into carotid body function under hypoperfusion and validates a computational model for its metabolic responses.
Abstract:
O2 microelectrode measurements were made in the cat carotid body (CB) at normal control blood pressures (C) and after hemorrhage (H) to reduce mean arterial blood pressure [C, 98.7 +/- 4.6 (SE) mmHg; H, 58.1 +/- 1.8; P less than 0.001; paired t test; n = 9 cats]. Mean tissue PO2 (PtiO2) was significantly lower (C, 78.4 +/- 3.0 Torr; H, 65.3 +/- 4.8; P less than 0.01). Except for two experiments with good autoregulation, the decrease in PtiO2 correlated with the reduction in blood pressure (r = 0.791, P less than 0.005). Measurements of O2 disappearance curves (DCs) and sinus nerve discharge (ND) were obtained after blood supply was occluded for 30-45 s (56 C DCs, 44 H DCs). Disappearance rates (dPO2/dt) were significantly slower after hemorrhage (C, -7.52 +/- 0.47 Torr/s; H, -6.60 +/- 0.44; P less than 0.01), decreasing by 0.656 Torr/s for each 10 Torr fall in PtiO2 (r = 0.626, P less than 0.05). Resting ND before occlusion increased during hypotension (11.6 +/- 2.9% of control, P less than 0.01) and correlated with the decrease in PtiO2 (r = -0.792, P less than 0.005). A computer simulation was performed for a two-cytochrome metabolic model with a second, low-O2-affinity oxidase in addition to normal oxidative metabolism. The effects of cat oxyhemoglobin and blood pH on the O2 DC measurement were also taken into account. The simulation for the two-cytochrome model was consistent with our experimental data and predicts reductions in blood flow and O2 metabolism with hypotension after hemorrhage that have similarities, as well as aspects that disagree, with previous reports in the literature.
