(555.16) Bilateral Nephrectomy Impairs Cerebral Oxygen Delivery After Acute Hemodilution Anemia in Rats

Poster Board Number: E76

Kyle Chin (St. Michaels Hospital, St. Michaels Hospital), Benjamin Steinberg (Hospital for Sick Children, Hospital for Sick Children), Neil Goldenberg (Hospital for Sick Children, Hospital for Sick Children), Andrew Baker (St. Michaels Hospital, St. Michaels Hospital, St. Michaels Hospital), C. Mazer (St. Michaels Hospital, St. Michaels Hospital, St. Michaels Hospital), Gregory Hare (St. Michaels Hospital, St. Michaels Hospital, St. Michaels Hospital)

Hypothesis:

We hypothesize that renal sensing of hypoxia is essential for activation of cardiovascular responses needed to maintain cerebral oxygen delivery during acute anemia and that bilateral nephrectomy will negatively affect brain oxygen delivery during acute hemodilutional anemia.

Methods:

All experiments were approved by the Animal Care and Use Committee at St. Michael’s Hospital and conducted in accordance with ARRIVE-2 guidelines. Sham or bilateral nephrectomy (n=5) were performed on isoflurane anesthetized Sprague-Dawley rats prior to performing acute hemodilution (50% estimated blood volume) 1:1 with 6% hydroxyethyl starch. Heart rate (HR), mean arterial pressure (MAP) and rectal temperature were monitored continuously. Arterial blood gases and cooximetry samples were measured before and after hemodilution. Continuous measurements of brain microvascular oxygen tension (PbrO2) were measured via a phosphorescence quenching method using an intravascular oxygen probe, Oxyphor PdG4, and an OxyLED phosphorometer. Data were tested for normality and analysis performed by two-way ANOVA with plt;0.05 taken to be significant.

Results:

Bilateral nephrectomy resulted in a reduction in baseline HR (plt;0.004). Hemodilution resulted in a comparable reduction in hemoglobin concentration in both groups (Sham: 5.1±0.3 g/dL; Nephrectomy: 4.2±0.4 g/dL) with no differences in arterial PaO2 or PaCO2. After hemodilution, HR increased significantly in both groups (plt;0.05). MAP tended to be lower in the bilateral nephrectomy group and decreased transiently in both groups following hemodilution (plt;0.01). Brain microvascular pO2 (PbrO2) was not significantly different between nephrectomy and sham at baseline. Post-hemodilution the PbrO2 was significantly lower in nephrectomised rats (11.5±5.1 mmHg) compared to sham operated rats (25.4±11.3 mmHg) (p=0.031).

Conclusions:

We observed that bilateral nephrectomy resulted in changes in baseline physiology, including a lower HR. Hemodilution resulted in a comparable reduction in hemoglobin concentration, without difference in PaO2 or PaCO2. MAP decreased more profoundly immediately after hemodilution in nephrectomised animals, and recovered with time. Nephrectomy resulted in a significant drop in brain microvascular pO2 (PbrO2) immediately after hemodilution. This was not observed in sham controls. These data suggest that the kidney serves an important sensing role during acute anemia which supports cardiovascular responses and preserves the adequacy of brain tissue oxygen delivery. Hypoxia sensing by the kidney, and other integrative systemic mechanisms, may be central to these findings.

Support or Funding Information

CAS RA Gordon Research Award



Real-time measurements of heart rate (HR), mean arterial pressure (MAP) and brain microvascular pO2 (PbrO2) in anesthetized rats. A. HR were significantly lower at baseline in bilateral nephrectomy rats compared to control (p < 0.004). Post-hemodilution HR increased in all groups (p < 0.05). B. MAP decreased in both groups post-hemodilution (p < 0.01). C. Baseline PbrO2 was not different between groups. Post-hemodilution PbrO2 was significantly lower in nephrectomy compared to control (p=0.031).