Extended Data Fig. 8: Translation of the neuroprosthetic baroreflex to non-human primates.
From: Neuroprosthetic baroreflex controls haemodynamics after spinal cord injury
Step 1(a): To further establish the efficacy of the neuroprosthetic baroreflex, we performed experiments in three non-human primates. First, we measured arterial blood pressure using an invasive catheter in the subclavian artery. Next, we performed a T3 spinal cord injury to mimic the experimental conditions of our rodent experiments. We next mapped the pressor responses to epidural stimulation from T7 to L3. We combined these results with ex vivo dissections of the anatomical dimensions of the lower thoracic spinal cord in rhesus macaques (n = 3) to design an electronic dura mater. Finally, we implemented all the features of the neuroprosthetic baroreflex. Step 2(b): We tested the efficacy of the neuroprosthetic baroreflex specifically within the context of acute traumatic SCI. We emulated all the features of standard neurointensive care including arterial blood pressure measurements, clinical grade anaesthesia (intravenous propofol), as well as temperature and respiration control. We integrated our stimulation approach into clinical-grade technologies using an implantable pulse generator and a spatially selective spinal implant. Step 3(c): All the features of the neuroprosthetic baroreflex were injected into our previously used clinical-grade stimulation approach. In brief, the neuroprosthetic baroreflex received beat-by-beat continuous blood pressure to provide closed loop control. Stimulation output control was sent to the neural research programmer interface, which communicates with the implantable pulse generator through a series of Bluetooth and infrared links. These commands were then sent directly to the customized spinal implant. Step 4(d): Similar to rodent experiments, we found that T3 spinal cord injury induced a significant surge in systolic blood pressure (paired one-tailed t-test; 127 mmHg vs 213 mmHg; t = 4.15; P = 0.027), mean arterial pressure (paired one-tailed t-test; 110 mmHg vs 172 mmHg; t = 3.96; P = 0.029), diastolic blood pressure (paired one-tailed t-test; 102 mmHg; vs 151 mmHg; t = 3.80; P = 0.031), and an accompanying decrease in heart rate (paired one-tailed t-test; 111 bpm vs 76 bpm; t = −4.05; P = 0.028). By one-hour after injury, we observed clinically relevant neurogenic shock, characterized by decreased systolic blood pressure (paired one-tailed t-test; 127 mmHg vs 110 mmHg; t = −3.20; P = 0.043), mean arterial pressure (paired one-tailed t-test; 110 mmHg vs 95 mmHg; t = −5.23; P = 0.017), and diastolic blood pressure (paired one-tailed t-test; 96 mmHg vs 102 mmHg; t = −6.24; P = 0.012). Step 5(e): Despite the fact that we observed an immediate decrease in resting blood pressure, epidural electrical stimulation was able to cause an immediate and transient pressor response in all three animals. In all cases, where percentage change is presented statistics were completed on raw values. *P < 0.05; **P < 0.01; ***P < 0.001.
