Controlling the heart via the brain: a potential new therapy for orthostatic hypotension

Objective: Electrical stimulation of the midbrain is known to influence blood pressure in animals. In humans, it is used for the treatment of chronic neuropathic pain. Our aim was to assess whether orthostatic hypotension can be successfully treated with deep brain stimulation of the periventricular/periaqueductal gray areas in humans.Methods: We recruited 11 patients who had chronic neuropathic pain and who had undergone implantation of a deep brain stimulator in the periventricular/periaqueductal gray areas. Patients were divided into three groups depending on whether they had orthostatic hypotension (one patient), mild orthostatic intolerance (five patients), or no orthostatic intolerance (five patients). Postoperatively, we continuously recorded blood pressure and heart rate with stimulation off and on and in both sitting and standing positions. From these values, we derived the blood pressure changing rate. Using autoregressive modeling techniques, we calculated changes in low- and high-frequency power spectra of heart rate and baroreflex sensitivity.Results: Electrical stimulation reduced the decrease in systolic blood pressure on standing from 28.2 to 11.1% in one patient with orthostatic hypotension (P < 0.001). In the mild orthostatic intolerance group, an initial drop in systolic blood pressure of 15.4% was completely reversed (P < 0.001). There were no side effects in the remaining group. These changes were accompanied by increases in the blood pressure changing rate, the baroreflex sensitivity, and the baseline (sitting) low-frequency power of the RR interval, but not the high-frequency power.Conclusion: Electrical stimulation of the human periventricular/periaqueductal gray areas can reverse orthostatic hypotension. The cause seems to be an increase in sympathetic outflow and in baroreflex sensitivity. This has important implications for future therapies