64 shown in 114 patients, with follow-up periods ranging from 1 to 132 months. Fourteen patients died; for nine of these, the cause of death (eg, bradycardia, ventricular fibrillation, heart failure, myocardial infarction, or pulmonary infarction) was related to the procedure. Problems and Side Effects Despite the initial positive and promising results, electrical activation of the baroreceptor system has remained restricted to a carefully selected group of patients in only a few institutions. Developments in this area probably were hampered by the simultaneous introduction of more effective and better tolerated antihypertensive drugs, but several questions also remain unanswered and several problems are unresolved. One of these is where the electrodes should be placed. In most of the humans treated, the electrodes were placed on the carotid sinus nerves, even though experiments in animals with placement of the electrodes on the carotid baroreceptors also showed good results. No advantages or disadvantages for a certain position of the electrodes were mentioned in the literature, but a nerve seems more fragile than an artery, and risks for trauma and devascularization are greater with dissection of the nerve than with dissection of the artery. Limitations of surgical techniques at that time were another problem; better techniques were necessary to limit the risks and shorten the duration of the implant procedure. Determining the best site of stimulation is another problem. Parsonnet and colleagues [37] showed similar effects on blood pressure with bilateral nerve stimulation or unilateral stimulation of the most responsive nerve. In contrast, Schwartz and colleagues [15] demonstrated that bilateral stimulation was more effective than the summation of the pressure reduction resulting from unilateral stimulation of the two nerves. It is difficult to determine the most responsive nerve preoperatively, and differences in respon- siveness could also occur as a result of surgical trauma. Another problem is the system of stimulation. In an open-loop system, the duration, frequency, and amplitude of impulses must be fixed after testing to find out the optimal adjustments. Possible changes in the sensitivity of the baroreceptors or the effect of the stimulation are not taken into consideration because there is no feedback of the actual cardiovascular status to the stimulator. From this point of view, the introduction of a feedback loop can improve the possibilities of electrical activation of the baroreceptor system [38]. In experimental studies, where closed-loop stimulation has been compared with open-loop stimulation, all patients achieved similar hemodynamic results, but a lower intensity of stimulation was required in the closed-loop stimulation system [39]. A final problem is the long-term effect of the procedure. Much uncertainty remains regarding damage and degeneration Curr Hypertens Rep (2010) 12:61–66 of the sinus nerve fibers, along with nerve fatigue and resetting of the baroreceptor mechanism after a long period of electrical stimulation. In addition, little is known about long-term effects on the function of the heart and other organs. Proper investigation of chronic stimulation is important to evaluate the long-term effects of baroreceptor system stimulation. Besides these problems, the reported side effects may have hampered developments in this area. The most obvious effect is the occurrence of pain in the mandible, teeth, external auditory canals, throat, and chest, as well as in the post- auricular, posterior neck, and suboccipital regions [12, 15, 28– 30, 40]. Also, adverse effects as dysphonia, dysphagia, hyperpnea, tachypnea, laryngospasm, gagging, coughing, edema around the electrodes, and hypotension have been reported [15, 22, 29, 41, 42]. These effects were caused by nonoptimal settings of the stimulator, leakage or spread of the electrical signal from the electrodes, and improper positioning of the electrodes. Improper positioning can weaken or disturb the electrical signals [15, 43]. It also can lead to stimulation of muscle fibers or motor nerves, with subsequent contraction of adjacent muscles [12, 40]. Recent Experiences and Developments Recently, the sympathetic nervous system has moved toward the center of cardiovascular medicine, because it seems to be a key factor in the genesis of essential hypertension [44]. More and more research strongly suggests that the baroreceptors play a role in the long- term control of arterial pressure [45]. As a result, interest is growing in antihypertensive therapies with beneficial effects on hypertension-related sympathetic activation [46, 47]. In 2004, Lohmeier et al. [48] published the results of a study of prolonged activation of the baroreflex. He showed sustained hypotension in six dogs that were subjected to continuous carotid baroreceptor stimulation for 7 days. With these results and today’s improved surgical techniques and microelectronics, it is time to reevaluate the possible role of electrical carotid baroreflex activation in treating patients with resistant hypertension. The Rheos Baroreflex Hypertension Therapy System (CVRx, Inc.; Minneapolis, MN, USA) recently became available. Detailed descriptions of this device and the surgical technique used have been previously published [49, 50 ]. In general, the Rheos System uses bilateral carotid artery stimulation with an open-loop system. The device is totally implantable, consisting of a pulse generator and two leads. It uses modern microelectronics and a special lead design for chronic electrical activation of the carotid sinus baroreflex to reduce blood pressure. The two leads conduct the activation energy from the pulse generator to the baroreceptors located on the left and right