Curr Hypertens Rep (2010) 12:61–66 Human Experiments Carlsten and colleagues [13] were the first to report on the effects of brief episodes of direct carotid sinus stimulation in humans. They studied five patients with neck cancer, in whom the cancer process made a dissection of the carotid sinus region necessary. Their findings were identical to those obtained in the animal experiments. Electrical stimulation of the carotid sinus nerve caused a typical response, with a prompt fall in mean blood pressure, pulse amplitude, and heart rate. In 1966, Bilgutay and Lillehei [14] reported on the results of the first two patients who were treated with an electronic implantable device for up to 12 months. These patients experienced an immediate and significant reduction in blood pressure of 70/35 and 100/ 40 mm Hg. In the first patient, blood pressure remained at the lower level, but in the second patient, the pressure tended to return towards baseline levels. At about the same time, Schwartz and colleagues [15] published their results on chronic electrical stimulation of the carotid sinus nerve in 11 humans. Eight patients, who had been subjected to carotid sinus nerve stimulation for periods varying between 5 months and 2½ years, were treated successfully, with a sustained reduction in blood pressure of 30 to 100 mm Hg systolic and 24 to 80 mm Hg diastolic. Two patients responded only minimally and one died of renal failure 2 months postoperatively. Since these initial observations, several investigators have applied electrical activation of the baroreceptor system in patients with resistant hypertension and those with severe angina pectoris. Altogether, 64 cases of chronic electrical 63 activation of the baroreceptor system in the treatment of hypertension have been reported (Table 1) [14–35]. In 44 of these, significant reductions in blood pressure were shown, ranging from 15 to 130 mm Hg systolic and from 10 to 80 mm Hg diastolic, with follow-up periods ranging from 1 to 37 months. In one study with three patients, the follow- up period was not specified [20]. Of these 44 responsive patients, 8 no longer received any antihypertensive drugs [15, 28]. Two other patients had a minimal response [15] and two patients had no response at all [31]. Most of the remaining 16 patients had a favorable response initially, but they died, stopped treatment, or were lost to follow-up within 3 months after implantation: two died because of stroke, three because of renal failure, two because of pulmonary embolism, and one because of hyperkalemia and ventricular arrhythmia [14, 15, 27–29, 35]. For two patients, the cause of death was not identified [24, 29]. Three patients stopped treatment because of serious side effects, one patient required removal of the stimulator, and two patients were lost to follow-up [15, 29, 32]. In 1967, Braunwald and colleagues [36] first reported the relief of angina pectoris by electrical activation of the baroreceptor system in humans. Because the oxygen requirements of the heart are directly related to heart rate, the inotropic state of the myocardium, and intraventricular pressure, these authors felt that if these factors could be reduced, the oxygen demands of the heart would also be diminished, resulting in a decrease in the incapacitating symptoms of angina. In total, 135 cases of chronic electrical stimulation in the treatment of angina pectoris have been reported in the literature, with significant relief of pain Table 1 Early publications on electrical activation of the carotid baroreceptor system in treating hypertension Year Study Earlier publications on same patients Patients, n Follow-up, mo Blood pressure results 1966 Bilgutay & Lillehei [14] – 1967 Schwartz et al. [15] – 1968 Khatri & Cohn [20] 1969 Parsonnet et al. [21] 1969 Warembourg et al. [24] 1970 Kaufmann et al. [26] 1970 Torresani et al. [27] 1972 Brest et al. [28] 1972 Tuckman et al. [29] 1973 Both et al. [30] 1973 Ernst et al. [31] 1973 Wagner et al. [32] 1975 Solti et al. [33] 1977 Myers [34] 1980 Saadjian et al. [35] ↓—decrease. – Rothfeld et al. [23] – – Jouve [19]; Torresani et al. [17, 18] Brest [25] Reich [22]; Tuckman et al. [16] – – – – – – 2 11 3 1 3 1 3 8 12 1 5 5 1 1 7 12 5–30 Unknown 3 5–8 1 12–15 7–16 4–37 6 5–10 2–18 13 96 10–36 1, significant ↓; 1, lost to follow-up 6, significant ↓; 2, minimal response; 3, lost to follow-up 3, significant ↓ 1, significant ↓ 2, significant ↓; 1, lost to follow-up 1, significant ↓ 2, significant ↓; 1, lost to follow-up 6, significant ↓; 2, lost to follow-up 7, significant ↓; 5, lost to follow-up 1, significant ↓ 3, significant ↓; 2, no response 4, significant ↓; 1, lost to follow-up 1, significant ↓ 1, significant ↓ 5, significant ↓; 2, lost to follow-up