Intravenous vagal stimulation catheter, JOHAKU, rapidly decreases heart rate and myocardial oxygen consumption without worsening hemodynamics

Abstract

Background Rapid reduction of heart rate (HR) is the most evident physiological response of vagal nerve stimulation (VNS). Since HR reduction is the most potent factor to decrease myocardial oxygen consumption rate (MVO2), the appropriate VNS can exert cardio-protective effects. It is also known that VNS reduces inflammation, oxidative stress, and sympathetic overload. In addition, the VNS during ischemia-reperfusion is known to attenuate myocardial damage by studies in various animal species. Despite the presence of preclinical evidence of VNS benefits, the lack of the device has limited the translation of this technology to clinical practice. We have recently developed an intravenous VNS catheter (JOHAKU, Neuroceuticals Inc.) that can stimulate the right vagal nerve via superior vena cava (SVC) (Figure 1) on temporary basis. Purpose We aimed to confirm the feasibility of JOHAKU as a device to modulate heart rate and MVO2 rapidly by a canine experiment. Methods In eight beagle dogs, JOHAKU was inserted from the right femoral vein and placed at the SVC level. The stimulation intensity was adjusted to 10–20 V (20 Hz). We simultaneously recorded electrocardiogram and intraarterial blood pressure (BP). In three of eight dogs, we measured the left anterior descending coronary artery flow and oxygen saturations of arterial and coronary sinus blood to calculate MVO2. We compared HR, BP, and MVO2 during JOHAKU stimulation to ones at baseline. Results As shown in Figure 2, JOHAKU attenuated HR immediately after stimulation. Compared with baseline, JOHAKU significantly reduced HR (baseline: 135±13 vs. 5 min on stimulation: 107±13 bpm, p<0.05), and did not affect mean BP significantly (96.2±22.8 vs. 89.4±26.6 mmHg, P=0.59). HR promptly recovered to baseline level after JOHAKU stopped. JOHAKU also reduced MVO2 (0.57±0.43 vs. 0.48±0.38 ml/min, p<0.05). Conclusion JOHAKU rapidly attenuated cardiac metabolism burden via the rapid HR reduction. The controllability of HR by JOHAKU without affecting BP enables us to apply the VNS even for patients with hemodynamic instability, such as heart failure and acute myocardial infarction. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Agency for Medical and Research Development