*2.1. Ethical Statement*

The animal test protocol was approved by the Institutional Animal Care and Use Committee of Seoul National University Hospital (IACUC Number: 17-0106). All animal care abided by the Laboratory Animal Act of the Korean ministry of Food and Drug Safety.

#### *2.2. Study Design and Setting*

An animal experiment was designed based on a VF swine model. The LUCAS machine (LUCAS2 Chest Compression System, Jolife AB, Sweden) was exploited for mechanical chest compressions (Figure 1a). The machine compressed the chest at a rate of 100 compressions/min with a depth of 5 cm. To prevent displacement of the piston, animals were fixed on the table and the back plate was positioned underneath the animal as a support for the machine. The exact location of the heart was identified by ultrasonic imaging, and then the piston was placed on the site. One emergency medical technician held the machine to prevent the displacement of the piston during CPR.

The assumed scenario of this study was a witnessed OHCA. The duration of untreated VF was determined by considering CA-CALL time (the time of cardiac arrest to call) for bystanders to recognize CA and call emergency services [20]. In addition, it was estimated that four consecutive basic life support (BLS) cycles were performed by the bystanders, with the help of an emergency center, before the dispatched emergency medical team (EMT) arrived at the site. The EMT performed the first defibrillation shock and checked the electrocardiogram (ECG). If the ECG rhythm was shockable, a biphasic defibrillation shock of 200 J was applied by the EMT to restart the heart. Monitoring was initiated when a palpable pulse with organized QRS complexes and systolic blood pressure over 60 mmHg appeared [21]. Sustained ROSC was confirmed if spontaneous circulation continued for 20 min [19]. Once a palpable pulse did not appear after the defibrillation, or VF occurred again during the monitoring session, one cycle of advanced cardiovascular life support (ACLS) was performed by

‐

‐ ‐

EMT immediately. If the ECG rhythm was still shockable, the defibrillation shock was applied. In case of pulseless electrical activity or asystole, however, the defibrillation shock was omitted, and the next cycle of ACLS was initiated immediately. If a palpable pulse appeared after the defibrillation, then monitoring for 20 min was initiated. Non-ROSC was confirmed if sustained ROSC was not achieved after 10 cycles of ACLS. During ACLS sessions, epinephrine of 1 mg was injected once every 3 min [22]. After the monitoring sessions or all 10 ACLS sessions, the animals were administered euthanasia, with an injection of potassium chloride. Simultaneous EEG and hemodynamic data were collected during the experiments. The entire test scenario, with a timeline, is described in Figure 2. ‐ ‐

‐

‐

‐ ‐

‐ ‐ ‐

‐

‐

‐

**Figure 1.** Experimental setup: (**a)** LUCAS2 chest compression system installed on the chest of animals; (**b**) A single-channel electroencephalography (EEG) device mounted on the forehead.

**Figure 2.** The entire test scenario: (**a**) flow chart from surgical procedure to basic life support (BLS), advanced cardiovascular life support (ACLS), and termination; (**b**) brief timeline of the test protocol.
