Revisiting Electrophysiological Mechanisms of VF/VT Arrest During Early Ischemia and Spontaneous Electrical Activity After Defibrillation: From Cell to ACLS

Review Article

Austin J Cerebrovasc Dis & Stroke. 2014;1(4): 1018.

Revisiting Electrophysiological Mechanisms of VF/VT Arrest During Early Ischemia and Spontaneous Electrical Activity After Defibrillation: From Cell to ACLS

Muramatsu H1* and Takayama M2

1Department of Medicine, Nippon Medical School, Japan

2Department of Cardiology, Sakakibara Heart Institute, Japan

*Corresponding author: Muramatsu H, Department of Medicine, Division of Cardiology, Nippon Medical School 7-3 Daiwa, Koufu, Yamanashi 400-0072, Japan

Received: July 25, 2014; Accepted: August 20, 2014; Published: August 22, 2014


K+ conductance and [K+]o increase during early (<10 min) regional and global ischemia. Early ischemia depolarizes the RMP and decreases INa (that is, residual INa) causing slow conduction, and shortens APD and ERP with dispersion. All of these factors contribute to the reentry mechanisms of VF/VT. While IK, ATP has a pivotal role in the increase in [K+]o, other currents such as IK, Na, IK, Ca, IK, FAA have simultaneously important effects on the increase in [K+]o. Up regulation of IK1, with an increase in inward-rectification, can also contribute to the increase in [K+]o in very early ischemia. VT is induced by ordered reentry of spiral waves, whereas VF is caused by random reentry of the spiral wavelets’ breakup. A biphasic waveform is more effective to defibrillate VF than a monophonic waveform, because, in the biphasic waveform the first hyper polarization resets every state of Na+ channels to prepare for reopening, and the subsequent depolarization simultaneously and uniformly inactivates almost all of the Na+ channels. Pacemaker restoration with spontaneous electrical activity can originate from either the SAN, AVN or Purkinje cells. Ischemia suppresses pacemaker activity, because pacemaker currents are sensitive to the ischemia, especially in the SAN, which has the fastest firing rate. Post ischemic early reperfusion injury induces a stunned myocardium and contractile disturbance, which can cause post-defibrillation pseudo PEA. After at least 5 min of an induced VF arrest, the reduction of PO2 was statistically significant, but that change was not remarkable; therefore, the estimated SaO2 does not decrease remarkably. High-quality CPR prevents global ischemia of the heart and brain due to VF/pulse less VT arrest. Therefore, it is essential to restore the organized electrical activity of pace making, to facilitate effective contraction of the ventricular muscle (that is, ROSC), and to minimize ischemic and post ischemic injury of these important organs.

Keywords: Acute coronary syndromes; Ventricular fibrillation; Cardiopulmonary and cerebral resuscitation; Defibrillation; Pacemaker cells; Ion channels


ACLS: Advanced Cardiopulmonary And Cerebral Life Supports; ACS: Acute Coronary Syndromes; ADP: Adenosine Di phosphate; aK o: Extracellular K+ Activity; AMI: Acute Myocardial Infarction; AP: Action Potential; APD: Action Potential Duration; ATP: Adenosine Triphosphate; [ATP]i: Intracellular ATP Concentration; AVN: Atrioventricular Node; BLS: Basic Life Supports; [Ca2+]i: Intracellular Ca2+Concentration; c AMP: Cyclic Adenosine Mono phosphate; CPR: Cardiopulmonary and Cerebral Resuscitation; Cx: Connexins; DAD: Delayed After depolarization; ECG: Electrocardiogram; ERP: Effective Refractory Period; [H+]i: Intracellular H+ Concentration; Ib: Background Current; ICa: Calcium Current; ICaT: T-type Calcium Current; ICaL: L-type Calcium Current; Ih(f): Hyper polarization- Activated (funny) current; IK1: Inwardly Rectifying K+ current; IK: ATP: ATP-Sensitive K+ Current; IK: Ca: Ca2+-Dependent K+ Current; IK: FAA: Fatty Acid-Activated K+ Current; IK: Na: Na+-Activated K+ Current; INa: Na+ Current; INa/Ca: Na+-Ca2+ Exchange Current; INa/K: Na+-K+ Pump Current; IKr: Rapid Component Of Delayed Rectifier Outward K+ Current; IKs: Slow Component Of Delayed Rectifier Outward K+> Current; INSC: Nonselective Cation Channel Current; Ist: Sustained Inward Current; Kd: Equilibrium Dissociation Constant; [K+]e: [K+] o: Extracellular K+ Concentration; LAD: Left Anterior Descending Artery; LCFA: Long Chain Fatty Acid; NA: Noradrenalin; [Na+]i: Intracellular Na+ Concentration; NADPH: Nicotinamide AdenineDinucleotide Phosphate; NBF: Nucleotide Binding Folds; NO: Nitric Oxide; NSTE ACS: Non St-Elevated Acute Coronary Syndromes; NSTEMI: Non St-Elevated Myocardial Infarction; NSVT: Non sustained Ventricular Tachycardia; PCO2: Partial Pressure Of Carbon Dioxide; PEA: Pulse less Electrical Activity; [pH]o: Extracellular Ph; PO2: Partial Pressure Of Oxygen; Q10: Temperature Coefficient; RMP:Resting Membrane Potential; ROS: Reactive Oxygen Species; ROSC: Return Of Spontaneous Circulation; SAN: Sinoatrial Node; SaO2: Saturation of Arterial Oxygen; SCD: Sudden Cardiac Death; SR: Sarcoplasmic Reticulum; STEMI: ST-Elevated Myocardial Infarction; SUR: Sulfonylurea Receptor; UA: Unstable Angina; VF: Ventricular Fibrillation; VT: Ventricular Tachycardia.


Patients with coronary atherosclerosis may develop a spectrum of clinical syndromes representing varying degrees of coronary artery occlusion. Acute coronary syndromes (ACS) include ST-elevated myocardial infarction (STEMI) and non ST-elevated ACS. The latter includes unstable angina (UA) and non ST-elevated myocardial infarction (NSTEMI) due to incomplete occlusion of the coronary artery: whereas the former is due to complete occlusion. Sudden cardiac death (SCD) may occur with each of these syndromes [1,2].

Approximately 52% of acute myocardial infarction (AMI) manifests as the SCD that relates to ventricular fibrillation (VF): and occurs mostly within the first hours after the onset of symptoms: inevitably causing prehospital deaths [1,2]. Furthermore: in about 30% of cases: lethal ventricular arrhythmias appear within 30 min from the onset of the AMI: leading to SCD without appropriate emergency cardiovascular care [3].

Basic life supports (BLS) and advanced cardiopulmonary and cerebral life supports (ACLS) are essential to emergency cardiovascular care. The chain of survival is a critical concept to perform resuscitation: including in adult patients (1) immediate recognition of cardiac arrest and activation of the emergency response system; (2) early cardiopulmonary and cerebral resuscitation (CPR) with an emphasis on chest compressions; (3) rapid defibrillation; (4) effective ACLS; (5) integrated immediate post-cardiac arrest care; and (6) rehabilitation [1,2]. The rehabilitation care for patients who survive SCD requires comprehensive cardiac and cerebral rehabilitation.

However: in order for the surviving patients to have a good prognosis: a critical component in both BLS and ACLS is continuous high-quality CPR in which the chest compressions are especially important [1]. Continuous high-quality CPR: early after arrest from VF or pulse less ventricular tachycardia (VT) and immediately after electrical defibrillation: maintains cerebral as well as coronary blood perfusions. High-quality CPR also can suppress progressive global ischemia in the whole heart during VF/VT arrest: decrease arrhythmogenic substrates: wash out ischemia-related injurious products: and provide oxygen and glucose for pacemaker cells to generate spontaneous electrical activity and for ventricular cells to contract.

Thus: understanding of the cellular pathophysiological and electrophysiological mechanisms that underscore the need for the continuous high-quality CPR and early defibrillation: besides simplified practical algorithms: could be helpful for BLS and ACLS education: training and clinical practice.

Understanding the electrophysiological mechanisms is crucial: especially for the following.

  1. Malignant ventricular arrhythmias: such as VT and/or VF: during early ischemia: i.e. a sudden cardiac arrest in the ACS.
  2. More beneficial effect of a biphasic waveform to electrically defibrillate the ventricles.
  3. Spontaneous electrical activity of pacemaker cells and ventricular contraction after successful defibrillation: which assure a return of spontaneous circulation (ROSC).
  4. Post-defibrillation pseudo pulse less electrical activity (PEA) associated with reperfusion contractile disturbance: i.e. ““stunned myocardium”: after the global ischemia due to the VF/VT arrest.

Although many resources now are available: a basic knowledge of the electrophysiological mechanisms during resuscitation: particularly ion channels and cellular metabolism: is quite limited. Therefore: here we briefly review and summarize what is known about those mechanisms: while emphasizing the need for high-quality CPR during early VF/VT arrest from ACS.

Mechanisms of VF/VT in early ischemia

The triphasic time course of extracellular K+ accumulation in acute regional myocardial ischemia

As is generally accepted: Figure 1 shows that increases in extracellular K+ concentration ([K+]o) and extracellular K+ activity (aKo) occur in a triphasic pattern: that is: phases I : II and III [4]. In phase I: the initial rapid phase of [K+]o accumulation or aKo increase began to rise within 15-20 sec. In phase II: a plateau occurred after approximately 10-15 min of ischemia: ranging 10.7-18 mM [K+] o or 8-13 mM aKo. The dotted line indicates an occasional minor decline that may appear in some experiments. In phase III: a second progressive increase was no longer reversible upon reperfusion [4]. The slope of phase I and the time and level of phase II varied with different experimental conditions and species.