Ventricular fibrillation pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Ventricular fibrillation is a cause of cardiac arrest and sudden cardiac death. The ventricular muscle twitches randomly rather than contracting in a coordinated fashion (from the apex of the heart to the outflow of the ventricles), and so the ventricles fail to pump blood into the arteries and systemic circulation. Ventricular fibrillation is a sudden lethal arrhythmia responsible for many deaths in the Western world, and it is mostly caused by ischemic heart disease. While most episodes occur in diseased hearts, others can afflict normal hearts as well. Despite considerable research, the underlying nature of ventricular fibrillation is still not completely understood.
Pathophysiology
- Ventricular fibrillation has been described as a "chaotic asynchronous fractionated activity of the heart. A more complete definition is that ventricular fibrillation is a "turbulent, disorganized electrical activity of the heart in such a way that the recorded electrocardiographic deflections continuously change in shape, magnitude, and direction".[1]
Triggered Activity
The triggered activity can occur due to the presence of after-depolarisations. These are depolarising oscillations in the membrane voltage induced by preceding action potentials. These can occur before or after full repolarisation of the fiber and as such are termed either early (EADs) or delayed after depolarisations (DADs). All after-depolarisations may not reach threshold potential, but if they do, they can trigger another after-depolarisation, and thus self-perpetuate.
Abnormal Automaticity
Automaticity is a measure of the propensity of fiber to initiate an impulse spontaneously. The product of a hypoxic myocardium can be hyperirritable myocardial cells. These may then act as pacemakers. The ventricles are then being stimulated by more than one pacemaker. Scar and dying tissue are inexcitable, but around these areas usually lies a penumbra of hypoxic tissue that is excitable. Ventricular excitability may generate re-entry arrhythmias.
It is interesting to note that most cardiac myocardial cells with an associated increased propensity to arrhythmia development have an associated loss of membrane potential. That is, the maximum diastolic potential is less negative and therefore exists closer to the threshold potential. Cellular depolarisation can be due to a raised external concentration of potassium ions K+, a decreased intracellular concentration of sodium ions Na+, increased permeability to Na+, or a decreased permeability to K+. The ionic basis automaticity is the net gain of an intracellular positive charge during diastole in the presence of a voltage-dependent channel activated by potentials negative to –50 to –60 mV.
Myocardial cells are exposed to different environments. Normal cells may be exposed to hyperkalemia, abnormal cells may be perfused by the normal environment. For example, with a healed myocardial infarction, abnormal cells can be exposed to an abnormal environment such as with myocardial infarction with myocardial ischemia. In conditions such as myocardial ischaemia, possible mechanism of arrhythmia generation include the resulting decreased internal K+ concentration, the increased external K+ concentration, norepinephrine release and acidosis. When myocardial cell are exposed to hyperkalemia, the maximum diastolic potential is depolarized as a result of the alteration of Ik1 potassium current, whose intensity and direction is strictly dependant on intracellular and extracellular potassium concentrations. With Ik1 suppressed, a hyperpolarizing effect is lost and therefore there can be activation of funny current even in myocardial cells (which is normally suppressed by the hyperpolarizing effect of coexisting potassium currents). This can lead to the in-saturation of automaticity in ischemic tissue.
Re-entry[2]
The role of re-entry or circus motion was demonstrated separately by Mines and Garrey. Mines created a ring of excitable tissue by cutting the atria out of the ray fish. Garrey cut out a similar ring from the turtle ventricle. They were both able to show that, if a ring of excitable tissue was stimulated at a single point, the subsequent waves of depolarisation would pass around the ring. The waves eventually meet and cancel each other out, but, if an area of transient block occurred with a refractory period that blocked one wavefront and subsequently allowed the other to proceed retrogradely over the other path, then a self-sustaining circus movement phenomenon would result. For this to happen, however, it is necessary that there be some form of non-uniformity. In practice, this may be an area of ischaemic or infarcted myocardium, or underlying scar tissue.
It is possible to think of the advancing wave of depolarisation as a dipole with a head and a tail. The length of the refractory period and the time taken for the dipole to travel a certain distance—the propagation velocity—will determine whether such a circumstance will arise for re-entry to occur. Factors that promote re-entry would include a slow-propagation velocity, a short refractory period with a sufficient size of the ring of conduction tissue. These would enable a dipole to reach an area that had been refractory and is now able to be depolarised with the continuation of the wavefront.
In clinical practice, therefore, factors that would lead to the right conditions to favour such re-entry mechanisms include increased heart size through hypertrophy or dilatation, drugs which alter the length of the refractory period and areas of cardiac disease. Therefore, the substrate of ventricular fibrillation is transient or permanent conduction block. Block due either to areas of damaged or refractory tissue leads to areas of myocardium for initiation and perpetuation of fibrillation through the phenomenon of re-entry.
Genetics
Genes involved in the pathogenesis of ventricular fibrillation include:[3][4][5][6][7][8]
- Gene mutations that affect cellular transmembrane ion channels.
- For example, in Brugada syndrome, sodium channels are affected. In certain forms of long QT syndrome, the potassium inward rectifier channel is affected.
- NOS1AP
- CASQ2
- ACYP2
- ZNF385B
- RAB3GAP1
- SCN5A
- GPD1L
- AGTR1
- GRIA1
- ZNF365
- GPC5
- AP1G2
- DEGS2
- CXADR
- KCTD1
Associated Conditions
Conditions associated with ventricular fibrillation include:
- Ischemic heart disease.
- Cardiomyopathy
- Myocarditis
- Brugada syndrome
- Other heart pathologies
- Electrolyte disturbance
- Overdoses of cardiotoxic drugs
References
- ↑ Robles de Medina EO, Bernard R, Coumel P; et al. (1978). "Definition of terms related to cardiac rhythm. WHO/ISFC Task Force". Eur J Cardiol. 8 (2): 127–44. PMID 699945.
- ↑ Samie FH, Jalife J (May 2001). "Mechanisms underlying ventricular tachycardia and its transition to ventricular fibrillation in the structurally normal heart". Cardiovasc. Res. 50 (2): 242–50. doi:10.1016/s0008-6363(00)00289-3. PMID 11334828.
- ↑ Jabbari, Reza; Risgaard, Bjarke; Fosbøl, Emil L.; Scheike, Thomas; Philbert, Berit T.; Winkel, Bo G.; Albert, Christine M.; Glinge, Charlotte; Ahtarovski, Kiril A.; Haunsø, Stig; Køber, Lars; Jørgensen, Erik; Pedersen, Frants; Tfelt-Hansen, Jacob; Engstrøm, Thomas (2015). "Factors Associated With and Outcomes After Ventricular Fibrillation Before and During Primary Angioplasty in Patients With ST-Segment Elevation Myocardial Infarction". The American Journal of Cardiology. 116 (5): 678–685. doi:10.1016/j.amjcard.2015.05.037. ISSN 0002-9149.
- ↑ Albert, Christine M.; MacRae, Calum A.; Chasman, Daniel I.; VanDenburgh, Martin; Buring, Julie E.; Manson, JoAnn E.; Cook, Nancy R.; Newton-Cheh, Christopher (2010). "Common Variants in Cardiac Ion Channel Genes Are Associated With Sudden Cardiac Death". Circulation: Arrhythmia and Electrophysiology. 3 (3): 222–229. doi:10.1161/CIRCEP.110.944934. ISSN 1941-3149.
- ↑ Westaway, Shawn K.; Reinier, Kyndaron; Huertas-Vazquez, Adriana; Evanado, Audrey; Teodorescu, Carmen; Navarro, Jo; Sinner, Moritz F.; Gunson, Karen; Jui, Jonathan; Spooner, Peter; Kaab, Stefan; Chugh, Sumeet S. (2011). "Common Variants in
CASQ2
,
GPD1L
, and
NOS1AP
Are Significantly Associated With Risk of Sudden Death in Patients With Coronary Artery Disease". Circulation: Cardiovascular Genetics. 4 (4): 397–402. doi:10.1161/CIRCGENETICS.111.959916. ISSN 1942-325X. line feed character in
|title=at position 19 (help) - ↑ Kronenberg, Florian; Arking, Dan E.; Reinier, Kyndaron; Post, Wendy; Jui, Jonathan; Hilton, Gina; O'Connor, Ashley; Prineas, Ronald J.; Boerwinkle, Eric; Psaty, Bruce M.; Tomaselli, Gordon F.; Rea, Thomas; Sotoodehnia, Nona; Siscovick, David S.; Burke, Gregory L.; Marban, Eduardo; Spooner, Peter M.; Chakravarti, Aravinda; Chugh, Sumeet S. (2010). "Genome-Wide Association Study Identifies GPC5 as a Novel Genetic Locus Protective against Sudden Cardiac Arrest". PLoS ONE. 5 (3): e9879. doi:10.1371/journal.pone.0009879. ISSN 1932-6203.
- ↑ Aouizerat, Bradley E; Vittinghoff, Eric; Musone, Stacy L; Pawlikowska, Ludmila; Kwok, Pui-Yan; Olgin, Jeffrey E; Tseng, Zian H (2011). "GWAS for discovery and replication of genetic loci associated with sudden cardiac arrest in patients with coronary artery disease". BMC Cardiovascular Disorders. 11 (1). doi:10.1186/1471-2261-11-29. ISSN 1471-2261.
- ↑ Refaat, Marwan M.; Aouizerat, Bradley E.; Pullinger, Clive R.; Malloy, Mary; Kane, John; Tseng, Zian H. (2014). "Association of CASQ2 polymorphisms with sudden cardiac arrest and heart failure in patients with coronary artery disease". Heart Rhythm. 11 (4): 646–652. doi:10.1016/j.hrthm.2014.01.015. ISSN 1547-5271.