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11.1 Electroporation of the Cell Membranes
Defibrillation and electrocution trauma all expose the heart cells to a potential gradient that increases the transmembrane potential Vm. At sufficiently high levels, the intensity of the increase in transmembrane potential can result in pathological changes in cell permeability. This is termed electroporation or electropermeabilisation. The result is a disruption of the cell membrane with an alteration to the transmembrane ion concentration resulting in depressed or unexcitable tissue [Tung L et al. 1994]
Electroporation can be identified by a step-wise increase in membrane conductance. Work on isolated frog hearts has shown that rectangular pulses of 1 Volt of 0.2 to 0.4 msec duration can permealise the cell membrane [Tovar O et al. 1991]. Of greater interest was the fact that pulses of 0.5 Volts and 1 to 10 msec duration can permealise the cell membrane for periods of time ranging from seconds to minutes and possibly longer. The subsequent effects of an alteration in the cellular ionic composition with depressed or unexcitable tissue may be a precursor for subsequent arrhythmogenesis.
Other authors have suggested that electroporation may actually be of benefit in achieving defibrillation. Krassowska has shown that electroporation does not impair the ability of the shock to reach the distant myocardium and may actually aid defibrillation by reducing nonuniformity of electrical conditions between regions close to the electrodes and in the bulk of tissue [Krassowska W. 1995].
The question of how electric fields terminate life-threatening arrhythmias remains largely unanswered. Irrespective of the theories it is likely that successful defibrillation is related to shock induced changes in the transmembrane potential. The problems however remain that in the setting of strong electric fields, reproducible and accurate measurements of Vm using a microelectrode become difficult. This has lead to the estimation of Vm from mathematical models. These models relating to defibrillation tend to use the biodomain model in which the effects of shocks on the transmembrane potential distribution are investigated in a two-dimensional rectangular sheet of cardiac muscle modeled as a biodomain with unequal anisotropy ratios [Aguel F et al. 1999]. Another model is the one-dimensional variation - the core conductor model. This model consists of the core conductor equation for a one-dimensional fibre, where excitability is represented by the Luo-Rudy dynamic model and electroporation is described by membrane conductance that increases exponentially with Vm squared [DeBruin KA et al. 1998].
These models are useful at predicting the transmembrane potential in physiological and subthreshold shocks, but when used to predict the Vm at threshold shocks they predict values that exceed the physiological range for the cell membrane. One example is that of a cardiac fibre between two electrodes exposed to a 25v/cm external field (well within the range seen in defibrillation) the core conductor model gives a Vm of 870 mV. Experimental work has shown that electroporation of the membrane occurs with 5 millisecond monophasic shocks at 500mV. Additional work has shown that there is an arrest in the development of the Vm in cells by the formation of pores adjacent to the electrodes that shunt part of the current directly into the extracellular space. Therefore, only a fraction of the deliverable current gives rise to Vm [Krassowska W et al. 1995].
11.2 Myocardial Injury with Defibrillation
Warner and co-workers showed that following 10 consecutive 400-Joule shocks in dogs, histological examination revealed myocardial necrosis in most animals. The lesions were characterised by sharply localised areas of muscle necrosis that progressed to fibrous scars. Mineralisation of damaged muscle and florid proliferation of large mononuclear cells were striking features of the lesions [Warner ED et al. 1975]. The characteristic features seen on electron microscopy were a marked dehiscence of the intercalated disks between the damaged myocytes [Doherty PW et al. 1979]. The threshold for significant injury was approximately 30 Joules for shocks applied directly to the heart.
Tacker showed that in dogs receiving high intensity multiple shocks that there was gross and microscopic evidence of cardiac damage. Lesions were observed in both right and left ventricular free walls and were sometimes transmural in extent. ECG analysis of the records from the dogs receiving multiple, high-intensity shocks showed second and third degree A-V block, ventricular ectopic beats, ventricular tachycardia, S-T segment changes and T-wave inversion. Although multiple, high-energy, high-current defibrillation shocks produce permanent cardiac damage in dogs, threshold shocks do not produce morphologic changes [Tacker WA et al. 1978].
In two recent studies investigators have looked at markers of heart damage including CKMB and Troponin T and found that following DC shock to terminate atrial arrhythmias that no rise in markers of cardiac damage was seen. There was a small rise in CK alone but this was elevated possibly due to skeletal muscle injury [Rao AC et al. 1998, Greaves K et al. 1998]. In an earlier study the energy threshold value for enzyme release was found to be around 4 J/kg for creatine kinase and 6 J/kg for creatine kinase MB isoenzyme when a DC shock was used to terminate atrial arrhythmias [Gheno G et al. 1996].
Other investigators have looked at the effects of antiarrhythmic drugs on cardiac damage following defibrillation. Patton was able to show that less damage occurred when measured by ECG findings, CK and histology if multiple low-energy shocks were given rather than high energy shocks of similar total energy. He also demonstrated that such damage could be partially ameliorated by preadministration of the calcium-channel blocker verapamil [Patton JN et al. 1984].
The development of biphasic and other more efficient waveforms with specific ratios of positive and negative components requiring less energy for successful defibrillation than monophasic is the dilemma that the more efficient waveforms might actually be more damaging. This has been assessed by Osswald, who demonstrated, using monophasic and biphasic waveforms in a canine model that the more efficient biphasic waveforms where actually associated with a less injurious effect on myocardial oxidative metabolism and haemodynamic performance than monophasic waveforms [Osswald S et al. 1994].
VanFleet and others looked at the Cardiac damage in dogs with chronically implanted cardioverter defibrillator devices. They found that the defibrillating lead induced mild cardiac alterations with myocardial necrosis and calcification concentrated in the ventricular septum and the RV free wall adjacent to the ventricular electrodes. The mean energy used was 17.6 Joules and the dogs had a mean of 21.3 shocks each [VanFleet JF et al. 1983].
