Roberto De Ponti, “Cryothermal Energy Ablation Of Cardiac Arrhythmias 2005:
State Of The Art”
cryoenergy are two-fold: 1) a direct cell injury and 2) a vascular mediated tissue injury.
14
The direct cellular injury is due to ice formation, which has different distribution
according to temperature reached during cooling. By cooling to mild temperature (0 to -20°C),
ice forms only extracellularly. Consequently, extracellular environment becomes hyperosmotic
and an intracellular to extracellular water shift occurs. This causes cellular shrinkage and damage
to membrane. Cooling to these temperature may result in cellular death, if the application is
enough prolonged. Using short applications with limited temperature, the effect produced on the
cell is reversible and cellular function recovers, although minimal cellular damage may be
produced. In the clinical use, the option of producing a functionally reversible lesion is quite
attractive to test the effect of cryoablation without producing a permanent lesion. Conversely, by
cooling down to -40°C and further, intracellular water freezes and formation of intracellular ice
results in major and irreversible disruption of organelles and cell membrane with cellular death.
Intracellular ice may propagate from one cell to another via intercellular channels.
The second mechanism underlying lesion formation by cryothermal energy delivery is a
vascular-mediated mechanism. In fact, the initial tissue response to cooling is vasoconstriction
with decreased blood flow. As tissue freezes, circulation ceases uniformly in the frozen tissue.
The uniformity of cell death in a lesion produced by cryothermal energy has suggested ischemic
necrosis as the main mechanism for tissue death, although it is impossible to distinguish the
tissue damage caused by this mechanism from the one produced by intracellular ice formation.
Upon re-warming, a hyperemic response is observed with increased vascular permeability and
edema formation. Other than producing increased permeability and edema, endothelial damage
results in platelet aggregation and micro-thrombus formation, with stagnation of
microcirculation in about 30-45 min.
Especially in the percutaneous closed chest cryoablation, the effect produced by energy
application is the result of a temperature gradient occurring at the electrode/tissue interface and
possibly influenced by different factors, such as contact or blood flow. At the interface, the
coldest area is the one adjacent to the catheter tip, where functional effects of energy delivery are
observed earlier. Conversely, the less cooled area is the one at the periphery of the cryolesion,
whose dimensions may also vary according to the duration of freezing. Due to limited (both in
time and temperature) cooling of outer limit of the lesion, reversible tissue damage is more likely
to occur in this area. As a consequence, the effects obtained late during cryothermal energy
application are likely to revert early upon re-warming and, therefore, any expected functional
modification induced by cryoenergy should occur early (usually within the first 30 s of the
application) in order to obtain a successful and permanent ablation of a given arrhythmogenic
substrate.
Cryothermal vs radiofrequency energy: differences and their clinical implications
In closed chest cryoablation, the effect of cryothermal energy application greatly depends
on the minimum temperature reached, the application duration and the temperature time
constant9. The latter value indicates the course of the descent of temperature to the target
temperature and a shorter value (expressed in seconds) identifies a more effective application.
Due to intrinsic characteristics of cryothermal energy at a fixed minimum temperature, the lesion
forms more slowly than the one produced by hyperthermic injury. This has two practical
implications. The first is that the application duration for cryoablation is significantly longer than
for radiofrequency energy and a lesion produced by cryothermal energy by a 4 mm tip 7 F
cryocatheter at -75°C for 240 s has a comparable depth to the one obtained by radiofrequency
energy applied in temperature control mode at 50 W, +70°C for 60 s10. Second, the longer
estimated time required to create a permanent lesion may be clinically useful to better modulate
the lesion formation in critical areas (i.e. close to the atrioventricular node-His bundle). In these
cases, if inadvertent modifications of conduction over the normal pathways is observed during
the application, immediate discontinuation of cryothermal energy application results in return to
Indian Pacing and Electrophysiology Journal (ISSN 0972-6292), 5(1): 12-24 (2005)