Counter Intuitive Relations Between in vivo RF Lesion Size, Power, and Tip Temperature

Background: Radiofrequency (RF) lesion size in vitro is positively correlated with applied power and catheter tip temperature. However, the relation between RF lesion size, power, and tip temperature in vivo remains unclear. We hypothesized that due to flow, anatomy and tip contact effects in vivo, increased tip temperature would be inversely related to applied power and RF lesion size. Methods: RF lesions were created on the endocardium of 16 pigs using 5, 6, and 7 Fr catheters. The ablation generator was set to achieve a temperature of 70°C. RF lesions were created in different regions of the heart so as to encompass a wide range of blood flow and catheter movement conditions. RF lesions were measured acutely (DIMEN, mm) and correlated with average power applied (POWER, W), and average tip temperature (TEMP, °C). The POWER and TEMP relation was also examined. Results: For TEMPs below 55°C, the power output from the generator was typically maximized at 50 W. At TEMPs above 55°C, POWER decreased exponentially with increasing TEMP {POWER = 50 – exp(-((41-TEMP)/7)), r = 0.98, p < 0.05}. Further, DIMEN tended to be inversely related to TEMP (Slope: –0.07 ± 0.04, r = –0.15, p = 0.07); but, was positively related to POWER (Slope: 0.04 ± 0.02, r = 0.23, p < 0.05). These relations varied by tip size and estimated local blood flow characteristics. Conclusion: In vivo, variable tissue contact and flow yield DIMEN-POWER-TEMP relations opposite to those found in vitro. These counterintuitive results suggest that maximum in vivo RF lesion size is achieved when power is maximized at tip temperatures between 50 and 60°C.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.