Successful Slow Pathway Ablation in a Patient with Atrioventricular Nodal Reentrant Tachycardia Having a Proximal Common Pathway

Radiofrequency catheter ablation was attempted in a patient with atrioventricular nodal reentrant tachycardia (AVNRT). AVNRT was easily inducible but an intermittent loss of the atrial activation was observed during AVNRT suggesting the presence of a proximal common pathway. During sinus rhythm, a relatively delayed activation that was compatible with a slow potential, was recorded anterior to the ostium of coronary sinus, and radiofrequency catheter ablation application (20 watts) to the site induced junction tachycardia. After an additional radiofrequency catheter ablation application to close the site, AVNRT became noninducible without deterioration of atrioventricular conduction through a fast pathway. This is the first case in which radiofrequency catheter ablation application to the slow potential recording site has been successful, even in AVNRT having a proximal common pathway.     

APC, K-ras codon 12 mutations and p53 gene expression in carcinoma and adenoma of the gall-bladder suggest two genetic pathways in gall-bladder carcinogenesis

Currant histopathoiogical evidence suggests that gall-bladder cancer has two main morphological pathways for Its development: de novo ( ab Inltlo ) origin and adenoma-carcinoma sequence. In order to investigate the genetic difference between them, APC mutations were examined by RNase protection analysis, K-ras mutations by nested porymerase chain reaction-restriction fragment length polymorphism analysis, and p53 gene overexpression by immunoriisto-chemical analysis in both tumors and benign lesions of the gall-bladder. Overexpression of the p53 gene was detected in 105 of 164 (64%) de novo carcinomas regardless of size and depth of Invasion, but not in 16 tumors of carcinoma-ln-pyloric-gland-type adenoma, or In 51 adenomas (47 pyloric gland-type and 4 Intestinal-type). K-ras codon 12 mutation was detected in 4 of 40 (10%) de novo carcinomas, ail four being associated with p53 gene overexpression, but not in 12 tumors of carcinoma in adenoma or 16 adenomas (14 pyloric gland-type and 2 intestinal-type). APC mutation was not found in 16 de novo carcinomas or the one pyloric gland-type adenoma examined. These results suggest that there are two distinct genetic pathways in gall-bladder carcinogenesis; that is, de novo carcinoma develops from a predominant p53 alteration with low K-ras mutation, and carclnoma-in-pylortc-gland-type adenoma develops from p53 -, K-ras -, and APC -gene-unrelated, as yet unknown, alteration.     

Parasympathetic Inhibition of Sympathetic Effects on Pacemaker Location and Rate in Hearts of Anesthetized Dogs

INTRODUCTION: The site of impulse origin in the right atrium generally is considered to be a single static locus within the sinoatrial (SA) node. Previous investigators showed that the pacemaker site may shift due to changes in sympathetic or parasympathetic neural activity. We investigated the interactions between sympathetic and parasympathetic influences on the site of impulse initiation in the right atrium in anesthetized dogs. METHODS AND RESULTS: We determined the site of impulse initiation and the spread of excitation over the anterior and posterior regions of the right atrium by a matrix of 48 unipolar recording electrodes. We assessed the spread of excitation at 3-msec intervals by constructing isochronal activation sequence maps. Sympathetic stimulation increased the frequency of atrial excitation (i.e., the heart rate), but also shifted the earliest activation region (EAR) from a locus in the SA node to a locus in the superior vena cava (the superior pacemaker site). Vagus stimulation decreased the heart rate and shifted the EAR to a lower site in the SA node or a site in the inferior right atrium along the sulcus terminalis (the inferior pacemaker site). A short period of vagus stimulation during a more prolonged sympathetic stimulation elicited a larger decrease in rate than did vagus stimulation alone and shifted the EAR from the superior site to the SA node or to the inferior site. After atropine, combined stimulation shifted the EAR to the superior site, but propranolol did not change EAR location. CONCLUSION: Our results suggest that parasympathetic activity predominates over sympathetic activity not only on heart rate, but also on the location of the EAR in the anesthetized dog.