Cardiac levels of NOS1AP RNA from right ventricular tissue recovered during lead extraction

Abstract

There is a scarcity of cardiac tissue available for research. (1) To investigate the feasibility of obtaining myocardial tissue from extracted pacemaker and defibrillator leads for gene expression analysis and (2) to examine the nitric oxide 1 adaptor protein (NOS1AP) RNA expression as a function of patient genotype. Seventeen patients (age = 56 ± 20 years; 12 men; 5 pacemakers; 12 defibrillators) undergoing lead extractions for standard indications (5 device erosion; 1 vascular occlusion; 11 lead malfunction or recall) were genotyped for 2 NOS1AP single nucleotide polymorphisms-rs10494366 (T to G) and rs10918594 (C to G)-and had RNA levels measured by real-time polymerase chain reaction for collagen I, troponin I, Ca(v)1.2, Kv4.3, HERG, KvLQT1, connexin 43, NOS1AP, and sodium-calcium exchanger. Ventricular tissue obtained from 3 failing hearts at transplantation served as reference. A high ratio of cardiac troponin I/collagen I RNA identified 9 of the 17 patient samples (muscle rich), in which the gene expression profile was similar to that of the reference ventricular samples and significantly different (P < .003) from the expression profile of samples with a low troponin I/collagen ratio (muscle poor). TT and CC polymorphisms were associated with significantly lower NOS1AP RNA levels (P < .01 compared with the GG genotype). Performing gene expression analyses on right ventricular tissue samples extracted with pacemaker and defibrillator leads is feasible. A significant number of samples contain cardiomyocytes that express troponin I and ion channels at levels comparable to those seen in explanted hearts. Decreased NOS1AP expression in rs10494366 TT and rs10918594 CC homozygotes may underlie shorter repolarization times.