Driving With Cardiovascular Disease: The Impact of Implantable Cardioverter Defibrillators on Driver Safety

Cardiovascular disease (CVD) is the leading cause of death in the United States. With America’s workforce rapidly aging, more attention is being placed on CVD and its treatment among employees in safety sensitive occupations, such as the transportation industry. Implantable cardioverter defibrillators (ICDs) are increasingly being used to treat certain cardiovascular conditions, but despite the fact that they are effective in preventing sudden death from cardiac arrhythmia, there is concern about allowing individuals with an ICD to drive. A systematic review and meta-analysis was conducted to examine the health and safety impacts ICDs on driving. We considered data pertaining to four outcomes among individuals with an ICD: crash rate, the occurrence of sudden death while driving, the occurrence of syncope while driving, and the occurrence of at least one shock from their ICD while driving. Currently, the impact of an ICD on driver safety cannot be determined. Our assessments of the evidence pertaining to crash rates and sudden incapacitation while driving were inconclusive. Our results do indicate, however, that some individuals with an ICD will experience an inappropriate ICD discharge while driving (Strength of Evidence Rating: Strong). Experiencing such a discharge while driving is a potential hazard to driver safety. Quantitative assessment of the available data suggests that approximately 6.3% (95% CI: 4.7%-8.4%) of all individuals with an ICD who drive will experience a discharge while driving. These findings have potential implications for regulatory agencies with responsibility for road safety; particularly those agencies that regulate safety sensitive industries

Characterization of novel splice variants of LGR7 and LGR8 reveals that receptor signaling is mediated by their unique low density lipoprotein class A modules

The relaxin and insulin-like peptide 3 receptors, LGR7 and LGR8, respectively, are unique members of the leucine-rich repeat-containing G-protein-coupled receptor (LGR) family, because they possess an N-terminal motif with homology to the low density lipoprotein class A (LDLa) modules. By characterizing several LGR7 and LGR8 splice variants, we have revealed that the LDLa module directs ligand-activated cAMP signaling. The LGR8-short variant encodes an LGR8 receptor lacking the LDLa module, whereas LGR7-truncate, LGR7-truncate-2, and LGR7-truncate-3 all encode truncated secreted proteins retaining the LGR7 LDLa module. LGR8-short and an engineered LGR7 variant missing its LDLa module, LGR7-short, bound to their respective ligands with high affinity but lost their ability to signal via stimulation of intracellular cAMP accumulation. Conversely, secreted LGR7-truncate protein with the LDLa module was able to block relaxin-induced LGR7 cAMP signaling and did so without compromising the ability of LGR7 to bind to relaxin or be expressed on the cell membrane. Although the LDLa module of LGR7 was N-glycosylated at position Asn-14, an LGR7 N14Q mutant retained relaxin binding affinity and cAMP signaling, implying that glycosylation is not essential for optimal LDLa function. Using real-time PCR, the expression of mouse LGR7-truncate was detected to be high in, and specific to, the uterus of pregnant mice. The differential expression and evolutionary conservation of LGR7-truncate further suggests that it may also play an important role in vivo. This study highlights the essential role of the LDLa module in LGR7 and LGR8 function and introduces a novel model of GPCR regulation.Biochemistry & Molecular BiologySCI(E)EI75ARTICLE4634942-3495428