Receptor-Induced Dilatation in the Systemic and Intrarenal Adaptation to Pregnancy in Rats

Normal pregnancy is associated with systemic and intrarenal vasodilatation resulting in an increased glomerular filtration rate. This adaptive response occurs in spite of elevated circulating levels of angiotensin II (Ang II). In the present study, we evaluated the potential mechanisms responsible for this adaptation. The reactivity of the mesangial cells (MCs) cultured from 14-day-pregnant rats to Ang II was measured through changes in the intracellular calcium concentration ([Cai]). The expression levels of inducible nitric oxide synthase (iNOS), the Ang II-induced vasodilatation receptor AT2, and the relaxin (LGR7) receptor were evaluated in cultured MCs and in the aorta, renal artery and kidney cortex by real time-PCR. The intrarenal distribution of LGR7 was further analyzed by immunohistochemistry. The MCs displayed a relative insensitivity to Ang II, which was paralleled by an impressive increase in the expression level of iNOS, AT2 and LGR7. These results suggest that the MCs also adapt to the pregnancy, thereby contributing to the maintenance of the glomerular surface area even in the presence of high levels of Ang II. The mRNA expression levels of AT2 and LGR7 also increased in the aorta, renal artery and kidney of the pregnant animals, whereas the expression of the AT1 did not significantly change. This further suggests a role of these vasodilatation-induced receptors in the systemic and intrarenal adaptation during pregnancy. LGR7 was localized in the glomeruli and on the apical membrane of the tubular cells, with stronger labeling in the kidneys of pregnant rats. These results suggest a role of iNOS, AT2, and LGR7 in the systemic vasodilatation and intrarenal adaptation to pregnancy and also suggest a pivotal role for relaxin in the tubular function during gestation

Significance of intraoperative testing in right-sided implantable cardioverter-defibrillators

BACKGROUND: Implantation of implantable cardioverter-defibrillators (ICD) from the left pectoral region is the standard therapeutical method. Increasing numbers of system revisions due to lead dysfunction and infections will consecutively increase the numbers of right-sided implantations. The reliability of devices implanted on the right pectoral side remains controversially discussed, and the question of testing these devices remains unanswered. METHODS: In a prospectively designed study all 870 patients (60.0 ± 14  years, 689 male) who were treated with a first ICD from July 2005 until May 2012 and tested intraoperatively according to the testing protocol were analyzed. The indication for implantation was primary prophylactic in 71.5%. Underlying diseases included ischemic cardiomyopathy (50%), dilative cardiomyopathy (37%), and others (13%). Mean ejection faction was 27 ± 12%. Implantation site was right in 4.5% and left in 95.5%. RESULTS: Five patients supplied with right-sided ICD (13%, p = 0.02 as compared to left-sided) failed initial intraoperative testing with 21 J. 3 patients were male. The age of the patients failing intraoperative testing with right-sided devices appeared higher than of patients with left-sided devices (p = 0.07). The ejection fraction was 28 ± 8%. All patients reached a sufficient DFT ≤ 21 J after corrective procedures. CONCLUSION: Implantation of ICDs on the right side results in significantly higher failure rate of successful termination of intraoperatively induced ventricular fibrillation. The data of our study suggest the necessity of intraoperative ICD testing in right-sided implanted ICDs

Catheter ablation of ventricular tachycardia.

Ventricular tachycardia (VT) due to reentry in and around regions of ventricular scar from an old myocardial infarction or cardiomyopathic process is often a difficult management problem. Radiofrequency catheter ablation is an option for controlling frequent VT episodes. Patient and VT characteristics determine the mapping and ablation approach and efficacy. In patients with a VT that is hemodynamically tolerated to allow mapping, prevention of recurrent VT is achieved in 54% to 66% of patients with a procedure related mortality of 1% to 2.7%. Multiple morphologies of monomorphic VT and circuits that are located deep to the endocardium are common problems that reduce efficacy. Mapping to identify target regions for ablation can be difficult if VT is rapid and not tolerated, or not inducible. Ablation of these "unmappable VTs" by designing ablation lines or areas based on the characteristics of the scar as assessed during sinus rhythm, and using approaches to assess global activation from a limited number of beats has been shown to be feasible. Ablation of multiple VTs, epicardial VTs, and poorly tolerated VTs are feasible. Future studies defining efficacy and risks are needed