Unusual case of post-operative suicide left ventricle in a patient with dynamic LVOT obstruction.

Suicide left ventricle (SLV) is a well-documented complication after surgical or transcatheter aortic valve replacement. We present an unusual case of a patient who developed left ventricular outflow tract (LVOT) obstruction with a native aortic valve, resulting in SLV after routine non-cardiac surgery. A 45-year-old male presented to the emergency room with abdominal pain and was diagnosed with acute cholecystitis. The patient had a known medical history of severe left ventricular hypertrophy. The patient underwent an uncomplicated laparoscopic cholecystectomy. Post-operatively, he went into shock during weaning from anesthesia. He was started on norepinephrine followed by epinephrine and vasopressin, without much improvement. Increasing doses of vasopressors failed to improve the patient's hemodynamics. A presumptive diagnosis of SLV was made. This was secondary to hemodynamic collapse due to vasoplegia from anesthesia, worsening LVOT obstruction and subsequent right ventricular failure. Despite being in shock, the patient was taken off pressors and started on esmolol infusion to increase diastolic filling and epoprostenol to decrease the right ventricle strain by pulmonary vasodilation. The patient responded promptly to these measures. A repeat echocardiogram showed a significant improvement in right and left ventricular function. Learning objective: Suicide left ventricle (SLV) is commonly seen in patients post aortic valve replacement. It presents as shock which does not respond to pressors and instead is treated by beta-blockers. Our patient developed SLV pathophysiology despite having native aortic valve. He developed shock which did not improve with pressors but responded to esmolol. This emphasizes the importance of fluid management in patients with severe left ventricular outflow tract obstruction. It also gives a different perspective to managing shock in such patients who are not responding to pressors.

A hierarchical NGF signaling cascade controls Ret-dependent and Ret-independent events during development of nonpeptidergic DRG neurons.

NGF controls survival, differentiation, and target innervation of both peptidergic and nonpeptidergic DRG sensory neurons. The common receptor for GDNF family ligands, Ret, is highly expressed in nonpeptidergic neurons, but its function during development of these neurons is unclear. Here, we show that expression of Ret and its coreceptors GFRalpha1 and GFRalpha2 is dependent on NGF. GFR/Ret signaling, in turn, autoregulates expression of both GFRalpha1 and GFRalpha2 and promotes expression of TrpA1, MrgA1, MrgA3, and MrgB4, acquisition of normal neuronal size, axonal innervation of the epidermis, and postnatal extinction of the NGF receptor TrkA. Moreover, NGF controls expression of several other genes characteristic of nonpeptidergic neurons, such as TrpC3, TrpM8, MrgD, and the transcription factor Runx1, via a Ret-independent signaling pathway. These findings support a model in which NGF controls maturation of nonpeptidergic DRG neurons through a combination of GFR/Ret-dependent and -independent signaling pathways.

An evolving NGF-Hoxd1 signaling pathway mediates development of divergent neural circuits in vertebrates.

Species are endowed with unique sensory capabilities that are encoded by divergent neural circuits. One potential explanation for how divergent circuits have evolved is that conserved extrinsic signals are differentially interpreted by developing neurons of different species to yield unique patterns of axonal connections. Although nerve growth factor (NGF) controls survival, maturation and axonal projections of nociceptors of different vertebrates, whether the NGF signal is differentially transduced in different species to yield unique features of nociceptor circuits is unclear. We identified a species-specific signaling module induced by NGF and mediated by a rapidly evolving Hox transcription factor, Hoxd1. NGF promoted robust expression of Hoxd1 in mice, but not chickens, both in vivo and in vitro. Mice lacking Hoxd1 displayed altered nociceptor circuitry that resembles that normally found in chicks. Conversely, ectopic expression of Hoxd1 in developing chick nociceptors promoted a pattern of axonal projections reminiscent of the mouse. Thus, conserved growth factors control divergent neuronal transcriptional events that mediate interspecies differences in neural circuits and the behaviors that they control.

A convenient tool to profile patients for generalized cardiovascular disease risk in primary care.

The early identification of and intervention in patients with increased risk factors for generalized cardiovascular disease greatly reduces their long-term mortality from hard coronary artery disease (CAD) events and other related co-morbidities. Thus, a number of multivariate risk factor analyses based on large-scale population studies have led to various risk-scoring models aimed at screening for those at high risk for CAD. These assessment systems, by virtue of novel diagnostic markers and better population data, have become increasingly adept at accurately predicting CAD risk in individual patients. Nevertheless, their practical application in the setting of primary care has lagged, because of a reluctance of many primary care physicians to adopt these methods. An effective risk assessment system should not only encompass the risk for hard CAD events but also include risks for related co-morbid conditions, such as stroke and heart failure, and be simple and accurate enough to be efficiently used in primary care clinics. In conclusion, in an attempt to simplify 1 of the more effective risk assessment devices for generalized cardiovascular disease risk that meets all these requirements, the investigators strongly support the model proposed by D'Agostino and colleagues and provide here a commentary on its utility in identifying patients at high risk for cardiovascular disease.

Serum response factor mediates NGF-dependent target innervation by embryonic DRG sensory neurons.

Serum response factor (SRF) is a prototypic transcription factor that mediates stimulus-dependent gene expression. Here, we show that SRF mediates NGF signaling, axonal growth, branching, and target innervation by embryonic DRG sensory neurons. Conditional deletion of the murine SRF gene in DRGs results in no deficits in neuronal viability or differentiation but causes defects in extension and arborization of peripheral axonal projections in the target field in vivo, similar to the target innervation defects observed in mice lacking NGF. Moreover, SRF is both necessary and sufficient for NGF-dependent axonal outgrowth in vitro, and NGF regulates SRF-dependent gene expression and axonal outgrowth through activation of both MEK/ERK and MAL signaling pathways. These findings show that SRF is a major effector of both MEK/ERK and MAL signaling by NGF and that SRF is a key mediator of NGF-dependent target innervation by embryonic sensory neurons.