Acute hypoxic pulmonary vasoconstriction (HPV) and the development of chronic hypoxic pulmonary hypertension (PHTN) are cardinal features of the pulmonary circulation that differentiate this vascular bed from the systemic circulation. Nitric oxide (NO) produced by pulmonary vascular endothelium is thought to modulate pulmonary vascular responses to a variety of vasoconstrictor stimuli, including hypoxia (1-8). However, despite intensive investigation over the past decade, the role of endotheliumderived nitric oxide (EDNO) in modulating tone and structural remodeling of the chronically hypoxic pulmonary circulation remains controversial (9-13).Simultaneous pharmacologic inhibition of all three isoforms of nitric oxide synthase (NOS) results in acutely increased pulmonary vascular resistance and augmented HPV (1,(14)(15). However, chronic NOS inhibition does not result in PHTN and does not augment the development of hypoxic PHTN (16). These results present a paradox: If EDNO modulates acute HPV, why is pharmacologic inhibition of NOS not associated with either normoxic PHTN or accentuated chronic hypoxic PHTN? One possibility is that HPV is redundantly modulated, and the loss of endothelial nitric oxide synthase (eNOS)-derived NO alone is not sufficient to produce PHTN. Alternatively, the experimental approaches taken in the past to test this question may have been inadequate because of nonspecific effects of pharmacologic inhibitors of NOS, difficulty maintaining NOS inhibition, or confounding effects of simultaneous inhibition of all three isoforms of NOS.Mice with targeted disruption of eNOS (eNOS -/-mice) have recently been constructed and the vascular phenotype explored (17,18). Systemic hypertension and augmented structural remodeling after vascular injury have been reported (19,20). Steudel et al. (21) investigated the pulmonary vascular phenotype of eNOS -/-mice, finding increased pulmonary vascular resistance, but only minimal PHTN, and no evidence of pulmonary vascular remodeling. More recently, this group also found enhanced chronic hypoxic PHTN in eNOS-null mice (22). These studies were limited, however, to mice exposed to severe hypoxia (FiO 2 = 11%) and studied under general anesthesia with hyperoxic (FiO 2 = 80%) mechanical ven- Acute hypoxic vasoconstriction and development of hypoxic pulmonary hypertension (PHTN) are unique properties of the pulmonary circulation. The pulmonary endothelium produces vasoactive factors, including nitric oxide (NO), that modify these phenomena. We tested the hypothesis that NO produced by endothelial nitric oxide synthase (eNOS) modulates pulmonary vascular responses to hypoxia using mice with targeted disruption of the eNOS gene (eNOS -/-). Marked PHTN was found in eNOS -/-mice raised in mild hypoxia when compared with either controls or eNOS -/-mice raised in conditions simulating sea level. We found an approximate twofold increase in partially and fully muscularized distal pulmonary arteries in eNOS -/-mice compared with controls. Consistent with vasoconstriction...

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ICD Shocks in Cardiac Sarcoidosis. Background: An implantable cardioverter defibrillator (ICD)is indicated for some patients with cardiac sarcoidosis (CS) for prevention of sudden death. However, there are little data regarding the event rates of ICD therapies in these patients. We sought to identify the incidence and characteristics of ICD therapies in this patient population.Methods: We performed a cohort study of patients with ICDs at 3 institutions. Cases were those patients with CS and an ICD implanted for primary or secondary prevention of sudden death. Additionally, we included a comparison with historical controls of ICD therapy rates reported in clinical trials evaluating the ICD for primary and secondary prevention of sudden death.Results ]).Conclusions: In our cohort of patients with CS and ICDs, almost one-third receive appropriate therapies. This may be due to a myocardial inflammatory process leading to increased triggered activity and subsequent scarring leading to reentrant tachyarrhythmias. Adjusted predictors of ICD therapies in this population include left or right ventricular dysfunction. (J Cardiovasc Electrophysiol, Vol. 23, pp. 925-929, September 2012) cardiac sarcoid, cardiomyopathy, heart failure, implantable cardioverter defibrillator, ventricular tachycardia

Our study highlights the dilemma that sarcoid experts face in their approach to cardiac sarcoidosis. It also highlights the lack of agreement among sarcoid experts on key aspects of diagnosis and management and stresses the importance of collaborative efforts to investigate the best strategies for screening for and management of cardiac sarcoidosis.