Citations

BackgroundSystemic hypertension is a common characteristic in acute heart failure (HF). This increasingly recognized phenotype is commonly associated with renal dysfunction and there is an unmet need for renal enhancing therapies. In a canine model ofHFand acute vasoconstrictive hypertension we characterized and compared the cardiorenal actions ofM‐atrial natriuretic peptide (M‐ANP), a novel particulate guanylyl cyclase (pGC) activator, and nitroglycerin, a soluble guanylyl cyclase (sGC) activator.Methods and ResultsHFwas induced by rapid RV pacing (180 beats per minute) for 10 days. On day 11, hypertension was induced by continuous angiotensin II infusion. We characterized the cardiorenal and humoral actions prior to, during, and following intravenousM‐ANP(n=7), nitroglycerin (n=7), and vehicle (n=7) infusion. Mean arterial pressure (MAP) was reduced byM‐ANP(139±4 to 118±3 mm Hg,P<0.05) and nitroglycerin (137±3 to 116±4 mm Hg,P<0.05); similar findings were recorded for pulmonary wedge pressure (PCWP) withM‐ANP(12±2 to 6±2 mm Hg,P<0.05) and nitroglycerin (12±1 to 6±1 mm Hg,P<0.05).M‐ANPenhanced renal function with significant increases (P<0.05) in glomerular filtration rate (38±4 to 53±5 mL/min), renal blood flow (132±18 to 236±23 mL/min), and natriuresis (11±4 to 689±37 mEq/min) and also inhibited aldosterone activation (32±3 to 23±2 ng/dL,P<0.05), whereas nitroglycerin had no significant (P>0.05) effects on these renal parameters or aldosterone activation.ConclusionsOur results advance the differential cardiorenal actions ofpGC(M‐ANP) andsGC(nitroglycerin) mediatedcGMPactivation. These distinct renal and aldosterone modulating actions makeM‐ANPan attractive therapeutic forHFwith concomitant hypertension, where renal protection is a key therapeutic goal.

The detection of serum free light (FLC) is useful in the diagnosis of several hematological diseases. The role and biological relevance of monoclonal or polyclonal FLC elevations in predicting long‐term outcome in diffuse large B‐cell lymphoma (DLBCL) is unknown. We determined the relationship of the type of FLC elevations to outcome, tumor genotype, and pattern of serum cytokine elevations in 276 patients with untreated DLBCL. Elevated FLC was an adverse prognostic factor through 6 years of follow‐up (monoclonal, Event free survival (EFS) HR = 3.56, 95% CI: 1.88–6.76, P <0.0001; polyclonal, EFS HR = 2.56, 95% CI: 1.50–4.38, P = 0.0006). About 73% of DLBCL tumors with monoclonal FLC elevations were activated B‐cell type (ABC) versus 33% from patients with normal FLC. Only ABC‐DLBCL lines secreted kappa FLC in vitro and this secretion could be inhibited by the NF‐κB inhibitor bortezomib. Patients with monoclonal FLC had significantly (all P <0.001) increased serum levels of IL‐12, sIL‐2Rα, IL‐1R, and IP‐10. Patients with polyclonal elevations of FLC had higher levels of IL‐6 (P = 0.033), IL‐8 (P =0.025), sIL2Rα (P = 0.011), and IL‐1R1 (P = 0.041). The combination of elevated FLC and a CXC superfamily chemokine IP‐10 predicted a particularly inferior outcome characterized by late relapse. These increased abnormal FLC and cytokines are potentially useful biomarkers for prognosis and selecting agents for untreated DLBCL. Am. J. Hematol. 89:417–422, 2014. © 2014 Wiley Periodicals, Inc.

The acute ischemic strokes amenable to intraarterial therapy probably number no more than 20,000 per year in the United States. The future demand for intraarterial reperfusion techniques may change, but the fraction of patients who require intraarterial thrombolysis is currently rather low, and the number of neurointerventionists is adequate. Each hospital caring for patients with acute stroke will need to determine its own demand for intraarterial therapy and employ an adequate supply of qualified neurointerventionists available to meet demand. Comprehensive stroke centers are now being designated and hopefully will foster a rational, regionalized approach to the delivery of endovascular therapies for stroke.