Stimulators and Activators of Soluble Guanylate Cyclase: Review and Potential Therapeutic Indications

The heme-protein soluble guanylyl cyclase (sGC) is the intracellular receptor for nitric oxide (NO). sGC is a heterodimeric enzyme with α and β subunits and contains a heme moiety essential for binding of NO and activation of the enzyme. Stimulation of sGC mediates physiologic responses including smooth muscle relaxation, inhibition of inflammation, and thrombosis. In pathophysiologic states, NO formation and bioavailability can be impaired by oxidative stress and that tolerance to NO donors develops with continuous use. Two classes of compounds have been developed that can directly activate sGC and increase cGMP formation in pathophysiologic conditions when NO formation and bioavailability are impaired or when NO tolerance has developed. In this report, we review current information on the pharmacology of heme-dependent stimulators and heme-independent activators of sGC in animal and in early clinical studies and the potential role these compounds may have in the management of cardiovascular disease

A dose-response analysis of crystalloid administration during esophageal resection

Objectives The purpose of this retrospective study was to investigate the role of intraoperative crystalloid administration on postoperative hospital length of stay (phLOS) and on the incidence of previously reported adverse events in 100 consecutive patients who underwent esophageal resection. Methods The role of previously reported patient demographics, clinical characteristics, and intraoperative crystalloid administration on the duration of phLOS underwent statistical screening criteria for multivariable analysis, including the use of an instrumental variable to measure the role of unmeasured confounders on phLOS. Tests to assess the likelihood of causality also were performed. Results When the volumes of intraoperative crystalloids were expressed as dose-response relationships to outcomes, progressive decreases in phLOS, variances in phLOS, and the incidences of unplanned surgical intensive care unit admission, postoperative pneumonia, respiratory failure requiring orotracheal intubation, nonsinus cardiac dysrhythmias, and anastomotic leak were observed. Intraoperative transfusion of packed red blood cells greatly increased the duration of phLOS, which was not associated with estimated blood loss, length of surgical operation, or unplanned surgical intensive care unit admission. Instrumental variable analysis revealed no significant influence on phLOS. Causality tests supported the role of intraoperative crystalloid administration in reducing the duration and variance of phLOS. Conclusions A dose-response relationship was clinically observed between intraoperative crystalloid administration and the duration and variance of phLOS and with commonly reported postoperative adverse events. Intraoperative transfusion of packed red blood cells greatly increased phLOS that was not associated with the severity of the surgical operation. Instrumental variables and tests for causality further supported the role of intraoperative crystalloid administration in reducing the duration and variance of phLOS

Use of biomarkers in the prediction of culture-proven infection in the surgical intensive care unit

Purpose: The purpose of this study was to prospectively analyze the predictive role of classic predictors for suspected infection (temperature, WBC and derivatives) with two biomarkers, procalcitonin and lactate, on the incidence of culture-proven infection in the surgical intensive care unit (SICU).Materials and methods: One hundred forty-six consecutive patients admitted for suspected infection had admission and 12-h procalcitonin values, admission and every 6-h lactate values for 24 h, and admission temperature, leukocyte count, lymphocyte count and percentage measured and analyzed in this study.Results: Peak (highest measured valu