Yotaro Shinozawa

Regulation of renal function in thermal injury.

Hypovolemia, low cardiac output, and systemic vasoconstriction are major etiologic factors in acute renal failure occurring in the early postburn period, and elevated levels of stress-related hormones (catecholamines, angiotensin, aldosterone, and vasopressin) are implicated in the mechanism. By counteracting the effects of the hormones, atrial natriuretic polypeptide (ANP) regulates the renal response to burns. ANP was elevated after burns, protecting the kidneys by increasing renal blood flow and urine output. In pulmonary acid injury, increased ANP levels were associated with natriuresis which was reduced by administration of anti-ANP serum. Exogenous ANP given to dogs under constant norepinephrine infusion resulted in improvement of hemodynamic and renal parameters. To prevent tubular damage due to hemoglobinuria, a haptoglobin preparation is administered to patients with extensive third-degree burns. With sufficient fluid replacement, these new treatments will reduce the incidence of acute renal failure in the early postburn period.

Induction of lipocalin-type prostaglandin D synthase in mouse heart under hypoxemia

Hypoxemia is a common manifestation of various disorders and generates pressure overload to the heart. Here we analyzed the expression of lipocalin-type prostaglandin D synthase (L-PGDS) in the heart of C57BL/6 mice kept under normobaric hypoxia (10% O2) that generates hemodynamic stress. Northern and Western blot analyses revealed that the expression levels of L-PGDS mRNA and protein were significantly increased (> twofold) after 14 days of hypoxia, compared to the mice kept under normoxia. Immunohistochemical analysis indicated that L-PGDS was increased in the myocardium of auricles and ventricles and the pulmonary venous myocardium at 28 days of hypoxia. Moreover, using C57BL/6 mice lacking heme oxygenase-2 (HO-2(-/-)), a model of chronic hypoxemia, we showed that the expression level of L-PGDS protein was twofold higher in the heart than that of wild-type mouse. L-PGDS expression is induced in the myocardium under hypoxemia, which may reflect the adaptation to the hemodynamic stress.

Correlation of Glomerular Permeability, Endothelial Injury, and Postoperative Multiple Organ Dysfunction

PurposeTo determine whether the degree of microalbuminuria correlates with the extent of endothelial cell injury, the severity of illness, and the magnitude of multiple organ dysfunction in patients who undergo emergency surgery.MethodsWe measured the urinary albumin : creatinine ratio (ACR) within 24 h after surgery in 31 patients and examined its relationship with various clinical measurements.ResultsThe ACR increased during the first 24 h postoperatively. The log ACR correlated with the serum thrombomodulin concentration measured on the same day, but not with the level of plasma von Willebrand factor antigen. The increase in the log ACR correlated with the acute physiology and chronic health evaluation score (APACHE III), the simplified acute physiology score, the multiple organ dysfunction score, and the score of sequential organ failure assessment (SOFA) calculated on the same day, and the blood volume lost during the operation. The log ACR did not correlate with the white blood cell count or the serum C-reactive protein measured at the same time. The log ACR correlated with SOFA on postoperative days 3, 7, and 10, and mortality increased in accordance with the increase in log ACR.ConclusionsThe urinary ACR correlated with the extent of endothelial cell injury, the severity of illness, and the magnitude of multiple organ dysfunction.

Hypoxemia induces expression of heme oxygenase-1 and heme oxygenase-2 proteins in the mouse myocardium

Heme oxygenase (HO) catalyzes oxidative breakdown of heme, and constitutes two isozymes, HO-1 and HO-2. Here, we explored the tissue-specific regulation of expression of HO-1 and HO-2 under hypoxemia. There was no significant change in the overall expression levels of HO-1 and HO-2 mRNAs and proteins in the lung during adaptation of C57BL/6 mice to normobaric hypoxia (10% O(2)). However, immunohistochemical analysis revealed the increased expression of HO-1 and HO-2 proteins after 28 days of normobaric hypoxia in the pulmonary venous myocardium that is the extension of the left atrial myocardium into pulmonary venous walls. Moreover, the expression of HO-2 protein was increased in the sub-endocardial myocardium of ventricles under hypoxia, while HO-1 protein level was increased in the full-thickness walls. Thus, hypoxemia induces expression of both HO-1 and HO-2 proteins in the myocardium. Using C57BL/6 mice lacking HO-2 (HO-2(-/-)), which manifest chronic hypoxemia, we also showed that the HO-1 protein level in the lung was similar between HO-2(-/-) mice and wild-type mice. Unexpectedly, HO-1 protein level was lower by 35% in the HO-2(-/-) mouse liver than the wild-type liver. These results indicate that the expression of HO-1 protein is regulated in a tissue-specific manner under hypoxemia.

Incidence and Characteristics of Ventricular Fibrillation in Bystander-witnessed Out-of-hospital Cardiac Arrest with Cardiac Etiology in the City of Sendai, Japan

Ventricular fibrillation (VF) in out‐of‐hospital cardiac arrest (OHCA) is a main target for resuscitation.