Yasushi Fukuta

Plasma proinflammatory and anti-inflammatory cytokine and catecholamine concentrations as predictors of neurological outcome in acute stroke patients

PurposeProinflammatory and anti-inflammatory cytokines may play a pivotal role in cerebral inflammation, which is implicated in the development of brain injury. Systemic cytokine release is mediated by the sympathetic nervous system and catecholamines. The aim of this study was to investigate which parameters, among plasma levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor alpha (TNF-α) and the levels of the catecholamines, epinephrine and norepinephrine, contribute to the clinical outcome in acute stroke patients.MethodsThirty-seven acute stroke patients (ischemic, n = 19; hemorrhagic, n = 18) were enrolled. All of them were admitted to our hospital within 8 h after stroke onset. Neurological status was evaluated by a modified National Institute of Health Stroke Scale (mNIHSS) on admission and by a modified Rankin Scale (mRS) at 1 month. An mRS score of 3 or more at 1 month was considered to indicate poor outcome. Serum samples for the cytokine and catecholamine measurements were collected on admission. Plasma levels of IL-1β, IL-6, IL-10, and TNF-α were determined by an enzyme-linked immunosorbent assay (ELISA) method and epinephrine and norepinephrine concentrations were determined by high-performance liquid chromatography with electrochemical detection (HPLC-EC).ResultsIn the ischemic stroke patients, poor outcome was noted in 9 (47%). There were no significant differences in cytokine or catecholamine concentrations between patients with poor and good outcomes, and there was no association between clinical outcome and cytokine and catecholamine concentrations. In the hemorrhagic stroke patients, poor outcome was noted in 10 (56%). IL-6 and IL-10 levels were higher in patients with poor outcome. On logistic regression analysis, higher values of IL-6 were significantly associated with clinical outcome at 1 month (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.02–1.54).ConclusionIn ischemic stroke, plasma cytokines and catecholamines were not predictors of neurological outcome at 1 month. In hemorrhagic stroke, high levels of IL-6 in the early phase indicated a poor neurological outcome.

Extracellulary administered lysophosphatidylcholine causes Ca2+ efflux from freshly isolated adult rat cardiomyocytes

Abstract It has previously been reported that ischemia and reperfusion of the heart cause accumulation of lyophosphatidylcholine (LPC) within the myocardium. While it is known that LPC causes the transient increase of intracellular free Ca2+ concentration ([Ca2+]i) during contraction of cardiac cells, little is known about the mechanism for decreasing [Ca2+]i in cardiomyocytes during LPC accumulation. Since cumulative elevation in [Ca2+]i leads to irreversible injury to cardiomyocytes, elevated [Ca2+]i must be restored to an unstimulated level to maintain cell functions. In the present study, we therefore examined the effect of LPC on Ca2+ efflux from freshly isolated adult rat cardiomyocytes. LPC stimulated the efflux of 45Ca2+ from the cells in a concentration‐dependent manner (10–7 M – 10–5 M). Other lysophospholipids, which are generated from phopholipids of the cell membrane, failed to induce 45Ca2+ efflux from the cells. Dilazep and K‐7259, which are known to inhibit the increase in [Ca2+]i caused by LPC, likewise reduced 45Ca2+ efflux caused by LPC addition. Furthermore, the LPC‐stimulated 45Ca2+ efflux was not affected by removal of extracellular Ca2+, but was dependent on the presence of extracellular Na+. On the other hand, inhibitors of Na+/Ca2+ exchange, amiloride and 5‐(N,N‐dimethyl)‐amiloride, inhibited LPC induced 45Ca2+ efflux. These results suggest that LPC stimulates extracellular Na+‐dependent 45Ca2+ efflux from freshly isolated adult rat cardiomyocytes, probably through Na+/Ca2+ exchange on the plasma membrane of cells.

The use of continuous hemodiafiltration in a patient with diabetic ketoacidosis.

A variety of fatal complications are associated with diabetes mellitus. Among these, diabetic ketoacidosis (DKA) figures largely in fatalities in young diabetics. Although hyperosmotic diuresis in DKA causes extreme fluid loss, acute renal failure is less common than expected in DKA. We treated a case of severe DKA with associated coma, acute respiratory failure, and acute renal failure in a 24-year-old man who had been diagnosed with type 1 diabetes mellitus at age 19. The comatose patient had been intubated before transfer to our hospital for intensive care. Despite infusion with isotonic saline and insulin, metabolic acidosis was refractory. On day 2, urine output decreased and pulmonary congestion developed, so we started continuous veno-venous hemodiafiltration (CVVHDF), which was effective against the metabolic acidosis; urine output increased gradually. CVVHDF was withdrawn on day 7, and the patients renal function recovered completely. He was discharged from the intensive care unit (ICU) on day 14.

Angiotensin II as a stimulator of Na+-dependent Ca2+ efflux from freshly isolated adult rat cardiomyocytes

In cardiac tissues, angiotensin II causes inotropic and chronotropic effects on the heart. It is indicated that the mechanism of the inotropic effect of angiotensin II is attributed to an increase in cytosolic free calcium ([Ca2+]i) in cardiomyocytes. However, increased [Ca2+]i should be restored to a physiological level because cumulative elevation in [Ca2+]i leads to irreversible injury in cardiomyocytes. Whereas it is known that angiotensin II causes the increase in [Ca2+]i in cardiac cells, little is known about the mechanisms of decrease in [Ca2+]i in cardiomyocytes upon angiotensin II stimulation. In the present study, we examined the effect of angiotensin II on Ca2+ efflux from freshly isolated adult rat cardiomyocytes. Angiotensin II stimulated the efflux of 45Ca2+ from the cells in a concentration-dependent manner (10(-7)-10(-5) M). The 45Ca2+ efflux from the cells was inhibited by type 1 angiotensin II receptor inhibitor. The angiotensin II-stimulated 45Ca2+ efflux was not affected by deprivation of the extracellular Ca2+, but was dependent on the presence of extracellular Na+. These results indicate that angiotensin II stimulates extracellular Na(+)-dependent 45Ca2+ efflux from freshly isolated adult rat cardiomyocytes, probably through its stimulatory effect on the plasma membrane type 1 angiotensin II receptors which may couple to Na+/Ca2+ exchange.

Evaluation of Cerebral and Systemic Flow/Metabolism During Brain Hypothermia Therapy

In this study we evaluated the clinical usefulness of jugular venous-arterial PCO2 difference (JAPCO2) as an indicator of cerebral blood flow and metabolism in five patients (male 3; female 2) with brain injury. In the neurointensive care unit under mechanical ventilation, JAPCO2, mixed venous-arterial PCO2 difference (VAPCO2), and jugular venous hemoglobin oxygen saturation (SjvO2) were calculated. JAPCO2 was maintained at approximately 10 mmHg except during brain herniation. JAPCO2 had an inverse linear relationship with SjvO2. JAPCO2 decreased to under 4mmHg and SjvO2 increased to over 95 mmHg during the brain herniation period in patients who died. JAPCO2 was greater than VAPCO2 except during the brain herniation period. JAPCO2 was a useful monitor of cerebral blood flow and metabolism.

Surgical Therapy for Prosthetic Graft Infection.

治療に難渋した人工血管感染5症例について検討した. 年齢は57～81歳, 初回手術時の基礎疾患は Leriche 症候群1例を含む閉塞性動脈硬化症3例, 悪性腫瘍の動脈浸潤2例であった. 人工血管感染部位は鼠蹊部3例, 膝上部1例, 腹部1例で, うち4例の起炎菌は Staph. aureus (MRSA3例) であった. 感染原因となった人工血管の手術から感染発現までの期間は, 腹膜炎症例は10日と短く, 末梢側の感染では2か月～14年と長かった. 腹膜炎例を除いた症例での感染巣のドレナージ, 洗浄等の保存的治療期間は40～64 (平均50) 日であった. 手術はグラフトの感染部位のみの除去またはグラフト全部を摘出し, 新たな血行再建術を施行した. 感染グラフトはPTFE4例, Woven-Dacron 1例で, 再手術にも同様のグラフトを用いた. 感染部を避けるため, 閉鎖孔経由など3例で別経路を用いた. 感染人工血管の全摘出が困難な症例では, 感染巣部のみの人工血管摘除と健常な周囲組織での再建術を行い良好な結果を得た. 手術成績は全例生存, 敗血症や下肢切断等の重篤な合併症は認めなかった. 再手術から現在までの8か月～8年間, 全例開存し再感染も認めていない.