|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1998 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1997 : ¥1,500,000 (Direct Cost : ¥1,500,000)
We measured the plasma levels of adrenomedullin (AM), a novel vasodilating peptide, in 89 patients with various forms of systemic inflammatory response syndrome and 13 healthy volunteers, as controls. Plasma levels of AM in SIRS (bums 20.5*3.2 fmol/ml : mean SEM ; pancreatitis 13.8*3.8 ; trauma 14.9*2.5 ; traumatic shock 41.1*7.8 ; severe sepsis 59.9*11.2 ; septic shock 193.5*30.1) were significantly elevated as compared with those in controls (5.1*0.2). Moreover, the patients with traumatic shock or septic shock showed higher levels of plasma AM than those with trauma or severe sepsis, respectively. These data showed that in patients with SIRS plasma AM levels increased in proportion to the severity of illness. Subsequently, we measured the plasma levels of mediators such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, plasminogen activator inhibitor (PAI)-1 and thrombomodulin (TM), in patients with traumatic shock and septic shock. A significant correlation was observ
ed between plasma A M and TNF-a levels in patients with septic shock, suggesting an important role for AM in the pathophysiology of inflammation as well as TNF-alpha. The plasma level of AM in patients with septic shock showed significant correlations with the values of cardiac index, stroke volume index, and heart rate, and with a decrease in diastolic blood pressure, systemic vascular resistance index (SVRI) and pulmonary vascular resistance index (PVRI). Plasma AM and IL-8 levels correlated positively with Acute Physiology and Chronic Health Evaluation (APACHE)-II score, peak multiple organ failure (MOF) score during the first month and prognosis in patients with septic shock, as well as plasma IL-6 levels in patients with traumatic shock. Enhanced production of adrenomedullin in patients with septic shock may contribute to a reduced vascular tone and/or hypotension in septic shock. Plasma AM level might serve as a useful marker for evaluating severity and as a early predictor of subsequent organ failure and outcome in septic shock.
We demonstrated that plasma AM levels increased in patients with SIRS in proportion to its severity, suggesting that AM, endothelium derived potent vasodilator, may play an important role in the pathophysiology of inflammation. Taken together with our findings that plasma AM levels correlate with relaxation of the vascular tone in patients with septic shock, especially in septic shock AM appears to be not only a marker for evaluating severity, but also an early predictor correlating with subsequent organ dysfunction and outcome. Although further studies are needed to clarify the contribution of AM in inflammation, the regulation and modulation of the function of AM may provide us a new therapeutical strategy for patients with SIRS including septic shock. Less