Cardiac fibroblasts are major production and target cells of adrenomedullin in the heart in vitro.

OBJECTIVE: Adrenomedullin (AM) is a potent vasodilator peptide. Plasma AM concentration is increased in patients with various heart diseases, and both myocytes (MCs) and non-myocytes (NMCs) secrete AM and express its receptors. These facts suggest that cardiac cells possess an autocrine/paracrine capability mediated by AM. METHODS: MCs and NMCs were prepared from cardiac ventricles of neonatal rats. AM and endothelin-1 concentrations were measured by radioimmunoassays, and interleukin-6 level by a specific bioassay. Total nitrite/nitrate contents were measured with a fluorescence assay kit. RESULTS: A basal secretion rate of AM from NMCs was 2.8-fold higher than that from MCs. Interleukin-1beta, tumor necrosis factor-alpha and lipopolysaccharide stimulated AM secretion from NMCs but not from MCs. AM stimulated interleukin-6 production in the presence of these cytokines or lipopolysaccharide, which was more prominent in NMCs. In the presence of interleukin-1beta, AM augmented nitric oxide synthesis 2.7-fold in NMCs, but slightly in MCs. NMCs secreted endothelin-1 at a rate nine times higher than MCs, and AM inhibited endothelin-1 secretion from NMCs. CONCLUSION: This in vitro study suggests that AM in the heart is mainly produced in NMCs and exerts its effects through NMCs, especially under inflammatory conditions.

[The efficacy of transesophageal echocardiography during the pericardial drainage of the cardiac tamponade after cardiac surgery].

For two cases of cardiac tamponade following cardiac surgery, the approaches for pericardial drainage were determined by the transesophageal echocardiography under general anesthesia. In most cases of cardiac tamponade after cardiac surgery the pericardial effusion is regional and localized due to adhesions of pericardium. Therefore subxiphoid incision approach of pericardial drainage cannot often be accomplished. In these cases transesophageal echocardiography can image the presence, location and size of the pericardial effusion and is an available method to determine the approach of pericardial drainage.

[Anesthetic management for AICD (automatic implantable cardioverter defibrillator) implant surgery].

We studied anesthetic management and monitoring during AICD (automatic implantable cardioverter defibrillator) implantation. For anesthetic management, complete sedation and amnesia are needed during implantation procedures with rapid awakening and extubation after the surgery. We chose inhalation anesthesia supplemented with small doses of fentanyl or thiamylal. Monitoring for AICD implantation should be less invasive, continuous and rapid in responsiveness. For brain and cardiac monitoring, a combination of near infrared spectroscopy and transesophageal echocardiography was quite useful.

[Optimal dose of indocyanine-green injected from the peripheral vein in cardiac output measurement by pulse dye-densitometry].

Cardiac output is measured by pulse dye-densitometry using indocyanine-green (ICG). This cardiac output is estimated by correlating with the cardiac output measured by pulmonary artery catheter using thermodilution method. Twenty-four patients scheduled for elective cardiovascular surgeries under general anesthesia were studied. The pulse dye-densitometry monitoring system used was DDG-2001 (Nihon Kohden, Japan). In group A (13 patients: 19 times), ICG was administered from the peripheral vein as bolus doses of 5, 10 or 20 mg (5 mg.ml-1 water solution). In group B (11 patients: 12 times), ICG was administered from the peripheral vein as bolus doses of 20, 10 or 5 mg (5 mg.ml-1 water solution). The correlation (Pearson's correlation coefficient) and precision (the method proposed by Bland and Altman) compared with cardiac output measured by pulmonary artery catheter were examined. Better correlation and precision were recognized after 20 mg ICG injection than 5 or 10 mg ICG injection. In conclusion, the measurement of cardiac output by pulse dye-densitometry with peripheral vein ICG injection was useful using a bolus dose of ICG 20 mg.

[Schizophrenia following prenatal exposure to influenza during second trimester].

Mednick et al and O'Callaghan et al have recently reported that individuals exposed to the 1957 A2 influenza pandemic during their second trimester in utero are at risk for later schizophrenia. In this study, we determined whether their findings could be reproducible in a Japanese sample. In Japan, there were two waves of the 1957 A2 influenza pandemic; the first occurred from June to July, and the second from November to December. In addition, an epidemic of influenza A/B mixed type prevailed from January to February 1957. We obtained information on all dates of birth of 1187 individuals born between June 1955 and May 1960, who were treated for schizophrenia during the study period. November 1991 to September 1992, at 18 mental hospitals around Tokyo metropolitan areas. Hospital clinical diagnosis was used. We defined the index year from June 1957, beginning the first wave of the pandemic, to May 1958. We compared the number of schizophrenic births in each month of the index year with the average number of births in the corresponding month of the two years before, and following, the index year. The observed number of births in June 1957 and April 1958 were found to be significantly high compared with the average number of births for the corresponding month in the four control years. The 63% excess of schizophrenic births in June 1957 ensued about 5 months after the peak of influenza A/B mixed type epidemic; there was also 49% increase in births about 5 months after the second wave of the pandemic. Given that full term delivery occurred in our sample (ie, 9 months pregnancy), our results support the view of Mednick et al and O'Callaghan et al that maternal exposure to influenza in the mid-pregnancy increases the risk of developing schizophrenia.

Relation of spasms and myoclonus to suppression-burst on EEG in epileptic encephalopathy in early infancy.

PURPOSE: This study was intended to clarify the relation between spasms in series and a suppression-burst (SB) EEG pattern which have a common nature of repetitive bursting activity in epileptic encephalopathy in early infancy. METHODS: The ictal EEG traces of spasms were temporally compressed and expanded to study the beginning and ending phases of series along with their spectral analysis in two patients with Ohtahara syndrome (OS) and one with early myoclonic encephalopathy (EME). The EEG bursts associated with myoclonus were also investigated. RESULTS: A mutual transition was indicated between the ictal activity of spasms and the bursts in the peri-series SB on EEG. Gamma rhythm was detected in common in the ictal activity and the peri-series and interictal bursts on EEG, and also in the bursts with myoclonus. CONCLUSION: The relation between the ictal activity of spasms and SB on EEG was shown to be close. The generative mechanisms of spasms and myoclonus might be linked to the bursting tendency intrinsic to immature brain function.

Effect of cardiopulmonary bypass on pulmonary clearance of adrenomedullin in humans.

BACKGROUND: Adrenomedullin is a potent vasodilatory peptide and its plasma concentration increases after cardiopulmonary bypass. We analyzed the contribution of the lung to the disposition of adrenomedullin before and after cardiopulmonary bypass in humans. METHODS: Thirty-five patients undergoing cardiac surgery with cardiopulmonary bypass were studied. Bloods were sampled from the pulmonary artery and left atrium at the following times: prior to systemic heparinization, during pulmonary reperfusion and after cardiopulmonary bypass. Plasma concentrations of total and mature adrenomedullin were measured using an immunoradiometric assay kit specific for human adrenomedullin. Intermediate adrenomedullin was calculated as the difference between total adrenomedullin and mature adrenomedullin. RESULTS: Before cardiopulmonary bypass, mature and intermediate adrenomedullin concentrations were reduced by the pulmonary circulation by approximately 30% and 20%, respectively. However, these effects were not observed during pulmonary reperfusion. Mature, but not intermediate, adrenomedullin was reduced after cardiopulmonary bypass. Furthermore, pulmonary clearance quantity of mature adrenomedullin was significantly enhanced after cardiopulmonary bypass. CONCLUSION: These results indicate that cardiopulmonary bypass temporally impairs the pulmonary clearance of mature and intermediate adrenomedullin, but clearance of mature, not intermediate adrenomedullin is enhanced after cardiopulmonary bypass.

Cerebral production of adrenomedullin afer hypothermic cardiopulmonary bypass in adult cardiac surgical patients.

UNLABELLED: Adrenomedullin is a potent vasodilatory peptide originally identified in human pheochromocytoma. Plasma adrenomedullin increases during and after cardiopulmonary bypass (CPB). However, the site at which production of adrenomedullin is augmented has not been identified. In the present study, we examined the contribution of the cerebral vasculature to the production of adrenomedullin in patients before, during, and after CPB. Ten patients undergoing coronary artery bypass grafting with mild hypothermic CPB were studied. Cerebral blood flow was measured using the Kety-Schmidt method before, during, and after CPB. Plasma adrenomedullin concentrations from radial artery and internal jugular bulb blood were measured by radioimmunoassay, and cerebral adrenomedullin production was evaluated. Adrenomedullin production in the cerebral vasculature was significantly enhanced after CPB and correlated with aortic cross-clamping time. The cerebral adrenomedullin production may contribute to the increased plasma level of adrenomedullin after CPB. IMPLICATIONS: Plasma adrenomedullin has been reported to increase in humans after cardiac surgery involving cardiopulmonary bypass. In this study, we demonstrated that cerebral adrenomedullin production may contribute to the increased plasma level of adrenomedullin after cardiopulmonary bypass.

Increased plasma concentration of adrenomedullin in patients with subarachnoid hemorrhage.

UNLABELLED: Adrenomedullin (AM) is a potent hypotensive peptide originally identified in pheochromocytoma tissues. Impaired cardiovascular conditions, such as hypertension, myocardial infarction, and septic shock, stimulate production of AM. This study was performed to determine whether subarachnoid hemorrhage (SAH) altered plasma AM concentration. Plasma concentrations of AM in 17 patients with SAH were measured for 2 wk after the onset of SAH by AM-specific radioimmunoassay. Plasma concentrations of AM were increased in patients with SAH throughout the study period, compared with those in control subjects. Plasma concentrations of AM in patients classified as Hunt and Kosnik grade III or IV were significantly higher than those classified as Hunt and Kosnik grade I or II on the day of and the day after the onset of SAH. However, plasma concentrations of AM were unaffected by angiographic vasospasm. These findings suggest that plasma concentrations of AM are increased in patients with SAH and may reflect the severity of SAH. IMPLICATIONS: Adrenomedullin has been reported to affect the cerebral circulation. This study was performed to determine whether subarachnoid hemorrhage, a typical cerebrovascular disorder, altered plasma adrenomedullin concentrations. We found that plasma adrenomedullin concentrations increased in patients with subarachnoid hemorrhage, although no relationship was found between plasma adrenomedullin concentration and angiographic vasospasm. Plasma adrenomedullin concentration may reflect the severity of hemorrhage.

Adrenomedullin gene transcription is decreased in peripheral blood mononuclear cells of patients with IgA nephropathy.

We measured mRNA levels of adrenomedullin (AM), C-type natriuretic peptide (CNP), vascular endothelial growth factor (VEGF), interleukin 1beta (IL-1beta) and interleukin 6 (IL-6) in peripheral blood mononuclear cells (PBMC) of patients with IgA nephropathy. To evaluate these mRNA levels, we employed a real-time quantitative PCR method which was performed using a hybridization probe labeled with two fluorescence dyes. This strategy was found to afford the standard curves with a high correlation, suggesting that this method is useful for evaluations of mRNA levels. By this method, levels of AM, CNP, VEGF, IL-1beta and IL-6 mRNA in PBMC of 49 IgA nephropathy patients and 35 healthy volunteers were evaluated. Among the mRNAs examined, AM mRNA levels were significantly lower in severe-grade than in mild-grade IgA nephropathy patients. Furthermore, AM mRNA levels correlated with CNP mRNA levels in PBMC of patients with IgA nephropathy, and each peptide generated from these mRNAs has antiproliferative effects on mesangial cells. These data indicate that gene expression of AM in PBMC is regulated according to the pathophysiological states of IgA nephropathy and that decreased AM production may contribute to the progression of IgA nephropathy.