Hirotsugu Fukuda

Diversity of Molecular Forms of Plasma Brain Natriuretic Peptide in Heart failure –Different proBNP-108 to BNP-32 Ratios in Atrial and Ventricular Overload–

Objective Recent studies have shown that plasma levels of brain natriuretic peptide (BNP)-32 and proBNP-108 are increased in heart failure (HF) and that the BNP-32 assay kit in current clinical use cross-reacts with proBNP-108. We investigated why proBNP is increased without processing in HF was investigated. Design, setting and patients Plasma BNP-32 and proBNP-108 in normal individuals (n=10) and in patients with atrial fibrillation (AF) (n=18) and HF (n=132) was measured. BNP-32 and proBNP-108 in ventricular and atrial tissue and in pericardial fluid using a specific fluorescent enzyme immunoassay following Sep-Pak C18 (Waters, Milford, Massachusetts, USA) cartridge extraction and gel filtration was also measured. Main outcome measures Levels of both BNP-32 and proBNP-108 were higher in HF than in control or AF (both p<0.01), and the levels of these peptides significantly correlated (r=0.94, p<0.001). The proBNP-108/total BNP (BNP-32+proBNP-108) ratio was widely distributed and lower in HF (0.33 (0.17)) than in control (0.41 (0.06), p<0.05) and AF (0.45 (0.04), p<0.002). The proBNP-108/total BNP ratio was higher in HF with ventricular than in HF with atrial overload (0.45 (0.10) vs 0.20 (0.11), p<0.001). Consistent with this finding, the major molecular form were proBNP-108 and BNP-32 in ventricular (n=6, 0.67 (0.04)) and atrial (n=7, 0.76 (0.05), p<0.0001) tissues, respectively. ProBNP-108 was also the major molecular form of BNP in pericardial fluid (n=8, 0.82 (0.05)). The proBNP-108/total BNP ratio increased and decreased with HF deterioration and improvement, respectively. Conclusion These results suggest that BNP-32 and proBNP-108 is increased in HF and that the proBNP/total BNP ratio increases in association with pathophysiological conditions such as ventricular overload.

Greater expression of inflammatory cytokines, adrenomedullin, and natriuretic peptide receptor-C in epicardial adipose tissue in coronary artery disease

BACKGROUND Growing evidence suggests that the epicardial adipose tissue may have local interactions with coronary arteries. In addition, vasoactive peptides such as adrenomedullin and natriuretic peptide has an interaction with adipose tissue. In this study, we investigated the relationship between adipokines, adipocytokines, and vasoactive peptides expressed in epicardial adipose tissue and subcutaneous adipose tissue in patients with and without coronary artery disease (CAD). METHODS We studied 20 patients with CAD and 14 patients without CAD. We obtained blood samples and epicardial and subcutaneous adipose tissue at open-heart surgery. We measured serum cytokine levels and used real-time polymerase chain reaction (PCR) to measure mRNA levels of various molecules in epicardial and subcutaneous tissue and investigated the relation between mRNA levels and clinical parameters. RESULTS The mRNA levels of IL-6, IL-1beta, MCP-1, and TNF-alpha were significantly higher in epicardial adipose tissue than in subcutaneous adipose tissue. Interestingly, the mRNA levels of IL-6, IL-1beta, MCP-1, natriuretic peptide receptor-C (NPR-C), adrenomedullin, and leptin in epicardial adipose tissue were higher in patients with CAD than those without CAD. In contrast, mRNA levels of adiponectin, PPAR-gamma, and NPR-A were similar in the two groups. In subcutaneous tissue, mRNA expressions of IL-6, IL-1beta, MCP-1, NPR-C, adrenomedullin, and leptin were modestly higher in patients with CAD than in those without CAD. There were no differences in plasma cytokine levels between the two groups. CONCLUSION The mRNA levels of inflammatory cytokines, adipokines, neurohumoral factors and their receptors appear to be increased in epicardial adipose tissue independent of plasma levels of these molecules. Further studies are necessary to elucidate the pathophysiological role of these molecules in CAD.

The effect of glycosylation on plasma N-terminal proBNP-76 levels in patients with heart or renal failure

Objective Pro-brain natriuretic peptide (proBNP)-108 and N-terminal proBNP-76 (NT-BNP) contain seven sites for O-linked oligosaccharide attachment. Currently, levels of glycosylated NT-BNP are probably underestimated because it is not recognised by one antibody in the sandwich assay system. The pathophysiological significance of cardiac and plasma levels of non-glycosylated (nonglyNT-BNP) and glycosylated NT-BNP (glyNT-BNP) in heart failure (HF) and chronic renal failure (CRF) was investigated. Methods Plasma samples from 186 patients with HF and 76 patients with CRF on haemodialysis were studied, together with 11 atrial tissue samples. To measure nonglyNT-BNP and glyNT-BNP, samples were incubated with or without deglycosylating enzymes and NT-BNP was measured using Roche Elecsys proBNP I. The percentage glyNT-BNP was calculated as glyNT-BNP/(glyNT-BNP + nonglyNT-BNP). Results In HF, plasma BNP, nonglyNT-BNP and glyNT-BNP levels all increased with increasing disease severity (New York Heart Association class; p<0.0001), though the molar ratio remained constant (molar ratio, BNP:nonglyNT-BNP:glyNT-BNP = 1:2.4:9.6). Before haemodialysis for CRF, plasma BNP and nonglyNT-BNP were somewhat elevated, and glyNT-BNP was markedly increased (molar ratio, BNP:nonglyNT-BNP:glyNT-BNP = 1:8.5:82). After haemodialysis, plasma BNP, nonglyNT-BNP, atrial natriuretic protein and cGMP all declined (p<0.0001), but glyNT-BNP was unchanged. Notably, the percentage of glyNT-BNP was elevated before haemodialysis, and was further increased after haemodialysis (p<0.0001). Atrial tissue levels of BNP, nonglyNT-BNP and glyNT-BNP were similar. Conclusion The findings suggest that most endogenous plasma NT-BNP is glycosylated and therefore undetectable with the current assay system, and that the relative glycosylation level is increased by haemodialysis.

Effect of high-frequency jet ventilation on oxygenation during one-lung ventilation in patients undergoing thoracic aneurysm surgery

PurposeTo evaluate the effect of high-frequency jet ventilation (HFJV) and continuous positive airway pressure (CPAP) on oxygenation and the shunt fraction (Qs/Qt) during one-lung ventilation (OLV).MethodsTwenty-five patients who were undergoing resection of a descending aortic aneurysm were studied. Arterial oxygenation, Qs/Qt, and hemodynamics were evaluated just before the initiation of OLV (T1), 15 min after OLV (T2), and 15 min (T3) and 30 min (T4) after the application of HFJV or CPAP to the nondependent lung.ResultsThere were no significant changes in the mean arterial blood pressure (MAP), heart rate (HR), central venous pressure (CVP), or mixed venous partial pressure of oxygen throughout this study. The arterial partial pressure of oxygen (PaO2) values after the application of HFJV or CPAP increased significantly, from 173.8 ± 39.6 mmHg (T2) to 344.1 ± 87.9 mmHg (T3) and 359.9 ± 82.4 mmHg (T4) in the HFJV group (P < 0.05), and from 153 ± 38.5 mmHg (T2) to 243 ± 48.5 mmHg (T3) and 249.7 ± 55.0 mmHg (T4) in the CPAP group (P < 0.05). The shunt fraction decreased significantly after the initiation of HFJV or CPAP, from 38.7% ± 8.9% (T2) to 27.0% ± 8.0% (T3) and 25.9% ± 8.7% (T4) in the HFJV group (P < 0.05), and from 44.6% ± 8.6% (T2) to 34.3% ± 10.2% (T3) and 32.6% ± 8.5% (T4) in the CPAP group (P < 0.05). The arterial saturation of oxygen (SaO2) increased significantly after the application of either HFJV or CPAP (P < 0.05).ConclusionsBoth HFJV and CPAP can improve oxygenation during OLV.

Hypopharyngeal perforation caused by intraoperative transesophageal echocardiography

Intraoperative transesophageal echocardiography (TEE) is an invaluable tool for cardiac surgical decision-making. TEE is considered reasonably noninvasive and safe, but insertion and manipulation of the TEE probe can lead to complications. Here, we report a patient with aortic stenosis who experienced TEE-associated hypopharyngeal perforation at the pyriform sinus complicated by esophageal trauma, pneumomediastinum and pneumoretroperitoneum. Based on this case, we suggest that rare complications be kept in mind when using TEE intraoperatively.

Effects of Continuous Infusion of Low-dose Human Atrial Natriuretic Peptide (hANP) on the Lungs during Cardiac Surgery

OBJECTIVE The objective of this study was to determine the effects of a continuous infusion of low-dose hANP on the lungs during cardiac surgery in patients under cardiopulmonary bypass (CPB). METHODS We analyzed 30 consecutive cases of cardiac surgery performed at our hospital from 2007-2008. The patients were divided into a group that received hANP (hANP group) or a group that received saline and no hANP (N-hANP group). We measured various parameters before and after surgery using a PiCCO monitor. RESULT There were no differences in the preoperative characteristics between the groups, although urine volume during the operation was significantly greater in the hANP group. After surgery, there were no significant differences between the groups in cardiac output index (CI), global enddiastolic volume index (GEDVI), intrathoracic blood volume index (ITBI), pulmonary blood volume index (PBI), extravascular lung water index (ELWI) and pulmonary vascular permeability index (PVPI), total protein, and creatine. In contrast, interleukin-6 (IL-6) and renin were significantly lower, and albumin was significantly higher in the hANP group. CONCLUSION We found that low-dose hANP during open cardiac surgery inhibited the secretion and plasma activity of IL-6 and renin. Although there were no differences in lung circulatory parameters such as the amount of fluid in the pulmonary blood vessels between the two groups, we believe that the strong diuretic effect of hANP reduced third-space fluid retention caused by CPB.

Serum adiponectin and TNFα concentrations are closely associated with epicardial adipose tissue fatty acid profiles in patients undergoing cardiovascular surgery

Background Epicardial adipose tissue (EAT) releases both adiponectin and TNFα, and these two adipokines play important roles in heart diseases such as coronary arterial disease. The aim of the present study was to clarify whether fatty acid (FA) profiles in EAT are linked to the serum concentration of these adipokines. The relationships between serum adipokine levels and FA profiles in patients undergoing cardiovascular surgery were analyzed. Methods Patients (n = 21) undergoing cardiovascular surgery (11 males, 70.4 ± 9.0 years, BMI 26.0 ± 5.1 kg/m2) were included. EAT samples were taken. We measured clinical biochemical data and FA profiles in venous blood and EAT samples using gas chromatography. Serum adiponectin and TNFα concentrations were also measured. Results The adiponectin and TNFα levels were not correlated with any fatty acid concentration in serum lipids. In contrast, there was a positive correlation between the serum adiponectin level and epicardial level of nervonic acid (C24:1ω9, r = 0.525, P = 0.025). In multiple regression analysis, adiponectin showed a positive association with the epicardial C24:1ω9 concentration after controlling for age and BMI, or TG, non-HDL-C, and BNP. The serum TNFα concentration was negatively correlated with the epicardial C18:3ω3, C12:0 and C18:0 content. In multiple regression analysis, the serum TNFα concentration showed a positive association with the epicardial C18:3ω3 level (β = − 0.575, P = 0.015). Conclusions These results suggest that there is a close relationship between epicardial FA profiles and serum levels of adiponectin and TNFα. Dietary therapy to target FA profiles may be helpful to modulate inflammation.

Massive mitral valve thrombosis following reversal of warfarin in a patient with rheumatic mitral valve stenosis

1Division of Cardiovascular Surgery, Gunma Prefectural Cardiovascular Centre, Gunma, Japan 2Department of Cardiac and Vascular Surgery, Dokkyo Medical University Hospital Heart Center, Tochigi, Japan *Correspondence Yasuyuki Yamada, M.D., Ph.D., Division of Cardiovascular Surgery, Gunma Prefectural Cardiovascular Centre, 3-12 Kameizumi, Maebashi, Gunma 371-0004, Japan. E-mail: yamada@dokkyomed.ac.jp

Association of serum concentrations of irisin and the adipokines adiponectin and leptin with epicardial fat in cardiovascular surgery patients

Epicardial fat located adjacent to the heart and coronary arteries is associated with increased cardiovascular risk. Irisin is a myokine produced by skeletal muscle after physical exercise, and originally described as a molecule able to promote the browning of white adipose tissue and energy expenditure. In order to decrease cardiovascular risk, it has been proposed as a promising therapeutic target in obesity and type 2 diabetes. We investigated the relationships between serum concentrations of irisin and the adipokines adiponectin and leptin and body fat including epicardial fat in patients undergoing cardiovascular surgery. We obtained serum samples from 93 patients undergoing cardiovascular surgery (age 69.6 (SD 12.8) years, BMI 24.1 ± 4.8 kg/m2). Computed tomography (CT) and echocardiographic data were obtained from the routine preoperative examination. Subcutaneous fat area (SFA, cm2) and visceral fat area (VFA, cm2) near the umbilicus were automatically measured using the standard fat attenuation range. Epicardial fat area (EFA, cm2) was measured at the position where the heart became a long axis image with respect to the apex of the heart in the coronal section image. Total body fat mass, body fat percentage, and skeletal muscle volume (SMV) were estimated using bioelectrical impedance analysis (BIA). Serum irisin concentration was measured by enzyme-linked immunosorbent assay, and compared with adiponectin and leptin concentrations. The data were also compared with the clinical biochemical data. EFA was strongly correlated with BMI (P = 0.0001), non-HDL-C (P = 0.029), TG (P = 0.004), body fat mass (P = 0.0001), and body fat percentage (P = 0.0001). Serum leptin concentration showed a significant positive correlation with BMI (P = 0.0001) and TG (P = 0.001). Adiponectin, but not irisin, showed a significant negative correlation with BMI (P = 0.006) and TG (P = 0.001). Serum leptin level had a significant positive correlation with EFA, VFA, and SFA. In contrast, the serum adiponectin level was significantly negatively correlated with EFA, VFA, and SFA. The serum irisin level was also negatively correlated with EFA (r = -0.249, P = 0.015), and SFA (r = -0.223, P = 0.039), and tended to correlate with VFA (r = -0.198, P = 0.067). The serum level of adiponectin was negatively correlated with that of leptin (r = -0.296, P = 0.012), but there were no significant correlations between irisin and either adiponectin or leptin. Multivariate linear regression demonstrated that EFA showed a positive association with serum leptin level (β = 0.438, P = 0.0001) and a negative correlation with serum irisin level (β = -0.204, P = 0.038) and serum adiponectin level (β = -0.260, P = 0.015) after adjusting for age, sex, and BMI. The present study provided the first evidence of associations of the serum irisin and adipokines (adiponectin and leptin) concentrations with epicardial fat in cardiovascular surgery patients. Irisin may play a role in preventing excess adiposity including epicardial fat, and consequently cardiovascular risk in patients.

Right internal jugular vein thrombosis caused by aneurysm of right-sided aortic arch

A right-sided aortic arch is normally asymptomatic. We report the case of an 84-year-old man with right internal jugular vein thrombosis caused by an aneurysm in a right-sided aortic arch. The patient had undergone open repair of an abdominal aortic aneurysm and had an uneventful postoperative course. However, a routine postoperative contrast-enhanced thoracic and abdominal computed tomography scan showed right internal jugular vein thrombosis. The patient had no history of catheter insertion in the right jugular veins and had no hereditary coagulopathy. It was presumed that the cause of this thrombosis was compression of the right brachiocephalic vein by an aneurysm of the right-sided ascending aorta that was considered too small to require surgical repair. The right internal jugular vein thrombosis was successfully treated with edoxaban. <Learning objective: This case report alerts us to consider that a right-sided aortic arch aneurysm considered too small for surgery can later cause upper-extremity deep vein thrombosis.>