[Combined pulmonary resection and cardiac operation; report of a case].

A 59-year-old woman was admitted because of an abnormal shadow on the chest X-ray film. Transbronchial lung biopsy revealed adenocarcinoma of the right lung, and chest computed tomography showed left atrial tumor. First, we performed a resection of left atrial tumor (myxoma) under cardiopulmonary bypass (CPB), followed by a right upper lobectomy with lymph node dissection. The postoperative course was uneventful, and she was discharged on the 14th postoperative day. It is safe and efficient that pulmonary resection and cardiac operation under CPB are surgically treated in a one-stage operation.

Prolonged lymphocytopenia after bendamustine therapy in patients with relapsed or refractory indolent B-cell and mantle cell lymphoma.

This corrects the article DOI: 10.1038/bcj.2015.86.

Effect of angiotensin-converting enzyme inhibitors on endothelium-dependent peripheral vasodilation in patients with chronic heart failure.

OBJECTIVES: This study was performed to determine whether acute inhibition of angiotensin-converting enzyme restores impaired endothelium-dependent vasorelaxation in patients with chronic heart failure. BACKGROUND: Recent reports have demonstrated that endothelium-dependent vasodilation induced by cholinergic stimuli is attenuated in the peripheral vascular bed of patients with chronic heart failure. METHODS: We examined the effects of local intraarterial infusion of enalaprilat (0.6 micrograms/min per 100 ml tissue volume) on responses initiated by acetylcholine or sodium nitroprusside in the forearm vascular bed in 8 normal subjects, 12 patients with mild heart failure (New York Heart Association functional classes I and II) and 10 patients with more advanced heart failure (functional classes III and IV). Forearm blood flow was measured by means of venous occlusion plethysmography. RESULTS: Although enalaprilat alone did not affect basal forearm blood flow, it significantly augmented the increase in forearm blood flow induced by acetylcholine in normal subjects (p < 0.01) and in those with mild heart failure (p < 0.05). However, the effect was not found in patients with more advanced heart failure. Coinfusion of enalaprilat did not enhance sodium nitroprusside-induced vasodilation in any of the groups. To explore the mechanism of the inhibitor's effect, an additional 20 patients with mild heart failure (functional class II) were pretreated with a cyclooxygenase inhibitor, acetylsalicylic acid (n = 10) or an inhibitor of nitric oxide synthesis, NG-monomethyl-L-arginine (n = 10), followed by administration of acetylcholine with or without enalaprilat. Acetylsalicylic acid reduced the converting enzyme inhibitor's effect, whereas NG-monomethyl-L-arginine failed to block the augmentation of blood flow. CONCLUSIONS: These results suggest that inhibition of angiotensin-converting enzyme potentiates endothelium-dependent vasodilation induced by cholinergic stimuli, presumably through modulation of prostaglandin metabolism, in the peripheral vasculature of patients with mild chronic heart failure.

Inducible nitric oxide synthase and tumor necrosis factor-alpha in myocardium in human dilated cardiomyopathy.

OBJECTIVES: We examined the mRNA expression and protein localization of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) in myocardial tissue obtained from patients with dilated cardiomyopathy (DCM). BACKGROUND: The etiology of DCM is unknown, but viral infection or autoimmune abnormalities that induce cytokine expression have been proposed as pathogenetic factors. Nitric oxide (NO), synthesized by nitric oxide synthase (NOS), has negative inotropic and cytotoxic effects on cardiomyocytes. Cytokines such as TNF-alpha are potent stimulators of iNOS expression. Expression of iNOS leads to excessive production of NO in the myocardium and may modulate cardiac contractility and ventricular morphology. METHODS: We examined the mRNA expression and protein localization of iNOS and TNF-alpha in myocardial tissue obtained from 24 patients with DCM, 20 patients with hypertrophic cardiomyopathy (HCM) and 15 control subjects, using the reverse transcriptase-polymerase chain reaction method and immunohistochemical studies. We then compared the differences in clinical characteristics between DCM patient subgroups with and without myocardial iNOS expression. RESULTS: Messenger RNA expression of iNOS and TNF-alpha was observed, respectively, in 13 (54%) and 18 (75%) patients with DCM. Gene expression of TNF-alpha was consistently detected in endomyocardial tissue from patients with DCM and INOS expression. Inducible NOS protein was evident only in cardiomyocytes, whereas TNF-alpha was apparent in both cardiomyocytes and endomyocardial endothelium. Neither mRNA expression nor protein localization of iNOS or TNF-alpha was observed in cardiac tissue obtained from patients with HCM or control subjects. Patients with DCM and iNOS mRNA showed a lower left ventricular ejection fraction (p < 0.01) and a higher left ventricular volume (p < 0.05) than the negative DCM group. CONCLUSIONS: Inducible NOS was consistently coexpressed with TNF-alpha in myocardial tissue obtained from a subgroup of patients with DCM and advanced left ventricular dysfunction.

Inhibitory effect of atrial natriuretic peptide on accelerated endothelin secretion from cultured human endothelial cells.

This study investigated the effect of atrial natriuretic peptide (ANP) on endothelin (ET) secretion from cultured human endothelial cells. Confluent umbilical venous endothelial cells were incubated with experimental agents in multi-well plates, and the level of immunoreactive ET in the medium was measured by radioimmunoassay. There was no significant effect of ANP (10(-8), 10(-7) and 10(-6) M) on ET secretion after a 3- or 6-hour incubation. However, with 24-hour incubation, ANP significantly inhibited ET secretion from cultured human endothelial cells (control, 139.0 +/- 7.2 fmol/well; 10(-7) M, 89.4 +/- 4.7 fmol/well; 10(-7) M, 79.4 +/- 8.2 fmol/well; 10(-6) M, 71.0 +/- 10.1 fmol/well, P < 0.01). Furthermore, the addition of 8-bromo-cyclic GMP to the medium inhibited ET secretion (control, 147.2 +/- 2.9 fmol/well; 10(-5) M, 140.9 +/- 2.3 fmol/well; 10(-4) M, 143.0 +/- 1.0 fmol/well; 10(-3) M, 96.6 +/- 6.3 fmol/well, P < 0.01). These findings demonstrate that ANP inhibits accelerated ET secretion from cultured human endothelial cells, probably due to augmentation of intracellular cyclic GMP levels by ANP-activated guanylate cyclase.

Effect of angiotensin II receptor blocker on angiotensin II stimulated DNA synthesis of cultured human aortic smooth muscle cells.

To examine the role of the renin-angiotensin system on human vascular smooth muscle cell (VSMC) replication, we studied the effect of DUP 753, an angiotensin II (ANG II) type 1 receptor antagonist, on ANG II stimulated tritiated-thymidine (3H-Tdr) incorporation into cultured human aortic VSMC. ANG II stimulated DNA synthesis of VSMC in a dose-dependent manner as estimated by 3H-Tdr incorporation (control; 2993 +/- 486 cpm, 10(-8)M; 3360 +/- 350 cpm, 10(-7)M; 3474 +/- 516 cpm, 10(-6)M; 4889 +/- 320 cpm, P < 0.01). The effects of ANG II were clearly inhibited by 10(-7) M DUP 753 (ANG II 10(-8) M; 3360 +/- 350 vs 509 +/- 39 cpm, 10(-7) M; 3474 +/- 516 vs 661 +/- 36 cpm, 10(-6) M; 4889 +/- 320 vs 806 +/- 76 cpm, each P < 0.01). This receptor antagonist decreased the basal 3H-Tdr incorporation of VSMC from 2933 +/- 486 to 411 +/- 78 cpm (P < 0.01). Furthermore, DUP 753 decreased 10(-7) M ANG II-stimulated 3H-Tdr incorporation of VSMC in a dose-dependent manner (control; 2627 +/- 256 cpm, 10(-9) M; 2145 +/- 143 cpm, 10(-8) M; 1047 +/- 543 cpm, 10(-7) M; 639 +/- 169 cpm, 10(-6) M; 642 +/- 59 cpm, P < 0.01). These observations suggest that, in human VSMC, ANG II type 1 receptors are important for the regulation of both stimulated and basal cell proliferation. It may therefore be worth while to examine the clinical usefulness of DUP 753 for preventing abnormal VSMC growth.

Impaired cholinergic peripheral vasodilation and its relationship to hyperemic calf blood flow response and exercise intolerance in patients with chronic heart failure.

This study examined the peripheral endothelium-dependent vasodilatory response to acetylcholine and the endothelium-independent vasodilatory response to nitroprusside in 19 patients with chronic heart failure and eight controls. These peripheral blood flow responses were compared with hyperemic calf blood flow changes after maximum leg exercise and 5-min femoral occlusion. The peripheral blood flow response to forearm intra-arterial infusion of acetylcholine and sodium nitroprusside, and reactive hyperemic calf blood flow changes were measured by plethysmography. All peripheral blood flow responses were significantly reduced in patients with chronic heart failure (P < 0.05). Reduction of acetylcholine-mediated changes in peripheral blood flow was correlated with exercise-induced calf blood flow response (r = 0.51, P < 0.05), but not with occlusion-induced calf blood flow response (r = 0.02, NS). Sodium nitroprusside-mediated changes were not correlated with any reactive hyperemic blood flow responses (exercise: r = 0.27, NS; occlusion: r = 0.11, NS). When the patients were divided into two subgroups based on the median exercise-induced calf blood flow change, the subgroup with the lower calf blood flow response showed a reduction in exercise capacity (anaerobic threshold: 11.8 +/- 0.6 vs. 14.6 +/- 1.0 ml/kg/min; P < 0.05). These findings suggest that endothelial dysfunction is related to a decrease in exercise-induced skeletal muscle blood flow and exercise capacity in patients with chronic heart failure.

Prognostic implications of plasma levels of atrial natriuretic factor in patients with acute myocardial infarction.

Several neurohormonal factors have been proposed as markers of the severity of acute myocardial infarction (MI). To determine whether plasma concentrations of atrial natriuretic factor (ANF) might predict post-MI prognosis, we studied 130 patients with acute MI (97 males and 33 females, mean age 62 years). Within one-half to one day after admission, a blood sample was taken for estimation of circulating ANF. The mean follow-up period was 37 months, and the follow-up rate was 97%. Of the 130 patients, 28 died from cardiac causes during the follow-up period. Patients were classified into three groups according to plasma ANF levels (group 1, < 99 pg/ml; group 2, 100-199 pg/ml; group 3; > 200 pg/ml). The survival curves were constructed by the Kaplan-Meier method. There were significant differences in the cumulative survival rate among the three groups (group 1 > group 2 > group 3; p < 0.001). The baseline characteristics (age, atrial pressure, and cardiac index) were different among the groups, therefore these variables were analyzed by a Cox multiple regression model. Significant predictors of cardiac mortality were plasma ANF class (p < 0.002) and pulmonary capillary wedge pressure (p < 0.007). In conclusion, these observations demonstrated that stratification of acute MI patients by plasma ANF level is a useful non-invasive method for predicting prognosis and for identifying individuals at high risk of cardiac death.

Noninvasive detection of iliac artery disease and prediction of its severity from Doppler spectral analysis in common femoral artery.

The direct interrogation of iliac artery disease (IAD) with color-coded duplex scanning is limited by the presence of intestinal gas or obesity. The purposes of this study were to examine the diagnostic accuracy of duplex ultrasound (DUS) analysis of spectral waves in common femoral artery (CFA) for detection of IAD and to predict its severity. DUS and arteriography were performed in 107 lower extremities in this study. The following were calculated from the CFA spectral waves obtained by DUS: peak systolic velocity (PSV), acceleration (PSV/pulse rise time), and deceleration (PSV/pulse decay time). In patients with isolated IAD, the treadmill exercise test was also performed to evaluate the ischemic severity expressed as recovery rate of ankle pressure index five minutes after exercise (RR-API). Forty-six lower extremities with IAD and 61 without IAD were diagnosed by arteriography. PSV was significantly reduced in lower extremities with IAD (109.5 +/- 32.7 vs 59.8 +/- 32.9 cm/s, P < 0.05). The deceleration detected IAD with a greater specificity and sensitivity vs acceleration (100.0 vs 82.0% and 97.8 vs 82.6%, respectively). Moreover, the acceleration and deceleration significantly correlated with the RR-API (r = 0.589, P < 0.05 and r = 0.779, P < 0.01, n = 14, respectively). The present evaluation is a simple and accurate technique to augment other examinations for detection of IAD and to assess its ischemic severity.

Circulating biochemical marker levels of collagen metabolism are abnormal in patients with abdominal aortic aneurysm.

Changes in extracellular matrix composition induced by abnormal collagen metabolism in the aortic wall may be an important factor in the progression of aortic structural changes. The authors have measured several types of biochemical marker for collagen metabolism in plasma: carboxyterminal propeptide of type Icollagen (PICP) for a pure collagen synthesis marker, matrix metalloproteinase-1 (MMP-1) for a degradation marker of collagen matrix, and tissue inhibitors of metalloproteinase-1 (TIMP-1) as a native inhibitor of MMP-1. Subjects of this study were 17 patients with abdominal aortic aneurysm (AAA), 14 patients with atherosclerosis obliterans (ASO), and 22 age/sex-matched healthy controls (HC). Blood samples were drawn from a forearm vein and measured by radioimmunoassay or enzyme-linked immunosorbent assay. Plasma concentrations of PICP in patients with AAA were significantly decreased compared to those in HC patients (82.0 +/- 16.4 vs 111.3 +/- 40.3 ng/mL; p < 0.01), but those in patients with ASO (105.4 +/- 55.4 ng/mL) were comparable to control concentrations. Although no differences in plasma concentrations of MMP-1 were observed among the three subject groups (HC, 20.0 +/- 5.6 ng/mL; ASO, 21.4 +/- 13.8 ng/mL; AAA, 24.5 +/- 11.7 ng/mL; NS), MMP-1/PICP ratio as an index of collagen degradation to collagen neosynthesis in AAA was significantly elevated compared to HC (0.32 +/- 0.18 vs 0.20 +/- 0.08; p < 0.01). Plasma concentrations of TIMP-1 in patients with AAA (293.8 +/- 61.2 ng/mL) or ASO (327.6 +/- 54.9 ng/mL) were significantly higher than in HC (227.3 +/- 60.2 ng/mL; both p < 0.01). In conclusion, these data suggest that although a compensatory mechanism such as increased TIMP-1 may be activated, collagen neosynthesis may decrease with relatively increased collagen degradation in patients with AAA.

[Long survival with chronic ventricular fibrillation under support of uni-left-ventricular assist system].

Few minutes of suspended malignant ventricular arrhythmia may be permitted for the patient with left ventricular assist system (LVAS). However, longer and continuous ventricular arrhythmia, especially ventricular fibrillation (Vf), may induce the low output of LVAS, which leads circulatory collapse immediately. Our presenting case is a female dilated cardiomyopathy patient who has been supported with LVAS. Four months after the LVAS installation, her electrocardiogram has changed to Vf without any symptoms. Her ventricular function has never recovered, even ventricular tachycardia. She has been a candidate of heart transplantation for more than 19 months with this rare hemodynamic condition (LVAS+Vf), like the Fontan circulation. Her performance status is limited due to deceasing of the LVAS flow, which caused by the change of her position: 2.5-2.9 l/min (lie down) to 2.0 l/min (rise). Her peak VO2/W is 6.9 ml/min/kg measured by the cardio-pulmonary exercise test. However, she has developed her general status by doing rehabilitation program and is able to walk for more than 100-150 meters.

Factors related to long-term prognosis in medically treated type B aortic dissection: a physical predisposing factor.

AIM: In medically treated patients with Stanford type B aortic dissection, it has been shown that the state of the dissecting aorta in the acute phase predicts the prognosis. The present study examined other crucial factors, including physical characteristics, related to the long-term prognosis in type B aortic dissection. METHODS: Two hundred and two patients with type B aortic dissection who were discharged alive with medical treatment in the acute phase (mean age 66.5 years, range 29-90 years, 160 males) were followed. RESULTS: During the mean follow-up period of 4.9 years (ranging up to 12.2 years), 37 all-cause deaths were confirmed. A surgical procedure related to aortic dissection was performed in 8, and re-dissection occurred in 3. The survival rate at 5 years after onset was 82%. On Cox regression analysis, increased height (greater than the median value) was significantly associated with all-cause death and the composite aortic event when adjusted by age and sex (hazard ratio [HR]=2.22, 95%confidence interval [CI] 1.15-4.83, P=0.021, and HR=4.53, 95%CI 1.26-16.35, P=0.021, respectively). Patients with coexisting true aortic aneurysms also had a higher risk than those without (composite aortic events, HR=3.63, 95%CI 1.41-9.35, P=0.008). CONCLUSION: More strict management in the chronic phase is needed in taller patients as well as patients with coexisting true aortic aneurysms. This common physical predisposing feature may also assist in making the decision for earlier surgical intervention to the affected aorta.