Good syndrome with thymic adenosquamous carcinoma--report of a case.

A 68-year-old man with recurrent bilateral severe pneumonia and invasive thymic carcinoma was admitted to our hospital. An extended thymo-thymectomy with lymph nodes dissection was performed for an irregular shaped anterior mediastinum mass. The tumor was mainly composed of type C, adenosquamous carcinoma, and found to have a small area of types B2 and B3 thymoma. History and laboratory findings were compatible with the diagnosis of Good syndrome. Although there are some reports of thymic carcinoma arising from thymoma, this is the first report of co-existence of adenosquamous carcinomas and thymoma with Good syndrome as far as reviewed articles. Thymic carcinoma with severe infection should be examined carefully for co-existence of thymoma, and co-existence of thymoma and thymic carcinoma suggests a close histogenetic relationship between the 2 tumors.

Monoclonal antibody 7F9 recognizes rat protein homologous to human carboxypeptidase-M in developing and adult rat lung.

BACKGROUND AND OBJECTIVE: The purpose of this study was to obtain an antibody that would be useful for investigating the yet unclear molecular mechanism underlying the differentiation of lung alveolar type I and II cells. METHODS: Monoclonal antibodies were raised against membrane proteins from embryonal day 18.5 rat lungs and characterized by immunoblotting on rat lung lysates at various developmental stages to select an appropriate clone. The antigen of the selected antibody was purified by serial column chromatography and immunoprecipitation and identified by mass spectrometry. RESULTS: 7F9 antibody recognizes a 65-kDa protein that is expressed most prominently from embryonal day 20.5 to postnatal day 1. This protein was identified as a rat protein that is similar to 5730456K23Rik protein. The protein is homologous to human carboxypeptidase-M. Although human carboxypeptidase-M is known as a marker of type I cells, the expression of this rat protein was detected in columnar epithelial cells expressing type II cell markers, SP-C and a lamellar body protein ABCA3, in developing lung. Its expression was detected in alveolar cells lacking T1alpha, a type I cell marker protein, in adult lung. It was also expressed in RLE-6TN cells derived from type II cells. The expression in RLE-6TN cells was down-regulated by transforming growth factor-beta1 and up-regulated by Wnt3a. CONCLUSIONS: 7F9 antibody detects a protein in rat lung cells expressing type II markers. The antibody is a useful tool for studying signalling triggered by transforming growth factor-beta1 and Wnt3a in rat type II cells.

The fundamental properties of Homer 1 in association with cardiac ryanodine receptor in mouse heart.

BACKGROUND: Homer, known as a scaffolding protein that regulates postsynapse signaling in neurons, has been poorly explored in cardiac research. We show the fundamental properties of Homer 1 in mouse heart in association with cardiac ryanodine receptor (RyR), a binding protein of Homer 1. METHODS AND RESULTS: Immunohistochemistry of adult mouse heart with Homer 1 antibody showed striated staining on Z-bands both in atria and ventricles. The interactions between Homer 1 and RyR were confirmed by co-immunoprecipitation assays. Immunostaining of adult isolated cardiomyocytes showed partial co-localization of both proteins. In neonatal primary cultures, targeting of Homer 1 preceded that of RyR in their Z-band arrangement. CONCLUSIONS: Homer 1 binds to RyR in adult mouse heart and precedes RyR in Z-band arrangement in the early postnatal period.

Skeletonized harvesting improves the early-term and mid-term perfect patency of a radial artery graft.

OBJECTIVE: A radial artery (RA) graft is frequently used for coronary artery bypass grafting (CABG), but little information exists regarding the early- and mid-term patency associated with the harvesting procedure. The objective of this study is to compare the early- and mid-term patency of the RA graft obtained using non-skeletonized and skeletonized harvesting. METHODS: Altogether, 131 patients and 159 anastomoses were studied. In 85 patients the RA was harvested non-skeletonized (group A: procedures between September 2000 and November 2002), whereas in 46 patients the RA was harvested skeletonized (group B: procedures between November 2002 and April 2004). Angiography results were analyzed before discharge [A: postoperative day (POD) 14.7 +/- 2.9, 75 patients, 90 anastomoses; B: POD 13.7 +/- 1.9, 38 patients, 47 anastomoses], and after 1 year (A: POD 386.8 +/- 149.3, 44 patients, 51 anastomoses; B: POD 267.1 +/- 148.7, 11 patients, 13 anastomoses). RESULTS: There was no difference in patency between the two groups (group A vs group B, 96.7% vs 100%, P = not significant [NS], in the early-term, 96.2% vs 100%, P = NS, in the mid-term). However, the perfect patency rates for groups A and B were 86.7% and 98.1%, respectively, in the early-term (P = 0.034) and 77.5% and 100%, respectively, in the mid-term (P = 0.048). The location and severity of the target vessel did not influence the angiographic results. CONCLUSION: The early- and mid-term patency of RA grafts was excellent, and skeletonized harvesting improved the perfect patency rates at both time points.

[Endoscopic radial artery harvesting].

The radial artery is a popular arterial conduit for coronary artery bypass grafting (CABG). However, the traditional open harvesting technique requires a long incision, and is therefore associated with some wound complications and cosmetic problems. In order to solve them, we introduced the endoscopic radial artery harvesting (ERAH) at our institution in February 2004 utilizing the VasoView system. The ERAH technique was performed as safely as the traditional open technique and the harvested radial arteries were acceptable as CABG conduits. In particular, patients are satisfied with the excellent cosmetic results of the procedure. Herein, we focus surgical technique, complications of ERAH and ways to prevent them by describing our initial experience and short-term clinical follow-up of the ERAH patients.

Cytosolic phospholipase A2 inhibition attenuates ischemia-reperfusion injury in an isolated rat lung model.

BACKGROUND: Arachidonic acid metabolites and platelet-activating factor (PAF) are potentially involved in ischemia-reperfusion (IR) lung injury. A key enzyme regulating their metabolism is cytosolic phospholipase A2 (cPLA2). Arachidonyl trifluoromethyl ketone (AACOCF3) is reported to be a potent cPLA2 inhibitor. In the present study, we hypothesized that pharmacological inhibition of cPLA2 might ameliorate IR lung injury. METHODS: To test the hypothesis, we examined the effects of AACOCF3 in an isolated rat lung model. Three groups were defined (n=6, each): in the vehicle group, lungs were perfused for 2 hours without an ischemic period. In the ischemic groups, 20 mg/kg of AACOCF3 (AACOCF3 group) or saline (control group) was i.v. administered 15 min before lung harvest. Lungs were flushed with LPD solution, cold-stored 18 hours, and reperfused for 2 hours. RESULTS: IR increased cPLA2 activity mainly via alveolar macrophages, sPLA2 activity, thromboxane and leukotriene formation, and the expression of PAF receptor, whereas AACOCF3 treatment significantly reduced all of these. Compared to the vehicle group, the wet-to-dry ratio, proteins in BAL, and MPO activity increased significantly by twofold, fourfold, and threefold, respectively. Furthermore, the PO2 dropped from 615.7+/-31.2 to 452.1+/-30.9 mmHg at the end of reperfusion (P<0.001). AACOCF3 treatment maintained the PO2 at a level similar to the vehicle group throughout reperfusion and reduced significantly the alveolar-capillary leakage, edema formation, and neutrophil extravasation. CONCLUSION: Pharmacological inhibition of the cPLA2 cascade decreases bioactive lipid formation and attenuates IR-induced lung injury.

An evaluation strategy for the early detection of postoperative delirium.

The aim of the present study was to identify clinical signs detective of the postoperative delirium at the early stage for nursing management. A total of 66 inpatients undergoing cardiac surgery were interviewed using the Delirium Rating Scale (DRS) and NEECHAM Confusion Scale (NCS) preoperatively and on days 1 and 3 postoperatively. The mean onset of delirium occurred on postoperative day 1.3. Development of delirium was detected early by cognitive impairments in the DRS subscales of perceptual disturbance, hallucination, and cognitive status, and the NCS subscales of attention, command, orientation, and verbal skill. These results suggest that assessment of cognitive status on postoperative day is an important strategy in the early detection of postoperative delirium.

Physiological comparison of off-pump and on-pump coronary artery bypass grafting in patients on chronic hemodialysis.

OBJECTIVES: Despite the long-term benefit, the operative results of conventional coronary artery bypass grafting for chronic hemodialysis patients remain unsatisfactory. The efficacy of off-pump coronary artery bypass grafting for hemodialysis patients is yet to be determined. The purpose of this study was to investigate the postoperative physiology of off-pump coronary artery bypass grafting for hemodialysis patients. METHODS: Twenty-five hemodialysis cases who underwent isolated coronary artery bypass grafting were reviewed. Fifteen of these patients underwent off-pump coronary artery bypass grafting (off-group) and 10 underwent on-pump coronary artery bypass grafting (on-group). Comparisons were made in cardiac function (cardiac index and stroke volume index), respiratory function (AaDO2), hemodialysis management (blood urea nitrogen, creatinine, right atrial pressure, pulmonary wedge pressure), and bleeding tendency (postoperative blood loss and blood transfusion). RESULTS: There was no operative mortality, but 3 major postoperative complications occurred (2 sternal wound infections in the off-group and 1 pneumonia in the on-group). There was no difference in cardiac index or stroke volume index. AaDO2 was significantly lower in the off-group. Plasma concentrations of blood urea nitrogen and creatinine were similar between groups. Right atrial pressure was lower and pulmonary wedge pressure tended to be lower in the off-group. Postoperative bleeding and blood transfusion were similar between groups. CONCLUSION: Our study confirmed that off-pump coronary artery bypass grafting is feasible for hemodialysis patients. Physiologic data showed that off-pump coronary artery bypass grafting might be effective in preserving postoperative lung oxygenation.

Matrix metalloproteinase inhibitor (ONO-4817) attenuates ischemia-reperfusion injury in rat lung.

BACKGROUND: Ischemia-reperfusion injury of the lungs seems to be initiated by the activation of alveolar macrophages, and mediated by matrix metalloproteinases (MMP)s, although their roles have not been fully elucidated. Therefore, we used a novel MMP inhibitor (ONO-4817) with high affinities for MMP-2 and MMP-9 to investigate the roles of MMPs in reperfusion injury of the lungs. MATERIAL/METHODS: After 18 h of cold ischemia, isolated rat lungs were ventilated and reperfused. Lungs without ischemia served as controls. Lungs were reperfused with fresh blood with or without the MMP inhibitor for 120 min at 37 degrees C. RESULTS: The oxygenation capacity of lungs after ischemia deteriorated progressively during 120 min of reperfusion, but was preserved by the MMP inhibitor (p<0.05). The histopathology of the lungs after ischemia-reperfusion showed interstitial edema accompanied by neutrophil migration, and the number of neutrophils, but not macrophages, in the broncho-alveolar lavage increased to more than two-fold the value in control lungs without ischemia (p<0.01). These changes were attenuated by the MMP inhibitor (p<0.01). Similarly, an increase in the tissue malondialdehyde level in lungs after ischemia-reperfusion was ameliorated by the MMP inhibitor (p<0.01). The expressions of CD11c and CD31 adhesion molecules in extracted alveolar macrophages increased in lungs after ischemia-reperfusion compared with control lungs without ischemia, and the MMP inhibitor had no obvious effect. CONCLUSIONS: Our data show that ONO-4817 prevented neutrophil migration into the interstitial space and alveolus in the lungs, and reduced the production of oxygen free radicals, suggesting that this is an important mechanism in reperfusion injury.

MCI-186 (edaravone), a free radical scavenger, attenuates ischemia-reperfusion injury and activation of phospholipase A(2) in an isolated rat lung model after 18 h of cold preservation.

OBJECTIVE: Increased microvascular permeability and extravasation of inflammatory cells are key events in ischemia-reperfusion (IR) injury. We hypothesized that edaravone, a free radical scavenger, is able to attenuate IR lung injury by decreasing oxidative stress and phospholipase A(2) (PLA(2)) activation, which otherwise may lead to lung injury through PAF receptor (PAF-R) activation. METHODS: We used an isolated rat lung model. Five groups were defined (n=7, each): in the sham and vehicle group, lungs were immediately washed after thoracotomy or perfused for 2h without an ischemic period, respectively. In the ischemic groups, 10mg/kg of MCI-186 (edavorane group), 1mg/kg of PAF-R inhibitor (ABT-491 group) or saline (control group) were i.v. administered 20 min before harvest. Lungs were flushed with LPD solution, stored at 4 degrees C for 18 h, and reperfused for 2h. RESULTS: Compared to vehicle group, IR significantly decreased the PO(2) level and increased the wet-to-dry ratio, proteins in bronchoalveolar lavage (BAL), and myeloperoxidase (MPO) activity in the control group, while edaravone treatment maintained the PO(2) similar to the vehicle group and significantly reduced edema formation and neutrophil extravasation. Consistently, IR significantly increased lipid peroxidation, cytosolic-PLA(2) activity mainly via alveolar macrophages, soluble-PLA(2) activity, leukotriene B(4), and PAF-R expression in control lungs, together with a decreased PAF acetylhydrolase (PAF-AH) activity. Edaravone significantly reduced all of these, but increased PAF-AH activity. Furthermore, pharmacological inhibition of the PAF-R attenuated IR injury resembling edaravone action. CONCLUSION: Edaravone attenuates lung IR injury by suppressing oxidative damage and PLA(2) activation, which otherwise partially mediates edema formation and neutrophil extravasation through PAF-R activation.

Radial artery graft for coronary artery bypass surgery: biological characteristics and clinical outcome.

The radial artery (RA) is gaining popularity as a bypass conduit for coronary artery bypass grafting, and its impact on clinical practice has been extensively explored. In the present article, we provide a review of postoperative hand circulation, vascular biological characteristics of the RA graft, the efficacy of vasodilator therapies, and mid-term clinical results of use of the RA graft. Fundamental studies revealed excellent vascular biological characteristics of the RA graft as a living arterial conduit, making it almost equivalent to the internal thoracic artery (ITA) graft. Clinical studies have yielded encouraging mid-term results. Most studies reported in favor of the RA graft over the saphenous vein graft with regard to patency rate, freedom from cardiac events, and survival. However, superiority of either the RA or right ITA graft has not been conclusively determined. The long-term results of RA grafts remain unknown, but at present, supplementary use of an RA graft with a left ITA graft appears feasible for CABG.

A new multisuction cardiac positioner for multivessel off-pump coronary artery bypass grafting.

OBJECTIVE: : To accomplish successful multivessel off-pump coronary artery bypass grafting, safe, reproducible, and effective exposure of all coronary territories is essential. For this purpose, we developed a new, simple, multisuction cardiac positioner. METHODS: : This new cardiac positioner consists of 3 small independent suction cups and suction tubes made of silicone. Unlike an apical suction cardiac positioner, this positioner has no arm. The suction cups can be applied with negative pressure of 300 mm Hg to various surfaces of the ventricle, including not only the apex but also the lateral, inferior, and right ventricular walls, according to surgeon preference. We applied this positioner in 15 clinical multivessel off-pump coronary artery bypass procedures. RESULTS: : In all cases, all target vessels including those on the lateral or inferior wall were successfully exposed and grafted without hemodynamic compromise. Surgical exposure, especially on the lateral and inferior walls, was quite similar to that of conventional coronary artery bypass graft procedures performed during cardiopulmonary bypass. CONCLUSIONS: : The multisuction cardiac positioner provided reproducible and easy access in multivessel off-pump coronary artery bypass surgery. This simple, variable, and inexpensive cardiac positioner may be used as a new tool to aid in the performance of successful multivessel off-pump coronary artery bypass surgery.

Hand circulation after radial artery harvest for coronary artery bypass grafting.

Despite wide spread use of the radial artery (RA) graft for coronary artery bypass grafting, the change of hand circulation after RA harvest has not been fully clarified. Severe hand ischemia such as resting pain or gangrene is a rare complication and has been reported in 4 patients. These cases resulted from occlusive artery disease in forearm, which should be carefully explored before RA harvest. Incidence of mild hand ischemia such as hand claudication or fatigue is unknown, but our study suggested that around 10% of the patients developed mild hand ischemia after RA harvest. The blood flow to the forearm territory was decreased by 20% after RA harvest despite the compensatory dilatation of ulnar artery. The presence of low perfusion in the affected hand has been pointed out in some studies. We reported the decreased tissue oxygenation of the affected hand during hand grip exercise. The Allen test is the most popular preoperative screening method, but is associated with considerable numbers of false-positive and false-negative results. Full length scanning of ulnar artery by ultrasonography seems to have a lower false-positive rate. But further clinical experience is necessary to establish a more reliable screening method.

Estrogen inhibits cell proliferation through in situ production in human thymoma.

PURPOSE: We showed previously estrogen receptor (ER) alpha as an independent prognostic marker in human thymoma. Estrogen sulfotransferase (EST), steroid sulfatase (STS), 17beta-hydroxysteroid dehydrogenase (17beta-HSD), and aromatase are considered to play important roles in hormone metabolism of estrogen-dependent tumors. EXPERIMENTAL DESIGN: We examined estrogen production using primary cultures of human thymoma epithelial cells (TEC), intratumoral estradiol (E(2)) concentrations, and status of these enzymes above using immunohistochemistry or semiquantitative reverse transcription-PCR. We then correlated these findings with clinicopathologic variables and/or clinical outcome in 132 patients. RESULTS: E(2) inhibited cell proliferation via ERalpha in TEC, which synthesized estrone and E(2). Intratumoral E(2) concentrations were inversely correlated with EST, positively correlated with STS or 17beta-HSD type 1, and significantly higher in lower-grade or early-stage thymoma. EST status was positively correlated with tumor size, clinical stage, histologic differentiation, and Ki-67 labeling index and significantly associated with adverse clinical outcome and turned out to be a potent independent prognostic factor. STS and/or 17beta-HSD type 1 status was inversely correlated with Ki-67 labeling index and associated with lower histologic grade or early clinical stages. CONCLUSIONS: E(2) inhibits proliferation of TEC through ERalpha, which suggests that E(2) may be effective in treatment of thymoma, especially inoperable tumor, possibly through suppressing its cell proliferation activity. EST status is a potent prognostic factor in thymoma through inactivating estrogens. In situ estrogen synthesis through intracrine mechanism therefore may play important roles in tumorigenesis and/or development of thymoma through regulation of cell proliferation in an intracrine manner.

Safe coronary artery occlusion with a new tourniquet in off-pump bypass grafting.

Coronary artery occlusion during off-pump coronary artery bypass grafting may lead to mechanical trauma of the arterial wall. My colleagues and I describe a safe coronary artery occlusion technique in off-pump bypass grafting that uses a new spring-equipped tourniquet, which enables precise adjustment of the least force necessary to occlude the coronary flow. This prevents snare-induced vessel wall damage.

Aprotinin attenuated ischemia-reperfusion injury in an isolated rat lung model after 18-hours preservation.

OBJECTIVE: Ischemia-reperfusion injury is a major factor in the early phase of lung transplantation. We hypothesized that aprotinin, a nonspecific serine protease inhibitor, attenuates ischemia-reperfusion lung injury by inhibiting the inflammatory response and suppressing NADPH oxidase. METHODS: We used an isolated rat lung model to test the above. A Control group was immediately perfused with fresh heparinized allogeneic blood after lung harvest without an ischemic period. Study lungs were flushed with low-potassium dextran (LPD) solution and stored for 18h at 4 degrees C then divided into two groups: the LPD group was flushed with LPD solution only, and the LPD+A group was flushed with LPD solution +200KIU/ml aprotinin. Lungs in all three groups were then reperfused with fresh heparinized allogeneic blood for 120min at 37 degrees C. RESULTS: Throughout reperfusion, PO(2) levels in the LPD+A group were similar to those in the Control group; although in the LPD group, PO(2) levels were significantly lower (P<0.05). Tissue MDA levels were significantly higher in the LPD group than the Control and LPD+A groups (P<0.05). IL-8 levels were significantly higher in the LPD group than the Control group (P<0.05), while in the LPD+A group they were similar to those in the Control group. Histological evaluation showed interstitial edema accompanied by neutrophil extravasation in the LPD group, whereas this effect was modest in the LPD+A group. An additional study of ischemia-reperfusion in an alveolar macrophage culture showed that the activitvation of NADPH oxidase, and translocation of p47(phox) from the cytosol to the membrane were suppressed in aprotinin group. CONCLUSIONS: Aprotinin attenuates ischemia-reperfusion lung injury by inhibiting the early inflammatory response, neutrophil extravasation and the production of oxygen free radicals through inhibition of the activation of the NADPH oxidase. The inhibition of p47(phox) translocation in alveolar macrophage seemed involved in this mechanism of aprotinin.

Stress response gene ATF3 is a target of c-myc in serum-induced cell proliferation.

The c-myc proto-oncogene encodes a transcription factor that promotes cell cycle progression and cell proliferation, and its deficiency results in severely retarded proliferation rates. The ATF3 stress response gene encodes a transcription factor that plays a role in determining cell fate under stress conditions. Its biological significance in the control of cell proliferation and its crosstalk regulation, however, are not well understood. Here, we report that the serum response of the ATF3 gene expression depends on c-myc gene and that the c-Myc complex at ATF/CREB site of the gene promoter plays a role in mediating the serum response. Intriguingly, ectopic expression of ATF3 promotes proliferation of c-myc-deficient cells, mostly by alleviating the impeded G1-phase progression observed in these cells, whereas ATF3 knockdown significantly suppresses proliferation of wild-type cells. Our study demonstrates that ATF3 is downstream of the c-Myc signaling pathway and plays a role in mediating the cell proliferation function of c-Myc. Our results provide a novel insight into the functional link of the stress response gene ATF3 and the proto-oncogene c-myc.

Frequent silencing of DBC1 is by genetic or epigenetic mechanisms in non-small cell lung cancers.

Genome-wide screening of DNA copy number aberrations in 27 cell lines derived from non-small cell lung cancers (NSCLCs), using a custom-made comparative genomic hybridization (CGH)-array, identified a homozygous deletion of the deleted in bladder cancer 1 gene (DBC1) in one cell line. Homozygous deletion of DBC1, located at 9q33.1, was also observed in two of 53 primary NSCLC tumors examined. Moreover, 21 of the other 26 cell lines showed complete loss of DBC1 expression, although normal lung tissues express this gene, and treatment with 5-aza-2'-deoxycytidine restored expression of DBC1. Hypermethylation in part of a CpG island around the exon 1 of DBC1 has been reported in urothelial cancers, but the potential association between methylation and expression status was never clarified in that disease. In our experiments, a different part of the same CpG island showed promoter activity in vitro and was frequently methylated in our cell lines and primary tumors of NSCLC, where methylation status correlated inversely with gene expression. Among our primary NSCLC cases, methylation of the DBC1 promoter occurred more frequently in men, elderly patients and smokers than in women, younger patients and nonsmokers respectively, but it was not correlated with tumor stage or histology. Exogenous overexpression of DBC1 in NSCLC cell lines lacking its expression inhibited cell growth. Our results provide the first evidence that DBC1 is a likely tumor suppressor for NSCLC; silencing of the gene through homozygous deletion or methylation of its promoter region may be associated with progression of this disease.

Effects of the postoperative administration of diltiazem on renal function after coronary artery bypass grafting.

BACKGROUND: Radial artery grafts are used for coronary artery bypass grafting (CABG), and postoperative antispasm therapy with diltiazem is performed widely. Some investigators have warned that diltiazem administration after cardiac surgery is harmful to renal function. We designed a retrospective study to investigate the renal and hemodynamic effects of the postoperative administration of diltiazem in patients undergoing CABG. METHODS: Subjects were 90 consecutive CABG patients. All were treated with diltiazem during surgery (a 0.1 mg/kg bolus injection followed by continuous infusion at 2 microg x kg(-1) x min(-1)). In the 50 patients (diltiazem group) with a radial artery graft, intravenous diltiazem administration was continued until the oral intake of diltiazem (90 mg/d) was begun to avoid graft spasms. In the remaining 40 patients without a radial artery graft, diltiazem was not continued postoperatively (control group). Postoperative renal function, assessed by serum creatinine level and creatinine clearance, and hemodynamic variables (heart rate, arterial pressure, pulmonary wedge pressure, cardiac index, left ventricular stroke work index) was compared between the two groups. RESULTS: Renal function: Serum creatinine concentrations on postoperative days 1 through 7 were lower, and the endogenous creatinine clearance in the early postoperative period was higher in diltiazem group than in control group, although the differences were not significant. Hemodynamics: Heart rate was lower in diltiazem group than in the control group, but blood pressure, pulmonary wedge pressure, cardiac index, left ventricular stroke work index, and urinary output were similar between the groups. CONCLUSIONS: Our results confirmed that intravenous diltiazem treatment in patients undergoing CABG is not harmful to renal function.

Synthetic salusins as cardiac depressors in rat.

Using bioinformatic analyses of full-length, enriched human cDNA libraries, we recently identified salusins, multifunctional related peptides ubiquitously expressed in major human tissues. Salusins cause transient and profound hypotension when injected intravenously to rats, the hypotensive effect of salusin-beta being especially striking. However, the mechanisms of this hypotensive action remain elusive. To determine whether salusins modulate cardiac function in rats, we studied serial changes of systemic hemodynamics and functions of isolated perfused working and nonworking hearts before and after salusin administration. Intravenous salusin-beta administration to intact anesthetized rats caused a temporary rapid, profound decrease in aortic blood flow concomitantly with hypotension and bradycardia without affecting systemic vascular resistance. Salusin-beta-induced hypotension and bradycardia were completely blocked by pretreatment with atropine, a muscarinic receptor antagonist, but not by propranolol. In isolated perfused working rat hearts, salusin-beta significantly decreased cardiac output, aortic flow, and stroke work. However, it did not affect coronary flow in isolated working and nonworking hearts. Our results indicate that salusins induce potent hypotension via negative inotropic and chronotropic actions. Salusin-beta promotes its actions by facilitating vagal outflows to the heart, whereas the negative inotropism of salusin-beta is also mediated via a direct myotropic effect.