ABSTRACT
PURPOSE: The diagnosis of leptomeningeal metastases is usually confirmed by the finding of malignant cells by cytologic examination in the cerebrospinal fluid (CSF). More sensitive and specific cancer biomarkers may improve the detection of tumor cells in the CSF. Promoter methylation of the human telomerase reverse transcriptase (hTERT) gene characterizes most cancer cells. The aim of this study was to develop a sensitive method to detect hTERT methylation and to explore its use as a cancer biomarker in CSF. EXPERIMENTAL DESIGN: In 77 CSF specimens from 67 patients, hTERT promoter methylation was evaluated using real-time methylation-sensitive high-resolution melting (MS-HRM) and real-time TaqMan PCR and MS-HRM in a single-tube assay. RESULTS: Real-time MS-HRM assay was able to detect down to 1% hTERT-methylated DNA in a background of unmethylated DNA. PCR products were obtained from 90% (69/77) of CSF samples. No false positive hTERT was detected in the 21 non-neoplastic control cases, given to the method a specificity of 100%. The sensitivity of the real-time MS-HRM compared with the cytologic gold standard analysis was of 92% (11/12). Twenty-six CSFs from 22 patients with an hTERT-methylated primary tumor showed cytologic results suspicious for malignancy; in 17 (65%) of them, a diagnosis of leptomeningeal metastases could be confirmed by the hTERT methylation test. CONCLUSION: The hTERT real-time MS-HRM approach is fast, specific, sensitive, and could therefore become a valuable tool for diagnosis of leptomeningeal metastases as an adjunct to the traditional examination of CSF.
Subject(s)
DNA Methylation , Neoplasms/genetics , Promoter Regions, Genetic/genetics , Telomerase/genetics , Biomarkers, Tumor/cerebrospinal fluid , Biomarkers, Tumor/genetics , DNA, Neoplasm/cerebrospinal fluid , DNA, Neoplasm/genetics , Female , Humans , Male , Meningeal Neoplasms/diagnosis , Meningeal Neoplasms/genetics , Meningeal Neoplasms/secondary , Neoplasms/enzymology , Neoplasms/pathology , Real-Time Polymerase Chain Reaction/methods , Reproducibility of Results , Sensitivity and SpecificityABSTRACT
INTRODUCTION: Previous research has demonstrated that sildenafil citrate users alter dosing-sexual attempt behavior when switched to tadalafil. The impact of geography and culture on sexual behavior with phosphodiesterase type 5 (PDE5) inhibitor treatment has not been fully investigated. AIM: To describe and compare the changes in dosing-sexual attempt behavior with sildenafil citrate vs. tadalafil treatment across four distinct geographies: Asia, Australia/New Zealand (ANZ), Central Eastern Europe/Middle East (CEE/ME), and Latin America (LA). METHODS: Data from a single-arm, open-label clinical trial conducted in 21 countries from November 2002 to May 2004 were used in this analysis. Men with erectile dysfunction and a history of > or =6-week prior sildenafil citrate use continued sildenafil citrate treatment for 4 weeks then switched to tadalafil for 8 weeks. Dosing instructions were provided. MAIN OUTCOMES MEASURES: Timing of dose and sexual intercourse was assessed through patient diaries for the final 4 weeks of each treatment period. RESULTS: A total of 2,760 men were enrolled: Asia 15.8%; ANZ 29.4%; CEE/ME 19.7%; LA 35.1%. The median time from dosing to intercourse was significantly increased during tadalafil treatment across all geographical regions; however, the magnitude of increase differed significantly by geography (P < 0.0001). The Asian cohort demonstrated the shortest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the least upon switching to tadalafil. The ANZ cohort demonstrated the longest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the most upon switching to tadalafil. CONCLUSION: Men with a history of established sildenafil citrate use alter their dose-attempt behavior when treated with tadalafil irrespective of geography. However, the extent to which sexual behavior alters is not uniform across geographical regions, suggesting that dosing instructions and duration of drug effectiveness, in combination with personal and cultural preferences, may determine sexual behavior with PDE5 inhibitor use.
Subject(s)
Carbolines/therapeutic use , Coitus , Impotence, Vasculogenic/drug therapy , Phosphodiesterase Inhibitors/therapeutic use , Piperazines/therapeutic use , Sulfones/therapeutic use , Analysis of Variance , Asia , Australia , Confidence Intervals , Europe , Geography , Health Status Indicators , Humans , Latin America , Male , Middle Aged , Middle East , New Zealand , Patient Satisfaction , Purines/therapeutic use , Sildenafil Citrate , Tadalafil , Time FactorsABSTRACT
OBJECTIVE: Patients with major depressive disorder (MDD) frequently report concomitant painful physical symptoms, which may negatively impact diagnosis and treatment. The purpose of this study was to estimate the frequency of painful physical symptoms in Asian patients treated for an acute episode of MDD and to describe the associated demographics, clinical status, treatment patterns, and socioeconomic burden. METHOD: This multicountry, observational study enrolled 909 patients with MDD (DSM-IV-TR or ICD-10 criteria) in the psychiatric care setting from June 14, 2006, to February 15, 2007. Patients were classified as positive for painful physical symptoms (PPS+) if they achieved a mean score >or= 2 on the modified Somatic Symptom Inventory. The Clinical Global Impressions-Severity of Illness scale (CGI-S) and 17-item Hamilton Rating Scale for Depression (HAM-D(17)) determined depression severity, and the EuroQoL Questionnaire-5 dimensions (EQ-5D) assessed subjective well-being. RESULTS: Overall, 51.8% of patients were classified as PPS+. PPS+ patients were more likely to be female (72.2% vs. 65.1%, p = .022), had relatively more medical comorbidity (29.7% vs. 21.0% with >or= 1 comorbidity, p = .003), were more significantly depressed (CGI-S mean [SE] score = 4.84 [0.03] vs. 4.63 [0.04], p < .001; HAM-D(17) mean [SE] score = 24.80 [0.26] vs. 22.39 [0.27], p < .001), and reported a lower quality of life (EQ-5D health state mean [SE] score = 42.96 [0.92] vs. 52.92 [0.95], p < .001) than PPS- patients. PPS+ and PPS- patients did not differ markedly, however, in terms of MDD medications prescribed or MDD-related disability at work. CONCLUSION: Painful physical symptoms are experienced by approximately half of patients with MDD in Asia and are associated with poor clinical status and perceived quality of life.
Subject(s)
Depressive Disorder, Major/epidemiology , Pain/epidemiology , Adult , Asia, Southeastern , Comorbidity , Cross-Sectional Studies , Depressive Disorder, Major/diagnosis , Depressive Disorder, Major/psychology , Asia, Eastern , Female , Health Surveys , Humans , Male , Middle Aged , Pain/psychology , Pain Measurement , Personality Inventory/statistics & numerical data , Prospective Studies , Psychometrics , Quality of Life/psychologyABSTRACT
Superficial primitive Ewing's sarcomas are rare and have been reported to be of favorable prognosis compared to conventional deep-seated tumors. In the skin and subcutis, the diagnosis is often difficult, and performing molecular cytogenetic techniques may be helpful. We performed a retrospective analysis of 14 cases of superficial Ewing's sarcomas, all confirmed by molecular cytogenetics. Clinical, histological, immunohistochemical, molecular cytogenetic, therapeutic, and follow-up data are reported. There were 11 female and 3 male patients aged from 12 to 77 years (median: 17 years). Seven tumors occurred in the extremities, five in the trunk wall, and two in the head. Tumor size ranged from 1 to 5 cm (median, 3 cm). They were all small round-cell proliferations with a strong membranous positivity for CD99. Ewing's sarcoma translocations/fusion gene transcripts were detected in eight cases, both by FISH and reverse transcriptase (RT)-PCR. Four tumors were positive by RT-PCR alone (FISH not done in three cases and not interpretable in one case), and two cases were positive by FISH alone (RT-PCR not done). Surgical resection was performed in all patients. Chemotherapy was given in ten patients and radiotherapy in six. At last medical examination (median follow-up, 47 months), two patients who underwent surgical resection alone had died from the tumor. Our results confirm that superficial Ewing's sarcomas are of good prognosis. Given the difficulty of the diagnosis and the importance of an adapted treatment, a confirmation of the diagnosis by molecular or cytogenetic techniques is recommended when dealing with a superficial tumor.
Subject(s)
Sarcoma, Ewing/genetics , Sarcoma, Ewing/pathology , Soft Tissue Neoplasms/genetics , Soft Tissue Neoplasms/pathology , 12E7 Antigen , Adolescent , Adult , Aged , Antigens, CD/biosynthesis , Calmodulin-Binding Proteins/genetics , Cell Adhesion Molecules/biosynthesis , Child , Cytogenetic Analysis , Female , Humans , Immunohistochemistry , In Situ Hybridization, Fluorescence , Male , Middle Aged , Oncogene Proteins, Fusion/genetics , RNA-Binding Protein EWS , RNA-Binding Proteins/genetics , Retrospective Studies , Reverse Transcriptase Polymerase Chain Reaction , Sarcoma, Ewing/therapy , Soft Tissue Neoplasms/therapyABSTRACT
Low-grade fibromyxoid sarcomas (LGFMS) bear either the t(7,16) (q32-34;p11) or t(11,16) (p11;p11) translocations, resulting in FUS-CREB3L2 or FUS-CREB3L1 fusions, respectively. Heretofore, fusion transcripts were mainly detected in frozen tissues, using reverse transcription-polymerase chain reaction. In this study, we aimed to develop a reliable method to detect these in paraffin-embedded tissues, and to examine the clinicopathologic characteristics of a series of translocation-positive LGFMS. Sixty-three neoplasms with typical morphologic features of LGFMS and 66 non-LGFMS tumors selected for their resemblance to LGFMS (LGFMS-like tumors) were examined. RNA of sufficient quality could be extracted from 111/129 (86%) cases (59 LGFMS, 52 non-LGFMS). Of all, 48/59 (sensitivity, 81%) LGFMS contained detectable transcripts (45 FUS-CREB3L2, 3 FUS-CREB3L1). Most relevant clinicopathologic features of fusion-positive LGFMS included predominance in lower extremities (22/48; thigh: 13/48), deep situation (46/48), and occasional presence of unusual histologic features, for example, hypercellular areas (16/48), foci of epithelioid cells (13/48), and giant rosettes (6/48). Most tumors expressed EMA (41/45), at least focally, CD99 (38/41) and bcl-2 (36/41) while being essentially negative for CD34 (2/45), mdm2 (1/41), smooth muscle actin (1/45), S100 protein (0/46), desmin (0/44), h-caldesmon (0/42), keratins (0/44), and CD117 (0/40). Eleven presumed LGFMS were fusion negative. Of all, 7/52 non-LGMFS neoplasms contained FUS-CREB3L2 transcripts, of which 4 had been diagnosed as sclerosing epithelioid fibrosarcoma. In conclusion, FUS-CREB3L1/L2 fusion transcripts can be detected in paraffin-embedded LGFMS in a sensitive manner, using reverse transcription-polymerase chain reaction. Most fusion-positive LGFMS are EMA-positive and CD34/S100/smooth muscle actin negative. The presence of epithelioid cells and fusion transcripts in both LGFMS and a subset of sclerosing epithelioid fibrosarcoma suggest that these neoplasms might be related.
Subject(s)
Basic-Leucine Zipper Transcription Factors/genetics , Biomarkers, Tumor/genetics , Cyclic AMP Response Element-Binding Protein/genetics , Epithelioid Cells/pathology , Fibroma/diagnosis , Fibrosarcoma/diagnosis , Gene Expression Regulation, Neoplastic , Nerve Tissue Proteins/genetics , RNA-Binding Protein FUS/genetics , Translocation, Genetic , Adolescent , Adult , Aged , Base Sequence , Biomarkers, Tumor/analysis , Child , Female , Fibroma/chemistry , Fibroma/genetics , Fibroma/pathology , Fibrosarcoma/chemistry , Fibrosarcoma/genetics , Fibrosarcoma/pathology , Humans , In Situ Hybridization, Fluorescence , Male , Middle Aged , Molecular Sequence Data , Neoplasm Invasiveness , Paraffin Embedding , Predictive Value of Tests , RNA, Messenger/analysis , Reproducibility of Results , Reverse Transcriptase Polymerase Chain Reaction , Sensitivity and SpecificityABSTRACT
The HeartPatch direct cardiac compression device consists of two separate, nonsurround patches placed on the left and right ventricular free walls. Although the device has been shown to effectively restore circulatory parameters in acute heart failure sheep, the impact of device inflation on left ventricular geometry is yet to be elucidated. This study used sonomicrometer crystal transducers to examine three orthogonal left ventricular dimensions under various cardiac states and assessed the feasibility of determining stroke volume from these dimensions. Seven sheep (weight, 51 +/- 5 kg) were implanted with six sonomicrometer crystals, and a heart patch was placed on each of the ventricles. The crystals were positioned to measure anterior-posterior, septal-lateral, and apex-base (long-axis) dimensions. Sheep were studied under both awake and anesthetized conditions. Septal-lateral shortening was increased with direct cardiac compression assist, whereas anterior-posterior and long-axis dimensions were either unchanged (awake) or decreased (anesthetized). Estimation of stroke volume, using the ellipsoid volume model, correlated well with stroke volume measured from an aortic flow probe; however, absolute stroke volumes were lacking in agreement.
Subject(s)
Cardiac Output, Low/surgery , Heart-Assist Devices , Models, Cardiovascular , Ventricular Function, Left/physiology , Acute Disease , Adrenergic beta-Antagonists , Anesthesia , Animals , Aorta , Cardiac Output, Low/chemically induced , Cardiac Volume , Disease Models, Animal , Female , Propanolamines , Prosthesis Design , Sheep , Stroke Volume , Transducers , WakefulnessABSTRACT
Direct cardiac compression (DCC) with implanted heart patches has previously demonstrated efficacy of biventricular (BiV) support in acute heart failure (HF) sheep. We hypothesized that this was primarily due to a left ventricular (LV) effect. This study compared BiV, LV, and right ventricular (RV) assists in terms of hemodynamic and energetic response. Ten sheep underwent instrumentation and device implantation at least 1 week prior to study. HF (50% reduction in cardiac output) was maintained with intravenous esmolol infusion. BiV, LV, and RV assists were activated randomly with intervening stable HF periods. BiV assist was more effective than either LV or RV assist in restoring hemodynamic parameters; however, there was no difference in efficacy of LV and RV support. RV assist preserved left coronary flow patterns and chamber geometry compared to other assist conditions, but increased LV preload. These results suggest that LV and RV support each make a significant contribution to the efficacy of BiV assist, albeit through different mechanisms.
Subject(s)
Assisted Circulation/instrumentation , Heart Failure/therapy , Heart-Assist Devices , Ventricular Function , Animals , Assisted Circulation/methods , Coronary Circulation/physiology , Coronary Vessels/physiology , Disease Models, Animal , Heart/physiology , Implants, Experimental , SheepABSTRACT
Cardiac remodeling following myocardial infarction (MI) is a maladaptive process, fundamental to the progression of ischemic heart failure. The extent of remodeling is influenced by mechanical stress, inflammatory response and activation of matrix metalloproteinases (MMPs). This study examined regional association between these parameters in response to acute MI. Coronary ligation was performed in ten sheep. Sonomicrometer transducers measured segmental length in the infarcted, border and non-infarcted region. Regional tissue samples obtained 3 h post MI from six sheep were analysed using RT-PCR, gelatin zymography and Western blot. Six sham-operated sheep served as controls.Region-specific dilation and reduced contraction was associated with corresponding alterations in matrix molecules.IL-6 and MMP-9 mRNA were increased in the infarcted and border regions compared to controls.MMP-2 and TIMP-1 mRNA increased in non-infarcted myocardium and both correlated positively with segmental shortening. IL-6 mRNA levels, in contrast, were negatively associated with segmental shortening. In summary, inflammatory cytokines and MMPs are altered early after MI in a region-specific manner, and these changes correspond to acute regional myocardial dysfunction. Therapies for LV remodeling from the time of reperfusion may benefit from further understanding this portfolio of acute alterations.
Subject(s)
Cytokines/metabolism , Matrix Metalloproteinases/metabolism , Myocardial Contraction/physiology , Myocardial Infarction/metabolism , Myocardium/metabolism , Animals , Female , Interleukin-6/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Sheep , Tissue Inhibitor of Metalloproteinase-1/metabolismABSTRACT
Left ventricular (LV) remodeling is a process whereby structural alterations attempt to compensate altered hemodynamic load. In the chronic setting this process becomes maladaptive, self-sustaining and is associated with worsened survival. The extracellular matrix (ECM) of the heart, once believed an inert scaffold for cardiomyocytes, is now known to play an important role in LV remodeling. The enzyme system primarily responsible for ECM turnover is the matrix metalloproteinases (MMPs), and these enzymes are robustly altered in cardiovascular pathologies, including myocardial infarction (MI) and ischemic heart failure. A cause-and-effect relationship has been established between MMPs and LV remodeling post MI, as MMP inhibition prevents LV dilation and preserves cardiac function in animal models of infarction. In spite of this, initial clinical experience with MMP inhibition post MI has been disappointing. This review examines the structural and functional roles of the myocardial ECM, the evidence for MMP involvement in LV remodeling, and recent investigations into MMPs as prognostic markers and therapeutic targets.
Subject(s)
Cardiac Output, Low/enzymology , Extracellular Matrix/enzymology , Matrix Metalloproteinases/metabolism , Myocardial Ischemia/enzymology , Myocardium/enzymology , Ventricular Remodeling , Animals , Cardiac Output, Low/drug therapy , Extracellular Matrix/chemistry , Fibrillar Collagens/chemistry , Fibrillar Collagens/metabolism , Fibrillar Collagens/physiology , Humans , Matrix Metalloproteinase Inhibitors , Myocardial Infarction/enzymology , Myocardial Ischemia/drug therapy , Myocardium/chemistryABSTRACT
PURPOSE: To assess the prognostic value of SYT-SSX fusion type, in comparison with other factors, in a population of 165 patients with synovial sarcoma (SS). PATIENTS AND METHODS: Data on 165 patients with SS (141 with localized disease at diagnosis) were studied retrospectively. The following parameters were examined for their potential prognostic value: age at diagnosis, sex, tumor site (extremities v proximal/truncal), size, histology, mitotic count, necrosis, histologic grade (Federation Nationale des Centres de Lutte Contre le Cancer system), stage (1997 tumor-node-metastasis system classification), surgical margin status (assessed histologically), and fusion type (SYT-SSX1 v SYT-SSX2). Median follow-up time was 37 months (range, 2 to 302 months). RESULTS: Among those patients with localized disease at diagnosis, median and 5-year disease-specific survivals (DSS) for the SYT-SSX1 and SYT-SSX2 subgroups were 126 months and 67.4% versus 82 months and 63.2%, respectively (P = .12). Median and 5-year metastasis-free survivals (MFS) were 84 months and 54.2% for SYT-SSX1 versus 50 months and 47.6% for SYT-SSX2 (P = .76). Univariate analyses showed that high histologic grade (grade 3), high mitotic count (>/= 10 mitoses/10 high-power fields), stage III disease, size greater than 7 cm, tumor necrosis, and presence of areas of poorly differentiated morphology were significant adverse prognostic factors for DSS and MFS, whereas SYT-SSX fusion type, tumor histology (biphasic v monophasic), and patient sex were not. Age greater than 35 years adversely affected DSS but not MFS. In multivariate analyses, histologic grade was the most significant prognostic factor for both DSS and MFS. CONCLUSION: For patients with localized SS, histologic grade but not SYT-SSX fusion type is a strong predictor of survival.
Subject(s)
Oncogene Proteins, Fusion/genetics , Sarcoma, Synovial/diagnosis , Adolescent , Adult , Age Factors , Biomarkers, Tumor/analysis , Child , Female , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Metastasis , Prognosis , Proportional Hazards Models , Retrospective Studies , Sarcoma, Synovial/pathology , Survival RateABSTRACT
BACKGROUND: Previous evidence from laboratory animal studies indicates that R-thiopental has a greater margin of safety than either the more potent S-thiopental or the clinically used rac-thiopental. Although thiopental can cause cardiovascular depression from direct myocardial effects as well as indirect central nervous system and peripheral effects, no studies have yet determined whether its myocardial effects are enantioselective. A lesser direct effect would provide further evidence supporting R-thiopental as a preferred single enantiomer replacement for rac-thiopental. METHODS: The direct myocardial effects of the thiopental enantiomers were compared to those of rac-thiopental and propofol, using a crossover design with small incremental doses infused over 3 min, on separate days, into the left coronary arteries of conscious sheep. Hemodynamic and electrocardiographic measurements were acquired, and serial blood samples were collected during the studies for drug analyses. RESULTS: All three forms of thiopental and propofol produced significant hemodynamic effects consisting of dose-related and rapid-onset decreases in left ventricular dP/dtmax and stroke volume, and increases in left coronary blood flow and heart rate. Cardiac output, mean arterial blood pressure, and central venous pressure remained unaltered. The effects did not differ significantly among rac-thiopental, enantiopure R- or S-thiopental, or propofol. Arterial blood drug concentrations were consistently less than those associated with systemic effects. CONCLUSIONS: Although previous evidence indicates that R-thiopental could make a suitable single-enantiomer replacement for rac-thiopental, the current study did not find a significant difference in direct cardiac effects among the thiopental enantiomers, racemate, or propofol.
Subject(s)
Coronary Vessels/drug effects , Heart/drug effects , Hypnotics and Sedatives/pharmacology , Propofol/pharmacology , Thiopental/pharmacology , Animals , Dose-Response Relationship, Drug , Electrocardiography/drug effects , Female , Hemodynamics/drug effects , Hypnotics and Sedatives/administration & dosage , Hypnotics and Sedatives/pharmacokinetics , Injections, Intra-Arterial , Propofol/administration & dosage , Propofol/pharmacokinetics , Sheep , Stereoisomerism , Thiopental/administration & dosage , Thiopental/pharmacokineticsABSTRACT
The mandatory use of pharmacotherapy in human heart failure (HF) impedes further study of natural history and remodeling mechanisms. We created a sheep model of chronic, severe, ischemic HF [left ventricular (LV) ejection fraction (LVEF) <35% stable over 4 wk] by selective coronary microembolization under general anesthesia and followed hemodynamic, energetic, neurohumoral, structural, and cellular responses over 6 mo. Thirty-eight sheep were induced into HF (58% success), with 23 sheep followed for 6 mo (21 sheep with sufficient data for analysis) after the LVEF stabilized (median of 3 embolizations). Early doubling of LV end-diastolic pressure persisted, as did increases in LV end-diastolic volume, LV wall stress, and LV wall thinning. Contractile impairment (LV end-systolic elastance, LV preload recruitable stroke work, and dobutamine-responsive contractile reserve) and diastolic dysfunction also remained stable. Cardiac mechanical energy efficiency did not recover. Plasma atrial natriuretic peptide levels remained elevated, but rises in plasma aldosterone and renin activity were transient. Collagen content increased 170%, the type I-to-III phenotype ratio doubled in the LV, but right ventricular collagen remained unaltered. Fas ligand cytokine levels correlated with expression of both caspase-3 and -2, suggesting a link in the apoptotic "death cascade." Caspase-3 activity also bore a close relationship to LV meridional wall stress calculated from echocardiographic and intraventricular pressure measurements. We concluded that the stability of chronic untreated severe ischemic HF depends on the recruitment of myocardial remodeling mechanisms that involve an interaction among hemodynamic load, contractile efficiency/energetics, neurohumoral activation, response of the extracellular matrix, wall stress, and the myocyte apoptotic pathway.
Subject(s)
Heart Failure/pathology , Heart Failure/physiopathology , Myocardial Ischemia/pathology , Myocardial Ischemia/physiopathology , Ventricular Remodeling/physiology , Aldosterone/blood , Angiotensin II/blood , Animals , Atrial Natriuretic Factor/blood , Caspase 2 , Caspase 3 , Caspase 8 , Caspases/metabolism , Chronic Disease , Collagen/metabolism , Coronary Vessels/physiopathology , Embolism/metabolism , Embolism/pathology , Embolism/physiopathology , Extracellular Matrix/pathology , Fas Ligand Protein , Female , Heart Failure/metabolism , Male , Membrane Glycoproteins/metabolism , Microcirculation , Microspheres , Myocardial Contraction , Myocardial Ischemia/metabolism , Myocardium/metabolism , Myocardium/pathology , Severity of Illness Index , Sheep , Stroke VolumeABSTRACT
A novel HeartPatch direct cardiac compression (DCC) device has been shown to effectively restore circulatory parameters in sheep with acute heart failure (HF). Its effect on the coronary circulation and myocardial perfusion, however, remains uncertain. The effect of DCC assist on coronary artery blood flow (CABF) and its patterns in acute HF sheep were examined in this study. Ten sheep (51 +/- 6 kg) were implanted with a heart patch on each of the left ventricular and right ventricular free walls 1 week before study. Stable HF [cardiac output (CO) at 51 +/- 8% of baseline] induced by intravenous esmolol resulted in CABF decreasing to 53 +/- 16% of baseline (p < 0.001). DCC device activation did not alter CABF (54 +/- 15% of baseline, N.S.) but was accompanied by increases in both peak antegrade and retrograde flow velocity (161 +/- 75%, p < 0.001 and 413 +/- 377%, p < 0.001). A shift in the proportion of flow occurring in diastole (%DF) also was observed: baseline, 81 +/- 9%; HF, 82 +/- 6%; DCC assist, 121 +/- 16% (p < 0.001). Despite significant changes in coronary artery flow pattern resulting from DCC of the failing heart, total antegrade coronary flow was maintained. These findings suggest that myocardial perfusion is not compromised by DCC.