RESUMO
A 55-year-old man with autoimmune deficiency syndrome presented with an infected left ventricular pseudoaneurysm and sepsis. The aneurysmectomy consisted of a Dor-style pericardial patch plus debridement of the abscess cavities. The infected pseudoaneurysm recurred, much larger, within five months due to persistent infected abscess cavities. The second repair was done without a Dor-style patch and with an omental flap. No recurrence has occurred one year after the second repair, but the patient has asymptomatic, partial gastric herniation inside the pericardium. This is the first description of a primary infected left ventricular pseudoaneurysm. The omental flap contributed to the successful treatment.
Assuntos
Falso Aneurisma/cirurgia , Aneurisma Infectado/cirurgia , Procedimentos Cirúrgicos Cardíacos/métodos , Aneurisma Cardíaco/cirurgia , Omento/transplante , Retalhos Cirúrgicos , Falso Aneurisma/diagnóstico , Aneurisma Infectado/diagnóstico , Ecocardiografia , Aneurisma Cardíaco/diagnóstico , Ventrículos do Coração , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: The therapeutic options for heart failure include inotropic agents, intraaortic balloon pumps, and left ventricular assist devices (LVAD). Implantable LVADs are not appropriate for all patients. The short-term devices require patients to stay in bed, connected to cannulas, which are usually inserted using a median sternotomy. This approach requires a subsequent sternotomy, midline cannulas (which can make sitting difficult), and immobility. We began using a right thoracotomy with cannulas placed through intercostal spaces for selected patients in need of temporary LVAD support. METHODS: This retrospective chart review examined our experience with CentriMag LVAD placement via right thoracotomy from August 2009 to June 2013. We reviewed the reasons for support, the degree of postoperative mobilization, and the outcomes of the patients treated in this manner. RESULTS: This approach was used in 6 patients. Four patients lacked financial or social support for a long-term, implantable LVAD. One patient was considered too ill to have an implantable LVAD placed, and one was treated with temporary support with hope for recovery from myocarditis. Five of these 6 patients were able to walk soon after LVAD implantation and initiate rehabilitation. One did not recover and had support withdrawn. Another suffered a stroke and had support withdrawn. Four of the 6 were transplanted successfully. CONCLUSIONS: CentriMag LVAD implantation via a right thoracotomy is a feasible approach that provides adequate hemodynamic support while allowing patients to ambulate, making subsequent cardiac transplantation less complicated by allowing the avoidance of a repeat sternotomy.
Assuntos
Insuficiência Cardíaca/reabilitação , Insuficiência Cardíaca/cirurgia , Coração Auxiliar , Toracotomia/métodos , Adolescente , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Caminhada , Adulto JovemRESUMO
BACKGROUND: About one-third of patients undergoing a Roux-en-Y anastomosis develop Roux stasis syndrome, likely because of disordered electrical conduction. GI electrical stimulation has been previously used successfully in the management of postsurgical gastroparesis. OBJECTIVE: Endoscopic placement of temporary electrodes and GI electrical stimulation in the management of severe Roux stasis syndrome in a patient with esophagojejunostomy and to determine whether the patient would be a candidate for surgical permanent electrode placement. DESIGN: Case report. SETTING: Academic medical center. PATIENTS: This study involved a patient with Roux stasis syndrome. INTERVENTION: Upper endoscopy was performed, followed by endoscopic placement of two temporary electrodes, one each in the two jejunal limbs. Electrical stimulation was provided by an external stimulation device. The patient was re-evaluated 5 days later. MAIN OUTCOME MEASUREMENTS: Electrogastrogram (EGG) parameters including frequency, amplitude, and frequency-amplitude ratio and total symptom score and health-related quality of life score. RESULTS: There was a significant improvement in EGG parameters with electrical stimulation. Also, the patient had a marked improvement in total GI symptom score, from 11 to 4, with a dramatic improvement in the health-related quality of life score from -3 to +3. LIMITATIONS: Single case report. CONCLUSION: Endoscopic placement of temporary electrodes is feasible and safe. GI electrical stimulation of the jejunal limb is a potentially effective treatment for Roux stasis syndrome.
Assuntos
Anastomose em-Y de Roux/efeitos adversos , Terapia por Estimulação Elétrica/métodos , Dor Abdominal/etiologia , Dor Abdominal/terapia , Esôfago/cirurgia , Feminino , Gastrectomia/efeitos adversos , Trânsito Gastrointestinal , Humanos , Jejunostomia/efeitos adversos , Pessoa de Meia-Idade , Náusea/etiologia , Náusea/terapia , Índice de Gravidade de Doença , Síndrome , Vômito/etiologia , Vômito/terapiaRESUMO
In cardiac transplantation settings, the initial myocardial ischemia and reperfusion may cause myocyte tissue injury and the release of allograft inflammatory factor-1 (AIF-1). This in part may trigger the innate immune response through the modulation of Toll-like receptor-2 (TLR-2) and AIF-1 expression and function, causing the release of proinflammatory cytokines. The goal was to demonstrate these markers in the peripheral blood and biopsy specimen from recipients with cardiac allograft rejection and coronary vasculopathy (CV). Peripheral blood and endomyocardial specimens were tested by reverse transcriptase-polymerase chain reaction and immunohistochemistry stains for identification of TLR-2, -4, interleukin-18, and AIF-1 markers and analyzed against clinical rejection grades for rejection. The differences for mRNA transcript levels were determined by one-way analysis of variance. The mRNA expression levels were significantly varied for TLR-2 in monocytes with different rejection grades (P < 0.0001). The mean +/- SEM level of mRNA expression for 3A grade rejection was 64.21 +/- 3.8; grade 1A, 38.4 +/- 3.5; and for Grade 0 was 38.46 +/- 2.8. The TLR-4 mRNA expression was increased but the specificity was not statistically significant. The TLR-2 immunoreactivity was strongly detected in infiltrating mononuclear cells and cardiac myocytes in Grade 3A rejection. AIF-1 expression was increased significantly in the group with 3A rejection and Grade III CV as compared with Grade 0 or 1A. Interleukin-18 receptors were strongly detected in Grade 3A rejection and CV. The expression profiles of AIF-1, TLR-2, and interleukin-18 were correlated with biopsy-proven allograft rejection in both peripheral blood and local tissue, suggesting a potential for diagnostic biomarkers for early detection of allograft rejection.
Assuntos
Biomarcadores/análise , Doença das Coronárias/diagnóstico , Proteínas de Ligação a DNA/análise , Rejeição de Enxerto/diagnóstico , Transplante de Coração , Interleucina-18/análise , Receptores Toll-Like/análise , Proteínas de Ligação ao Cálcio , Endocárdio/química , Humanos , Imuno-Histoquímica , Proteínas dos Microfilamentos , Reação em Cadeia da Polimerase , RNA Mensageiro/análiseRESUMO
BACKGROUND AND PURPOSE: The association between left atrial (LA) size, ischemic stroke, and death has not been well established in African Americans despite their disproportionately higher rates of stroke and cardiovascular mortality compared to non-Hispanic whites. METHODS: For the analysis, participants in the Jackson cohort of the Atherosclerosis Risk in Communities Study were followed from the date of the echocardiogram in cycle three to the date of the first ischemic stroke event (or death) or to December 31, 2004 if no ischemic stroke event (or death) was detected. RESULTS: There were 1886 participants in the study population (mean age 58.9 years, 65% women). Participants in the top quintile of LA diameter indexed to height (LA diameter/height; 2.57 to 3.55 cm/m) were more likely women, hypertensive, diabetic, and obese compared to those not in the top quintile. Over a median follow-up of 9.8 years for ischemic stroke and 9.9 years for all-cause mortality, there were 106 strokes and 242 deaths. In a multivariable model adjusting for traditional clinical risk factors, the top quintile of LA diameter/height was significantly related to ischemic stroke (HR 1.7; 95% CI: 1.1, 2.7) and all-cause mortality (HR 2.0; 95% CI: 1.5, 2.7). After further adjustment for left ventricular (LV) hypertrophy and low LV ejection fraction, the top quintile remained significantly related to all-cause mortality (HR 1.8; 95% CI: 1.3, 2.5). CONCLUSIONS: In this population-based cohort of African Americans, LA size was a predictor of all-cause mortality after adjusting for traditional cardiovascular risk factors, LV hypertrophy, and low LV ejection fraction.
Assuntos
Átrios do Coração/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/mortalidade , Negro ou Afro-Americano , Idoso , Aterosclerose/complicações , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de RiscoRESUMO
This is an interesting case of a young patient suffering an acute embolic stroke in the middle cerebral artery distribution, who was later found to have a papillary fibroelastoma on the mitral valve. The mass was first recognized by transesophageal echocardiography and eventually resected surgically. The retrieved specimen had classic histologic findings of a papillary fibroelastoma. A thrombus was noted on the tip of the specimen, supporting the theory that these masses are risks for strokes secondary to damage along the endothelial lining predisposing to subsequent fibrin deposition and mural thrombus formation.
Assuntos
Fibroma/diagnóstico , Neoplasias Cardíacas/diagnóstico , Embolia Intracraniana/diagnóstico , Músculos Papilares/patologia , Acidente Vascular Cerebral/diagnóstico , Adulto , Negro ou Afro-Americano , Procedimentos Cirúrgicos Cardíacos , Diagnóstico Diferencial , Ecocardiografia Transesofagiana , Fibroma/complicações , Fibroma/patologia , Fibroma/cirurgia , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/patologia , Neoplasias Cardíacas/cirurgia , Humanos , Embolia Intracraniana/etiologia , Masculino , Músculos Papilares/cirurgia , Acidente Vascular Cerebral/etiologia , Tomografia Computadorizada por Raios XRESUMO
For repair of interrupted aortic arch, unfavorable anatomy challenges a tension-free anastomosis. We describe a useful alternative surgical technique used in five neonates/infants, involving splitting the ascending aorta from the sinotubular junction to the arch origin, leftward and posterior "sliding" of the flap with anastomosis to the distal arch creating a native tissue bridge, and reconstruction with a patch. With wide interruption gaps between proximal and distal aortic portions, the ascending aortic slide is a safe and reproducible technique, providing a tension-free native tissue bridge with potential for growth, and a scaffold for patch augmentation in biventricular hearts, or for Norwood stage I in univentricular palliation.
Assuntos
Aorta Torácica/cirurgia , Coartação Aórtica/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Anastomose Cirúrgica/métodos , Aorta Torácica/anormalidades , Feminino , Seguimentos , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Although matrix metalloproteinase (MMP) activity increases, endothelial function decreases after myocardial infarction (MI). The antibiotic doxycycline inhibits MMP activity in vitro. The role of doxycycline-mediated MMP inhibition in endothelial function is unclear. HYPOTHESIS: Doxycycline ameliorates endothelial dysfunction, in part, by inhibiting MMP activity. METHODS: We subjected Sprague-Dawley male rats to MI by ligating the left anterior descending arteries. We subjected another group of rats to sham surgery. We administered doxycycline in drinking water (0.67 mg/ml) to both groups 2 days before surgery: the sham group underwent sham surgery and received doxycycline therapy, and the MI group underwent MI and received doxycycline therapy (n = 6 in each group). After 4 weeks, we anesthetized rats and prepared left ventricular rings from infarcted-ischemic (I), non-infarcted near-infarcted (NI), and sham surgery hearts with and without doxycycline treatment. RESULTS: The MMP-2 activity increased significantly in I and NI hearts, and we observed a selective increase in MMP-9 activity only in I hearts, when compared with other groups (p < 0.05), measured by zymography. Cardiac inhibitor of metalloproteinase decreased only in I hearts (p < 0.05 vs other groups), measured by Western analysis, and doxycycline treatment reversed this decrease. Contractile response of rings to acetylcholine was attenuated in the I group, suggesting nitric oxide-mediated dysfunction, and was reversed by doxycycline. The response to nitroprusside was attenuated in I hearts and ameliorated by doxycycline, suggesting cardiomyocyte dysfunction. Bradykinin induced relaxation in rings from sham surgery hearts and from NI hearts, but induced paradoxic contraction in rings from I hearts. Treatment with doxycycline reversed the paradoxic contraction. CONCLUSION: Results suggest a protective action of doxycycline in the ischemic heart, possibly because of additional pharmacologic actions such as metalloproteinase inhibition.
Assuntos
Cardiotônicos/farmacologia , Doxiciclina/farmacologia , Endocárdio/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Infarto do Miocárdio/metabolismo , Remodelação Ventricular/efeitos dos fármacos , Animais , Endocárdio/fisiopatologia , Hidroxiprolina/metabolismo , Metaloproteinase 2 da Matriz/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/efeitos dos fármacos , Inibidores de Metaloproteinases de Matriz , Ratos , Ratos Sprague-Dawley , Inibidores Teciduais de Metaloproteinases/efeitos dos fármacos , Inibidores Teciduais de Metaloproteinases/metabolismo , Inibidor Tecidual 4 de MetaloproteinaseAssuntos
Endocardite Bacteriana/complicações , Staphylococcus aureus Resistente à Meticilina , Infecção Puerperal/microbiologia , Insuficiência da Valva Pulmonar/complicações , Valva Pulmonar , Infecções Estafilocócicas/complicações , Ecocardiografia Transesofagiana , Endocardite Bacteriana/diagnóstico , Endocardite Bacteriana/cirurgia , Feminino , Próteses Valvulares Cardíacas , Humanos , Infecção Puerperal/cirurgia , Valva Pulmonar/diagnóstico por imagem , Insuficiência da Valva Pulmonar/cirurgia , Infecções Estafilocócicas/cirurgia , Adulto JovemRESUMO
PURPOSE: This study was designed to assess the use of the intrathoracic vacuum-assisted management of persistent and infected pleural spaces. DESCRIPTION: Five patients with a persistent and infected pleural space after pulmonary resection underwent intrathoracic vacuum-assisted management to reduce the duration and frequency of dressing changes and to accelerate the formation of granulation tissue and the obliteration of the pleural space. Three patients also underwent a pleural space filling procedure. EVALUATION: Resolution of the infection or complete obliteration of the pleural space, or both, was in all patients achieved using fewer dressing changes than with traditional methods. No major complications related to the vacuum-assisted management were reported. CONCLUSIONS: The use of intrathoracic vacuum-assisted management of a persistent and infected pleural space after lung resection may reduce the duration and frequency of dressing changes necessary to allow spontaneous chest closure or a space filling procedure. Its use may decrease patient discomfort and contribute to a faster resolution of the infectious process.
Assuntos
Fístula Brônquica/cirurgia , Doenças Pleurais/cirurgia , Adulto , Fístula Brônquica/etiologia , Fístula Brônquica/microbiologia , Empiema Pleural/microbiologia , Empiema Pleural/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tratamento de Ferimentos com Pressão Negativa , Doenças Pleurais/etiologia , Doenças Pleurais/microbiologia , Pneumonectomia/efeitos adversos , Pneumonia/complicações , ToracotomiaRESUMO
We report the case of a 29-year-old woman with combined bronchial rupture and aortic valve tear after blunt chest trauma. She was successfully treated with primary repair of both lesions. The importance of chest computed tomography and transthoracic echocardiography in the diagnosis of these lesions is discussed.
Assuntos
Valva Aórtica/lesões , Brônquios/lesões , Traumatismos Torácicos/complicações , Ferimentos não Penetrantes/complicações , Acidentes de Trânsito , Adulto , Valva Aórtica/cirurgia , Brônquios/cirurgia , Feminino , Humanos , Ruptura , Traumatismos Torácicos/diagnóstico , Traumatismos Torácicos/cirurgiaAssuntos
Procedimentos Cirúrgicos Cardíacos , Mediastinite/etiologia , Mediastinite/terapia , Cuidados Pós-Operatórios , Sucção/métodos , Infecção da Ferida Cirúrgica/etiologia , Infecção da Ferida Cirúrgica/terapia , Cicatrização , Antibacterianos/uso terapêutico , Humanos , Infecções Estafilocócicas/etiologia , Infecções Estafilocócicas/terapiaAssuntos
Ponte de Artéria Coronária/métodos , Remoção de Dispositivo/métodos , Endarterectomia/métodos , Intubação Intratraqueal/métodos , Idoso , Estenose das Carótidas/diagnóstico , Estenose das Carótidas/cirurgia , Dor no Peito/diagnóstico , Dor no Peito/cirurgia , Terapia Combinada , Estenose Coronária/complicações , Estenose Coronária/diagnóstico , Estenose Coronária/cirurgia , Seguimentos , Humanos , Masculino , Monitorização Fisiológica/métodos , Cuidados Pós-Operatórios , Fatores de Tempo , Resultado do TratamentoAssuntos
Competência Clínica , Esofagectomia/normas , Avaliação de Processos e Resultados em Cuidados de Saúde , Centros Médicos Acadêmicos , Adolescente , Adulto , Idoso , Comorbidade , Esofagectomia/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Internato e Residência , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Reoperação/estatística & dados numéricos , Estudos RetrospectivosRESUMO
PURPOSE: The use of the denervated intrathoracic stomach as esophageal substitute can rarely lead to severe delayed gastric emptying. We describe the use of electrostimulation for this condition. DESCRIPTION: Gastric electrical stimulation (GES) is used to treat medically refractory gastroparesis and uses a battery powered neurostimulator connected to the gastric antrum with two electrodes. We implant the electrodes through a right thoracotomy and tunnel them to the right subcostal area where the pacemaker is placed. EVALUATION: Medically refractory gastroparesis developed in 2 male patients, aged 52 and 60 years, who underwent Ivor-Lewis esophagectomies for esophageal adenocarcinoma and were dependant on jejunostomy feedings. These patients initially had endoscopic placement of temporary stimulating electrodes with significant improvement in symptoms and radionucleotide gastric emptying. The patients subsequently underwent implantation of a permanent GES device. Relief of symptoms was persistent with no nausea or vomiting and a decrease of total symptom score (maximum 20) from 12.5 and 16 to 6 and 9, respectively. CONCLUSIONS: Patients with intractable delayed gastric emptying after esophagogastrectomy may benefit from a GES device implanted through a thoracotomy.
Assuntos
Terapia por Estimulação Elétrica/métodos , Esofagectomia/efeitos adversos , Gastroparesia/terapia , Qualidade de Vida , Adenocarcinoma/diagnóstico , Adenocarcinoma/cirurgia , Eletrodos Implantados , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Junção Esofagogástrica/cirurgia , Seguimentos , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Esvaziamento Gástrico/fisiologia , Gastroparesia/etiologia , Gastroparesia/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Cavidade Torácica , Resultado do TratamentoAssuntos
Angioplastia com Balão/instrumentação , Mediastinite/complicações , Esclerose/complicações , Stents , Síndrome da Veia Cava Superior/etiologia , Síndrome da Veia Cava Superior/terapia , Angioplastia com Balão/métodos , Feminino , Seguimentos , Humanos , Mediastinite/diagnóstico por imagem , Pessoa de Meia-Idade , Flebografia/métodos , Medição de Risco , Estudos de Amostragem , Esclerose/diagnóstico por imagem , Síndrome da Veia Cava Superior/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento , Grau de Desobstrução Vascular/fisiologia , Adulto JovemRESUMO
An interesting case of a young patient presenting with Austrian's Triad: pneumococcal pneumonia, pneumococcal meningitis, and pneumococcal endocarditis. On echocardiogram the patient was noted to have a noncoronary sinus of Valsalva aneurysm and vegetations on the aortic cusps resulting in disruption of valvular integrity and severe aortic insufficiency. Color Doppler also revealed rupture of the aneurysm into the right atrium. The patient was taken to surgery where the noncoronary cusp was noted to be completely replaced with vegetative lesions. The aortic valve was replaced with a No. 21 Carpentier-Edwards bioprosthetic valve (Edwards Lifesciences, Irvine, CA), and the noncoronary sinus of Valsalva was repaired with concomitant closure of the fistula using glutaraldehyde autologous pericardium.
Assuntos
Aneurisma Aórtico/complicações , Insuficiência da Valva Aórtica/cirurgia , Infecções Pneumocócicas/complicações , Seio Aórtico , Adulto , Aneurisma Aórtico/congênito , Aneurisma Aórtico/cirurgia , Insuficiência da Valva Aórtica/etiologia , Ecocardiografia Doppler em Cores , Endocardite Bacteriana/diagnóstico por imagem , Endocardite Bacteriana/etiologia , Endocardite Bacteriana/cirurgia , Implante de Prótese de Valva Cardíaca , Humanos , Masculino , Meningite Pneumocócica/etiologia , Pneumonia Pneumocócica/etiologiaRESUMO
CYP 3A4 plays a vital role in the metabolism of many drugs including immunosuppressants. An association between a transition of A --> G at position -290 of the 5'-regulatory region of the CYP 3A4 gene and an effect on the level of transcription has been reported. The CYP 3A4-G variant frequency varies substantially in different populations. In addition it has been demonstrated in association with several disease conditions, including clinical grades of prostate cancer, breast cancer, secondary leukemia, hypercholesterolemia and diabetes. We sought to determine the frequency distributions, in African American (AFAM) and Caucasian (CAU) populations as well as patients with multiple complex diseases, such as those that had undergone cardiac or renal transplantation. Sequence-specific primers and PCR were used to determine genotype variation in 206 AFAM and 108 CAU individuals. CYP 3A4-G genotype was present with a higher frequency in AFAM individuals as compared with CAU (83% vs. 3%, p < 0.0001, RR = 3.9). The homozygous AA allele was predominantly present in CAU (97%) but only 17% in AFAM (p < 0.0001, RR = 2.5). In contrast, the homozygous GG allele was only detected in AFAM group (14.6%). The frequency distribution of homozygous GG and AA alleles were inversely present in male vs. female patients with CTx or RTx. Pre-transplantation clinical conditions demonstrated that hypertension (HTN), hyperlipidemia and to a lesser extent diabetes (DM) were present in CTx and RTx patients with homozygous GG alleles. In addition, 75% of AFAM patients with homozygous GG genotype experienced multiple rejection episodes with severity grades of 3A after cardiac transplantation, and 31.5% of homozygous GG patients with RTx suffered from rejections (p < 0.05; RR = 2.4). In conclusion, CYP 3A4 genotype demonstrated a remarkable interindividual variation between AFAM and CAU populations, and furthermore CTx patients with homozygous GG genotype were at higher risk of developing rejection as compared with RTx patients. This indicates an underlying heterogeneity with regard to the disease characteristics as well as the therapy regimen.
Assuntos
Sistema Enzimático do Citocromo P-450/genética , Rejeição de Enxerto/genética , Transplante de Coração/imunologia , Transplante de Rim/imunologia , Polimorfismo Genético , Negro ou Afro-Americano/genética , Alelos , Citocromo P-450 CYP3A , Feminino , Frequência do Gene , Rejeição de Enxerto/imunologia , Heterozigoto , Homozigoto , Humanos , Masculino , Fatores Sexuais , Transplante Homólogo , População Branca/genéticaRESUMO
Extracellular matrix (ECM) turnover is regulated by matrix metalloproteinases (MMPs) and plays an important role in cardiac remodeling. Previous studies from our lab demonstrated an increase in gelatinolytic-MMP-2 and -9 activities in endocardial tissue from ischemic cardiomyopathic (ICM) and idiopathic dilated cardiomyopathic (DCM) hearts. The signaling mechanism responsible for the left ventricular (LV) remodeling, however, is unclear. Administration of cardiac specific inhibitor of metalloproteinase (CIMP) prevented the activation of MMP-2 and -9 in ailing to failing myocardium. Activation of MMP-2 and -9 leads to induction of proteinase activated receptor-1 (PAR-1). We hypothesize that the early induction of MMP-9 is a key regulator for modulating intracellular signaling through activation of PAR and various downstream events which are implicated in development of cardiac fibrosis in an extracellular receptor mediated kinase-1 (ERK-1) and focal adhesion kinase (FAK) dependent manner. To test this hypothesis, explanted human heart tissues from ICM and DCM patients were obtained at the time of orthotopic cardiac transplants. Quantitative analysis of MMP-2 and -9 gelatinolytic activities was made by real-time quantitative zymography. Gel phosphorylation staining for PAR-1 showed a significant increase in ICM hearts. Western blot and RT-PCR analysis and in-situ labeling, showed significant increased expression of PAR-1, ERK-1and FAK in ICM and DCM. These observations suggest that the enhanced expression and potentially increased activity of LV myocardial MMP-9 triggers the signal cascade instigating cardiac remodeling. This early mechanism for the initiation of LV remodeling appears to have a role in end-stage human heart failure.