RESUMO
The purpose of this work was to evaluate the level of antimicrobial resistant Escherichia coli isolates in freshwaters and hospital effluents in Belgium. The samples were collected from 24 locations along the Ourthe, Vesdre, Amblève and Meuse rivers and in the wastewater effluents of several hospitals. The sampling stations in rivers were classified according to the dominant land covers of the rivers (rural, urban and forest areas). Two sampling campaigns were organized in May and October 2019 to highlight a possible seasonal effect. A total of 938 E. coli strains were isolated on Chromogenic Selective Tryptone Bile X-glucuronide (TBX) and TBX supplemented with amoxicillin (TBX+AMX) media. Disk diffusion assays were performed following the EUCAST's recommendations to assess the antimicrobial resistance against 12 antibiotics. A total of 32·7% of strains were at least resistant to one antibiotic and 24·6% were multiple antimicrobial resistant strains on TBX. The highest resistance rates were found for ampicillin (AMP), amoxicillin coupled with clavulanic acid (AMC) and sulfamethoxazole/trimethoprim (SXT). The lowest resistance rates were observed for meropenem (MEM) and ertapenem (ETP), which are last resort antibiotics. No significant difference was observed between both campaigns for the resistance rate to antibiotics.
Assuntos
Anti-Infecciosos , Escherichia coli , Antibacterianos/farmacologia , Bélgica , Farmacorresistência Bacteriana , Água Doce , Hospitais , Testes de Sensibilidade MicrobianaRESUMO
Prostaglandins (PGs) are ubiquitous lipid mediators derived from cyclooxygenase metabolism of arachidonic acid that exert a broad range of physiologic activities, including modulation of inflammation, ovulation and arterial blood pressure. PGE2, a chief cyclooxygenase product, modulates blood pressure and fertility, although the specific G protein-coupled receptors mediating these effects remain poorly defined. To evaluate the physiologic role of the PGE2 EP2 receptor subtype, we created mice with targeted disruption of this gene (EP2-/-). EP2-/- mice develop normally but produce small litters and have slightly elevated baseline systolic blood pressure. In EP2-/- mice, the characteristic hypotensive effect of intravenous PGE2 infusion was absent; PGE2 infusion instead produced hypertension. When fed a diet high in salt, the EP2-/- mice developed profound systolic hypertension, whereas wild-type mice showed no change in systolic blood pressure. Analysis of wild-type and EP2-/- mice on day 5 of pregnancy indicated that the reduced litter size of EP2-/- mice is due to a pre-implantation defect. This reduction of implanted embryos could be accounted for by impaired ovulation and dramatic reductions in fertilization observed on day 2 of pregnancy. These data demonstrate that the EP2 receptor mediates arterial dilatation, salt-sensitive hypertension, and also plays an essential part in female fertility.
Assuntos
Hipertensão/complicações , Infertilidade Feminina/etiologia , Receptores de Prostaglandina E/fisiologia , Animais , Blastocisto , Clonagem Molecular , Desenvolvimento Embrionário , Feminino , Hipertensão/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Gravidez , Receptores de Prostaglandina E/genética , Receptores de Prostaglandina E Subtipo EP2 , Sódio na Dieta/efeitos adversos , VasodilataçãoRESUMO
Prostaglandin E2 (PGE2), a major cyclooxygenase (COX) metabolite, plays important roles in tumor biology. We studied the role of EP2, a receptor for PGE2, in tumor angiogenesis using EP2 knockout mice. We found that deletion of the EP2 receptor impaired tumor angiogenesis and this finding was confirmed by an in vivo corneal angiogenesis model and an ex vivo aortic ring assay. To further characterize the cellular mechanisms of the EP2 receptor in angiogenesis, we isolated primary pulmonary endothelial cells (ECs) from wild-type (wt) and EP2-/- mice and observed that EP2-/- ECs exhibited defects in vascular branch formation when compared to wt ECs. In addition, EP2-/- ECs showed impaired cell motility on collagen-coated surface and they responded poorly to PGE2-induced cell migration compared to control cells. However, no difference in cell proliferation was observed between the EP2-/- and wt Ecs. In addition, EP2-/- ECs were more susceptible to apoptosis than wt cells under growth factor depletion conditions. Collectively, our data demonstrate that EP2 signaling in endothelium directly regulates tumor angiogenesis by contributing to cell survival and endothelial cell motility. Moreover, our finding suggests that EP2 is a major receptor in PGE2-mediated cell motility in ECs.
Assuntos
Movimento Celular , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Neoplasias/irrigação sanguínea , Neoplasias/metabolismo , Receptores de Prostaglandina E/metabolismo , Animais , Sobrevivência Celular , Transplante de Células , Células Cultivadas , Meios de Cultura Livres de Soro , DNA/biossíntese , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Neoplasias/genética , Neoplasias/patologia , Receptores de Prostaglandina E/deficiência , Receptores de Prostaglandina E/genética , Receptores de Prostaglandina E Subtipo EP2RESUMO
PGE2 exerts potent diuretic and natriuretic effects on the kidney. This action is mediated in part by direct inhibition of collecting duct Na+ absorption via a Ca++-coupled mechanism. These studies examine the role the Ca++-coupled PGE-E EP1 receptor plays in mediating these effects of PGE2 on Na+ transport. Rabbit EP1 receptor cDNA was amplified from rabbit kidney RNA. Nuclease protection assays demonstrated highest expression of EP1 mRNA in kidney, followed by stomach, adrenal, and ileum. In situ hybridization, demonstrated renal expression of EP1 mRNA was exclusively over the collecting duct. In fura-2-loaded microperfused rabbit cortical collecting duct, EP1 active PGE analogs were 10-1, 000-fold more potent in raising intracellular Ca++ than EP2, EP3, or EP4-selective compounds. Two different EP1 antagonists, AH6809 and SC19220, completely blocked the PGE2-stimulated intracellular calcium increase. AH6809 also completely blocked the inhibitory effect of PGE2 on Na+ absorption in microperfused rabbit cortical collecting ducts. These studies suggest that EP1 receptor activation mediates PGE2-dependent inhibition of Na+ absorption in the collecting duct, thereby contributing to its natriuretic effects.
Assuntos
Dinoprostona/farmacologia , Túbulos Renais Coletores/efeitos dos fármacos , Receptores de Prostaglandina E/efeitos dos fármacos , Absorção , Sequência de Aminoácidos , Animais , Cálcio/metabolismo , Clonagem Molecular , Feminino , Humanos , Túbulos Renais Coletores/metabolismo , Camundongos , Dados de Sequência Molecular , RNA Mensageiro/análise , Coelhos , Receptores de Prostaglandina E Subtipo EP1RESUMO
The present study examined the expression and role of the thiazolidinedione (TZD)-activated transcription factor, peroxisome proliferator-activated receptor gamma (PPARgamma), in human bladder cancers. In situ hybridization shows that PPARgamma mRNA is highly expressed in all human transitional epithelial cell cancers (TCCa's) studied (n=11). PPARgamma was also expressed in five TCCa cell lines as determined by RNase protection assays and immunoblot. Retinoid X receptor alpha (RXRalpha), a 9-cis-retinoic acid stimulated (9-cis-RA) heterodimeric partner of PPARgamma, was also co-expressed in all TCCa tissues and cell lines. Treatment of the T24 bladder cancer cells with the TZD PPARgamma agonist troglitazone, dramatically inhibited 3H-thymidine incorporation and induced cell death. Addition of the RXRalpha ligands, 9-cis-RA or LG100268, sensitized T24 bladder cancer cells to the lethal effect of troglitazone and two other PPAR- activators, ciglitazone and 15-deoxy-delta(12,14)-PGJ2 (15dPGJ(2)). Troglitazone treatment increased expression of two cyclin-dependent kinase inhibitors, p21(WAF1/CIP1) and p16(INK4), and reduced cyclin D1 expression, consistent with G1 arrest. Troglitazone also induced an endogenous PPARgamma target gene in T24 cells, adipocyte-type fatty acid binding protein (A-FABP), the expression of which correlates with bladder cancer differentiation. In situ hybridization shows that A-FABP expression is localized to normal uroepithelial cells as well as some TCCa's. Taken together, these results demonstrate that PPARgamma is expressed in human TCCa where it may play a role in regulating TCCa differentiation and survival, thereby providing a potential target for therapy of uroepithelial cancers.
Assuntos
Carcinoma de Células de Transição/metabolismo , Proteínas de Neoplasias , Receptores Citoplasmáticos e Nucleares/biossíntese , Tiazolidinedionas , Fatores de Transcrição/biossíntese , Proteínas Supressoras de Tumor , Neoplasias da Bexiga Urinária/metabolismo , Alitretinoína , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma de Células de Transição/patologia , Proteínas de Transporte/metabolismo , Morte Celular , Cromanos/farmacologia , Ciclina D1/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/metabolismo , DNA/biossíntese , DNA Complementar/metabolismo , Relação Dose-Resposta a Droga , Proteína 7 de Ligação a Ácidos Graxos , Proteínas de Ligação a Ácido Graxo , Fase G1/efeitos dos fármacos , Humanos , Immunoblotting , Hibridização In Situ , Ligantes , Luciferases/metabolismo , Proteína P2 de Mielina/metabolismo , Ácidos Nicotínicos/farmacologia , Receptores Citoplasmáticos e Nucleares/genética , Receptores do Ácido Retinoico/biossíntese , Receptores do Ácido Retinoico/genética , Receptores X de Retinoides , Ribonucleases/metabolismo , Tetra-Hidronaftalenos/farmacologia , Tiazóis/farmacologia , Fatores de Transcrição/genética , Ativação Transcricional , Transfecção , Tretinoína/farmacologia , Troglitazona , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/patologiaRESUMO
Prostaglandin E2 (PGE2) stimulates the formation of osteoclast-like tartrate-resistant acid phosphatase-positive multinucleated cells (TRAP + MNC) in vitro. This effect likely results from stimulation of adenylyl cyclase, which is mediated by two PGE2 receptors, designated EP2 and EP4. We used cells from mice in which the EP2 receptor had been disrupted to test its role in the formation of TRAP + MNC. EP2 heterozygous (+/-) mice in a C57BL/6 x 129/SvEv background were bred to produce homozygous null (EP2 -/-) and wild-type (EP2 +/+) mice. PGE2, PTH, or 1,25 dihydroxyvitamin D increased TRAP+ MNC in 7-day cultures of bone marrow cells from EP2 +/+ mice. In cultures from EP2 -/- animals, responses to PGE2, PTH, and 1,25 dihydroxyvitamin D were reduced by 86%, 58%, and 50%, respectively. A selective EP4 receptor antagonist (EP4RA) further inhibited TRAP+ MNC formation in both EP2 +/+ and EP2 -/- cultures. In cocultures of spleen and calvarial osteoblastic cells, the response to PGE2 or PTH was reduced by 92% or 85% when both osteoblastic cells and spleen cells were from EP2 -/- mice, by 88% or 68% when only osteoblastic cells were from EP2 -/- mice and by 58% or 35% when only spleen cells were from EP2 -/- mice. PGE2 increased receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) messenger RNA expression in osteoblastic and bone marrow cell cultures from EP2 +/+ mice 2-fold but had little effect on cells from EP2 -/- mice. Spleen cells cultured with RANKL and macrophage colony stimulating factor produced TRAP+ MNC. PGE2 increased the number of TRAP+ MNC in spleen cell cultures from EP2 +/+ mice but not in cultures from EP2 -/- mice. EP4RA had no effect on the PGE2 response in spleen cell cultures. PGE2 decreased the expression of messenger RNA for granulocyte-macrophage colony stimulating factor in spleen cell cultures from EP2 +/+ mice but had little effect on cells from EP2 -/- mice. These data demonstrate that the prostaglandin EP2 receptor plays a role in the formation of osteoclast-like cells in vitro. A major defect in EP2 -/- mice appears to be in the capacity of osteoblastic cells to stimulate osteoclast formation. In addition, there appears to be a defect in the response of cells of the osteoclastic lineage to PGE2 in EP2 -/- mice.
Assuntos
Osteoclastos/fisiologia , Receptores de Prostaglandina E/fisiologia , Fosfatase Ácida/análise , Animais , Células da Medula Óssea/metabolismo , Calcitriol/farmacologia , Proteínas de Transporte/genética , Células Cultivadas , Técnicas de Cocultura , Dinoprostona/farmacologia , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Isoenzimas/análise , Masculino , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoblastos/metabolismo , Hormônio Paratireóideo/farmacologia , Ligante RANK , Receptor Ativador de Fator Nuclear kappa-B , Receptores de Prostaglandina E/deficiência , Receptores de Prostaglandina E/genética , Receptores de Prostaglandina E Subtipo EP2 , Baço/metabolismo , Fosfatase Ácida Resistente a TartaratoRESUMO
Glioma invasiveness is a complex process involving recognition and attachment of tumor cells to particular extracellular matrix (ECM) molecules prior to migrating into proteolytically modified matrix and inducing angiogenesis. CD44 is a group of transmembrane adhesion molecules found on a wide variety of cells including gliomas that has been suggested as the principal mediator of migration/invasion. The aim of the present study was to demonstrate whether antibody specific for the standard form of CD44 (CD44s, 85-90 kDa) might prevent invasion, thus blocking growth of the 9L gliosarcoma in vivo. High expression of CD44s on the surface of 9L cells and brain tumors was demonstrated by immunochemistry. Fluorescence-activated cell sorting (FACS) demonstrated binding saturation of anti-CD44s monoclonal antibody (mAb) to the receptor at 1 microg/5 x 10(5) cells. Blocking of CD44s in vitro resulted in a dose-dependent progressive, up to 95%+/-2.5% detachment of 9L cells from ECM-coated culture surfaces. Blocking of CD44s in vivo resulted in significantly reduced 9L brain tumors (2.5%+/-0.4%)--measured as the quotient: tumor surface (mm2)/brain surface (mm2) x 100--as compared to untreated (16.1%+/-2.2%) or sham-treated rats (16%+/-3.7% to 16.1%+/-3%). We conclude that CD44s-targeted treatment with specific mAb may be an effective means for preventing glioma progression.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Gliossarcoma/tratamento farmacológico , Receptores de Hialuronatos/imunologia , Invasividade Neoplásica/prevenção & controle , Animais , Adesão Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Citometria de Fluxo , Gliossarcoma/patologia , Imuno-Histoquímica , Masculino , Camundongos , Ratos , Ratos Nus , Testes de Toxicidade , Células Tumorais CultivadasRESUMO
Recent studies have shown that stimulation of osteoclastogenesis in cocultures of osteoblasts and spleen cells in response to prostaglandin E2 (PGE2) is markedly decreased when the osteoblasts are derived from cells lacking either the EP2 or the EP4 receptor. Induction of osteoclast formation requires upregulation of receptor activator of nuclear factor-kappaB ligand (RANKL) on cells of the osteoblastic lineage, which then binds to the RANK receptor on cells of the osteoclast lineage. Osteoprotegerin (OPG) is a decoy receptor for RANKL that can block its interaction with RANK. In addition, macrophage-colony stimulating factor (M-CSF) is essential for osteoclast formation. Finally, PGE2 can increase interleukin-6 (IL-6), which may further enhance osteoclastogenesis. To study the relative influence of the EP2 and EP4 receptors on response of these factors to PGE2, we examined mRNA levels for RANKL, OPG, M-CSF, and IL-6 in primary osteoblastic cell cultures derived from two lines of EP2 knockout mice (EP2-/-) and one line of EP4 knockout mice (EP4-/-) and the relevant wild-type controls (EP2+/+ and EP4+/+). The responses of cells from wild-type animals of all three lines were similar. After PGE2 treatment, RANKL mRNA levels were increased at 2 h, and this was sustained over 72 h. Basal RANKL expression was moderately reduced in EP2-/- cells and markedly reduced in EP4-/- cells. PGE2 increased RANKL mRNA in EP2-/- cells and EP4-/- cells, but the levels were significantly reduced compared with wild-type cells. There were no consistent changes in expression of M-CSF or OPG in the different genotypes or with PGE2 treatment. IL-6 mRNA was variably increased by PGE2 in both wild-type and knockout cells, although the absolute levels were somewhat lower in both EP2-/- and EP4 -/- cultures. Parathyroid hormone (PTH) increased RANKL and IL-6 and decreased OPG mRNA levels similarly in both wild-type and EP2-/- or EP4-/- cells. The major defect in the response to PGE2 in animals lacking either EP2 or EP4 receptors is a reduction in basal and stimulated RANKL levels. Loss of EP4 receptor appears to have a greater effect on basal RANKL expression than EP2.
Assuntos
Dinoprostona/farmacologia , Osteoblastos/fisiologia , Receptores de Prostaglandina E/genética , Animais , Proteínas de Transporte/genética , Células Cultivadas , Expressão Gênica/efeitos dos fármacos , Glicoproteínas/genética , Interleucina-6/genética , Fator Estimulador de Colônias de Macrófagos/genética , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteoblastos/citologia , Osteoprotegerina , Hormônio Paratireóideo/farmacologia , Ligante RANK , RNA Mensageiro/análise , Receptor Ativador de Fator Nuclear kappa-B , Receptores Citoplasmáticos e Nucleares/genética , Receptores de Prostaglandina E Subtipo EP2 , Receptores de Prostaglandina E Subtipo EP4 , Receptores do Fator de Necrose TumoralRESUMO
Second primary carcinomas of the lung are well described. However, their occurrence following initial diagnosis of small cell lung carcinoma is rare. The development and antemortem diagnosis of metachronous second primary bronchogenic carcinomas in two long-term (more than four years) survivors of small cell lung cancer is described. The histologic types of the second carcinomas were mucoepidermoid and bronchoalveolar. On the basis of a review of the literature, only eight similar cases have been reported; none of the second primaries was mucoepidermoid or bronchoalveolar. The question of whether second primaries after small cell lung cancer represent true metachronous carcinomas, different degrees of differentiation of the same tumor, or the emergence of a previously unrecognized synchronous tumor is discussed. The need for awareness of this complication and the necessity for life-long follow-up in long-term survivors of small cell lung cancer is emphasized.
Assuntos
Carcinoma Broncogênico/patologia , Carcinoma de Células Pequenas/patologia , Carcinoma/patologia , Neoplasias Pulmonares/patologia , Neoplasias Primárias Múltiplas/patologia , Carcinoma/diagnóstico por imagem , Carcinoma Broncogênico/diagnóstico por imagem , Carcinoma de Células Pequenas/diagnóstico por imagem , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , RadiografiaRESUMO
The purpose of this study was to characterize the prostanoid receptors coupled to intracellular calcium in human erythroleukemia (HEL) cells, a cell line with platelet/megakaryocytic characteristics. Both prostaglandin E1 (PGE1) and iloprost increased cyclic AMP (cAMP) in HEL cells, but modulated [Ca2+]i by different mechanisms. Iloprost (10(-9) to 10(-6) M) had no effect on basal [Ca2+]i, but greatly potentiated the increase in [Ca2+]i produced by thrombin. This effect was mimicked by cholera toxin and other Gs-coupled receptors, and involved calcium influx since iloprost had no effect on [Ca2+]i in cells incubated in Ca2+-free buffer. Furthermore, iloprost did not increase the generation of baseline or thrombin-induced inositol phosphates at these concentrations. In contrast, PGE1 (10(-7) to 10(-5) M), but not iloprost, increased basal [Ca2+]i through a pertussis toxin-sensitive mechanism that involved stimulation of inositol phosphate generation and mobilization of intracellular calcium. The order of potencies of other prostaglandins that increased [Ca2+]i was not consistent with known IP, EP, DP, FP, or TP receptors. 11-Deoxy-16,16-dimethyl PGE2 was the most potent of the analogs tested (EC50 = 28 nM). In summary, at least two prostaglandin receptors are functionally coupled to intracellular calcium in HEL cells: a putative IP receptor coupled to Gs proteins that increases cAMP and enhances calcium influx, and a novel prostanoid receptor that evokes calcium mobilization through stimulation of phospholipase C by a pertussis toxin-sensitive pathway.
Assuntos
Cálcio/metabolismo , Leucemia Eritroblástica Aguda/metabolismo , Receptores de Prostaglandina/efeitos dos fármacos , 16,16-Dimetilprostaglandina E2/análogos & derivados , 16,16-Dimetilprostaglandina E2/farmacologia , Alprostadil/farmacologia , AMP Cíclico/metabolismo , Humanos , Iloprosta/farmacologia , Fosfatos de Inositol/metabolismo , Leucemia Eritroblástica Aguda/patologia , Receptores de Epoprostenol , Receptores de Prostaglandina/metabolismo , Transdução de Sinais , Trombina/administração & dosagem , Células Tumorais CultivadasRESUMO
The present paper explores the mechanism of calcium-overloaded cardiac cell exocytosis during reperfusion of ischemic myocardium. A novel specific inhibitor of calmodulin, CGS 9343B, was used to pretreat an ischemic heart in an effort to enhance myocardial preservation. The experimental model employed an isolated in situ pig heart subjected to 120 min of ischemic insult by reversibly occluding the left anterior descending coronary artery, the last 60 min being superimposed with global hypothermic cardioplegic arrest. This ischemic episode was followed by 60 min of revascularization. CGS 9343B enhanced post-ischemic myocardial recovery, as judged by improved regional as well as global myocardial functions, better preservation of high-energy phosphate compounds, and reduced release of creatine kinase. Since this compound blocks calmodulin without inhibiting protein kinase C, the results of this study suggest that calmodulin-dependent kinase, rather than protein kinase C, is primarily involved in expressing calcium-overloaded cell exocytosis, and a specific calmodulin antagonist such as CGS 9343B can be used to salvage an ischemic heart from reperfusion injury.
Assuntos
Benzimidazóis/farmacologia , Cálcio/metabolismo , Calmodulina/antagonistas & inibidores , Doença das Coronárias/fisiopatologia , Coração/fisiopatologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Circulação Coronária , Miocárdio/metabolismo , Consumo de Oxigênio , Traumatismo por Reperfusão/fisiopatologia , SuínosRESUMO
The following report describes a case of culture-negative subacute bacterial endocarditis complicated by disseminated intravascular coagulation which failed to respond to therapy with antibiotics and heparin. The coagulopathy resolved within 24 hours after the affected heart valves were replaced with prosthetic valves.
Assuntos
Coagulação Intravascular Disseminada/etiologia , Endocardite Bacteriana Subaguda/complicações , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/cirurgia , Feminino , Heparina/uso terapêutico , Humanos , Pessoa de Meia-IdadeRESUMO
An analysis of patients undergoing coronary artery bypass for unstable postinfarction angina (less than or equal to 30 days of infarct) during two time periods was undertaken: Group I, January, 1982, through December, 1982; Group II, September, 1983, through August, 1984. Clinical, angiographic, and operative data were coded, and statistical analysis was used to compare the two patient groups, evaluate operative results, and identify risk factors. The incidence of unstable postinfarction angina as an indication for bypass grafting increased significantly (p less than 0.01) from the first to the second time frame, 8.7% (24/276) to 18% (51/283). A greater proportion of Group II patients were operated upon within 7 days of infarct (37% versus 21%, p less than 0.01). All other variables examined were similar in the two patient groups. Analysis of the combined Group I and II patients (N = 75) indicates the following: The ratio of transmural to nontransmural infarction was 39%/61%, and 39% of patients had a previous infarction. Three-vessel disease was present in 76%, two-vessel in 21%, one-vessel in 3%, and left main disease in 20%. Left ventricular ejection fraction was greater than or equal to 40% in 27% of patients, less than 40% in 32%, and not obtained in 41%. Mean left ventricular end-diastolic pressure was 19.5 mm Hg. Intra-aortic balloon pumping was necessary preoperatively in 39%. The mean interval from infarction to revascularization was 12 days, and the mean number of grafts was 3.1 (range one to six). The overall in-hospital mortality was 8% (6/75). Statistical analysis demonstrated that decreased ejection fraction was associated with an increased risk of mortality. No other variables were correlated with mortality. Mean follow-up for the combined Group I and II patients is 13 months (range 4 to 32). Ninety percent of survivors remain in Canadian Heart Association Functional Class I and 6% in Class II. No late deaths have occurred. Patients with unstable postinfarction angina constitute an ever-increasing subset of the coronary bypass population of the 1980s. Operation can be performed with a satisfactory mortality and excellent long-term outlook compared to less acceptable published results with medical management alone. Preoperative left ventricular function constitutes the major indicator of operative risk.
Assuntos
Angina Pectoris/etiologia , Ponte de Artéria Coronária/mortalidade , Infarto do Miocárdio/complicações , Angina Pectoris/classificação , Angina Pectoris/cirurgia , Humanos , Infarto do Miocárdio/classificação , Infarto do Miocárdio/cirurgiaRESUMO
Phrenic nerve injury has been reported with the use of iced slush for topical cardiac hypothermia. To study this problem in both valve and coronary procedures, we tried to detect phrenic nerve injury in five groups of patients undergoing cardiac operations in which different techniques of topical hypothermia were used. The results indicate a 24% incidence of left phrenic nerve paresis in patients undergoing coronary bypass with iced slush used for topical hypothermia, 12.5% in patients in whom the cardiac cooling jacket was used in association with cold saline, and 22.9% in patients in whom both the cardiac cooling jacket and iced slush were used in the pericardial sac. There was no phrenic nerve injury when saline alone was used. Phrenic paresis is transient and of no clinical significance except when bilateral. Avoidance of contact of either the cooling jacket or iced slush with the phrenic nerve could avoid this complication.
Assuntos
Temperatura Baixa/efeitos adversos , Hipotermia Induzida/efeitos adversos , Paralisia/etiologia , Nervo Frênico/lesões , Ponte de Artéria Coronária , Próteses Valvulares Cardíacas , Humanos , Hipotermia Induzida/instrumentaçãoRESUMO
A total of 284 patients undergoing myocardial revascularization were prospectively studied to determine if the use of intraoperative autotransfusion or intraoperative autotransfusion plus postoperative reinfusion of shed mediastinal blood decreased transfusion requirements and the use of one or both techniques was cost effective. The Haemonetics Cell Saver System was used for intraoperative autotransfusion and the Sorenson Receptaseal autotransfusion system for postoperative reinfusion of shed mediastinal blood. During Phase 1, the Cell Saver System was used for 57 patients and 93 patients served as a control group. During Phase 2, the Cell Saver System plus the autotransfusion system were used in 43 patients and 91 patients were in the control group. Separate parallel analyses to compare the blood conservation groups to control groups were conducted for each phase of the study. The patient groups were comparable with regard to age, sex, preoperative red cell mass, preoperative hematocrit value, number of bypasses, and use of internal mammary grafts. Blood conservation techniques resulted in significant reductions in the use of bank blood. During Phase 1, Cell Saver System patients received an average of 2.8 units of packed cells versus 4.7 units for control patients. Transfusion was avoided entirely in 14% of Cell Saver System patients compared to 3% of control patients. During Phase 2, patients subjected to both the Cell Saver System and the autotransfusion system received an average of 1 unit of packed red cells versus 3 units for control patients. Transfusion was required in only 42% of patients subjected to both the Cell Saver System and the autotransfusion system compared to 85% of control patients. Multiple logistic regression analysis confirmed that the use of the Cell Saver System in Phase 1 and the Cell Saver System and autotransfusion system in Phase 2 were each independently predictive of decreased transfusion requirements. The total "blood-related costs" (including cost for all bank blood products plus Receptaseal and Cell Saver System equipment) was slightly lower for the blood conservation patients in both Phase 1 ($555.00 versus $615.00, no significant difference) and Phase 2 ($373.00 versus $426.00, no significant difference). Intraoperative use of the Cell Saver System is associated with substantial savings of bank blood, and the addition of postoperative reinfusion of shed mediastinal blood results in further bank blood savings. The use of blood conservation techniques is cost effective; that is, the costs incurred for the blood conservation equipment are more than offset by the resultant dollar savings for blood products.
Assuntos
Transfusão de Sangue Autóloga/economia , Revascularização Miocárdica , Transfusão de Sangue Autóloga/métodos , Análise Custo-Benefício , Transfusão de Eritrócitos , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos ProspectivosRESUMO
Postoperative mediastinal effusion after cardiac operations is a common phenomenon and has a potential for serious complications, such as tamponade necessitating urgent drainage. Computed tomography of the chest provides excellent postoperative visualization of the mediastinum. Catheter insertion or paracentesis guided by computed tomography has been used to accomplish nonoperative drainage of symptomatic postoperative mediastinal effusion in six cases. This technique offers simplicity, safety, and cost effectiveness.
Assuntos
Drenagem/métodos , Doenças do Mediastino/terapia , Complicações Pós-Operatórias , Tomografia Computadorizada por Raios X , Idoso , Valva Aórtica/cirurgia , Cateteres de Demora , Exsudatos e Transudatos , Humanos , Masculino , Doenças do Mediastino/diagnóstico por imagem , Doenças do Mediastino/etiologiaRESUMO
The ideal temperature and hematocrit level of blood cardioplegia has not been clearly established. This study was undertaken (a) to determine the optimal temperature of blood cardioplegia and (b) to study the effect of hematocrit levels in blood cardioplegia. A comparison of myocardial preservation was done among seven groups of animals on the basis of variations in hematocrit levels and temperature of oxygenated cardioplegic solution. The experimental protocol consisted of a 2-hour hypothermic cardioplegic arrest followed by 1 hour of normothermic reperfusion. Group 1 received oxygenated crystalloid cardioplegic solution at 10 degrees C. Groups 2 through 7 received oxygenated blood cardioplegic solution with the following hematocrit values and temperatures: (2) 10%, 10 degrees C; (3) 10%, 20 degrees C; (4) 10%, 30 degrees C; (5) 20%, 10 degrees C; (6) 20%, 20 degrees C; and (7) 20%, 30 degrees C. Parameters studied include coronary blood flow, myocardial oxygen extraction, myocardial oxygen consumption, and myocardial high-energy phosphate levels of adenosine triphosphate and creatine phosphate during control (prearrest), arrest, and reperfusion. Myocardial oxygen consumption at 30 degrees C during arrest was significantly higher than at 10 degrees C and 20 degrees C, which indicates continued aerobic metabolic activity at higher temperature. Myocardial oxygen consumption and the levels of adenosine triphosphate and creatine phosphate during reperfusion were similar in all seven groups. Myocardial oxygen extraction (a measure of metabolic function after ischemia) during initial reperfusion was significantly lower in the 30 degrees C blood group than in the 10 degrees C blood group at either hematocrit level and in the oxygenated crystalloid group, which suggests inferior preservation. The hematocrit level of blood cardioplegia did not affect adenosine triphosphate or myocardial oxygen consumption or extraction. It appears from this study that blood cardioplegia at 10 degrees C and oxygenated crystalloid cardioplegia at 10 degrees C are equally effective. Elevating blood cardioplegia temperature to 30 degrees C, however, reduces the ability of the solution to preserve metabolic function regardless of hematocrit level. Therefore, the level of hypothermia is important in blood cardioplegia, whereas hematocrit level has no detectable impact, and cold oxygenated crystalloid cardioplegia is as effective as hypothermic blood cardioplegia.
Assuntos
Sangue , Soluções Cardioplégicas/farmacologia , Parada Cardíaca Induzida , Coração/fisiologia , Hematócrito , Temperatura , Trifosfato de Adenosina/metabolismo , Animais , Circulação Coronária , Feminino , Masculino , Miocárdio/metabolismo , Consumo de Oxigênio , Perfusão , Fosfocreatina/metabolismo , Suínos , Fatores de TempoRESUMO
Thirteen dogs were subjected to bypass grafting from the aorta to the left circumflex coronary artery with the saphenous vein to determine whether the angle of insertion of the saphenous vein into the aorta influences the functional and histologic fate of the grafts. The angle of the aortic anastomosis was obtuse in 6 dogs, acute in 5, and perpendicular in 2. Histologic examination of all 13 grafts 6 to 19 months (mean 9.4) postoperatively showed fibrous intimal proliferative lesions of variable severity along the entire length of the grafts, occasionally with extension into the native coronary arteries. Loss of medical smooth muscle and adventitial fibrosis also occurred in all 13 grafts. The extent and severity of these changes, however, were not related to the angle aortic anastomosis.
Assuntos
Ponte de Artéria Coronária , Veia Safena/patologia , Animais , Aorta Torácica/cirurgia , Vasos Coronários/cirurgia , Cães , Sobrevivência de Enxerto , Métodos , Músculo Liso/patologia , Veia Safena/transplante , Transplante AutólogoRESUMO
The best means of managing tricuspid regurgitation associated with mitral or mitral and aortic valve disease is still to be determined. During the period 1972 to 1974, we treated 76 patients who had tricuspid regurgitation along with associated valvular dysfunction. Patients with mold regurgitation were treated conservatively, those with moderate regurgation underwent annuloplasty, and those with severe regurgitation had tricuspid valve replacement. We found the results to be less satisfactory in the group treated by annuloplasty than in the other two groups. We still manage conservatively those patients with mild regurgitation, but we believe it appropriate to replace the valve in an increasing number of subjects who have tricuspid regurgitation of moderate severity.
Assuntos
Próteses Valvulares Cardíacas , Insuficiência da Valva Tricúspide/terapia , Valva Tricúspide , Animais , Insuficiência da Valva Aórtica/complicações , Feminino , Humanos , Masculino , Insuficiência da Valva Mitral/complicações , Suínos , Transplante Heterólogo , Valva Tricúspide/cirurgia , Valva Tricúspide/transplante , Insuficiência da Valva Tricúspide/complicações , Insuficiência da Valva Tricúspide/cirurgiaRESUMO
We studied the effects of oxygen free radicals on cardiac performance during reperfusion of ischemic myocardium. The pig heart, isolated in situ, was subjected to 60 minutes of regional ischemia at normothermia by occlusion of the left anterior descending coronary artery followed by 60 minutes of hypothermic cardioplegic arrest and 60 minutes of normothermic reperfusion. The oxygen free-radical scavengers, superoxide dismutase and catalase, were administered before occlusion of the left anterior descending coronary artery in the experimental group. The generation of free radicals in the untreated group, estimated by the measurement of malondialdehyde in the perfusate, was significant during reperfusion and was associated with a corresponding increase in creatine kinase. Superoxide dismutase and catalase significantly slowed the appearance of malondialdehyde and the release of creatine kinase during reperfusion. Superoxide dismutase and catalase did not alter coronary flow and myocardial oxygen extraction or consumption during occlusion of the left anterior descending coronary artery; however, coronary flow and oxygen consumption were significantly higher (p less than 0.05) during reperfusion in hearts treated with antioxidants. Left ventricular developed pressure and its maximum first derivative were measured under isovolumic conditions. In the untreated group, left ventricular developed pressure and its maximum first derivative declined to 61.1% and 57.1% of baseline values, respectively, after 60 minutes' occlusion of the left anterior descending, and to 45% of baseline values after 15 minutes of reperfusion. The decline in left ventricular developed pressure and its maximum first derivative during reperfusion was significantly (p less than 0.05) inhibited by superoxide dismutase and catalase, but left ventricular end-diastolic pressure was not significantly altered. These results implicate oxygen-derived free radicals in the injury resulting from reperfusion of ischemic myocardium and suggest that oxygen free-radical scavengers effectively protect against such injury.