RESUMEN
The outcome of patients with penetrating heart injuries depends to a great extent on aggressive primary care and fast transport to the closest appropriate trauma center. There, after confirming the diagnosis, the injured victim has to be transferred without any delay to the operating room where the penetrating injury can be dealt with. The importance of resolute emergency management is shown based on a case presentation and a review of the current literature. The employment of extracorporal circulation (heart-lung machine) is rather subordinate in the primary care of these patients.
Asunto(s)
Urgencias Médicas , Lesiones Cardíacas/cirugía , Ventrículos Cardíacos/lesiones , Heridas Punzantes/cirugía , Adulto , Taponamiento Cardíaco/diagnóstico por imagen , Taponamiento Cardíaco/cirugía , Ecocardiografía , Lesiones Cardíacas/diagnóstico por imagen , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/cirugía , Máquina Corazón-Pulmón , Humanos , Masculino , Intento de Suicidio , Toracotomía/métodos , Heridas Punzantes/diagnóstico por imagenRESUMEN
The objective was to investigate whether the renin-angiotensin (RA) system and related peptides endothelin-1 (ET-1) and vasopressin (VP) influence the development of coronary artery disease (CAD). Angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism has been associated with the risk of CAD. The ACE I/D polymorphism determines ACE activity, but plasma levels of other RA system components remain unchanged. However, ET-1 and VP production could be increased by RA system-dependent stimulation, continually promoted by paracrine stimulation and sustained by neointimal growth. ET-1 and VP have not been associated with the ACE I/D polymorphism so far. The present study investigated the association of the ACE I/D polymorphism with plasma concentrations of ET-1 and VP, as well as with renin, angiotensin-II (AT-II) and ACE activity in 98 Caucasian individuals with CAD. ACE I/D polymorphism showed no association with plasma levels of VP, ET-1, AT-II or renin. These parameters were also not associated taking into consideration different patient variables, such as diabetes mellitus, hypertension or severity of CAD. Only plasma ACE activity was associated with the D allele. In conclusion, the ACE I/D polymorphism could not be related to plasma concentrations of VP, ET-1, renin or AT-II, but as previously demonstrated, it could only be related to ACE activity in patients with CAD. Differences in ACE activity between ACE I/D genotype subgroups are probably compensated within the RA system itself or within non-ACE pathways, so that plasma concentrations of the related peptides ET-1 and VP remain unaffected.
Asunto(s)
Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/genética , Endotelina-1/sangre , Endotelina-1/genética , Eliminación de Gen , Mutagénesis Insercional/genética , Peptidil-Dipeptidasa A/sangre , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético/genética , Vasoconstrictores/sangre , Vasopresinas/sangre , Adulto , Anciano , Anciano de 80 o más Años , Angiotensina II/sangre , Angiotensina II/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Renina/sangre , Renina/genéticaRESUMEN
The sodium pump (Na(+),K(+)-ATPase; EC 3.6.1.37) of animal cell membranes is the enzyme responsible for the maintenance of membrane potential, for the function of secondary active transporters, and for osmoregulation of the cell. Since inhibition of the enzyme by cardiac glycosides results in increased contractility of the heart muscle and increased blood pressure, we were interested in whether there is a correlation between hypertension and expression of the various isoforms of the sodium pump. In addition, we also examined the expression of the isoforms of the sarcoplasmic and plasma membrane Ca(2+)-ATPase, the Na(+)/Ca(2+)- and Na(+)/H(+)-exchangers, and Na(+) channel and Ca(2+) channel isoforms. Total mRNA was isolated from 50 mg tissue from the right atrium of hypertensive and normotensive patients who were undergoing cardiac surgery. After reverse transcription and subsequent amplification of ion transporter-specific cDNA fragments by polymerase chain reaction (PCR) in the presence of [alpha-(32)P]dCTP, quantification of the amplified fragments was carried out by the Phosphorimager technique. The data obtained show that the alphal subunit mRNA is expressed similarly in normotensive and hypertensive patients. The amount of alpha2 subunit mRNA, however, is increased 5-fold in hypertensive patients. In the same group, the amount of alpha3 isoform is also significantly increased, although not as dramatically as the alpha2 isoform. Besides the Na(+),K(+)-ATPase isoforms, a significant increase in the expression of mRNA for the Na(+)/Ca(2+)-exchanger and the plasma membrane Ca(2+)-ATPase isoforms was detected. It is possible that the observed changes in mRNA expression for these ion transporters reflect compensatory mechanisms to overcome a defective Na(+) and Ca(2+) metabolism in the tissues of hypertensive patients or reflect defects directly involved in the cause of hypertension. The expression of mRNA for all other transporters investigated was unaltered.
Asunto(s)
ATPasas Transportadoras de Calcio/biosíntesis , Hipertensión/metabolismo , Miocardio/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/biosíntesis , Adulto , Anciano , Animales , ATPasas Transportadoras de Calcio/genética , Membrana Celular/enzimología , Femenino , Atrios Cardíacos , Humanos , Masculino , Persona de Mediana Edad , Ouabaína/metabolismo , Reacción en Cadena de la Polimerasa , Isoformas de Proteínas/biosíntesis , ARN Mensajero/aislamiento & purificación , Intercambiadores de Sodio-Hidrógeno/biosíntesis , ATPasa Intercambiadora de Sodio-Potasio/genéticaRESUMEN
BACKGROUND: The clinical observation of distinct reduction of wound secretion tendency during treatment of venous leg ulcer with topically applied factor XIII let us speculate that this enzyme may be involved in modulation of vascular permeability. METHODS: For experimental study porcine aortic endothelial cells were cultured on filter membrane to confluent monolayer. Endothelial covered filters then were used in a two-compartment modell creating an artificial luminal and abluminal compartment. To investigate the influence of factor XIII on endothelial barrier function, we measured the flux of trypan blue-labeled albumin through endothelial monolayers by spectrophotometer. RESULTS: Monolayers that were exposed to factor XIII showed a distinct (n = 10, p < 0.05) decrease of albumin flux in contrast to control. This effect was not dependent on serum substrates. Partially, the permeability reducing effect was due to a certain amount of albumin that is a stabilizing component of Fibrogammin HS. CONCLUSION: Although the mechanism is unclear at the moment, we conclude that reduction of endothelial permeability can be achieved by factor XIII which may play an important role in wound healing of venous leg ulcer.
Asunto(s)
Permeabilidad Capilar/efectos de los fármacos , Factor XIII/administración & dosificación , Úlcera Varicosa/tratamiento farmacológico , Administración Tópica , Animales , Células Cultivadas , Endotelio Vascular/efectos de los fármacos , Humanos , PorcinosRESUMEN
BACKGROUND: Disturbances in fibrinolytic activity, such as increase in plasminogen activator inhibitor (PAI) activity, have been linked with an increased risk for coronary artery disease (CAD) and myocardial infarction (MI). Since 4G4G homozygotes of an insertion/deletion (4G/5G) gene variation in the promoter of PAI-I have been shown to have increased levels of PAI-I, we analysed the relation of this gene polymorphism to CAD and MI in a population of 2565 participants who underwent coronary angiography for diagnostic purposes. RESULTS: In the total sample, the PAI-I 4G/4G genotype was associated with the presence, but not with the extent of CAD. However, in a subgroup of former and present smokers (n = 1782) or of individuals with a BMI above the mean value of 26.9 kg x m(-2) (n = 1269), the PAI-I 4G4G genotype was not only associated with the presence, but also with the extent of CAD, defined either by the number of diseased vessels or by the CHD score according to Gensini. This observation also applied to other high-risk groups of individuals with high BMI and hypertension (n = 869), of subjects with high fibrinogen plasma levels (>3.53 g x l(-1), mean value) and hypertension (n = 599) and of former and present smokers with high fibrinogen and hypertension (n = 452). An association of the gene variation with MI was not detected. CONCLUSIONS: The present data indicate that the 4G/4G genotype of the PAI-I gene polymorphism is an independent risk factor for coronary artery disease and that the additional presence of major cardiovascular risk factors accelerates the risk for this disease.
Asunto(s)
Enfermedad de la Arteria Coronaria/genética , Inhibidor 1 de Activador Plasminogénico/genética , Polimorfismo Genético , Anciano , Enfermedad de la Arteria Coronaria/etiología , Enfermedad Coronaria/etiología , Enfermedad Coronaria/genética , Frecuencia de los Genes , Genotipo , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Modelos Genéticos , Infarto del Miocardio/etiología , Infarto del Miocardio/genética , Factores de RiesgoRESUMEN
BACKGROUND: The relations of the angiotensinogen (AGT) T174M and M235T gene polymorphisms to the risk of coronary heart disease (CHD) have been investigated in only a few studies with conflicting results. RESULTS: Therefore, we analysed the relationship of the AGT gene polymorphisms to the presence and extent of CHD in 2250 male Caucasians whose coronary anatomy was defined by means of coronary angiography. The relative frequencies of the T and M alleles of the T174M and of the M235T gene variation did not significantly differ between patients without or with single-, double- or triple-vessel disease and between subjects without or with myocardial infarction (MI). In contrast the mean CHD score--defined by Gensini--was higher within MM homozygotes of the T174M gene variation than within TT genotypes; TM subjects had intermediate values. In M235T genotypes, mean CHD scores were similar in the total sample and in older individuals (> or = 62 years), whereas in younger individuals (< 62 years) a higher CHD score was found within AGT 235 T allele carriers than within MM homozygotes. In younger individuals with high apoAI plasma levels, the mean CHD score was clearly higher within TT homozygotes of the M235T gene variation than within MM genotypes; MT subjects had intermediate values. An interaction between both angiotensinogen gene polymorphisms on the extent of CHD or on the risk of non-fatal MI were not observed when the M allele of AGT T174M was combined either with the T allele or the TT genotype of M235T. CONCLUSIONS: The present study strengthens the hypothesis of an association of both angiotensinogen gene polymorphisms with the extent of coronary heart disease.
Asunto(s)
Angiotensinógeno/genética , Enfermedad de la Arteria Coronaria/genética , Polimorfismo Genético , Alelos , Angiotensinógeno/sangre , Apolipoproteína A-I/sangre , Apolipoproteínas B/sangre , Codón , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Frecuencia de los Genes , Marcadores Genéticos , Genotipo , Humanos , Desequilibrio de Ligamiento , Masculino , Persona de Mediana Edad , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
Several diseases show an impairment of vascular barrier function. In the past, we found out that topically applied plasmatic factor XIII distinctly reduced secretion tendency and improved granulation in venous ulcer. Increased vascular permeability is also discussed in patients with a long lasting diabetic status being a relevant cause of impaired local wound healing. Therefore, we introduced the topical application of factor XIII into the therapy of diabetic foot ulcer. After basic experimental investigations revealed that factor XIII significantly reduces endothelial permeability of cultured endothelial cells, the first clinically treated diabetic patients showed encouraging results, too.
Asunto(s)
Pie Diabético/terapia , Factor XIII/administración & dosificación , Administración Tópica , Anciano , Animales , Permeabilidad de la Membrana Celular/efectos de los fármacos , Células Cultivadas , Pie Diabético/etiología , Pie Diabético/patología , Endotelio Vascular/patología , Factor XIII/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Albúmina Sérica/metabolismo , Porcinos , Resultado del Tratamiento , Cicatrización de Heridas/efectos de los fármacosRESUMEN
BACKGROUND: There are conflicting results on the relationship of N5,N10-methylenetetrahydrofolate reductase C677T gene variation in coronary artery disease and myocardial infarction. METHODS AND RESULTS: We analysed this gene variation in 2453 male Caucasians whose coronary anatomy was defined by coronary angiography. In the total sample, the C677T gene polymorphism was not associated with the presence or the extent of coronary artery disease (defined by the degree of vessel disease or by the coronary heart disease score according to Gensini). However, after excluding individuals with low risk profiles, an association between the C677T TT genotype and the Gensini score was found. This observation applies only to individuals (i) with high glucose levels, (ii) with low apolipoprotein Al/apolipoprotein B ratios, (iii) with low apolipoprotein Al/apolipoprotein B ratios and high lipoprotein (a) levels and (iv) with low apolipoprotein Al/apolipoprotein B ratios and high glucose concentrations. In patients with high glucose levels, the paraoxonase 191 A/B gene variation presupposed whether differences in Gensini scores between C677T C allele carriers and TT homozygotes became apparent, since only in paraoxonase 191 AA homoxygotes, but not in paraoxonase 191 B allele carriers, did C677T TT homozygotes have clearly higher Gensini scores than C allele carriers (two-way interaction; P = 0.013). The MTHFR C677T gene polymorphism was not associated with non-fatal myocardial infarction. CONCLUSION: The present study extends previous observations by the finding that carriers of the N5,N10-methylenetetrahydrofolate reductase C677T TT genotype with various coronary high risk profiles had clearly higher coronary heart disease scores than individuals with at least one C677T C allele.
Asunto(s)
Enfermedad de la Arteria Coronaria/genética , Homocisteína/genética , Infarto del Miocardio/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Polimorfismo Genético , Adulto , Anciano , Análisis de Varianza , Enfermedad de la Arteria Coronaria/fisiopatología , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Genotipo , Homocisteína/metabolismo , Humanos , Modelos Logísticos , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Persona de Mediana Edad , Infarto del Miocardio/fisiopatología , Pronóstico , Medición de Riesgo , Factores de Riesgo , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadRESUMEN
The effect of factor XIII on endothelial barrier function was studied in a model of cultured monolayers of porcine aortic endothelial cells and saline-perfused rat hearts. The thrombin-activated plasma factor XIII (1 U/ml) reduced albumin permeability of endothelial monolayers within 20 min by 30 +/- 7% (basal value of 5.9 +/- 0.4 x 10(-6) cm/s), whereas the nonactivated plasma factor XIII had no effect. Reduction of permeability to the same extent, i.e., by 34 +/- 9% could be obtained with the thrombin-activated A subunit of factor XIII (1 U/ml), whereas the iodoacetamide-inactivated A subunit as well as the B subunit had no effect on permeability. Endothelial monolayers exposed to the activated factor XIII A exhibited immunoreactive deposition of itself at interfaces of adjacent cells; however, these were not found on exposure to nonactivated factor XIII A or factor XIII B. Hyperpermeability induced by metabolic inhibition (1 mM potassium cyanide plus 1 mM 2-deoxy-D-glucose) was prevented in the presence of the activated factor XIII A. Likewise, the increase in myocardial water content in ischemic-reperfused rat hearts was prevented in its presence. This study shows that activated factor XIII reduces endothelial permeability. It can prevent the loss of endothelial barrier function under conditions of energy depletion. Its effect seems related to a modification of the paracellular passageways in endothelial monolayers.
Asunto(s)
Endotelio Vascular/fisiología , Factor XIII/metabolismo , Animales , Aorta/citología , Agua Corporal , Permeabilidad de la Membrana Celular , Células Cultivadas , Endotelio Vascular/citología , Masculino , Ratas , Ratas Wistar , Coloración y Etiquetado , PorcinosRESUMEN
BACKGROUND: G to A transitions at nucleotide position 20210 of the factor II (Fll) gene and at 1691 of the factor V (FV) gene have been shown to be associated with an increased risk of venous thrombosis. Since it is still unclear whether both gene variations are also related to an increased risk of coronary heart disease (CHD), we studied the relation of both gene variations to coronary artery disease (CAD) and myocardial infarction (MI) in a sample of 2210 male individuals whose coronary anatomy were defined by coronary angiography. RESULTS: In the total sample, the FII G20210A gene variation was not associated with the presence or the extent of CAD, the latter defined either by the degree of vessel disease or by a CHD score according to Gensini. However, individuals with unfavourable lipid profiles showed pronounced differences in CHD scores between GA heterozygotes and GG homozygotes: this observation applied in particular to younger patients (<62 years; mean age of total sample) who simultaneously had low apoAI/apoB ratios (< 1.19, mean value) and high Lp(a) plasma levels (>28 mg/dl; mean value). In addition, in subjects without acetylsalicylic acid treatment GA heterozygotes had clearly higher CHD scores than AA genotypes. Further restriction to smokers, to subjects with high fibrinogen plasma levels (>3.47 g/l; mean value) or to patients with high glucose concentrations (>112 mg/dl; mean value) tended to increase the difference in CHD score between FII G20210A genotypes. An association of the FII G20210A gene variation with non-fatal MI was not observed. In the total sample and in high and low risk subpopulations, an association of the FV G1691A gene variation was not detected neither with presence and extent of CAD or with nonfatal MI. CONCLUSION: The importance of the factor II G20210A gene variation for CHD may be restricted to individuals with major cardiovascular risk factors. In addition, the present study did not strengthen the hypothesis of the factor V G 1691 A transition as a risk factor of coronary heart disease neither in the total sample nor in subgroups of individuals who were at high or low risk of CHD.
Asunto(s)
Enfermedad Coronaria/etiología , Deficiencia del Factor V/genética , Factor V/genética , Hipoprotrombinemias/genética , Mutación Puntual , Protrombina/genética , Trombofilia/genética , Adulto , Anciano , Comorbilidad , Angiografía Coronaria , Enfermedad Coronaria/diagnóstico por imagen , Enfermedad Coronaria/epidemiología , Diabetes Mellitus/epidemiología , Deficiencia del Factor V/complicaciones , Deficiencia del Factor V/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Variación Genética , Genotipo , Humanos , Hiperlipidemias/epidemiología , Hipertensión/epidemiología , Hipoprotrombinemias/complicaciones , Hipoprotrombinemias/epidemiología , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/etiología , Factores de Riesgo , Índice de Severidad de la Enfermedad , Fumar/epidemiología , Trombofilia/complicaciones , Trombofilia/epidemiologíaRESUMEN
AIM: There is evidence that interaction between angiotensin II type 1 receptor A1166C gene polymorphism and angiotensin I-converting enzyme Insertion/Deletion gene variation might have an effect on the risk of myocardial infarction. The study was carried out in a population of 2244 male Caucasians, whose coronary anatomy was defined by means of coronary angiography. We analysed the relationship, on the risk of ischaemic heart disease, of angiotensin II type 1 receptor A1166C gene variation, not only to myocardial infarction but also to coronary artery disease, and its potential interaction with angiotensin I-converting enzyme Insertion/Deletion gene polymorphism. METHODS AND RESULTS: No association was detected between angiotensin II type 1 receptor A1166C gene polymorphism and coronary artery disease. Similarly, there was no link to myocardial infarction, either in the total population or in low risk groups. In addition, most importantly, we found no interaction between angiotensin II type 1 receptor A1166C gene variation and angiotensin I-converting Insertion/Deletion polymorphism, either in connection with the risk of coronary artery disease or myocardial infarction. CONCLUSION: This angiotensin II type 1 receptor A1166C gene variation is not associated with any detectable increase in risk of ischaemic heart disease. The findings of the present study do not suggest that, as regards risk of coronary artery disease and myocardial infarction, there is interaction between gene polymorphism and angiotensin I-converting enzyme Insertion/Deletion gene variation.
Asunto(s)
Angiotensina II/metabolismo , Enfermedad Coronaria/genética , Infarto del Miocardio/genética , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , Receptores de Angiotensina/genética , Anciano , Enfermedad Coronaria/enzimología , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/enzimología , Factores de RiesgoRESUMEN
The Del allele of the apolipoprotein B (apoB) signal peptide (SP) insertion/deletion (Ins/Del) polymorphism has been shown to be associated with elevated plasma levels of apoB, cholesterol and low density lipoprotein. It was the aim of the present study to analyse the relation of this gene variation to the risk of coronary artery disease (CAD) and of myocardial infarction (MI) in a population of 2259 male Caucasians, whose coronary anatomy was defined by means of coronary angiography. ApoB SP DelDel genotypes had significantly higher apoB plasma concentrations than InsIns homozygotes (P = 0.0001) and InsDel heterozygotes (P = 0.002); however, the apoB plasma levels of InsIns and InsDel genotypes were essentially the same (P = 0.54). Similar observations were made with respect to ApoB SP genotype-dependent cholesterol plasma concentrations. Since the apoB plasma level was not only associated with the apoB SP Ins/Del gene variation but also to the extent of coronary artery disease (P <0.0001), individuals with an InsIns genotype and without CAD had the lowest and subjects with a DelDel genotype and triple vessel disease the highest apoB plasma levels (P <0.0001). An association of the apoB SP Ins/Del gene variation with CAD was not detected, neither in the total population nor in low risk groups. In contrast, the gene variation was associated with MI (P <0.05). An Odds ratio of 1.18 (95% CI, 1.01-1.39) associated with the Del allele was detected in the total sample (P <0.02). In a subpopulation of individuals with low plasma triglyceride levels ( <154 mg/dl; mean value) and an DD genotype of the angiotensin I-converting enzyme insertion/deletion gene polymorphism an Odds ratio of 2.01 (1.42-3.05) was calculated (P <0.001). The present study presents evidence for a statistically significant difference in the development of MI between genotype classes of the apoB SP Ins/Del gene polymorphism.
Asunto(s)
Apolipoproteínas B/genética , Infarto del Miocardio/genética , Polimorfismo Genético , Señales de Clasificación de Proteína/genética , Alelos , Apolipoproteínas B/sangre , Colesterol/sangre , Enfermedad Coronaria/genética , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Factores de RiesgoRESUMEN
BACKGROUND: The platelet membrane glycoprotein IIb/IIIa functions as a receptor for fibrinogen and von Willebrand factor during platelet aggregation. In a small case-control study, evidence has been presented that the PlA2 allele of the platelet glycoprotein GPIIIa PlA/A2 gene polymorphism might be an independent risk factor for acute myocardial infarction (MI). METHODS AND RESULTS: We explored the association of the PlA1A2 to the severity of coronary artery disease (CAD), as assessed angiographically in 2252 male individuals, and to myocardial infarction (MI). The severity of coronary heart disease (CHD) was also estimated by calculating a CHD score according to Gensini. The PlA genotype was determined by allele specific restriction digestion. Relation of the PlA2 allele to CAD: In the total population, the frequency of the PlA2 allele was not associated to the presence or to the extent of CAD. Also the CHD scores of PlA1/PlA2 genotypes were essentially the same. However, after exclusion of individuals with high BMI (> or =26.9 kg/m2) and/or low apoAI (< 1.43 g/l) PlA2PlA2 carriers had clearly higher CHD scores than PlA1PlA1 genotypes: PlA1PlA2 heterozygotes had intermediate values (p <0.05). After division of the study population into one group of individuals without any angiographic signs of CAD (CHD score = 0) and into another group of patients with severe CAD (CHD score (> or = 120), a strong association of the PlA2 allele with severe CAD was also found in the same low risk groups: e.g. exclusion of persons with high BMI and low apoAI resulted in an Odds ratio of 5.37 (1.46-19.7) (p <0.02). Relation of the PlA2 allele to MI: No association was found between PlA1/PlA2 genotypes and risk of MI neither in the total population nor in low risk subgroups. CONCLUSIONS: Whereas no difference in the distribution of allele and genotype frequencies between controls and survivors of MI could be detected, the PlA2 allele is associated with CHD in low risk patients.
Asunto(s)
Enfermedad Coronaria/genética , Infarto del Miocardio/genética , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/genética , Polimorfismo Genético , Anciano , Alelos , Estudios de Casos y Controles , Angiografía Coronaria , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Factores de Riesgo , SobrevivientesRESUMEN
BACKGROUND: Presence of the D allele or homozygosity for the deletion (D) allele of the ACE insertion/deletion (I/D) polymorphism has been discussed as potent risk factor for coronary artery disease (CAD) and myocardial infarction (MI). METHODS AND RESULTS: In 2267 male Caucasians the relation of the ACE I/D gene polymorphism to CAD and MI were investigated. An association of the D allele to CAD was detected in younger subjects (e.g. < 61.7 years, mean value), but not in older patients (e.g. > or = 61.7 years). Additional exclusion of individuals with other cardiovascular risk factors (e.g. high BMI) produced an even stronger association of the D allele to CAD. In contrast, a relation of this polymorphism to non-fatal MI was only observed in older subjects; additional limitation to individuals without cardiovascular risk factors (e.g. BMI and/or diabetes) yielded a further enhancement of this association to MI. In younger subjects (e.g. < 61.7 years) the gene polymorphism was not related to non-fatal MI even after exclusion of additional risk factors. CONCLUSIONS: The present large case-control study strengthens the assumption of an association of the ACE D allele with the risk of ischemic heart disease.
Asunto(s)
Enfermedad Coronaria/etiología , Enfermedad Coronaria/genética , Peptidil-Dipeptidasa A/genética , Adulto , Anciano , Envejecimiento , Alelos , Estudios de Casos y Controles , Angiografía Coronaria , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/genética , Polimorfismo Genético , Factores de Riesgo , Población BlancaRESUMEN
Therapy for the hypoplastic left heart syndrome (HLHS) is still under debate. We report about our experience in the treatment of this cardiac malformation using heart transplantation and Norwood palliation. From 1988 to 1997 a total number of 30 infants with hypoplastic left heart underwent heart transplantation. Mean age at transplantation was 66 days. Mean waiting time was 53 days. Donor-recipient weight ratio ranged from 0.6 to 3.9. There were 6 early hospital deaths and one late death until now. Causes of death were rejection (3), right heart failure (2), infection (1) and multi system organ failure (1). Overall survival was 77%. Increasing experience improved results substantially. From 1988 to 1993 (n=12) survival rate was 58%, whereas from 1994 to 1997 (n=18) survival rate increased to 88%. Quality of life is excellent in the 23 surviving infants. Only one infant shows severe morbidity (neurological defect). The Norwood procedure has been performed in 18 patients since 1993. Five patients died after the first stage. Up until now 10 infants have undergone the second stage and one infant the third stage procedure. None of them have died. Survival rate is 72% for the whole group. Taking into account that 12 infants died on the waiting list for transplanatation (28%), we have comparable results in terms of the survival rate for transplantation and the Norwood procedure in infants with HLHS since 1994. However quality of life and physical development are far better in infants after transplantation according to our experience. Therefore we prefer, whenever possible heart transplantation in the treatment of hypoplastic left heart syndrome. Certainly not all infants with this malformation can undergo transplantation because of the lack of donor organs. Criteria for the decision regarding the operative strategy in our opinion are function of the right ventricle and tricuspid valve, size of the interaterial communication and parental request.
Asunto(s)
Procedimientos Quirúrgicos Cardíacos/métodos , Síndrome del Corazón Izquierdo Hipoplásico/cirugía , Procedimientos Quirúrgicos Cardíacos/mortalidad , Angiografía Coronaria , Estudios de Seguimiento , Rechazo de Injerto/diagnóstico por imagen , Rechazo de Injerto/mortalidad , Trasplante de Corazón , Humanos , Síndrome del Corazón Izquierdo Hipoplásico/diagnóstico por imagen , Síndrome del Corazón Izquierdo Hipoplásico/mortalidad , Lactante , Recién Nacido , Cuidados Paliativos , Complicaciones Posoperatorias/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Tasa de Supervivencia , Donantes de Tejidos , Listas de EsperaRESUMEN
Maintaining an adequate cerebral oxygen supply is a serious problem in aortic arch surgery. Deep hypothermic circulatory arrest is the most common method used for cerebral protection, but guarantees only a time-limited safety period. Based on experimental investigations, we applied selective cerebral perfusion via the innominate artery alone with only moderate hypothermia (28 degrees C) and without circulatory arrest in 25 consecutive patients undergoing surgical treatment of an aneurysm (n = 10) or acute type-A dissection (n = 15) involving the aortic valve and arch. In every case a test perfusion was carried out to assess whether the cerebral perfusion achieved would be adequate for the whole operation. In no case was the perfusion inadequate. As a new perioperative monitoring system, we used computer-aided topographical electroencephalometry (CATEEM). There were 18 male and 7 female patients, their age was 47.0 +/- 15.1 years (mean +/- SD). Mean time periods were 155.1 +/- 37.3 min for aortic cross-clamping, and 69.3 +/- 35 min for selective cerebral perfusion. Postoperatively, two patients (8%) revealed a temporary left-sided hemiparesis, and 4 patients (16%) died within 30 days. The overall mortality rate was 16% in a follow-up period of 24.2 +/- 9.5 months. In this small group the CATEEM monitoring enabled an intraoperative selection of patients with sufficient bihemispheric collateral circulation and therefore suitable for simple innominate artery perfusion.
Asunto(s)
Aneurisma de la Aorta/cirugía , Disección Aórtica/cirugía , Rotura de la Aorta/cirugía , Tronco Braquiocefálico , Encéfalo/metabolismo , Perfusión/métodos , Enfermedad Aguda , Adulto , Femenino , Humanos , Hipotermia Inducida , Masculino , Persona de Mediana Edad , Monitoreo FisiológicoRESUMEN
Currently the most used perfusion techniques during aortic arch surgery to prevent cerebral damage include hypothermic circulatory arrest, retrograde cerebral perfusion and selective cerebral perfusion (SCP). The application of simplified SCP, which does not require deep hypothermia, has become an alternative procedure for brain protection. Including the physiological principle of autoregulated cerebral blood flow, cerebral perfusion flow is not predetermined, but differentiated from the different cannula sizes for the lower and upper body perfusion. In a mock circulation loop, we could show that resistance changes in the two compartments led to flow shifts between the systemic and brachiocephalic regions. In addition to mechanical factors cerebral perfusion is determined from physiological changes. In practice, these shifts can be initiated with disrupted autoregulation due to ph-stat management or dramatic pressure changes. To prevent mismatched cerebral perfusion extended perioperative monitoring was included in our clinical setting. With bilateral somatosensory evoked potentials, a computer aided topographical electroencephalometry system, transcranial doppler-sonography and jugular venous bulb saturation, we could provide a sufficient bihemispheric perfusion. Between 1990 and 1995 we operated on 21 patients using SCP. Intraoperatively no signs of cerebral ischaemia due to inadequate perfusion could be observed. Only temporary neurological changes were found postoperatively. In summary, the simplified SCP, despite its physiological basis, is intricately involved in control and influence. We think that the application of SCP is safe if extended neurophysiological monitoring is included in the clinical setting.
Asunto(s)
Circulación Cerebrovascular , Humanos , PerfusiónRESUMEN
BACKGROUND: Fibrinogen has been demonstrated to be an independent risk factor of cardiovascular disease. The absence of the HaeIII cutting site (H2 allele) of an H1/H2 gene variation in the promoter region of the beta fibrinogen gene was associated with increased levels of fibrinogen. METHODS AND RESULTS: In the present study, the effects of the H1/H2 gene variation not only on plasma fibrinogen concentrations but also on coronary artery disease (CAD) and myocardial infarction (MI) were investigated in 923 individuals who underwent coronary angiography for diagnostic purposes. Relation of the H1/H2 genotype to fibrinogen plasma levels: A strong association was observed between the H1/H2 gene variation and fibrinogen levels. The differences in fibrinogen plasma levels between H2H2 and H1H1 homozygotes were almost threefold more pronounced within subjects with clinical chemical signs of an acute phase reaction (CRP > or = 7.5 mg/l) than within a subgroup of subjects without these signs (CRP < 7.5 mg/l) (median of CRP distribution: 7.5 mg/l). In 207 patients who underwent aortocoronary bypass surgery plasma fibrinogen levels were almost identical directly after surgery. Two days after operation fibrinogen increased to clearly higher levels in H2H2 homozygotes than in H1H2 and H1H1 genotypes, whereas almost the same maximal increases in fibrinogen concentrations were reached 3-4 days after surgery in all individuals. Relation of the H1/H2 genotype to CAD and MI. Whereas in the total population the plasma fibrinogen concentrations were strongly associated with smoking, CAD and MI, an association of the H1/H2 gene variation to CAD and MI was not detected. However, mean age at first MI of H2H2 individuals (62.9 years) was clearly higher than of H1H2 genotypes (56.9 years) and of H1H1 subjects (56.4 years). In addition, in a subgroup of individuals with a higher risk of MI by either high apoB and/or low apoA1 plasma levels the portion of MI patients was clearly smaller within H2H2 homozygotes than within H1H2 or H1H1 genotypes, although-also in these high risk groups-mean age at first MI of H2H2 individuals were higher than of the other two genotypes. CONCLUSIONS: Obviously, the H2 allele of the fibrinogen H1/H2 genotype does not only influence basal fibrinogen concentrations, but particularly also the extent of fibrinogen level increase during acute phase reaction. Whereas the fibrinogen plasma level is positively associated with coronary artery disease and myocardial infarction, the H2 allele-although exhibiting an association with elevated fibrinogen levels-was not positively associated with CAD and MI.
Asunto(s)
Reacción de Fase Aguda/sangre , Alelos , Enfermedad Coronaria/sangre , Fibrinógeno/genética , Infarto del Miocardio/sangre , Reacción de Fase Aguda/genética , Biomarcadores , Enfermedad Coronaria/genética , Fibrinógeno/análisis , Homocigoto , Humanos , Masculino , Infarto del Miocardio/genéticaRESUMEN
The introduction of fixed reimbursement rates in Germany for cardiac surgery of adults, mainly coronary artery bypass grafting (CABG) and valve surgery, has shifted the financial risk from insurers to providers of medical care, namely hospitals. Costs in turn are closely related to the preoperative condition of a patient, implicating that surgery in high-risk patients may result in financial losses for the operating institution. Furthermore, reports from the Society of Thoracic Surgeons national database indicate a trend over time towards a higher proportion of patients with adverse risk factors for the United States. To determine whether these trends are holding true for Germany, we conducted an analysis of the data from two institutions with the following questions: 1. Is there a trend over time towards unfavourable risk factors, and 2. Is there a relation between preoperative risk factors and postoperative length of stay? From 1987 to 1995, 3872 patients underwent CABG at the Departments of Cardiovascular Surgery of Justus-Liebig University Giessen and German Heart Center Munich. Medical history, preoperative condition, intra-, and postoperative course were recorded for these patients according to the protocol of the German quality assurance program. Preoperative condition of the patient was summarized with an additive risk score. The correlation between postoperative length of stay in the intensive care unit (ICU) and preoperative risk was investigated. For a subgroup of 30 patients, detailed cost analysis was performed and the relationship to preoperative risk examined. For all risk factors examined, a significant increase in prevalence between 1987 and 1995 was observed. A close correlation between preoperative risk and postoperative length of stay in the ICU was found. A similar correlation existed between preoperative risk and actual costs of treatment. In addition, high-risk patients had a significantly higher likelihood of being discharged directly from our ICU to the ICU of other hospitals. Postoperatively, high-risk patients suffer more often from morbidity with subsequent prolonged intensive care and are, therefore, a financial burden for the operating institution in a reimbursement system with fixed rates. This is aggravated by the fact that a trend towards adverse risk profiles among patients undergoing cardiac surgery can be observed. Both factors combined may result in a scenario where those who would benefit most are denied surgical treatment.
Asunto(s)
Puente de Arteria Coronaria/economía , Unidades de Cuidados Intensivos/economía , Tiempo de Internación/economía , Sistema de Pago Prospectivo , Anciano , Asignación de Costos , Alemania , Investigación sobre Servicios de Salud , Costos de Hospital , Humanos , Prevalencia , Factores de Riesgo , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene has been postulated to be associated with an increased risk of coronary artery disease (CAD) and myocardial infarction (MI). METHODS AND RESULTS: In the present study, the effects of I/D gene polymorphism and of ACE activity on CAD and MI were investigated in 920 individuals who underwent coronary angiography for diagnostic purposes. In the total population and in all CAD and MI groups, a strong association was observed between the gene polymorphism and ACE activities; DD genotypes had approximately twofold higher ACE activities than II genotypes. Although classic risk and protective factors of CAD and MI were identified, associations of ACE genotype and of ACE activity to CAD and MI were not detected in the total population. Among subjects defined to be at lower risk of MI by low body mass index and low cigarette consumption, however, an association of the DD genotype with MI was found. Exclusion of individuals with triglyceride levels > 140 mg/dL and cholesterol levels > 180 mg/dL revealed an association of the DD genotype with CAD. An association of the ACE activity with CAD or MI could not be demonstrated in any of the low-risk populations. CONCLUSIONS: Increased ACE activity obviously is not a risk factor of CAD or MI. The importance of the deletion polymorphism for the development of CAD and MI may be restricted to individuals without classic risk factors.