The effectiveness of infrainguinal percutaneous transluminal angioplasty in the treatment of critical limb ischaemia

Critical chronic lower limb ischaemia (CLI) is the most severe form of peripheral arterial disease. Even though the treatment of CLI has evolved during the last decade, CLI is still associated with considerable morbidity, mortality and a decreased quality of life, in addition to a large financial impact on society. ---- Bypass surgery has traditionally been considered the approach of choice to treat CLI patients in order to avoid amputation. However, there are increasing data on the efficacy of endovascular revascularization procedures, such as percutaneous transluminal angioplasty (PTA), to achieve good leg salvage rates as well. Data gathered on all the 2,054 CLI patients revascularized at the Helsinki University Central Hospital between 2000 and 2007 were retrospectively analyzed. This patient cohort was used to compare the results of infrainguinal PTA and bypass surgery as well as to investigate predictors of failure after PTA. This study showed that infrainguinal PTA and bypass surgery yielded rather similar results in terms of survival, amputation-free survival and freedom from any re-intervention. When the femoropoliteal segment was treated, leg salvage was significantly better in the bypass surgery group, whereas no significant difference was observed between the two treatment methods when the revascularization extended to the infrapopliteal segment. PTA resulted in a significantly lower freedom from surgical re-interventions when compared to surgical revascularization. In this study the most important predictors of poor outcome after PTA for CLI were cardiac morbidity, nonambulatory status upon hospital arrival, and gangrene as a manifestation of CLI. Thus, when feasible, PTA seems to be a valid alternative for bypass surgery in the treatment of CLI provided that active redo-surgery is utilized. The optimal revascularization strategy should always be sought for each CLI patient individually considering the clinical state of the leg, the occlusive lesions to be treated, co-morbidities, life-expectancy, and the availability of a suitable vein for bypass.

Carotid Surgery : A posse ad esse non valet consequentia

According to a large body of evidence, carotid endarterectomy (CEA) can prevent strokes, provided that appropriate inclusion criteria and high-quality perioperative treatment methods are utilised with low complication rates. From the patient s perspective, it is of paramount importance that the operation is as safe and effective as possible. From the community s point of view, it is important that CEA provision prevents as many strokes as possible. In order to define the stroke preventing potential of CEA in different communities, a comparison between eight European countries and Australia was performed including 53 077 carotid interventions. A more detailed evaluation was performed in Finland, the United Kingdom and Egypt. It could be estimated that many potentially preventable strokes occur due to insufficient diagnostics and CEA provision. The number of CEAs should be at least doubled in the Helsinki region. The theoretical power of CEA provision in stroke prevention varied significantly between the countries. Delay from symptom to surgery has been identified as one of the most important factors influencing the effectiveness of CEA. In 2008 only 11% of CEAs in Helsinki university central hospital (HUCH) were performed within the recommended14 days. Registered data of 673 CEAs in HUCH during 2000-2005 was analyzed. There was no systematic error that would have changed the outcome analysis. However it is important that registers are audited regularly and cross matching of different registries is possible. A previously unpublished method of combining medial mandibulotomy, neck incision and carotid artery interposition was carried out as a collaboration of maxillofacial, ear, nose and throat and vascular surgeons. Five patients were operated on with a technique that was feasible and possible to perform with little morbidity, but due to the significant risks involved, this technique should be reserved for carefully selected cases. In stroke prevention, organisational decisions seem far more important than details in interventional procedures when CEA is performed with low complication rates, as was the case in the present study. A TIA clinic approach with close co-operation between the on-call vascular surgeons, neurologists and radiologists should be available at all centres treating these patients. Patients should have a direct and fast admission to the hospital performing CEA.

Sydämen hypertrofian ja kroonisen vajaatoiminnan farmakologinen hoito

Sydämen krooninen vajaatoiminta on merkittävä maailmanlaajuinen ongelma. Se on erilaisten sydän- ja verisuonisairauksien aiheuttama monimuotoinen oireyhtymä. Sydämen vasemman kammion hypertrofia eli sydämen seinämien paksuuntuminen on yksi keskeinen tekijä, joka voi olla sydämen vajaatoiminnan taustalla. Kohonnut verenpaine on yleisin syy, joka johtaa sydänlihaksen paksuuntumiseen. Tämä johtaa sydämen pumppaustoiminnan häiriintymiseen, erilaisten neurohormonaalisten mekanismien aktivaatioon ja edelleen sydämen vajaatoimintaan. Sydämen vajaatoiminnan neurohormonaalisista mekanismeista tärkeimmät ovat reniini-angiotensiini-aldosteroni-järjestelmän ja sympaattisen hermoston aktivaatio, sydämen rakenteiden uudelleenmuovautuminen, sydänlihassolujen apoptoosi ja systeeminen tulehdustila. Sydämen hypertrofiaa ja sen syntymistä pyritään estämään kohonneen verenpaineen lääkehoidolla. Reniini-angiotensiini-aldosteronijärjestelmällä on keskeinen merkitys sydämen vajaatoiminnassa. Sydämen vajaatoiminnan ennusteeseen vaikuttavista lääkeaineista angiotensiinikonvertasin estäjät (ACEestäjät) ovat säilyttäneet johtoasemansa jo vuosikymmenten ajan. Angiotensiinireseptoreiden salpaajien (AT1-salpaajien) odotettiin syrjäyttävän ACE-estäjät sydämen vajaatoiminnan hoidossa, mutta toistaiseksi niitä pidetään vain vaihtoehtoisina lääkkeinä. Sympaattisen hermoston aktivaatiota vähentävät β-salpaajat ovat vakiinnuttaneet asemansa toiseksi tärkeimpänä lääkeryhmänä. Diureetit ovat paljon käytetty lääkeaineryhmä sydämen vajaatoiminnan hoidossa, mutta niistä ainoastaan aldosteroniantagonisteilla on tutkitusti ennustetta parantavaa vaikutusta. Kroonisen vajaatoiminnan hoidossa käytetään edelleen myös digoksiinia. Tulevaisuudessa sydämen vajaatoiminnan ennusteeseen vaikuttavia lääkeaineita voivat olla reniinin estäjät, neutraaliendopeptidaasin estäjät, vasopressiinin antagonistit tai inflammatroisiin sytokiineihin vaikuttavat molekyylit. Erikoistyön kokeellisessa osiossa tarkoituksena oli tutkia sydämen hypertrofian kehittymistä vatsa-aortta kuristetuilla rotilla ja kalsiumherkistäjä levosimendaanin sekä AT1-salpaaja valsartaanin vaikutuksia hypertrofian kehittymiseen. Kokeellisessa osiossa arvioitiin myös sydämen hypertrofian ja vajaatoiminnan jyrsijämallina käytetyn vatsa-aortan kuristuksen (koarktaation) toimivuutta ja vaikutuksia ultraäänen avulla määritettyihin kardiovaskulaarisiin parametreihin. Vatsa-aortta kuristettiin munuaisvaltimoiden yläpuolelta. Kuristus saa aikaan verenpaineen kohoamisen ja sydämen työtaakan lisääntymisen. Pitkittyessään tila johtaa sydänlihaksen hypertrofiaan ja vajaatoimintaan. 64 eläintä jaettiin ryhmiin, siten että jokaiseen ryhmään tuli kahdeksan eläintä. Ryhmistä kolmelle annettiin lääkeaineena levosimendaania kolmella eri päiväannoksella (0,01 mg/kg; 0,10 mg/kg; 1,00 mg/kg) ja kolmelle valsartaania kolmella eri päiväannoksella (0,10 mg/kg; 1,00 mg/kg; 10,00 mg/kg) juomaveden mukana. Lääkitys aloitettiin leikkauksen jälkeen ja jatkettiin kahdeksan viikon ajan. Kardiovaskulaariset parametrit, kuten isovolumetrinen relaksaatioaika (IVRT), vasemman kammion läpimitta systolessa ja diastolessa sekä seinämäpaksuudet, ejektiofraktio (EF), supistuvuusosuus (FS), minuuttitilavuus (CO) ja iskutilavuus (SV) määritettiin kahdeksan viikon kuluttua leikkauksesta ultraäänitutkimuksen avulla. Lisäksi määritettiin eläinten sydämen paino suhteessa ruumiin painoon. Tuloksia verrattiin ilman lääkehoitoa olleeseen koarktaatioryhmään. Eläinmallin toimivuutta arvioitiin vertaamalla koarktaatioryhmän tuloksia sham-operoidun ryhmän tuloksiin. Levosimendaanilla havaittiin työssä sydämen systolista toimintaa parantava vaikutus. Tämä näkyi tendenssinä parantaa ejektiofraktioita ja vasemman kammion supistuvuusosuuksia. Sydämen diastoliseen toimintaan ei kummallakaan lääkeaineella ollut merkittävää vaikutusta. Diastolista toimintaa arvioitiin isovolumetrisen relaksaatioajan muutoksilla. Sydämen hypertrofian kehittymiseen ei kummallakaan lääkeaineella ollut merkittävää vaikutusta. Eläinmallin todettiin mallintavan hyvin sydämen hypetrofiaa ihmisellä, mutta ei niinkään sydämen vajaatoimintaa.

Cardiac remodeling in Drosophila arises from changes in actin gene expression and from a contribution of lymph gland-like cells to the heart musculature

Understanding the basis of normal heart remodeling can provide insight into the plasticity of the cardiac state, and into the potential for treating diseased tissue. In Drosophila, the adult heart arises during metamorphosis from a series of events, that include the remodeling of an existing cardiac tube, the elaboration of new inflow tracts, and the addition of a layer of longitudinal muscle fibers. We have identified genes active in all these three processes, and studied their expression in order to characterize in greater detail normal cardiac remodeling. Using a Transglutaminase-lacZ transgenic line, that is expressed in the inflow tracts of the larval and adult heart, we confirm the existence of five inflow tracts in the adult structure. In addition, expression of the Actin87E actin gene is initiated in the remodeling cardiac tube, but not in the longitudinal fibers, and we have identified an Act87E promoter fragment that recapitulates this switch in expression. We also establish that the longitudinal fibers are multinucleated, characterizing these cells as specialized skeletal muscles. Furthermore, we have defined the origin of the longitudinal fibers, as a subset of lymph gland cells associated with the larval dorsal vessel. These studies underline the myriad contributors to the formation of the adult Drosophila heart, and provide new molecular insights into the development of this complex organ. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Scroll-Wave Dynamics in Human Cardiac Tissue: Lessons from a Mathematical Model with Inhomogeneities and Fiber Architecture

Cardiac arrhythmias, such as ventricular tachycardia (VT) and ventricular fibrillation (VF), are among the leading causes of death in the industrialized world. These are associated with the formation of spiral and scroll waves of electrical activation in cardiac tissue; single spiral and scroll waves are believed to be associated with VT whereas their turbulent analogs are associated with VF. Thus, the study of these waves is an important biophysical problem. We present a systematic study of the combined effects of muscle-fiber rotation and inhomogeneities on scroll-wave dynamics in the TNNP (ten Tusscher Noble Noble Panfilov) model for human cardiac tissue. In particular, we use the three-dimensional TNNP model with fiber rotation and consider both conduction and ionic inhomogeneities. We find that, in addition to displaying a sensitive dependence on the positions, sizes, and types of inhomogeneities, scroll-wave dynamics also depends delicately upon the degree of fiber rotation. We find that the tendency of scroll waves to anchor to cylindrical conduction inhomogeneities increases with the radius of the inhomogeneity. Furthermore, the filament of the scroll wave can exhibit drift or meandering, transmural bending, twisting, and break-up. If the scroll-wave filament exhibits weak meandering, then there is a fine balance between the anchoring of this wave at the inhomogeneity and a disruption of wave-pinning by fiber rotation. If this filament displays strong meandering, then again the anchoring is suppressed by fiber rotation; also, the scroll wave can be eliminated from most of the layers only to be regenerated by a seed wave. Ionic inhomogeneities can also lead to an anchoring of the scroll wave; scroll waves can now enter the region inside an ionic inhomogeneity and can display a coexistence of spatiotemporal chaos and quasi-periodic behavior in different parts of the simulation domain. We discuss the experimental implications of our study.

Nonlinear measures of QT interval series: novel indices of cardiac repolarization lability: MEDqthr and LLEqthr

In this study, we investigated nonlinear measures of chaos of QT interval time series in 28 normal control subjects, 36 patients with panic disorder and 18 patients with major depression in supine and standing postures. We obtained the minimum embedding dimension (MED) and the largest Lyapunov exponent (LLE) of instantaneous heart rate (HR) and QT interval series. MED quantifies the system's complexity and LLE predictability. There was a significantly lower MED and a significantly increased LLE of QT interval time series in patients. Most importantly, nonlinear indices of QT/HR time series, MEDqthr (MED of QT/HR) and LLEqthr (LLE of QT/HR), were highly significantly different between controls and both patient groups in either posture. Results remained the same even after adjusting for age. The increased LLE of QT interval time, series in patients with anxiety and depression is in line with our previous findings of higher QTvi (QT variability index, a log ratio of QT variability corrected for mean QT squared divided by heart rate variability corrected for mean heart rate squared) in these patients, using linear techniques. Increased LLEqthr (LLE of QT/HR) may be a more sensitive tool to study cardiac repolarization and a valuable addition to the time domain measures such as QTvi. This is especially important in light of the finding that LLEqthr correlated poorly and nonsignificantly with QTvi. These findings suggest an increase in relative cardiac sympathetic activity and a decrease in certain aspects of cardiac vagal function in patients with anxiety as well as depression. The lack of correlation between QTvi and LLEqthr suggests that this nonlinear index is a valuable addition to the linear measures. These findings may also help to explain the higher incidence of cardiovascular mortality in patients with anxiety and depressive disorders. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Nonequilibrium arrhythmic states and transitions in a mathematical model for diffuse fibrosis in human cardiac tissue

We present a comprehensive numerical study of spiral-and scroll-wave dynamics in a state-of-the-art mathematical model for human ventricular tissue with fiber rotation, transmural heterogeneity, myocytes, and fibroblasts. Our mathematical model introduces fibroblasts randomly, to mimic diffuse fibrosis, in the ten Tusscher-Noble-Noble-Panfilov (TNNP) model for human ventricular tissue; the passive fibroblasts in our model do not exhibit an action potential in the absence of coupling with myocytes; and we allow for a coupling between nearby myocytes and fibroblasts. Our study of a single myocyte-fibroblast (MF) composite, with a single myocyte coupled to N-f fibroblasts via a gap-junctional conductance G(gap), reveals five qualitatively different responses for this composite. Our investigations of two-dimensional domains with a random distribution of fibroblasts in a myocyte background reveal that, as the percentage P-f of fibroblasts increases, the conduction velocity of a plane wave decreases until there is conduction failure. If we consider spiral-wave dynamics in such a medium we find, in two dimensions, a variety of nonequilibrium states, temporally periodic, quasiperiodic, chaotic, and quiescent, and an intricate sequence of transitions between them; we also study the analogous sequence of transitions for three-dimensional scroll waves in a three-dimensional version of our mathematical model that includes both fiber rotation and transmural heterogeneity. We thus elucidate random-fibrosis-induced nonequilibrium transitions, which lead to conduction block for spiral waves in two dimensions and scroll waves in three dimensions. We explore possible experimental implications of our mathematical and numerical studies for plane-, spiral-, and scroll-wave dynamics in cardiac tissue with fibrosis.

Turbulent electrical activity at sharp-edged inexcitable obstacles in a model for human cardiac tissue

Wave propagation around various geometric expansions, structures, and obstacles in cardiac tissue may result in the formation of unidirectional block of wave propagation and the onset of reentrant arrhythmias in the heart. Therefore, we investigated the conditions under which reentrant spiral waves can be generated by high-frequency stimulation at sharp-edged obstacles in the ten Tusscher-Noble-Noble-Panfilov (TNNP) ionic model for human cardiac tissue. We show that, in a large range of parameters that account for the conductance of major inward and outward ionic currents of the model fast inward Na+ current (INa), L-type slow inward Ca2+ current (I-CaL), slow delayed-rectifier current (I-Ks), rapid delayed-rectifier current (I-Kr), inward rectifier K+ current (I-K1)], the critical period necessary for spiral formation is close to the period of a spiral wave rotating in the same tissue. We also show that there is a minimal size of the obstacle for which formation of spirals is possible; this size is similar to 2.5 cm and decreases with a decrease in the excitability of cardiac tissue. We show that other factors, such as the obstacle thickness and direction of wave propagation in relation to the obstacle, are of secondary importance and affect the conditions for spiral wave initiation only slightly. We also perform studies for obstacle shapes derived from experimental measurements of infarction scars and show that the formation of spiral waves there is facilitated by tissue remodeling around it. Overall, we demonstrate that the formation of reentrant sources around inexcitable obstacles is a potential mechanism for the onset of cardiac arrhythmias in the presence of a fast heart rate.

Monitorización avanzada en el posoperatorio de las cardiopatías congénitas : motorización hemodinámica avanzada en el posoperatorio de cardiopatías congénitas mediante termodilución transpulmonar y espectroscopia cercana al infrarrojo

196 p. : graf.

Novel equation to determine the hepatic triglyceride concentration in humans by MRI: diagnosis and monitoring of NAFLD in obese patients before and after bariatric surgery

Background: Non-alcoholic fatty liver disease (NAFLD) is caused by abnormal accumulation of lipids within liver cells. Its prevalence is increasing in developed countries in association with obesity, and it represents a risk factor for non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Since NAFLD is usually asymptomatic at diagnosis, new non-invasive approaches are needed to determine the hepatic lipid content in terms of diagnosis, treatment and control of disease progression. Here, we investigated the potential of magnetic resonance imaging (MRI) to quantitate and monitor the hepatic triglyceride concentration in humans. Methods: A prospective study of diagnostic accuracy was conducted among 129 consecutive adult patients (97 obesity and 32 non-obese) to compare multi-echo MRI fat fraction, grade of steatosis estimated by histopathology, and biochemical measurement of hepatic triglyceride concentration (that is, Folch value). Results: MRI fat fraction positively correlates with the grade of steatosis estimated on a 0 to 3 scale by histopathology. However, this correlation value was stronger when MRI fat fraction was linked to the Folch value, resulting in a novel equation to predict the hepatic triglyceride concentration (mg of triglycerides/g of liver tissue = 5.082 + (432.104 * multi-echo MRI fat fraction)). Validation of this formula in 31 additional patients (24 obese and 7 controls) resulted in robust correlation between the measured and estimated Folch values. Multivariate analysis showed that none of the variables investigated improves the Folch prediction capacity of the equation. Obese patients show increased steatosis compared to controls using MRI fat fraction and Folch value. Bariatric surgery improved MRI fat fraction values and the Folch value estimated in obese patients one year after surgery. Conclusions: Multi-echo MRI is an accurate approach to determine the hepatic lipid concentration by using our novel equation, representing an economic non-invasive method to diagnose and monitor steatosis in humans.

Construção de barreiras para diminuir as falhas nas mensurações glicêmicas realizadas pela enfermagem em pacientes críticos com insulina intravenosa

Esta pesquisa tem como objeto os fatores que influenciam a mensuração glicêmica realizada pela enfermagem em pacientes que recebem insulina contínua intravenosa utilizando glicosímetros portáteis à beira leito. Vários fatores podem influenciar a mensuração glicêmica, tais como a amostra sanguínea, a calibração do aparelho, a estocagem das fitas-teste, o hematócrito dos pacientes, o uso de vasoaminas e falhas do operador. A partir da Tese de que: A identificação dos fatores que influenciam a mensuração glicêmica realizada pela enfermagem através de glicosímetros é determinante para a eficiência das barreiras de salvaguarda voltadas para a minimização de falhas na sua execução, a fim de garantir resultados glicêmicos confiáveis e, consequentemente, realizar a titulação da insulina com segurança, teve-se como objetivo geral propor ações de enfermagem que funcionem como barreiras para diminuir as falhas nas mensurações glicêmicas realizadas pela enfermagem em pacientes que recebem infusão contínua de insulina. Espera-se contribuir com ações para garantir a adequação e o controle rigoroso da insulina administrada. Estudo observacional, transversal, prospectivo com abordagem quantitativa na análise dos dados, em uma unidade intensiva cirúrgica cardiológica de um hospital público do Rio de Janeiro. As variáveis do estudo foram submetidas a tratamentos estatísticos não paramétricos e às medidas de associação. Foram investigados 42 pacientes com observação de 417 glicemias. Predominaram pacientes do sexo feminino (57,14%), média de idade de 48 (15,85) anos, sem insuficiência renal e sem tratamento dialítico (90,48%). Observou-se PAM com média de 77(10,29) mmHg, uso de vasoaminas (80,95%), PaO2 ≥ 90mmHg em 85,71% e hematócrito <35% em 71,42%. Encontrou-se uma incidência de hipoglicemia de 35,7%, sendo a população dividida em dois grupos, o primeiro (G1) com pacientes que apresentaram hipoglicemia ≤ 60mg/dl (n=15), e o segundo (G2), com pacientes sem hipoglicemia (n=27). O hematócrito baixo foi a característica clínica que apresentou maior associação com a hipoglicemia. Pacientes com esta condição apresentaram 5,60 vezes mais risco de apresentarem hipoglicemia. O uso de vasoaminas elevou 3,3 vezes o risco de hipoglicemia em pacientes com estas medicações. A realização de cirurgias de emergência, a presença de insuficiência renal com tratamento dialítico, e a elevação da PaO2 acima de 90mmHg também apresentaram associação positiva com a hipoglicemia. Das 417 mensurações observadas, predominou o uso de amostra sanguínea de origem arterial. Observou-se que em todas as etapas da técnica de mensuração houve desvio de execução, com exceção de compressão da polpa digital. Os desvios observados que mostraram associação positiva (RR>1) para pacientes com hipoglicemia foram: a falta de calibração do glicosímetro, a falta de verificação da validade/integridade da fita teste, a falta da higienização das mãos e a falta da coleta de até 1 ml de sangue. Construiu-se uma revisão da técnica de mensuração glicêmica com enfoque nos fatores que podem comprometer o resultado glicêmico levando em conta o risco de hipoglicemia. Tornou-se evidente que a compreensão apropriada dos fatores que influenciam a glicemia e a mensuração glicêmica é indispensável para o enfermeiro na obtenção de resultados glicêmicos confiáveis, e assim, evitar erros na titulação das doses de insulina administrada.