Factors involved in initiation and regulation of complement lectin pathway influence postoperative outcome after pediatric cardiac surgery involving cardiopulmonary bypass.

Congenital heart disease (CHD) often requires surgical intervention, and is sometimes associated with life-threatening post-operative complications. We have investigated some factors of the innate immune system involved in the initiation or regulation of complement lectin pathway activation (MASP-1, MASP-2 MASP-3, MAp19, MAp44, ficolin-3) and related them to complications and prognosis in 190 pediatric patients undergoing CHD repair with the use of cardiopulmonary bypass (CPB). Patients with MAp44 levels ≤1.81 µg/ml more frequently experienced low cardiac output syndrome (LCOS), renal insufficiency, systemic inflammatory response syndrome (SIRS) and multiorgan dysfunction (MODS). Low MASP-3 (≤5.18 µg/ml) and high MASP-1 (≥11.7 µg/ml) levels were often associated with fatal outcome. Low ficolin-3 concentrations (≤10.1 µg/ml) were more common among patients experiencing SIRS and MODS than in those without complications. However, patients suffering from SIRS and MODS with low ficolin-3 had a much better prognosis (91% survival vs. 37% among other patients; p = 0.007). A discriminating value of 12.7 µg/ml ficolin-3 yielded 8% vs. 60% mortality (p = 0.001). Our data extend the knowledge concerning involvement of proteins of the lectin pathway in development of post-CPB complications. The potential prognostic value of low preoperative MAp44 and high preoperative ficolin-3 seems promising and warrants independent confirmation.

Levosimendan for Perioperative Cardioprotection: Myth or Reality?

BACKGROUND: Levosimendan is a calcium sensitizer drug causing increased contractility in the myocardium and vasodilation in the vascular system. It is mainly used for the therapy of acute decompensated heart failure. Several studies on animals and humans provided evidence of the cardioprotective properties of levosimendan including preconditioning and anti-apoptotic. In view of these favorable effects, levosimendan has been tested in patients undergoing cardiac surgery for the prevention or treatment of low cardiac output syndrome. However, initial positive results from small studies have not been confirmed in three recent large trials. AIM: To summarize levosimendan mechanisms of action and clinical use and to review available evidence on its perioperative use in a cardiac surgery setting. METHODS: We searched two electronic medical databases for randomized controlled trials studying levosimendan in cardiac surgery patients, ranging from January 2000 to August 2017. Metaanalyses, consensus documents and retrospective studies were also reviewed. RESULTS: In the selected interval of time, 54 studies on the use of levosimendan in heart surgery have been performed. Early small size studies and meta-analyses have suggested that perioperative levosimendan infusion could diminish mortality and other adverse outcomes (i.e. intensive care unit stay and need for inotropic support). Instead, three recent large randomized controlled trials (LEVO-CTS, CHEETAH and LICORN) showed no significant survival benefits from levosimendan. However, in LEVO-CTS trial, prophylactic levosimendan administration significantly reduced the incidence of low cardiac output syndrome. CONCLUSIONS: Based on most recent randomized controlled trials, levosimendan, although effective for the treatment of acute heart failure, can't be recommended as standard therapy for the management of heart surgery patients. Further studies are needed to clarify whether selected subgroups of heart surgery patients may benefit from perioperative levosimendan infusion.

Mannose-binding lectin (MBL) insufficiency protects against the development of systemic inflammatory response after pediatric cardiac surgery.

We investigated MBL2 and MASP2 genotypes, serum MBL (mannose-binding lectin) levels and activities of its complexes with associated serine proteases (MASP-1, MASP -2), in relation to complications following cardiac surgery in 195 children. The incidence of SIRS was lower in patients carrying MBL2 A/O and O/O genotypes (p=0.024). Children with MBL levels <500ng/ml had a lower risk of SIRS (p=0.014) and fever (p=0.044). Median MBL concentration was higher in patients who developed SIRS (p=0.048) but lower in those with post-operative infections (p=0.046). MBL-MASP-2 activities <100mU/ml protected from SIRS (p=0.007), low cardiac output syndrome (p=0.03) and multiorgan failure (p=0.012). In contrast, MBL2 YA/YA genotypes were associated with SIRS (p=0.018), low cardiac output syndrome (p=0.018), fever (p=0.018) and high inotropic score (VIS>30) (p=0.021). Thus, low MBL concentrations and associated genotypes may protect patients from systemic inflammation while high MBL serum levels and corresponding genotypes are risk factors of postoperative complications.

[DEFORMITY OF LEFT VENTRICLE WALLS IN PATIENTS WITH AORTAL VALVE STENOSIS].

Parameters of longitudinal deformity of left ventricle walls in patients, suffering aortal valve stenosis (AVS), were analyzed. While the process of heart contraction in norm and in AVS occurs, longitudinal deformity is expressed maximally in its apical divisions. AVS deformity of apical divisions of left ventricle, as well as middle divisions of interventricular septum and lower wall, practically did not differ from such in norm, and deformity of basal divisions of all walls and middle divisions of posterior, lateral and anterior walls of left ventricle was trustworthy less than a norm. Thus, a reduction of the deformity indices in basal divisions of left ventricle and middle segments of its posterior, lateral and anterior walls in patients, suffering AVS with preserved output fraction, precedes the disorders of its hemodynamics and constitutes a predictor for the cardiac output reduction.

Síndrome de bajo gasto cardiaco en el niño en estado crítico, consideraciones para enfermería / Low cardiac output syndrome in critically ill child, nursing considerations

Para el profesional de enfermería que labora en el área asistencial y especialmente en las unidades de cuidados intensivos, es fundamental contar con literatura actualizada y completa de las patologías y estados clínicos más frecuentes de los pacientes a su cuidado. Este artículo es una recopilación de información útil y específica cuyo objetivo es aportar las herramientas necesarias para la identificación, el análisis y la intervención en los procesos fisiológicos que se desarrollan y varían de manera continua en el síndrome de bajo gasto cardiaco. El síndrome de bajo gasto cardiaco es una entidad frecuente en la Unidad de Cuidado Intensivo Pediátrico. En especial, los lactantes (niños menores de 2 años) por su inmadurez fisiológica y sus particulares mecanismos de respuesta y compensación hemodinámica, son más propensos a desarrollar bajo gasto cardiaco por múltiples causas. El monitoreo invasivo y continuo del gasto cardiaco en los lactantes es difícil y a menudo contraproducente, por lo que resulta indispensable para enfermería conocer los signos clínicos de mayor sensibilidad, especificidad en la detección y vigilancia del bajo gasto cardiaco en pediatría; estos signos son, en orden de aparición: taquicardia, disminución del llenado capilar, caída del gasto urinario y finalmente hipotensión arterial sistólica, entre otras.

For the nurse who works in nursing care and especially in intensive care units, it is essential to have complete and current and more frequent pathologies of patients in their care clinical literature states. This article is a compilation of useful and specific information aimed at providing the necessary tools for the identification, analysis and intervention in the physiological processes that develop and vary continuously in the low cardiac output syndrome. The low cardiac output syndrome is a common condition in the Pediatric Intensive Care Unit. In particular, infants (children under 2 years) for their physiological immaturity and their particular coping mechanisms and hemodynamic compensation, are more likely to develop low cardiac output by multiple causes. Invasive and continuous monitoring of cardiac output in infants is difficult and often counterproductive, making it essential to know the nursing clinical signs of greater sensitivity and specificity in detecting low cardiac output monitoring in pediatrics; these signs are, in order of appearance: tachycardia, decreased capillary refill, falling urine output and finally systolic blood pressure, among others.

[Inflammatory borrelia - associated dilated cardiomyopathy]. / Zánetlivá borreliová dilatacní kardiomyopatie.

A case of a 44-year-old female patient is described, examined for several weeks with shortness of breath and the symptoms of heart decompensation after repeated untreated respiratory infections. Echocardiographically determined diffuse hypokinesis of dilated left ventricle with ejection fraction of 20%. Coronarographic examination without any significant finding at the coronary bed. MRI of the myocardium supported the suspicion of myocarditis, followed by the endomyocardial biopsy with electron microscopic evidence of borrelia fragments. After the causal and symptomatic treatment, the patient experienced significant clinical improvement and full normalisation of the finding.

[Immunsuppressive therapy in virus-negative eosinophilic inflammatory cardiomyopathy]. / Immunsuppressive Therapie bei Virus-negativer eosinophiler inflammatorischer Kardiomyopathie.

HISTORY AND ADMISSION FINDINGS: A 52 year-old women presented with long-standing dyspnoea at exercise as a symptom of heart failure. A coronary heart disease had been excluded by coronary angiography a year before. The symptoms had persisted despite application of guideline-based anticongestive medication. INVESTIGATIONS: Electrocardiography showed sinus rhythm with decreased anterior wall amplitudes without acute ischemic signs. The white blood count revealed elevated leucocytes with high numbers of eosinophilic granulocytes. Echocardiography demonstrated severe left ventricular dysfunction with an ejection fraction of 30 % and a left ventricular end-diastolic diameter of 75 mm. Magnetic resonance imaging showed a pathologic late enhancement in the left ventricular wall. Six myocardial biopsies were obtained and revealed virus-negative eosinophilic inflammatory cardiomyopathy with focal fibrotic scarring. DIAGNOSIS, TREATMENT AND COURSE: The patient was treated according to a previously published study on virus-negative inflammatory heart disease with prednisone 1 mg/kg daily for 4 weeks followed by 0.33 mg/kg daily for 5 month and azathioprine 2 mg/kg daily for 6 month. The echocardiography of the left ventricular function showed an increase from 30 to 45 % and the clinical symptoms of the heart failure resolved to NYHA II. CONCLUSION: In patients with virus-negative eosinophilic inflammatory cardiomyopathy standardized therapy with prednisone and azathioprine can improve LV function and clinical symptoms.

Autonomic consequences of kainic acid-induced limbic cortical seizures in rats: peripheral autonomic nerve activity, acute cardiovascular changes, and death.

PURPOSE: Autonomic consequences of seizures are common, but can be severe. We sought to define changes in autonomic activity from limbic cortical seizures and their impact on the heart. METHODS: We studied kainic acid (KA)-induced seizures in urethane-anesthetized rats using peripheral nerve, blood pressure (BP), and ECG recordings and echocardiography. RESULTS: Seizures were associated with massive increases in parasympathetic (vagus nerves) and sympathetic (cervical sympathetic ganglion >renal nerve >splanchnic nerve) activity. Seizure-associated activity increases were greater than activity changes induced by nitroprusside or phenylephrine (each producing BP changes of >50 mmHg). Increases in c-fos expression were found in both sympathetic and parasympathetic medullary regions (as well as hypothalamic areas). Baroreceptor reflex function (tested with nitroprusside and phenylephrine) was impaired during seizures. Finally, a significant fraction of the animals died and the mechanism of death was defined through ECG, BP, and echocardiographic measures to be profound cardiac dilatation and bradyarrhythmia leading to hypoperfusion of the brain and ultimately hypoperfusion of the heart. Cardiovascular changes occur within seconds (or less) of autonomic nerve activity changes and death by these mechanisms takes minutes. DISCUSSION: We propose that the massive parasympathetic and sympathetic outflow that occurs during a seizure gets compounded by respiratory distress (driving both autonomic nervous system divisions in the same direction) causing mechanical dysfunction, slowing the heart, and hypoperfusing the brain.

[The influence of intracardiac asynchronism on the clinical course of chronic cardiac insufficiency].

Intracardiac asynchronism presents systolic and/or diastolic dyscoordination in different myocardial areas within one and/or between different cardiac chambers. QRS complex widening is the marker of electric asynchronism. In 1/3 of patients with chronic cardiac insufficiency (CCI), the width of QRS complex is more than 120 msec. sixty-five CCI patients (56 men aged 63.7 +/- 7.3 years and 9 women aged 66.8 +/- 8.2 years) were divided into two groups: the group with a wide QRS (more than 120 msec) and the group with a narrow QRS (less than 120 msec), 30 and 35 patients, respectively. In the group with a wide QRS, 96.6% of patients suffered from clinically significant CCI (functional class III to IV); in the other group it was observed in 65.7% of patients. The patients were observed during three years. CCI dynamics was evaluated, quality of life was assessed using the Russian version of SF questionnaire, and three-year survival rate was assessed by Kaplan-Meyer method. The presence of electric asynchronism in a form of a wide QRS complex promotes CCI progression, accompanied by CCI functional class deterioration as well as clinical worsening and decreased physical exercise tolerance according to 6-min walking test. The frequency of seeking medical aid was significantly higher among patients with a wide QRS complex.

A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart.

Marked sarcomere disorganization is a well-documented characteristic of cardiomyocytes in the failing human myocardium. Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC2v), which is involved in the development of human cardiomyopathy, is an important structural protein that affects physiologic cardiac sarcomere formation and heart development. Integrated cDNA expression analysis of failing human myocardia uncovered a novel protein kinase, cardiac-specific myosin light chain kinase (cardiac-MLCK), which acts on MLC2v. Expression levels of cardiac-MLCK were well correlated with the pulmonary arterial pressure of patients with heart failure. In cultured cardiomyocytes, knockdown of cardiac-MLCK by specific siRNAs decreased MLC2v phosphorylation and impaired epinephrine-induced activation of sarcomere reassembly. To further clarify the physiologic roles of cardiac-MLCK in vivo, we cloned the zebrafish ortholog z-cardiac-MLCK. Knockdown of z-cardiac-MLCK expression using morpholino antisense oligonucleotides resulted in dilated cardiac ventricles and immature sarcomere structures. These results suggest a significant role for cardiac-MLCK in cardiogenesis.

[Regenerative and plastic heart failure: molecular biological mechanisms and morphological bases].

Regenerative and plastic heart failure resulted in impaired or inhibited biosynthetic processes (plastic metabolism) and hence decreased or ceased intracellular cardiomyocytic regeneration. Atrophic (involutional) processes of cardiomyocytes and their progressive deficiency due to apoptotic death (diffuse cardiomyocytic depopulation), accompanied by the development of diffuse cardiosclerosis play the key role in regenerative and plastic heart failure. Diffuse myocardial sclerosis may be regarded as a corrected compensatory connective tissue response to a pronounced decrease in muscle fiber mass. In anthracycline-induced cardiomyopathy, myocardial remodeling as a result of changes in the pattern of parenchymal and stromal interactions occurs in the dilatation mode and induces no severe cardiac deformation, which is a favorable factor in restoring the normal myocardial architectonics when regenerative processes are resumed.

[Pathophysiology of heart failure]. / Pathophysiologie der Herzinsuffizienz.

Chronic heart failure is a clinical syndrome and the final common pathway of different cardiac diseases. Heart failure is accompanied by activation of the renin-angiotensin-aldosterone-system and the adrenergic nervous system. In addition, recent data emphasize important roles of maladaptive intracellular signaling pathways, decreased capillary density, altered calcium handling, metabolic changes, genetic polymorphisms, and programmed cell death in the failing heart. In this context, traditional pathophysiological concepts, e. g. concerning the role of cardiac hypertrophy, had to be given up. Thus, an increasingly complex scenario emerges with interdependent changes on the biochemical, molecular, metabolic, and cellular level. Novel therapeutic strategies may soon be based on these new pathophysiological concepts.

Activation of apoptotic processes during transition from hypertrophy to heart failure in guinea pigs.

Changes in oxidative stress and apoptotic process were studied during the progression of a compensated hypertrophy to a decompensated heart failure in guinea pigs. Banding of the ascending aorta resulted in heart hypertrophy. At 10 wk, ventricle-to-body weight ratio and thickness of the interventricular septum as well as the left ventricular wall were increased significantly. Although fractional shortening and ejection fraction were decreased, there were no signs of heart failure. Furthermore, there was no increase in wet-to-dry weight ratios for the lungs and liver at this stage. However, at 20 wk, heart failure was characterized by a significant depression in heart function as indicated by a decrease in fractional shortening, and ejection fraction and a lesser increase in wall thickness from diastole to systole. Animals also showed clinical signs of heart failure, and the wet-to-dry weight ratios of the lungs and liver were significantly higher. Cardiomyocyte oxidative stress was significantly higher in the 20-wk aortic-banded group. The ratio of Bax to Bcl-xl showed an increase at 10 wk, and there was a further increase at 20 wk. Mitochondrial membrane potential in the aortic-banded animals was significantly decreased at 10 and 20 wk. Cytochrome c levels were higher in the cytosol compared with the mitochondria, leading to a considerable increase in the expression of p17 subunit of caspase-3. At 20 wk, both early and late stages of apoptosis were observed in isolated cardiomyocytes. It is suggested that an increase in oxidative stress initiates mitochondrial death pathway during the hypertrophic stage, leading to apoptosis and heart failure at a later stage.

The TandemHeart pVAD in the treatment of acute fulminant myocarditis.

Acute fulminant myocarditis commonly manifests itself as severe, rapidly progressive hemodynamic deterioration and circulatory collapse that may be resistant to high doses of inotropic agents and steroids and to mechanical support by intra-aortic balloon pump. Acute myocarditis has a high mortality rate and may necessitate heart transplantation. The best short-term therapy available to support the patient may be a percutaneous left ventricular assist device. One such unit, the TandemHeart percutaneous ventricular assist device, can enable patients to recover in a few days. Two of our patients who experienced profound, therapy-resistant heart failure arising from acute myocarditis were successfully supported by the TandemHeart. To the best of our knowledge, these are the 1st reported cases in which the TandemHeart percutaneous ventricular assist device served as a bridge to recovery from acute fulminant myocarditis.

Effects of heart failure on brain-type Na+ channels in rabbit ventricular myocytes.

AIMS: Brain-type alpha-subunit isoforms of the Na(+) channel are present in various cardiac tissue types and may control pacemaker activity and excitation-contraction coupling. Heart failure (HF) alters pacemaker activity and excitation-contraction coupling. Here, we studied whether HF alters brain-type Na(+) channel properties. METHODS AND RESULTS: HF was induced in rabbits by volume/pressure overload. Na(+) currents of ventricular myocytes were recorded in the cell-attached mode of the patch-clamp technique using macropatches. Macropatch recordings were conducted from the middle portions of myocytes or from intercalated disc regions between cell pairs. Both areas exhibited a fast activating and inactivating current, 8.5 times larger in intercalated disc regions. Tetrodotoxin (TTX) (50 nM) did not block currents in the intercalated disc regions, but did block in the middle portions, indicating that the latter currents were TTX-sensitive brain-type Na(+) currents. Macropatch recordings from these regions were used to study the effects of HF on brain-type Na(+) current. Neither current density nor gating properties (activation, inactivation, recovery from inactivation, slow inactivation) differed between CTR and HF. CONCLUSION: The density and gating properties of brain-type Na(+) current are not altered in our HF model. In the volume/pressure-overload rabbit model of HF, the role of brain-type Na(+) current in HF-induced changes in excitation-contraction coupling is limited.