Cardiac anomalies associated with Escobar syndrome: A case report and a review of the literature.

RATIONALE: Escobar syndrome (ES) is an autosomal recessive disorder. It is highly characterized by facial abnormalities, congenital diaphragmatic muscle weakness, myasthenic-like features, and skin pterygiums on multiple body legions. ES is a rare condition associated with many external and internal abnormalities. The internal malformations described in ES affect many organs including the heart, lungs, esophagus, liver, spleen, and intestine. The purpose of this paper is to explore the cardiac manifestations associated with ES. PATIENT CONCERNS: A 3.5-year-old girl, who was born for double first cousins, was admitted to the hospital for neuromuscular evaluation of multiple congenital contractures. DIAGNOSIS: The girl was diagnosed with ES and isolated dextrocardia which is a rare cardiac manifestation. However, to the best of our knowledge, no similar cases have been reported to date, and this case is thus believed to be very rare. INTERVENTIONS: The patient underwent an operative intervention to correct the bilateral fixed flexion deformity at her knees which was related to the posterior bilateral fibrotic bands/pterygia. OUTCOMES: Post-operatively, complete knee extension was obtained, the patient was fitted with a cast and extension night splint. She was discharged alive and had no complications. The patient was followed regularly in the orthopedic clinic and had periodic physiotherapy sessions. CONCLUSIONS: ES and isolated dextrocardia concurrence in the presented case resulted from different pathogenic mechanisms. Our findings suggest that ES might be caused by dysfunction in the acetylcholine receptor throughout fetal life, which may have affected muscle strength and movement. Other cardiac conditions include hypoplastic left-sided heart, Hypertrophic cardiomyopathy, patent ductus arteriosus, and heterotaxia.

Adult human heart slices are a multicellular system suitable for electrophysiological and pharmacological studies.

Electrophysiological and pharmacological data from the human heart are limited due to the absence of simple but representative experimental model systems of human myocardium. The aim of this study was to establish and characterise adult human myocardial slices from small patients' heart biopsies as a simple, reproducible and relevant preparation suitable for the study of human cardiac tissue at the multicellular level. Vibratome-cut myocardial slices were prepared from left ventricular biopsies obtained from end-stage heart failure patients undergoing heart transplant or ventricular assist device implantation, and from hearts of normal dogs. Multiple slices were prepared from each biopsy. Regular contractility was observed at a range of stimulation frequencies (0.1-2 Hz), and stable electrical activity, monitored using multi-electrode arrays (MEA), was maintained for at least 8 h from slice preparation. ATP/ADP and phosphocreatine/creatine ratios were comparable to intact organ values, and morphology and gap junction distribution were representative of native myocardium. MEA recordings showed that field potential duration (FPD) and conduction velocity (CV) in human and dog slices were similar to the values previously reported for papillary muscles, ventricular wedges and whole hearts. Longitudinal CV was significantly faster than transversal CV, with an anisotropic ratio of 3:1 for human and 2.3:1 for dog slices. Importantly, slices responded to the application of E-4031, chromanol and 4-aminopyridine, three potassium channel blockers known to affect action potential duration, with an increase in FPD. We conclude that viable myocardial slices with preserved structural, biochemical and electrophysiological properties can be prepared from adult human and canine heart biopsies and offer a novel preparation suitable for the study of heart failure and drug screening.

Prolonged mechanical unloading affects cardiomyocyte excitation-contraction coupling, transverse-tubule structure, and the cell surface.

Prolonged mechanical unloading (UN) of the heart is associated with detrimental changes to the structure and function of cardiomyocytes. The mechanisms underlying these changes are unknown. In this study, we report the influence of UN on excitation-contraction coupling, Ca(2+)-induced Ca(2+) release (CICR) in particular, and transverse (t)-tubule structure. UN was induced in male Lewis rat hearts by heterotopic abdominal heart transplantation. Left ventricular cardiomyocytes were isolated from the transplanted hearts after 4 wk and studied using whole-cell patch clamping, confocal microscopy, and scanning ion conductance microscopy (SICM). Recipient hearts were used as control (C). UN reduced the volume of cardiomyocytes by 56.5% compared with C (UN, n=90; C, n=59; P<0.001). The variance of time-to-peak of the Ca(2+) transients was significantly increased in unloaded cardiomyocytes (UN 227.4+/-24.9 ms(2), n=42 vs. C 157.8+/-18.0 ms(2), n=40; P<0.05). UN did not alter the action potential morphology or whole-cell L-type Ca(2+) current compared with C, but caused a significantly higher Ca(2+) spark frequency (UN 3.718+/-0.85 events/100 mum/s, n=47 vs. C 0.908+/-0.186 events/100 microm/s, n=45; P<0.05). Confocal studies showed irregular distribution of the t tubules (power of the normal t-tubule frequency: UN 8.13+/-1.12x10(5), n=57 vs. C 20.60+/- 3.174x10(5), n=56; P<0.001) and SICM studies revealed a profound disruption to the openings of the t tubules and the cell surface in unloaded cardiomyocytes. We show that UN leads to a functional uncoupling of the CICR process and identify disruption of the t-tubule-sarcoplasmic reticulum interaction as a possible mechanism.

Genetic background affects function and intracellular calcium regulation of mouse hearts.

AIMS: The genetic background is currently under close scrutiny when determining cardiovascular disease progression and response to therapy. However, this factor is rarely considered in physiological studies, where it could influence the normal behaviour and adaptive responses of the heart. We aim to test the hypothesis that genetic strain variability is associated with differences in excitation-contraction coupling mechanisms, in particular those involved in cytoplasmic Ca(2+) regulation, and that they are concomitant to differences in whole-heart function and cell morphology. METHODS AND RESULTS: We studied 8- to 10-week-old male C57BL/6, BALB/C, FVB, and SV129 mice. Echocardiography and radiotelemetry were used to assess cardiac function in vivo. FVB mice had increased left ventricular ejection fraction and fractional shortening with significantly faster heart rate (HR) and lack of diurnal variation of HR. Confocal microscopy, sarcomere length tracking, and epifluorescence were used to investigate cell volume, t-tubule density, contractility, and Ca(2+) handling in isolated ventricular myocytes. Sarcomere relaxation and time-to-peak of the Ca(2+) transient were prolonged in BALB/C myocytes, with more frequent Ca(2+) sparks and significantly higher sarcoplasmic reticulum (SR) Ca(2+) leak. There were no strain differences in the contribution of different Ca(2+) extrusion mechanisms. SV129 had reduced SR Ca(2+) leak with elevated SR Ca(2+) content and smaller cell volume and t-tubule density compared with myocytes from other strains. CONCLUSION: These results demonstrate that a different genetic background is associated with physiological differences in cardiac function in vivo and differences in morphology, contractility, and Ca(2+) handling at the cellular level.