Paediatric myocarditis remains challenging from the perspectives of diagnosis and management. Multiple aetiologies exist and the majority of cases appear to be related to viral illnesses. Enteroviruses are believed to be the most common cause, although cases related to adenovirus may be more frequent than suspected. The clinical presentation is extremely varied, ranging from asymptomatic to sudden unexpected death. A high index of suspicion is crucial. There is emerging evidence to support investigations such as serum N-terminal B-type natriuretic peptide levels, as well as cardiac magnetic resonance imaging as adjuncts to the clinical diagnosis. In the future, these may reduce the necessity for invasive methods, such as endomyocardial biopsy, which remain the gold standard. Management generally includes supportive care, consisting of cardiac failure medical management, with the potential for mechanical support and cardiac transplantation. Treatments aimed at immunosuppression remain controversial. The paediatric literature is extremely limited with no conclusive evidence to support or refute these strategies. This article summarises the current literature regarding aetiology, clinical presentation, diagnosis, and management of myocarditis in paediatric patients.

The development of newer, load-independent indices of contractility has not substantially reduced general clinical reliance on ejection fraction and shortening fraction to detect abnormalities of contractility, in spite of common understanding of the preload and afterload dependence of percent fiber shortening. The more widespread application of sensitive indices of contractility has been impeded in part by complex methods of acquisition and analysis of data as well as uncertainty concerning the clinical importance of the additional derived information. Substantial recent experience with analysis of stress-shortening and stress-velocity, nonetheless, demonstrates that physiologically meaningful indices of afterload, preload, and contractility can be obtained noninvasively without hemodynamic interventions. There is extensive theoretical and experimental basis for these methods, and the limitations are similar to other global indices of myocardial mechanics. The superiority of methods which allow distinction between contractile abnormalities and abnormal load are particularly important when altered ventricular loading conditions are a prominent feature of the disease state. Several clinical situations have been identified for which analysis of stress-shortening and stress-velocity demonstrates that assessment by fiber shortening alone has resulted in misrepresentation of myocardial status. The clinical utility of assessment of ventricular function is considerably enhanced when the relative contribution of load and contractile performance is determined.

The persistence of so-called spongy myocardium was first reported in humans in the 1960s. Subsequently, a few reports described the condition, utilizing inconsistent facts and terminology. In 1990 the first report appeared using the term “noncompaction”, and detailed its clinical implications. Following this report, more descriptions of patients with noncompaction entered the literature. Prior to the availability of high resolution cross-sectional echocardiography, most cases of noncompacted myocardium escaped detection, as few patients underwent angiography. In this essay, I seek to adjudicate and clarify several confusions and controversies in the current literature including the acquired nature of hypertrabeculation, the fate of the so-called sinusoids, the relationship to coronary arteries, and noncompaction as another congenital malformation. The embryonic timing of cessation and reinitiation of compaction is conjectured as an explanation of the varied configurations of noncompaction as seen as a clinical entity. The clinical outcomes of decreased contractility, arrhythmia, and thromboembolism, have been stressed in the current literature, but more study is needed of the gray area between the normal variant and minimal noncompaction. A plea is made for the standardization of methods and terminology.

Detailed descriptions of cardiacgeometry and architecture are necessary for examining andunderstanding structural changes to the myocardium that are theresult of pathologies, for interpreting the results ofexperimental studies of propagation, and for use as athree-dimensional orthotropically anisotropic model for thecomputational reconstruction of propagation during arrhythmias.Diffusion tensor imaging (DTI) provides a means to reconstructfibre and sheet orientation throughout the ventricles. Wereconstruct and quantify canine cardiac architecture in selectedregions of the left and right ventricular free walls and theinter-ventricular septum. Fibre inclination angle rotates smoothlythrough the wall in all regions, from positive in the endocardiumto negative in the epicardium. However, fibre transverse and sheetangles show large variability in basal regions. Additionally,regions where two populations (positive and negative) of sheetstructure merge are identified. From these data, we conclude thata single DTI-derived atlas model of ventricular architectureshould be applicable to modelling propagation in wedges from theequatorial and apical left ventricle, and allow comparisons toexperimental studies carried out in wedge preparations. However,due to inter-individual variability in basal regions, individual(rather than atlas) DTI models of basal wedges or of the wholeventricles will be required.

We derive a constitutive law for the myocardium from the description of both the geometrical arrangement ofcardiomyocytes and their individual mechanical behaviour. We model a set of cardiomyocytes by a quasiperiodic discretelattice of elastic bars interacting by means of moments. We work in a large displacement framework and we use a discretehomogenization technique. The macroscopic constitutive law is obtained through the resolution of anonlinear self-equilibrum system of the discrete lattice reference cell.

Background and objective: Myocardial ischaemic preconditioning is characterized by a reduction in the rate of glycolysis. Brief myocardial ischaemia also reduces the glycogen content of the heart. The first objective was to determine whether augmenting glucose oxidation by activation of the pyruvate dehydrogenase complex would prevent the infarct limitation of ischaemic preconditioning. The second part of the study evaluates whether glycogen depletion before ischaemia mimics the infarct-limiting effect of ischaemic preconditioning.

Methods: Dichloroacetate (300 + 150 mg kg−1), an activator of the pyruvate dehydrogenase complex, was administered intravenously in the anaesthetized open-chest rabbit. All animals underwent 45 min of regional ischaemia and 3 h of reperfusion. Ischaemic preconditiong was elicited by 5 min of coronary occlusion. Control rabbits, those with ischaemic preconditioning with no dichloroacetate, received a saline vehicle. An isolated perfused rabbit heart model was employed to test the second hypothesis. Hearts were depleted of glycogen by perfusing them with a substrate-free buffer. Infarction was assessed by triphenyl tetrazolium chloride and area at risk determined with fluorescent particles.

Results: (a) Pyruvate dehydrogenase complex activation experiments. Treatment with dichloroacetate alone did not alter infarct size (58 ± 7% control vs. 60 ± 5% dichloroacetate). Addition of dichloroacetate did not attenuate the infarct-limiting effect of ischaemic preconditioning as evidenced by a similar reduction in infarct size in the ischaemic preconditioning group (22 ± 5%) and in the ischaemic preconditioning + dichloroacetate group (27 ± 7%). (b) Glycogen depletion experiments. Compared with control hearts with a normal glycogen content (4.84 ± 0.15 mg g−1 wet weight), glycogen depleted and ischaemic preconditioning hearts had reduced glycogen content before ischaemia (2.15 ± 0.26, 1.62 ± 0.17 mg g−1 wet weight, respectively; P < 0.01). Glycogen depletion did not reduce infarct size: 25.0 ± 4.5% cf. 27.9 ± 3.4% in the control group. However, ischaemic preconditioning resulted in a significant reduction of infarct size (11.5 ± 2.3% vs. 27.9 ± 3.4% control; P < 0.01).

Conclusions: Augmentation of oxidative glycolysis by dichloroacetate in in situ rabbit hearts does not alter the effect of ischaemic preconditioning, and glycogen depletion in the isolated rabbit heart does not influence infarct size after subsequent coronary occlusion.

Background and objective Volatile anaesthetic effects on altering tone after blocking nitric oxide synthase, cyclo-oxygenase-prostaglandin synthase and KATP channel pathways are controversial. We examined in isolated guinea pig hearts whether anaesthetics alter bradykinin and 5-hydroxytryptamine-induced effects on coronary flow and percentage oxygen extraction after blocking these pathways.

Methods Before and during exposure to sevo-flurane, halothane or isoflurane, hearts were infused with 10−13–10−8 M bradykinin, or 10−8–10−6 M 5-hydroxytryptamine (serotonin), with either L-NAME, indomethacin, or glibenclamide. Bradykinin or 5-hydroxytryptamine alone increased flow and decreased percentage oxygen extraction in a concentration-dependent manner; these effects were largely blocked by L-NAME (nitro-L-arginine methylester), which also decreased basal flow and increased basal percentage oxygen extraction.

Results The anaesthetics restored bradykinin and 5-hydroxytryptamine-induced increases in flow or decreases in percentage oxygen extraction after inhibition by L-NAME. Indomethacin or glibenclamide alone had little effect on basal flow and percentage oxygen extraction. The anaesthetics restored bradykinin and 5-hydroxytryptamine-induced increases in flow or decreases in percentage oxygen extraction after inhibition by L-NAME. Indomethacin or glibenclamide alone had little effect on basal flow and percentage oxygen extraction. Drug-induced increases in flow and decreases in percentage oxygen extraction in the absence or presence of glibenclamide or indomethacin were not altered at either of the two concentrations of anaesthetics.

Conclusions Endothelium-dependent vasodilatation is not affected by blocking prostaglandin release or KATP channels in the intact heart even in the presence of an anaesthetic. However, the diminished responses to vasodilators after nitric oxide synthase inhibition is largely restored or enhanced by anaesthetics.

Background and objective Although there is concern that cibenzoline, an antidysrhythmic drug for the treatment of ventricular and supraventricular dysrhy-thmias, may be associated with dose-dependent inhibition of myocardial contractility there are few reports about the relationship between myocardial metabolism and cardiac function when it is used. The present study was designed to investigate the effects of cibenzoline on cardiac function and metabolism. The effects of cibenzoline on cardiac function and myocardial metabolism were assessed in the isolated rat heart-lung preparation.

Methods Thirty-two male Wistar-ST rats were divided into four groups: control, and those to receive cibenzoline, either 300, 900 or 3000 ngmL−1. The cibenzoline was administered into the perfusate 5min after the start of perfusion. Heart rates in the 3000ngmL−1 group were significantly lower than those in the control group. Cardiac output in the 3000 ng mL−1 group at 15 and 30 min was significantly lower than in the control group. In all groups, values for %LV dP/df max (the ratio of values at each time to those at 5 min) at 20, 25, 30 min were significantly higher than at 5min. Myocardial adenosine tripho-sphate concentration in the 3000ngmL−1 group was significantly lower than in controls. There was no difference between groups in the lactate/pyruvate ratio.

Conclusion The therapeutic range of cibenzoline has few effects on cardiac function and metabolism, although concentrations 10 times greater may cause a deterioration in myocardial metabolism.

The retrospective analysis of 1700 forensic autopsies over 17 years (1981–97) following unexpected sudden cardiac death revealed a group of 50 cases that could have been related to surgery and/or anaesthesia. Patients were young with no history of cardiac disease. Surgery was performed for uncomplicated disorders, all classified as ASA 1. Cardiac arrest took place at induction of anaesthesia in 16% of cases, during surgery in 64% and at the end of surgery in 20%. Investigation and expertise reports ordered by the public prosecutor revealed none of the typical causes of death usually associated with surgery or anaesthesia. Pathological examination showed cardiac lesions in 47 cases: arrhythmogenic right ventricular cardiomyopathy in 18 cases, coronary artery disease in 10 cases, cardiomyopathy in eight cases, structural abnormalities of the His bundle in nine cases, mitral valve prolapse in one case, and acute myocarditis in one case. Identification of the cause of death of patients at low risk may provide major relief to the family of the patient and the medical staff.

Macrophages are important in inflammatory processes in heart disease and in transplantation rejection. A resurgence of interest in the macrophage has emanated from recent evidence implicating it as an effector cell in atherosclerosis and transplantation rejection. The detailed distribution of the macrophage within the normal human heart is unknown. We quantified macrophage numbers in the different chambers of the heart. Large tissue blocks (1.5–2.0 cm3) were removed from specific sites in 5 ‘normal’ control hearts (2 males, 3 females, age range 19–46 y). Paraffin-embedded sections were stained with a CD68 pan macrophage marker. Positive cells were enumerated within 20 random fields. Results were analysed using a generalised linear modelling method using the Poisson distribution. Macrophages were identified within septa, and often close to blood vessels, in the myocardium, and in the majority of areas in all hearts. Macrophage numbers varied significantly between areas (range 0–6 cells/high power field; P<0.001), and between the 5 hearts analysed (P<0.001). In general, there were significantly more macrophages in the ventricles (RV P<0.01, LV P<0.05), but these differences were affected by heart differences. This study provides a baseline for the range of macrophage numbers within normal hearts, thus enabling comparisons with macrophage numbers within diseased and transplanted hearts.