Trabeculations of the porcine and human cardiac ventricles are different in number but similar in total volume.

An intricate meshwork of trabeculations lines the luminal side of cardiac ventricles. Compaction, a developmental process, is thought to reduce trabeculations by adding them to the neighboring compact wall which is then enlarged. When pig, a plausible cardiac donor for xenotransplantation, is compared to human, the ventricular walls appear to have fewer trabeculations. We hypothesized the trabecular volume is proportionally smaller in pig than in human. Macroscopically, we observed in 16 pig hearts that the ventricular walls harbor few but large trabeculations. Close inspection revealed a high number of tiny trabeculations, a few hundred, within the recesses of the large trabeculations. While tiny, these were still larger than embryonic trabeculations and even when considering their number, the total tally of trabeculations in pig was much fewer than in human. Volumetrics based on high-resolution MRI of additional six pig hearts compared to six human hearts, revealed the left ventricles were not significantly differently trabeculated (21.5 versus 22.8%, respectively), and the porcine right ventricles were only slightly less trabeculated (42.1 vs 49.3%, respectively). We then analyzed volumetrically 10 pig embryonic hearts from gestational day 14-35. The trabecular and compact layer always grew, as did the intertrabecular recesses, in contrast to what compaction predicts. The proportions of the trabecular and compact layers changed substantially, nonetheless, due to differences in their growth rate rather than compaction. In conclusion, processes that affect the trabecular morphology do not necessarily affect the proportion of trabecular-to-compact myocardium and they are then distinct from compaction.

Field conditions is a risk factor for traumatic injury in youth football-A joint venture of medicine and hydrology.

INTRODUCTION: The risk of traumatic injury in football has been suggested to be affected by field conditions. This study, therefore, aimed to investigate whether near surface water content of the football field, influenced the risk of traumatic injuries during a youth football tournament. METHODS: At Dana Cup, an annual international youth football tournament in Denmark, all injuries were registered and classified at the on-site emergency department over 7 years. The incidence rate of traumatic injury was computed. Meteorological data and soil characteristics were used to simulate near surface water content of the playing fields. The incidence rate ratio (IRR) between water content and injury incidence rate was analyzed using a multivariate Poisson regression, controlling for tournament stage and demographical parameters. RESULTS: About 2704 injuries were recorded corresponding to a risk time of 284 905 player hours. An inverse relation between water contents and the incidence rate of traumatic injury was found (IRR = 0.24 95% CI 0.1-0.7, p = 0.01). The incidence rate of traumatic injury increased with advancing tournament stage, that is, for the finals (IRR = 4.30 95% CI 2.8-6.6, p < 0.001). Also we found an interaction between dry fields and the final stage of tournament, further exacerbating this effect. CONCLUSIONS: Our data suggest that the incidence rate of traumatic injury is increased with drier field conditions and advanced tournament stages.

Anatomically correct assessment of the orientation of the cardiomyocytes using diffusion tensor imaging.

Diffusion tensor imaging has been used for assessing the orientation of cardiac myocytes for decades. Striking methodological differences exist between studies when quantifying these orientations. This limits the comparability between studies, and impedes collaboration and the drawing of appropriate physiological conclusions. We have sought to elucidate these differences, permitting us to propose a standardised "tool set" that might better establish consensus in future studies. We fixed hearts from seven 25 kg pigs in formalin, and scanned them using diffusion tensor imaging. Using various angle definitions as found in literature, we assessed the orientations of cardiomyocytes, comparing them in terms of helical and intrusion angles, along with the orientation of their aggregations. The difference between assessment of the helical angle with and without relation to the epicardial curvature was 25.2° (SD: 7.9) at the base, 5.8° (1.9) at the equatorial level, and 28.0° (7.0) at the apex, ANOVA P = 0.001. In comparable fashion, the intrusion angle differed by 25.9° (12.9), 7.6° (0.98) and 17.5° (4.7), P = 0.01, and the angle of the aggregates (E3-angle) differed by 25.0° (13.5) at the base, 9.4° (1.7) at the equator, and 23.1° (6.2) apically, P = 0.003. When assessing 14 definitions used in literature to calculate the orientation of aggregates, only 4 rendered identical results. The findings show that any attempt to use projection of eigenvectors introduces considerable bias. The epicardial curvature of the ventricular cone needs to be taken into account when seeking to provide accurate quantification of the orientation of the aggregated cardiomyocytes, especially in the apical and basal regions. This means that projection of eigenvectors should be avoided prior to quantifying myocyte orientation, especially when assessing radial orientation. Based on our results, we suggest appropriate methods for valid assessment of myocyte orientation using diffusion tensor imaging.

How are the cardiomyocytes aggregated together within the walls of the left ventricular cone?

The manner of packing together of the cardiomyocytes within the walls of the cardiac ventricles has now been investigated for over half a millennium. In 1669, Lower dissected the ventricular mass, likening the arrangement to skeletal musculature, in the form of a myocardial band extending between the right and left atrioventricular junctions. Pettigrew subsequently showed obvious helical arrangements to be evident within the ventricular walls, but emphasised that the cardiomyocytes were attached to each other, and could not justifiably be compared with skeletal cardiomyocytes. Torrent-Guasp then reactivated the notion that the ventricular mass was formed of a solitary band. Unlike Lower, he dissected the band as extending between the pulmonary to the aortic roots. Multiple investigations conducted using gross dissection and histology, and more recently diffusion tensor magnetic resonance imaging and computed tomographic analysis, have shown an absence of any anatomical boundaries within the walls that might permit the mass uniformly to be dissected so as to reveal the band. A response to a recent letter to the Journal, nonetheless, claimed that the dissections had been validated by clinicians interpreting the findings so as to provide an explanation for ventricular cardiodynamics, arguing that the findings provided a suitable anatomical model for this purpose. Anatomical models, however, are of no value unless they are anatomically correct. In this review, therefore, we summarise the evidence showing that the cardiomyocytes making up the ventricular walls, rather than forming a ventricular myocardial band, are instead aggregated together to form a three-dimensional myocardial mesh.

Resolving the natural myocardial remodelling brought upon by cardiac contraction; a porcine ex-vivo cardiovascular magnetic resonance study of the left and right ventricle.

BACKGROUND: The three-dimensional rearrangement of the right ventricular (RV) myocardium during cardiac deformation is unknown. Previous in-vivo studies have shown that myocardial left ventricular (LV) deformation is driven by rearrangement of aggregations of cardiomyocytes that can be characterised by changes in the so-called E3-angle. Ex-vivo imaging offers superior spatial resolution compared with in-vivo measurements, and can thus provide novel insight into the deformation of the myocardial microstructure in both ventricles. This study sought to describe the dynamic changes of the orientations of the cardiomyocytes in both ventricles brought upon by cardiac contraction, with particular interest in the thin-walled RV, which has not previously been described in terms of its micro-architecture. METHODS: The hearts of 14 healthy 20 kg swine were excised and preserved in either a relaxed state or a contracted state. Myocardial architecture was assessed and compared between the two contractional states by quantification of the helical, transmural and E3-angles of the cardiomyocytes using high-resolution diffusion tensor imaging. RESULTS: The differences between the two states of contraction were most pronounced in the endocardium where the E3-angle decreased from 78.6° to 24.8° in the LV and from 82.6° to 68.6° in the RV. No significant change in neither the helical nor the transmural angle was found in the cardiomyocytes of the RV. In the endocardium of the LV, however, the helical angle increased from 35.4° to 47.8° and the transmural angle increased from 3.1° to 10.4°. CONCLUSION: The entire myocardium rearranges through the cardiac cycle with the change in the orientation of the aggregations of cardiomyocytes being the predominant mediator of myocardial wall thickening. Interestingly, differences also exist between the RV and LV, which helps in the explanation of the different physiological capabilities of the ventricles.

The hypertrabeculated (noncompacted) left ventricle is different from the ventricle of embryos and ectothermic vertebrates.

Ventricular hypertrabeculation (noncompaction) is a poorly characterized condition associated with heart failure. The condition is widely assumed to be the retention of the trabeculated ventricular design of the embryo and ectothermic (cold-blooded) vertebrates. This assumption appears simplistic and counterfactual. Here, we measured a set of anatomical parameters in hypertrabeculation in man and in the ventricles of embryos and animals. We compared humans with left ventricular hypertrabeculation (N=21) with humans with structurally normal left ventricles (N=54). We measured ejection fraction and ventricular trabeculation using cardiovascular MRI. Ventricular trabeculation was further measured in series of embryonic human and 9 animal species, and in hearts of 15 adult animal species using MRI, CT, or histology. In human, hypertrabeculated left ventricles were significantly different from structurally normal left ventricles by all structural measures and ejection fraction. They were far less trabeculated than human embryonic hearts (15-40% trabeculated volume versus 55-80%). Early in development all vertebrate embryos acquired a ventricle with approximately 80% trabeculations, but only ectotherms retained the 80% trabeculation throughout development. Endothermic (warm-blooded) animals including human slowly matured in fetal and postnatal stages towards ventricles with little trabeculations, generally less than 30%. Further, the trabeculations of all embryos and adult ectotherms were very thin, less than 50 µm wide, whereas the trabeculations in adult endotherms and in the setting of hypertrabeculation were wider by orders of magnitude. It is concluded in contrast to a prevailing assumption, the hypertrabeculated left ventricle is not like the ventricle of the embryo or of adult ectotherms. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

Changes in overall ventricular myocardial architecture in the setting of a porcine animal model of right ventricular dilation.

BACKGROUND: Chronic pulmonary regurgitation often leads to myocardial dysfunction and heart failure. It is not fully known why secondary hypertrophy cannot fully protect against the increase in wall stress brought about by the increased end-diastolic volume in ventricular dilation. It has been assumed that mural architecture is not deranged in this situation, but we hypothesised that there might be a change in the pattern of orientation of the aggregations of cardiomyocytes, which would contribute to contractile impairment. METHODS: We created pulmonary valvular regurgitation by open chest, surgical suturing of its leaflets in seven piglets, performing sham operations in seven control animals. Using cardiovascular magnetic resonance imaging after 12 weeks of recovery, we demonstrated significantly increased right ventricular volumes in the test group. After sacrifice, diffusion tensor imaging of their hearts permitted measurement of the orientation of the cardiomyocytes. RESULTS: The helical angles in the right ventricle approached a more circumferential orientation in the setting of right ventricular RV dilation (p = 0.007), with an increased proportion of surface-parallel cardiomyocytes. In contrast, this proportion decreased in the left ventricle. Also in the left ventricle a higher proportion of E3 angles with a value around zero was found, and conversely a lower proportion of angles was found with a numerical higher value. In the dilated right ventricle the proportion of E3 angles around -90° is increased, while the proportion around 90° is decreased. CONCLUSION: Contrary to traditional views, there is a change in the orientation of both the left ventricular and right ventricular cardiomyocytes subsequent to right ventricular dilation. This will change their direction of contraction and hinder the achievement of normalisation of cardiomyocytic strain, affecting overall contractility. We suggest that the aetiology of the cardiac failure induced by right vetricular dilation may be partly explained by morphological changes in the myocardium itself.

The myocardial architecture changes in persistent pulmonary hypertension of the newborn in an ovine animal model.

BACKGROUND: Persistent pulmonary hypertension in the newborn remains a syndrome with high mortality. Knowledge of changes in myocardial architecture in the setting of heart failure in persistent pulmonary hypertension is lacking, and could aid in the explanation of the prevailing high mortality. METHODS: Persistent pulmonary hypertension was induced by antenatal ligation of the arterial duct in six ovine fetuses. The hearts were compared ex vivo with five matched control hearts, using diffusion tensor imaging to provide the overall anatomical arrangement, and assessment of the angulations and course of the cardiomyocytes. Fibrosis was assessed with histology. RESULTS: We found an overall increase in heart size in pulmonary hypertension, with myocardial thickening confined to the interventricular septum. An increase of 3.5° in angulation of myocyte aggregations was found in hypertensive hearts. In addition, we observed a 2.2% increase in collagen content in the right ventricular free wall. Finally, we found a previously undescribed subepicardial layer of strictly longitudinally oriented cardiomyocytes confined to the right ventricle in all hearts. CONCLUSION: Myocardial fibrosis and possibly changes in angulations of myocytes seem to play a part in the etiology of persistent pulmonary hypertension. Moreover, a new anatomical arrangement of right ventricular mural architecture is described.

Insights from echocardiography, magnetic resonance imaging, and microcomputed tomography relative to the mid-myocardial left ventricular echogenic zone.

BACKGROUND: The anatomical substrate for the mid-mural ventricular hyperechogenic zone remains uncertain, but it may represent no more than ultrasound reflected from cardiomyocytes orientated orthogonally to the ultrasonic beam. We sought to ascertain the relationship between the echogenic zone and the orientation of the cardiomyocytes. METHODS: We used 3D echocardiography, diffusion tensor imaging, and microcomputed tomography to analyze the location and orientation of cardiomyocytes within the echogenic zone. RESULTS: We demonstrated that visualization of the echogenic zone is dependent on the position of the transducer and is most clearly seen from the apical window. Diffusion tensor imaging and microcomputed tomography show that the echogenic zone seen from the apical window corresponds to the position of the circumferentially orientated cardiomyocytes. An oblique band seen in the parasternal view relates to cardiomyocytes orientated orthogonally to the ultrasonic beam. CONCLUSIONS: The mid-mural ventricular hyperechogenic zone represents reflected ultrasound from cardiomyocytes aligned orthogonal to the ultrasonic beam. The echogenic zone does not represent a space, a connective tissue sheet, a boundary between ascending and descending limbs of a hypothetical helical ventricular myocardial band, nor an abrupt change in cardiomyocyte orientation.

The functional architecture of skeletal compared to cardiac musculature: Myocyte orientation, lamellar unit morphology, and the helical ventricular myocardial band.

How the cardiomyocytes are aggregated within the heart walls remains contentious. We still do not fully understand how the end-to-end longitudinal myocytic chains are arranged, nor the true extent and shape of the lamellar units they aggregate to form. In this article, we show that an understanding of the complex arrangement of cardiac musculature requires knowledge of three-dimensional myocyte orientation (helical and intrusion angle), and appreciation of myocyte packing within the connective tissue matrix. We show how visualization and segmentation of high-resolution three-dimensional image data can accurately identify the morphology and orientation of the myocytic chains, and the lamellar units. Some maintain that the ventricles can be unwrapped in the form of a "helical ventricular myocardial band," that is, as a compartmentalized band with selective regional innervation and deformation, and a defined origin and insertion like most skeletal muscles. In contrast to the simpler interpretation of the helical ventricular myocardial band, we provide insight as to how the complex myocytic chains, the heterogeneous lamellar units, and connective tissue matrix form an interconnected meshwork, which facilitates the complex internal deformations of the ventricular wall. We highlight the dangers of disregarding the intruding cardiomyocytes. Preparation of the band destroys intruding myocytic chains, and thus disregards the functional implications of the antagonistic auxotonic forces they produce. We conclude that the ventricular myocardium is not analogous to skeletal muscle, but is a complex three-dimensional meshwork, with a heterogeneous branching lamellar architecture.

Effects of milrinone and epinephrine or dopamine on biventricular function and hemodynamics in an animal model with right ventricular failure after pulmonary artery banding.

Right ventricular (RV) failure due to chronic pressure overload is a main determinant of outcome in congenital heart disease. Medical management is challenging because not only contractility but also the interventricular relationship is important for increasing cardiac output. This study evaluated the effect of milrinone alone and in combination with epinephrine or dopamine on hemodynamics, ventricular performance, and the interventricular relationship. RV failure was induced in 21 Danish landrace pigs by pulmonary artery banding. After 10 wk, animals were reexamined using biventricular pressure-volume conductance catheters. The maximum pressure in the RV increased by 113% (P < 0.0001) and end-diastolic volume by 43% (P < 0.002), while left ventricular (LV) pressure simultaneously decreased (P = 0.006). Concomitantly, mean arterial pressure (MAP; -16%, P = 0.01), cardiac index (CI; -23%, P < 0.0001), and mixed venous oxygen saturation (SvO2 ; -40%, P < 0.0001) decreased. Milrinone increased CI (11%, P = 0.008) and heart rate (HR; 21%, P < 0.0001). Stroke volume index (SVI) decreased (7%, P = 0.03), although RV contractility was improved. The addition of either epinephrine or dopamine further increased CI and HR in a dose-dependent manner but without any significant differences between the two interventions. A more pronounced increase in biventricular contractility was observed in the dopamine-treated animals. LV volume was reduced in both the dopamine and epinephrine groups with increasing doses In the failing pressure overloaded RV, milrinone improved CI and increased contractility. Albeit additional dose-dependent effects of both epinephrine and dopamine on CI and contractility, neither of the interventions improved SVI due to reduced filling of the LV.

Effects of milrinone and epinephrine or dopamine on biventricular function and hemodynamics in right heart failure after pulmonary regurgitation.

Right ventricular failure (RVF) secondary to pulmonary regurgitation (PR) impairs right ventricular (RV) function and interrupts the interventricular relationship. There are few recommendations for the medical management of severe RVF after prolonged PR. PR was induced in 16 Danish landrace pigs by plication of the pulmonary valve leaflets. Twenty-three pigs served as controls. At reexamination the effect of milrinone, epinephrine, and dopamine was evaluated using biventricular conductance and pulmonary catheters. Seventy-nine days after PR was induced, RV end-diastolic volume index (EDVI) had increased by 33% (P = 0.006) and there was a severe decrease in the load-independent measurement of contractility (PRSW) (-58%; P = 0.003). Lower cardiac index (CI) (-28%; P < 0.0001), mean arterial pressure (-15%; P = 0.01) and mixed venous oxygen saturation (SvO2) (36%; P < 0.0001) were observed compared with the control group. The interventricular septum deviated toward the left ventricle (LV). Milrinone improved RV-PRSW and CI and maintained systemic pressure while reducing central venous pressure (CVP). Epinephrine and dopamine further improved biventricular PRSW and CI equally in a dose-dependent manner. Systemic and pulmonary pressures were higher in the dopamine-treated animals compared with epinephrine-treated animals. None of the treatments improved stroke volume index (SVI) despite increases in contractility. Strong correlation was detected between SVI and LV-EDVI, but not SVI and biventricular contractility. In RVF due to PR, milrinone significantly improved CI, SvO2, and CVP and increased contractility in the RV. Epinephrine and dopamine had equal inotropic effect, but a greater vasopressor effect was observed for dopamine. SV was unchanged due to inability of both treatments to increase LV-EDVI.

Optimal preservation of porcine cardiac tissue prior to diffusion tensor magnetic resonance imaging.

The effects of ex vivo preservation techniques on the quality of diffusion tensor magnetic resonance imaging in hearts are poorly understood, and the optimal handling procedure prior to investigation remains to be determined. Therefore, 24 porcine hearts were examined in six groups treated with different preservation techniques, including chemical fixation and freezing. Diffusion properties of each heart were assessed with diffusion tensor imaging in terms of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (Da) and radial diffusivity (Dr). Tractography was performed to visualize the course of the cardiomyocytes, assuming greater diffusivity in the longitudinal than the transverse axis of individual cardiomyocytes. Significant differences in MD, Da and Dr were found, as well as in FA between groups (P < 0.001). Freezing of specimens resulted in the lowest mean FA of 0.21 (0.06) and highest Dr of 8.92 (1.5) mm2 s(-1) . The highest mean FA was found to be 0.43 (0.11) in hearts perfusion-fixed with formalin. Calculated tractographies were indistinguishable among groups except in frozen specimens, where no fibres could be tracked. Perfusion fixation with formalin provided the best tractography, but immersion fixation yielded diffusion data most similar to fresh hearts. These findings suggest that parameters derived from diffusion tensor imaging in ex vivo hearts are sensitive to fixation and storage methods. In particular, freezing of specimens should be avoided prior to diffusion tensor imaging investigation due to significant changes in diffusion parameters and subsequent image deteriorations.

A 72-h sedated porcine model of traumatic spinal cord injury.

Introduction: There is an increasing focus on the prevention of secondary injuries following traumatic spinal cord injury (TSCI), especially through improvement of spinal cord perfusion and immunological modulation. Such therapeutic strategies require translational and controlled animal models of disease progression of the acute phases of human TSCI. Research question: Is it possible to establish a 72-h sedated porcine model of incomplete thoracic TSCI, enabling controlled use of continuous, invasive, and non-invasive modalities during the entire sub-acute phase of TSCI? Material and methods: A sham-controlled trial was conducted to establish the model, and 10 animals were assigned to either sham or TSCI. All animals underwent a laminectomy, and animals in the TSCI group were subjected to a weight-drop injury. Animals were then kept sedated for 72 h. The amount of injury was assessed by ex-vivo measures MRI-based fiber tractography, histology and immunohistochemistry. Results: In all animals, we were successful in maintaining sedation for 72 h without comprising vital physiological parameters. The MRI-based fiber tractography showed that all TSCI animals revealed a break in the integrity of spinal neurons, whereas histology demonstrated no transversal sections of the spine with complete injury. Notably, some animals displayed signs of secondary ischemic tissue in the cranial and caudal sections. Discussion and conclusions: This study succeeded in producing a porcine model of incomplete TSCI, which was physiologically stable up to 72 h. We believe that this TSCI model will constitute a potential translational model to study the pathophysiology secondary to TSCI in humans.

Contraction Patterns of Post-Fontan Single Right Ventricle Versus Normal Left and Right Ventricles in Children: Insights From Principal Strain Analysis.

BACKGROUND: Principal strain (PS) analysis quantifies three-dimensional myocardial deformation using three-dimensional speckle-tracking echocardiography. It defines both the amplitude and direction of the principal myocardial contraction, expressed as PS, and a perpendicular secondary strain of lower intensity. The aims of this study were to apply PS analysis to describe the contractile pattern in the single right ventricle (SRV) functioning as a systemic chamber in hypoplastic left heart syndrome, compared with the normal left ventricle (LV) and right ventricle (RV), and to compare SRV function using conventional echocardiographic evaluations. METHODS: Fifty-four post-Fontan patients with hypoplastic left heart syndrome and age-matched control subjects (normal LV, n = 64; normal RV, n = 48) underwent computation of PS lines, ejection fraction (EF), end-diastolic volume indexed to body surface area, PS, secondary strain, circumferential strain, and longitudinal strain. The PS lines were compared between groups. Linear regressions with coefficient determination (R2) of strains, fractional area change, and tricuspid annular plane systolic excursion with EF and end-diastolic volume index were assessed in SRV. Additionally, the hypoplastic left heart syndrome cohort was equally divided into two groups with higher and lower EFs, followed by comparison of all parameters. RESULTS: The pattern of PS lines demonstrated a left-handed direction in the anterior free wall, a right-handed direction in the posterior free wall, and a circumferential direction in the medial wall in SRV. In contrast, in the normal LV, the principal contraction is in the circumferential direction, whereas in the normal RV, it is predominantly longitudinal. The R2 values for PS, secondary strain, and circumferential strain on EF were high (0.88, 0.72, and 0.90, respectively), whereas the R2 value for longitudinal strain was comparable with that for fractional area change (0.56 and 0.55). All parameters were independent of end-diastolic volume index. PS lines in the higher EF group showed a more circumferential orientation than in the lower EF group in SRV. CONCLUSION: PS analysis provides a unique functional map of SRV contraction. This map differs from corresponding maps of the normal LV and RV. This may be helpful in understanding the mechanisms of SRV function, although future longitudinal studies are needed.

Left ventricular active strain energy density is a promising new measure of systolic function.

The left ventricular ejection fraction does not accurately predict exercise capacity or symptom severity and has a limited role in predicting prognosis in heart failure. A better method of assessing ventricular performance is needed to aid understanding of the pathophysiological mechanisms and guide management in conditions such as heart failure. In this study, we propose two novel measures to quantify myocardial performance, the global longitudinal active strain energy (GLASE) and its density (GLASED) and compare them to existing measures in normal and diseased left ventricles. GLASED calculates the work done per unit volume of muscle (energy density) by combining information from myocardial strain and wall stress (contractile force per unit cross sectional area). Magnetic resonance images were obtained from 183 individuals forming four cohorts (normal, hypertension, dilated cardiomyopathy, and cardiac amyloidosis). GLASE and GLASED were compared with the standard ejection fraction, the corrected ejection fraction, myocardial strains, stroke work and myocardial forces. Myocardial shortening was decreased in all disease cohorts. Longitudinal stress was normal in hypertension, increased in dilated cardiomyopathy and severely decreased in amyloid heart disease. GLASE was increased in hypertension. GLASED was mildly reduced in hypertension (1.39 ± 0.65 kJ/m3), moderately reduced in dilated cardiomyopathy (0.86 ± 0.45 kJ/m3) and severely reduced in amyloid heart disease (0.42 ± 0.28 kJ/m3) compared to the control cohort (1.94 ± 0.49 kJ/m3). GLASED progressively decreased in the hypertension, dilated cardiomyopathy and cardiac amyloid cohorts indicating that mechanical work done and systolic performance is severely reduced in cardiac amyloid despite the relatively preserved ejection fraction. GLASED provides a new technique for assessing left ventricular myocardial health and contractile function.

Norepinephrine and dobutamine improve cardiac index equally by supporting opposite sides of the heart in an experimental model of chronic pulmonary hypertension.

BACKGROUND: Pulmonary hypertension is a significant risk factor in patients undergoing surgery. The combined effects of general anaesthesia and positive pressure ventilation can aggravate this condition and cause increased pulmonary blood pressures, reduced systemic blood pressures and ventricular contractility. Although perioperative use of inotropic support or vasopressors is almost mandatory for these patients, preference is disputed. In this study, we investigated the effects of norepinephrine and dobutamine and their ability to improve the arterio-ventricular relationship and haemodynamics in pigs suffering from chronic pulmonary hypertension. METHOD: Pulmonary hypertension was induced in five pigs by banding the pulmonary artery at 2-3 weeks of age. Six pigs served as controls. After 16 weeks of pulmonary artery banding, the animals were re-examined under general anaesthesia using biventricular conductance catheters and a pulmonary artery catheter. After baseline measurements, the animals were exposed to both norepinephrine and dobutamine infusions in incremental doses, with a stabilising period in between the infusions. The hypothesis of differences between norepinephrine and dobutamine with incremental doses was tested using repeated two-way ANOVA and Bonferroni multiple comparisons post-test. RESULTS: At baseline, pulmonary artery-banded animals had increased right ventricular pressure (+ 39%, p = 0.04), lower cardiac index (- 23% p = 0.04), lower systolic blood pressure (- 13%, p = 0.02) and reduced left ventricular end-diastolic volume (- 33%, p = 0.02). When incremental doses of norepinephrine and dobutamine were administered, the right ventricular arterio-ventricular coupling was improved only by dobutamine (p < 0.05). Norepinephrine increased both left ventricular end-diastolic volume and left ventricular contractility to a greater extent (p < 0.05) in pulmonary artery-banded animals. While the cardiac index was improved equally by norepinephrine and dobutamine treatments in pulmonary artery-banded animals, norepinephrine had a significantly greater effect on mean arterial pressure (p < 0.05) and diastolic arterial pressure (p < 0.05). CONCLUSION: While norepinephrine and dobutamine improved cardiac index equally, it was obtained in different manners. Dobutamine significantly improved the right ventricular function and the arterio-ventricular coupling. Norepinephrine increased systemic resistance, thereby improving arterial pressures and left ventricular systolic function by maintaining left ventricular end-diastolic volume.

Veno-occlusive unloading of the heart reduces infarct size in experimental ischemia-reperfusion.

Mechanical unloading of the left ventricle reduces infarct size after acute myocardial infarction by reducing cardiac work. Left ventricular veno-occlusive unloading reduces cardiac work and may reduce ischemia and reperfusion injury. In a porcine model of myocardial ischemia-reperfusion injury we randomized 18 pigs to either control or veno-occlusive unloading using a balloon engaged from the femoral vein into the inferior caval vein and inflated at onset of ischemia. Evans blue and 2,3,5-triphenyltetrazolium chloride were used to determine the myocardial area at risk and infarct size, respectively. Pressure-volume loops were recorded to calculate cardiac work, left ventricular (LV) volumes and ejection fraction. Veno-occlusive unloading reduced infarct size compared with controls (Unloading 13.9 ± 8.2% versus Control 22.4 ± 6.6%; p = 0.04). Unloading increased myocardial salvage (54.8 ± 23.4% vs 28.5 ± 14.0%; p = 0.02), while the area at risk was similar (28.4 ± 6.7% vs 27.4 ± 5.8%; p = 0.74). LV ejection fraction was preserved in the unloaded group, while the control group showed a reduced LV ejection fraction. Veno-occlusive unloading reduced myocardial infarct size and preserved LV ejection fraction in an experimental acute ischemia-reperfusion model. This proof-of-concept study demonstrated the potential of veno-occlusive unloading as an adjunctive cardioprotective therapy in patients undergoing revascularization for acute myocardial infarction.

Comparison between TachoComb and TachoSil for surgical hemostasis in arterial bleeding: an animal experimental study.

BACKGROUND: TachoComb has frequently been used for the treatment of both venous and arterial bleeding. However, anaphylactic reactions have been reported after repeated use of hemostatic agents containing aprotinin such as TachoComb. Because aprotinin is also associated with risk of renal failure, manufacturing of a new product--TachoSil--which lacks aprotinin seems a logic evolvement. Furthermore, thrombin on the TachoSil material has been changed from bovine in TachoComb to human origin. These changes in the biochemical composition could lead to changes in the hemostatic performance. Therefore, we aimed to disclose any difference in hemostatic efficacy of the two products. METHODS: Twelve 70-kg pigs had controlled insults to the thoracic aorta with and without heparin administration. The iatrogenic lesion was randomly covered with either TachoComb or TachoSil and the time to hemostasis was measured. RESULTS: Time to hemostasis when using TachoSil compared with TachoComb was increased 14% (-13% to 48%) with heparin and 10% (-26% to 66%) without heparin (mean +/- 95% confidence interval; p > 0.05 in both). Time to hemostasis with heparin administration increased significantly in both treatments: TachoComb 80% (26%-156%) (p = 0.001) and TachoSil 75% (18%-158%) (p = 0.005). CONCLUSION: We found neither statistical nor clinical evidence that TachoComb should have better hemostatic properties than does TachoSil in arterial bleeding. Both TachoSil and TachoComb can be used with heparin administration, but significant prolongation of the time to hemostasis is to be expected for both products. TachoSil should be preferred to TachoComb due to the potential lower risk of side effects when using the former.