Perfusion of the interventricular septum during ventilation with positive end-expiratory pressure (PEEP)

Objective: To determine whether regional hypoperfusion of the interventricular septum occurs during ventilation with positive end-expiratory pressure. Design: Animal study. Animals: Anesthetized, closed chest dogs (n = 8). Interventions: Induction of experimental adult respiratory distress syndrome (ARDS) and then ventilation with 10,15, and 20 cm H2O of positive end-expiratory pressure. Measurements and Main Results: Cardiac output and regional interventricular septum blood flow 'were assessed at control, at induction of experimental ARDS, and at each level of positive end-expiratory pressure. Ventilation with 20 cm H2O of positive end-expiratory pressure decreased cardiac output (-32% vs. control, p <.05), and did not change absolute, but increased relative (to cardiac output) interventricular septum blood flow. During experimental ARDS and ventilation at 20 cm H2O end-expiratory pressure, there was a redistribution of flow toward the right ventricular free wall (+93%, p < .001) and the right ventricular part of the interventricular septum (+68%, p < .01), while flow to the left ventricular interventricular septum and to the left ventricular free wall remained unchanged. Locally hypoperfused interventricular septum areas or findings indicative of interventricular septum ischemia were not observed during positive end-expiratory pressure. Conclusions: The decrease in cardiac output during positive end-expiratory pressure is not caused by impaired interventricular septum blood supply. The preferential perfusion of the right ventricular interventricular septum indicates increased local right ventricular interventricular septum oxygen-demand and suggests that during positive end-expiratory pressure, this part of the interventricular septum functionally dissociates from the left ventricular interventricular septum and the left ventricular free wall to support the stressed right ventricle

Ventricular androgenic-anabolic steroid-related remodeling: an immunohistochemical study

Background: Several fatal cases of bodybuilders, following a myocardial infarction after long exposure to androgenicanabolic steroids (AAS), are reported. In recent years, evidence has emerged of cases of heart failure related to AAS consumption, with no signs of coronary or aorta atherosclerosis. This study aims to further investigate the pathogenesis of the ventricular AAS-related remodeling performing immunohistochemistry (IHC). Method: In order to examine innate immunity activity and myocytes and endothelial cell apoptosis, IHC analyses were performed on heart tissue of two cases of bodybuilders who died after years of supratherapeutic use of metelonone and nandrolone and where no atherosclerosis or thrombosis were found, using the following antibodies: anti-CD68, anti-iNOS, anti-CD163, anti-CD 15, anti-CD8, anti-CD4, anti-HIF1 α, and in situ TUNEL staining. Results: Results confirm the experimental findings of recent research that, in the absence of other pathological factors, if intensive training is combined with AAS abuse, myocytes and endothelial cells undergo apoptotic alterations. The absence of inflammatory reactions and the presence of an increased number of M2 macrophages in the areas of fibrotic remodeling confirm that the fibrotic changes in the heart are apoptosisrelated and not necrosis-related. Conclusions In conclusion, the study indicates that, in very young subjects with chronic hypoxia-related alterations of the heart, signs of a heart failure in the other organs and a history of AAS abuse, death can be ascribed to progressive heart failure due to the direct apoptotic cardiac and endothelial changes produced by AAS

The cardiac sodium channel displays differential distribution in the conduction system and transmural heterogeneity in the murine ventricular myocardium

Cardiac sodium channels are responsible for conduction in the normal and diseased heart. We aimed to investigate regional and transmural distribution of sodium channel expression and function in the myocardium. Sodium channel Scn5a mRNA and Na(v)1.5 protein distribution was investigated in adult and embryonic mouse heart through immunohistochemistry and in situ hybridization. Functional sodium channel availability in subepicardial and subendocardial myocytes was assessed using patch-clamp technique. Adult and embryonic (ED14.5) mouse heart sections showed low expression of Na(v)1.5 in the HCN4-positive sinoatrial and atrioventricular nodes. In contrast, high expression levels of Na(v)1.5 were observed in the HCN4-positive and Cx43-negative AV or His bundle, bundle branches and Purkinje fibers. In both ventricles, a transmural gradient was observed, with a low Na(v)1.5 labeling intensity in the subepicardium as compared to the subendocardium. Similar Scn5a mRNA expression patterns were observed on in situ hybridization of embryonic and adult tissue. Maximal action potential upstroke velocity was significantly lower in subepicardial myocytes (mean +/- SEM 309 +/- 32 V/s; n = 14) compared to subendocardial myocytes (394 +/- 32 V/s; n = 11; P < 0.05), indicating decreased sodium channel availability in subepicardium compared to subendocardium. Scn5a and Na(v)1.5 show heterogeneous distribution patterns within the cardiac conduction system and across the ventricular wall. This differential distribution of the cardiac sodium channel may have profound consequences for conduction disease phenotypes and arrhythmogenesis in the setting of sodium channel diseas

A Study of the Dynamics of Cardiac Ischemia using Experimental and Modeling Approaches

The dynamics of cardiac ischemia was investigated using experimental studies and computer simulations. An experimental model consisting of an isolated and perfused canine heart with full control over blood flow rate to a targeted coronary artery was used in the experimental study and a realistically shaped computer model of a canine heart, incorporating anisotropic conductivity and realistic fiber orientation, was used in the simulation study. The phenomena investigated were: (1) the influence of fiber rotation on the epicardial potentials during ischemia and (2) the effect of conductivity changes during a period of sustained ischemia. Comparison of preliminary experimental and computer simulation results suggest that as the ischemic region grows from the endocardium towards the epicardium, the epicardial potential patterns follow the rotating fiber orientation in the myocardium. Secondly, in the experimental studies it was observed that prolonged ischemia caused a subsequent reduction in the magnitude of epicardial potentials. Similar results were obtained from the computer model when the conductivity of the tissue in the ischemic region was reduce

Impaired coronary blood flow at higher heart rates during atrial fibrillation: investigation via multiscale modelling

Background. Different mechanisms have been proposed to relate atrial fibrillation (AF) and coronary flow impairment, even in absence of relevant coronary artery disease (CAD). However, the underlying hemodynamics remains unclear. Aim of the present work is to computationally explore whether and to what extent ventricular rate during AF affects the coronary perfusion. Methods. AF is simulated at different ventricular rates (50, 70, 90, 110, 130 bpm) through a 0D-1D multiscale validated model, which combines the left heart-arterial tree together with the coronary circulation. Artificially-built RR stochastic extraction mimics the \emph{in vivo} beating features. All the hemodynamic parameters computed are based on the left anterior descending (LAD) artery and account for the waveform, amplitude and perfusion of the coronary blood flow. Results. Alterations of the coronary hemodynamics are found to be associated either to the heart rate increase, which strongly modifies waveform and amplitude of the LAD flow rate, and to the beat-to-beat variability. The latter is overall amplified in the coronary circulation as HR grows, even though the input RR variability is kept constant at all HRs. Conclusions. Higher ventricular rate during AF exerts an overall coronary blood flow impairment and imbalance of the myocardial oxygen supply-demand ratio. The combined increase of heart rate and higher AF-induced hemodynamic variability lead to a coronary perfusion impairment exceeding 90-110 bpm in AF. Moreover, it is found that coronary perfusion pressure (CPP) is no longer a good measure of the myocardial perfusion for HR higher than 90 bpm.Comment: 8 pages, 5 figures, 3 table

Osborn Waves: History and Significance

The Osborn wave is a deflection with a dome or hump configuration occurring at the R-ST junction (J point) on the ECG (Fig. 1). In the historical view, different names have been used for this wave in the medical literature, such as “camel-hump sign”, “late delta wave”, “hathook junction”, “hypothermic wave”, “J point wave”, “K wave”, “H wave” and “current of injury”.1 Although there is no definite consensus about terminology of this wave, either “Osborn wave” or “J wave” are the most commonly used names for this wave in the current clinical and experimental cardiology. The Osborn wave can be generally observed in hypothermic patients,1,2,3,4 however, other conditions have been reported to cause Osborn waves, such as hypercalcemia,5 brain injury,6 subarachnoid hemorrhage,7 cardiopulmonary arrest from oversedation,8 vasospastic angina,9 or idiopathic ventricular fibrillation.10,11,12 Our knowledge about the link between the Osborn waves and cardiac arrhythmias remains sparse and the arrhythmogenic potential of the Osborn waves is not fully understood. In this paper, we present a historic review of Osborn waves and discuss their clinical significance in the various clinical settings

Small conductance calcium-activated potassium current is important in transmural repolarization of failing human ventricles

BACKGROUND: The transmural distribution of apamin-sensitive small conductance Ca(2+)-activated K(+) (SK) current (IKAS) in failing human ventricles remains unclear. METHODS AND RESULTS: We optically mapped left ventricular wedge preparations from 12 failing native hearts and 2 rejected cardiac allografts explanted during transplant surgery. We determined transmural action potential duration (APD) before and after 100 nmol/L apamin administration in all wedges and after sequential administration of apamin, chromanol, and E4031 in 4 wedges. Apamin prolonged APD from 363 ms (95% confidence interval [CI], 341-385) to 409 (95% CI, 385-434; P<0.001) in all hearts, and reduced the transmural conduction velocity from 36 cm/s (95% CI, 30-42) to 32 cm/s (95% CI, 27-37; P=0.001) in 12 native failing hearts at 1000 ms pacing cycle length (PCL). The percent APD prolongation is negatively correlated with baseline APD and positively correlated with PCL. Only 1 wedge had M-cell islands. The percentages of APD prolongation in the last 4 hearts at 2000 ms PCL after apamin, chromanol, and E4031 were 9.1% (95% CI, 3.9-14.2), 17.3% (95% CI, 3.1-31.5), and 35.9% (95% CI, 15.7-56.1), respectively. Immunohistochemical staining of subtype 2 of SK protein showed increased expression in intercalated discs of myocytes. CONCLUSIONS: SK current is important in the transmural repolarization in failing human ventricles. The magnitude of IKAS is positively correlated with the PCL, but negatively correlated with APD when PCL is fixed. There is abundant subtype 2 of SK protein in the intercalated discs of myocytes

Diagnostic value of transmural perfusion ratio derived from dynamic CT-based myocardial perfusion imaging for the detection of haemodynamically relevant coronary artery stenosis

Objectives: To investigate the additional value of transmural perfusion ratio (TPR) in dynamic CT myocardial perfusion imaging for detection of haemodynamically significant coronary artery disease compared with fractional flow reserve (FFR). Methods: Subjects with suspected or known coronary artery disease were prospectively included and underwent a CT-MPI examination. From the CT-MPI time-point data absolute myocardial blood flow (MBF) values were temporally resolved using a hybrid deconvolution model. An absolute MBF value was measured in the suspected perfusion defect. TPR was defined as the ratio between the subendocardial and subepicardial MBF. TPR and MBF results were compared with invasive FFR using a threshold of 0.80. Results: Forty-three patients and 94 territories were analysed. The area under the receiver operator curve was larger for MBF (0.78) compared with TPR (0.65, P = 0.026). No significant differences were found in diagnostic classification between MBF and TPR with a territory-based accuracy of 77 % (67-86 %) for MBF compared with 70 % (60-81 %) for TPR. Combined MBF and TPR classification did not improve the diagnostic classification. Conclusions: Dynamic CT-MPI-based transmural perfusion ratio predicts haemodynamically significant coronary artery disease. However, diagnostic performance of dynamic CT-MPI-derived TPR is inferior to quantified MBF and has limited incremental value. Key Points: • The transmural perfusion ratio from dynamic CT-MPI predicts functional obstructive coronary artery disease• Performance of the transmural perfusion ratio is inferior to quantified myocardial blood flow• The incremental value of the transmural perfusion ratio is limite

Will the real ventricular architecture please stand up?

Ventricular twisting, essential for cardiac function, is attributed to the contraction of myocardial helical fibers. The exact relationship between ventricular anatomy and function remains to be determined, but one commonly used explanatory model is the helical ventricular myocardial band (HVMB) model of Torrent-Guasp. This model has been successful in explaining many aspects of ventricular function, (Torrent-Guasp et al. Eur. J. Cardiothorac. Surg., 25, 376, 2004; Buckberg et al. Eur. J. Cardiothorac. Surg., 47, 587, 2015; Buckberg et al. Eur. J. Cardiothorac. Surg. 47, 778, 2015) but the model ignores important aspects of ventricular anatomy and should probably be replaced. The purpose of this review is to compare the HVMB model with a different model (nested layers). A complication when interpreting experimental observations that relate anatomy to function is that, in the myocardium, shortening does not always imply activation and lengthening does not always imply inactivation

Diffusion MR Tractography of the Heart

Histological studies have shown that the myocardium consists of an array of crossing helical fiber tracts. Changes in myocardial fiber architecture occur in ischemic heart disease and heart failure, and can be imaged non-destructively with diffusion-encoded MR. Several diffusion-encoding schemes have been developed, ranging from scalar measurements of mean diffusivity to a 6-dimensional imaging technique known as diffusion spectrum imaging or DSI. The properties of DSI make it particularly suited to the generation of 3-dimensional tractograms of myofiber architecture. In this article we review the physical basis of diffusion-tractography in the myocardium and the attributes of the available techniques, placing particular emphasis on DSI. The application of DSI in ischemic heart disease is reviewed, and the requisites for widespread clinical translation of diffusion MR tractography in the heart are discussed