Beating Porcine Heart Research Articles

Abstract 4135872: Effects of In-vivo Contact Force on Pulsed Field Ablation Lesion Size in Porcine Ventricles

Background: Pulsed field ablation (PFA) is an innovative modality for treating arrhythmias that is mostly non-thermal and renders myocardial tissue non-viable by creating pores in cardiac cell membranes. The impact of contact force (CF) on PFA efficacy is not well characterized. Hypothesis: We hypothesize that, while contact is necessary for PFA, increasing CF will not have a significant effect on in vivo ablation lesion size. Aim: We seek to investigate the effects of CF on acute PFA lesions in a beating porcine heart model. Methods: The ventricles of 7 porcine animals were ablated in vivo with PFA (500V, at 20μs for 50 pulses separated by 200ms) using a focal bipolar irrigated ablation catheter and BTX 830 electroporation generator (Harvard Apparatus). CF was measured before and after each PFA application using CARTO 3. Lesions were divided into standard CF (5-15g), high CF (16-30g), and very high CF (>31g). Results: A total of 46 lesions were analyzed. Gross pathology showed no significant difference in maximum width, lesion depth, and lesion volume between the three groups ( Figure 1A-B ). Linear regression showed a decrease of 0.003 mm in depth (depth = -0.003 × CF + 1.8, R = 0.05), an increase of 0.01 mm in width (width = 0.01 × CF + 5.7, R = 0.09), and a decrease of 0.05 mm 3 in volume (volume = -0.05 × CF + 26.8, R = 0.03) for each additional gram of CF ( Figure 1C ). Conclusion: While contact is necessary, increasing CF did not have a significant effect on in-vivo PFA lesion dimensions in a beating porcine heart model.

Design and Assembly of a Miniature Catheter Imaging System for In Vivo Heart Endoscopic Imaging.

In this paper, we present the design and fabrication of a novel chip-on-tip catheter, which uses a microcamera and optical fibres to capture in vivo images in a beating porcine heart thanks to a saline flush to clear the blood field. Here, we demonstrate the medical utility and mechanical robustness of this catheter platform system, which could be used for other optical diagnostic techniques, surgical guidance, and clinical navigation. We also discuss some of the challenges and system requirements associated with developing a miniature prototype for such a study and present assembly instructions. Methods of clearing the blood field are discussed, including an integrated flush channel at the distal end. This permits the capture of images of the endocardial walls. The device was navigated under fluoroscopic guiding, through a guiding catheter to various locations of the heart, where images were successfully acquired. Images were captured at the intra-atrial septum, in the left atrium after a trans-septal cross procedure, and in the left ventricle, which are, to the best of our knowledge, the first images captured in an in vivo beating heart using endoscopic techniques.

Modified Clover Technique Using Automated Suture Placement and Securing Technology in a Passive Beating Heart Model.

Tricuspid regurgitation (TR) is a prevalent finding in echocardiography and in case of severe disease is associated with impaired patient outcome. Clover repair offers a surgical solution that can be applied for the treatment of primary and secondary TR. An ex vivo passive beating porcine heart model was created to test a modified clover technique using automated suturing devices and to compare this approach to standard ring annuloplasty. Secondary TR was induced in 10 porcine hearts and the backflow of fluid was assessed. The primary endpoint of this study was regurgitant volume measured in mL at the site right atrial cannula. The baseline regurgitation was 43.3 ± 10.8 mL. The mean regurgitant volume was significantly reduced after all repair procedures to 22.2 ± 5.9 mL with isolated ring annuloplasty, 12 ± 3.9 mL with the modified clover, and 7.6 ± 3.4 mL with the combined procedure (p < 0.0001). The modified clover technique shows how to effectively reduce TR in an ex vivo model. This method may be suitable to facilitate tricuspid repair, especially for totally endoscopic valve surgery.

A honeybee stinger-inspired self-interlocking microneedle patch and its application in myocardial infarction treatment

Weak tissue adhesion remains a major challenge in clinical translation of microneedle patches. Mimicking the structural features of honeybee stingers, stiff polymeric microneedles with unidirectionally backward-facing barbs were fabricated and embedded into various elastomer films to produce self-interlocking microneedle patches. The spirality of the barbing pattern was adjusted to increase interlocking efficiency. In addition, the micro-bleeding caused by microneedle puncturing adhered the porous surface of the patch substrate to the target tissue via coagulation. In the demonstrative application of myocardial infarction treatment, the bioinspired microneedle patches firmly fixed on challenging beating hearts, significantly reduced cardiac wall stress and strain in the infarct, and maintained left ventricular function and morphology. In addition, the microneedle patch was minimally invasively implanted onto beating porcine heart in 10 minutes, free of sutures and adhesives. Therefore, the honeybee stinger-inspired microneedles could provide an adaptive and convenient means to implant patches for various medical applications. Statement of significanceAdhesion between tissue and microneedle patches with smooth microneedles is usually weak. We introduce a novel barbing method of fabricating unidirectionally backward facing barbs with controllable spirality on the microneedles on microneedle patches. The microneedle patches self-interlock on mechanically dynamic beating hearts, similar to honeybee stingers. The micro-bleeding and coagulation on the porous surface provide additional adhesion force. The microneedle patches attenuate left ventricular remodeling via mechanical support and are compatible with minimally invasive implantation.

Cardiac Strain Imaging Using Multi-Perspective Ultrafast Ultrasound

The heart is a complex organ with a high level of deformation occurring in different directions. Ultrasound imaging has proven to be a valuable tool to quantify these deformations. However, strain is not always measured accurately in vital parts of the heart when only using a single probe, even at a high frame rate, because of the anisotropic spatial resolution and contrast. Therefore, a multi-perspective ultrafast ultrasound (US) strain imaging method was developed, aiming at investigating improvements in strain while operating two probes at different relative angles. In an ex-vivo experiment of a beating porcine heart, parasternal short axis views of the left ventricle (LV) were acquired by two phased array probes with different relative angles (30°–75°) at a frame rate of 170 frames per second (FPS). A fully automatic registration algorithm was developed to register the image datasets for all cases. Next, radio frequency (RF) based strain imaging was performed. Axial displacements were compounded based on the unit axial vectors of the dual probes to improve motion tracking and strain estimation. After performing multi-perspective strain imaging, compounded radial and circumferential strain both improve compared to single probe strain imaging. While increasing the inter-probe angle from 30° to 75°, the mean tracking error (ME), mean drift error (MDE) and strain variability (SV) decreased, and signal-to-noise ratio (SNRe) increased for both strain components. For the largest angle (75°), large reductions in ME (−42%), MDE (−50%) and SV (−48%) were observed. The SNRe increased by 253 and 39% for radial and circumferential strain, respectively, and strain curves revealed less noise for each region. In summary, a multi-perspective ultrafast US strain imaging method was introduced to improve cardiac strain estimation in an ex-vivo beating porcine heart setup.

High frame rate multi-perspective cardiac ultrasound imaging using phased array probes

Ultrasound (US) imaging is used to assess cardiac disease by assessing the geometry and function of the heart utilizing its high spatial and temporal resolution. However, because of physical constraints, drawbacks of US include limited field-of-view, refraction, resolution and contrast anisotropy. These issues cannot be resolved when using a single probe. Here, an interleaved multi-perspective 2-D US imaging system was introduced, aiming at improved imaging of the left ventricle (LV) of the heart by acquiring US data from two separate phased array probes simultaneously at a high frame rate.In an ex-vivo experiment of a beating porcine heart, parasternal long-axis and apical views of the left ventricle were acquired using two phased array probes. Interleaved multi-probe US data were acquired at a frame rate of 170 frames per second (FPS) using diverging wave imaging under 11 angles. Image registration and fusion algorithms were developed to align and fuse the US images from two different probes. First- and second-order speckle statistics were computed to characterize the resulting probability distribution function and point spread function of the multi-probe image data.First-order speckle analysis showed less overlap of the histograms (reduction of 34.4%) and higher contrast-to-noise ratio (CNR, increase of 27.3%) between endocardium and myocardium in the fused images. Autocorrelation results showed an improved and more isotropic resolution for the multi-perspective images (single-perspective: 0.59 mm × 0.21 mm, multi-perspective: 0.35 mm × 0.18 mm). Moreover, mean gradient (MG) (increase of 74.4%) and entropy (increase of 23.1%) results indicated that image details of the myocardial tissue can be better observed after fusion.To conclude, interleaved multi-perspective high frame rate US imaging was developed and demonstrated in an ex-vivo experimental setup, revealing enlarged field-of-view, and improved image contrast and resolution of cardiac images.

Ultrastructural Characteristics of Myocardial Reperfusion Injury and Effect of Selective Intracoronary Hypothermia: An Observational Study in Isolated Beating Porcine Hearts.

In acute myocardial infarction (AMI), myocardial reperfusion injury may undo part of the recovery after revascularization of the occluded coronary artery. Selective intracoronary hypothermia is a novel method aimed at reducing myocardial reperfusion injury, but its presumed protective effects in AMI still await further elucidation. This proof-of-concept study assesses the potential protective effects of selective intracoronary hypothermia in an ex-vivo, isolated beating heart model of AMI. In four isolated Langendorff perfused beating pig hearts, an anterior wall myocardial infarction was created by inflating a balloon in the mid segment of the left anterior descending (LAD) artery. After one hour, two hearts were treated with selective intracoronary hypothermia followed by normal reperfusion (cooled hearts). In the other two hearts, the balloon was deflated after one hour, allowing normal reperfusion (control hearts). Biopsies for histologic and electron microscopic evaluation were taken from the myocardium at risk at different time points: before occlusion (t = BO); 5 minutes before reperfusion (t = BR); and 10 minutes after reperfusion (t = AR). Electron microscopic analysis was performed to evaluate the condition of the mitochondria. Histological analyses included evaluation of sarcomeric collapse and intramyocardial hematoma. Electron microscopic analysis revealed intact mitochondria in the hypothermia treated hearts compared to the control hearts where mitochondria were more frequently damaged. No differences in the prespecified histological parameters were observed between cooled and control hearts at t = AR. In the isolated beating porcine heart model of AMI, reperfusion was associated with additional myocardial injury beyond ischemic injury. Selective intracoronary hypothermia preserved mitochondrial integrity compared to nontreated controls.

CineCT imaging platform for in-vivo and ex-vivo measurement of myocardial biomechanics post myocardial infarction and following intramyocardial delivery of theranostic hydrogel

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Institute of Health (NIH) Purpose Myocardial infarction (MI) induces acute regional changes in myocardial strain and stiffness in the infarct and the remote areas of the left ventricle (LV), which lead to adverse changes in LV geometry and function. We hypothesize that cineCT imaging could evaluate these biomechanical changes along with the effects of intramyocardial delivery of theranostic hydrogels. Introduction We present an experimental platform to assess changes in the deformation of the LV myocardium using contrast cineCT (CCT) imaging of the beating porcine heart (active deformation) before and after acute MI and intramyocardial delivery of an imageable theranostic hydrogel. We then assess the acute effects of hydrogel delivery early post-MI on biomechanics (passive deformation) using an ex vivo perfused heart preparation. Methods Contrast cineCT imaging was performed using 64-slice CT on 5 Yorkshire pigs without MI (n = 3) or with MI (n = 2). MI pigs had serial imaging performed before and 1 hour after acute surgical coronary occlusion to induce anterolateral MI. One MI pig was also imaged 1 hour after intramyocardial injection of a novel imageable theranostic iodinated hydrogel within the MI region. Post euthanasia, excised hearts were flushed with chilled UW cardioplegic solution and mounted on a custom inflation apparatus for cineCT imaging during LV inflation by external pump. LV pressure was cycled between 10 and 60 mmHg at 35 bpm. Dilute iohexol was injected into aortic root and UW perfusate (15 ml, 1 ml/sec). CineCT image series were reconstructed, contrast enhanced, resampled to the LV long axis (Z), and exported as a series of 10 CT volumes covering 0-90% of the cardiac/inflation cycle. Volumes were registered incrementally using nonlinear image registration (BioImageSuite) and the calculated displacement at each time point was exported at a resolution of 1 mm. A custom Matlab program was used to fit the displacement field to local trilinear polynomials and then calculate the displacement gradients and 3D Lagrangian strains. To estimate the accuracy of this approach, cardiac volumes were also numerically deformed using a 10 pixel translation and 5% triaxial stretch. Results We successfully acquired serial in-vivo and ex-vivo 3D CineCT images for assessment of the active and passive LV myocardial deformation and tracked deformation through the full cardiac/inflation cycle (Figure 2). Numerical deformation tests showed average tracking errors of &amp;lt; 0.2 mm (1/4 pixel) in the X,Y,Z directions of the volume. These resulted in Lagrangian strain errors of &amp;lt; 0.47% for the in-plane strains EXX and EYY (radial and circumferential plane) and &amp;lt; 0.5% for EZZ (long axis). Conclusions We have developed a novel CineCT imaging platform that allows for high resolution in-vivo and ex-vivo measurement of myocardial biomechanics post-MI and following intramyocardial delivery of imageable theranostic hydrogels, which may improve early active and passive biomechanics.

A novel intra-ventricular assist device enhances cardiac performance in normal and acutely failing isolated porcine hearts.

Background:We recently demonstrated that a novel intra-ventricular membrane pump (IVMP) was able to increase the pump function of isolated beating porcine hearts. In follow-up, we now investigated the impact of the IVMP on myocardial oxygen consumption and total mechanical efficiency (TME) and assessed the effect of IVMP-support in acutely failing hearts.Methods:In 10 ex vivo beating porcine hearts, we studied hemodynamic parameters, as well as arterial and coronary venous oxygen content. We assessed cardiac power (CP), myocardial oxygen consumption (MVO2), and TME (CP divided by MVO2) under baseline conditions and during IVMP-support. Additionally, five isolated hearts were subjected to global hypoxia to investigate the effects of IVMP-support on CP under conditions of acute heart failure.Results:Under physiological conditions, baseline CP was 0.36 ± 0.10 W, which increased to 0.65 ± 0.16 W during IVMP-support (increase of 85% ± 24, p < 0.001). This was accompanied by an increase in MVO2 from 18.6 ± 6.2 ml/min at baseline, to 22.3 ± 5.0 ml/min during IVMP-support (+26 ± 31%, p = 0.005). As a result, TME (%) increased from 5.9 ± 1.2 to 8.8 ± 1.8 (50 ± 22% increase, p < 0.001). Acute hypoxia-induced cardiac pump failure reduced CP by 35 ± 6%, which was fully restored to baseline levels during IVMP-support in all hearts.Conclusion:IVMP-support improved mechanical efficiency under physiological conditions, as the marked increase in cardiac performance only resulted in a modest increase in oxygen consumption. Moreover, the IVMP rapidly restored cardiac performance under conditions of acute pump failure. These observations warrant further study, to evaluate the effects of IVMP-support in in vivo animal models of acute cardiac pump failure.

An epicardial bioelectronic patch made from soft rubbery materials and capable of spatiotemporal mapping of electrophysiological activity

An epicardial bioelectronic patch is an important device for investigating and treating heart diseases. The ideal device should possess cardiac-tissue-like mechanical softness and deformability, and be able to perform spatiotemporal mapping of cardiac conduction characteristics and other physical parameters. However, existing patches constructed from rigid materials with structurally engineered mechanical stretchability still have a hard–soft interface with the epicardium, which can strain cardiac tissue and does not allow for deformation with a beating heart. Alternatively, patches made from intrinsically soft materials lack spatiotemporal mapping or sensing capabilities. Here, we report an epicardial bioelectronic patch that is made from materials matching the mechanical softness of heart tissue and can perform spatiotemporal mapping of electrophysiological activity, as well as strain and temperature sensing. Its capabilities are illustrated on a beating porcine heart. We also show that the patch can provide therapeutic capabilities (electrical pacing and thermal ablation), and that a rubbery mechanoelectrical transducer can harvest energy from heart beats, potentially providing a power source for epicardial devices. An epicardial patch made from materials that match the mechanical softness of heart tissue can perform spatiotemporal mapping of electrophysiological activity, as well as strain and temperature sensing, pacing and ablation therapies, and energy harvesting, while deforming with a beating heart.

Proof of principle of a novel co-pulsating intra-ventricular membrane pump.

In this proof of principle study, we investigated the effectiveness and safety of hemodynamic support with the Intra-Ventricular Membrane Pump (IVMP). The IVMP was implanted into the apex of the left ventricle. Hemodynamic assessment was performed in six ex vivo beating porcine hearts (PhysioHeart platform). The cardiac output (CO), mean arterial pressure (MAP), coronary flow (CF) and pulse pressure (PP) were obtained before and during IVMP support and reported as means±standard deviations. In two additional visualization experiments, the integrity of the mitral valve was assessed during IVMP support. We found a significant increase of the CO (+1.4±0.2 L/min, P<.001), MAP (+13±6mm Hg, P=.008), CF (+0.23±0.1 L/min, P=.004), and PP (+15±4mm Hg, P=.002) during IVMP support, when compared to baseline. No interference of the IVMP with mitral valve function was observed. An increase of premature ventricular complexes (PVC) was observed during support with the IVMP (mean PVC-burden 4.3% vs. 0.7% at baseline), negatively influencing hemodynamic parameters. The IVMP is able to significantly improve hemodynamic parameters in a co-pulsatile fashion, without hampering the function of the mitral valve. These findings provide a basis for future development of a catheter-based IVMP.

Feasibility of a Mitral Annuloplasty With the Capability for Peri- and Postoperative Adjustment

Abstract Surgical repair with implantation of a mitral annuloplasty ring is the gold standard treatment for mitral regurgitation. However, outcomes are variable and recurrent mitral regurgitation is not uncommon. A REshapeable Mitral Annuloplasty DevIce (REMADI) is proposed, which consists of a fully encapsulated low melting temperature alloy. The alloy is solid and rigid at body temperature and provides traction force to shape the annulus. When heated using a noncontact method, the alloy melts and the REMADI becomes malleable. The REMADI is engaged with the mitral valve annulus using anchors which automatically deploy upon contact. A passive beating porcine heart model was used to demonstrate the feasibility of the REMADI device, which was deployed, engaged, and used to reduce the diameter of the mitral valve annulus.

Fast in vivo detection of myocardial norepinephrine levels in the beating porcine heart.

The sympathetic nervous system modulates cardiac function by controlling key parameters such as chronotropy and inotropy. Sympathetic control of ventricular function occurs through extrinsic innervation arising from the stellate ganglia and thoracic sympathetic chain. In the healthy heart, sympathetic release of norepinephrine (NE) results in positive modulation of chronotropy, inotropy, and dromotropy, significantly increasing cardiac output. However, in the setting of myocardial infarction or injury, sympathetic activation persists, contributing to heart failure and increasing the risk of arrhythmias, including sudden cardiac death. Methodologies for detection of norepinephrine in cardiac tissue are limited. Present techniques rely on microdialysis for analysis by high-performance liquid chromatography coupled to electrochemical detection (HPLC-ED), radioimmunoassay, or other immunoassays, such as enzyme-linked immunosorbent assay (ELISA). Although significant information about the release and action of norepinephrine has been obtained with these methodologies, they are limited in temporal resolution, require large sample volumes, and provide results with a significant delay after sample collection (hours to weeks). In this study, we report a novel approach for measurement of interstitial cardiac norepinephrine, using minimally invasive, electrode-based, fast-scanning cyclic voltammetry (FSCV) applied in a beating porcine heart. The first multispatial and high temporal resolution, multichannel measurements of NE release in vivo are provided. Our data demonstrate rapid changes in interstitial NE profiles with regional differences in response to coronary ischemia, sympathetic nerve stimulation, and alterations in preload/afterload.NEW & NOTEWORTHY Pharmacological, electrical, or surgical regulation of sympathetic neuronal control can be used to modulate cardiac function and treat arrhythmias. However, present methods for monitoring sympathetic release of norepinephrine in the heart are limited in spatial and temporal resolution. Here, we provide for the first time a methodology and demonstration of practice and rapid measures of individualized regional autonomic neurotransmitter levels in a beating heart. We show dynamic, spatially resolved release profiles under normal and pathological conditions.

A predictive computational model to estimate myocardial temperature during intracoronary hypothermia in acute myocardial infarction

Hypothermia, if provided before coronary reperfusion, reduces infarct size in animal models of acute myocardial infarction (AMI). Translation to humans has failed so far, because the target temperature is not reached in time within the endangered myocardium using systemic hypothermia method. Hence, a clinically applicable method has been developed to provide intracoronary hypothermia using cold saline, selectively infused locally into the infarct area.In this study, a lumped parameter model has been designed to support the clinical method and to describe this myocardial cooling process mathematically. This model is able to predict the myocardial temperature changes over time, which cannot be measured, based on the temperature and flow of the intracoronary injected cold saline and coronary arterial blood. It was validated using data from an isolated beating porcine heart model and applied on data from patients with AMI undergoing intracoronary hypothermia.In prospect, the computational model may be used as an assistive tool to calculate the patient specific flow rate and temperature of saline required for reliable achievement of the target myocardial temperature in the hypothermia enhanced clinical treatment of AMI.

Development of a transplant injection device for optimal distribution and retention of human induced pluripotent stem cell‒derived cardiomyocytes.

Induced pluripotent stem cell (iPSC)‒based regenerative therapy is a promising strategy for cardiovascular disease treatment; however, the method is limited by the myocardial retention of grafted iPSCs. Thus, an injection protocol that efficiently introduces and retains human iPSC-derived cardiomyocytes (hiPSC-CMs) within the myocardium is urgently needed. The objective of the present study was to develop a method to improve the retention of hiPSCs in the myocardium for cardiac therapy. We efficiently produced hiPSC-CM spheroids in 3-dimensional (3D) culture using microwell plates, and developed an injection device for optimal 3D distribution of the spheroids in the myocardial layer. Device biocompatibility was assessed with purified hiPSC-CM spheroids. Device effectiveness was evaluated in 10- to 15-month-old farm pigs (n = 15) and 5- to 24-month-old micro-minipigs (n = 20). The pigs were euthanized after injection, and tissues were harvested for retention and histologic analysis. We demonstrated an injection device for direct intramyocardial transplantation of hiPSC-CM spheroids from large-scale culture. The device had no detrimental effects on cell viability, spheroid shape, or size. Direct epicardial injection of spheroids mixed with gelatin hydrogel into beating porcine hearts using this device resulted in better distribution and retention of transplanted spheroids in a layer within the myocardium than did conventional needle injection procedures. The combination of the newly developed transplant device and spheroid formation promotes the retention of transplanted CMs. These findings support the clinical application of hiPSC-CM spheroid‒based cardiac regenerative therapy in patients with heart failure.

Melt Electrowriting Allows Tailored Microstructural and Mechanical Design of Scaffolds to Advance Functional Human Myocardial Tissue Formation

AbstractEngineering native‐like myocardial muscle, recapitulating its fibrillar organization and mechanical behavior is still a challenge. This study reports the rational design and fabrication of ultrastretchable microfiber scaffolds with controlled hexagonal microstructures via melt electrowriting (MEW). The resulting structures exhibit large biaxial deformations, up to 40% strain, and an unprecedented compliance, delivering up to 40 times more elastic energy than rudimentary MEW fiber scaffolds. Importantly, when human induced pluripotent stem cell‐derived cardiomyocytes (iPSC‐CM) are encapsulated in a collagen‐based hydrogel and seeded on these microstructured and mechanically tailored fiber scaffolds, they show an increase in beating rate (1.5‐fold), enhanced cell alignment, sarcomere content and organization as well as an increase in cardiac maturation‐related marker expression (Cx43 1.8‐fold, cardiac Actin 1.5‐fold, SERCA2a 2.5‐fold, KCNJ2 1.5‐fold, and PPARGC1a 3.6‐fold), indicative of enhanced iPSC‐CM maturation, as compared to rudimentary fiber scaffolds. By combining these novel fiber scaffolds with clinically relevant human iPSC‐CMs, a heart patch that allows further maturation of contractile myocytes for cardiac tissue engineering is generated. Moreover, the designed scaffold allows successful shape recovery after epicardial delivery on a beating porcine heart, without negative effects on the engineered construct and iPSC‐CM viability.

1159Electrical isolation by electroporation of right ventricular myocardium in an ex-vivo beating porcine heart: a potential novel use of the alert internal cardioversion catheter

1159Electrical isolation by electroporation of right ventricular myocardium in an ex-vivo beating porcine heart: a potential novel use of the alert internal cardioversion catheter

Design of a Coupled Thermoresponsive Hydrogel and Robotic System for Postinfarct Biomaterial Injection Therapy

In preclinical testing, ventricular wall injection of hydrogels has been shown to be effective in modulating ventricular remodeling and preserving cardiac function. For some approaches, early-stage clinical trials are under way. The hydrogel delivery method varies, with minimally invasive approaches being preferred. Endocardial injections carry a risk of hydrogel regurgitation into the circulation, and precise injection patterning is a challenge. An epicardial approach with a thermally gelling hydrogel through the subxiphoid pathway overcomes these disadvantages. A relatively stiff, thermally responsive, injectable hydrogel based on N-isopropylacrylamide and N-vinylpyrrolidone (VP gel) was synthesized and characterized. VP gel thermal behavior was tuned to couple with a transepicardial injection robot, incorporating a cooling feature to achieve injectability. Ventricular wall injections of the optimized VP gel have been performed exvivo and on beating porcine hearts. Thermal transition temperature, viscosity, and gelling time for the VP gel were manipulated by altering N-vinylpyrrolidone content. The target parameters for cooling in the robotic system were chosen by thermal modeling to support smooth, repeated injections on an exvivo heart. Injections at predefined locations and depth were confirmed in an infarcted porcine model. A coupled thermoresponsive hydrogel and robotic injection system incorporating a temperature-controlled injectate line was capable of targeted injections and amenable to use with a subxiphoid transepicardial approach for hydrogel injection after myocardial infarction. The confirmation of precise location and depth injections would facilitate a patient-specific planning strategy to optimize injection patterning to maximize the mechanical benefits of hydrogel placement.

Intra-Aortic Balloon Pump Support in the Isolated Beating Porcine Heart in Nonischemic and Ischemic Pump Failure.

The blood pressure changes induced by the intra-aortic balloon pump (IABP) are expected to create clinical improvement in terms of coronary perfusion and myocardial oxygen consumption. However, the measured effects reported in literature are inconsistent. The aim of this study was to investigate the influence of ischemia on IABP efficacy in healthy hearts and in shock. Twelve slaughterhouse porcine hearts (hearts 1-12) were connected to an external circulatory system, while physiologic cardiac performance was restored. Different clinical scenarios, ranging from healthy to cardiogenic shock, were simulated by step-wise administration of negative inotropic drugs. In hearts 7-12, severe global myocardial ischemia superimposed upon the decreased contractile states was created. IABP support was applied in all hearts under all conditions. Without ischemia, the IABP induced a mild increase in coronary blood flow and cardiac output. These effects were strongly augmented in the presence of persisting ischemia, where coronary blood flow increased by 49 ± 24% (P < 0.01) and cardiac output by 17 ± 6% (P < 0.01) in case of severe pump failure. As expected, myocardial oxygen consumption increased in case of ischemia (21 ± 17%; P < 0.01), while it slightly decreased without (-3 ± 6%; P < 0.01). In case of progressive pump failure due to persistent myocardial ischemia, the IABP increased hyperemic coronary blood flow and cardiac output significantly, and reversed the progressive hemodynamic deterioration within minutes. This suggests that IABP therapy in acute myocardial infarction is most effective in patients with viable myocardium, suffering from persistent myocardial ischemia, despite adequate epicardial reperfusion.

Fusion of structural and functional cardiac magnetic resonance imaging data for studying ventricular fibrillation.

Magnetic Resonance Imaging (MRI) techniques such as Current Density Imaging (CDI) and Diffusion Tensor Imaging (DTI) provide a complementing set of imaging data that can describe both the functional and structural states of biological tissues. This paper presents a Joint Independent Component Analysis (jICA) based fusion approach which can be utilized to fuse CDI and DTI data to quantify the differences between two cardiac states: Ventricular Fibrillation (VF) and Asystolic/Normal (AS/NM). Such an approach could lead to a better insight on the mechanism of VF. Fusing CDI and DTI data from 8 data sets from 6 beating porcine hearts, in effect, detects the differences between two cardiac states, qualitatively and quantitatively. This initial study demonstrates the applicability of MRI-based imaging techniques and jICA-based fusion approach in studying cardiac arrhythmias.