Lars M. Mattison

Prolonged EVLP Using OCS Lung: Cellular and Acellular Perfusates.

Background We report the ability to extend lung preservation up to 24 hours (24H) by using autologous whole donor blood circulating within an ex vivo lung perfusion (EVLP) system. This approach facilitates donor lung reconditioning in a model of extended normothermic EVLP. We analyzed comparative responses to cellular and acellular perfusates to identify these benefits. Methods Twelve pairs of swine lungs were retrieved after cardiac arrest and studied for 24H on the Organ Care System (OCS) Lung EVLP platform. Three groups (n = 4 each) were differentiated by perfusate: (1) isolated red blood cells (RBCs) (current clinical standard for OCS); (2) whole blood (WB); and (3) acellular buffered dextran-albumin solution (analogous to STEEN solution). Results Only the RBC and WB groups met clinical standards for transplantation at 8 hours; our primary analysis at 24H focused on perfusion with WB versus RBC. The WB perfusate was superior (vs RBC) for maintaining stability of all monitored parameters, including the following mean 24H measures: pulmonary artery pressure (6.8 vs 9.0 mm Hg), reservoir volume replacement (85 vs 1607 mL), and PaO2:FiO2 ratio (541 vs 223). Acellular perfusion was limited to 6 hours on the OCS system due to prohibitively high vascular resistance, edema, and worsening compliance. Conclusions The use of an autologous whole donor blood perfusate allowed 24H of preservation without functional deterioration and was superior to both RBC and buffered dextran-albumin solution for extended lung preservation in a swine model using OCS Lung. This finding represents a potentially significant advance in donor lung preservation and reconditioning.

The ABCs of autologous blood collection for ex vivo organ preservation

Abstract Ex vivo organ perfusion (EVOP) using autologous whole donor blood (AWDB) allows prolonged preservation and extracorporeal assessment of solid organs for transplant. We present a straightforward methodology for ADWB collection that may be incorporated into standard clinical procurement.

An Experimental Study of the Recovery of Injured Porcine Lungs with Prolonged Normothermic Cellular Ex Vivo Lung Perfusion Following Donation after Circulatory Death

Donation after circulatory death (DCD) is an underused source of donor lungs. Normothermic cellular ex vivo lung perfusion (EVLP) is effective in preserving standard donor lungs but may also be useful in the preservation and assessment of DCD lungs. Using a model of DCD and prolonged EVLP, the effects of donor warm ischemia and postmortem ventilation on graft recovery were evaluated. Adult male swine underwent general anesthesia and heparinization. In the control group (n = 4), cardioplegic arrest was induced and the lungs were procured immediately. In the four treatment groups, a period of agonal hypoxia was followed by either 1 h of warm ischemia with (n = 4) or without (n = 4) ventilation or 2 h of warm ischemia with (n = 4) or without (n = 4) ventilation. All lungs were studied on an EVLP platform for 24 h. Hemodynamic measures, compliance, and oxygenation on EVLP were worse in all DCD lungs compared with controls. Hemodynamics and compliance normalized in all lungs after 24 h of EVLP, but DCD lungs demonstrated impaired oxygenation. Normothermic cellular EVLP is effective in preserving and monitoring of DCD lungs. Early donor postmortem ventilation and timely procurement lead to improved graft function.

Medtronic Reveal LINQ™ Devices Provide Better Understanding of Hibernation Physiology in the American Black Bear (Ursus Americanus)

The American black bear (Ursus americanus) has been called a metabolic marvel. In northern Minnesota, where we have conducted long-term physiological and ecological studies of this species, bears may remain in their winter dens for 6 months or more without eating, drinking, urinating or defecating and yet lose very little muscle mass. We also found that hibernating black bears elicit asystolic events of over 30 seconds and experience an exaggerated respiratory sinus arrhythmia. In this previous work we employed Medtronic Reveal XT devices that required us to visit the den and temporarily extract the bear (under anesthesia) to download the stored data. Here we describe Medtronic’s latest generation of Insertable Cardiac Monitor (ICM), the Reveal LINQ, which enables continuous transmission of data via a relay station from the den site. Black bear hibernation physiology remains of high interest because of the multiple potential applications to human medicine. ICMs have been used for nearly two decades by clinicians as a critical diagnostic tool to assess the nature of cardiac arrhythmias in humans. Such devices are primarily implanted subcutaneously to record electrocardiograms. The device size, battery life and transmission capabilities have evolved in recent years. The first devices were relatively large and a programmer was needed to retrieve information during each clinical (or in our case, den visit). These devices were programmed to capture cardiac incidents such as asystolic events, arrhythmias and tachycardias and apply algorithms that ensure proper data collection: e.g. ectopy rejection and p-wave presence algorithms. The new generation Reveal LINQ was made to telemetrically transmit heart data from human patients, but we needed to develop a system to enable transmission from bear dens, which are remote (cannot easily be checked and adjusted) and are subject to extreme winter weather conditions. Besides the advantage of these devices transmitting data automatically, they are considerably smaller and thus less prone to rejection by the extraordinary immune system of the hibernating bear.

Lung transplant after prolonged ex vivo lung perfusion: predictors of allograft function in swine

Portable normothermic EVLP has been evaluated in clinical trials using standard and extended‐criteria donor lungs. We describe a swine model of lung transplant following donation after circulatory death using prolonged normothermic EVLP to assess the relationship between EVLP data and acute lung allograft function. Adult swine were anesthetized and heparinized. In the control group (n = 4), lungs were procured, flushed, and transplanted. Treatment swine underwent either standard procurement (n = 3) or agonal hypoxia followed by 1 (n = 4) or 2 hours (H) (n = 4) of ventilated warm ischemia. Lungs were preserved for 24H using normothermic blood‐based EVLP then transplanted. Recipients were monitored for 4 H. After 24H of preservation, mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and dynamic compliance (Cdyn) were improved in all EVLP groups. After transplant, EVLP groups showed similar allograft oxygenation. EVLP PVR, mPAP, and lung block weights had significant negative correlations with post‐transplant allograft oxygenation. EVLP P:F ratio did not correlate with acute post‐transplant allograft function until 24H of preservation. Data measured in the first 8H of EVLP were sufficient for predicting acute post‐transplant allograft function. This study provides a benchmark and platform for evaluation of therapies for donor‐related allograft injury in injured lungs treated with prolonged normothermic EVLP.

Effects of Ablation (Radio Frequency, Cryo, Microwave) on Physiologic Properties of the Human Vastus Lateralis

Objective: Ablative treatments can sometimes cause collateral injury to surrounding muscular tissue, with important clinical implications. In this study, we investigated the changes in muscle physiology of the human vastus lateralis when exposed to three different ablation modalities: radiofrequency ablation, cryoablation, and microwave ablation. Methods: We obtained fresh vastus lateralis tissue biopsy specimens from nine patients (age range: 29–73 years) who were undergoing in vitro contracture testing for malignant hyperthermia. Using leftover waste tissue, we prepared 46 muscle bundles that were utilized in tissue baths before and after ablation. Results: After ablation with all the three modalities, we noted dose-dependent sustained reductions in peak force (strength of contraction), as well as transient increases in baseline force (resting muscle tension). But, over the subsequent 3-h recovery period, peak force improved and the baseline force consistently recovered to below its preablation levels. Conclusion: The novel in vitro methodologies we developed to investigate changes in muscle physiology after ablation can be used to study a spectrum of ablation modalities and also to make head-to-head comparisons of different ablation modalities. Significance: As the role of ablative treatments continues to expand, our findings provide unique insights into the resulting changes in muscle physiology. These insights could enhance the safety and efficacy of ablations and help individuals design and develop novel medical devices.

Direct visualization of the removal of chronically implanted pacing leads from an unfixed human cadaver

Introduction As the number of patients with cardiac implanted pacemakers and defibrillators increases, the need for associated lead removal will increase as well. Additionally, many patients do not currently have access to a center of excellence for lead extraction, indicating a clear need for more highly trained extractors. An extraction procedure is defined as lead removal after it has been implanted for more than a year or if specialized imaging and/or when removal equipment is required. Extraction can be performed using manual traction or by employing mechanical or cutting sheaths (radiofrequency or laser). Chronically implanted leads are removed for many reasons, including infection, malfunction, venous occlusion impeding additional lead placement, and/or an acute need for magnetic resonance imaging. Further, these implanted leads can adhere to the walls of the venous vasculature, the tricuspid valve, and/or other cardiac tissues, thus potentially making their extractions high-risk procedures that can lead to serious complications, including death. Highly trained physicians with unique experience (ie, those in high-volume centers) are commonly recruited to perform such lead extractions because of the extensive imaging knowledge required for safe removal. It is commonly noted by these skilled extractors that it is difficult to adequately train and maintain the skillset needed for extraction.

Assessment of Ablative Therapies in Swine: Response of Respiratory Diaphragm to Varying Doses

Ablation is a common procedure for treating patients with cancer, cardiac arrhythmia, and other conditions, yet it can cause collateral injury to the respiratory diaphragm. Collateral injury can alter the diaphragm’s properties and/or lead to respiratory dysfunction. Thus, it is important to understand the diaphragm’s physiologic and biomechanical properties in response to ablation therapies, in order to better understand ablative modalities, minimize complications, and maximize the safety and efficacy of ablative procedures. In this study, we analyzed physiologic and biomechanical properties of swine respiratory diaphragm muscle bundles when exposed to 5 ablative modalities. To assess physiologic properties, we performed in vitro tissue bath studies and measured changes in peak force and baseline force. To assess biomechanical properties, we performed uniaxial stress tests, measuring force–displacement responses, stress–strain characteristics, and avulsion forces. After treating the muscle bundles with all 5 ablative modalities, we observed dose-dependent sustained reductions in peak force and transient increases in baseline force—but no consistent dose-dependent biomechanical responses. These data provide novel insights into the effects of various ablative modalities on the respiratory diaphragm, insights that could enable improvements in ablative techniques and therapies.

Transcatheter Valve Repair and Replacement

Cardiac device technologies continue to advance at a rapid pace, with heart valve design and placement procedures continuing to be one of the major focus areas. Minimally or less invasive procedures to replace cardiac valves will enable an increasing number of individuals to receive this therapy, including the older and more frail individual, the adult patient with prior surgeries for repair of congenital defects, and/or an individual with previous valve replacement (valve-in-valve procedures). Transcatheter-delivered replacement valves for the four heart valves are either available on the market today or are in development. This chapter provides a brief introduction to this rapidly emerging device area, as well as general considerations related to delivering a device via catheter into the heart (e.g., percutaneous beating heart interventional procedures performed under fluoroscopic and/or echocardiographic guidance).