Abstract For many patients with terminal/advanced cardiac failure, heart transplantation is the most effective, durable treatment option, and offers the best prospects for a high quality of life. The number of potentially life-saving donated human organs is far fewer than the population who could benefit from a new heart, resulting in increasing numbers of patients awaiting replacement of their failing heart, high waitlist mortality, and frequent reliance on interim mechanical support for many of those deemed among the best candidates but who are deteriorating as they wait. Currently, mechanical assist devices supporting left ventricular or biventricular heart function are the only alternative to heart transplant that is in clinical use. Unfortunately, the complication rate with mechanical assistance remains high despite advances in device design and patient selection and management, and the quality of life of the patients even with good outcomes is only moderately improved. Cardiac xenotransplantation from genetically multi-modified (GM) organ-source pigs is an emerging new option as demonstrated by the consistent long-term success of heterotopic (non-life-supporting) abdominal and life-supporting orthotopic porcine heart transplantation in baboons, and by a recent ‘compassionate use’ transplant of the heart from a GM pig with 10 modifications into a terminally ill patient who survived for 2 months. In this review, we discuss pig heart xenotransplantation as a concept, including pathobiological aspects related to immune rejection, coagulation dysregulation, and detrimental overgrowth of the heart, as well as GM strategies in pigs to prevent or minimize these problems. Additional topics discussed include relevant results of heterotopic and orthotopic heart transplantation experiments in the pig-to-baboon model, microbiological and virologic safety concepts, and efficacy requirements for initiating formal clinical trials. An adequate regulatory and ethical framework as well as stringent criteria for the selection of patients will be critical for the safe clinical development of cardiac xenotransplantation, which we expect will be clinically tested during the next few years.

https://academic.oup.com/cardiovascres/article-pdf/118/18/3499/49201403/cvac180.pdf

Cardiac xenotransplantation: from concept to clinic

Summary
Recently, a new interstitial cell type called telocyte has been identified. Telocytes are found in many organs including the heart, where they are especially well described. However, their presence in the porcine heart has not yet been proven. The pig is a valuable animal model in research because of its resemblance with man, making it interesting to determine whether telocytes can be found in pigs as well. The focus of this study is the identification and ultrastructural description of telocytes in the heart tissue of pig. Using transmission electron microscopy, telocytes were found in both left and right atrium and ventricle, usually close to cardiomyocytes and/or blood vessels. Their most important characteristic is the long cytoplasmic processes called telopodes, which have a moniliform aspect, measure tens of μm and usually have a thickness below 0.2 μm. This unique morphological feature enables telocytes to be recognized from other interstitial cells such as fibroblasts. Additional observations include the ability to release extracellular vesicles and to make contacts with other structures such as endothelial cells, suggesting a role in intercellular communication.

Identification of telocytes in the porcine heart.

https://biblio.ugent.be/publication/7027804/file/7027808.pdf

The morphology of the canine omentum and its surgical implications

Information on ultrasound examination of equine pulmonary veins is scarce due to a lack of in-depth anatomical information. Each pulmonary vein drains a specific lung lobe region, after which those veins merge into a collecting antrum, before opening into the left atrium through their respective ostia. The aim of this study was, by using anatomical dissection and silicone casting of equine cardiopulmonary sets, to study the venous drainage of both lungs and the position of the ostia and to investigate whether the ostia can be identified and differentiated using ultrasound. Three out of the four ostia could be observed echocardiographically in the standing horse. The ostium draining the most caudal aspects of both lungs showed little variability, while the ostium draining the rest of the right lung could be used as an easily recognisable landmark, since it was located adjacent to the interatrial septum. The identification of the equine pulmonary vein ostia using ultrasound might allow for the determination of size and flow patterns in the assessment of cardiovascular disease.

Topography and ultrasonographic identification of the equine pulmonary vein draining pattern.

Ganglia and telocytes were identified inside the porcine pulmonary veins wall near myocardial sleeve tissue at the atriopulmonary junction. These structures are reported to play a role in the initiation of pulses from outside the heart, which potentially can cause cardiac conduction disorders such as atrial fibrillation. In-depth knowledge on the fine structure of the pulmonary vein wall is a pre-requisite to better understand the underlying pathophysiology of atrial fibrillation and the origin and conduction of ectopic pulses. The importance of pulmonary vein myocardial sleeves as triggering foci for atrial fibrillation has been shown in human patients. In this context, the fine structure of the pulmonary vein wall was investigated qualitatively by light and transmission electron microscopy in the pig, which is a frequently used animal model for development of new treatment strategies. Additionally, intra and extramural ganglia, containing telocytes that create a network near the neurone cell bodies, were identified in pigs. Detailed illustration of the distribution and organization of tissues and cell types, potentially involved in the origin and propagation of ectopic stimuli originating from the pulmonary veins, might lead to a better insight on the actual composition of the tissues affected by ablation as studied in pigs.

Presence of Ganglia and Telocytes in Proximity to Myocardial Sleeve Tissue in the Porcine Pulmonary Veins Wall

The layout of the porcine atriopulmonary junction and immediately adjacent structures was investigated by gross anatomical and vascular corrosion casting studies to meet the need for more in-depth anatomical insights when using the pig as an animal model in the development of innovative approaches for surgical cardiac ablation in man. The veins from the right cranial and middle lung lobes drain through a common ostium in the left atrium, whereas a second ostium receives the blood returning from all other lung lobes, although limited variation to this pattern was observed. Surrounding anatomical structures that are most vulnerable to ablation damage as reported in man are located at a safer distance from the pulmonary veins in pigs, yet a certain locations, comparable risks are to be considered. Additionally, it was histologically confirmed that myocardial sleeves extend to over a centimetre in the wall of the pulmonary veins.

The Pulmonary Veins of the Pig as an Anatomical Model for the Development of a New Treatment for Atrial Fibrillation

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The Pulmonary Veins of the Pig as an Anatomical Model for the Development of a New Treatment for Atrial Fibrillation