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Early Results of an Infant Model of Orthotopic Cardiac Xenotransplantation

Mitchell et al., Journal of Heart and Lung Transplantation. 2025.

https://pubmed.ncbi.nlm.nih.gov/39778609

This study evaluated the potential of genetically engineered pig hearts for human pediatric heart failure patients, with 11 infantile pig heart transplants performed in size-matched infant baboons (Papio anubis) (sex not specified). All grafts supported normal cardiac functions post-operatively, and six animals survived beyond 3 months. While early cardiac function was not a limiting factor for survival, systemic inflammation led to pulmonary edema and pleural effusions, which impeded long-term outcomes. These findings highlight the feasibility of cardiac xenotransplantation in infants and underscore the need for targeted therapies to manage inflammation and improve survival. Supported by ORIP (P40OD024628) and NHLBI.

Surgical Protocol for Partial Heart Transplantation in Growing Piglets

Medina, World Journal for Pediatric and Congenital Heart Surgery. 2024.

https://pubmed.ncbi.nlm.nih.gov/38780414/

Researchers are interested in using partial heart transplantation (i.e., only the part of the heart containing the necessary heart valve is transplanted) to deliver growing heart valve implants. This novel technique allows partial heart transplants to grow, similar to the valves in heart transplants. More work is needed, however, to understand the underlying biological mechanisms of this approach and achieve progress in clinical care. In the present study, the authors present a surgical protocol for partial heart transplantation in growing piglets. This model will enable other researchers to seek fundamental knowledge about the nature of partial heart transplants. Supported by ORIP (U42OD011140) and NHLBI.

Mineralocorticoid Receptor Blockade Normalizes Coronary Resistance in Obese Swine Independent of Functional Alterations in Kv Channels

Goodwill et al., Basic Research in Cardiology. 2021.

https://pubmed.ncbi.nlm.nih.gov/34018061/

Impaired coronary microvascular function (e.g., reduced dilation and coronary flow reserve) predicts cardiac mortality in obesity. Mineralocorticoid receptor (MR) antagonism improves coronary microvascular function in obese humans and animals. Inhibition of Kv channels reduced coronary blood flow and augmented coronary resistance under baseline conditions in lean but not obese swine and had no impact on hypoxemic coronary vasodilation. MR blockade prevented obesity-associated coronary arteriolar stiffening independent of cardiac capillary density and changes in cardiac function. These data indicate that chronic MR inhibition prevents increased coronary resistance in obesity independent of Kv channel function and is associated with mitigation of obesity-mediated coronary arteriolar stiffening. Supported by ORIP (U42OD011140, S10OD023438), NHLBI, and NIBIB.