Development and Evaluation of a Novel Solution, Somah, for the Procurement and Preservation of Beating and Nonbeating Donor Hearts for Transplantation

Abstract

Background-Injury to myocytes, endocardium, and the coronary endothelium during harvesting and storage can compromise outcomes after heart transplantation. Safeguarding of structure and function of cardiomyocytes and endothelium in donor hearts may lead to improved patient survival after transplantation. Information gained from porcine hearts stored in standard transplant solution was used to design a superior preservation solution that would optimally protect and maintain organs from beating heart and/or nonbeating heart donors during long-term storage. Methods and Results-Multiphoton microscopy was used to image deep within cardiac biopsies and coronary artery tissue harvested from porcine hearts obtained from beating heart and nonbeating heart donors for analysis of myocyte and endothelial cell structure and function. Cell structural integrity and viability, calcium mobilization, and nitric oxide generation were determined with fluorescence viability markers, immunofluorescence, and Western blots. During hypothermic storage in standard preservation solution, Celsior, myocyte, and endothelial viability was markedly attenuated in hearts obtained from beating heart donors. In contrast, hearts from beating and nonbeating heart donors stored in the newly formulated Somah solution demonstrated an increase in high-energy phosphate levels, protection of cardiac myocyte viability, mitochondrial membrane polarization, and structural proteins. Similarly, coronary artery endothelial organization and function, calcium mobilization, and nitric oxide generation were well maintained during temporal storage in Somah. Conclusions-The

S262A mutation abolishes protective effects of connexin 43 against hypothermic preservation–induced injury in cardiomyocytes

“…8,9 Some organ preservation solutions have been developed and applied in transplantation, but cold ischemic storage of the heart is still limited to 4 to 6 hours because preservation solutions have been unable to significantly inhibit the ensuing I/R injury. 10 Cx43, as an important player in the pathophysiology of myocardial I/R injury, has a role in protection during ischemic and pharmacologic pre-conditioning. 11 Using a transgenic mouse model, Roell et al reported that cardiac engraftment of Cx43-overexpressing myoblasts in vivo prevents post-infarct arrhythmia.…”

The Critical Role of Bioenergetics in Donor Cardiac Allograft Preservation

“…A paradigm shift is emerging in the field, with a new focus on providing organs with necessary metabolic nutrients instead of slowing metabolism. Somah solution attempts to meet the energy requirements of cardiomyocytes and coronary endothelium by preserving anaerobic metabolism and high-energy phosphates, while safeguarding the mitochondrial gradient [33]. Interestingly, the Somah solution is most effective at 21°C [34], adding to the question whether conventional low ex vivo storage temperature is justified.…”

The Progression of Isoflurane-induced Malignant Hyperthermia and Its Attenuation by Cisatracurium in a Pre-clinical Porcine Model of Heart Transplant

“…While investigating the role of our novel heart storage solution in a porcine orthotopic heart transplant model, we observed the development of unusual signs of hypermetabolism and multi-systemic involvement in both the donors and recipients [8]. Anesthetic used in these surgeries was inhalational isoflurane and the severity of observed signs was found to be proportional to duration of anesthesia.…”