Organ preservationImproved Myocardial Function After Cold Storage With Preservation Solution Supplemented With a Carbon Monoxide–Releasing Molecule (CORM-3)
Section snippets
Reagents
CORM-3 was synthesized as described previously.19 Stock solutions of CORM-3 in distilled water were prepared fresh each day. The inactive counterpart (iCORM-3) was prepared by leaving the solution for 24 hours to liberate its entire CO content, and finally bubbled with nitrogen gas for 5 minutes.19 A creatine kinase (CK) kit was supplied by Alpha Laboratories, UK, and a lactate dehydrogenase (LDH) kit supplied by Roche Applied Science, UK. All other reagents were purchased from Sigma.
Isolated Rat Heart Preparation
All
Results
There were no statistically significant differences in baseline LVDP, coronary flow (CF), dP/dtmax and dP/dtmin among the groups studied. The baseline values from these groups were identical to those obtained with freshly isolated hearts (Table 1), as reported previously.30
Discussion
In this study we have examined the potential effects of a novel bioactive compound that releases controlled amounts of CO (CORM-3) to protect the myocardium against the injury associated with cold ischemic storage and reperfusion. Cold preservation of the heart provides a rapid arrest of cardiac metabolism while maintaining structural viability and limiting reperfusion injury.31 A number of preservation solutions containing a variety of protective components, including inhibitors of free
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Cited by (48)
Carbon monoxide and a change of heart
2021, Redox BiologyEmerging role of carbon monoxide in intestinal transplantation
2021, Biomedicine and PharmacotherapyCitation Excerpt :The challenges associated with the use of CO gas protocol was partially overcome following the development of CO-RMs. Although there is currently no studies on the use of CO-RMs in intestinal transplantation, there are studies showing salutary effects of various CO-RMs in experimental transplantation of kidney, heart, lung, liver and pancreatic islets [68–72]. These studies should be expanded to cover the use of CO-RMs in intestinal transplantation.
Application of carbon monoxide in kidney and heart transplantation: A novel pharmacological strategy for a broader use of suboptimal renal and cardiac grafts
2021, Pharmacological ResearchCitation Excerpt :Besides, the concentration of iCORM (50 μM) used by the authors is lower than what is used in other studies, which suggests its potency. The report by Musameh and colleagues [92] corroborates that of a previous study involving cardiac transplant rejection model in mice, where intraperitoneal administration of donor mice with 10 μM of CORM-3 at 24 h before organ procurement, and in recipient mice 24 h prior to reperfusion followed by 1 h after transplantation and daily administration from post-operative day 1–8 displayed a substantial cardioprotection against the damaging effects of cold IRI, and improved graft quality and prolonged graft survival compared to control group that received 10 μM of iCORM [94]. Further evidence supporting the protection by CO against myocardial IRI was strengthened in a model of IRI using isolated rat hearts.
Targeting heme oxygenase-1 and carbon monoxide for therapeutic modulation of inflammation
2016, Translational ResearchCitation Excerpt :Finally, applications for CORMs in transplantation models have also been described. For example, in a cardiac transplantation model, inclusion of CORM-3 in the preservation fluid was shown to improve cardiac function after transplantation.319 These examples of salutary effects of CORMs are suggestive of possible therapeutic applications of CORMs in human disease, although more research regarding safety and efficacy of these compounds for human application is needed.
Enzyme-triggered CO-releasing molecules (ET-CORMs): Evaluation of biological activity in relation to their structure
2013, Free Radical Biology and Medicine
Supported by grants from the Foundation for Al-Quds University Medical School and Karim Rida Said Foundation.