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Updated: Jul 2, 2025
Pre-clinical Model of Cardiac Donation after Circulatory Death
Published on: August 2, 2019
HTK vs. HTK-N for Coronary Endothelial Protection during Hypothermic, Oxygenated Perfusion of Hearts Donated after
Lars Saemann1,2, Kristin Wächter1, Nitin Gharpure1
1Department of Cardiac Surgery, University Hospital Halle (Saale), University of Halle, 06120 Halle (Saale), Germany.
Insights
The novel HTK-N solution better preserves coronary artery endothelial function in donation-after-circulatory-death (DCD) donor hearts compared to traditional HTK solution during hypothermic oxygenated perfusion (HOP). This improved preservation may reduce allograft vasculopathy risk.
Area of Science:
- Cardiology
- Transplantation Immunology
- Vascular Biology
Background:
- Coronary artery protection is crucial for donor heart maintenance and preventing allograft vasculopathy.
- While hypothermic, oxygenated perfusion (HOP) effects on microvasculature are known, macrovasculature impact remains unclear.
- Donation-after-circulatory-death (DCD) hearts present unique preservation challenges.
Purpose of the Study:
- To investigate the effect of a novel HTK-N solution versus traditional HTK solution on the coronary macrovasculature of DCD porcine hearts during HOP.
- To compare endothelial-dependent and -independent vasomotor function of the left anterior descending coronary artery (LAD) post-perfusion.
- To analyze the transcriptome of LAD samples to understand underlying molecular mechanisms.
Main Methods:
- Porcine DCD hearts were preserved using HOP with either HTK or HTK-N for 4 hours.
- Hearts underwent 2 hours of transplantation-equivalent reperfusion with blood.
- Vasomotor function (bradykinin, sodium-nitroprusside) and LAD transcriptome (microarrays) were assessed.
Main Results:
- HTK-N significantly improved endothelial-dependent relaxation compared to HTK.
- Endothelial-independent relaxation was comparable between groups.
- Transcriptome analysis revealed HTK-N upregulated genes involved in cell preservation and downregulated those related to ischemia/reperfusion injury and immune response.
Conclusions:
- The novel HTK-N solution offers superior preservation of coronary artery endothelial function in DCD donor hearts compared to the traditional HTK solution.
- HTK-N's molecular profile suggests enhanced protection against ischemia/reperfusion injury and improved vascular health.
- These findings support HTK-N as a promising preservation solution for DCD donor hearts.
Abstract:
Protection of the coronary arteries during donor heart maintenance is pivotal to improve results and prevent the development of coronary allograft vasculopathy. The effect of hypothermic, oxygenated perfusion (HOP) with the traditional HTK and the novel HTK-N solution on the coronary microvasculature of donation-after-circulatory-death (DCD) hearts is known. However, the effect on the coronary macrovasculature is unknown. Thus, we maintained porcine DCD hearts by HOP with HTK or HTK-N for 4 h, followed by transplantation-equivalent reperfusion with blood for 2 h. Then, we removed the left anterior descending coronary artery (LAD) and compared the endothelial-dependent and -independent vasomotor function of both groups using bradykinin and sodium-nitroprusside (SNP). We also determined the transcriptome of LAD samples using microarrays. The endothelial-dependent relaxation was significantly better after HOP with HTK-N. The endothelial-independent relaxation was comparable between both groups. In total, 257 genes were expressed higher, and 668 genes were expressed lower in the HTK-N group. Upregulated genes/pathways were involved in endothelial and vascular smooth muscle cell preservation and heart development. Downregulated genes were related to ischemia/reperfusion injury, oxidative stress, mitochondrion organization, and immune reaction. The novel HTK-N solution preserves the endothelial function of DCD heart coronary arteries more effectively than traditional HTK.
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