Mechanisms of Cold Preservation and Reperfusion Injury for Solid Organ Transplantation: Implications for Partial Heart Transplantations
Round 1
Reviewer 1 Report
Dear Authors,
thank you for the opportunity to review your paper.
In part 5 (Discussion) it appears as if the text is missing. Or perhaps it is included in the Conclusion section?
A description of the technique of partial heart transplantation would most probably be of interest to the readers of the journal. Also where the technique stands in comparison to aortic and mitral valve homografts (you mentioned that briefly) and in the light of tissue conservation.
Regarding tissue damage in the setting of transplantation, please add a short paragraph on the relevance of iron ions, as that is a current target for improvement in cold static storage (Custodiol-N for example).
Regarding the English language I would recommend seeking advice from a native speaker (Punctuation appears to be a bit odd sometimes. However, I am not a native speaker myself...).
Author Response
- In part 5 (Discussion) it appears as if the text is missing. Or perhaps it is included in the Conclusion section?
- First off, thank you for taking the time to read and improve this review. The first reviewer is correct to point out that the discussion section was unfortunately not transferred to the Transplantology format correctly. To resolve this issue, we have included the discussion section as Section 5, which was mistakenly in Section 4 labelled “Variation in CIT/WIT Among Solid Organs” of the first submission. In addition, we have added the original text intended for section 4.
- A description of the technique of partial heart transplantation would most probably be of interest to the readers of the journal. Also where the technique stands in comparison to aortic and mitral valve homografts (you mentioned that briefly) and in the light of tissue conservation.
- Reviewer 1 makes an important point that the description of the actual partial heart transplantation procedure was lacking in sustenance. To address this issue, we have added a more thorough description of partial heart transplantation, mechanical valve replacement surgery, and aortic and pulmonic homograft implantation surgery in the discussion (Section 5) starting on line 439. We have also included current best practices for procedures to fix congenital valvular defects and their benefits and obstacles compared to partial heart transplantation in the discussion.
- Regarding tissue damage in the setting of transplantation, please add a short paragraph on the relevance of iron ions, as that is a current target for improvement in cold static storage (Custodiol-N for example).
- As reviewer 1 has stated, it is important to discuss the very interesting and novel use of iron chelators and mitigation of damage caused by iron ions in the context of ischemia and reperfusion injury. To address this shortcoming in the paper, we have included a section labelled 3.2.3 “Iron-Dependent Mechanisms of ROS Production,” under the subsection detailing the role of reactive oxygen species in ischemia and reperfusion injury. We included the physiological basis of iron ions role in ischemia reperfusion injury, recent research in the field, and potential future therapies, such as Custodiol-N.
Reviewer 2 Report
Overall the paper is interesting and is well written. It will be of interest to the readers of the journal. However, we have to acknowledge that not all readers have the same understanding of the ischemic time and heart transplant process. I would have a few suggestions:
- Expand the first section some and detail a bit more the warm and cold ischemic time, and describe a bit more the pHT concept
- some words appear to be missing here and there, suggest re-reading the manuscript
- Discussion section is missing, suggest removing the entire section
Overall well written
Author Response
- Overall the paper is interesting and is well written. It will be of interest to the readers of the journal. However, we have to acknowledge that not all readers have the same understanding of the ischemic time and heart transplant process. I would have a few suggestions:
- First off, thank you for taking the time and effort to read and improve this submission for publication. Reviewer 2 raises an important point. Due to the complexity of procurement and transplantation, it is important to give a more comprehensive discussion of these processes which we failed to do in the previous version. To aid readers of this article, we have added a more thorough description of cold ischemic time and warm ischemic time in the introduction starting at line 44 of the revised submission. Additionally, we have added a more detailed description of the procurement and partial heart transplantation process/procedure to the discussion section starting at line 449. We appreciate this feedback and hope that these additions will improve the reader’s experience and understanding of our manuscript.
- Some words appear to be missing here and there, suggest re-reading the manuscript
- Thank you, Reviewer 2, for catching this mistake. Certain sections and sentences were unfortunately transferred incorrectly when added to the Transplantology template. Additionally, we made some grammatical errors in the first submission that were missed prior to submission. We have addressed missing words, misplaced sections, and have read the paper individually to address poor readability. We believe this version of the paper will provide a more comprehensive and enjoyable read for journal readers.
- Discussion section is missing, suggest removing the entire section
- The second reviewer is correct to point out that the discussion section was unfortunately not transferred to the Transplantology format correctly. To resolve this issue, we have included the discussion section as section 5, which was mistakenly in Section 4 labelled “Variation in CIT/WIT Among Solid Organs” of the first submission. In addition, we have added the original text intended for section 4.
Round 2
Reviewer 1 Report
All issues addressed, thank you, best wishes!
