Peer Review History

Original SubmissionOctober 11, 2024
Decision Letter - Vadim Ten, Editor

PONE-D-24-45627A modified rat model of 8 minutes asphyxial cardiac arrest and cardiopulmonary resuscitationPLOS ONE

Dear Dr. Ye,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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ACADEMIC EDITOR: 

  • Please address minor concerns raised by the reviewer 2

Please ensure that your decision is justified on PLOS ONE’s publication criteria  and not, for example, on novelty or perceived impact.

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Please submit your revised manuscript by Feb 28 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

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We look forward to receiving your revised manuscript.

Kind regards,

Vadim Ten MD, PhD

Academic Editor

PLOS ONE

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2. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Dear Qingshan Ye.

Your manuscript has been reviewed by two independent reviewers and requires a minor revision to to be published.

Please, address minor concerns of the reviewer 2

Sincerely,

Vadim S. Ten MD, PhD

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: In this manuscript, the Authors endeavored to develop a refined protocol for a rat model of cardiac arrest and cardiopulmonary resuscitation. They argue that the described by them model “aligns closely with the pathophysiological changes observed in in-hospital cardiac arrest scenarios and effectively simulates a majority of clinical situations involving cardiac arrest”. The Authors now provide a very helpful narrative for step-by-step procedures and guidelines for standardization of experimental outcomes.

There are many merits to this manuscript. The study is well planned, experiments are well executed, and the document is expertly written. I concur with the Authors that longitudinal (14 days) evaluation of mortality and neurological outcomes is very helpful and provides peer researchers with a benchmark for sample size calculations at different experimental design time points. The limitations of the work are well described.

Below are several specific suggestions for improvements in data reporting and discussion of the literature:

[1] Moderate concern: As the proposed approach is not original, it would be very helpful to compare this study’s outcomes to the previous reports, both in the context of successful resuscitation and longer-term survival. The original methodological articles by HHL Hendrickx et al. (Resuscitation, 1984) and L Katz et al (JFRBM, 1995) are mentioned in Introduction but largely excluded from Discussion. To the best of this reviewer’s knowledge, Katz and colleagues reported much higher 72-h survival rates while using qualitatively similar procedure (why?). This and other studies deserve additional discussion.

[2] Moderate concern: The supplemental file is missing primary data for neurological outcomes presented in Figure 7C and 7D.

[3] Minor concern and suggestion for improvement: I would suggest including in the Supplemental files additional H&E staining images from more animals and more EM images. Such additional information will provide the specialists with a stronger basis for evaluating neurological damage in ACA brains. There is significant demand for such data for research and educational purposes.

Reviewer #2: The authors in this study established a stable 8 minutes asphyxial cardiac arrest and

cardiopulmonary resuscitation rat model and assessed the long-term prognosis,

providing a foundation for the researchers in the field into the mechanisms underlying cardiac

arrest and potential intervention strategies. This is an elegant study with extensive details on methodology that can serve as an experimental reference for the field. Further limitations of the study has been considered such as the use of only male but not the female rats. Overall, this is a very timely and well conducted study and is viewed as a significant resource for the field.

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Reviewer #1: No

Reviewer #2: No

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Revision 1

Dear Editors and Reviewers:

Thank you for the opportunity to revise our manuscript and address the reviewers’ comments. We appreciate the thorough evaluation by the academic editor and reviewers, and we have carefully revised the manuscript to incorporate their suggestions. Below, we provide a point-by-point response to all concerns raised.

Response to Academic Editor’s Comments

Editor’s Comment: [Address minor concerns raised by the reviewer].

Response: We thank the editor for this observation. We have discussed the issues raised by the reviewers in more detail in the revised manuscript and clearly marked the revisions. We supplemented the re-uploaded attachment with more detailed original neurobehavioral data and uploaded additional HE images and TEM images of animals in the PACE system.

Response to Reviewer 1’s Comments

Reviewer 1:

Opinion 1: [Please compare the results of this study with those reported by HHL Hendrickx (Resuscitation, 1984) and L Katz (JFRBM, 1995) in the discussion, and answer why the 72-hour survival rate was higher in the Katz’s study when a similar procedure was used.]

Response: We appreciate this suggestion. In the newly submitted manuscript, we discuss and contrast the original methods presented in the article by Hendrickx and Katz, which are marked in red under "Revised Manuscript with Track Changes." Regarding the difference in the 72-hour survival rate between our experiment and that of Katz, a certain elaboration has also been made in the discussion section of the revised manuscript. I summarize the possible reasons as follows:

①Use of sodium bicarbonate during cardiopulmonary resuscitation. To minimize the effect of drugs on blood gas results after ROSC, sodium bicarbonate was not used in our experiment, which may be one of the reasons for the lower ROSC rate and 72-hour survival rate compared to the Katz study.

②Post-ROSC longer pure oxygen mechanical ventilation. After ROSC, when the spontaneous breathing of the rats recovered to the extubation conditions, we implemented the weaning and extubation protocol, and did not use muscle relaxants to keep the rats on pure oxygen mechanical ventilation continuously. However, Katz's protocol maintained at least 1 hour of pure oxygen ventilation. The rapid extubation protocol without longer ICU monitoring may lead to an increase in the number of rats that died due to respiratory system dysfunction in the early stage of resuscitation.

③The difference in body weight of SD rats leads to different tolerance to hypoxia. We selected rats weighing 250-300g, which were in the early adult stage. Katz selected rats weighing 350-400g. Adult rats with lower body weight and younger age have more active basal metabolism, higher oxygen consumption, faster lactate accumulation during hypoxia, are prone to acidosis, and have poorer tolerance to hypoxia in brain tissues [M J Durkot�Aviat Space Environ Med,1986�,M A Holliday(Pediatr Res,1967)].

To sum up, in our experimental results, the ROSC rate and 72-hour survival rate of rats were lower than those observed in Katz's study. However, based on the comprehensive neurological function score, behavior, and pathological results, 72 hours after resuscitation, the neurological function damage in our rats was more severe compared to that in Katz's rats. The neurological function damage in Katz's experiment was mild at 72 hours. We consider that more severe neurological function damage in the early stage of resuscitation may be more representative of the clinical situation.

Opinion 2: [The supplemental file is missing primary data for neurological outcomes presented in Figure 7C and 7D.]

Response: We agree with the reviewer’s concern. We uploaded all the original data of SD rats in the research in the previous attachment, including the data of "mNSS score and Chimney test in Neurobehavioral experiments". This time, we supplemented the scores of each part within the total score of mNSS score in the original data of SD rats. Their locations can be found in the newly submitted Excel file "SDrat - raw data" .

Opinion 3: [It is recommended to supplement additional H&E staining images of more animals and more EM images.]

Response: We appreciate the suggestions of the reviewers. We have supplemented more HE images and TEM images of animals in PACE. For their locations, please refer to the newly submitted supplementary PDF file: "Supplement Raw Image - HE & TEM".

We believe the revised manuscript now addresses all concerns. We are grateful for the reviewers’ time and constructive feedback. Please do not hesitate to contact us if further revisions are required.

Sincerely,

Qingshan Ye

People's Hospital of Ningxia Hui Autonomous Region,Ningxia Medical University

No.301 Zhengyuan North Street, Yinchuan, Ningxia,China,750001

E-mail:yeqingshan@hotmail.com

22/02/2025

Attachments
Attachment
Submitted filename: Response to Reviewers.docx
Decision Letter - Vadim Ten, Editor

A modified rat model of 8 minutes asphyxial cardiac arrest and cardiopulmonary resuscitation

PONE-D-24-45627R1

Dear Dr. Qingshan Ye,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Vadim Ten

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The authors have addressed concerns raised during review of the previous version of this manuscript.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #1: No

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Formally Accepted
Acceptance Letter - Vadim Ten, Editor

PONE-D-24-45627R1

PLOS ONE

Dear Dr. Ye,

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on behalf of

Professor Vadim Ten

Academic Editor

PLOS ONE

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