The Dual Cardiovascular Effect of Centrally Administered Clonidine: A Comparative Study between Pentobarbital- and Ketamine/Xylazine-Anesthetized Rats
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors
While the paper might not introduce revolutionary concepts, it does contribute incrementally to the existing knowledge about the central effects of alpha-2 receptor ligands.
The clarity in the presentation of ideas and methods is a strong point of this paper.
I suggest separating Figure 2 into two figures with lesser panels and use colors in Figure 3 to enhance clarity.
Please carefully revise English language.
Author Response
Please see the attachment.
Author Response File: 
Author Response.docx
Reviewer 2 Report
Comments and Suggestions for AuthorsComments:
Dear Authors, I lent enough time and consideration to peruse this manuscript titled “The dual cardiovascular effect of centrally administered 2 clonidine: a comparative study between pentobarbital and keta- 3 mine/xylazine anesthetized rats”
I have found that generally speaking it is a well written manuscript which addresses the scientific problem. The present study discusses explore the impact of two different anaesthetic protocols (pentobarbital and ketamine/xylazine) on the central nervous system-dependent cardio vascular effect of clonidine which could be significant for the development of central nervous system-dependent cardio vascular system. The aims, materials and techniques, findings, and conclusion parts of the report are all well outlined and follow an organized format. The study is overall meaningful, however, there are some concerns that should be addressed by authors, including:
1. A slight disparity in describing purpose in the abstract can leave readers bewildered. Line 24 (This study discloses-------) needs to be rewritten for better meaning of the sentence. Acronyms should be removed from the abstract.
2. Write the full form of acronym GABA in the introduction.
3. Rewrite the entire last para of Introduction section, line 74-79, in active voice and maintain it throughout the manuscript.
4. Impact of yohimbine in the cardiovascular effect of centrally administered clonidine and dexmedetomidine must be documented in the introduction section with appropriate references.
5. I would like to ask the authors why only male wistar rats population were considered.
6. In Material and methods section, note the number of male wistar rats in preliminary experiments, losses during anaesthesia and surgical procedures.
7. In the Materials and Methods section, line no- 139-140, “separated groups received an i.c.v. microinjection of 139 clonidine (10 μg/5 μL) or dexmedetomidine (0.6 μg/5 μL)” solvent for the drugs must be mentioned.
8. The manuscript is devoid of mechanisms-related information figure in the discussion section.
9. The authors could mention the limitation section separately also.
Comments on the Quality of English LanguageMinor editing required.
Author Response
Please see the attachment.
Author Response File: Author Response.docx
Reviewer 3 Report
Comments and Suggestions for AuthorsThis paper delves into the cardiovascular effects of clonidine, a 𝛽2-adrenergic receptor (𝛽2-AR) agonist, when administered intracerebroventricularly in rats anesthetized with either pentobarbital or ketamine/xylazine. The authors have meticulously summarized the findings, shedding light on the influence of anesthetic choice on the cardiovascular effects of clonidine. The paper provides a comprehensive overview of the methodology, experimental setup, and results, which aids readers in understanding the scope and depth of the study. The authors also touch upon the historical context of clonidine, its FDA approval, and its various applications.
Specific Comments
1. Abstract and Introduction: The abstract provides a concise summary of the study's objectives and findings. However, the introduction could benefit from a more detailed background on the significance of studying the cardiovascular effects of clonidine in different anesthetic conditions.
2. Methodology: The methods section is detailed, providing insights into the experimental setup and the drugs used. However, it would be beneficial to elaborate on the rationale behind the choice of specific drugs and solutions, such as Evans blue and dexmedetomidine hydrochloride.
3. Results: The results section begins with a discussion on the cardiovascular effects of clonidine based on the choice of anesthetic. While the initial findings are presented, it would be helpful to have a more in-depth analysis of the data, including statistical significance and potential implications.
4. Figures and Data Interpretation: The paper would benefit from a clearer presentation of figures and data. Specifically:
- The cardiovascular effects of clonidine in different anesthetic conditions should be visually represented for easier interpretation. Some supplementary data needed.
5. Discussion: The discussion section should delve deeper into the implications of the findings. How do these results impact the broader understanding of clonidine's effects under different anesthetics? Are there potential clinical implications?
6. Language and Clarity: The manuscript is well-written but could benefit from a review by a native English speaker to enhance clarity and fluency.
General Comments:
- The choice of anesthetic and its potential influence on drug effects is a crucial aspect of pharmacological studies. The authors should discuss the broader implications of their findings in this context.
- It would be beneficial to compare these findings with previous studies on clonidine and its cardiovascular effects, if any.
- The authors might consider discussing potential future studies or experiments that could further elucidate the mechanisms behind the observed effects.
Author Response
Please see the attachment.
Author Response File: Author Response.docx
Round 2
Reviewer 2 Report
Comments and Suggestions for AuthorsNo further comments
