Beneficial Effects of RNS60 in Cardiac Ischemic Injury
, Barbara Wierzbicka 3, Andreas Kalmes 4, Ewa M. Slominska 1, Magdi H. Yacoub 5 and Ryszard T. Smolenski 1
Ameesh M. Isath
Round 1
Reviewer 1 Report
Major concerns:
1. RNS60:
a. Insufficient drug information: structure or composition and resources for RNS60 must be provided in the manuscript. The doses or concentrations of RNS60 must be provided.
b. Design: Why did authors only designate one group in the report? Did authors have positive control group for this study?
2. Methods
a. ECG: How did authors measure ECG STU area?
3. Results
a. Figure 1. (a) A and B ECG were unclear images. They must be replaced with new images.
b. Figure 3. "*,**, ***, ***" must be indicated in the figure panels.
c. Figure 3. Why did authors use two names "RNS60" and "Revalesio" in this figure?
Minor comments:
1. Grammar and spelling corrections are needed. e.g. "Baloon" in Figure 3 must be corrected.
Author Response
Reviewer 1
Major concerns:
- RNS60:
- Insufficient drug information: structure or composition and resources for RNS60 must be provided in the manuscript. The doses or concentrations of RNS60 must be provided.
Response: We are grateful for the comments on our manuscript. Composition of the RNS60 was added to the introduction part. Doses and concentrations were included in the materials and methods part.
- Design: Why did authors only designate one group in the report? Did authors have positive control group for this study?
Response: We had used only 0,9% sodium chloride as a control fluid.
- Methods
- ECG: How did authors measure ECG STU area?
Response: We calculated the ECG STU area manually with the use of a ruler.
Response
- Results
- Figure 1. (a) A and B ECG were unclear images. They must be replaced with new images.
Response: More visible pictures were added.
- Figure 3. "*,**, ***, ***" must be indicated in the figure panels.
Response: Pictures were changed.
- Figure 3. Why did authors use two names "RNS60" and "Revalesio" in this figure?
Response: Names were changed.
Minor comments:
- Grammar and spelling corrections are needed. e.g. "Baloon" in Figure 3 must be corrected.
Response: Spelling and grammar corrections have been made.
Author Response File: 
Author Response.docx
Reviewer 2 Report
Magdalena et al report the effect of novel molecule RNS60 containing charge stabilized nanostructures on “cardioprotection” during myocardial hypoxia and cardioplegia in mice/rat models. This is a well-done study with appropriate control demonstrating that RNS60 decreased the hypoxia induced myocardial injury through studying changes in ECG, Troponin T and CK levels in mice models and had a cardioprotective effect during cardioplegia/hypothermia in rat models.
I would suggest the following minor revisions/grammatical errors.
Minor comments:
1. Authors state “It was had been shown earlier in multiple disease models, in preclinical in vitro and in vivo studies, that RNS60 has broad anti-inflammatory and cytoprotective effects” – NEED reference
2. Incorrect sentence especially after “what”; break up and reword – “It was previously found by Ogino and Katayama that rapid washout of purine precursors at reperfusion, did not provide sub- strates for nucleotide synthesis in the heart what is linked to problems with the restoration of contractile function”
3. The second approach to estimate the efficiency of cardioplegic solutions is the meas- uring of the myocardial energy-rich phosphates in the heart homogenates. - change to “is the measurement of”
4. Again incorrect sentence – “It was previously checked that ATP con- centration is 30% lower in the failing heart what is in the opposite to RNS60 treatment which had a positive influence on the ATP content”
5. Suggest rewording “initial” to baseline – “Post-reperfusion ATP levels were 62% and 89% of the initial”
6. Again the sentence reads incorrectly and suggest breaking down or using appropriate punctuations; “In our study, all hearts recovered mechanical function after 4 h of ischemia but consistent with improved energy status of the heart both systolic (+dP/dt, LVDP, LVSP) and diastolic functions
Author Response
Reviewer 2
Magdalena et al report the effect of novel molecule RNS60 containing charge stabilized nanostructures on “cardioprotection” during myocardial hypoxia and cardioplegia in mice/rat models. This is a well-done study with appropriate control demonstrating that RNS60 decreased the hypoxia induced myocardial injury through studying changes in ECG, Troponin T and CK levels in mice models and had a cardioprotective effect during cardioplegia/hypothermia in rat models.
I would suggest the following minor revisions/grammatical errors.
Minor comments:
- Authors state “It was had been shown earlier in multiple disease models, in preclinical in vitro and in vivo studies, that RNS60 has broad anti-inflammatory and cytoprotective effects” – NEED reference
Response: We are grateful for the comments on our manuscript. Response: Grammar corrections have been made, references added.
- Incorrect sentence especially after “what”; break up and reword – “It was previously found by Ogino and Katayama that rapid washout of purine precursors at reperfusion, did not provide sub- strates for nucleotide synthesis in the heart what is linked to problems with the restoration of contractile function”
Response: Grammar corrections have been made.
- The second approach to estimate the efficiency of cardioplegic solutions is the meas- uring of the myocardial energy-rich phosphates in the heart homogenates. -àchange to “is the measurement of”
Response: Grammar corrections have been made.
- Again incorrect sentence – “It was previously checked that ATP con- centration is 30% lower in the failing heart what is in the opposite to RNS60 treatmentwhich had a positive influence on the ATP content”
Response: Grammar corrections have been made.
- Suggest rewording “initial” to baseline – “Post-reperfusion ATP levels were 62% and 89% of the initial”
Response: Grammar corrections have been made.
- Again the sentence reads incorrectly and suggest breaking down or using appropriate punctuations; “In our study, all hearts recovered mechanical function after 4 h of ischemia but consistent with improved energy status of the heart both systolic (+dP/dt, LVDP, LVSP) and diastolic functions
Response: Grammar corrections have been made.
Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
All concerns from this reviewer have been addressed in the revised manuscript.
