Reviewer's report
Title:Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics
of the liver
Version: 3Date:11 August 2009
Reviewer: Martin Hennenberg
Reviewer's report:
Comments:
Based on the reviewer comments, the authors performed changes in the
manuscript and of the presentation of their data. Indeed, the manuscript and the
presentation of the data has been improved. As explained by the authors, the
discrepant findings of different authors and for different substances may raise a
requirement of further investigations of the effects of PDE5 inhibitors on liver
hemodynamics and/or portal hypertension. However, some concerns with regard
to the necessity of the study, and with the missing citations may still remain.
It remains hard to understand why the authors argue that such studies in
non-cirrhotic animals are required before starting clinical trials, although they
already performed studies in patients with cirrhosis and portal hypertension.
Thus, in the introduction the authors explain that the current study is based on
findings obtained from studies patients with cirrhosis, while the discussion leads
to the final conclusion that the current animal study raises the need of further
studies in patients with cirrhosis.
With regard to the other existing studies performed with PDE5 inhibitors in animal
models of cirrhosis, it is right that these did not deal with hepatic hemodynamics.
However, citation in the current manuscript may be useful to underline that
extrahepatic hemodynamic effects of PDE5 inhibitors may strongly dependent on
the dose and the mode of application, as this represents an important conclusion
made by the authors of the current study (although it is not the major conclusion).
As the effects of PDE5 inhibitors on hemodynamics in the liver and in cirrhosis
are poorly understood and discussed controversely, the current study may
represent a further contribution to this discussion, which may be appreciated by
publication of the data.
Minor points:
References should be checked again. Some confusion exists, as the paper of
Colle et al. is mentioned as reference 36 in the comments, but as number 41 in
the manuscript.
Likewise, all doses and their spelling should be checked again for correctness. In
the comments, the authors mention ?1000 or 1.000 microgram/kg? within one
sentence, but regard them as different.
Reviewer's report
Title:Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics
of the liver
Version: 3Date:11 August 2009
Reviewer: Martin Hennenberg
Reviewer's report:
Comments:
Based on the reviewer comments, the authors performed changes in the
manuscript and of the presentation of their data. Indeed, the manuscript and the
presentation of the data has been improved. As explained by the authors, the
discrepant findings of different authors and for different substances may raise a
requirement of further investigations of the effects of PDE5 inhibitors on liver
hemodynamics and/or portal hypertension. However, some concerns with regard
to the necessity of the study, and with the missing citations may still remain.
It remains hard to understand why the authors argue that such studies in
non-cirrhotic animals are required before starting clinical trials, although they
already performed studies in patients with cirrhosis and portal hypertension.
Thus, in the introduction the authors explain that the current study is based on
findings obtained from studies patients with cirrhosis, while the discussion leads
to the final conclusion that the current animal study raises the need of further
studies in patients with cirrhosis.
With regard to the other existing studies performed with PDE5 inhibitors in animal
models of cirrhosis, it is right that these did not deal with hepatic hemodynamics.
However, citation in the current manuscript may be useful to underline that
extrahepatic hemodynamic effects of PDE5 inhibitors may strongly dependent on
the dose and the mode of application, as this represents an important conclusion
made by the authors of the current study (although it is not the major conclusion).
As the effects of PDE5 inhibitors on hemodynamics in the liver and in cirrhosis
are poorly understood and discussed controversely, the current study may
represent a further contribution to this discussion, which may be appreciated by
publication of the data.
Minor points:
References should be checked again. Some confusion exists, as the paper of
Colle et al. is mentioned as reference 36 in the comments, but as number 41 in
the manuscript.
Likewise, all doses and their spelling should be checked again for correctness. In
the comments, the authors mention ?1000 or 1.000 microgram/kg? within one
sentence, but regard them as different.
Please review this paper.
user
Reviewer's report
Title:Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics
of the liver
Version: 3Date:11 August 2009
Reviewer: Martin Hennenberg
Reviewer's report:
Comments:
Based on the reviewer comments, the authors performed changes in the
manuscript and of the presentation of their data. Indeed, the manuscript and the
presentation of the data has been improved. As explained by the authors, the
discrepant findings of different authors and for different substances may raise a
requirement of further investigations of the effects of PDE5 inhibitors on liver
hemodynamics and/or portal hypertension. However, some concerns with regard
to the necessity of the study, and with the missing citations may still remain.
It remains hard to understand why the authors argue that such studies in
non-cirrhotic animals are required before starting clinical trials, although they
already performed studies in patients with cirrhosis and portal hypertension.
Thus, in the introduction the authors explain that the current study is based on
findings obtained from studies patients with cirrhosis, while the discussion leads
to the final conclusion that the current animal study raises the need of further
studies in patients with cirrhosis.
With regard to the other existing studies performed with PDE5 inhibitors in animal
models of cirrhosis, it is right that these did not deal with hepatic hemodynamics.
However, citation in the current manuscript may be useful to underline that
extrahepatic hemodynamic effects of PDE5 inhibitors may strongly dependent on
the dose and the mode of application, as this represents an important conclusion
made by the authors of the current study (although it is not the major conclusion).
As the effects of PDE5 inhibitors on hemodynamics in the liver and in cirrhosis
are poorly understood and discussed controversely, the current study may
represent a further contribution to this discussion, which may be appreciated by
publication of the data.
Minor points:
References should be checked again. Some confusion exists, as the paper of
Colle et al. is mentioned as reference 36 in the comments, but as number 41 in
the manuscript.
Likewise, all doses and their spelling should be checked again for correctness. In
the comments, the authors mention ?1000 or 1.000 microgram/kg? within one
sentence, but regard them as different.
assistant