Reviewer's report
Title:Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics
of the liver
Version: 1Date:18 May 2009
Reviewer: Toshishige Shibamoto
Reviewer's report:
This is a basic in-vivo study that determined effects of two kinds of
phosphodiesterase-5 (PDE-5) inhibitors (1-100 microg/kg) on hepatic circulation
as well as systemic circulation of rats. The authors demonstrated that the dose of
10 #g/kg PDE-5 inhibitors reduce most effectively portal and hepatic arterial
resistances. The experiment seems to be well done, but presentation of the data
is not adequate. However, this study may provide useful data for clinical
application of PDE-5 inhibitors in the cirrhotic patients.
1. The authors showed that heart rate did not change and remained constant
(abstract and results). The reviewer expected that heart rate should have
increased in response to a fall of arterial pressure at least at the early stage after
injection of drugs due to the arterial baroreceptor reflex. The authors should
check more carefully the heart rate data again. If heart rate did not change, the
authors should explain why it did not change. Possible increased nitric oxide
production caused by PDE-5 inhibitors might affect the arterial baroreceptor
reflex.
2. The mean values of cardiac out of 104.1-127.5 ml/min (Table) seems to be
higher than that were reported by other investigators (Exp Physiol.
2005;90(4):627-34; Shock. 2008;29(6):733-9). Te authors should provide more
detail description of the methods of thermodilution cardiac output measurement
in this study; the intracatheter dead space; injection volume. The reviewer is
afraid that the high values of cardiac output may be ascribed to a large dead
space, in which the saline was warmed up to 37 degree C, resulting in
overestimation of cardiac output.
3. In the results section, hepatic arterial resistance was not designated (Pgae 8,
last paragraph). The reviewer is familiar with the presentation of the data as
means ± standard error (SE) or standard deviation (SD), but not 95% confidence
intervals. The SE or SD is preferable.
4. Page 9, line 18; “The initial drop of MAP and SVR was presumably due to a
transiently higher drug”. The reviewer does not agree with the authors that these
responses are non-specific and dependent on high concentrations of the solutes.
The initial drop could be due to PDE-5 inhibitor-induced vasodilatation but not
high concentrations of the drugs. The author should show the reason for your
description. Furthermore, the author should show the results of other doses of
the drugs, 1 and 100 microg/kg, simultaneously in the Figures 1 and 2, using
different symbols. This seems important for the authors to conclude that the most
effective dose is 10 microg/kg.
5. Page 11, line 3. This study is not the first experiment on the effect of PDE-5
inhibitor on hepatic (portal pressure) and systemic circulation in anesthetized
rats. References 36 is the first.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Reviewer's report
Title:Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics
of the liver
Version: 1Date:18 May 2009
Reviewer: Toshishige Shibamoto
Reviewer's report:
This is a basic in-vivo study that determined effects of two kinds of
phosphodiesterase-5 (PDE-5) inhibitors (1-100 microg/kg) on hepatic circulation
as well as systemic circulation of rats. The authors demonstrated that the dose of
10 #g/kg PDE-5 inhibitors reduce most effectively portal and hepatic arterial
resistances. The experiment seems to be well done, but presentation of the data
is not adequate. However, this study may provide useful data for clinical
application of PDE-5 inhibitors in the cirrhotic patients.
1. The authors showed that heart rate did not change and remained constant
(abstract and results). The reviewer expected that heart rate should have
increased in response to a fall of arterial pressure at least at the early stage after
injection of drugs due to the arterial baroreceptor reflex. The authors should
check more carefully the heart rate data again. If heart rate did not change, the
authors should explain why it did not change. Possible increased nitric oxide
production caused by PDE-5 inhibitors might affect the arterial baroreceptor
reflex.
2. The mean values of cardiac out of 104.1-127.5 ml/min (Table) seems to be
higher than that were reported by other investigators (Exp Physiol.
2005;90(4):627-34; Shock. 2008;29(6):733-9). Te authors should provide more
detail description of the methods of thermodilution cardiac output measurement
in this study; the intracatheter dead space; injection volume. The reviewer is
afraid that the high values of cardiac output may be ascribed to a large dead
space, in which the saline was warmed up to 37 degree C, resulting in
overestimation of cardiac output.
3. In the results section, hepatic arterial resistance was not designated (Pgae 8,
last paragraph). The reviewer is familiar with the presentation of the data as
means ± standard error (SE) or standard deviation (SD), but not 95% confidence
intervals. The SE or SD is preferable.
4. Page 9, line 18; “The initial drop of MAP and SVR was presumably due to a
transiently higher drug”. The reviewer does not agree with the authors that these
responses are non-specific and dependent on high concentrations of the solutes.
The initial drop could be due to PDE-5 inhibitor-induced vasodilatation but not
high concentrations of the drugs. The author should show the reason for your
description. Furthermore, the author should show the results of other doses of
the drugs, 1 and 100 microg/kg, simultaneously in the Figures 1 and 2, using
different symbols. This seems important for the authors to conclude that the most
effective dose is 10 microg/kg.
5. Page 11, line 3. This study is not the first experiment on the effect of PDE-5
inhibitor on hepatic (portal pressure) and systemic circulation in anesthetized
rats. References 36 is the first.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
Please review this paper.
user
Reviewer's report
Title:Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics
of the liver
Version: 1Date:18 May 2009
Reviewer: Toshishige Shibamoto
Reviewer's report:
This is a basic in-vivo study that determined effects of two kinds of
phosphodiesterase-5 (PDE-5) inhibitors (1-100 microg/kg) on hepatic circulation
as well as systemic circulation of rats. The authors demonstrated that the dose of
10 #g/kg PDE-5 inhibitors reduce most effectively portal and hepatic arterial
resistances. The experiment seems to be well done, but presentation of the data
is not adequate. However, this study may provide useful data for clinical
application of PDE-5 inhibitors in the cirrhotic patients.
1. The authors showed that heart rate did not change and remained constant
(abstract and results). The reviewer expected that heart rate should have
increased in response to a fall of arterial pressure at least at the early stage after
injection of drugs due to the arterial baroreceptor reflex. The authors should
check more carefully the heart rate data again. If heart rate did not change, the
authors should explain why it did not change. Possible increased nitric oxide
production caused by PDE-5 inhibitors might affect the arterial baroreceptor
reflex.
2. The mean values of cardiac out of 104.1-127.5 ml/min (Table) seems to be
higher than that were reported by other investigators (Exp Physiol.
2005;90(4):627-34; Shock. 2008;29(6):733-9). Te authors should provide more
detail description of the methods of thermodilution cardiac output measurement
in this study; the intracatheter dead space; injection volume. The reviewer is
afraid that the high values of cardiac output may be ascribed to a large dead
space, in which the saline was warmed up to 37 degree C, resulting in
overestimation of cardiac output.
3. In the results section, hepatic arterial resistance was not designated (Pgae 8,
last paragraph). The reviewer is familiar with the presentation of the data as
means ± standard error (SE) or standard deviation (SD), but not 95% confidence
intervals. The SE or SD is preferable.
4. Page 9, line 18; “The initial drop of MAP and SVR was presumably due to a
transiently higher drug”. The reviewer does not agree with the authors that these
responses are non-specific and dependent on high concentrations of the solutes.
The initial drop could be due to PDE-5 inhibitor-induced vasodilatation but not
high concentrations of the drugs. The author should show the reason for your
description. Furthermore, the author should show the results of other doses of
the drugs, 1 and 100 microg/kg, simultaneously in the Figures 1 and 2, using
different symbols. This seems important for the authors to conclude that the most
effective dose is 10 microg/kg.
5. Page 11, line 3. This study is not the first experiment on the effect of PDE-5
inhibitor on hepatic (portal pressure) and systemic circulation in anesthetized
rats. References 36 is the first.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests.
assistant