Reviewer's report
Title:Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics
of the liver
Version: 1Date:21 May 2009
Reviewer: Han-Chieh Lin
Reviewer's report:
Major points
1. -Recently, phosphodiesterase-5 (PDE-5) inhibitor has been studied by
different investigators to improve pulmonary hypertension in cirrhotic patients
with primary pulmonary hypertension and to decrease portal pressure in cirrhotic
patients with portal hypertension. A dys-regulation of hepatic NO-cGMP system
due to over-expression of hepatic PDE-5 has been observed in cirrhotic patients
and animals. Thus, the hemodynamic effects of PDE-5 inhibitors should be
explored in cirrhotic animals. However, the current study only performed in
non-cirrhotic rats. Moreover, it is more important to explore the mechanistic
details of PDE-5 inhibitors in portal hypertension. Unfortunately, this study failed
to do so. In fact, both acute and chronic hemodynamic and mechanism of
different PDE-5 inhibitors had already been explored in the past [Aliment
Pharmacol Ther 2005;23:121-8; Liver Int 2004;24:63-8; Eur J Pharmacol
2007;572:49-56]. Accordingly, the current study lacks of originality.
2 Regarding methodology
-How were the doses of sildenafil and vardenafil chosen?
-How can authors measure the portal venous pressure (by cannulation of portal
vein) and portal venous blood flow (by ultrasound flow probes) at the same time?
In general, the cannulation of portal vein may interfere with the measurement of
blood flow with ultrasound flow probes at the same location.
Minor points
-The formula to calculate fractional liver flow (portal venous + hepatic arterial
blood flow/cardiac output = proportion of cardiac output passing through the liver)
should move to “Method”.
-The sentence “These data support the interpretation that PDE-5 inhibitors at low
concentration have distinct effects on the hemodynamics of the liver” is not clear.
-Most of the description in discussion is focusing on the role of PDE-5 inhibitor in
cirrhosis and portal hypertension. Nonetheless, the current study was only
performed in normal rats.
-Duplicated references: reference 34 & reference 50 are the same paper
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
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:21 May 2009
Reviewer: Han-Chieh Lin
Reviewer's report:
Major points
1. -Recently, phosphodiesterase-5 (PDE-5) inhibitor has been studied by
different investigators to improve pulmonary hypertension in cirrhotic patients
with primary pulmonary hypertension and to decrease portal pressure in cirrhotic
patients with portal hypertension. A dys-regulation of hepatic NO-cGMP system
due to over-expression of hepatic PDE-5 has been observed in cirrhotic patients
and animals. Thus, the hemodynamic effects of PDE-5 inhibitors should be
explored in cirrhotic animals. However, the current study only performed in
non-cirrhotic rats. Moreover, it is more important to explore the mechanistic
details of PDE-5 inhibitors in portal hypertension. Unfortunately, this study failed
to do so. In fact, both acute and chronic hemodynamic and mechanism of
different PDE-5 inhibitors had already been explored in the past [Aliment
Pharmacol Ther 2005;23:121-8; Liver Int 2004;24:63-8; Eur J Pharmacol
2007;572:49-56]. Accordingly, the current study lacks of originality.
2 Regarding methodology
-How were the doses of sildenafil and vardenafil chosen?
-How can authors measure the portal venous pressure (by cannulation of portal
vein) and portal venous blood flow (by ultrasound flow probes) at the same time?
In general, the cannulation of portal vein may interfere with the measurement of
blood flow with ultrasound flow probes at the same location.
Minor points
-The formula to calculate fractional liver flow (portal venous + hepatic arterial
blood flow/cardiac output = proportion of cardiac output passing through the liver)
should move to “Method”.
-The sentence “These data support the interpretation that PDE-5 inhibitors at low
concentration have distinct effects on the hemodynamics of the liver” is not clear.
-Most of the description in discussion is focusing on the role of PDE-5 inhibitor in
cirrhosis and portal hypertension. Nonetheless, the current study was only
performed in normal rats.
-Duplicated references: reference 34 & reference 50 are the same paper
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
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:21 May 2009
Reviewer: Han-Chieh Lin
Reviewer's report:
Major points
1. -Recently, phosphodiesterase-5 (PDE-5) inhibitor has been studied by
different investigators to improve pulmonary hypertension in cirrhotic patients
with primary pulmonary hypertension and to decrease portal pressure in cirrhotic
patients with portal hypertension. A dys-regulation of hepatic NO-cGMP system
due to over-expression of hepatic PDE-5 has been observed in cirrhotic patients
and animals. Thus, the hemodynamic effects of PDE-5 inhibitors should be
explored in cirrhotic animals. However, the current study only performed in
non-cirrhotic rats. Moreover, it is more important to explore the mechanistic
details of PDE-5 inhibitors in portal hypertension. Unfortunately, this study failed
to do so. In fact, both acute and chronic hemodynamic and mechanism of
different PDE-5 inhibitors had already been explored in the past [Aliment
Pharmacol Ther 2005;23:121-8; Liver Int 2004;24:63-8; Eur J Pharmacol
2007;572:49-56]. Accordingly, the current study lacks of originality.
2 Regarding methodology
-How were the doses of sildenafil and vardenafil chosen?
-How can authors measure the portal venous pressure (by cannulation of portal
vein) and portal venous blood flow (by ultrasound flow probes) at the same time?
In general, the cannulation of portal vein may interfere with the measurement of
blood flow with ultrasound flow probes at the same location.
Minor points
-The formula to calculate fractional liver flow (portal venous + hepatic arterial
blood flow/cardiac output = proportion of cardiac output passing through the liver)
should move to “Method”.
-The sentence “These data support the interpretation that PDE-5 inhibitors at low
concentration have distinct effects on the hemodynamics of the liver” is not clear.
-Most of the description in discussion is focusing on the role of PDE-5 inhibitor in
cirrhosis and portal hypertension. Nonetheless, the current study was only
performed in normal rats.
-Duplicated references: reference 34 & reference 50 are the same paper
Level of interest: An article of limited interest
Quality of written English: Needs some language corrections before being
published
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.
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