Reviewer's report
Title:Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics
of the liver
Version: 1Date:15 May 2009
Reviewer: Martin Hennenberg
Reviewer's report:
In the current manuscript, Halverscheid et al. tested the effects of PDE5
inhibitors on intrahepatic microcirculation of normal rats. Hepatic blood flow
regulation is of particular importance for portal hypertension in liver cirrhosis. Due
to the lack of sufficient therapeutic options, complications of portal hypertension
are still frequent and highly life-threatening in patients with cirrhosis. Therefore,
new therapies are urgently required. The authors assume that their current
results obtained from non-cirrhotic rats may provide the basis for subsequent
investigations in animal models of cirrhosis with portal hypertension.
To my opionion, the current manuscript of Halverscheid et al. should absolutely
not be regarded for publication in ?BMC Gastroenterology?.
Major points:
There are already at least 2 publications describing the effects of sildenafil in rats
with experimentally-induced cirrhosis (Ghali-Ghoul et al 2007;
Tahseldar-Roumieh et al 2006) ! These authors concluded that PDE5 inhibitors
are unsuitable for therapies in cirrhosis (e.g. for portal hypertension), since they
severely aggravate extrahepatic vasodilation ! Even 3 authors (Clemmesen et al
2008; Lee et al 2008;Thiesson et al 2005) investigated the hemodynamic effects
of sildenafil in patients with cirrhosis. These studies confirmed the aggravation of
extrahepatic vasodilation for the human setting, and did not reveal any beneficial
porto-hypotensive effect. However, only one of these studies is cited and
discussed in the current manuscript. With this background, the current
manuscript appears totally superfluous, as different studies already suggested
that the use of PDE5 inhibitors in cirrhotic patients and animals may be
disappointing.
Although the NO/cGMP system is investigated as a mediator and possible
therapeutic target in portal hypertension since almost 2 decades, absolutely none
NO/cGMP-based or ?targeting therapies emerged to the clinical use to date ! To
my opinion, any NO/cGMP-research in the context of portal hypertension is
therefore superfluous, and only led to success with regard to the carreers of
clinical scientist so far but not to new therapies. As currently available therapies
for complications of portal hypertension target vasoconstrictors and their direct
effectors, research should to my opinion concentrate on vasoconstrictor systems
in cirrhosis instead on NO/cGMP if promising results and new therapies are
desired in future.
From another point of view, it remains unclear to me, why the authors conclude
the need of studies in animal models of cirrhosis, but do not provide them. As
stated by the authors, their results can not answer the important questions
associated with their work (p. 15). In such a case, they should prepare and
submit a manuscript when having finished their studies.
Reviewer's report
Title:Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics
of the liver
Version: 1Date:15 May 2009
Reviewer: Martin Hennenberg
Reviewer's report:
In the current manuscript, Halverscheid et al. tested the effects of PDE5
inhibitors on intrahepatic microcirculation of normal rats. Hepatic blood flow
regulation is of particular importance for portal hypertension in liver cirrhosis. Due
to the lack of sufficient therapeutic options, complications of portal hypertension
are still frequent and highly life-threatening in patients with cirrhosis. Therefore,
new therapies are urgently required. The authors assume that their current
results obtained from non-cirrhotic rats may provide the basis for subsequent
investigations in animal models of cirrhosis with portal hypertension.
To my opionion, the current manuscript of Halverscheid et al. should absolutely
not be regarded for publication in ?BMC Gastroenterology?.
Major points:
There are already at least 2 publications describing the effects of sildenafil in rats
with experimentally-induced cirrhosis (Ghali-Ghoul et al 2007;
Tahseldar-Roumieh et al 2006) ! These authors concluded that PDE5 inhibitors
are unsuitable for therapies in cirrhosis (e.g. for portal hypertension), since they
severely aggravate extrahepatic vasodilation ! Even 3 authors (Clemmesen et al
2008; Lee et al 2008;Thiesson et al 2005) investigated the hemodynamic effects
of sildenafil in patients with cirrhosis. These studies confirmed the aggravation of
extrahepatic vasodilation for the human setting, and did not reveal any beneficial
porto-hypotensive effect. However, only one of these studies is cited and
discussed in the current manuscript. With this background, the current
manuscript appears totally superfluous, as different studies already suggested
that the use of PDE5 inhibitors in cirrhotic patients and animals may be
disappointing.
Although the NO/cGMP system is investigated as a mediator and possible
therapeutic target in portal hypertension since almost 2 decades, absolutely none
NO/cGMP-based or ?targeting therapies emerged to the clinical use to date ! To
my opinion, any NO/cGMP-research in the context of portal hypertension is
therefore superfluous, and only led to success with regard to the carreers of
clinical scientist so far but not to new therapies. As currently available therapies
for complications of portal hypertension target vasoconstrictors and their direct
effectors, research should to my opinion concentrate on vasoconstrictor systems
in cirrhosis instead on NO/cGMP if promising results and new therapies are
desired in future.
From another point of view, it remains unclear to me, why the authors conclude
the need of studies in animal models of cirrhosis, but do not provide them. As
stated by the authors, their results can not answer the important questions
associated with their work (p. 15). In such a case, they should prepare and
submit a manuscript when having finished their studies.
Please review this paper.
user
Reviewer's report
Title:Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics
of the liver
Version: 1Date:15 May 2009
Reviewer: Martin Hennenberg
Reviewer's report:
In the current manuscript, Halverscheid et al. tested the effects of PDE5
inhibitors on intrahepatic microcirculation of normal rats. Hepatic blood flow
regulation is of particular importance for portal hypertension in liver cirrhosis. Due
to the lack of sufficient therapeutic options, complications of portal hypertension
are still frequent and highly life-threatening in patients with cirrhosis. Therefore,
new therapies are urgently required. The authors assume that their current
results obtained from non-cirrhotic rats may provide the basis for subsequent
investigations in animal models of cirrhosis with portal hypertension.
To my opionion, the current manuscript of Halverscheid et al. should absolutely
not be regarded for publication in ?BMC Gastroenterology?.
Major points:
There are already at least 2 publications describing the effects of sildenafil in rats
with experimentally-induced cirrhosis (Ghali-Ghoul et al 2007;
Tahseldar-Roumieh et al 2006) ! These authors concluded that PDE5 inhibitors
are unsuitable for therapies in cirrhosis (e.g. for portal hypertension), since they
severely aggravate extrahepatic vasodilation ! Even 3 authors (Clemmesen et al
2008; Lee et al 2008;Thiesson et al 2005) investigated the hemodynamic effects
of sildenafil in patients with cirrhosis. These studies confirmed the aggravation of
extrahepatic vasodilation for the human setting, and did not reveal any beneficial
porto-hypotensive effect. However, only one of these studies is cited and
discussed in the current manuscript. With this background, the current
manuscript appears totally superfluous, as different studies already suggested
that the use of PDE5 inhibitors in cirrhotic patients and animals may be
disappointing.
Although the NO/cGMP system is investigated as a mediator and possible
therapeutic target in portal hypertension since almost 2 decades, absolutely none
NO/cGMP-based or ?targeting therapies emerged to the clinical use to date ! To
my opinion, any NO/cGMP-research in the context of portal hypertension is
therefore superfluous, and only led to success with regard to the carreers of
clinical scientist so far but not to new therapies. As currently available therapies
for complications of portal hypertension target vasoconstrictors and their direct
effectors, research should to my opinion concentrate on vasoconstrictor systems
in cirrhosis instead on NO/cGMP if promising results and new therapies are
desired in future.
From another point of view, it remains unclear to me, why the authors conclude
the need of studies in animal models of cirrhosis, but do not provide them. As
stated by the authors, their results can not answer the important questions
associated with their work (p. 15). In such a case, they should prepare and
submit a manuscript when having finished their studies.
assistant