The Hatter Institute of Cardiology,
UCL Hospitals & Medical School,
London, UK
To the Editor:
We read with great interest the article by Tomai et
al1 on the role of
What the authors fail to mention in their discussion is the fact
that phentolamine, independent of its
References
1.
Tomai F, Crea F, Gaspardone A, Versaci F, Ghini AS, De
Paulis R, Chiariello L, Gioffrè PA. Phentolamine prevents
adaptation to ischemia during coronary angioplasty:
role of
2.
Tomai F, Crea F, Gaspardone F, Versaci R, De Paulis R,
Polisca P, Chiariello L, Gioffrè PA. Effects of A1
adenosine receptor blockade by bamiphylline on ischaemic
preconditioning during coronary angioplasty. Eur
Heart J. 1996;17:846–853.
3.
Tomai F, Crea F, Gaspardone A, Versaci F, De Paulis R,
Penta de Peppo A, Chiariello L, Gioffrè PA. Ischemic
preconditioning during coronary angioplasty is prevented by
glibenclamide, a selective ATP-sensitive K+ channel
blocker. Circulation. 1994;90:700–705.
4.
Plant TD, Henquin JC. Phentolamine and
yohimbine inhibit ATP sensitive K+ channels in mouse
pancreatic ß-cells. Br J Pharmacol. 1990;101:115–120.[Medline]
[Order article via Infotrieve]
5.
McPherson GA, Angus JA. Phentolamine and
structurally related compounds selectively antagonize the vascular
actions of the K+ channel opener, cromakalim.
Br J Pharmacol. 1989;97:941–949.[Medline]
[Order article via Infotrieve]
6.
Murray MA, Boyle JP, Small RC. Cromakalim-induced
relaxation of guinea-pig isolated trachealis: antagonism by
glibenclamide and by phentolamine. Br J
Pharmacol. 1989;98:865–874.[Medline]
[Order article via Infotrieve]
7.
Wilde AAM, Veldkamp MW, van Ginneken ACG, Opthof T.
Phentolamine blocks ATP sensitive potassium channels in cardiac
ventricular cells. Cardiovasc Res. 1994;28:847–850.
8.
Gross GJ, Mei DA, Schultz JJ, Mizumura T. Criteria for
a mediator or effector of myocardial preconditioning: do
KATP channels meet the requirements? Basic Res
Cardiol. 1996;91:31–34.[Medline]
[Order article via Infotrieve]
9.
Speechly-Dick ME, Grover GJ, Yellon DM. Does
ischemic preconditioning in the human involve protein kinase C
and the ATP-dependent K+ channel? Studies of contractile
function after simulated ischemia in an atrial in vitro model.
Circ Res. 1995;77:1030–1035.
10.
Cleveland JC, Meldrum DR, Cain BS, Banerjee A, Harken
AH. Oral sulfonylurea hypoglycemic agents prevent ischemic
preconditioning in human myocardium.
Circulation. 1997;96:29–32.
Divisione di Cardiochirurgia,
Università di Roma Tor Vergata,
European Hospital,
Rome, Italy
In the setting of coronary angioplasty,
ATP-sensitive potassium (KATP) channels play a
pivotal role in ischemic preconditioning and probably
represent the final mediator of this
phenomenon.1 Because phentolamine has
been shown to act directly on KATP channels in
experimental models,2 3 4 5 Dr Yellon and colleagues
correctly suggest that in our study6
phentolamine might have abolished the adaptation to
ischemia observed during sequential coronary balloon
inflations not only by blockade of
References
1.
Tomai F, Crea F, Gaspardone A, Versaci F, De
Paulis R, Penta de Peppo A, Chiariello L, Gioffrè PA.
Ischemic preconditioning during coronary angioplasty is
prevented by glibenclamide, a selective ATP-sensitive K+
channel blocker. Circulation. 1994;90:700–705.
2.
Plant TD, Henquin JC. Phentolamine and
yohimbine inhibit ATP sensitive K+ channels in mouse
pancreatic ß-cells. Br J Pharmacol. 1990;101:115–120.
3.
McPherson GA, Angus JA. Phentolamine and
structurally related compounds selectively antagonize the vascular
actions of the K+ channel opener, cromakalim.
Br J Pharmacol. 1989;97:941–949.
4.
Murray MA, Boyle JP, Small RC. Cromakalim-induced
relaxation of guinea-pig isolated trachealis: antagonism by
glibenclamide and by phentolamine. Br J
Pharmacol. 1989;98:865–874.
5.
Wilde AA, Veldkamp MW, van Ginneken ACG, Opthof T.
Phentolamine blocks ATP sensitive potassium channels in cardiac
ventricular cells. Cardiovasc Res. 1994;28:847–850.
6.
Tomai F, Crea F, Gaspardone A, Versaci F, Ghini AS, De
Paulis R, Chiariello L, Gioffrè PA. Phentolamine prevents
adaptation to ischemia during coronary angioplasty:
role of
© 1998 American Heart Association, Inc.
Correspondence
Phentolamine and Preconditioning During Coronary Angioplasty
-adrenergic receptors in
ischemic preconditioning during coronary angioplasty.
They provide evidence that pretreatment with phentolamine, a
nonselective -adrenoceptor blocking agent, abolishes the adaptation
to myocardial ischemia during sequential coronary
balloon inflations. The authors conclude a role for -adrenergic
receptors in mediating ischemic preconditioning in this model.
This work extends previous work by the same group implicating a role
for adenosine A1
receptors2 and the ATP-sensitive potassium
channels (KATP)3 in
ischemic preconditioning using the same model. -blocking properties,
has been shown to block KATP channels in
insulin-producing cells,4 in
vascular5 and nonvascular smooth muscle
cells,6 and more recently, in cardiac
ventricular myocytes.7 The
involvement of KATP channels in the mechanism of
ischemic preconditioning has been demonstrated in a number of
animal models,8 as well as in isolated human
atrial trabeculae.9 10 Furthermore,
Tomai et al3 have previously shown that blockade
of KATP channels abolishes the myocardial
adaptation observed during sequential coronary balloon
inflations. It is therefore not possible to draw any conclusions about
the exact mode of action of phentolamine and consequently about
the mechanisms of ischemic preconditioning during
coronary angioplasty from the presented
data.1 Although, as the authors suggest, the
-blocking properties of phentolamine may be responsible for
the loss of adaptation to ischemia, their observations can also
be explained by blockade of KATP channels by
phentolamine. Thus, while the findings of this study can be
appreciated, one has to bear in mind the confounding effect of the
multiple actions of this agent. -adrenergic receptors in ischemic preconditioning.
Circulation. 1997;96:2171–2177.
Response
-adrenergic receptors but also
via blockade of KATP channels. This hypothesis is
attractive; however, we have some concerns about this possible
interpretation of our results. First, all studies showing blockade of
KATP channels by phentolamine
independently of its -blocking properties were performed in
vitro.2 3 4 5 To the best of our knowledge, an in
vivo demonstration of such a mechanism is still lacking. Second, the
doses of phentolamine able to block KATP
channels in vitro are far higher than those used in our study. In fact,
in the majority of in vitro studies, phentolamine concentration
needed to block KATP channels was 
100
µmol/L, whereas in our study the estimated plasma concentration was
0.2 to 0.4 µmol/L. Indeed, we used the lowest
phentolamine dose able to reduce systolic
arterial pressure by 10 mm Hg or to increase heart
rate by 10 bpm (effects obviously mediated by -adrenergic receptor
blockade and not by KATP channel blockade, which
would have had an opposite effect), in the absence of any significant
coronary blood flow velocity changes. Thus, it is likely that
the loss of adaptation to ischemia observed in our study was
mainly accounted for by -adrenergic receptor blockade by
phentolamine. -adrenergic receptors in ischemic
preconditioning. Circulation. 1997;96:2171–2177.
This article has been cited by other articles:
 |
|
 |
|
  E. M. Carvalho, E. A Gabriel, and T. A Salerno Pulmonary Protection During Cardiac Surgery: Systematic Literature Review Asian Cardiovasc Thorac Ann, December 1, 2008; 16(6): 503 - 507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Huang, T. Yao, W. Wang, D. Zhu, W. Zhang, H. Chen, and W. Fu Continuous ultrafiltration attenuates the pulmonary injury that follows open heart surgery with cardiopulmonary bypass Ann. Thorac. Surg., July 1, 2003; 76(1): 136 - 140. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||