Peter Ferdinandy talks with
ScienceWatch.com and answers a few questions about
this month's Fast Breaking Paper in the field of
Pharmacology & Toxicology.
Article Title: Interaction of cardiovascular risk
factors with myocardial ischemia/reperfusion injury,
preconditioning, and postconditioning
Authors:
Ferdinandy,
P;Schulz, R;Baxter, GF
Journal: PHARMACOL REV
Volume: 59
Issue: 4
Page: 418-458
Year: DEC 2007
Univ Szeged, Dept Biochem, Cardiovasc Res Grp,
Pharmahungary Grp, H-6720 Szeged, Hungary
Univ Duisburg Gesamthsch, Inst Pathophysiol, Zentrum Innere
Med, Essen, Germany
(addresses have been truncated)
Why do you think your paper is highly
cited?
Our paper provided a new aspect of a more than 20-year-old research field,
i.e., the endogenous stress adaptation of the myocardium.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
Our review paper describes a synthesis of knowledge which accumulated over
the past decade and highlights a clinically very important, novel aspect of
the field, which was neglected by most of the opinion leaders for many
years. We are very happy that the paper is now highly cited. It was a long
way to go, but we are certain that our approach to this scientific field
will be recognized by scientists and the pharmaceutical/biotech industry
quite soon.
Would you summarize the significance of your paper in
layman's terms?
Ischemic heart disease (i.e., insufficient blood flow in the heart muscle
leading to myocardial infarction and heart failure) is the leading cause of
death in the industrialized world. The treatment of acute ischemic heart
disease has entered a new era where mortality can be approximately halved
by procedures which allow the rapid return of blood flow to the ischemic
zone of the myocardium, i.e., "reperfusion." Reperfusion, however, may lead
to further complications such as diminished cardiac contractile function
and arrhythmia.
"The aim of our review was to show
the potential for developing cardioprotective
drugs based on endogenous cardiac stress
adaptation and to review the evidence that
comorbidities and aging accompanying ischemic
heart disease modify responses to
ischemia/reperfusion and the cardioprotection
conferred by preconditioning and
postconditioning.."
Earlier pharmacological approaches to attenuate the consequences of
ischemia/reperfusion injury have been of limited experimental efficacy or
have failed to translate into useful clinical treatments. However, the
heart has been shown to possess a remarkable ability to adapt to
ischemia/reperfusion stress and it has been the focus of intense research.
"Ischemic preconditioning" is a well-described adaptive response in which
brief exposure to ischemia markedly enhances the ability of the heart to
withstand a subsequent ischemic injury. Moreover, brief cycles of
ischemia/reperfusion applied following a longer period of ischemia also
confer cardioprotection against the consequences of myocardial
ischemia/reperfusion, a phenomenon called "ischemic postconditioning." The
discovery of these two major forms of endogenous cardioprotective
mechanisms has encouraged the exploration of new ways to protect the
ischemic/reperfused myocardium, but still has not led to a translation into
clinical therapies.
Most experimental studies on cardioprotection have been undertaken in
animal models, in which ischemia/reperfusion is imposed in the absence of
other disease processes. However, ischemic heart disease in humans is a
complex disorder caused by or associated with known cardiovascular risk
factors, including hypertension, hyperlipidemia, diabetes, insulin
resistance, atherosclerosis, and heart failure; additionally, aging is an
important modifying condition. In these diseases and aging, the
pathological processes are associated with fundamental molecular
alterations that can potentially affect the development of
ischemia/reperfusion injury and adaptation processes per se and responses
to cardioprotective interventions.
The aim of our review was to show the potential for developing
cardioprotective drugs based on endogenous cardiac stress adaptation and to
review the evidence that comorbidities and aging accompanying ischemic
heart disease modify responses to ischemia/reperfusion and the
cardioprotection conferred by preconditioning and postconditioning.
We emphasized the critical need for more detailed and mechanistic
preclinical studies that examine cardioprotection, specifically in relation
to complicating disease states. These are now essential to maximize the
likelihood of successfully developing rational approaches to therapeutic
protection for the majority of patients with ischemic heart disease who are
aged and/or have modifying comorbid conditions.
How did you become involved in this research, and were
there any problems along the way?
I was inspired by the late Dr. Matyas Koltai of L'Institut Henri Beaufour,
Le Plessis Robinson, France, and Dr. Arpad Tosaki of the Department of
Pharmacology, Szeged Medical University, my mentors who introduced me into
cardiovascular research in the early '90s. At that time, research on
ischemic preconditioning was very new and hot. During the years 1995
through 1997, we had first shown that endogenous cardiac adaptation in
hypercholesterolemic and in nitrate-tolerant animals was not as effective
as in healthy animals. We knew that these were very important findings but
surprisingly, very few research groups got involved in this line of
research.
In 1998, we published a review which highlighted that preconditioning could
be a phenomenon that works only in healthy experimental animals, but we had
received very few citations. However, we continued to do follow-up on this
line and identified some cardioprotective pathways that are disrupted in
the presence of hyperlipidemia. In the meantime, we realized that more and
more research groups were becoming interested in this field. I realized, in
2007, that the time was right to write an extensive review in a
high-ranking journal in order to increase interest in this filed, and, in
2009, our review published in Pharmacological Reviews has been
selected as a "Fast Breaking Paper" by ScienceWatch.com
from Clarivate.
Where do you see your research leading in the
future?
As a scientist, my research group shall continue exploring the disruption
of cardioprotective signaling pathways in the presence of hyperlimidemia
and diabetes and identifying new therapeutic targets for potential drug
development. As an entrepreneur, PharmaHungary™ will develop new
animal models for preclinical pharmacology services and develop drugs that
protect the ischemic myocardium even in the presence of hyperlipidemia or
metabolic diseases such as diabetes. And this is where I see our research
leading, toward the identification of new drug targets and the development
of new cytoprotective drugs which are effective against ischemic heart (and
other organs) disease, even in the presence of major cardiovascular risk
factors.
Do you foresee any social or political implications for
your research?
If research on cardiac stress adaptation will follow the direction which we
have highlighted in this paper, more efficient drugs will be developed to
prevent and to treat ischemic heart disease, including myocardial
infarction, and the success rate of drug development in this field will
definitely be increased.
Peter Ferdinandy, M.D., Ph.D., M.B.A.
Professor of Biochemistry and Clinical Pharmacology
Cardiovascular Research Group (cardiovasc™)
Department of Biochemistry
University of Szeged
Szeged, Hungary
and
Chief Executive Officer
PharmaHungary™ Group
Szeged, Hungary Web ¦ Web