Download 5.9.2006 Dear Mrs Selz, I hereby include a summary taken from my

EIDGENÖSSISCHE TECHNISCHE HOCHSCHULE LAUSANNE
POLITECNICO FEDERALE DI LOSANNA
SWISS FEDERAL INSTITUTE OF TECHNOLOGY LAUSANNE
LABORATORY OF HEMODYNAMICS AND
CARDIOVASCULAR TECHNOLOGY
ÉCOLE POLYTECHNIQUE
FÉDÉRALE DE LAUSANNE
BAT. AA-B
CH - 1015 Lausanne
Telephone: +41 21 693 83 43
Fax:
+41 21 693 86 60
e-mail: [email protected]
Novartis Stiftung für med.-biol.
Forschung - Ihr Gesuch Nr.
04A24
5.9.2006
Dear Mrs Selz,
I hereby include a summary taken from my PhD thesis which was recently and successfully
defended on the 19June 2006. It describes the different manuscripts we have prepared for
publication and two that have already been accepted for publication. We also take this
opportunity in thanking you for your support. We also give permission to you to publish this
on your homepage. I include the 2 accepted articles as well as attachments with your financial
support acknowledged in “Acknowledgements” at the end of the manuscript.
Yours sincerely
David Jegger, PhD
Summary
In this thesis we study ventricular-arterial coupling in rodents under the influence of arterial
stiffening and myocardial infarction (MI), combination of the two considered as a novel
cardiovascular research model for diseased hearts pumping against an aged, stiffened arterial
tree. The stiffened arterial tree yields isolated systolic hypertension and is obtained by
administration of vitamin D and nicotine (VDN). The investigation cardiac performance and
ventricular-arterial coupling using such a combined model (VDN/MI) is of particular
relevance to cardiac research, as cardiac disease in elderly often takes place in presence of a
atherosclerotic or stiff arterial tree. The thesis consists of an Introduction, 4 scientific papers
and a brief Conclusion.
The Introduction is an overview of the epidemiology of heart failure, structure and functional
changes that occur during MI and VDN, material and methods used in evaluating cardiac
function invasively and non-invasively (using trans-thoracic echocardiography, TTE),
methods for evaluating arterial function, and finally an overview of the interaction between
the heart and vessels.
Paper 1: This paper addresses the issue of the universality of the normalized time-varying
elastance curve. It is demonstrated that the waveform of the normalized time-varying
elastance curve (En(tn)) is qualitatively comparable between the control and MI hearts,
however, when En(tn) is compared quantitatively between the two groups, statistical
significance is found at the ejection phase and during diastole. These differences need to be
taken into account when assessing cardiac contractility based on a generalized En(tn) in
different animal models or in the human in different physiological or pathological states.
Paper 2: Using trans-thoracic echo (TTE), we were able to follow serial changes of cardiac
function post MI using two novel parameters, the myocardioal performance index (MPI) and
its ratio to left ventricular fractional shortening (LVFS/MPI), both indices being monitor
successfully and as efficiently as other classical TTE parameters. More so, LVFS/MPI
visually expressed better the serial modifications in cardiac function. Both MPI and
LVFS/MPI were correlated to the load-independent contractile parameter, PRSW, and to the
preload parameter, LVEDP, being thus pertinent in following preload changes post MI.
Finally, chamber remodeling post MI can successfully be followed due to the fact that ESV
and EDV both correlate to MPI and LVFS/MPI.
Paper 3: We studied hemodynamics, arterial function, cardiac function and ventricular-arterial
coupling in a rat model of reduced arterial compliance. The results show that arterial
stiffening after VDN treatment provokes important changes in vascular impedance and wave
reflections, leading to isolated systolic hypertension and LV hypertrophy, Ventricular-arterial
coupling was also altered. The effects are quantitatively similar to those of arterial stiffening
with age.
Paper 4: We studied changes in cardiac geometry, structure and function in response to MI in
control and VDN-treated (stiffened aorta) rats. The combined VDN/MI model showed the
largest compromise in cardiac structure and function and exhibited the strongest biochemical
signs of heart failure as compared to all other groups. The addition of MI on top of a raised
afterload, seems to have accelerated the progression of heart failure. Vascular alterations also
reflected well a model of ageing and calcification. This combined pathology model of failing
hearts in presence of a stiff arterial tree might be fruitful in better understanding the evolution
of disease and may help improving or developing novel treatment therapies.
The Conclusion chapter summarizes the findings of the thesis and brings into perspective their
importance and future relevance into cardiovascular research models.
Keywords: calcium, echocardiography, heart failure, hypertension, myocardial infarction.
Publications:
1. Jegger D, da Silva R, Lartaud I, Gaillard V, Tevaearai H, Jeanrenaud X, Nasratullah M,
von Segesser LK, Atkinson J, Stergiopulos N. A novel cardiovascular research model:
combined myocardial infarction and isolated systolic hypertension in rats. (submitted to
Circulation)
2. Jegger D, Mallik AS, Nasratullah M, Jeanrenaud X, Tevaearai H, Westerhof N, von
Segesser LK, Stergiopulos N. Evaluating the Effect of Heart Failure Post Myocardial
Infarction on the Normalised Time-Varying Elastance Curve. (submitted to JAP)
3. Jegger D, Di Gilio C, Lartaud I, Gaillard V, da Silva R, Tevaearai HT, von Segesser LK,
Atkinson J, Stergiopulos N. Mechanical properties and structure of carotid arteries in
hypervitaminosis D and nicotine treated rats. (manuscript in preparation for AJP)
4. Jegger D, da Silva R, Jeanrenaud X, Nasratullah M, Tevaearai HT, von Segesser LK,
Segers P, Gaillard V, Atkinson J, Lartaud I, Stergiopulos N. Ventricular-arterial coupling
analyzed by a conductance catheter in a rat model of reduced arterial compliance provoked
by hypervitaminosis D and nicotine. (accepted AJP)
5. Jegger D, Jeanrenaud X, Nasratullah M, Chassot P-G, Mallik A, Tevaearai HT, von
Segesser LK, Segers P, Stergiopulos N. Noninvasive Doppler-derived myocardial
performance index in rats with myocardial infarction: validation and correlation by
conductance catheter. Am J Physiol Heart Circ Physiol 2005 (accepted)