Track 14. Cardiovascular Mechanics 14.2. Cardiac Mechanics and Biology S277

cardiovascular variabilities demonstrates the disagreement with this specious hypothesis. Rather, human cardiovascular system exhibits plenty of rhythms, otherwise cardiac arrest will happen. In addition to the basic cardiac cycle, there are multi-scale rhythms that have quasi-periods of several seconds to a month or more. They spatially reflect the coupling of the cardiovascular system with other physiological systems. Our investigation to 24 hr. heart rate variability of health, coronary heart disease (CHD) and congestive heart failure (CHF) reveals close correlation of chaos detection in nonlinear characteristic via Volterra-Wiener series [2] and high frequency component, which is accepted as a mark of parasympathetic activity, in linear spectrum [3,4] of auto-regression model for normal (r=0.80, p =0.0000) and CHD (r=0.80, p=0.0000) groups, but not for CHF (r = 0.18, p = 0.049) group. Unlike detection rate, the noise limit of titration [5] did not show any circadian rhythms for all groups. Unexpected large noise limit found in CHF patients may acts as a particular index in clinical diagnosis. This result links nonlinear heartbeat dynamics to autonomic nervous system. Supported by NSFC No. 30370353, 30370529

References [1] McDonald A., Blood flow in arteries. Edward Arnold, London 1974. [2] Poon CS. Merrill CK., Nature 1997; 389: 492-495. [3] Akselrod S, Gordon D, Ubel FA, et al. Science 1981; 213: 220-222. [4] Task Force of the European Society of Cardiology and the North American

Society of Pacing and Electrophysiology. Circ. 1996; 93(5): 1043-1065. [5] Poon C.-S. and Barahona M., PNAS 2001; 98(13): 7107-7112.

7180 Th, 09:00-09:15 (P38) Cardiac function in growth hormone receptor knockout mice

A.K. Reddy 1 , C.J. Hartley 1 , E Huq 2, T.T. Pham 1,2, D. Amador-Noguez 2, M.L. Entman 1 , G.J. Darlington 2, G.E. Taffet 1,2. 1Department efMedicine, 2 Huffington Center on Aging, Baylor College of Medicine, Houston, Texas, USA

Growth hormone receptor knock out (GHR- / - ) mice are about 30% smaller in size, but live about 25-30% longer than their wild-type (WT) littermates. While the anabolic effects of GH/IGF-1 are well known, the effects of GH deficiency on cardiac function are not well characterized. We performed studies to see if altered cardiac function was a contributing factor to the longevity in these mice. We measured aortic and mitral flow velocities using 10MHz pulsed Doppler ultrasound and left ventricle (LV) pressure (baseline and post- dobutamine) using a RADI PressureWire catheter in 17 (7 GHR- / - and 10 WT) 4-month old mice. Mice were anesthetized with pentobarbital sodium given intraperitoneally (4 mg/ml, 10 ~tl/g BW in grams). Peak systolic velocity (cm/s) and E-peak velocity (cm/s) were obtained from Doppler signals. Maximum ±dP/dt (mmHg/s) and T (ms; time constant of -dP/dt) were calculated from the LV pressure signal. The results (mean±SE) show that GHR- / - mice have markedly decreased peak systolic velocity (76.2±3.5 vs. 86.9±3.0, p<0.05) and E-peak veloc- ity (58.4±4.0 vs. 73.5±1.7, p<0.01) at baseline compared to WT mice. Baseline +dP/dtmax and -dP/dtmax were significantly lower in the GHR- / - mice, (5079±449 vs. 7006±290, p<0.01) and ( -4941±434 vs. -6919±419, p <0.01), respectively, but not T (12.7±1.0 vs. 11.4±0.8, p = NS). There were no differences in response post-dobutamine (as % baseline) between GHR- / - and WT mice for +dP/dtmax (176±17% vs. 195±16%, p=NS), -dP/dtmax (140±12% vs. 128±7%, p=NS), or T (54±5% vs. 52±3%, p=NS). These data show that the GHR- / - mice have impaired cardiac function at baseline. Also, they have no increased ionotropic (contractile) reserve post-dobutamine compared to WT animals. Despite the reduced cardiac function, the GHR- / - mice are active and healthy. We conclude that the extended longevity of the GHR- / - mice is not due to augmented cardiac reserves.

7312 Th, 09:15-09:30 (P38) Cellular cardiomyoplasty using embryonic cardiomyocytes and adult stem cells W. Roell 1, M. Breitbach 2, T. Hashemi 2, O. Dewald 1, A. Welz 1, B.K. Fleischmann 2. 1Department of Cardiac Surgery, University of Bonn, Germany, 2Institute of Physiology I, University of Bonn, Germany

Introduction: Terminal heart failure is independent to the underlying disease caused by a loss of functional cardiomyocytes. Currently in clinical trials and in animal experiments different cell types are used for cellular cardiomyoplasty. Methods: Experiments were performed in an autologous setting using trans- genic mouse strains. Transgenic embryonic cardiomyocytes (n =98) and bone marrow cells (n =30) were injected into lesioned hearts of wild type mice. In control mice medium only was applied. Survival and further differentiation of transplanted cells was investigated by immunohistochemistry, alterations of myocardial function by left ventricular catheterization. Results: After transplantation of embryonic cardiomyocytes histology showed an elongated cell shape as well as cell contacts, suggesting differentiation,

alignment and functional assembly. Immunohistochemistry demonstrated cross striation of transplanted cells. Furthermore left ventricular catheterization re- vealed significant improvement of left ventricular ejection fraction as well as cardiac output in treated compared to sham operated mice. Also transplanted transgenic bone marrow cells could be identified at different time points after injection. Immunohistochemistry showed no evidence for cardiac differentia- tion and functional investigation yielded no hemodynamic difference between treated and sham operated animals. Conclusions: Employing embryonic cardiomyocytes further differentiation of transplanted cells and a significant improvement of left ventricular function after cellular cardiomyoplasty could be shown. Intra-myocardial injected bone marrow cells showed no evidence for cardiac differentiation and failed to improve left ventricular function.

5540 Th, 09:30-09:45 (P38) Intercalated discs create and dispose sarcomeres - An observation of volume overloaded and/or overload-removed rabbit hearts H. Masuda 1 , M. Yoshida 1 , K. Kawamura 1 , M. Kobayashi 1 , M. Takahashi 1 , H. Nanjo 2, E. Sho 3, M. Komatsu 4, M. Honma 1 . 1Department ef Pathology and Immunology, Akita Universioty School of Medicine, Akita, Japan, 2 Clinical Pathology, Akita Universioty School of Medicine, Akita, Japan, 3 Vascular Surgery, Stanford University School of Medicine, Stanford, CA, USA, 4Clinical Pathology, Yamamoto-Kumiai General Hospita, Noshiro, Japan

Heart adapts to volume load by changing its ventricle volume. Because number of myocardial cells in adult heart is almost constant, ventricle volume enlargement or normalization, which correspond to the ventricle wall expan- sion or contraction, would correlate myocardial cell elongation or shortening, respectively. Because lengths of myocardial cells consist of integral number of sarcomeres, it is assumed that myocardial cell elongation or shortening corresponds increase of sarcomeres (sarcomerogenesis) or decrease of sar- comeres (sarcomere-disposal), respectively. However, mechanism of cardiac enlargement is still unclear. We hypothesize myocardial cell elongation and shortening happen at intercalated discs (ICDs). Here, we investigate ICDs morphologically under various patterns of volume load. Arterio-venous fistula (AVF) constructed between carotid artery and jugular vein induced volume overload in adult male rabbits (3-5 kg). AVF closure removed overload. Hearts were traced with echocardiography. Overload induced significant dilatation within 1-week and distinct dilatation at 4-week. At 1.5-day, all ICDs became wide (1-sarcomere wide). They were remarkably folded like bellows. The folding step was almost constant of -0.1-~tm wide. At 2.25-2.5-day, many folded sarcomeres divided into two layers, between which new sarcomeres appeared. At 3-day, new sarcomeres were added to myocardial cells. Removal of overload of 4-week-overload hearts induced contraction to normal size within 6-weeks. At 1-day of AVF closure, all ICDs became wide (1-sarcomere wide). Within widened ICDs, there appeared spaces consisting of one sarcomere- wide. At 3-day, after the spaces disappeared, myocardial cells shortened by one sarcomere. In the disappeared spaces, there appeared mitochondria and/or microtubuli, which would have been within myocardial cells. We consider that sarcomere appeared and disappeared within ICDs.

4021 Th, 11:00-11:15 (P42) Myocardial material parameter estimation: the influences of constitutive relation and experimental protocol H. Schmid 1 , M.P. Nash 1 , W. Lin 1 , R. Kirton 1 , P. O'Calaghan 2, I.J. LeGrice 1 , A.A. Young 1 , P.J. Hunter 1 . 1University of Auckland, Auckland, New Zealand, 2AgResearch, Hamilton, New Zealand

The study of ventricular mechanics - analysing the distribution of strain and stress in myocardium throughout the cardiac cycle - is critically dependent on the accuracy of the constitutive law chosen to represent the highly nonlinear and orthotropic properties of passive cardiac muscle. A recent study has examined four of these laws and has compared them [1]. This study, however, had been restricted to the assumption of a homogeneous simple shear deformation. Here we relax the assumption of a homogeneous deformation and study a full 3D finite element model. Furthermore, we enriched the scope of experimental protocols by including uniaxial extension along all three microstructural axes. A tri-linear finite element model was built. Displacement boundary conditions of the corresponding deformation modes were specified. Firstly, we investigated the effects of incorporating the non-homogeneous deformation and compared the parameter fits to those obtained from the homogeneous model. Secondly, we investigated the effects of the various experimental protocols as the basis for the inverse material parameter investigation. Here we compared the results of using a) simple shear, b) combinations of simple shear and uniaxial data. We were able to show that for the case of including only simple shear data the incorporation of the non-homogeneous deformation stayed very closely to the results of the homogeneous model (difference o f -15%) .