82 Sunday, 10 June 2007 Poster Display III. Animal models and experimentation 356 Human embryonic stem cells improve diastolic function in rats with acute myocardial infarction M. Lindbom, T. Ramunddal, E. Bollano, E. Omerovic, M. Sharin-Tang Wallenberg Laboratory at Sahlgrenska Academy, Gothenburg, Sweden Introduction: Human embryonic stem cells (hES) have emerged as an attractive and promising new therapeutic approach for treatment of heart diseases. The aim of this study was to evaluate in rats with acute my- ocardial infarction (MI): 1) effects of myocardial transplantation of un- differentiated hES on left ventricular (LV) function and morphology and 2) to determine whether potential improvement in LV function requires the presence of hES in the myocardium. Methods: Male Sprague-Dawley rats ∼200 g were used. MI was induced by cryo-injury (protocol 1) and by ligation of left coronary artery (pro- tocol 2). These procedures resulted in anterior MI engaging ∼30-40% of left ventricle (LV). In the protocol 1, the rats were randomized into two groups: rats with MI treated with vehicle (n = 8) and rats with MI treated with 1 million hES cells (n = 8). Rats treated with hES cells re- ceived cyclosporine (5 mg/kg/d). The hES cells were suspended in 0,05 ml buffer and transplanted by intramyocardial injection into the viable myocardium close to the infracted area directly after cryo-injury. The rats were followed for 1 week. In order to evaluate hypothetical paracrine effects of hES, in the protocol 2, the rats were randomised into three groups: rats with MI treated with vehicle (n = 4), rats with MI treated with cell medium (n = 6) and rats with MI treated with supernatant extracted from hES cell culture (n = 6). The animals received i.p. injec- tions 3 times/week during 4 weeks. All animals were investigated with transthoracal echocardiography, continuous ECG and LV catheterization. Post-mortem, the hearts were evaluated histologically. Results: In the protocol 1 neither deaths nor arrhythmias occurred in the rats treated with hES cells. dP/dT was similar in both groups. There were no signs of abnormal tissue growth at the site of hES cell engraftment after one week. There was no difference in the indices of LV systolic function while diastolic function was significantly improved in the hES rats (p < 0.05). hES were detected in 1/8 rats in the infarcted area. In the protocol 2, no difference was found between the groups in indices of LV function and morphology after 4 weeks of treatment. Conclusion: Transplantation of undifferentiated hES cells have positive effect on LV diastolic function in the rat model of acute MI. This effect requires the presence of hES in the tissue. The use of hES may be an important approach for cardio-reparation and reconstitution of normal cardiac structure and function in the future. 357 Comparative effects on LV performance, arterial hemodynamics and ventriculo-arterial coupling of two models of coronary artery occlusion in pigs P.H. Kolh 1 , V. Tchana-Sato 1 , A. Ghuysen 1 , B. Lambermont 1 , S. Rolin 2 , V. D’orio 1 , R. Limet 1 , J.M. Dogne 2 1 University Hospital of Liege, Liege, Belgium; 2 University of Namur, Namur, Belgium Objective: To evaluate the hemodynamic effects of two models of coro- nary artery occlusion in pigs. Methods: Experiments were performed in 12 pigs in which LV func- tion was assessed by the slope (Ees) of ESPVR and stroke work (SW), and systemic arterial properties, including peripheral resistance (R2), compliance (C), and arterial elastance (Ea) with a windkessel model. Ventriculo-arterial (VA) coupling was defined as Ees/Ea, and mechanical efficiency as SW/pressure-volume area (PVA). After baseline, the pigs were randomised in 2 groups: in group LIG (n = 6), the LAD coronary artery was ligated, while in group FeCl3 (n =6), it was wrapped for 45 minutes with a strip satured with FeCl3. The animals were followed for three hours. Results: LAD coronary artery flow dropped immediately to zero in group LIG, but progressively decreased in group FeCl3 (occlusion time 23.2±1.2 min). In group LIG, mean aortic pressure (Pmean) and flow (Qmean) decreased abruptly, between baseline and T60, from 101±3 to 78±6 mmHg and from 56.4±5.4 to 34.9±3.8 ml/sec, respectively, while heart rate (HR) was unchanged; R2 and Ea increased from 1.77±0.33 to 2.33±0.22 mmHg.sec/ml, and from 3.12±0.22 to 4.24±0.28 mmHg/sec, respectively, while Ees dropped from 2.7±0.3 to 1.7±0.4 mmHg/sec. As a consequence, VA coupling falled from 0.90±0.19 to 0.41±0.12. SW and PVA decreased from 4963±596 to 2712±225 mmHg.ml and from 5371±358 to 4553±309 mmH.ml, while SW/PVA dropped from 0.85±0.12 to 0.59±0.06. Most significant hemodynamic changes were observed in the first 30 min after the LAD ligation. In group FeCl3, Pmean remained constant, while Qmean progressively decreased from 57.8±6.6 to 47.3±5.5 ml/sec, and HR increased from 107±10 to 142±13 beats/min, between baseline and T180; R2 and Ea increased from 1.72±0.22 to 1.95±0.28 mmHg.sec/ml, and from 2.99±0.33 to 3.55±0.22 mmHg/sec, respectively, while Ees decreased from 2.7±0.4 to 2.2±0.3 mmHg/sec. As a consequence, VA coupling falled from 0.90±0.16 to 0.63±0.18. SW and PVA decreased from 4903±157 to 3744±299 mmHg.ml and from 5733±366 to 5137±299 mmH.ml, while SW/PVA dropped from 0.85±0.07 to 0.72±0.07. Most hemodynamic changes observed in the FeCl3 were progressive. Conclusion: Progressive coronary artery occlusion, as obtained by top- ical FeCl3 application, is responsible for a less impaired hemodynamic condition. This model, closer to the clinical condition of coronary artery thrombus formation, could be more suitable to assess pharmaceutical or mechanical cardiac support during acute myocardial ischemia. 358 Effects of complete heart block on myocardial function; morphology and energy metabolism in rat model S. Gizurarsson 1 , T. Ramunddal 1 , M. Lorentzon 1 , L. Bergfeldt 2 , F. Waagstein 2 , E. Omerovic 2 1 Wallenberg Laboratory at Sahlgrenska Academy, Gothenburg, Sweden; 2 Departement of Cardiology, Sahlgrenska Hosp, Gothenburg, Sweden Introduction: Severe sustained bradycardia may cause acute and possi- bly even chronic congestive heart failure (CHF). The aims of this study were: a) to set up a small-animal model of complete heart block (CHB) in rats, and b) to investigate acute and chronic effects of CHB on cardiac function, morphology and energy metabolism Methods: CHB was induced in 6 male Sprague-Dawley rats (∼ 250 g) by means of electrocautery applied to the region of AV node and were compared to controls (n=15). The rats were investigated 1, 3 and 12 weeks after induction of CHB with transthoracic ultrasound. After 12 weeks the animals were anesthetized and intubated. The chest was opened and right respectively left ventricular pressure curves were obtained. After the sacrifice, the hearts were freeze-clamped for analysis of myocardial creatine, adenine nucleotides, catecholamines and intracellular lipids. Results: The efficacy of operative procedure was 100%. The periopera- tive mortality rate was 20%. While heart rate was decreased by ∼ 50% (p < 0.01), stroke volume doubled (p < 0.01) in the CHB rats. Cardiac index remained unchanged. The rats with CHB grew normally and were in no apparent distress. Filling pressures in left and right ventricle were normal. The CHB rats developed cardiomegaly with biventricular dilata- tion and hypertrophy with markedly increased left ventricular mass (LV) (p < 0.01). There was no change in the myocardial content of creatine and adenine nucleotides. Conclusions: Rats with CHB are compensating for reduction in heart rate with dramatically increased stroke volume without hemodynamical signs of heart failure even after prolonged period of time. Markedly increased LV mass is probably due to volume overload but is not associated with metabolical derangement as seen in other forms of pathologic LV hyper- trophy. This model may be useful to study the effects of severe bradycar- dia on myocardial structure, function, electrophysiology and metabolism as well as for different aspects of LV hypertrophy. Similarly, the model may be useful for studies of cell therapy for reparation of AV node.