- Email: [email protected]
Different rate dependence of repolarization between EPI- and endocardium: Role of a transient outward current
J Mel
Cell
Cardiol
21
(Supplemenr
IV) (19891
FC85
THE PRESENCE OF VENTRICULAR MYOBLAST IN MAMMALIAN OFFSPRINGS AS A CAUSE OF PROLONGED QT SYNDROM. 2. Hecht, A. Fein, M. Newman, D. Varon, M. Manoach. The pathogenesis of prolonged QT interval (PQT) in children remains unclear, althouqh many hypotheses have been proposed. The fact that P9T in children is congenital and tendes to normalize with age, led us to search the QT.interval in pre and post natal development of mammalian heart. In a previous study on mice we showed that QT is prolonged in the early embryonic stage and shortens at 14-17 day of gestation. In this study we examined the ECGand myocardial cell structure in normal and affected (exhibiting PQT)rats. The shortening of QT interval in rats appears after delivery. This fact enables us to examine the post natal changes of QT interval. At different ages, lo-20 affected and lo-20 normal rat offspring according to their ECG have been sacrificed. The hearts were examined under ligh microscope. In the "affected" newborn and offspring clear retardation in the myocarrats at various ages, like in affected newborn mice, dial histo deferentiation was shown. In these cases large numbers of myoblasts were found in different parts of the ventricular walls and septum, scattered between normal myocytes. These myoblasts showed negative PAS staining and they could hardly be identified in newborn ahd offspring with normal QT interval. Differentiation of myofibers with age was demonstrated in the majority of normal.newborn, accompanied by matching shortening of QT. Such a "normalization" has not been found in "affected" offspring up to 14 days after birth. This study shows clear correlation between P9T and undeferentiated myoblast at any age.
fC86
ELECTRICAL AND MECHANICAL ACTIVATION IN THE BORDER ZONE OF ISCHEMIC MYOCARDIUM. FW Prinzen, CH Augustijn, T Arts, MA Allessie, RS Reneman. Departments of Physiology and Biophysics, University of Limburg, Maastricht, The Netherlands. It was investigated to which extent in the ischemic border zone delayed activation influences the relation between fiber shortening and blood flow. In 11 anesthetized open-chest dogs the left anterior descending coronary artery was occluded for lo-15 min. In the ischemic border zone the sequence of epicardial electrical (E) activation was mapped by a 192 multiple electrode. Epicardial fiber shortening (FSepi) in the border zone was mapped by simultaneously measuring epicardial deformation in 35 regions using a video technique. The sequence of mechanical (M) activation was assessed from the FSepi tracings using correlation techniques. FSepi during the ejection phase (AFSepi) was used as measure of regional mechanical function. Epicardial blood flow (BFepi) was measured with radioactive microspheres. BFepi and FSepi were normalized to the central ischemic (0%) and remote non-ischemic values (100%). In the average the location of the 50% contourlines of BFepi and FSepi was similar. However, the transition of AFSepi was more gradual than that of BFepi, as illustrated by the larger distance between the 20 and 80% contourlines (FSepi:l5*5 vs BFepi:l0?5 mm, ~~0.05). E and M activation time in the ischemic region increased by O-20 ms (n=4) and the region with delayed activation, if any, did not coincide with the ischemic region. Conclusion: in the acute phase of ischemia the more gradual transition of function than blood flow in the ischemic border zone is not likely to be caused by gradients in E and M activation across this border. (Supported by Medigon/NWO)
F~~~L~F~~RAIE’B(P~~~-AN)B
RCXJIOFA~CWIHARD-. E.Mortensen, P.M.Tarrde, N.E.Klm & H.Refsum, Department of Physiology, IMB, University of Tram@, Norway. A transient outward current has recently ken &imnstrated to be tx-mimnt in epicardial cells in vitro. lb investigate its axkrikutim to repolarisation in vivo, ly epi- and endocardial ventricular -sic action potentiws recorded simulals (MAP)inanesthetized,openchestdogs.Epicardial~had agreaterphaee2than *se 1 amplitude at toth spontaneous heart rate and paced cycle length of 300 ms. This 'kpike-and4ane~ axfiguration of the epicardial MAP nearly disappeared at progressively shorter extrastimulus intervals (Fig). Mwever, there YBS no difference between phase 2 arid 1 amplitude of the er&CardialMAP, and this was not affected by shorter extrastimulus intervals. The study indicates a significant contribution of a transient outward current to repolarizaticm of the ventricular epicardium hut not erxbardiun in viva. EPI h EN00 b t.
S.88
Cell
Cardiol
21
(Supplemenr
IV) (19891
FC85
THE PRESENCE OF VENTRICULAR MYOBLAST IN MAMMALIAN OFFSPRINGS AS A CAUSE OF PROLONGED QT SYNDROM. 2. Hecht, A. Fein, M. Newman, D. Varon, M. Manoach. The pathogenesis of prolonged QT interval (PQT) in children remains unclear, althouqh many hypotheses have been proposed. The fact that P9T in children is congenital and tendes to normalize with age, led us to search the QT.interval in pre and post natal development of mammalian heart. In a previous study on mice we showed that QT is prolonged in the early embryonic stage and shortens at 14-17 day of gestation. In this study we examined the ECGand myocardial cell structure in normal and affected (exhibiting PQT)rats. The shortening of QT interval in rats appears after delivery. This fact enables us to examine the post natal changes of QT interval. At different ages, lo-20 affected and lo-20 normal rat offspring according to their ECG have been sacrificed. The hearts were examined under ligh microscope. In the "affected" newborn and offspring clear retardation in the myocarrats at various ages, like in affected newborn mice, dial histo deferentiation was shown. In these cases large numbers of myoblasts were found in different parts of the ventricular walls and septum, scattered between normal myocytes. These myoblasts showed negative PAS staining and they could hardly be identified in newborn ahd offspring with normal QT interval. Differentiation of myofibers with age was demonstrated in the majority of normal.newborn, accompanied by matching shortening of QT. Such a "normalization" has not been found in "affected" offspring up to 14 days after birth. This study shows clear correlation between P9T and undeferentiated myoblast at any age.
fC86
ELECTRICAL AND MECHANICAL ACTIVATION IN THE BORDER ZONE OF ISCHEMIC MYOCARDIUM. FW Prinzen, CH Augustijn, T Arts, MA Allessie, RS Reneman. Departments of Physiology and Biophysics, University of Limburg, Maastricht, The Netherlands. It was investigated to which extent in the ischemic border zone delayed activation influences the relation between fiber shortening and blood flow. In 11 anesthetized open-chest dogs the left anterior descending coronary artery was occluded for lo-15 min. In the ischemic border zone the sequence of epicardial electrical (E) activation was mapped by a 192 multiple electrode. Epicardial fiber shortening (FSepi) in the border zone was mapped by simultaneously measuring epicardial deformation in 35 regions using a video technique. The sequence of mechanical (M) activation was assessed from the FSepi tracings using correlation techniques. FSepi during the ejection phase (AFSepi) was used as measure of regional mechanical function. Epicardial blood flow (BFepi) was measured with radioactive microspheres. BFepi and FSepi were normalized to the central ischemic (0%) and remote non-ischemic values (100%). In the average the location of the 50% contourlines of BFepi and FSepi was similar. However, the transition of AFSepi was more gradual than that of BFepi, as illustrated by the larger distance between the 20 and 80% contourlines (FSepi:l5*5 vs BFepi:l0?5 mm, ~~0.05). E and M activation time in the ischemic region increased by O-20 ms (n=4) and the region with delayed activation, if any, did not coincide with the ischemic region. Conclusion: in the acute phase of ischemia the more gradual transition of function than blood flow in the ischemic border zone is not likely to be caused by gradients in E and M activation across this border. (Supported by Medigon/NWO)
F~~~L~F~~RAIE’B(P~~~-AN)B
RCXJIOFA~CWIHARD-. E.Mortensen, P.M.Tarrde, N.E.Klm & H.Refsum, Department of Physiology, IMB, University of Tram@, Norway. A transient outward current has recently ken &imnstrated to be tx-mimnt in epicardial cells in vitro. lb investigate its axkrikutim to repolarisation in vivo, ly epi- and endocardial ventricular -sic action potentiws recorded simulals (MAP)inanesthetized,openchestdogs.Epicardial~had agreaterphaee2than *se 1 amplitude at toth spontaneous heart rate and paced cycle length of 300 ms. This 'kpike-and4ane~ axfiguration of the epicardial MAP nearly disappeared at progressively shorter extrastimulus intervals (Fig). Mwever, there YBS no difference between phase 2 arid 1 amplitude of the er&CardialMAP, and this was not affected by shorter extrastimulus intervals. The study indicates a significant contribution of a transient outward current to repolarizaticm of the ventricular epicardium hut not erxbardiun in viva. EPI h EN00 b t.
S.88