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Development of the cardiac conducting system
j Mol Cell Cardiol 18 (Supplement 1) (1986) 49DEVELOPMENT OF THE CARDIAC CONDUCTING SYSTEM. G.R. CAMPBELL, E. CANALE, *J.J. SMOLICH. Department of Anatomy, University of Melbourne, Parkville, 3052; *Baker Medical Research Institute, Commercial Road, Prahran, 3181; Australia. In the adult, the Purkinje cells of the atrio-ventricular bundle (AVB) are smaller and contain fewer myofibrils than those of the ventricles. The development of the ventricular conduction system has been followed in the sheep heart, and the differentiation of Purkinje cells in the AVB observed to d i f f e r from those of the ventricles. P r i o r to the development of Purkinje cells, the AVB was distinguishable as a primordium of small, undifferentiated myocytes. No primordium of the Purkinje system was observed in the ventricles. Purkinje fibres f i r s t differentiate at the bifurcation of the AVB. Subsequent differentiation extends gradually in both directions from this region. Therefore, in the ventricles the peripheral intramural branches of the Purkinje system are the last to differentiate ( f i r s t observed at 60 days gestation). In the AVB, the primordial cells connecting to the AV node are the last to develop Purkinje characteristics ( f i r s t observed at 46 days gestation). As well, the AVB is innervated early in fetal l i f e and innervation of the ventricular Purkinje system lags behind. These observations suggest that morphological differences between AVB and ventricular Purkinje cells are related to the different origins of the cells.
~OTHE ~ V~qT 'AMPLIFIER' IN HYPERTENSION. P.I. Korner, G. Jennings, M. Esler, A . Broughton. Baker Medical Research Institute, Melbourne, Australia. We studied the contractile and imm~ing function of the left ventricle (LV) in concentric LV hypertrophy (LVH) in dogs with chronic renovascular hypertension. Under controlled loading conditions isovoltTnic (dP/dt)mmx ~ s increased by about 30%, i.e. in proportion to the greater LV wall thickness. During ejection the change in force to generate a given flow was disproportionately greater in LVH end the LV en%otied further than the normal heart owing to the increased wall/itm~ ratio. Differences in ar~plifying capacities of the hypertrophied and resistance vessels a c c o s t for the characteristic evolution of haemodynamic patterns in primary hypertension. In another study in patients ~ rotund that reversal of hypertrophy of the muscles of the LV and resistance vessels in primary hypertension required prolonged anti-hypertensive drug treatment. Our findings suggest that reversal of LVH was more difficult than reversal of vascular hypertrophy. Redevelopment of hypertension and stopping drug therapy was slowest after substantial reversal of both c~rdiac and vascular hypertrophy. In some patients blood pressure could be maintained at normal levels by moderate bicycle exercise for over a year. q~ne LV amplifier contributes significantly to the hypertension at an early stage and the crm~ined amplifier effects of the hypertrophied LV and the resistance vessels account for about 70% of the elevated pressure in established hypertension.
5 1 MEMBRANE ALTERATIONS IN CARDIAC HYPERTROPHY DUE TO PRESSURE OVERLOAD. N.S. Dhalla,
C.E~ Heyllger. Dept. of Physlology, University of Manitoba, Winnipeg, Canada R3E 0W3 It is generally assumed that changes in heart function in oaPdlao hypertrophy ape due to altered characteristics of the contractile proteins. Although different membrane systems, saroolemma (SL), sarooplas~o Petloulum (SR) and mltoohondrla (MT), ape known to regulate heart function, their exact role in adaptive changes during the development of hypertrophy is not clear. Recent experiments have indicated that narrowlng of the abdo~nal aorta in rabbits for 20 weeks increased left ventrlole to b o ~ weIEht ratio, +dP/dt and -dP/dt by about 50%,wlthout any changes in myoflbrillar Ca ~ stimulated ATPase activity. Na +- induced Ca E§ Pelease, ATP-dependent C~~§ uptake and Ca~§ ATPa~e activity were Increased in hypertrophied SL without alterations in Na+-dependent Ca ~§ uptake and Na+-E§ ATRase activities T~e activity of Ca~§ - ATPase ~ which requires mM oonoentratlons of CaE§ was increased whereas ATPindependen~ CaZ§ was unaltered in hypertrophied SL. No ohan~es in MT Ca z§ uptake, Mg~§ and oxidative phosphorylatlon were noted in hypePtrophled hearts. ATP-dependent Ca E+ uptake was depressed and CaZ§ ATPase activity was increased in SR ~reparatlons fPom experimental animals. These results suggest that char~es in SL CaE§ transport play an adaptive role whereas changes in heart Function may he due to increased muscle mass of the hypertrophied myooardlum. (Supported by the Manitoba Heart Foundation).
~OTHE ~ V~qT 'AMPLIFIER' IN HYPERTENSION. P.I. Korner, G. Jennings, M. Esler, A . Broughton. Baker Medical Research Institute, Melbourne, Australia. We studied the contractile and imm~ing function of the left ventricle (LV) in concentric LV hypertrophy (LVH) in dogs with chronic renovascular hypertension. Under controlled loading conditions isovoltTnic (dP/dt)mmx ~ s increased by about 30%, i.e. in proportion to the greater LV wall thickness. During ejection the change in force to generate a given flow was disproportionately greater in LVH end the LV en%otied further than the normal heart owing to the increased wall/itm~ ratio. Differences in ar~plifying capacities of the hypertrophied and resistance vessels a c c o s t for the characteristic evolution of haemodynamic patterns in primary hypertension. In another study in patients ~ rotund that reversal of hypertrophy of the muscles of the LV and resistance vessels in primary hypertension required prolonged anti-hypertensive drug treatment. Our findings suggest that reversal of LVH was more difficult than reversal of vascular hypertrophy. Redevelopment of hypertension and stopping drug therapy was slowest after substantial reversal of both c~rdiac and vascular hypertrophy. In some patients blood pressure could be maintained at normal levels by moderate bicycle exercise for over a year. q~ne LV amplifier contributes significantly to the hypertension at an early stage and the crm~ined amplifier effects of the hypertrophied LV and the resistance vessels account for about 70% of the elevated pressure in established hypertension.
5 1 MEMBRANE ALTERATIONS IN CARDIAC HYPERTROPHY DUE TO PRESSURE OVERLOAD. N.S. Dhalla,
C.E~ Heyllger. Dept. of Physlology, University of Manitoba, Winnipeg, Canada R3E 0W3 It is generally assumed that changes in heart function in oaPdlao hypertrophy ape due to altered characteristics of the contractile proteins. Although different membrane systems, saroolemma (SL), sarooplas~o Petloulum (SR) and mltoohondrla (MT), ape known to regulate heart function, their exact role in adaptive changes during the development of hypertrophy is not clear. Recent experiments have indicated that narrowlng of the abdo~nal aorta in rabbits for 20 weeks increased left ventrlole to b o ~ weIEht ratio, +dP/dt and -dP/dt by about 50%,wlthout any changes in myoflbrillar Ca ~ stimulated ATPase activity. Na +- induced Ca E§ Pelease, ATP-dependent C~~§ uptake and Ca~§ ATPa~e activity were Increased in hypertrophied SL without alterations in Na+-dependent Ca ~§ uptake and Na+-E§ ATRase activities T~e activity of Ca~§ - ATPase ~ which requires mM oonoentratlons of CaE§ was increased whereas ATPindependen~ CaZ§ was unaltered in hypertrophied SL. No ohan~es in MT Ca z§ uptake, Mg~§ and oxidative phosphorylatlon were noted in hypePtrophled hearts. ATP-dependent Ca E+ uptake was depressed and CaZ§ ATPase activity was increased in SR ~reparatlons fPom experimental animals. These results suggest that char~es in SL CaE§ transport play an adaptive role whereas changes in heart Function may he due to increased muscle mass of the hypertrophied myooardlum. (Supported by the Manitoba Heart Foundation).