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THE INFLUENCE OF HEART PERFORMANCE ON CARDIOVASCULAR PARAMETERS IN DEVELOPING ZEBRAFISH (DANIO RERIO) Renate Kopp Department of Zoology and

Limnology, University of Innsbruck, Austria P one !"# $%& $'( )%*#, +a, !"# $%& $'( &*#', e-ail Renate Kopp .csac)$)#/uibk0ac0at1 2 orsten 3c 4erte and 5ernd Pelster Department of Zoology and Limnology, University of Innsbruck, Austria EXTENDED ABSTRACT ONLY - DO NOT CITE 2 e first organ t at functions during larval development is t e cardiovascular system0 Zebrafis larvae ac6uire t e o,ygen by bulk diffusion until about %&dpf 7Pelster and 5urggren, %**)8 9acob et al0 &''&:, t erefore t e cardiovascular system obviously is not only needed for t e transport of o,ygen0 Among ot er t ings also t e distribution of nutritions and ormones appear to be important, and t e immune system may in part also depend on convective transport0 2 us, control over t e cardiovascular system s ould be establis ed 6uite early during development0 It is kno4n t at ;ebrafis larvae are responsive to adrenaline beginning at #dpf and respond according to t e +rank<3tarling mec anism at $dpf 73c 4erte et al0, personal communication:0 +ritsc e et al0 7&''': described observations of vascular reactivity against => starting at (dpf old ;ebrafis larvae0 It is also already kno4n t at t ere is a link bet4een blood pressure and?or s ear stress and angiogenesis as 4ell as cardiogenesis 7@ove et al0, &''#: If s ear stress is connected to angiogenesis it mig t be possible t at alterations in cardiac output and blood flo4 may cause c anges in vasculari;ation of tissues0 Anot er interesting aspect 4ould be t e 6uestion 4 ic of t e various parameters connected to cardiovascular performance or depending on sufficient blood supply 4ould be most important for controlling cardiovascular activityA An overvie4 of our current kno4ledge of s ort and medium term regulation of cardiovascular activity in larvae is s o4n in figure %0

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A reduced cardiac performance can be observed in numerous mutants 7e0g0 breakdance < bre:, it can also be induced by p armacons 7e0g0 Buinidine:0 Using ig speed video imaging enables us to monitor t e contracting eart and t e developing vessel system of t e transparent ;ebrafis larvae0 Bre<;ebrafis larvae typically s o4 an atrioventricular block, i0e0 t e atrium contracts t4ice 4 ile t e ventriclecontracts only once0 2 e e,pression of t is &C% r yt m is not constant, but it depends on t e upbringing temperature and t e age of t e larvae0 At lo4er temperature a %C% eart beat often is observed, but eart rate is significantly lo4er t an t at of 4ildtype ;ebrafis 0 2 e same is true for older larvae0 Remarkable is t e temperature insensitivity during &C% contraction0 Larvae raised at &$DE, &FDE or #%DE ave a ventricular contraction rate of about F' bpm, irrespective of t e temperature0 If beating in t e %C% r yt m temperature sensitivity of eart rate even appears to be reversed0 Animals raised at #%oE ave a lo4er eart rate in t e %C% r yt m t an animals raised at &$ oE0 5lood pressure in bre G mutants is reduced compared to 4ild type animals0 An artificial reduction in eart rate to $'H can be triggered by incubation of larvae 4it t e p armacon Buinidine, a blocker of K !<c annels0 Zebrafis larvae incubated in Buinidine create a very lo4 enddiastolic volume0 2 is combined 4it t e lo4 eart rate caused a significantly reduced cardiac output0 Anot er conse6uence of Buinidine 4as t e dilatation of larger vessels 7Eald4ell et al0, %*F#:0 2 us, a decreased blood pressure can be e,pected, and 4as confirmed by -ariano et al0, %**& 4 o also mentioned an I<adrenergic neurotransmission blocking0 Eomparing bre, Buinidine incubated and 4ildtype ;ebrafis larvae a different blood allocation is seen but no significant c anges in t e main vasculari;ation pattern could be detected0 2 us, t e basic development of vessels 7at least of t e maJor vessels: appears to be independent of t e blood pressure0 Eurrently 4e are focussing on blood vessels t at develop in t e angiogenetic processes0 2 is mig t be a more potent field to find blood pressure related c anges in t e construction of t e vascular bed0 Reference Eald4ell R0K0, Llam 9020, -ecca 20L0 and E050 =as 0 %*F# >ct &F0 Mascular alp a<adrenergic blocking properties of 6uinidine0 Eur J Pharmacol, *"7#< ":C%F$<*&0

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+ritsc e, R0, 3c 4erte, 20 and 50 Pelster0 =itric o,ide and vascular reactivity in developing ;ebrafis , Danio rerio. &'''0 Am J Physiol Regulatory Integrative Comp Physiol. &(*C R&&''GR&&'(0 @ove 90R0 et al0 &''#0 Intracardiac fluid forces are an essential epigenetic factor for embryonic cardiogenesis0 ature0 "&% 7)*%*:C%(&<%((0 9acob, L0, Dre,el, -0, 3c 4erte, 20 and 50 Pelster0 &''&0 Influence of ypo,ia and of ypo,emia on t e development of cardiac activity in ;ebrafis larvae0 Am J Physiol Regul Integr Comp Physiol. &F#7":CR*%%<(0 Pelster 5 and K0K0 5urggren0 %**)0 Disruption of @emoglobin >,ygen 2ransport Does =ot Impact >,ygen<Dependent P ysiological Processes in Developing Lmbryos of Zebra +Is 7Danio rerio:0 Circulation. Research0 (*C#$F<#)&0

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