| Abstract | U ljudskoj slezeni je uskladišteno oko 30% ukupnih trombocita u tijelu. Oni imaju veći
volumen i protrombotsku moć od onih u perifernoj cirkulaciji, u koju se ispuštaju u
stanjima povećanog adrenergičkog tonusa. Cilj ovoga istraţivanja je bio: 1) usporediti
učinak bisoprolola i karvedilola na veličinu slezene, te na broj i volumen trombocita u
perifernoj krvi u novootkrivenih hipertoničara, 2) utvrditi učinak malih doza adrenalina na
promjene veličine slezene, širinu jetrenih vena i protok krvi kroz njih, 3) utvrditi dinamiku
promjena u perifernoj krvnoj slici, s obzirom na ulogu hepatalnog sfinktera na ušću vena
jetre u donju šuplju venu, 4) procijeniti je li kontrakcija slezene potaknuta infuzijom malih
doza adrenalina posljedica periferne humoralne stimulacije ili aktivacije simpatičkog
ţivčanog sustava zbog smanjenog podraţivanja baroreceptora.
Osamnaest novootkrivenih hipertoničara i devet zdravih osoba su na početku istraţivanja
uradili test opterećenja po Bruce-ovu protokolu, a prije i nakon toga je ultrazvukom
izmjeren volumen slezene te su uzeti uzorci krvi za analizu broja i srednjeg volumena
trombocita. Potom su hipertoničari nakon randomizacije bili liječeni bisoprololom 5
mg/dan (n=9) ili karvedilolom 25 mg/dan (n=9) tijekom mjesec dana, a spomenuta
mjerenja su bila ponovljena 15-og i 30-og dana liječenja, prije i nakon testa opterećenja.
Nakon petnaest i trideset dana liječenja, zapaţeno je značajno smanjenje volumena slezene
uz porast srednjeg volumena trombocita u perifernoj krvi, podjednako u obje skupine
ispitanika. Smanjenje volumena slezene nakon testa opterećenja kao i porast broja i
srednjeg volumena trombocita je uočen samo prije početka liječenja, dok su bili znatno
manji nakon petnaestog i tridesetog dana liječenja bisoprololom i karvedilolom. Iz
istraţivanja proizlazi da liječenje arterijske hipertenzije selektivnim ili neselektivnim
betablokatorom uzrokuje kontrakciju slezene i posljedični porast srednjeg volumena
trombocita u perifernoj cirkulaciji, što moţe povećati rizik nastanka trombotskih dogaĎaja.
Devetorici mladih zdravih muškaraca je primijenjena infuzija adrenalina u maloj dozi
(0,06-0,12 µg/kg/min) tijekom devet minuta uz trajno, neinvazivno mjerenje
hemodinamskih parametara. Izmjereni su volumen slezene, promjer i protok kroz jetrene
vene te periferna krvna slika, prije i na kraju infuzije te u 1., 5., 10. i 20. minuti nakon završetka infuzije. Trojici ispitanika je za vrijeme infuzije adrenalina i tijekom dvadeset
minuta oporavka trajno mjerena periferna mišićna simpatička aktivnost, kao pokazatelj
periferne simpatičke aktivnosti. Neposredno nakon početka infuzije adrenalina značajno
se smanjio volumen slezene za 36% (p=0,008), uz povećanje promjera jetrene vene i
protoka krvi kroz nju. U isto vrijeme je došlo do pada srednjeg arterijskog tlaka i ukupne
periferne rezistencije uz porast frekvencije bila, udarnog volumena srca i mišićne
simpatičke ţivčane aktivnosti. Maksimalan porast srednjeg volumena trombocita registrira
se tek u 1. min oporavka i ostaje značajno povećan cijelo vrijeme praćenja (20 minuta po
prestanku infuzije adrenalina), dok je ukupni broj trombocita u perifernoj krvi rastao do
pete minute oporavka, a potom se biljeţi pad njihovog broja do kraja oporavka. Iako se
kontrakcija slezene javila neposredno nakon početka infuzije adrenalina, broj krvnih
stanica na periferiji, uključujući i velike trombocite se povećao tek u prvoj minuti
oporavka, dakle sa zakašnjenjem od devet minuta. Istovremeno, maksimalni porast
protoka i širine jetrenih vena uočeni su u prvoj minuti oporavka, što potvrĎuje da se
istisnuta krv iz slezene zadrţava jetrenim venama uz kontrolu hepatokavalnog sfinktera.
Ovo istraţivanje je pokazalo da je slezena skladište velikih trombocita koji imaju
veliku protrombotsku moć. Njihovo otpuštanje u perifernu cirkulaciju pod različitim
adrenergičkim podraţajima kontrolira hepatokavalni sfinkter na ušću jetrenih vena u donju
šuplju venu.
Kako se kontrakcija slezene javila na samom početku primjene adrenalina uz istovremeni
pad srednjeg arterijskog tlaka i porast periferne simpatičke aktivnosti, to potvrĎuje da je
slezena sastavni dio simpatičkog ţivčanog sustava za vrijeme stresnih situacija, a da je
manje pod utjecajem perifernih posrednika. |
| Abstract (english) | The spleen contains approximately one-third of all the body‟s platelets. These
platelets are relatively larger and haemostatically more active than platelets in the systemic
circulation and can be released into the systemic circulation by stimulation of αadrenoceptors or inhibition of β-adrenoceptors. The purpose of this study was: 1) to
evaluate the effects of two beta-blockers, bisoprol and carvedilol, on mean platelet volume
(MPV) and spleen size in hypertensive patients at rest and after exercise, 2) to test whether
changes in peripheral platelet count and MPV in conjunction with changes in spleen
volume and hepatic vein blood flow occur after a low dose of epinephrine intravenous
infusion in healthy young men, 3) to investigate dynamics of transhepatic passage of large
platelets in order to test the hypothesis that cavo-hepatic venous junctions (sphincters)
control this process in man, 4) to answer weather the reduction in spleen size in response
to epinephrine infusion is a consequence of peripheral humoral stimulation or neurally
mediated mechanism by downloading of baroreceptors.
Blood pressure, heart rate, platelet count, MPV and spleen volume were measured
in 18 newly diagnosed hypertensive patients, as well as in nine healthy control subjects,
subjected to treadmill exercise test at their first visit and, for the hypertensive group, after
15 and 30 days of treatment with the selective β1-adrenoceptor antagonist bisoprolol 5
mg/day (n=9) or the nonselective α1-, β1- and β2-adrenoceptor antagonist carvedilol 25
mg/day (n=9). Increases in resting MPV values with concomitant decreases in spleen
volume were found after 15 and 30 days treatment with either bisoprolol or carvedilol.
The pronounced decrease in splenic volume after exercise and the increased MPV and
platelet counts seen at first visit were halved after 15 and 30 days of treatment with either
drug. We conclude that in hypertensive patients treated with either selective or nonselective beta-blockers, the spleen contracts and MPV increases, which may increase the
risk of atherothrombosis.
We undertook the continuous ultrasonic measurements of spleen volume in
response to intravenous infusion of low doses of epinephrine (0.06 and 0.12 µg/kg/min)
with simultaneous continuous noninvasive measurements of hemodynamic parameters and
peripheral blood count in nine healthy young subjects. For further understanding of possible neurally mediated spleen contraction, in subgroup of three subjects, we also
continuously measured muscle sympathetic nerve activity (MSNA), as an index of
peripheral sympathetic activation. We found a massive spleen contraction ( 30%,
p=0.008) at the onset of epinephrine infusion, in parallel with simultaneous decreases in
MAP, TPR and an increase in HR, SV and MSNA. The number of total platelets increased
in response to spleen contraction in a sequence with MPV until the 5th min of recovery
when we observed decline in platelets count while the MPV remained significantly
elevated until the end of recovery. Massive spleen contraction (~40%) has been achieved
already during second min of epinephrine infusion, but the maximum of total platelets,
leucocytes, RBCV and MPV increase was observed at 1st min of recovery, indicating the
time delay of 8 mins until the spleen content, including large platelets, reached peripheral
blood. Concomitantly, maximal increase in hepatic vein width and velocity time integral
were observed in 1
st min of recovery, suggesting a shift of splenic blood into an area of
hepatic veins most likely controlled by cavo-hepatic sphincters.
The results of this study showed that the spleen is a dynamic reservoir of the large
platelets recognized as a strong independent factor of thrombosis. The spleen contraction
is followed by dilatation of hepatic veins and delayed increased in peripheral MPV
suggesting a shift of splenic blood into an area of hepatic veins most likely controlled by
cavo-hepatic sphincters. This rapid splenic response to stimulation of β - adrenoreceptors
argues against peripheral triggers and together with observed increase in MSNA favors the
idea about spleen as a constitutive part of the sympathetic nervous system during stressful
situations. |
