Comparision of the Inotropic Effects of Levosimendan, Rolipram, and Dobutamine on Human Atrial Trabeculae

Usta, Coşkun; Puddu, Paolo Emilio; Papalia, Ugo; Santis, Vincenzo De; Vitale, Domenico; Tritapepe, Luigi; Mazzesi, Giuseppe; Miraldi, Fabio; Özdem, Sebahat

doi:10.1097/00005344-200411000-00017

Cited by 22 publications

(16 citation statements)

References 32 publications

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“…4 were performed to confirm that the effect of 5-HD on RPP was due specifically to inhibition of contractility. Superfusion of human atrial trabeculae in vitro with dobutamine increased contractility to 161 Ϯ 32% of baseline, as is typical of this preparation (29). 5-HD caused a 61% reduction in the dobutamine response, and 1 M glyburide caused a 30 Ϯ 3% (n ϭ 3 experiments) reduction in the dobutamine response (data not shown).…”

Section: Methodsmentioning

confidence: 68%

“…Samples of right atria appendages were obtained during cannulation for cardiac surgery. The methods to obtain human atrial trabeculae working isometrically in vitro have been previously described in detail (3,9,29). Briefly, a sample of the right atrial appendage (1 cm 2 , 500 -1,000 mg) was removed and immersed in preoxygenated and modified Tyrode solution containing (in mM) 120 NaCl, 4 KCl, 2.7 CaCl 2, 1.1 MgCl2, 25.7 NaHCO3, 1.8 NaH2PO4, and 11 glucose at 22°C.…”

Section: Methodsmentioning

confidence: 99%

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Inhibition of cardiac contractility by 5-hydroxydecanoate and tetraphenylphosphonium ion: a possible role of mitoK_ATP in response to inotropic stress

Garlid

Puddu²,

Pasdois³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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. Inhibition of cardiac contractility by 5-hydroxydecanoate and tetraphenylphosphonium ion: a possible role of mitoK ATP in response to inotropic stress. Am J Physiol Heart Circ Physiol 291: H152-H160, 2006. First published February 10, 2006 doi:10.1152/ajpheart.01233.2005.-This study investigates the role of the mitochondrial ATP-sensitive K ϩ channel (mitoK ATP ) in response to positive inotropic stress. In Langendorffperfused rat hearts, inotropy was induced by increasing perfusate calcium to 4 mM, by adding 80 M ouabain or 0.25 M dobutamine. Each of these treatments resulted in a sustained increase in ratepressure product (RPP) of ϳ60%. Inhibition of mitoK ATP by perfusion of 5-hydroxydecanoate (5-HD) or tetraphenylphosphonium before induction of inotropic stress resulted in a marked attenuation of RPP. Inhibition of mitoK ATP after induction of stress caused the inability of the heart to maintain a high-work state. In human atrial fibers, the increase in contractility induced by dobutamine was inhibited 60% by 5-HD. In permeabilized fibers from the Langendorffperfused rat hearts, inhibition of mitoK ATP resulted, in all cases, in an alteration of adenine nucleotide compartmentation, as reflected by a 60% decrease in the half-saturation constant for ADP [K 1/2 (ADP)]. We conclude that opening of cardiac mitoK ATP is essential for an appropriate response to positive inotropic stress and propose that its involvement proceeds through the prevention of stress-induced decrease in mitochondrial matrix volume. These results indicate a physiological role for mitoK ATP in inotropy and, by extension, in heart failure. mitochondria; creatine kinase; calcium; dobutamine; ouabain AN INCREASING BODY OF EVIDENCE supports the hypothesis that opening the mitochondrial ATP-sensitive K ϩ channel (mitoK ATP ) is cardioprotective in ischemia-reperfusion (7, 17). However, little is known about the normal physiological role of mitoK ATP in the heart. Under ischemic conditions, we have shown that the protective ability of mitoK ATP openers is associated with preservation of the mitochondrial intermembrane space (IMS) volume, leading to the preservation of adenine nucleotide compartmentation and energy transfer (5). Ongoing K ϩ cycling in mitochondria is a balance between diffusive K ϩ uptake and K ϩ /H ϩ exchange, and matrix and IMS volumes vary reciprocally in response to net movements of K ϩ and H 2 O across the mitochondrial inner membrane. Because K ϩ uptake is exponential with the mitochondrial membrane potential (⌬⌿), any perturbation of ⌬⌿ will cause changes in matrix and IMS volume (5, 13). On this basis, we proposed that the decrease in ⌬⌿ caused by ischemia was responsible for the disruption of intracellular adenine nucleotide compartmentation and that mitoK ATP opening reversed this effect by adding a parallel K ϩ conductance to compensate for the lower driving force (13).This study is designed to investigate the role of mitoK ATP during positive inotropic stress, a condition in which ⌬⌿ will decrease, because myocardia...

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Section: Methodsmentioning

confidence: 68%

Section: Methodsmentioning

confidence: 99%

Inhibition of cardiac contractility by 5-hydroxydecanoate and tetraphenylphosphonium ion: a possible role of mitoK_ATP in response to inotropic stress

Garlid

Puddu²,

Pasdois³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…18 It is well known that levosimendan increases Ca +2 sensitivity of the heart by myofibrillar Ca +2 sensitization via Ca +2 -dependent stabilization of the Ca +2 -bound conformation of cardiac troponin C 1,20,21 without affecting the Ca +2 affinity of troponin C. Phosphodiesterase inhibition may also play a role in the cardiac effect of levosimendan. 22,23 Accordingly, it has been noted that the activity of phosphodiesterases may prevent intracellular cAMP accumulation following levosimendan application in both human and guinea-pig myocardium.…”

Section: Discussionmentioning

confidence: 99%

“…The methods to obtain human atrial trabeculae working isometrically in vitro have been previously described in detail. [17][18][19] Briefly, a sample of the right atrial appendage (1 cm 2 , 500-1000 mg) was removed and immersed in preoxygenated and modified Tyrode's solution (in mM: NaCl, 120; KCl, 4; CaCl 2 , 2.7; MgCl 2 , 1.1; NaHCO 3 , 25.7; Na H 2 PO 4 , 1.8; and glucose, 11) at 22 ºC. The time between excision and beginning of laboratory processing was 1-5 min.…”

Section: Subjects and Patientsmentioning

confidence: 99%

“…18 Levosimendan (Abbott, Roma,Italy) was superfused for 15 min at incremental concentrations, from 10 -9 to 10 -4 M. Potassium channel blockers were added to superfusion solution 15 min prior to the beginning of experiment and continued thereafter. The effects of 4-AP (500 mM), glibenclamide (1 mM) and 5-HD (300 mM) on basal DT were also studied.…”

Section: Experimental Protocolsmentioning

confidence: 99%

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Positive Inotropic Effects of Levosimendan are Modulated by KATP Channels in Isolated Human Atrial Trabeculae

Usta¹,

Puddu²,

Papalia³

et al. 2010

Turkiye Klinikleri J Med Sci

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A AB BS S T TR RA AC CT T O Ob b j je ec c t ti i v ve e: : The aim of this study was to in ves ti ga te whet her po tas si um chan nel bloc king agents we re ab le to mo du la te po si ti ve inot ro pic ef fect of le vo si men dan in iso la ted hu man at rial tra be cu lar musc les or not. M Ma a t te e r ri i a al l a an nd d M Me et t h ho od ds s: : The right at ri al ap pen da ge samp les (1 cm 2 , 500-1000 mg) we re re mo ved and im mer sed in pre oxy ge na ted and mo di fi ed Tyro de's so lu ti on. Prepa ra ti ons we re used to in ves ti ga te the con cen tra ti on-ef fect re la ti on of le vo si men dan (10-9 to 10-4 M) alo ne or in the pre sen ce of Ca2+-de pen dent po tas si um chan nel bloc ker 4-ami nop yri di ne (4-AP: 500 µM), ATP-de pen dent po tas si um chan nel bloc ker gli benc la mi de (1 µM) or mi toc hon dri al ATP-de pen dent po tas si um chan nel bloc ker 5-hydroxy de ca no a te (5-HD: 300 µM) on per cent de ve lo ped ten si on (%DT). R Re e s su ul lt ts s: : Le vo si men dan pro du ced con cen tra ti on-de pen dent in cre ments in %DT. Both the sen si ti vity (pD2) and ma xi mum res pon se (Emax) of hu man at ri al tra be cu la e to levo si men dan (7.31 ± 0.02 and 29.2 ± 1.1 mN, res pec ti vely) sig ni fi cantly and similarly re du ced in pre sen ce of gli benc la mi de (5.83 ± 0.04 and 17.4 ± 1.61 mN) and 5-HD (6.14 ± 0.05 and 18.5 ± 3.1 mN). Ho we ver, 4-AP did not ca u se a sig ni fi cant al te ra ti on in sen si ti vity (pD2= 6.77 ± 0.05) or Emax (27.6 ± 2.0 mN) to le vo si men dan. C Co on nc c l lu u s si i o on n: : Both sar co lem mal and mi toc hon dri al ATP-de pen dent po tas si um chan nels are imp li ca ted to mo du la te po si ti ve inot ro pic ef fect of le vo si men dan in hu man at ri al tra be cu la e. K Ke ey y W Wo or rd ds s: : Simendan; potassium channels; cardiotonic agents Ö ÖZ ZE ET T A Am ma aç ç: : Bu ça lış ma nın ama cı izo le in san at ri yal tra be kü ler ka sın da po tas yum ka nal blo ke edici ajan la rın le vo si men da nın po zi tif inot ro pik et ki le ri ni mo dü le edip ede me di ği ni araş tır mak tır. G Ge e --r re eç ç v ve e Y Yö ön n t te em m l le er r: : Sağ at ri yal apen diks ör nek le ri (1 cm 2 , 500-1.000 mg) alın dı ve ön ce den ok si je ni ze edil miş mo di fi ye Tyro de so lüs yo nu na ko nu la rak or gan ban yo su na asıl dı. Le vo si men da nın kon santras yon-et ki iliş ki si tek ba şı na (10-9 ile 10-4 M), Ca2 -ba ğım lı po tas yum ka nal blo kö rü 4-ami no piri din (4-AP: 500 µM), ATP-ba ğım lı po tas yum ka nal blo kö rü gli benk la mid (1µM) ve ya mi to kon dri al ATP-ba ğım lı po tas yum ka nal blo kö rü 5-hid rok si de ko nat (5-HD: 300 µM) ile bir lik te olu şan ka sıl -ma gü cü araş tı rıl mak ama cıy la pre pa rat lar ha zır lan dı. B Bu ul l g gu u l la ar r: : Le vo si men dan % ka sıl ma gü cün de kon san tras yon-ba ğım lı ar tı şa ne den ol du. İnsan at ri yal tra be kü la sı nın le vo si men dan için hem sensi ti vi te si (PD2) hem de mak si mum ya nı tı (Emax), gli benk la mid (5.83 ± 0.04 ve 17.4 ± 1.61 mN) ve 5-HD...

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Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression

et al. 2005

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Comparision of the Inotropic Effects of Levosimendan, Rolipram, and Dobutamine on Human Atrial Trabeculae

Cited by 22 publications

References 32 publications

Inhibition of cardiac contractility by 5-hydroxydecanoate and tetraphenylphosphonium ion: a possible role of mitoK_ATP in response to inotropic stress

Inhibition of cardiac contractility by 5-hydroxydecanoate and tetraphenylphosphonium ion: a possible role of mitoK_ATP in response to inotropic stress

Positive Inotropic Effects of Levosimendan are Modulated by KATP Channels in Isolated Human Atrial Trabeculae

Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression

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Comparision of the Inotropic Effects of Levosimendan, Rolipram, and Dobutamine on Human Atrial Trabeculae

Cited by 22 publications

References 32 publications

Inhibition of cardiac contractility by 5-hydroxydecanoate and tetraphenylphosphonium ion: a possible role of mitoKATP in response to inotropic stress

Inhibition of cardiac contractility by 5-hydroxydecanoate and tetraphenylphosphonium ion: a possible role of mitoKATP in response to inotropic stress

Positive Inotropic Effects of Levosimendan are Modulated by KATP Channels in Isolated Human Atrial Trabeculae

Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression

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Inhibition of cardiac contractility by 5-hydroxydecanoate and tetraphenylphosphonium ion: a possible role of mitoK_ATP in response to inotropic stress

Inhibition of cardiac contractility by 5-hydroxydecanoate and tetraphenylphosphonium ion: a possible role of mitoK_ATP in response to inotropic stress