Search

A vérnyomás változása befolyásolhatja az áramlástani jellemzőket, és ezáltal a vesék hemodinamikáját is. Fél vesés állapotban ez a hatás még jelentősebb lehet. A veseartéria környezetének in vivo mérhetetlen áramlástani jellemzőit numerikus áramlástani szimulációval hatékonyan lehet vizsgálni. A kutatás elsődleges célja annak bizonyítása volt, hogy a magas vérnyomás és az izolált szisztolés hypertonia változásokat eredményez a veseartéria áramlástani jellemzőiben, amelyek fél vesés esetben jelentősebbek. Módszer: Egy véletlenszerűen kiválasztott betegcsoport aorta-veseartéria jobb és bal oldali elágazási szögeit mértük retrospektív módon, in vivo. A veseartéria áramlástani jellemzőinek mérésére egy numerikus áramlástani szimulációsorozatot végeztünk egészséges és fél vesés modelleken. A vérnyomást először fokozatosan növeltük 120/80 Hgmm értékről 200/90 Hgmm értékig. Ezt követően az izolált szisztolés hypertonia esetét szimuláltuk a diasztolés vérnyomást fokozatosan csökkentve 200/50 Hgmm értékig. A szimuláció kimenő paraméterei a nyomás, turbulens kinetikus energia, sebesség és térfogatáram értékei voltak a veseartériák kilépő keresztmetszetén. Eredmény: A veseartéria-elágazási szögek átlaga a bal oldalon 78°, a jobb oldalon 66° volt. A szimuláció eredményei azt mutatták, hogy a magas vérnyomás és az izolált szisztolés hypertonia következetesen változtatják a veseartéria áramlástani jellemzőit, fél vesés esetben nagyobb mértékben. Konklúziók: A vesét károsíthatja a nagyobb nyomás, a turbulencianövekedés atherosclerosishoz vezethet a veseartéria elágazásánál. Ezek a jellemzők nagyobb mértékben változnak fél vesés állapotban, így ez veszélyesebb a vesére nézve. Az áramlási sebesség és térfogatáram értékei azonban nem függenek szignifikánsan a fél vesés állapottól.

A párhuzamos szövegek a nyelvi közvetítésnek nélkülözhetetlen, de a magyar nyelvű fordítástudományban csak elvétve tárgyalt segédeszközei. A tanulmány először is rámutat, hogy a terminusnak két jelentése van. A szűkebb meghatározás szerint a párhuzamos szöveg nem fordítás, a tágabb szerint viszont fordítás is lehet. A párhuzamos szöveg Genette transztextualitási modelljében (1982) a hiper- és az intertextualitás egyik válfaja, Heltai szerint (2020a) pedig felfogható plágiumként is. Nord (1997) azzal indokolja a párhuzamos szövegek szükségessé- gét, hogy a fordítóknak egyelőre nem állnak összehasonlító szövegtipológiai tan- könyvek a rendelkezésükre. Nordnál a párhuzamos szöveg csak egyike az ún. segédszövegeknek, amelyek közé a minta-, az összehasonlítható és a referenciaszövegek tartoznak. A fordító kényelemből és időnyerés céljából használ párhuzamos szövegeket, hiszen a kommunikatív helyzetekben sok az ismétlődés, így sosem kell nulláról kezdeni. Ugyanakkor a párhuzamos szöveg segít megtalálni a természetes ekvivalenciát (Pym 2007), azaz a fordítástól független, az adott helyzetre jellemző célnyelvi kifejezésmódot. A tanulmány számos példával szemlélteti, hogy a párhuzamos szövegek vizsgálatával a fordító hogyan kerülheti el az elavult vagy a szaknyelvbe nem illő köznyelvi szavak és szerkezetek használatát. Végül egy rövid esettanulmány bemutatja a magyar és a spanyol büntető törvénykönyvnek mint párhuzamos szövegeknek azokat a jegyeit, amelyek megkönnyítik a stílusos spa- nyol és magyar fordítás elkészítését.

Background In the GLOBAL LEADERS trial, ticagrelor monotherapy beyond 1 month compared with standard antiplatelet regimens after coronary stent implantation did not improve outcomes at intention‐to‐treat analysis. Considerable differences in treatment adherence between the experimental and control groups may have affected the intention‐to‐treat results. In this reanalysis of the GLOBAL LEADERS trial, we compared the experimental and control treatment strategies in a per‐protocol analysis of patients who did not deviate from the study protocol. Methods and Results Baseline and postrandomization information were used to classify whether and when patients were deviating from the study protocol. With logistic regressions, we derived time‐varying inverse probabilities of nondeviation from protocol to reconstruct the trial population without protocol deviation. The primary end point was a composite of all‐cause mortality or nonfatal Q‐wave myocardial infarction at 2 years. At 2‐year follow‐up, 1103 (13.8%) of 7980 patients in the experimental group and 785 (9.8%) of 7988 patients in the control group qualified as protocol deviators. At per‐protocol analysis, the rate ratio for the primary end point was 0.88 (95% CI, 0.75–1.03; P =0.10) on the basis of 274 versus 325 events in the experimental versus control group. The rate ratio for the key safety end point of major bleeding was 1.00 (95% CI, 0.79–1.26; P =0.99). The per‐protocol and intention‐to‐treat effect estimates were overall consistent. Conclusions Among patients who complied with the study protocol in the GLOBAL LEADERS trial, ticagrelor plus aspirin for 1 month followed by ticagrelor monotherapy was not superior to 1‐year standard dual antiplatelet therapy followed by aspirin alone at 2 years after coronary stenting. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01813435.

If Bicska Maxi exists, where is Egjaro Lukacs?Translating meaning in literary names The study offers a review of the strategies employed in the translation of charactonyms from literary works, comic books, and live-action, puppet, and cartoon movies written in foreign languages in Hungarian literary translations, subtitles, and dubbed texts. The approximately 300 names in the corpus are organised according to the categories set out by J. Soltesz: signalling names (names with obscure etymologies) and word names (names with discernible origins). These can come into contact in four ways: (1) signalling name → signalling name, (2) signalling name → word name, (3) word name → signalling name, and (4) word name → word name. Based on the analysis of these types, translators perform about 20 different operations, from preserving names unaltered to the literal translation of names. Some of these methods can be classified into several groups. Thus, future research should compare the results with the typology outlined by Vermes, and research should be extended to translations with Hungarian as a source language.

BACKGROUND: Despite primary PCI (PPCI), ST-elevation myocardial infarction (STEMI) can still result in large infarct size (IS). New technology with rapid intravascular cooling showed positive signals for reduction in IS in anterior STEMI. AIMS: We investigated the effectiveness and safety of rapid systemic intravascular hypothermia as an adjunct to PPCI in conscious patients, with anterior STEMI, without cardiac arrest. METHODS: Hypothermia was induced using the ZOLL™ Proteus™️ intravascular cooling system. After randomisation of 111 patients, 58 to hypothermia and 53 to control groups, the study was prematurely discontinued by the sponsor due to inconsistent patient logistics between the groups resulting in significantly longer total ischaemic delay in the hypothermia group (232 vs 188 minutes; p

Purpose Psoriasis is one of the most common lifelong lasting dermatologic diseases. According to the latest studies, psoriatic patients have a higher risk of developing cardiovascular diseases. Psoriasis is considered as a systemic inflammatory disease. Several oxidative stress markers have been shown to be elevated in psoriasis. However, a panel of biomarkers has not been used yet. This study was aimed at exploring the connection between a panel of biomarkers (C-reactive protein, asymmetric dimethylarginine, uric acid, total antioxidant capacity, malondialdehyde, and orosomucoid [ORM]) and cardiovascular risk in psoriatic patients. Patients and methods The inclusion criterion was the onset of psoriasis with skin lesions. Exclusion criteria were impaired renal function (eGFR

Background: The authors analyzed data from the Hungarian Myocardial Infarction Registry (HUMIR) to examine the potential impact of gender on the treatment and 30-day and 1-year mortality o...

The development of heart failure is the most powerful predictor of long-term mortality in patients surviving acute myocardial infarction (MI). There is an unmet clinical need for prevention and therapy of post-myocardial infarction heart failure (post-MI HF). Clinically relevant pig models of post-MI HF are prerequisites for final proof-of-concept studies before entering into clinical trials in drug and medical device development. Here we aimed to characterize a closed-chest porcine model of post-MI HF in adult Gottingen minipigs with long-term follow-up including serial cardiac magnetic resonance imaging (CMRI) and to compare it with the commonly used Landrace pig model. MI was induced by intraluminal balloon occlusion of the left anterior descending coronary artery for 120 min in Gottingen minipigs and for 90 min in Landrace pigs, followed by reperfusion. CMRI was performed to assess cardiac morphology and function at baseline in both breeds and at 3 and 6 months in Gottingen minipigs and at 2 months in Landrace pigs, respectively. Scar sizes were comparable in the two breeds, but MI resulted in a significant decrease of left ventricular ejection fraction (LVEF) only in Gottingen minipigs, while Landrace pigs did not show a reduction of LVEF. Right ventricular (RV) ejection fraction increased in both breeds despite the negligible RV scar sizes. In contrast to the significant increase of left ventricular end-diastolic (LVED) mass in Landrace pigs at 2 months, Gottingen minipigs showed a slight increase in LVED mass only at 6 months. In summary, this is the first characterization of post-MI HF in Gottingen minipigs in comparison to Landrace pigs, showing that the Gottingen minipig model reflects post-MI HF parameters comparable to the human pathology. We conclude that the Gottingen minipig model is superior to the Landrace pig model to study the development of post-MI HF.

Aims Interleukin-1β (IL-1β) is an important pathogenic factor in cardiovascular diseases including chronic heart failure (HF). The CANTOS trial highlighted that inflammasomes as primary sources of IL-1 β are promising new therapeutic targets in cardiovascular diseases. Therefore, we aimed to assess inflammasome activation in failing hearts to identify activation patterns of inflammasome subtypes as sources of IL-1β. Methods and results Out of the four major inflammasome sensors tested, expression of the inflammasome protein absent in melanoma 2 (AIM2) and NLR family CARD domain-containing protein 4 (NLRC4) increased in human HF regardless of the aetiology (ischaemic or dilated cardiomyopathy), while the NLRP1/NALP1 and NLRP3 (NLR family, pyrin domain containing 1 and 3) inflammasome showed no change in HF samples. AIM2 expression was primarily detected in monocytes/macrophages of failing hearts. Translational animal models of HF (pressure or volume overload, and permanent coronary artery ligation in rat, as well as ischaemia/reperfusion-induced HF in pigs) demonstrated activation pattern of AIM2 similar to that of observed in end-stages of human HF. In vitro AIM2 inflammasome activation in human Tohoku Hospital Pediatrics-1 (THP-1) monocytic cells and human AC16 cells was significantly reduced by pharmacological blockade of pannexin-1 channels by the clinically used uricosuric drug probenecid. Probenecid was also able to reduce pressure overload-induced mortality and restore indices of disease severity in a rat chronic HF model in vivo. Conclusions This is the first report showing that AIM2 and NLRC4 inflammasome activation contribute to chronic inflammation in HF and that probenecid alleviates chronic HF by reducing inflammasome activation. The present translational study suggests the possibility of repositioning probenecid for HF indications.

Background We hypothesised that ticagrelor, in combination with aspirin for 1 month, followed by ticagrelor alone, improves outcomes after percutaneous coronary intervention compared with standard antiplatelet regimens. Methods GLOBAL LEADERS was a randomised, open-label superiority trial at 130 sites in 18 countries. Patients undergoing percutaneous coronary intervention with a biolimus A9-eluting stent for stable coronary artery disease or acute coronary syndromes were randomly assigned (1:1) to 75-100 mg aspirin daily plus 90 mg ticagrelor twice daily for 1 month, followed by 23 months of ticagrelor monotherapy, or standard dual antiplatelet therapy with 75-100 mg aspirin daily plus either 75 mg clopidogrel daily (for patients with stable coronary artery disease) or 90 mg ticagrelor twice daily (for patients with acute coronary syndromes) for 12 months, followed by aspirin monotherapy for 12 months. Randomisation was concealed, stratified by centre and clinical presentation (stable coronary artery disease vs acute coronary syndrome), and blocked, with randomly varied block sizes of two and four. The primary endpoint at 2 years was a composite of all-cause mortality or non-fatal centrally adjudicated new Q-wave myocardial infarction as assessed by a core lab in a blinded manner. The key secondary safety endpoint was site-reported bleeding assessed according to the Bleeding Academic Research Consortium criteria (grade 3 or 5). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01813435, and is closed to new participants, with followup completed. Findings Between July 1, 2013, and Nov 9, 2015, 15 968 participants were randomly assigned, 7980 to the experimental group and 7988 to the control group. At 2 years, 304 (3.81%) participants in the experimental group had died or had a non-fatal centrally adjudicated new Q-wave myocardial infarction, compared with 349 (4.37%) participants in the control group (rate ratio 0.87 [95% CI 0. 75-1. 01]; p=0.073]). There was no evidence for a difference in treatment effects for the primary endpoint across prespecified subgroups of acute coronary syndromes and stable coronary artery disease (p=0.93). Grade 3 or 5 bleeding occurred in 163 participants in the experimental group and 169 in the control group (2.04% vs 2.12%; rate ratio 0.97 [95% CI 0. 78-1. 20]; p=0.77). Interpretation Ticagrelor in combination with aspirin for 1 month followed by ticagrelor alone for 23 months was not superior to 12 months of standard dual antiplatelet therapy followed by 12 months of aspirin alone in the prevention of all-cause mortality or new Q-wave myocardial infarction 2 years after percutaneous coronary intervention. Copright (C) 2018 Elsevier Ltd. All rights reserved. European Clinical Research Institute; Biosensors International; AstraZeneca; Medicines Company; Canada Research Chairs Programme

Aim: We aimed to investigate the effects of a single carbon dioxide (CO(2)) treatment on arterial stiffness by monitoring the changes of aortic pulse-wave velocity (PWV) and aortic augmentation index (AIXao), which are indicators of arterial stiffness. Patients and Methods: PWV and AIXao were measured by an invasively validated oscillometric device. The measurements of stiffness parameters were performed before the CO(2) treatment, and at 1, 4 and 8 h after the first treatment. Results: Thirty-one patients were included. No significant changes were found in PWV. AIXao decreased significantly 1 h and 4 h after CO(2) treatment compared to baseline values (p=0.034 and p

Increased production of reactive oxygen species has been implicated in the pathogenesis of congestive heart failure. However, emerging evidence suggests a role for reactive oxygen species in regulating various physiological cellular processes in the myocardium. The authors summarize the current understanding of involvement of reactive oxygen species in the regulation of cardiac contractility under physiological conditions. Orv. Hetil., 2015, 156(47), 1912–1915.

Background The impact of high platelet reactivity (HPR) on clinical outcomes after elective percutaneous coronary interventions (PCI) with drug-eluting balloons (DEB) due to in-stent restenosis (ISR) is unknown. Objective We sought to evaluate the prognostic importance of HPR together with conventional risk factors in patients treated with DEB. Methods Patients treated with DEB due to ISR were enrolled in a single-centre, prospective registry between October 2009 and March 2015. Only patients with recent myocardial infarction (MI) received prasugrel, others were treated with clopidogrel. HPR was defined as an ADP-test >46U with the Multiplate assay and no adjustments were done based on results. The primary endpoint of the study was a composite of cardiovascular mortality, MI, any revascularization or stroke during one-year follow-up. Results 194 stable angina patients were recruited of whom 90% were treated with clopidogrel. Clinical characteristics and procedural data were available for all patients; while platelet function testing was performed in 152 subjects of whom 32 (21%) had HPR. Patients with HPR had a higher risk for the primary endpoint (HR: 2.45; CI: 1.01–5.92; p = 0.03). The difference was primarily driven by a higher risk for revascularization and MI. According to the multivariate analysis, HPR remained a significant, independent predictor of the primary endpoint (HR: 2.88; CI: 1.02–8.14; p = 0.04), while total DEB length and statin treatment were other independent correlates of the primary outcome. Conclusion HPR was found to be an independent predictor of repeat revascularization and MI among elective patients with ISR undergoing PCI with DEB.

Aims: We aimed to investigate the rapid induction of therapeutic hypothermia using the ZOLL Proteus Intravascular Temperature Management System in patients with anterior ST-elevation myocardial infarction (STEMI) without cardiac arrest. Methods and results: A total of 50 patients were randomised; 22 patients (88%; 95% confidence interval [CI]: 69-97%) in the hypothermia group and 23 patients (92%; 95% CI: 74-99) in the control group completed cardiac magnetic resonance imaging at four to six days and 30-day follow-up. Intravascular temperature at coronary guidewire crossing after 20.5 minutes of endovascular cooling decreased to 33.6°C (range 31.9-35.5°C). There was a 17-minute (95% CI: 4.6-29.8 min) cooling-related delay to reperfusion. In “per protocol” analysis, median infarct size/left ventricular mass was 16.7% in the hypothermia group versus 23.8% in the control group (absolute reduction 7.1%, relative reduction 30%; p=0.31) and median left ventricular ejection fraction (LVEF) was 42% in the hypothermia group and 40% in the control group (absolute reduction 2.4%, relative reduction 6%; p=0.36). Except for self-terminating paroxysmal atrial fibrillation (32% versus 8%; p=0.074), there was no excess of adverse events in the hypothermia group. Conclusions: We rapidly and safely cooled patients with anterior STEMI to 33.6°C at the time of coronary guidewire crossing. This is ≥1.1°C lower than in previous cooling studies. Except for self-terminating atrial fibrillation, there was no excess of adverse events and no clinically important cooling-related delay to reperfusion. A statistically non-significant numerical 7.1% absolute and 30% relative reduction in infarct size warrants a pivotal trial powered for efficacy. ClinicalTrials.gov Identifier: NCT02509832

Objectives This study sought to evaluate the impact of treatment with prasugrel and high-dose clopidogrel on the basis of platelet function testing in patients with acute coronary syndrome (ACS) who are undergoing percutaneous coronary intervention (PCI). Background The clinical impact of treatment with prasugrel in patients with ACS who have high platelet reactivity (HPR) is unknown. Methods Patients with ACS who were pre-treated with clopidogrel and undergoing successful PCI were enrolled in a single-center, prospective registry. Platelet function was measured 12 to 36 h after PCI with the Multiplate device (Roche Diagnostics GmbH, Mannheim, Germany). Patients with HPR (>46 U) were switched to prasugrel or treated with high-dose clopidogrel, and those without HPR continued treatment with 75 mg of clopidogrel. Results A total of 741 consecutive patients were enrolled in the study between September 2011 and August 2012, and 219 of these patients (29.5%) had HPR. Although platelet reactivity decreased after treatment adjustments in those with HPR, prasugrel provided significantly more potent platelet inhibition compared with high-dose clopidogrel (p Conclusions Switching patients with ACS who have HPR to treatment with prasugrel reduces thrombotic and bleeding events to a level similar to that of those without HPR; however, there is a higher risk of both thrombotic and bleeding complications with high-dose clopidogrel.

The diagnostic characteristics of electromechanical mapping (EMM) were evaluated in porcine myocardial infarction (MI) models with the parallel application of cardiac magnetic resonance imaging (cMRI) from the aspect of different pathophysiology and localization. Balloon occlusion in the left anterior descending coronary artery (LAD balloon group) or coil deployment in the LAD (LAD coil group) or circumflex artery (Cx coil group) was applied percutaneously in 16 domestic pigs. Regional left ventricular viability data were captured via cMRI and EMM. The unipolar voltage (UV) value was significantly decreased in segments containing transmural and subendocardial late enhancement compared with viable segments in the LAD balloon, LAD coil, and Cx coil groups. Receiver operating characteristic analysis revealed area under the curve values of 0.809 and 0.691 in the LAD infarct territory, and 0.864 and 0.855 in the Cx infarct territory for the UV compared with cMRI viability results as transmural late enhancement or viable tissue and subendocardial late enhancement or viable tissue, respectively. In conclusion, the UV value detected the presence of scar tissue with differential transmural extent and which represented proper diagnostic features both in the reperfused and nonreperfused models. This data could provide additional benefit in the clinical use of EMM for diagnostic purposes.

Background: In our earlier studies both corticosterone and cortisol had antioxidant effect in vitro. Objectives: Our aim was to clarify whether corticosterone and cortisol oral administration results in beneficial antioxidant changes in Sprague-Dawley adult male rats in vivo. Methods: Experimental animals were fed a lipid rich diet and treated with corticosterone or cortisol in the drinking fluid. Control group was fed only lipid rich diet with untreated drinking water. The untreated group was fed a normal diet with untreated water. Total scavenger capacity (TSC) was measured before and after 4 weeks of treatment in blood samples using a chemiluminometric assay. Results: Both corticosterone and cortisol treatment caused increased TSC. The control group and the untreated group showed no significant changes in TSC. Conclusion: Our results support the hypothesis that corticosterone and cortisol administration can improve the antioxidant status not only in vitro but also in vivo.

Objectives The aim of this landmark exploratory analysis, ATLANTIC-H 24 , was to evaluate the effects of pre-hospital ticagrelor during the first 24 h after primary percutaneous coronary intervention (PCI) in the ATLANTIC (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery) study. Background The ATLANTIC trial in patients with ongoing ST-segment elevation myocardial infarction showed that pre-hospital ticagrelor was safe but did not improve pre-PCI coronary reperfusion compared with in-hospital ticagrelor. We hypothesized that the effect of pre-hospital ticagrelor may not have manifested until after PCI due to the rapid transfer time (31 min). Methods The ATLANTIC-H 24 analysis included 1,629 patients who underwent PCI, evaluating platelet reactivity, Thrombolysis In Myocardial Infarction flow grade 3, ≥70% ST-segment elevation resolution, and clinical endpoints over the first 24 h. Results Following PCI, largest between-group differences in platelet reactivity occurred at 1 to 6 h; coronary reperfusion rates numerically favored pre-hospital ticagrelor, and the degree of ST-segment elevation resolution was significantly greater in the pre-hospital group (median, 75.0% vs. 71.4%; p = 0.049). At 24 h, the composite ischemic endpoint was lower with pre-hospital ticagrelor (10.4% vs. 13.7%; p = 0.039), as were individual endpoints of definite stent thrombosis (p = 0.0078) and myocardial infarction (p = 0.031). All endpoints except death (1.1% vs. 0.2%; p = 0.048) favored pre-hospital ticagrelor, with no differences in bleeding events. Conclusions The effects of pre-hospital ticagrelor became apparent after PCI, with numerical differences in platelet reactivity and immediate post-PCI reperfusion, associated with reductions in ischemic endpoints, over the first 24 h, whereas there was a small excess of mortality. (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery [ATLANTIC, NCT01347580 ])

Background: Randomized trials assess the potential of a medical device in well defined indications while “all comer studies” reveal the device performance in the real clinical environment. Aims: This ‘all comers’ registry assessed the 10-month outcome of the Coroflex® Please drug-eluting stent in Europe and Asia by clinically driven major adverse cardiac events. Methods: The Coroflex® Please Registry was an international, prospective, multicenter registry enrolling patients with symptomatic ischemic heart disease. The primary endpoint was clinically driven target lesion revascularization (TLR) at 9 months. Secondary endpoints were technical success, in-hospital outcomes, definite stent thrombosis and major adverse cardiac events (death, myocardial infarction, or TLR) for subgroup analyses. Results: Of the enrolled 1230 patients (63.6 ± 11.2 years, 33.9% diabetics), 339 (27.6%) had an acute coronary syndrome, 148 (12.1%) STEMI and 191 (15.6%) NSTEMI. After 10.5 ± 3.8 months (follow-up rate 92.8%), the target lesion revascularization rate (TLR) was 7.8% overall, 8.3% in STEMI, and 11.3% in NSTEMI patients. Total MACE was 11.1% and significantly higher in ACS with either diabetes mellitus (22.9%, p = 0.017) or age ≥75 years (25.4%, p = 0.026). In European and Asian patients MI rates (5.2% vs 3.1%, p = 0.135) and cardiac death rates (1.6% vs 0.9%, p = 0.414) were similar. The MACE rate was higher in Europe (13.6% vs 4.7%, p

Increased production of reactive oxygen species has been implicated in the pathogenesis of congestive heart failure. However, emerging evidence suggests a role for reactive oxygen species in regulating various physiological cellular processes in the myocardium. The authors summarize the current understanding of involvement of reactive oxygen species in the regulation of cardiac contractility under physiological conditions.

Eur J Clin Invest 2012; 42 (4): 384–392 Abstract Background The GRAVITAS trial showed that 150 mg clopidogrel did not improve outcome in patients with high on-clopidogrel platelet reactivity (HPR) screened by the VerifyNow assay. We aimed to determine the impact of 150 mg clopidogrel in stable angina patients with HPR identified with conventional aggregometry (LTA). Materials and methods Clopidogrel-naive stable angina patients before ad hoc percutaneous coronary intervention were recruited into a randomized, double-blind, placebo-controlled trial (NCT00638326). Twelve to 24 h after the 600-mg loading dose of clopidogrel, ADP5μM-stimulated maximal (AGGmax), late platelet aggregation (AGGlate) and vasodilator-stimulated phosphoprotein phosphorylation (VASP-PRI) were evaluated. Patients with HPR (AGGmax ≥ 34%) were randomly allocated to 75 or 150 mg clopidogrel after 4 weeks. After control platelet function measurements at day 28, 75 mg clopidogrel was administered to all patients until 1 year. Results The study was prematurely terminated at the stage of 200 enroled patients. Administration of 150 mg clopidogrel significantly reduced platelet aggregation (AGGmax: 45·0 ± 6·8 vs. 33·8 ± 15·1, P

Coronary angiography is currently the gold standard in the diagnosis of coronary heart disease. Selective coronary artery opacification provides invaluable information of the residual vascular lumen; however, the method itself has several limitations in terms of low resolution and lack of information about the adjacent tissues. Hence, several alternative methods have been introduced to improve the diagnostic value of cardiac catheterization. These include physiological measurements as well as auxiliary methods that provide more detailed anatomical information such as intravascular ultrasound imaging. Optical coherence tomography (OCT) is a novel method providing high-resolution imaging of the internal coronary surface and the underlying tissues. In this article, we review the background of optical coherence imaging, providing context to its applicability in relation to the current practice of coronary catheterization. Applicability of OCT is demonstrated by the presentation of the first case of coronary OCT in Hungary.

A growing number of observational studies suggest that high on-clopidogrel platelet reactivity (HPR) is associated with recurrent thrombotic events after percutaneous coronary intervention. We aimed to perform an updated systematic review and meta-analysis on the clinical relevance of HPR to summarize the available evidence and to define more precise effect estimates.Relevant observational studies published between January 2003 and February 2010 were searched that presented intent-to-treat analyses on the clinical relevance of HPR measured with an adenosine diphosphate (ADP)-specific platelet function assay. The main outcome measures were cardiovascular (CV) death, definite/probable stent thrombosis (ST), nonfatal myocardial infarction (MI), and a composite end point of reported ischemic events. The outcome parameters were pooled with the random-effect model via generic inverse variance weighting.Twenty studies comprising a total number of 9,187 patients qualified. High on-clopidogrel platelet reactivity appeared to be a strong predictor of MI, ST, and the composite end point of reported ischemic events (odds ratios [95% CI]: 3.00 [2.26-3.99], 4.14 [2.74-6.25], and 4.95 [3.34-7.34], respectively; P.00001 for all cases). According to the meta-analysis, patients with HPR had a 3.4-fold higher risk for CV death compared with patients with normal ADP reactivity (odds ratio 3.35, 95% CI 2.39-4.70, P.00001). Although there were large differences in the methodology as well as in the definition of HPR between studies, the predicted risk for CV death, MI, or ST was not heterogeneous (I(2): 0%, 0%, and 12%, respectively; P = not significant for all cases).High on-clopidogrel platelet reactivity, measured by an ADP-specific platelet function assay, is a strong predictor of CV death, MI, and ST in patients after percutaneous coronary intervention.

Background Although transradial percutaneous coronary intervention (TRPCI) is widely applied for percutaneous procedures, its safety in the setting of ST-segment elevation (STEMI) is controversial. Our aim was to assess the safety and efficacy of TRPCI versus transfemoral PCI in the context of treating patients suffering acute myocardial infarction with STEMI. Methods Randomized, case-control, and cohort studies comparing access-related complications were analyzed. Our objective was to determine if radial access reduces major bleeding and thereby reduces death and ischemic events compared to femoral access in this setting. A fixed-effects model was used with random effects for sensitivity analysis. Results Twelve studies involving 3324 patients were identified. Transradial PCI reduced major bleeding compared to transfemoral PCI ( P = .0001), and significant reductions were found in the composite of death, myocardial infarction, or stroke ( P = .001). Mortality reduction showed a significant toward benefit in the case of TRPCI (2.04% vs 3.06%, OR 0.54 [95% CI 0.33-0.86], P = .01). The fluoroscopic time was longer, and access site crossover was more frequent for TRPCI ( P = .001, P Conclusions Transradial PCI reduces the risk of periprocedural major bleeding and major adverse events in the STEMI setting.

Clinical significance of resistance to aspirin and thienopyridine therapy is poorly defined. The authors aimed to evaluate whether more effective antiplatelet therapy is associated with better outcome in patients on dual-antiplatelet treatment. Using optical aggregometer, maximal platelet aggregation values were measured with induction of adenosine diphosphate, collagen, and adrenaline 30 ± 5 days after coronary stent implantation in 134 patients. Markers of platelet activation were also analyzed with fluorescent immunoassay in 57 patients. After 10 months of follow-up, 33 patients reached the composite endpoint of cardiovascular death, myocardial infarction, and revascularisation. Adenosine diphosphate-induced maximal aggregation values were in significant relationship with the development of major adverse cardiac events ( P < .01). Level of soluble P-selectin proved to be an independent risk factor of adverse outcome ( P < .05). As efficacy of thienopyridine therapy showed significant relation with clinical outcome, the authors conclude that interindividual variability in response to adenosine diphosphate-receptor antagonists may be of substantial clinical importance.

Summary Background Intracoronary stenting can improve procedural success and reduce restenosis compared with balloon angioplasty in patients with acute coronary syndromes, but can also increase the rate of thrombotic complications including stent thrombosis. The TRITON–TIMI 38 trial has shown that prasugrel—a novel, potent thienopyridine—can reduce ischaemic events compared with standard clopidogrel therapy. We assessed the rate, outcomes, and prevention of ischaemic events in patients treated with prasugrel or clopidogrel with stents in the TRITON–TIMI 38 study. Methods Patients with moderate-risk to high-risk acute coronary syndromes were included in our analysis if they had received at least one coronary stent at the time of the index procedure following randomisation in TRITON-TIMI 38, and were further subdivided by type of stent received. Patients were randomly assigned in a 1 to 1 fashion to receive a loading dose of study drug (prasugrel 60 mg or clopidogrel 300 mg) as soon as possible after randomisation, followed by daily maintenance therapy (prasugrel 10 mg or clopidogrel 75 mg). All patients were to receive aspirin therapy. Treatment was to be continued for a minimum of 6 months and a maximum of 15 months. Randomisation was not stratified by stents used or stent type. The primary endpoint was the composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke. Stent thrombosis was assessed using Academic Research Consortium definitions, and analysis was by intention to treat. TRITON-TIMI 38 is registered with ClinicalTrials.gov, number NCT00097591. Findings 12 844 patients received at least one coronary stent; 5743 received only drug-eluting stents, and 6461 received only bare-metal stents. Prasugrel compared with clopidogrel reduced the primary endpoint (9·7 vs 11·9%, HR 0·81, p=0·0001) in the stented cohort, in patients with only drug-eluting stents (9·0 vs 11·1%, HR 0·82, p=0·019), and in patients with only bare-metal stents (10·0 vs 12·2%, HR 0·80, p=0·003). Stent thrombosis was associated with death or myocardial infarction in 89% (186/210) of patients. Stent thrombosis was reduced with prasugrel overall (1·13 vs 2·35%, HR 0·48, p vs 2·31%, HR 0·36, p vs 2·41%, HR 0·52, p=0·0009). Interpretation Intensive antiplatelet therapy with prasugrel resulted in fewer ischaemic outcomes including stent thrombosis than with standard clopidogrel. These findings were statistically robust irrespective of stent type, and the data affirm the importance of intensive platelet inhibition in patients with intracoronary stents. Funding TRITON–TIMI 38 was supported by research grants from Daiichi Sankyo and Eli Lilly.

Bland-White-Garland syndrome (BWG) is a rare congenital anomaly that is predominantly discovered in infancy. BWG is characterized by an anomalous origin of the left coronary trunk from the pulmonary artery that produces a coronary steal phenomenon, left-to-right shunt, and thus an abnormal left ventricular perfusion. The latter may induce myocardial necrosis, left ventricular dysfunction and commonly associated with mitral regurgitation. Despite its high mortality without surgical repair in infancy, several cases were reported to reach adulthood. In some patients, however, BWG was revealed only in older age, and may cause mild symptoms. Recent developments in cardiovascular MRI enable the determination of heart function, viability and perfusion with high resolution. We present three middle-aged female BWG cases indicating that MRI studies may give further insight into the therapeutic decision making in this age-group.

Aims To evaluate clinical outcomes in patients receiving the next-generation, paclitaxel-eluting, platinum-chromium TAXUS Element stent in a real-world setting. The PERSEUS Workhorse and Small Vessel studies showed positive results with the TAXUS Element stent in a clinical trial setting. Methods and results TE-PROVE was a prospective, open-label, multicentre, "all-comers" study which enrolled 1,014 patients at 37 European sites. Follow-up was at 30 days, six months and one year, and will continue annually up to five years. The primary endpoint was overall and stent-related target vessel failure (TVF), defined as cardiac death, target vessel-related myocardial infarction (MI) and target vessel revascularisation (TVR) at one year post implantation. Secondary endpoints included the components of TVF, all-cause mortality, and ARC definite/probable stent thrombosis. Follow-up was available in 97.3% (987/1,014) of patients. Patients were 75.0% male (760/1,014), mean age was 65.1±10.8 years, 25.5% had medically treated diabetes (259/1,014), and 10.7% (109/1,014) were treated for STEMI. At baseline, mean lesion length among 1,299 treated lesions was 19.8±12.0 mm and mean reference vessel diameter was 3.1±0.5 mm. At one year, the rate of TVF (primary endpoint) was 6.0% (59/987) overall; 3.7% (37/987) of TVF events were stent-related. Cardiac death was 0.7% (7/987), target vessel-related MI was 1.1% (11/987), and TVR was 4.7% (46/987). All-cause death occurred in 1.2% (12/987) of patients and ARC definite/probable ST was 0.5% (5/987). Conclusions The primary endpoint results from the TE-PROVE registry demonstrate good performance and safety for the TAXUS Element paclitaxel-eluting stent at one year in everyday clinical practice. Clinical trial registration information NCT01242696.

Purpose To demonstrate that contrast-enhanced MRI (ceMRI) with the aid of Gd(ABE-DTTA) is able to detect ischemic events in the heart in a canine ischemia/reperfusion (30/40 minutes) model. Materials and Methods ECG-gated, T1-weighted MR image sets (four to five slices each) with three-minute time resolution were collected in transiently LAD-occluded dogs. Following the acquisition of control image sets, ischemia was started by occluding the LAD. Either Gd(ABE-DTTA) (N = 6) or Gd(DTPA) (N = 6) was injected, and imaging was continued for 30 minutes of ischemia and 40 minutes of reperfusion. The contrast agent (CA)-induced MRI signal intensity enhancement (SIE) and contrast were monitored. Microspheres measured myocardial perfusion (MP) to verify areas of ischemia and reperfusion. Results SIEs of 86% ± 3% and 97% ± 3% in nonischemic, and 25% ± 5% and 29% ± 8% in ischemic regions were found within three minutes of onset of ischemia with Gd(ABE-DTTA) and Gd(DTPA), respectively. For the rest of the 30 minutes of ischemia, with Gd(ABE-DTTA) SIE of 60% ± 3% and 25% ± 5% persisted in the nonischemic and ischemic regions, respectively. With Gd(DTPA), however, SIE in the nonischemic areas decreased rapidly after the first three minutes of ischemia, while SIE in the ischemic areas increased, abolishing contrast. Thus, there was a persistent contrast with Gd(ABE-DTTA) and a short-lived contrast with Gd(DTPA) during ischemia. Furthermore, with Gd(ABE-DTTA) some contrast was still visible in the early reperfusion period. Conclusion Gd(ABE-DTTA) in an ischemia/reperfusion model induces a persistent MRI contrast between regions of normal and ischemic myocardium, and verifies reperfusion. Therefore, it can be used to detect myocardial ischemic events. J. Magn. Reson. Imaging 2005;21:536–545. © 2005 Wiley-Liss, Inc.

Coronary thrombosis and secondary embolization remain two of the major challenges of intervention in myocardial infarction. Pharmacological dissolution as well as instruments to evacuate the thrombotic mass with or without distal protection have been applied in the acute interventions with variable degrees of success. With time, cross-linking of the fibrin strands results in a resilient, partially organizing coagulate that is more or less attached to the wall of the artery. The currently used devices designed to cope with recently formed thrombus may fail to disrupt these flexible structures, and pharmacological dissolution is also usually ineffective. Here, we report a case with a subacute occlusion; after failure of thrombus extraction, mechanical comminution of a clot with cutting balloons was successfully performed.

BackgroundApelin, the endogenous ligand for the G protein-coupled apelin receptor, is an important regulator of the cardiovascular homoeostasis. We previously demonstrated that apelin is one of the most potent endogenous stimulators of cardiac contractility; however, its underlying signaling mechanisms remain largely elusive. In this study we characterized the contribution of protein kinase C (PKC), extracellular signal-regulated kinase 1/2 (ERK1/2) and myosin light chain kinase (MLCK) to the positive inotropic effect of apelin.Methods and resultsIn isolated perfused rat hearts, apelin increased contractility in association with activation of prosurvival kinases PKC and ERK1/2. Apelin induced a transient increase in the translocation of PKCε, but not PKCα, from the cytosol to the particulate fraction, and a sustained increase in the phosphorylation of ERK1/2 in the left ventricle. Suppression of ERK1/2 activation diminished the apelin-induced increase in contractility. Although pharmacological inhibition of PKC attenuated the inotropic response to apelin, it had no effect on ERK1/2 phosphorylation. Moreover, the apelin-induced positive inotropic effect was significantly decreased by inhibition of MLCK, a kinase that increases myofilament Ca2+ sensitivity.ConclusionsApelin increases cardiac contractility through parallel and independent activation of PKCε and ERK1/2 signaling in the adult rat heart. Additionally MLCK activation represents a downstream mechanism in apelin signaling. Our data suggest that, in addition to their role in cytoprotection, modest activation of PKCε and ERK1/2 signaling improve contractile function, therefore these pathways represent attractive possible targets in the treatment of heart failure.

Purpose To explore the response pattern of plasma adipokine and ghrelin levels to coronary artery bypass graft (CABG) surgery in patients with (on-pump) and without (off-pump) cardiopulmonary bypass (CPB). Material/methods Sixteen consecutive patients (age: 62 ± 10 years, male: 10) with obstructive coronary artery disease (CAD) who underwent elective CABG surgery with CPB and intraoperative GIK infusion were selected for on-pump group and 19 CAD patients (age: 63 ± 10 years, male: 16) were included in the off-pump group. Blood samples were taken before, during and after surgery. Intraoperative samples were withdrawn simultaneously for peripheral vein and sinus coronarius (SC). Plasma adipokine concentrations were measured by ELISA, those of ghrelin by RIA kits. Results In response to surgical intervention there was an early, transient fall in plasma levels of adiponectin ( p p = 0.002) followed by an increase to approach their initial values. Plasma ghrelin also increased ( p = 0.045), this increase, however, was confined to the period of GIK supported CPB. Plasma insulin ( p = 0.003) and resistin ( p = 0.009) was significantly higher in the peripheral vein than in SC. The perioperative hormone profile of patients without CPB (off-pump) proved to be comparable to that of on-pump patients in spite of the insulin administration and greater oxidative and inflammatory stress. Conclusions Adipose tissue-derived factors appear to mediate the metabolic and vascular changes that occur in patients with CABG surgery. Epicardial adipose tissue is unlikely to have major contribution to the development of CAD as adipokines are not elevated in SC independent of the mode of intervention.

Similarly to patients presenting with acute coronary syndrome two kinds of animal models were evaluated by cardiac magnetic resonance imaging (cMRI) and electromechanical mapping (EMM). The balloon occlusion model characterizes the features of patients receiving reperfusion therapy, the coil

There are several experimental models for the in vivo investigation of myocardial infarction (MI) in small (mouse, rat) and large animals (dog, pig, sheep and baboons). The application of large animal models raises ethical concerns, the design of experiments needs longer follow-up times, requiring proper breeding and housing conditions, therefore resulting in higher cost, than in vitro or small animal studies. On the other hand, the relevance of large animal models is very important, since they mostly resemble to human physiological and pathophysiological processes. The first main difference among MI models is the method of induction (open or closed chest, e.g. surgical or catheter based); the second main difference is the presence or absence of reperfusion. The former (i.e. reperfused MI) allows the investigation of reperfusion injury and new catheter based techniques during percutaneous coronary interventions, while the latter (i.e. nonreperfused MI) serves as a traditional coronary occlusion model, to test the effects of new pharmacological agents and biological therapies, as cell therapy. The reperfused and nonreperfused myocardial infarction has different outcomes, regarding left ventricular function, remodelling, subsequent heart failure, aneurysm formation and mortality. Our aim was to review the literature and report our findings regarding experimental MI models, regarding the differences among species, methods, reproducibility and interpretation.

Background: Arterial stiffness parameters are commonly used to determine the development of atherosclerotic disease. The independent predictive value of aortic stiffness has been demonstrated for coronary events. Hypothesis: The aim of our study was to compare regional and local arterial functional parameters measured by 2 different noninvasive methods in patients with verified coronary artery disease (CAD). We also compared and contrasted these stiffness parameters to the coronary SYNTAX score in patients who had undergone coronary angiography. Methods: In this study, 125 CAD patients were involved, and similar noninvasive measurements were performed on 125 healthy subjects. The regional velocity of the aortic pulse wave (PWVao) was measured by a novel oscillometric device, and the common carotid artery was studied by a Doppler echo-tracking system to determine the local carotid pulse wave velocity (PWVcar). The augmentation index (AIx), which varies proportionately with the resistance of the small arteries, was recorded simultaneously. Results: In the CAD group, the PWVao and aortic augmentation index (Alxao) values increased significantly (10.1 ± 2.3 m/sec and 34.2% ± 14.6%) compared to the control group (9.6 ± 1.5 m/sec and 30.9% ± 12%; P < 0.05). We observed similar significant increases in the local stiffness parameters (PWVcar and carotid augmentation index [Alxcar]) in patients with verified CAD. Further, we found a strong correlation for PWV and AIx values that were measured with the Arteriograph and those obtained using the echo-tracking method (r = 0.57, P < 0.001 for PWV; and r = 0.65, P < 0.001 for AIx values). Conclusions: Our results indicate that local and regional arterial stiffness parameters provide similar information on impaired arterial stiffening in patients with verified CAD. © 2011 Wiley Periodicals, Inc. This study was supported by the Hungarian National Research Foundation (OTKA) No.78480. The authors have no other funding, financial relationships, or conflicts of interest to disclose.

BACKGROUND The importance of measuring aortic pulse wave velocity (PWVao), aortic augmentation index (Aix) and central systolic blood pressure (SBPao) has been shown under different clinical conditions; however, information on these parameters is hard to obtain. The aim of this study was to evaluate the accuracy of a new, easily applicable oscillometric device (Arteriograph), determining these parameters simultaneously, against invasive measurements. METHODS Aortic Aix, SBPao and PWVao were measured invasively during cardiac catheterization in 16, 55 and 22 cases, respectively, and compared with the values measured by the Arteriograph. RESULTS We found strong correlation between the invasively measured aortic Aix and the oscillometrically measured brachial Aix on either beat-to-beat or mean value per patient basis (r = 0.9, P < 0.001; r = 0.94, P < 0.001), which allowed the noninvasive calculation of the aortic Aix without using generalized transfer function. Similarly strong correlation (r = 0.95, P < 0.001) was found between the invasively measured and the noninvasively calculated central SBPao; furthermore, the BHS assessment of the paired differences fulfilled the 'B' grading. The PWVao values measured invasively and by Arteriograph were 9.41 ± 1.8 m/s and 9.46 ± 1.8 m/s, respectively (mean ± SD); furthermore, the Pearson's correlation was 0.91 (P < 0.001). The limits of agreement were 11.4% for aortic Aix and 1.59 m/s for PWVao. CONCLUSION Aix, SBPao and PWVao, measured oscillometrically, showed strong correlation with the invasively obtained values. The observed limits of agreement are encouragingly low for accepting the method for clinical use. Our results suggest that the PWVao values, measured by Arteriograph, are close to the true aortic PWV, determined invasively.

Clinical impact of the concomitant clopidogrel therapy on clinical outcomes in patients undergoing cardiac surgery is unclear. We aimed to pool and systematically analyze outcomes in clopidogrel-treated patients undergoing cardiac operations to achieve greater statistical power and to define precise effect-estimates.PubMed and Central databases were searched for relevant studies published between January 2001 and May 2010. The main outcome measures were the rates of red blood cell (RBC) transfusion, reoperation, myocardial infarction and postoperative mortality. The outcome parameters were pooled with the random-effect model via generic-inverse variance-weighting.Twenty studies comprising a total number of 23,668 patients were analyzed. Pooled analysis revealed that the administration of clopidogrel had a higher risk for postoperative mortality (OR: 1.24; 95% CI: 1.03-1.49, p=0.03) that was consistent among studies. The rates of myocardial infarction were similar between groups. Clopidogrel-exposed patients were associated with a significantly higher rate of RBC transfusion (OR: 1.82; 95% CI: 1.40-2.37; p0.00001) and reoperation (OR: 2.15; 95% CI: 1.38-3.34; p0.00001), although there was a marked heterogeneity among studies. According to subgroup analysis the mortality and the rates of transfusions were higher in studies in which clopidogrel was not discontinued 5 days prior to surgery, while the higher risk for reoperation was only apparent in studies published before 2006.Meta-analysis of observational studies demonstrated that concomitant treatment with clopidogrel before cardiac surgery is associated with a significant risk of bleeding-related complications and with a higher mortality.

Raising the maintenance dose of clopidogrel to 150 mg enhances platelet inhibition (PI) in patients with elevated platelet reactivity (EPR); however, large differences were observed between individuals in the extent of this benefit. We aimed to find clinical and platelet function variables that might predict the response to 150 mg clopidogrel in patients with EPR. ADP 5 microM-stimulated peak aggregation (Agg(max)), 6-minute late aggregation (Agg(late)) and 6-minute disaggregation (disAgg) were measured with light transmission aggregometry (LTA) in a consecutive cohort of 202 patients admitted for emergent or elective percutaneous coronary intervention (PCI) after receiving a 600-mg loading dose of clopidogrel. PI was assessed 12 to 18 hours after loading dose and 30 days after the intervention. EPR was defined as a Agg(max) value greater than 34%. From the first day of PCI, 85 patients with EPR received 150 mg clopidogrel for 30 days, while others with normal platelet reactivity (NPR) took 75 mg clopidogrel. Baseline clinical and LTA variables were analyzed in multivariable regression models. Administration of 150 mg clopidogrel enhanced PI and decreased the prevalence of EPR at 30 days compared to the peri-interventional period (Agg(max): 46.9 +/- 8.3 vs. 37.3 +/- 11.5; EPR: 100% vs. 62.4%; p < 0.001 in both cases); however, the achieved level of platelet reactivity was higher than patients with NPR (Agg(max): 20.6 +/- 8.1 vs. 25.3 +/- 10.8, p < 0.001). Multivariable logistic regression revealed low platelet disaggregation (odds ratio (OR): 12.49; 95% CI: 2.52-62.00; P = 0.002) and acute coronary syndrome (OR: 4.83; 95% CI: 1.54-15.09; P = 0.008) as independent predictors of EPR. The area under the receiver-operating-characteristic curve was 0.72 +/- 0.06 for disaggregation to predict NPR after 150 mg clopidogrel. The optimal disaggregation cut-off was 16.5% with a sensitivity of 94% and a specificity of 43%. Administering 150 mg maintenance dose of clopidogrel enhanced antiplatelet potency; however, more than half of the patients persisted with EPR. Acute coronary syndrome and low (

High levels of specific prolactin-releasing peptide (PrRP) binding sites have been found in the myocardium; however, the functional importance of PrRP in the regulation of cardiac function is unknown. In isolated perfused rat hearts, infusion of PrRP (1-100 nM) induced a dose-dependent positive inotropic effect. Inhibition of cAMP catabolism by IBMX, a phosphodiesterase inhibitor, failed to augment the contractile effect of PrRP. The protein phosphatase (PP1/PP2A) inhibitor calyculin A increased the inotropic response to PrRP, whereas the PP2A inhibitor okadaic acid had no effect. Ro32-0432, a protein kinase C alpha (PKC alpha) inhibitor, significantly enhanced the inotropic effect of PrRP as well as the phosphorylation of phospholamban at Ser-16. In conclusion, the present data define a hitherto unrecognized role for PrRP in the regulation of cardiovascular system by showing that PrRP exerts a direct positive inotropic effect. Moreover, our results suggest that the cAMP-independent inotropic response to PrRP is suppressed by concurrent activation of PKC alpha and PP1.