Role of the rabbit whole-heart model for electrophysiologic safety pharmacology of non-cardiovascular drugs

EP Europace ◽  
2020 ◽  
Author(s):  
Christian Ellermann ◽  
Julian Wolfes ◽  
Lars Eckardt ◽  
Gerrit Frommeyer
Keyword(s):  
Action Potential ◽  
Qt Interval ◽  
Cardiac Electrophysiology ◽  
Rabbit Heart ◽  
Cardiovascular Drugs ◽  
Similar Distribution ◽  
Clinical Safety ◽  
In Vivo Models ◽  
Whole Heart

Abstract Plenty of non-cardiovascular drugs alter cardiac electrophysiology and may ultimately lead to life-threatening arrhythmias. In clinical practice, measuring the QT interval as a marker for the repolarization period is the most common tool to assess the electrophysiologic safety of drugs. However, the sole measurement of the QT interval may be insufficient to determine the proarrhythmic risk of non-cardiovascular agents. Several other markers are considered in pre-clinical safety testing to determine potential harm on cardiac electrophysiology. Besides measuring typical electrophysiologic parameters such as repolarization duration, whole-heart models allow the determination of potential predictors for proarrhythmia. Spatial and temporal heterogeneity as well as changes of shape of the action potential can be easily assessed. In addition, provocation manoeuvers (either by electrolyte imbalances or programmed pacing protocols) may induce sustained arrhythmias and thereby determine ventricular vulnerability to arrhythmias. Compared with the human heart, the rabbit heart possesses a similar distribution of ion currents that govern cardiac repolarization, resulting in a rectangular action potential configuration in both species. In addition, similar biophysical properties of rabbit and human cardiac ion channels lead to a comparable pharmacologic response in human and rabbit hearts. Of note, arrhythmia patterns resemble in both species due to the similar effective size of human and rabbit hearts. Thus, the rabbit heart is particularly suitable for testing the electrophysiologic safety of drugs. Several experimental setups have been developed for studying cardiac electrophysiology in rabbits, ranging from single cell to tissue preparations, whole-heart setups, and in vivo models.

scholarly journals The study on optogenetic tachyarrhythmia termination under pathological conditions from the single cell to the whole heart

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Ordog ◽  
E.C.A Nyns ◽  
M.S Fontes ◽  
T Van Den Heuvel ◽  
C.I Bart ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Gene Delivery ◽  
The Netherlands ◽  
Cardiac Disease ◽  
Neonatal Rat ◽  
Funding Source ◽  
In Vivo Models ◽  
Pathological Conditions ◽  
Whole Heart

Abstract Background Ventricular tachyarrhytmias (VTs) are common among patients suffering from cardiac remodeling and cause significant morbidity and mortality. Current research and treatment options for such VTs are suboptimal, hence new strategies are urgently needed. Optogenetics offers efficacious means to control cardiac rhythm, including shock-free VT termination. However, this has not been demonstrated in diseased hearts in vivo, while clinical translation would not only require such demonstration, but also an in-depth understanding of cellular responses. Purpose To assess the optogenetic response at the cardiac cell, tissue, and whole heart level in terms of rhtyhm control under pathological conditions by an integrative experimental platform including in vitro and in vivo models of cardiac disease. Methods Remodeling was induced in neonatal rat ventricular cardiomyocytes (NRVMs) by phenylephrine (PE) exposure. Pathological conditions leading to ventricular remodeling were mimicked by transverse aortic constriction (TAC) surgery in adult rats. The light-activated ion channel ReaChR was ectopically expressed in NRVMs and in hearts of TAC and sham animals by viral vector-based gene delivery. Results Electrical and structural remodeling was evidenced by elongated action potential durations (p<0.05) and increased cell capacitance (p<0.05) in PE-treated, but not in control cells (CTL). Light-induced ionic currents in ReaChR-expressing PE-treated and CTL NRVMs displayed comparable kinetic properties and current densities (p>0.05). Illumination (1 s) caused a sudden shift in membrane potential leading to a plateau at −7.3 mV for PE-treated and −18.9 mV for CTL cells (p>0.05). Hearts explanted from TAC animals showed increased average heart weight to body weight ratio, ventricular fibrosis and expression of hypertrophy markers (ANP, aSkMA, p<0.05), while tissue preparations showed significant APD increase compared to sham. In vivo gene delivery resulted in expression of the ReaChR-citrine transgene in ∼80% of isolated ventricular myocytes (VMs). Photocurrent densities were not different (p>0.05) in VMs from TAC and sham animals, which currents led to comparable shifts in membrane potential (65.3 mV for TAC and 63.9 mV for CTL). In line with this, illumination caused marked depolarization in tissue preparations (from −77.6 to −16.4 mV) in TAC animals as assessed by conventional sharp electrode measurements. Importantly, as anticipated, electrically-induced VT episodes could be terminated in open chest experiments in TAC animals (n=6; 76.3% of cases) by epicardial illumination in vivo. Conclusions Key operational parameters of the optogenetic response remained unaffected in models of cardiac disease, which allowed efficacious optogenetic VT termination in the diseased rat heart exhibiting structural and electrical remodeling. These findings corroborate the translational potential of shock-free therapy of cardiac arrhythmia by optogenetics. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): This work was supported by personal funding from the Netherlands Organization for Scientific Research (NWO, Vidi grant 1714336 to D.A.P.). D.A.P. is also a recipient of the European Research Council (ERC), Starting grant (716509). Additional support was provided by the Netherlands Heart Institute (ICIN grant 230.148-04 to A.A.F.d.V.).

scholarly journals Age-dependent changes in electrophysiology and calcium handling: implications for pediatric cardiac research

2020 ◽  
Vol 318 (2) ◽  
pp. H354-H365 ◽  
Author(s):  
Luther M. Swift ◽  
Morgan Burke ◽  
Devon Guerrelli ◽  
Marissa Reilly ◽  
Manelle Ramadan ◽  
...  
Keyword(s):  
Heart Rate ◽  
Postnatal Development ◽  
Cardiac Electrophysiology ◽  
Disease Modeling ◽  
Calcium Transient ◽  
Atrioventricular Conduction ◽  
Calcium Handling ◽  
Multiparametric Imaging ◽  
Whole Heart

Rodent models are frequently employed in cardiovascular research, yet our understanding of pediatric cardiac physiology has largely been deduced from more simplified two-dimensional cell studies. Previous studies have shown that postnatal development includes an alteration in the expression of genes and proteins involved in cell coupling, ion channels, and intracellular calcium handling. Accordingly, we hypothesized that postnatal cell maturation is likely to lead to dynamic alterations in whole heart electrophysiology and calcium handling. To test this hypothesis, we employed multiparametric imaging and electrophysiological techniques to quantify developmental changes from neonate to adult. In vivo electrocardiograms were collected to assess changes in heart rate, variability, and atrioventricular conduction (Sprague-Dawley rats). Intact, whole hearts were transferred to a Langendorff-perfusion system for multiparametric imaging (voltage, calcium). Optical mapping was performed in conjunction with an electrophysiology study to assess cardiac dynamics throughout development. Postnatal age was associated with an increase in the heart rate (181 ± 34 vs. 429 ± 13 beats/min), faster atrioventricular conduction (94 ± 13 vs. 46 ± 3 ms), shortened action potentials (APD80: 113 ± 18 vs. 60 ± 17 ms), and decreased ventricular refractoriness (VERP: 157 ± 45 vs. 57 ± 14 ms; neonatal vs. adults, means ± SD, P < 0.05). Calcium handling matured with development, resulting in shortened calcium transient durations (168 ± 18 vs. 117 ± 14 ms) and decreased propensity for calcium transient alternans (160 ± 18- vs. 99 ± 11-ms cycle length threshold; neonatal vs. adults, mean ± SD, P < 0.05). Results of this study can serve as a comprehensive baseline for future studies focused on pediatric disease modeling and/or preclinical testing. NEW & NOTEWORTHY This is the first study to assess cardiac electrophysiology and calcium handling throughout postnatal development, using both in vivo and whole heart models.

scholarly journals Utility of Zebrafish Models of Acquired and Inherited Long QT Syndrome

2021 ◽  
Vol 11 ◽  
Author(s):  
Kyle E. Simpson ◽  
Ravichandra Venkateshappa ◽  
Zhao Kai Pang ◽  
Shoaib Faizi ◽  
Glen F. Tibbits ◽  
...  
Keyword(s):  
Long Qt Syndrome ◽  
Cardiac Electrophysiology ◽  
Toxicological Screening ◽  
Long Qt ◽  
Zebrafish Model ◽  
Qt Syndrome ◽  
Organ Models ◽  
Whole Heart ◽  
Herg Channels

Long-QT Syndrome (LQTS) is a cardiac electrical disorder, distinguished by irregular heart rates and sudden death. Accounting for ∼40% of cases, LQTS Type 2 (LQTS2), is caused by defects in the Kv11.1 (hERG) potassium channel that is critical for cardiac repolarization. Drug block of hERG channels or dysfunctional channel variants can result in acquired or inherited LQTS2, respectively, which are typified by delayed repolarization and predisposition to lethal arrhythmia. As such, there is significant interest in clear identification of drugs and channel variants that produce clinically meaningful perturbation of hERG channel function. While toxicological screening of hERG channels, and phenotypic assessment of inherited channel variants in heterologous systems is now commonplace, affordable, efficient, and insightful whole organ models for acquired and inherited LQTS2 are lacking. Recent work has shown that zebrafish provide a viable in vivo or whole organ model of cardiac electrophysiology. Characterization of cardiac ion currents and toxicological screening work in intact embryos, as well as adult whole hearts, has demonstrated the utility of the zebrafish model to contribute to the development of therapeutics that lack hERG-blocking off-target effects. Moreover, forward and reverse genetic approaches show zebrafish as a tractable model in which LQTS2 can be studied. With the development of new tools and technologies, zebrafish lines carrying precise channel variants associated with LQTS2 have recently begun to be generated and explored. In this review, we discuss the present knowledge and questions raised related to the use of zebrafish as models of acquired and inherited LQTS2. We focus discussion, in particular, on developments in precise gene-editing approaches in zebrafish to create whole heart inherited LQTS2 models and evidence that zebrafish hearts can be used to study arrhythmogenicity and to identify potential anti-arrhythmic compounds.

scholarly journals Tetrodotoxin-sensitive Navs contribute to early and delayed afterdepolarizations in long QT arrhythmia models

2018 ◽  
Vol 150 (7) ◽  
pp. 991-1002 ◽  
Author(s):  
Megan Koleske ◽  
Ingrid Bonilla ◽  
Justin Thomas ◽  
Naveed Zaman ◽  
Stephen Baine ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Action Potential ◽  
Qt Interval ◽  
Torsades De Pointes ◽  
Cellular Level ◽  
Polymorphic Ventricular Tachycardia ◽  
Wild Type ◽  
Long Qt ◽  
Delayed Afterdepolarizations

Recent evidence suggests that neuronal Na+ channels (nNavs) contribute to catecholamine-promoted delayed afterdepolarizations (DADs) and catecholaminergic polymorphic ventricular tachycardia (CPVT). The newly identified overlap between CPVT and long QT (LQT) phenotypes has stoked interest in the cross-talk between aberrant Na+ and Ca2+ handling and its contribution to early afterdepolarizations (EADs) and DADs. Here, we used Ca2+ imaging and electrophysiology to investigate the role of Na+ and Ca2+ handling in DADs and EADs in wild-type and cardiac calsequestrin (CASQ2)-null mice. In experiments, repolarization was impaired using 4-aminopyridine (4AP), whereas the L-type Ca2+ and late Na+ currents were augmented using Bay K 8644 (BayK) and anemone toxin II (ATX-II), respectively. The combination of 4AP and isoproterenol prolonged action potential duration (APD) and promoted aberrant Ca2+ release, EADs, and DADs in wild-type cardiomyocytes. Similarly, BayK in the absence of isoproterenol induced the same effects in CASQ2-null cardiomyocytes. In vivo, it prolonged the QT interval and, upon catecholamine challenge, precipitated wide QRS polymorphic ventricular tachycardia that resembled human torsades de pointes. Treatment with ATX-II produced similar effects at both the cellular level and in vivo. Importantly, nNav inhibition with riluzole or 4,9-anhydro-tetrodotoxin reduced the incidence of ATX-II–, BayK-, or 4AP-induced EADs, DADs, aberrant Ca2+ release, and VT despite only modestly mitigating APD prolongation. These data reveal the contribution of nNaVs to triggered arrhythmias in murine models of LQT and CPVT-LQT overlap phenotypes. We also demonstrate the antiarrhythmic impact of nNaV inhibition, independent of action potential and QT interval duration, and provide a basis for a mechanistically driven antiarrhythmic strategy.

In vivo gene transfer of Kv1.5 normalizes action potential duration and shortens QT interval in mice with long QT phenotype

2003 ◽  
Vol 285 (1) ◽  
pp. H194-H203 ◽  
Author(s):  
Michael Brunner ◽  
Sodikdjon A. Kodirov ◽  
Gary F. Mitchell ◽  
Peter D. Buckett ◽  
Katsushi Shibata ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Qt Interval ◽  
Direct Injection ◽  
Dominant Negative ◽  
Dominant Negative Effect ◽  
Long Qt ◽  
Dispersion Of Repolarization ◽  
Surface Ecg

Mutations in cardiac voltage-gated K+channels cause long QT syndrome (LQTS) and sudden death. We created a transgenic mouse with a long QT phenotype (Kv1DN) by overexpression of a truncated K+channel in the heart and investigated whether the dominant negative effect of the transgene would be overcome by the direct injection of adenoviral vectors expressing wild-type Kv1.5 (AV-Kv1.5) into the myocardium. End points at 3–10 days included electrophysiology in isolated cardiomyocytes, surface ECG, programmed stimulation of the right ventricle, and in vivo optical mapping of action potentials and repolarization gradients in Langendorff-perfused hearts. Overexpression of Kv1.5 reconstituted a 4-aminopyridine-sensitive outward K+current, shortened the action potential duration, eliminated early afterdepolarizations, shortened the QT interval, decreased dispersion of repolarization, and increased the heart rate. Each of these changes is consistent with a physiologically significant primary effect of adenoviral expression of Kv1.5 on ventricular repolarization of Kv1DN mice.

scholarly journals Field and action potential recordings in heart slices: correlation with established in vitro and in vivo models

2012 ◽  
Vol 166 (1) ◽  
pp. 276-296 ◽  
Author(s):  
Herbert M Himmel ◽  
Alexandra Bussek ◽  
Michael Hoffmann ◽  
Rolf Beckmann ◽  
Horst Lohmann ◽  
...  
Keyword(s):  
Action Potential ◽  
In Vivo Models

scholarly journals Genetic Loss of I K1 Causes Adrenergic-Induced Phase 3 Early Afterdepolariz ations and Polymorphic and Bidirectional Ventricular Tachycardia

2020 ◽  
Vol 13 (9) ◽  
Author(s):  
Louise Reilly ◽  
Francisco J. Alvarado ◽  
Di Lang ◽  
Sara Abozeid ◽  
Hannah Van Ert ◽  
...  
Keyword(s):  
Ventricular Tachycardia ◽  
Action Potential ◽  
Cardiac Function ◽  
Ventricular Myocytes ◽  
Optical Mapping ◽  
Adrenergic Stimulation ◽  
Phase 3 ◽  
Early Afterdepolarizations ◽  
Whole Heart

Background: Arrhythmia syndromes associated with KCNJ2 mutations have been described clinically; however, little is known of the underlying arrhythmia mechanism. We create the first patient inspired KCNJ2 transgenic mouse and study effects of this mutation on cardiac function, I K1 , and Ca 2+ handling, to determine the underlying cellular arrhythmic pathogenesis. Methods: A cardiac-specific KCNJ2 -R67Q mouse was generated and bred for heterozygosity (R67Q +/− ). Echocardiography was performed at rest, under anesthesia. In vivo ECG recording and whole heart optical mapping of intact hearts was performed before and after adrenergic stimulation in wild-type (WT) littermate controls and R67Q +/− mice. I K1 measurements, action potential characterization, and intracellular Ca 2+ imaging from isolated ventricular myocytes at baseline and after adrenergic stimulation were performed in WT and R67Q +/− mice. Results: R67Q +/− mice (n=17) showed normal cardiac function, structure, and baseline electrical activity compared with WT (n=10). Following epinephrine and caffeine, only the R67Q +/− mice had bidirectional ventricular tachycardia, ventricular tachycardia, frequent ventricular ectopy, and/or bigeminy and optical mapping demonstrated high prevalence of spontaneous and sustained ventricular arrhythmia. Both R67Q +/− (n=8) and WT myocytes (n=9) demonstrated typical n-shaped I K1 IV relationship; however, following isoproterenol, max outward I K1 increased by ≈20% in WT but decreased by ≈24% in R67Q +/− ( P <0.01). R67Q +/− myocytes (n=5) demonstrated prolonged action potential duration at 90% repolarization and after 10 nmol/L isoproterenol compared with WT (n=7; P <0.05). Ca 2+ transient amplitude, 50% decay rate, and sarcoplasmic reticulum Ca 2+ content were not different between WT (n=18) and R67Q +/− (n=16) myocytes. R67Q +/− myocytes (n=10) under adrenergic stimulation showed frequent spontaneous development of early afterdepolarizations that occurred at phase 3 of action potential repolarization. Conclusions: KCNJ2 mutation R67Q +/− causes adrenergic-dependent loss of I K1 during terminal repolarization and vulnerability to phase 3 early afterdepolarizations. This model clarifies a heretofore unknown arrhythmia mechanism and extends our understanding of treatment implications for patients with KCNJ2 mutation.

scholarly journals Helium-Induced Changes in Circulating Caveolin in Mice Suggest a Novel Mechanism of Cardiac Protection

2019 ◽  
Vol 20 (11) ◽  
pp. 2640 ◽  
Author(s):  
Nina C. Weber ◽  
Jan M. Schilling ◽  
Moritz V. Warmbrunn ◽  
Mehul Dhanani ◽  
Raphaela Kerindongo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Critical Role ◽  
Reactive Oxygen Species Generation ◽  
Heart Tissue ◽  
Organ Protection ◽  
Perfused Heart ◽  
Transmission Electron Microscopy Analysis ◽  
In Vivo Models ◽  
Whole Heart

The noble gas helium (He) induces cardioprotection in vivo through unknown molecular mechanisms. He can interact with and modify cellular membranes. Caveolae are cholesterol and sphingolipid-enriched invaginations of the plasma-membrane-containing caveolin (Cav) proteins that are critical in protection of the heart. Mice (C57BL/6J) inhaled either He gas or adjusted room air. Functional measurements were performed in the isolated Langendorff perfused heart at 24 h post He inhalation. Electron paramagnetic resonance spectrometry (EPR) of samples was carried out at 24 h post He inhalation. Immunoblotting was used to detect Cav-1/3 expression in whole-heart tissue, exosomes isolated from platelet free plasma (PFP) and membrane fractions. Additionally, transmission electron microscopy analysis of cardiac tissue and serum function and metabolomic analysis were performed. In contrast to cardioprotection observed in in vivo models, the isolated Langendorff perfused heart revealed no protection after He inhalation. However, levels of Cav-1/3 were reduced 24 h after He inhalation in whole-heart tissue, and Cav-3 was increased in exosomes from PFP. Addition of serum to muscle cells in culture or naïve ventricular tissue increased mitochondrial metabolism without increasing reactive oxygen species generation. Primary and lipid metabolites determined potential changes in ceramide by He exposure. In addition to direct effects on myocardium, He likely induces the release of secreted membrane factors enriched in caveolae. Our results suggest a critical role for such circulating factors in He-induced organ protection.

Abstract 362: Cardioprotective Effects of Adiponectin in Volume Overload Induced Electrophysiological Remodeling

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Juming Zhong ◽  
Lili Wang ◽  
Dori Miller ◽  
Dean Schwartz ◽  
Rajesh Amin ◽  
...  
Keyword(s):  
Action Potential ◽  
Protein Expression ◽  
Qt Interval ◽  
Ventricular Myocytes ◽  
Volume Overload ◽  
Infrarenal Aorta ◽  
Duration Of Action ◽  
Western Blots ◽  
Qt Interval Prolongation

The electrophysiological hallmark of the failing heart is the prolongation of action potential duration that induces arrhythmia and sudden death. Depressed outward potassium currents (Ito) has been implicated as the major cause of altered action potential during ventricular remodeling. The molecular mechanism underlying depressed Ito in the diseased heart is still poorly understood. Recent studies have demonstrated that adiponectin (APN) has a cardio-protective effect in response to various pathological stimuli; however, little information is available regarding the potential effects of APN on electrophysiological remodeling under pathological conditions. The present study were to determine the effect of adiponectin treatment on ventricular potassium channel function in a rat model of volume overload induced heart failure. Volume-overload was induced by surgical creation of an infrarenal aorta-vena cava fistula. Rats were administrated with or without adenovirus-mediated overexpression of adiponectin (Ad-APN) at 2-, 5- and 8- weeks post-fistula. In vivo ECGs were used to evaluate changes in QT interval in rats at 10 weeks post-fistula. Ventricular myocytes were isolated at 10 weeks post-fistula. Western blots were used to measure cytoplasmic and membrane protein expression of potassium channels Kv4.2 and Kv 4.3, as well as, KChIP2. Whole cell patch clamp was used to evaluate action potential and Ito currents. Results showed that adiponectin levels in serum and myocytes were significantly reduced following fistula. The duration of action potential was prolonged in ventricular myocytes following 10-week fistula, which was correlated with the in vivo QT interval prolongation, as well as a depression of functional Ito and decreased protein expression of Ito channel subunits in ventricular myocytes. In vivo supplementation of Ad-APN increased the protein levels of Ito channel subunits and prevented Ito depression in ventricular myocytes following 10-week fistula. This further restored the duration of action potential and the QT interval on the ECG back to the normal. These results indicate that adiponectin was able to prevent volume overload-induced ventricular electrophysiological remodeling.

The Peptide hLF1-11 as Broad Spectrum Antmicrobial Prophylaxis in HSCT Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3241-3241 ◽  
Author(s):  
Marty Wulferink ◽  
Carlo P. Brouwer ◽  
Astrid M.C. Sluiter-van Dijk ◽  
Nicole N.A. Blijlevens ◽  
J. Peter Donnelly ◽  
...  
Keyword(s):  
Broad Spectrum ◽  
Opportunistic Infections ◽  
Safety Data ◽  
Clinical Safety ◽  
In Vivo Models ◽  
Dose Study ◽  
Bacteria And Fungi ◽  
Anti Fungal

Abstract hLF1-11, comprising the N-terminal 11 AA of the human lactoferrin protein, has previously been shown to have a broad antimicrobial spectrum. The efficacy towards several strains of bacteria and fungi was demonstrated in in vitro and in vivo models. At this moment, hLF1-11 is in clinical development for use as broad spectrum anti-fungal and anti-bacterial prophylaxis in hematopoetic stem cell transplantation (HSCT) patients. There is data to support that the hLF1-11 mechanism of action is not restricted to direct killing of the pathogen, but that the indirect, immune modulatory and immune activating properties are important for hLF1-11 efficacy in vivo at low doses. In earlier studies, efficacy of hLF1-11 was shown in neutropenic animals systemically infected with Candida albicans. In the present studies antimicrobial efficacy and safety of hLF1-11 was tested in animal models that resemble the immune compromised state of HSCT patients shortly after transplantation. In cyclophosphamid and cyclosporin treated animals, hLF1-11 significantly reduced intra muscular infection with methicillin resistant Staphylococcus aureus (MRSA) when injected 24 hours after infection. In the same model hLF1-11 showed prophylactic properties in that it was effective even when administered as a single injection 24 hours before local infection with MRSA. In order to assess drug-drug interactions of hLF1-11 with common antibiotics, hLF1-11 was co administered with either vancomycin or ciprofloxacin in the local MRSA infection. Data from these models show that hLF1-11 is effective in combination with standard antibiotic and immunosuppressive care in a HSCT setting. Moreover, the hLF1-11 peptide does not inhibit antibiotic activity of currently used antibiotics. Besides these preclinical safety data, clinical safety was evaluated in a single and multiple ascending dose study in human volunteers. During these studies pharmacokinetic and pharmacodynamic parameters were measured and no drug related adverse effects were observed. Now, preparations are made to evaluate safety and efficacy of hLF1-11 in autologous and allogenic HSCT patients as anti-fungal and anti-bacterial prophylaxis. In conclusion, hLF1-11 is a promising peptide to prevent and treat opportunistic infections in HSCT patients and other immune suppressed patient populations.

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