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Funding Acknowledgements Type of funding sources: None. Background Catheter ablation is the most effective rhythm control treatment for atrial fibrillation (AF). While it was indicated as a symptomatic treatment in the past years, prognostic benefits of early rhythm control (ERC) were recently demonstrated and catheter ablation advances more and more into this indication. Restrictions in patient selection for catheter ablation seem to melt. Only few data on comorbidity burden in patients undergoing AF ablation is available. Purpose To determine prevalence of common cardiovascular and related comorbidities in patients undergoing left-atrial (LA) procedures between 2010 and 2021 at a large tertiary-care ablation center.. Method Eligible cases with LA procedures were identified through analysis of coded OPS data between 2010 and 2021. Analysis included patients with atrial fibrillation undergoing an ablation procedure including a transseptal puncture and mapping in the left atrium, not for other supraventricular tachycardias. Analysis accounted for different versions of the ICD-10-GM and OPS-ICHI catalogues. Comorbidities were defined as derived variables on a case-wise analysis from documented ICD-10 and OPS codes. CHA2DS2-VASc-score was calculated from these derived variables and demographic parameters. Procedures were clustered by intervention year in one of following ranges 2010-2012, 2013-2015, 2016-2018 and 2019-2021. Results 8396 left atrial procedures in 6184 individual patients (35% female, 63.6±11.0 years old at index procedure) were identified. Median CHA2DS2-VASc was 2 (IQR 1;3) in the overall cohort. Mean age increased constantly from 60.3±11.4 years in 2011 to 64.5±11.1 years in 2021. Median CHA2DS2-VASc-score remained constant at 2 points. While the share of non-paroxysmal AF patients was 52% between 2010 and 2012, it increased to 59% in 2016-2018 and decreased again to 55% in 2019-2021. The relative number of cases in which patients suffered from diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA), pulmonary hypertension, coronary artery disease and prior myocardial infarction increased constantly between 2010-2012. While the share of patients with heart failure was highest between 2013 and 2015 (1368/2117 cases, 65%), it decreased to 833/2318 cases (36%) in 2019-2021. the absolute number of procedures nearly doubled from 2010-2012 to 2013-2015, it increased by only 36% from range 2013-2015 to 2016-2018. The number of procedures decreased again from 2016-2018 to 2019-2021 by 19%, likely due to COVID19-pandemic restrictions. Conclusion Over the last decade, the age and number of comorbidities increased in patients undergoing AF ablation procedures. These results put emphasis on offering safe procedures and perform adequate pre-procedural assessment of comorbidity burden.

Funding Acknowledgements Type of funding sources: None. Background A novel multi-electrode radiofrequency balloon (RFB) catheter has been released for pulmonary vein isolation (PVI). Objectives First multicenter real-world study to evaluate predictors of single shot PVI with the novel RFB catheter. Methods In this observational study consecutive patients with drug refractory paroxysmal or persistent atrial fibrillation (AF) undergoing first-time PVI were enrolled in two high-volume ablation centers. All procedures were conducted in conjunction with a 3D-mapping system. Clinical, procedural and ablation parameters were systematically analyzed. Results 105 patients (58% males; 52% paroxysmal AF, 68 ± 11.3 mean age, left atrial volume index 38.6 ± 14.8 ml/m2) were included. 241/412 (58.5%) pulmonary veins were successfully isolated with a single shot (SS), with a time to isolation of 11.6 ± 8 s. Total number of radio frequency applications was 892 (mean 2.2/PV), resulting in successful isolation of 408/412 (99%) PVs at the end of the procedure. Mean electrodes’ impedance drop was significantly higher in the SS-PVI compared to the non-SS applications (21.5 ± 6.6 vs. 18.6 ± 6.5 Ohm). Concordantly, higher temperature rise was observed in the SS versus non-SS applications (10.9 ± 4.9°C vs. 9.6 ± 4.7°C). Conclusion In this multicenter real-world study, mean impedance drop and temperature rise emerged as valid predictors for SS-PVI with the novel RFB catheter. These parameters may help to guide efficient usage of the new RF balloon.

Funding Acknowledgements Type of funding sources: None. Background Pulsed-field ablation (PFA) integrated into a pentaspline catheter is a novel single shot device to perform pulmonary vein isolation (PVI) for treatment of atrial fibrillation (AF). While initial data demonstrated high safety and efficacy, long-term PVI durability and reconnection patterns are unknown. Here, we analyzed findings from repeat ablation procedures after index PFA compared to cryoballoon ablation (CBA) based PVI. Methods We prospectively included consecutive patients with index PVI applying PFA (n=161) or CBA (n=302) who underwent repeat ablation due to symptomatic recurrence of AF or atrial tachycardia (AT) after a blanking period of 3 months. All repeat procedures were performed with a 3D mapping system and RF energy. Results We identified a total of 14 patients after previous PFA and 23 patients after previous CBA. PV reconnection was detected in 9/14 (64%) patients after PFA and in 16/23 (70%) after CBA (p=1.000). A total of 24/55 (44%) vs. 34/92 (37%) initially isolated PVs demonstrated electrical reconduction (p=0.487) after PFA and CB ablation. In both groups the right inferior PV was reconnected most frequently (9/24 (38%) patients after PFA and 10/34 (29%; p=0.578) patients after CBA). Distribution of conduction gaps is shown in figure 1. All PVs were successfully reisolated. Repeat procedures after index PFA and CBA showed similar duration (115±32 min vs. 114±49 min; p=0.785), fluoroscopy time (13±4 min vs. 14±8 min; p=0.558) and number of RF applications (38±23 vs. 36±34, p=0.738). Conclusion During repeat AF/AT ablation after previous PFA- or CBA-based PVI a comparable incidence of PV reconduction gaps was found. Repeat procedure times and fluoroscopy exposure were similar. Randomized controlled trials and longer follow-up are necessary to draw further conclusions.

Funding Acknowledgements Type of funding sources: None. Background Catheter ablation is the most effective rhythm control treatment for atrial fibrillation (AF) and benefits of early rhythm control (ERC) were recently demonstrated to be enhanced in patients with a high comorbidity burden (CHA2DS2-VASc ≥ 4). Incidence of pericardial effusion, a dreaded, potentially life-threatening complication that is associated with catheter ablation,has not been analyzed in larger patient cohorts stratified by CHA2DS2-VASc. Purpose To determine incidence of pericardial effusion and drained pericardial effusion related to left-atrial (LA) procedures in billing data between 2010 and 2021 of a large tertiary-care ablation center in Germany. Method Eligible cases of LA procedures were identified through analysis of coded OPS data between 2010 and 2021. This analysis included patients with atrial fibrillation undergoing an ablation procedure including a transseptal puncture and mapping in the left atrium, not for other supraventricular tachycardias. Analysis accounted for different versions of the ICD-10-GM and OPS-ICHI catalogues. Comorbidities and occurrences of complications were defined as derived variables on a case-wise analysis from documented ICD-10 and OPS codes. CHA2DS2-VASc-score was calculated from these derived variables and demographic parameters (age and sex). Results 8396 left atrial procedures in 6184 patients (35% female, 63.6±11.0 years old at index procedure) were analysed. Derived CHA2DS2-VASc was < 4 in 6529 (78%) and ≥ 4 in 1867 (22%) cases, median CHA2DS2-VASc was 2 (IQR 1;3) in the overall cohort. Non-paroxysmal AF was more prevalent in the CHA2DS2-VASc ≥ 4 group (62.5%) than in the overall cohort (56%) and in the CHA2DS2-VASc < 4 group (54%). Hypertension was the most common comorbidity in 5285 (63%) patients. Coronary artery disease was present in 1433 (17%), heart failure in 3757 (45%), chronic kidney disease in 899 (11%) patients, thereof 591 (7%) at a stage ≥ KDIGO III. Pericardial effusion was documented in 78/6529 (1.2%) in the CHA2DS2-VASc < 4 group. Thereof 35/78 (45%) required interventional or surgial drainage. In the CHA2DS2-VASc ≥ 4 group, pericardial effusion occurred in 21/1867 (1.1%) cases. Here, 10/21 (48%) required drainage. Occurrence of pericardial effusion did not differ between CHA2DS2-VASc-score stratified groups (χ2 p=0.805). Pericardial effusion requiring drainage was not different petween groups (χ2 p=0.822). Conclusion Patients with a higher comorbidity burden undergoing catheter ablation for atrial fibrillation in the past 10 years were not subject to an increased risk for pericardial effusion or drainage. This observation allows to perform highly efficient ablation procedures equally in patients with low and high comorbidity burden safely. Further analysis of the dataset regarding further left atrial ablation associated complications and their predictors will be provided.

Background Pulsed field ablation (PFA) is a novel non-thermal energy source to conduct catheter ablation of atrial fibrillation (AF). However, real-world multi-center data regarding acute procedural efficacy and safety is sparse. Purpose To study acute procedural success and safety in patients undergoing PFA for catheter ablation of AF in a multicenter registry. Methods Consecutive paroxysmal and persistent AF patients undergoing PFA-based catheter ablation using a multispline catheter were enrolled. The cohort included first and repeat ablation procedures. Procedural parameters, acute success and in-hospital safety were evaluated. A follow-up of all patients was conducted. Results Five German centers enrolled a total of 154 patients undergoing PFA in this study. Mean age was 68±12 years, median CHA2DS2-VASc Score was 3 (Q1-Q3: 2–4). Patients suffered from paroxysmal AF (n=55; 36%), persistent AF (n=93; 60%) and consecutive atrial tachycardias (AT) due to previous CA (n=6; 4%). The median left atrial (LA) PFA and total procedure times were 33 (Q1-Q3: 24–53) and 90 (Q1-Q3: 73–116) minutes, respectively. Mean LA PFA fluoroscopy and total fluoroscopy times were 12.1±5.5 and 20.2±8.7 minutes. Of all 154 procedures, 130 (84%) were index ablation procedures with isolation of pulmonary veins (PVI) only and 24 (16%) were repeat procedures (including re-PVI and ablation of consecutive AT). Acute PV reconnection following primary PVI and the initial set of PFA-applications was found in 20/130 (15%) patients, necessitating additional PFA ablation. Finally, successful PFA-guided PVI was achieved in all patients. Additional PFA lesion sets (including LA posterior wall isolation, anterior ablation, mitral isthmus ablation) were applied in 17/154 (11%) patients. Complications occurred in a total of 6/154 (3.8%) patients (including three groin site complications, two pericardial tamponades, one transient coronary spasm without sequela). The follow up data is still being assessed and will be provided by the time of the ESC 2022 meeting. Conclusion PFA performed in patients with atrial fibrillation demonstrates high acute procedural success rates and a favorable safety profile in this first real-world multicenter registry. Funding Acknowledgement Type of funding sources: None.

Funding Acknowledgements Type of funding sources: None. Background Conventional mapping systems do not provide wall-thickness data, which is, however, known to be a determinant of radiofrequency ablation lesion transmurality. KODEX-EPD is a novel open-platform system, which uses dielectric tissue properties to provide real-time, high-resolution cardiac images, tissue characteristics and wall-thickness measurement to guide ablation procedures. Aim The aim of this case series was to report on our first experiences with KODEX-EPD regarding estimation of myocardial wall-thickness during catheter ablation of atrial fibrillation (AF). Methods We retrospectively analyzed consecutive patients undergoing radiofrequency AF-ablation in combination with KODEX-EPD. A high-resolution image from the left atrium (LA) and the pulmonary veins (PV) was obtained prior to ablation using a spiral mapping catheter in conjunction with KODEX-EPD. Wall-viewer points were collected within the LA, the PVs and the left atrial appendage (LAA) using a standard radiofrequency non-contact force ablation catheter and analyzed for wall-thickness applying the latest KODEX-EPD software version (1.5.0, not yet commercially released). Wall-viewer points were divided into a total of 10 segments (PV ostia, anterior wall, posterior wall, LA roof, LA floor, LAA and PV carina, details see Figure 1) in order to characterize wall-thickness in respective areas. Results A total of 570 wall-viewer points in 5 patients were analyzed. Most of the wall-viewer points were collected at the PV ostia as well as along the posterior and anterior wall (449/570, 79%). Actual myocardial atrial thickness ranged from 1.6 to 3.9 mm. Thickest myocardial LA-tissue was measured at the anterior wall (median 3.1 mm) and thinnest at the LA-roof (median 2.2 mm). Figure 2 gives a detailed distribution of wall-thickness measurements at different sites in the LA and PVs. Conclusion Atrial wall thickness can be estimated in patients during AF ablation procedures using dielectric tissue properties. Further evaluation and validation of the method are needed to study its reliability and utility for clinical practice.

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): FARAPULSE, Inc. Introduction Thermal energy sources damage the entire atrial tissue during pulmonary vein isolation (PVI) including cardiac nerves and ganglia. This induces a postinterventional increase in heart rate. Pulsed-field ablation (PFA), a new non-thermal energy source for PVI, primarily damages cardiomyocytes by electroporation. Whether use of PFA reduces damage to cardiac nerves and ganglia and influences postinterventional increase of heart rate is not known. Purpose We compared the acute effects of PFA with a pentaspline catheter and cryoballoon ablation (CBA) on secretion of circulating biomolecules reflecting cardiomyocyte and neuronal injury and postinterventional increase in heart rate to estimate damage to the cardiac autonomic nervous system and autonomic dysfunction after PVI. Methods Blood samples were taken before and after PVI in consecutive patients undergoing PFA and CBA. All patients participated in the TRUST registry. Serum concentrations of high-sensitive Troponin I (hsTropI, Immunoassay) and S100b (ELISA), a surrogate marker for neuronal injury, were quantified in blood samples taken prior to PVI and directly after PVI. Pre- and postinterventional heart rates were measured in ECGs and Holter-ECGs. Results Fifty-six patients underwent PVI, either by PFA (n=28, age 63 [54; 75] y, 64% males, 57% persistent AF) or CBA (n=28, age 71 [62; 78] y, 61% males, 54% persistent AF). All 112 blood samples were analyzable. Acute success of PVI was 100% in both groups without major complications, especially, no TIA and no stroke. After CBA, one patient suffered from phrenic palsy, which reversed after 3 months. HsTropI increased 3.3-fold more after PFA compared to CBA (625±138 vs. 185±42 pg/ml; p=0.004) suggesting more damage to cardiomyocytyes. S100b increased 2.9-fold less after PFA compared to CBA (21.1±3.7 vs. 61.2±8.1 pg/ml; p Conclusion This study in patients validates the experimental concept that PFA-based AF ablation leads to more specific damage to cardiomyocytes than to cardiac nerves and ganglia, reflected by lower S100B concentrations and no post-interventional heart rate increase compared to CBA.

Funding Acknowledgements Type of funding sources: None. Introduction Pulsed-field ablation (PFA) and the multi-electrode radiofrequency balloon (RFB) are two novel ablation technologies to perform pulmonary vein isolation (PVI). It is currently unknown whether these technologies differ in lesion formation and lesion extent. Purpose We compared the acute lesion extent after PVI induced by PFA and RFB by measuring low-voltage area in high-density maps and the release of biomolecules reflecting cardiac injury. Methods PVI was performed with a pentaspline catheter (FARAPULSE) applying PFA or with the compliant multi-electrode radiofrequency balloon (HELIOSTAR). Before and after PVI high-density mapping with CARTO3 was performed. In addition, blood samples were taken before transseptal puncture and after post-PVI remapping. Serum concentrations of high-sensitive Troponin I (hsTropI) were quantified by Immunoassay. Results 50 patients undergoing PVI by PFA (n=26, age 71±10 y, 58% males, 58% persistent AF) or RFB (n=24; age 64±13 y, 54% males, 25% persistent AF) were evaluated. Acute PVI was achieved in all patients in both groups. Mean number of PFA pulses were n=34±5 and mean number RFB applications were n=8±3. Total posterior ablation area was bigger in PFA (19.0±6.2 cm²) than in RFB (9.0±2.2 cm²; p Conclusion Pulse-field ablation delivers larger acute lesion areas and higher troponin release upon successful pulmonary vein isolation than multi-electrode array balloon-based pulmonary vein isolation in this single-center series.

Background Cryoballoon (CB)-based pulmonary vein isolation (PVI) currently requires to verify occlusion of each pulmonary vein (PV) using fluoroscopy and dye injection. Objective The current study evaluated whether the novel CB-occlusion tool integrated into the wide-band dielectric imaging system KODEX-EPD reliably verifies occlusion of PV according to a novel dye-injection based algorithm. Methods Consecutive patients suffering from symptomatic atrial fibrillation (AF) underwent CB-based PVI using the KODEX-EPD and the novel occlusion-tool (group I). To confirm accurate display of the PVs, selective PV-angiography was performed in the first half of the patients of group I (group Ia) in addition to a three-dimensional left atrial (LA) map using a spiral mapping catheter (Achieve, SMC1, Medtronic, MN, USA). PV-angiographies were waived for the following patients (group Ib). Procedural duration and radiation exposure were compared to a control group of patients undergoing conventional CB-based PVI. Results CB-based PVI was successful in 50/50 patients of group I (mean age 63±11 years, 18 paroxysmal (36%)) and 25/25 patients of group II (66±10 years, 9 paroxysmal (60%)). Concordance of PV-occlusion as assessed by either PV-occlusion-angiography or KODEX-EPD, was documented in 237/272 (87%) occlusion-analyses among 198 PVs (95% for left superior PV, 93% for left inferior PV, 86% for right inferior PV and 77% for right superior PV). In the final evaluation phase (group Ib) LA fluoroscopy times and dose area products were comparable to the conventional CB-ablation group (10.5±5 vs 8.8±4 minutes (p=0.23) and 403±425 vs 321±202 cGycm2 (p=0.44), whereas the amount of dye could be significantly reduced (group Ib: 31±10 ml vs group II: 70±20 ml, p Conclusion The novel KODEX-EPD PV-occlusion tool allows for accurate PV-occlusion assessment in the majority of PVs and a high acute success rate. The system has the potential to reduce dye and radiation exposure. This should be evaluated in controlled clinical trials. Funding Acknowledgement Type of funding sources: None.

Earth observation satellites yield a wealth of data for scientific, operational and commercial exploitation. However, the redistribution of mass in the system Earth is not yet part of the standard inventory of Earth Observation (EO) data products to date. It is derived from the Gravity Recovery and Climate Experiment (GRACE) mission and its Follow-On mission (GRACE-FO). Among many other applications, mass redistribution provides fundamental insights into the global water cycle. Changes in continental water storage impact the regional water budget and can, in extreme cases, result in floods and droughts that often claim a high toll on infrastructure, economy and human lives. The initiative for a European Gravity Service for Improved Emergency Management (EGSIEM) established three different prototype services to promote the unique value of mass redistribution products for Earth Observation in general and for early-warning systems in particular. The first prototype service is a scientific combination service to derive improved mass redistribution products from the combined knowledge of the European GRACE analysis centres. Secondly, the timeliness and reliability of such products is a primary concern for any early-warning system and therefore EGSIEM established a prototype for a near real-time service that provides dedicated gravity field information with a maximum latency of five days . Third, EGSIEM established a prototype of a hydrological / early warning service that derives wetness indices as indicators of hydrological extremes and assessed their potential for timely scheduling of high-resolution optical/radar satellites for follow-up observations in case of evolving hydrological extreme events.

Introduction Atrial fibrillation (AF) is common in hypertrophic cardiomyopathy (HCM) and is generally associated with a significant deterioration of clinical status. Non-pharmacological treatment such as surgical and catheter ablation has become an established therapy for symptomatic AF but in patients with HCM often having a chronically increased left atrial pressure and extensive atrial cardiomyopathy the long-term outcome is uncertain. Purpose The present study aimed to analyse the long-term outcome of AF ablation in HCM and the mechanism of recurrent atrial arrhythmias using high-density mapping systems. Methods A total of 65 patients (age 64.5±9.9 years, 42 (64.6%) male) with HCM undergoing AF ablation for symptomatic AF were included in our study. The ablation strategy for catheter ablation included pulmonary vein isolation in all patients and biatrial ablation of complex fractionated electrograms with additional ablation lines if appropriate. In patients with suspected atrial tachycardia (AT) high-density activation and substrate mapping were performed. A surgical ablation at the time of an operative myectomy for left ventricular outflow tract obstruction was performed in 8 (12.3%) patients. The outcome was analysed using clinical assessment, Holter ECG and continuous rhythm monitoring of cardiac implantable electric devices. Results Paroxysmal AF was present in 27 (41.6%), persistent AF in 37 (56.9%) and primary AT in 1 (1.5%) patients. The mean left atrial diameter was 54.1±12.5 ml. In 11 (16.9%) patients with AT high-density mapping was used to characterize the mechanism of the ongoing tachycardia. After 1.9±1.2 ablation procedures and a follow-up of 48.5±37.2 months, ablation success was demonstrated in 58.9% of patients. The success rate for paroxysmal and persistent AF was 70.0% and 55.8%, respectively (p=0.023). Of those patients with AT high-density mapping guided ablation was successful in 44.4% of patients. The LA diameter of patients with a successful ablation was smaller (52.2 vs. 58.1 mm; p=0.003). Conclusion Non-pharmacological treatment of AF in HCM is effective during long-term follow-up. Paroxysmal AF and a smaller LA diameter are favourable for successful ablation. In patients with complex AT the use of high-density mapping can guide ablation resulting in further ablation success in a reasonable number of patients.

著者人数: H.E.S.S. Collaboration 233名 (所属. 宇宙航空研究開発機構宇宙科学研究所(JAXA)(ISAS): 桂川, 美穂; 中島, 真也; 小高, 裕和; 高橋, 忠幸), Number of authors: H.E.S.S. Collaboration 233 (Affiliation. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency(JAXA)(ISAS): Katsuragawa, Miho; Nakashima, Shinya; Odaka, Hirokazu; Takahashi, Tadayuki), Accepted: 2018-09-29, 資料番号: SA1180422000

We combined two-dimensional kinematic and morphology information on the Halpha emission, obtained using near-infrared integral field spectroscopy, with broad-band photometry to investigate the dynamical structure and the physical properties of a sample of ten late-type galaxies at 1.0 < z < 1.5. The sample displays a range of kinematical types which include one merger, one face-on galaxy, and eight objects showing evidence of rotation. Among these eight objects, half are rotation-dominated galaxies, while the rest are dispersion-dominated. We found also that two galaxies out of the rotation-dominated galaxies are pure rotationally supported disks. They achieve a maximum velocity of ~180-290 km/s within ~0.5-1 kpc, similar to local spirals with thin disks. The galaxies of our sample have relatively young stellar populations (< 1.5 Gyr) and possess a range of stellar mass of 0.6-5 X10^10 Msun. In addition, most of them have not yet converted the majority of their gas into stars (six galaxies have their gas fraction >50 per cent). Therefore, those of them which already have a stable disk will probably have their final stellar mass similar to the present-day spirals, to which these rotating systems can be seen as precursors. We conclude our study by investigating the stellar mass Tully-Fisher relation at 1.2 < z < 1.5., Comment: 18 pages. Accepted 2009 November 20 for publication in MNRAS

Surface mass redistribution within the Earth system, especially in the atmosphere, oceans, continents and ice sheets, causes the position of the centre of mass to vary in a reference frame attached to the solid Earth. Space techniques are now precise enough to measure the centre of mass motion. Here we present a determination of the centre of mass coordinates at regular monthly intervals using DORIS data on SPOT-2, SPOT-3 and Topex–Poseidon (1993–1997) and laser data on Lageos-1 and Lageos-2 (1993–1996). The amplitude and phase of the space-geodesy-derived annual cycle for each coordinate are further compared to estimates based on surface mass redistribution at the Earth surface derived from various climatic data sources: surface pressure, soil moisture, snow depth and ocean mass variations.

The cycling status of cord blood progenitors and the culture conditions triggering their activation into S-phase have been studied using flow cytometry and a 3H-thymidine suicide assay. Mononuclear cells cultured either in Iscove's modified Dulbecco's medium (IMDM) +/- 10% fetal calf serum ([FCS]; IMDM + FCS) or in Dulbecco's modified Eagle's medium (DMEM) +/- 10% newborn bovine serum ([NBS]; DMEM + NBS) were stimulated by various growth factors (GFs). Results showed that CD34+ cells, clonogenic progenitors (colony forming cells [CFCs]) and long-term culture initiating cells (LTC-IC) present in freshly harvested cord blood were quiescent. CFC numbers were maintained without cycling after 48-h cultures in serum-containing media without GFs. Addition of interleukin 3 (IL-3) + IL-6 + stem cell factor stimulated into S-phase approximately 40% of CFCs within 24-48 h, without modifying their number except in DMEM + NBS where erythroid progenitors decreased. When cells were stimulated in IMDM + FCS by these three GFs + insulin-like growth factor I and basic fibroblast growth factor used at high concentration, more than 50% of CFCs were in S-phase and their total number was maintained. The latter culture conditions also recruited up to 66% of LTC-IC into S-phase. Our data underline the importance of the combination of GFs and culture media used for optimizing the cycling and maintenance of CFCs and LTC-IC within two days.

The tetrapeptide Acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), isolated from fetal calf marrow and now chemically synthetized, inhibits the entry of murine CFU-S into DNA synthesis and so protects mice against the toxicity of high doses of chemotherapy. In view of its potential clinical use as a marrow protector, we have investigated its effects on human normal and leukemic cells. The synthetic tetrapeptide reduced significantly the percentage in DNA synthesis of bone marrow progenitors CFU-GM, BFU-E and CFU-E and inhibited the colony growth by about 40% at nanomolar concentration. This inhibition was reversible and affected cycling cells. Furthermore, cord blood progenitors, which were highly cycling, were also significantly inhibited by the peptide. AcSDKP was then assayed on the peripheral blood cells from chronic myeloid leukemic (CML) patients. No change in the number nor in the percentage of progenitors in S phase was observed whatever the doses used. The leukemic origin of the colonies was confirmed by PCR analysis. Thus, the selective inhibitory effect of the peptide on normal progenitors represents a potential therapeutic advantage for marrow protection during chemotherapy.