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Background: Previous studies established a link between high screen time and mental health problems in childhood. The role of possible influencing factors is currently unclear. This study aims at testing correlations among mental health problems, high screen time, parenting stress, and inconsistent and positive parenting behavior., Methods: This study is based on data from the KiGGS and BELLA studies. For the present study, data from preschool children (age: 3-5 years, N = 417) and school children (age: 7-13 years, N = 239) were analyzed. Binary-logistic regressions were carried out to test for correlations between high screen time and children's mental health problems in cross-sectional and longitudinal analyses. Socioeconomic status, the child's gender, the parent's gender, parenting stress, and inconsistent and positive parenting behavior were used as control variables., Results: In the cross-sectional analysis, mental health problems in preschool children were associated with high screen time (OR = 3.02; p = 0.003), parenting stress (OR = 17.00; p < 0.001), and positive parenting behavior (OR = 0.24; p < 0.001). In the longitudinal analysis, mental health problems in school children were associated with parenting stress (OR = 4.04; p < 0.001). Socioeconomic status and the child's and parent's gender were at no point associated with mental health problems., Discussion: The sole existence of high screen time cannot explain mental health problems in children. Parental variables seem to be critical for children's mental health and should be considered in a holistic apporach on children's mental health in terms of strengthening parental competencies., (© 2023. The Author(s).)

Background: Continuous nationwide health monitoring is important to track the well-being of children and adolescents and to map developmental trajectories. Based on the results of three selected epidemiological studies, developments in child well-being over the past 20 years are presented., Methods: Data are based on (1) the mental health module of the German National Health Interview and Examination Survey among Children and Adolescents (BELLA study, 2003-2017, N = 1500 to 3000), which is a module of the KiGGS study; (2) the COvid-19 and PSYchological Health Study (COPSY, 2020-2022, N = 1600-1700), which is based on the BELLA Study; and (3) the International Health-Behaviour in School-aged Children Study (HBSC, 2002-2018, N = 4300-7300). Well-being was assessed in 7‑ to 17-year-olds using indicators of health-related quality of life (KIDSCREEN-10), life satisfaction (Cantril Ladder), and mental health problems (Strenghts and Difficulties Questionnaire (SDQ), Screen for Child Anxiety Related Emotional Disorders (SCARED), and Center for Epidemiological Studies Depression Scale for Children (CES-DC))., Results: Overall, children and adolescents show consistently high health-related quality of life and high overall life satisfaction pre-pandemic (2002-2018), which initially worsened with the onset of the 2020 COVID-19-pandemic. Two years later, improvements are evident but have not yet reached baseline levels. Psychological problems, as well as symptoms of anxiety and depression, increased by up to 12 percentage points at the beginning of the pandemic and are still higher two years after the onset of the pandemic compared to pre-pandemic studies., Conclusion: The epidemiology of child well-being provides a necessary data basis to assess the support needs of children and adolescents and to use this as a basis for developing measures of health promotion, prevention, and intervention., (© 2023. The Author(s).)

Background: The COVID-19 pandemic has impacted the learning and health of children and adolescents. The aim of this paper is to examine school students' mental health problems, family burden, and support needs during the pandemic depending on the type of school. Approaches to school-based prevention and health promotion are discussed., Methods: Findings are based on data from the population-based COPSY study (T1: 05/2020 - T4: 02/2022) and the BELLA study (T0, pre-pandemic comparison). Approximately 1600 families with children aged 7 to 19 years were surveyed at each measurement point (T). Mental health problems were assessed using the SDQ, while family burden and support needs were captured with individual items in the parent report., Results: Mental health problems increased among students in all school types at the beginning of the pandemic and have stabilized at a high level. Elementary school students are particularly affected (increase from 16.9% pre-pandemic to 40.0% at T2), especially in behavioral problems (11.7% to 24.6%) and hyperactivity (13.9% to 34.0%). Secondary school students also show higher levels of mental health problems (21.4% to 30.4%). Pandemic-related burden is consistently high, as is the need for family support received from schools/teachers and experts., Discussion: There is a high need for mental health promotion and prevention measures in the school setting. These should start at primary school age in the sense of a "whole school approach" at different levels and include external stakeholders. In addition, binding legal requirements are needed in all federal states to create framework conditions and structures for school-based health promotion and prevention, including access to necessary resources., (© 2023. The Author(s).)

Background: The drastic changes during the COVID-19 pandemic may have a negative impact on the psychological wellbeing of children and adolescents., Objectives: COPSY is the first national, representative German study to examine mental health and quality of life of children and adolescents during the pandemic. Results are compared with data of the representative longitudinal BELLA study conducted before the pandemic., Materials and Methods: Internationally established instruments for measuring health-related quality of life and mental health (including anxiety and depressive symptoms) were administered to n = 1586 parents with 7‑ to 17-year-old children and adolescents, of whom n = 1040 11- to 17-year-olds also provided self-reports, from 26 May to 10 June 2020. Data were analyzed using descriptive statistics and bivariate tests., Results: Seventy-one percent of the children and adolescents and 75% of the parents felt burdened by the first wave of the COVID-19 pandemic. Compared to the time before the pandemic, the children and adolescents reported a lower health-related quality of life, the percentage of children and adolescents with mental health problems almost doubled, and their health behavior worsened. Socially disadvantaged children felt particularly burdened by the COVID-19 pandemic. Two-thirds of the parents would like to receive support in coping with their child during the pandemic., Conclusions: The COVID-19 pandemic poses a mental health risk to children and adolescents. Schools, doctors, and society are called to react by providing low-threshold and target-group-specific prevention and mental health promotion programs., (© 2021. The Author(s).)

Background: Health-related quality of life (HRQoL) is increasingly established as an indicator for the subjective health of children and adolescents. The aim of this study was to describe the current HRQoL among children and adolescents in Germany aged between 11 and 17 years taking into account common chronic diseases (bronchial asthma, atopic dermatitis, obesity, ADHD) and mental health problems., Methods: The analysis is based on information obtained from 6,599 children and adolescents (51.9% girls; 48.1% boys) from KiGGS Wave 2 (2014-2017). HRQoL was measured with the multidimensional KIDSCREEN-27. The chronic diseases and mental health problems under investigation were assessed by several indicators., Results: Differences in HRQoL could be found as a function of age and gender. The HRQoL among girls was lower at an older age across all dimensions. These age-related differences are less pronounced among boys. The HRQoL of children and adolescents with chronic diseases and mental health problems was lower compared to their healthy peer groups. The comparison of the investigated chronic diseases and mental health problems revealed significant differences. Particularly, HRQoL was lower for children and adolescents with obesity and mental health problems., Discussion: The distinction of several dimensions of HRQoL allows a comprehensive understanding of age- and gender-related effects and provides a detailed assessment of the impact of chronic diseases and mental health problems. The present findings underline the importance of HRQoL as an indicator for the subjective health of children and adolescents.

Background: The basis for healthy development is established during the first years of one's life. In this early phase, parents can significantly influence the health conditions under which their child grows up. Parental education can play a key role in this regard. This study examines the association of maternal education with health and health behavior in infants., Methods: A subsample of the representative German KiGGS study (Wave 1, 2009-2012) on the health of children and adolescents was investigated. Data from 1727 mothers who reported on health-specific characteristics of their infants (0 to 2 years), on their own educational background, and on characteristics of the family were analyzed. The influence of maternal education on indices of health and health behavior in infants was investigated by means of logistic regression; additional predictors were considered in regression models., Results: Higher maternal education was associated with better health behavior, but not with overall infant health. The impact of maternal education on health behavior remained significant when considering other predictors (financial worries, low maternal age at childbirth, premature birth/low birth weight). Overall, low maternal education was accompanied by an accumulation of additional risks., Conclusions: Higher maternal education can help infants have a good start in their lives. The impact of poor health behavior on infant health may not become apparent until later in their lives. For prevention and intervention, it is important to identify sensitive stages of development during childhood and the underlying mechanisms of the relationship between maternal education and infant health behavior.

Ex vivo recorded action potentials (APs) in human right atrial tissue from patients in sinus rhythm (SR) or atrial fibrillation (AF) display a characteristic spike-and-dome or triangular shape, respectively, but variability is huge within each rhythm group. The aim of our study was to apply the machine-learning algorithm ranking instances by maximizing the area under the ROC curve (RIMARC) to a large data set of 480 APs combined with retrospectively collected general clinical parameters and to test whether the rules learned by the RIMARC algorithm can be used for accurately classifying the preoperative rhythm status. APs were included from 221 SR and 158 AF patients. During a learning phase, the RIMARC algorithm established a ranking order of 62 features by predictive value for SR or AF. The model was then challenged with an additional test set of features from 28 patients in whom rhythm status was blinded. The accuracy of the risk prediction for AF by the model was very good (0.93) when all features were used. Without the seven AP features, accuracy still reached 0.71. In conclusion, we have shown that training the machine-learning algorithm RIMARC with an experimental and clinical data set allows predicting a classification in a test data set with high accuracy. In a clinical setting, this approach may prove useful for finding hypothesis-generating associations between different parameters.

Child and adolescent mental health problems burden not only the individual, but also their families and their social environment and may, therefore, be regarded as a highly relevant public health issue. The data on mental health problems of children and adolescents from the KiGGS Wave 1 study (sample period 2009-2012) make it possible to report on both current prevalence rates and time trends over the 6-year period beginning with the KiGGS baseline survey (2003-2006). The assessment of emotional and behavioral problems in KiGGS Wave 1 was carried out with the symptoms questionnaire of the Strengths and Difficulties Questionnaire (SDQ) in a telephone interview with 10,353 guardians of children and adolescents aged 3-17 years. Moreover, using the SDQ impact supplement, the KIGGS Wave 1 data provide information on psychosocial impairment following child and adolescent mental health problems. Subjects with a borderline or abnormal SDQ score, according to German normative data, were considered at risk. A total of 20.2% (95% CI: 18.9-21.6%) of the study subjects were identified as being at risk for a mental health disorder, compared with 20.0% (19.1-20.9%) during the KiGGS baseline study (age-standardized based on population from 12 December 2010). Thus, no significant changes over time in the prevalence of mental health problems were detected. Also, there were no statistically significant differences in prevalence by sex, age group, or socioeconomic status between the KiGGS baseline survey and KiGGS Wave 1. The statistical comparison of the subscale mean values for both girls and boys showed higher values with respect to the subscales for emotional problems, behavioral problems, and prosocial behavior and lower mean values for the peer problems subscale in KiGGS Wave 1. These partly small temporal trends, however, may be due to possible mode effects (written questionnaire in the KiGGS baseline study versus telephone interview in KiGGS Wave 1). The hyperactivity subscale remained stable across the two sample periods. Regarding impairments following mental health problems at the second sample period, boys were more affected in the areas of chronicity, family burden, and impact score. The high and stable prevalence rates and magnitude of emotional and behavioral problems should prompt increased preventive efforts.

In recent years, there has been a change in the health and disease spectrum among children and adolescents, with an increase in mental health problems and a shift from acute to chronic illness. In this phase, the health-related quality of life (HRQoL) has increased in importance as a dimension of subjective health. The aim of this study is to describe the HRQoL of children and adolescents measured with the internationally standardized screening instrument KIDSCREEN-10. In the follow-up of the KiGGS study in 2009-2012 (KiGGS Wave 1), 2,567 parents of children aged 7-10 years and 4,878 adolescents aged 11 years or older completed the KIDSCREEN-10 questionnaire. In all, 94% of parents of 7- to 10-year-old girls and boys estimate the HRQoL of their children to be "very good" or "good." Of the 11- to 17-year-old adolescents, 96% report their HRQoL as "very good" or "good." Somatic diseases and pain as well as mental health problems and a low social status are included in the HRQoL in only a limited way. Potential differences in HRQoL by social status were not confirmed in multivariate models. The HRQoL of the examined children and adolescents is predominantly very good or good. Interventions to improve the HRQoL of children and adolescents with diseases and psychopathological problems are necessary, regardless of their social status.

Aim: Different providers of obesity treatment in children and adolescents in Germany were compared using the following criteria: outpatient/inpatient; with/without AGA certification; good/less good quality., Methods: A total of 1,916 patients (8-16.9 years) from 48 study centers were examined before (t0), after (t1), and at least 1 year after therapy (t2/3). Body mass index (BMI), blood pressure, blood lipids, and psychosocial data were measured., Results: Patients from inpatient rehabilitation centers were older and more obese. Patients from AGA-certified centers were more obese, and the completeness of comorbidity screening was higher. There were no differences in short- or long-term BMI reduction. "Good" treatment centers (classified after the UKE study 2004) did not differ from those centers not rated as "good" in weight reduction. Patients treated in "good" centers were more obese, and screening for comorbidity was better. No differences in drop out and loss to follow-up were found., Conclusion: There were only small differences between the different groups. Pronounced differences were found between the individual treatment centers. In order to improve therapy processes and outcomes, benchmarking and quality management have to be extended.

Numerous forms of therapy exist for the increasing number of obese children and adolescents in Germany, but these are heterogeneous and have not been evaluated. Access to health care, long- and short-term treatment outcome, as well as factors determining success of therapy were examined for the first time using standardized instruments to measure somatic and psychosocial variables. A total of 1,916 children aged 8-16 years from 48 (5 rehabilitation, 43 outpatient) institutions were examined. Data were collected for height, weight, blood pressure, and lipid status before treatment started (t0), at the end of treatment (t1), and 1 year after completion of treatment (t2). Furthermore, psychosocial variables were documented using questionnaires for parents and children. The mean BMI-SDS (body mass index standard deviation score) reduction at t1 was -0.27 and 1 year later at t2 was -0.23 (per protocol analysis; intention to treat: t1=-0.24; t2=-0.06). Psychological health and quality of life, which were markedly impaired at the beginning, improved. However, physical activity, media consumption, and nutrition remained basically unchanged. A reduction in weight is associated with an improvement in cardiovascular risk profiles, and long-term behavior changes are possible. However, the institutions differed considerably in the percentage of follow-up examinations and in the weight reduction accomplished.

This article analyzes emotional and behavioral problems in children and adolescents with chronic somatic disorders. Within the German Health Interview and Examination Survey for Children and Adolescents (Kinder- und Jugendgesundheitssurvey, KIGGS), chronic somatic conditions and obesity were assessed in 11,529 children and adolescents aged 7-17 years old. Special health care needs (CSHCN), emotional and behavioral problems (SDQ), as well as personal, familial, and social resources were surveyed. About 10.8% of the respondents displayed special health care needs and declared a chronic somatic disorder. Of these cases, 20.6% were classified as abnormal in the SDQ (non-somatic conditions: 6.4%). In a logistic regression analysis, male gender (OR=2.0), low socioeconomic status (Winkler index; OR=2.6), family structure (OR>1), and deficits in familial (OR=2.4) and personal (OR=2.1) resources were found to be significantly associated with psychological comorbidity in chronic somatic conditions. The results confirmed previous findings. Especially socioeconomic, structural, and functional aspects of a family have to be considered in the development and prevention of psychological comorbidity in chronic somatic conditions in childhood and adolescence.

DPP10 is a transmembrane glycosylated protein belonging to the family of dipeptidyl aminopeptidase-like proteins (DPPLs). DPPLs are auxiliary subunits involved in the regulation of voltage-gated Kv4 channels, key determinants of cardiac and neuronal excitability. Although it is known that DPPLs are needed to generate native-like currents in heterologous expression systems, the molecular basis of this involvement are still poorly defined. In this study, we investigated the functional relevance of DPP10 glycosylation in modulating Kv4.3 channel activities. Using transfected Chinese hamster ovary (CHO) cells to reconstitute Kv4 complex, we show that the pharmacological inhibition of DPP10 glycosylation by tunicamycin and neuraminidase affects transient outward potassium current (I (to)) kinetics. Tunicamycin completely blocked DPP10 glycosylation and reduced DPP10 cell surface expression. The accelerating effects of DPP10 on Kv4.3 current kinetics, i.e. on inactivation and recovery from inactivation, were abolished. Neuraminidase produced different effects on current kinetics than tunicamycin, i.e., shifted the voltage dependence to more negative potentials. The effects of tunicamycin on the native I (to) currents of human atrial myocytes expressing DPP10 were similar to those of the KV4.3/KChIP2/DPP10 complex in CHO cells. Our results suggest that N-linked glycosylation of DPP10 plays an important role in modulating Kv4 channel activities.

Urinary bladder function is known to mature during fetal and postnatal development, including changes in neurotransmitter regulation of detrusor contraction. However, only few experimental data are available about muscarinic receptor antagonist function in the urinary bladder from young animals. In the present study, we compare the muscarinic receptor-mediated contractions in juvenile and adult porcine detrusor and the effects of antimuscarinic compounds. Urinary bladders from young (8-12 weeks; 12- to 35-kg body weight) and mature pigs (>40 weeks; >100 kg) were compared. Muscarinic receptor expression was assessed by real time polymerase chain reaction and radioligand binding. Muscle contraction was measured with a force transducer; L-type Ca2+ currents (ICa,L) of isolated detrusor myocytes were recorded with standard voltage clamp technique. Juvenile and adult detrusor expressed similar quantities of the messenger RNA of M2 and M3 receptors. The number of [3H]QNB-binding sites and their affinity for the radioligand were also similar between juvenile and adult detrusor. In contrast, maximum contractile responses to the muscarinic receptor agonist carbachol were slightly larger in juvenile than adult bladders. On the other hand, carbachol was slightly less potent in juvenile than in adult tissue. The M3 antagonist DAU 5884 and the spasmolytic drug propiverine inhibited contractile responses with comparable efficacies and potencies in juvenile and adult tissue. ICa,L was somewhat smaller in juvenile than in adult cells. Taken together, these data suggest that expression and function of M2 and M3 receptors are similar in the detrusor of juvenile and mature pigs. Therefore, similar responses to antimuscarinic compounds could be expected in young and adult patients.

Objective: Apoptotic processes may be implicated in the molecular pathomechanisms of ventricular remodeling after myocardial infarction (MI). The modulation of apoptosis by pro- and anti-apoptotic pathways in the myocardium remote from the infarction, including its link to protein kinase C (PKC), was focus of the present study., Methods: Rats were subjected to MI by LAD ligation in situ. Some animals were pretreated with the PKC inhibitor chelerythrine. After 1 h up to 28 days, pro- and anti-apoptotic signals (caspase-3, Bcl-2/Bax ratio, Akt, Bad), and marker of apoptosis execution (DNA laddering, TUNEL) were quantified in the myocardium remote from the infarction., Results: Activation of caspase-3, a pro-apoptotic shift of the Bcl-2/Bax ratio, and DNA fragmentation were observed as early as 3 h after infarction and persisted up to 28 days. Akt- and Bad-phosphorylation was unchanged. Chelerythrine markedly reduced DNA fragmentation. Caspase-3 activation was unchanged. Surprisingly, Bad and Akt phosphorylation were highly increased (180% and 750% of control)., Conclusion: Chelerythrine influences the balance of pro- and anti-apoptotic pathways in the remote myocardium after infarction, with an inhibition of proapoptotic and an activation of anti-apoptotic signals.

Mental health problems in children and adolescents constitute health impairments with major implications regarding individual wellbeing as well as daily and social functioning. In addition, these problems often burden the social partners of the individual. Within the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), the parents of 14478 children and adolescents aged 3-17 answered the Strengths and Difficulties Questionnaire (SDQ) which assesses behavioral problems and strengths in the areas emotional problems, hyperactivity, behavioral problems, peer problems and prosocial behavior. According to the results of the Total Difficulties Score (SDQ) 11,5 % girls (G) and 17,8 % boys (B) are classified borderline or abnormal, respectively. 92,5 % (G) and 86,3 % (B) display an adequate pro social behavior. Most prevalent problem areas are behavioral problems (G = 11,9 %, B = 17,9 %), emotional problems (G = 9,7 %, B = 8,6 %) and hyperactivity problems (G = 4,8 %, B = 10,8 %). The test-data of approximately 8,1 % of the respondents with high socio-economic status (SES), 13,4 % of those with middle SES and 23,2 % of those with low SES hinted at mental health problems. Migrants are more frequently affected than non-migrants. Results point at the need for early detection and prevention of commencing mental health problems. Especially the noneasily accessible groups like those with low socioeconomic status or migrants have to be considered.

The Mental Health Module (BELLA study) examines emotional well-being and behaviour in a representative sub-sample of 2,863 families with children aged 7 to 17 from the National Health Interview and Examination Survey for Children and Adolescents (KiGGS). The prevalence of mental health problems was determined using the Strengths and Difficulties Questionnaire (SDQ) and additional standardised screening measures. Of children and adolescents, 21.9 % (95 %CI: 19.9-24.0) showed signs of mental health problems. The psychiatric disorders observed included anxiety (10.0 %; 95 % CI: 8.7-11.6), conduct disorder (7.6 %; 95 % CI: 6.5-8.7) and depression (5.4 %; 95 % CI: 4.3-6.6). Of the risk factors examined, adverse family climate and low socioeconomic status stand out particularly as negative contributors. When several risk factors occur simultaneously, the prevalence of mental health problems increases markedly. Conversely, positive individual, family and social resources coincide with an absence of mental health problems. Children and adolescents with mental health problems display distinctly impaired health-related quality of life, and far from all of them are receiving treatment. Identifying high risk groups therefore requires the assessment of available resources in addition to the usual risk factors for mental and subjective health. Strengthening these resources should be a key objective, both in prevention and in interventions.

This study investigates the health-related quality of life of children and adolescents in Germany, using the internationally employed KINDL-R questionnaire for measuring the health-related quality of life of children and adolescents. In the National Health Interview and Examination Survey for Children and Adolescents (KiGGS) the parents of 14,836 children and adolescents aged 3-17 years completed the KINDL-R, as well as 6,813 children and adolescents (11-17 years old). The reliability (Cronbach's alpha = 0.85) and validity of the measurements using the KINDL-R were confirmed. The differences in health-related quality of life of children and adolescents from different social backgrounds and with different health statuses, which were to be expected on theoretical grounds, were demonstrated by the KINDL-R scores (size of effect "d" up to 1.52). The means and percentiles were calculated for the total sample as well as stratified by age group, sex, geographical region (East/West), migratory status and socio-economic status. The results of this study can be used as representative, normative data for the population of children and adolescents in Germany in general, as well as stratified for sociodemographic and socio-economic subpopulations, in order to interpret test scores on health-related quality of life (KINDL-R).

Along with the salutogenetic approach in health sciences, the quest for factors exerting a protective effect on mental development and health has increasingly gained importance, complementing the study of risk factors. A total of 6,691 children and adolescents aged 11 to 17 years answered questionnaires on personal, social and family resources as part of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS). Children with low socioeconomic status (SES) more frequently show deficits in their personal, social and family resources. Similarly, in children with migration background a higher percentage with poorly developed personal and social protective factors is found. Older children report less family resources but more social resources than younger children; in comparison to boys, girls have more social but less personal resources at their disposal. Clear connections are observed between protective factors and health-related risk-taking behaviour. Deficits in personal and family resources are associated with an increased risk for smoking. Although an increased percentage of smoking and alcohol consuming children and adolescents is found to be associated with well-developed social resources, the risk for drug experiences is not increased. The results prove the necessity to build up protective factors as a preventative measure. Especially in children and adolescents with weak protective factors, an increased risk of mental health problems can be expected in the presence of stressful events.

Within a comprehensive comparison of telephone and postal survey methods the SF-8 was applied to assess adult's health-related quality of life. The 1690 subjects were randomly assigned to a telephone survey and a postal survey. Comparisons across the different modes of administration addressed the response rates, central tendency, deviation, ceiling and floor effects observed in the SF-8 scores as well as the inter-item correlation. The importance of age and gender as moderating factors was investigated. Results indicate no or small statistically significant differences in the responses to the SF-8 depending on the actual mode of administration and the health aspect questioned. It was concluded that further investigations should focus on the exact nature of these deviations and try to generate correction factors.

The SF-8, a relatively new instrument for measuring health-related quality of life, was used in the German National Telephone Health Survey 2003. The SF-8 provides results which are comparable to those of the SF-36, the instrument most commonly used internationally. The German National Telephone Health Survey provides nationally representative data for the residential population in Germany aged 18 and older. In addition to the measurement of health-related quality of life, comprehensive information on chronic illnesses and complaints, health care needs, utilisation of health care, risk factors, risk behaviour and social status is also collected, making differentiated analyses possible. According to the data collected, men rate their quality of life in all dimensions higher than women. With increasing age, quality of life for both men and women decreases in the physical dimensions, while increasing in the mental health dimensions. Apart from chronic disease and pain having a negative impact on health-related quality of life, social differences are also observable, in that worse health-related quality of life is reported by respondents with lower socioeconomic status.

Inhibitors of phosphodiesterase type III (PDE III) enhance cardiac contractile force by elevating the intracellular calcium concentration [Ca2+]i by impairing cAMP degradation thus increasing cAMP levels. The drugs are more effective in healthy than in failing hearts since basal cAMP production is diminished in the latter. However, long term treatment with PDE-III inhibitors does not appear to be beneficial due to increased risk of potentially lethal arrhythmias caused by augmentation of [Ca2+]i[1). This risk should be absent in Ca2+ sensitizers. Recently, thiadiazinone derivatives have been synthetized in which the potency for Ca2+ sensitization is many-fold larger than the potency for PDE-III inhibition. The Ca(2+)-sensitizing action resides in the [+]-enantiomers, while the [-]-enantiomers show weak PDE-III inhibition. In the enantiomer pair [+]-EMD 60263 and [-]-EMD 60264, only the former concentration-dependently increased force of contraction in isolated cardiac preparations and myocytes. In the Langendorff-perfused guinea-pig heart, force was reversibly increased, whereas [-]-EMD 60264 even produced a negative inotropic response despite of its PDE inhibitory activity. Heart rate, however, was reduced by both enantiomers. Perfusion pressure remained unaffected. The effects were fully reversible upon wash-out of the enantiomers. [+]-EMD 60263 also enhanced cell shortening of human myocytes from both normal and failing hearts. In contrast to the opposite effects on contractility, both enantiomers prolong the action potential duration by blocking the rapidly activating component of the delayed rectifier K+ current. Thus they also possess class III antiarrhythmic activity. The therapeutic potential of these agents has yet to be assessed in clinical studies.