Mechanism Of Contraction Research Articles

Abstract 4139162: Optical coherence tomography measures mechanical contractile properties of the beating murine heart

Introduction: Optical imaging techniques can characterize properties of tissue at high temporal and spatial resolution, offering unique insights into electrically excitable tissues such as nerve and muscle. We hypothesized that the gated high-speed optical coherence tomography (OCT) could profile the contractile properties of mouse myocardial tissue and facilitate investigations of microscale mechanical function in the beating heart. Methods: C57BL/6 male mice (n=6) underwent a sternotomy while anesthetized and ventilated and were imaged at baseline with OCT. Another cohort of C57BL/6 male mice (n=6) were sacrificed and the hearts were ex vivo perfused with crystalloid using a Langendorff system. These hearts were imaged at baseline and after inhibition of contractile function with blebbistatin. OCT was performed using a custom tissue stabilizer and a Thorlabs TEL 321 OCT system, which was synchronized to physiologic signals using custom hardware and software and cardiac pacing protocols (Fig. 1A and 1B). OCT cross-sectional B-scan images (Fig. 1C) were obtained throughout multiple cardiac cycles in both in vivo and ex vivo preparations. Data were processed in MATLAB and ImageJ using the workflow in Fig. 1D. Results: Highly reproducible cross-sectional mean intensity changes were observed over the contractile cycle in vivo and ex vivo (Fig. 1E, left and middle). With mechanical contraction inhibited by blebbistatin, this cyclical intensity extinguished, linking the optical scattering change measured by OCT to myocardial contraction (Fig. 1E, right). B-scan curves averaged over multiple mice and temporally aligned with the ECG waveform (Fig. 1F) demonstrate a signal intensity waveform that reproducibly varies with the contractile cycle for both in vivo and ex vivo preparations. In vivo and ex vivo baseline waveforms both had peak intensity during systole and minimum in end-diastole (Fig. 1F). Reproducibility in ex vivo beating heart preparations without blood perfusion provides evidence that myocardial mechanical properties, not red blood cell flow, generate the intensity changes. Conclusion: Gated high-speed OCT imaging can quantify the mechanical contraction wave in the myocardium. Combined with gated OCT angiography, OCT techniques will provide high resolution imaging of both blood flow and mechanical contractility of the beating heart in small animal models of heart disease.

The Relationship Between the Psychological Contract and Job Satisfaction of Beginning College Student Employees

In the context of the rapidly evolving economic landscape, the relationship between the psychological contracts of newly-graduated entry-level employees and their job satisfaction has emerged as a pivotal research topic within the realm of organizational management. The psychological contract, an informal and subjective promise of employment relations, directly influences employees' attitudes and performance. Various types of psychological contracts, such as transactional, relational, and developmental, to some extent, impact employees' job satisfaction. By effectively managing psychological contracts, enterprises can enhance employees' job satisfaction, thereby achieving a win-win situation. This article elucidates the impact mechanism of psychological contracts on job satisfaction and proposes a series of measures to improve the job satisfaction of newly-graduated entry-level employees. These measures include establishing a robust psychological contract, providing systematic introductory training, fostering a supportive work environment, implementing fair performance management, and promoting teamwork and social interaction.

High-resolution chromosome-level genome of Scylla paramamosain provides molecular insights into adaptive evolution in crabs

BackgroundEvolutionary adaptation drives organismal adjustments to environmental pressures, exemplified in the diverse morphological and ecological adaptations seen in Decapoda crustaceans, particularly brachyuran crabs. Crabs thrive in diverse ecosystems, from coral reefs to hydrothermal vents and terrestrial habitats. Despite their ecological importance, the genetic mechanisms underpinning their developmental processes, reproductive strategies, and nutrient acquisition remain poorly understood.ResultsHere, we report a comprehensive genomic analysis of the green mud crab Scylla paramamosain using ultralong sequencing technologies, achieving a high-quality chromosome-level assembly. The refined 1.21 Gb genome, with an impressive contig N50 of 11.45 Mb, offers a valuable genomic resource. The genome exhibits 33,662 protein-coding genes, enriched in various pathways related to development and environmental adaptation. Gene family analysis shows expansion in development-related pathways and contraction in metabolic pathways, indicating niche adaptations. Notably, investigation into Hox gene regulation sheds light on their role in pleopod development, with the Abd-A gene identified as a linchpin. Post-transcriptional regulation involving novel-miR1317 negatively regulates Abd-A levels. Furthermore, the potential role of fru gene in ovarian development and the identification of novel-miR35 as a regulator of Spfru2 add complexity to gene regulatory networks. Comparative functional analysis across Decapoda species reveals neo-functionalization of the elovl6 gene in the synthesis of long-chain polyunsaturated fatty acids (LC-PUFA), suggesting its importance in environmental adaptation.ConclusionsOur findings shed light on various aspects of crab biology, including genome sequencing, assembly, and annotation, as well as gene family expansion, contraction, and regulatory mechanisms governing crucial developmental processes such as metamorphosis, reproductive strategies, and fatty acid metabolism.

Precursory crater contraction associated with the 2017 eruption of Shinmoe-dake volcano (Japan) detected by PALSAR-2 and Sentinel-1 InSAR

The time series of PALSAR-2 and Sentinel-1 images reveal inflation at the volcanic flank and contraction at the crater for approximately 5 months before the 2017 eruption of Shinmoe-dake volcano, Japan. While the observation of inflation at the volcano’s flank is ubiquitous, few studies have reported crater contraction preceding an eruption. The flank inflation stopped after the 2017 eruption, while the contraction at the crater continued until the 2018 eruption. We found that a pipe-shaped deformation source above sea level best fits the observation preceding the 2017 eruption. Suppose the flux of ejected materials constrains the conduit radius during the previous 2011 eruption. In that case, the amount of deformation of the pipe-shaped deformation source, whether open or closed at its top, is too large to be realistic. Although constraining the conduit radius from the eruption flux overestimates the pressure change of the pipe-shaped deformation source, water-saturated fractures along the volcanic conduit could extend the effective conduit radius of the pressure source. We propose one potential scenario for the mechanism of the crater contraction preceding volcanic eruptions based on the combination of compaction due to cooling by ambient groundwater and material withdrawal within the conduit. The groundwater inflows from the ambient aquifer through cracks in the porous conduit wall, which are generated by conduit expansion during the magma ascent. Decoupling from the conduit wall due to a decrease in volume of the material promotes material instability and crater contraction. The interaction between the groundwater and the magma triggers the 2017 eruption of Shinmoe-dake volcano, as previous studies have reported.Graphical

Assessment of ventricular mechanics by means of myocardial work in patients undergoing physiologic versus right ventricular apical stimulation:a prospective study

Abstract Introduction Left bundle branch area (LBBA) pacing has recently gained widespread acceptance in patients that need pacemaker (PM) stimulation. This type of physiologic pacing may improve ventricular mechanical contraction and reduce the risk of PM-induced left ventricular (LV) dysfunction. Myocardial work (MW), a new tool, based on the analysis of pressure-strain loops, combines the information from speckle tracking strain imaging and non-invasive estimate of LV pressure. It provides a better characterization of LV performance and detection of LV myocardial dysfunction. The aim of this study was to compare MW after PM implantation in LBBA pacing patients (group 1) vs right ventricular apical (RVA, group 2) pacing patients. A control group (group 3) was also enrolled for establishing MW normal values. Methods We studied 30 patients (56% females, age 80 y, IQR 75-84) who underwent PM implantation and had a high probability of a high % of stimulation and 21 controls (57% females, age 79 y, IQR 73-85, p=0.46 and p=0.73 respectively) Patients were prospectively included at two large university hospitals from March 23 until February 24. The mode of stimulation was chosen at their physician’s discretion. Exclusion criteria included LVEF <50% or significant structural or valvular disease. We compared MW parameters between group 1 and group 2 before PM implantation, and 24 hours and 3 months post PM implantation by Kruskal Wallis test. Additionally, we compared MW parameters between group 3 and PM patients after 24 hours using U Mann-Whitney test. Results The % of stimulation was 93%±12. There were no differences in baseline characteristics between group 1 (n=21, 71%) and group 2. At baseline, global work index (GWI), global constructive work (GCW), global wasted work (GWW) or global work efficiency (GWE) did not differ significantly between Group 1 and 2. At 24 hours, all the components of MW significantly improved in Group 1 and 2 and were maintained at 3 months, but the improvement was notably greater in Group 1 (see Table 1). Group 3 and PM patients were similar at baseline (HTN, 86% vs 80%, p=0.7197; DM, 29% vs 30%, p=0.91; coronary artery disease, 14% vs 10%, p=0.68; sinus rhythm, 76% vs 83%, p=0.68). Comparing group 3 and PM at 24 h, GWI, GCW, GWE was significantly higher in group 3 (p=0.0023, p=0.009, p=<0.0001) and GWW was significantly lower (p=<0.0001). Regarding the type of stimulation, MW parameters values in Group 1 were still lower than in Group 3 but clearly better than Group 2 values (see Figure 1). Discussion Our results showed that MW parameters improved to a greater extent in LBBA compared to RVA pacing immediately and after 3 months of PM implantation. Compared to our control group, LBBA pacing group achieved better performance than RVA pacing patients, yielding a more coordinated LV contraction. Nevertheless, more studies are needed to clarify if LBBA pacing causes less PM induced LV dysfunction compared to RVA pacing.

Genomic insights into Aspergillus tamarii TPD11: enhancing polyphyllin production and uncovering potential therapeutic applications.

The excavation and utilization of endophytic fungi from medicinal plants is highly important for the development of new drugs. The endophytic fungus Aspergillus tamarii TPD11, which was isolated and obtained by the authors in the previous stage, can produce a variety of polyphyllins with important potential applications in hemostasis, inflammation and antitumor activities; however, the genomic information of TPD11 is still unknown. In this study, we sequenced and assembled the whole genome of the endophytic fungus A. tamarii TPD11, resolved the genome evolutionary relationships of 24 Aspergillus strains, and phylogenetic analysis of the genomes of 16 strains revealed the evolutionary differences between Aspergillus and Penicillium and the mechanisms of genome expansion and contraction. CAZy annotation analysis revealed that TPD11 obtains nutrients mainly by ingesting starch from the host plant. TPD11 has a biosynthesis-related gene cluster for the synthesis of squalestatin S1, and the silencing of this biosynthesis-related gene cluster might increase the content of polyphyllin. Annotation of 11 UDP-glycosyltransferase genes helps to further reveal the biosynthetic pathway of polyphyllin. In addition, secondary metabolism gene cluster and CAZy analyses confirmed the potential probiotic, insecticidal and antimicrobial activities of TPD11 on host plants. This study reveals the intrinsic mechanism by which endophytic fungi increase the content of polyphyllin, which provides a basis for the synthetic synthesis of the natural product polyphyllin.

Investment Climate in the MENA Region: Are the Stabilisation Clauses in Foreign Direct Investment Agreements an Obstacle to Progress?

Abstract Foreign direct investment agreements between Western corporations and the countries of the Middle East and North Africa region (MENA) deserve attention. On one side, the MENA region is a developing region rich in natural resources and therefore a destination interesting to Western investors. On the other, the MENA region is perceived as a volatile and unstable investment environment. Therefore, international investment agreements in the said region often include stabilisation clauses that serve as contractual mechanisms protecting investors from any changes in the laws and acts of nationalisation and expropriation by the host states. As stabilisation clauses have serious adverse effects on the sovereignty of the host states and the development of human rights, this article will take a deeper view of the stabilisation practice and aim to reveal how this contractual mechanism might represent a Catch 22 with respect to the further development of the MENA region countries, especially with respect to human rights and internal governance.

Performance evaluation of the static thrust and efficiency of an actuated biomimetic jellyfish model

Abstract This study offers an in-depth analysis of a jellyfish-inspired robotic model designed to simulate the expansion and contraction mechanisms found in natural jellyfish. By employing variable Duty Cycles to replicate the cyclic motions of the jellyfish, the thrust generation of the model is measured through static thrust assessments using a load cell, while its efficiency is evaluated using the Thrust-to-Power Ratio, TPR. The findings indicate that increasing the amplitude of the motion leads to more complex wave patterns, which in turn reduce the peak-to-peak force generated. Specifically, a 25% increase in the A/D ratio results in a significant 30% decrease in static thrust. It was observed that higher actuation frequencies do not notably influence thrust generation when the A/D ratio remains constant. Importantly, the TPR was found to be highest at an A/D ratio of 0.10, with an increase of up to 6% observed at higher Duty Cycles, suggesting that smaller actuation amplitudes are more efficient in enhancing thrust performance. These results highlight the critical role of amplitude in the efficiency of static thrust generation within a given Duty Cycle, emphasizing that lower amplitudes generally lead to higher efficiency. The study underscores the importance of optimizing both geometric and kinematic parameters for improved propulsion performance. It suggests that future research should focus on fine-tuning A/D ratios and Duty Cycles, as well as exploring alternative geometric configurations and materials to further enhance the hydrodynamic performance of jellyfish-inspired robots. The insights gained from this study provide a valuable foundation for developing more efficient and effective bio-inspired underwater vehicles.

Technology and new work

The article aims to evaluate, through an evolutionary overview of social achievements related to labor law, the impact of reducing working hours on the productivity and health of Brazilian workers. Specifically, it seeks to answer the following questions: Will worker productivity increase with a temporary reduction in working hours? Are there positive health impacts for workers who experience a reduction in working hours? To address these questions, the hypothetical-deductive method was used. The methodological approach was based on historical-typological analysis, with the interpretation framed through a sociological lens. The research, qualitative in nature, employs bibliographic and documentary sources on the topic, with a primarily explanatory objective. The study highlights the need for closer monitoring of labor relations, focusing on the enhancement of human work, particularly in the context of current technological advancements. It argues that personal development can lead to increased productive capacity and a greater balance in the work-life relationship, thereby fostering continuous evolution. To achieve this, public policies aimed at enhancing the employability of Brazilian workers will be necessary, alongside the involvement of representative groups through collective labor law. These efforts should focus on developing effective contractual mechanisms to improve labor quality and drive economic development.

Is It Possible to Regenerate the Underactive Detrusor? Part 1 Molecular and Stem Cell Therapies Targeting the Urinary Bladder and Neural Axis ICI-RS 2024.

Detrusor muscle weakness is commonly noted on urodynamics in patients with refractory voiding difficulty. No approved therapies have been proven to augment the strength of a detrusor voiding contraction. This subject was discussed by a think-tank at the International Consultation on Incontinence- Research Society (ICI-RS) meeting held in Bristol, June 2024. The discussions of the think-tank are being published in two parts. This first part discusses molecular and stem cell therapies targeting the urinary bladder and the neural axis. Senescence of the urothelium and extracellular ATP acting through P2X3 receptors might be important in detrusor underactivity. Several molecules such as parasympathomimetics, acotiamide, ASP8302, neurokinin-2 agonists have been explored but none has shown unequivocal clinical benefit. Different stem cell therapy approaches have been used, chiefly in neurogenic dysfunction, with some studies showing benefit. Molecular targets for the neural axis have included TRPV-4, Bombesin, and serotoninergic receptors and TAC-302 which induces neurite growth. Several options are currently being pursued in the search for an elusive molecular or stem cell option for enhancing the power of the detrusor muscle. These encompass a wide range of approaches that target each aspect of the contraction mechanism including the urothelium of bladder and urethra, myocyte, and neural pathways. While none of these have shown unequivocal clinical utility, some appear promising. Lessons from other fields of medicine might prove instructive. Not necessary. Not a clinical trial.

Актуальные вопросы правового регулирования трудовой функции

The article considers the importance of legal regulation of labor function for the science of labor law and law enforcement today. The analysis of legislation, positions of state authorities, doctrinal provisions and current court practice proves that at the moment at different stages of labor relations in the legal regulation of labor function there are still significant gaps. The conclusion is formulated that it is necessary to specify a number of provisions of labor legislation concerning the documents fixing and changing the labor function of a particular employee, the use of contractual mechanism of changing the labor function.

Mechanisms for Ensuring Professional Responsibility of Medical Workers through Contractual Means

This article examines the use of contractual mechanisms to promote and enforce professional responsibility among medical workers. As healthcare systems face increasing pressures and scrutiny, there is a growing need for effective ways to ensure high standards of care and ethical conduct. The study analyzes how employment contracts, codes of conduct, and other formal agreements can be structured to clearly delineate professional expectations, incentivize best practices, and provide accountability. Key contractual elements explored include specific performance metrics, ongoing training requirements, incident reporting protocols, and disciplinary procedures. The potential benefits and limitations of relying on contractual means to shape professional behavior are critically assessed. While contracts alone cannot guarantee responsible conduct, when thoughtfully designed and consistently enforced, they can serve as powerful tools for health organizations to uphold professional standards and protect patient welfare.

Buoyancy regulation in insects.

Multiple insect lineages have successfully reinvaded the aquatic environment, evolving to complete either part or all of their life cycle submerged in water. While these insects vary in their reliance on atmospheric oxygen, with many having the ability to extract dissolved oxygen directly from the water, all retain an internal air-filled respiratory system, their tracheal system, due to their terrestrial origins. However, carrying air within their tracheal system, and even augmenting this volume with additional air bubbles carried on their body, dramatically increases their buoyancy which can make it challenging to remain submerged. But by manipulating this air volume a few aquatic insects can deliberately alter or regulate their position in the water column. Unlike cephalopods and teleost fish that control the volume of gas within their hydrostatic organs by either using osmosis to pull liquid from a rigid chamber or secreting oxygen at high pressure to inflate a flexible chamber, insects have evolved hydrostatic control mechanisms that rely either on the temporary stabilization of a compressible air-bubble volume using O2 unloaded from hemoglobin, or the mechanical expansion and contraction of a gas-filled volume with rigid, gas-permeable walls. The ability to increase their buoyancy while submerged separates aquatic insects from the buoyancy compensation achieved by other air-breathing aquatic animals which also use air within their respiratory systems to offset their submerged weight. The mechanisms they have evolved to achieve this are unique and provide new insights into the function and evolution of mechanochemical systems.

Native mechano-regulative matrix properties stabilize alternans dynamics and reduce spiral wave stabilization in cardiac tissue.

The stability of wave conduction in the heart is strongly related to the proper interplay between the electrophysiological activation and mechanical contraction of myocytes and extracellular matrix (ECM) properties. In this study, we statistically compare bioengineered cardiac tissues cultured on soft hydrogels ( kPa) and rigid glass substrates by focusing on the critical threshold of alternans, network-physiological tissue properties, and the formation of stable spiral waves that manifest after wave breakups. For the classification of wave dynamics, we use an improved signal oversampling technique and introduce simple probability maps to identify and visualize spatially concordant and discordant alternans as V- and X-shaped probability distributions. We found that cardiac tissues cultured on ECM-mimicking soft hydrogels show a lower variability of the calcium transient durations among cells in the tissue. This lowers the likelihood of forming stable spiral waves because of the larger dynamical range that tissues can be stably entrained with to form alternans and larger spatial spiral tip movement that increases the chance of self-termination on the tissue boundary. Conclusively, we show that a dysfunction in the excitation-contraction coupling dynamics facilitates life-threatening arrhythmic states such as spiral waves and, thus, highlights the importance of the network-physiological interplay between contractile myocytes and the ECM.

Near-Infrared Stimuli-Responsive Hydrogel Promotes Cell Migration for Accelerated Diabetic Wound Healing.

Diabetic wound healing including diabetic foot ulcers is a major clinical challenge, which could bring an increased level of mortality and morbidity. However, conventional wound dressings exhibit limited healing efficacy due to their lack of active modulation for the healing process. Here, a near-infrared (NIR) stimuli-responsive composite hydrogel dressing with the synergistic effect of both mechanical contraction and epithelial-mesenchymal transition (EMT) was developed to facilitate cell migration and vascularization for diabetic wound healing. In the methacrylated gelatin-based composite hydrogel, N-isopropylacrylamide and polydopamine nanoparticles were incorporated to endow the composite hydrogel with thermosensitive and photothermal properties. Linagliptin (LIN) was loaded into the composite hydrogel, and the drug release rate could be controlled by NIR laser irradiation. NIR-triggered on-demand active contraction of wound area and LIN release for biological stimulation were potentially realized in this responsive system due to the thermally induced sol-gel transition of the composite hydrogel. The release of loaded LIN could effectively promote cell migration by activating EMT and enhancing angiogenesis. In the full-thickness skin defect model, the LIN-loaded composite hydrogel with NIR laser irradiation had the highest wound closure rate as compared with the pure hydrogel and LIN-loaded hydrogel groups. Therefore, this composite hydrogel can serve as an excellent platform for promoting wound healing and will find more practical value in clinical treatment.

How does contractual governance affect construction project performance? The mediating role of the contractor’s behavior

ABSTRACT The contractor’s performance behavior is fundamental in improving project performance. However, few studies have investigated the impact of contractual mechanisms on contractor’s performance behavior and how this impacts project performance. Therefore, this study developed and tested a theoretical model to examine the mediating role of contractor’s performance behavior between risk allocation(contractual governance) and project performance. A total of 208 valid questionnaires collected from project managers in the Chinese construction industry were analyzed by partial least squares structural equation modeling (PLS-SEM) to test the theoretical hypotheses. The empirical results show that proper risk allocation can induce both contractors’ perfunctory and consummate behavior and restrict opportunistic behavior, thus achieving basic project performance. Although the mediating effect of perfunctory behavior is insignificant, consummate and opportunistic behavior can mediate between proper risk allocation and value-added project performance, where the mediating role of consummate behavior is more critical. The findings contribute to the impact of contractual mechanisms on the construction project performance and guide the owner’s contract design strategy and the contractor’s choice of performance strategy.

Security design: A review

Security design, which broadly speaking deals with the issue of designing optimal contractual mechanisms for overcoming various frictions between agents, is the subject of an extensive literature. This paper presents a review of recent work on security design and is organized around the applications of security design in various fields of finance starting with classic corporate finance applications such as capital structure and corporate governance, financial intermediation applications such as securitization and contingent capital, the interaction of market and security design, as well as emerging applications such as fintech, sustainable finance and healthcare finance. Future research is also discussed.

Unlocking Energy Efficiency: Debunking Myths on the Road to Decarbonization

Energy efficiency is widely recognized as the foundational and most critical strategy for decarbonizing the manufacturing sector. Misconceptions surrounding energy efficiency measures often hinder their widespread adoption. This article aims to debunk five common myths and provides data and resources to help implement efficiency projects faster and more effectively to achieve greater decarbonization. First, the article challenges the myth that organizations have exhausted all possible energy efficiency opportunities by achieving voluntary energy intensity goals or energy performance certification. Second, it also addresses the misconceptions that efficiency projects are capital-intensive, require many qualified specialists, and have long investment return periods. By presenting real-world case studies and referencing commonly found efficiency opportunities, the article illustrates that energy-savings opportunities are ubiquitous. Organizations can use various contracting mechanisms as well as financial and technical resources from utility companies and government programs to lessen their burden. The notion that efficiency measures can be implemented solely in proprietorship facilities is dispelled. This article emphasizes the importance of green leases and explains that aligning decarbonization goals between the lessor and lessee can help drive savings for both parties. Finally, using unbundled renewable energy certificates as the sole pathway to decarbonization is strongly discouraged. By debunking these prevalent myths, this article aims to foster a deeper understanding of energy efficiency’s potential as a cornerstone of decarbonization efforts and to embrace it as a critical pathway toward a sustainable future.

On the mechanisms of stress-induced human spleen contraction: training for a higher blood oxygen-carrying capacity.

Despite its comparatively limited size in humans, spleen has been shown able to expel red-blood cells in the circulation and thus augment blood oxygen-carrying capacity under certain physiologic conditions. In the present state-of-the-art review, the short- and long-term regulation of spleen volume will be discussed. With regards to the physiological mechanism underlying spleen contraction, sympathetic activation stands as the prime contributor to the response. A dose-dependent relationship between specific interventions of apnea, exercise and hypoxia (imposed separately or in combination) and spleen contraction alleges to the trainability of the spleen organ. The trainability of the spleen is further substantiated by virtue of cross-sectional and longitudinal studies reporting robust increases in both organ volume at rest and subsequent spleen contraction. Alternative ways to assess the relationship between hematologic gains and the magnitude of spleen contraction (i.e., the reduction of spleen volume) will be presented herein. In extension of changes in the conventional measures of hemoglobin concentration and hematocrit, assessment of hemoglobin mass and total blood volume using the (safe, low-cost and time-efficient) CO-rebreathing technique could deepen scientific knowledge on the efficiency of human spleen contraction.

Developmental Changes in the Excitation-Contraction Mechanisms of the Ventricular Myocardium and Their Sympathetic Regulation in Small Experimental Animals.

The developmental changes in the excitation-contraction mechanisms of the ventricular myocardium of small animals (guinea pig, rat, mouse) and their sympathetic regulation will be summarized. The action potential duration monotonically decreases during pre- and postnatal development in the rat and mouse, while in the guinea pig it decreases during the fetal stage but turns into an increase just before birth. Such changes can be attributed to changes in the repolarizing potassium currents. The T-tubule and the sarcoplasmic reticulum are scarcely present in the fetal cardiomyocyte, but increase during postnatal development. This causes a developmental shift in the Ca2+ handling from a sarcolemma-dependent mechanism to a sarcoplasmic reticulum-dependent mechanism. The sensitivity for beta-adrenoceptor-mediated positive inotropy decreases during early postnatal development, which parallels the increase in sympathetic nerve innervation. The alpha-adrenoceptor-mediated inotropy in the mouse changes from positive in the neonate to negative in the adult. This can be explained by the change in the excitation-contraction mechanism mentioned above. The shortening of the action potential duration enhances trans-sarcolemmal Ca2+ extrusion by the Na+-Ca2+ exchanger. The sarcoplasmic reticulum-dependent mechanism of contraction in the adult allows Na+-Ca2+ exchanger activity to cause negative inotropy, a mechanism not observed in neonatal myocardium. Such developmental studies would provide clues towards a more comprehensive understanding of cardiac function.