An Interactive Web-Based Platform for Support Generation and Optimisation for Metal Laser Powder Bed Fusion.

Powder bed fusion-laser beam (PBF-LB), a prevalent and rapidly advancing additive manufacturing (AM) technology nowadays, serves the industry by producing thin, complex, and lightweight components for various sectors, including healthcare, automotive, defence, and aerospace. However, this technology encounters challenges related to the construction of critical parts and the high overall process costs. Equally significant is the role of support structures in metal laser powder bed fusion (PBF-LB/M). The absence of supports can lead to defective and collapsed parts, while the incorrect selection of a support type or the addition of unnecessary supports results in increased material usage and additional post-processing efforts. Therefore, there is a pressing need for advanced software capable of generating appropriate support structures and predicting the thermomechanical behaviour of a part under PBF-LB/M printing conditions. Such software would be beneficial for the industry to avoid printing defects caused by high thermal stresses, minimise material usage, reduce printing time, and ensure high-quality prints. In this study, we introduce a web-based support generation and optimisation platform for PBF-LB/M. Through this platform, among other features, users can import three-dimensional (3D) parts and generate block-type support structures with diamond perforations based on the PySLM library, all within a user-friendly web environment. The first release of the platform (v0.6) is fully interactive and accessible online at no cost.

Pigmented Squamous Cell Carcinoma In Situ of the Eyelid.

This case report describes a diagnosis of pigmented squamous cell carcinoma in situ in a female patient aged 61 years who presented with a pigmented lesion on her medial canthus that had been growing over a 2-year period.

Tendon-Sparing Extraocular Muscle Enlargement Associated With Chronic Inflammatory Demyelinating Polyradiculoneuropathy.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an inflammatory, sensorimotor polyneuropathy. It has presented with a variety of orbital and neuro-ophthalmic manifestations, including cranial nerve hypertrophy and a single case of extraocular muscle enlargement. The authors present a second case of tendon-sparing, extraocular muscle enlargement, resulting in new-onset diplopia and strabismus in a teenager with CIDP. The workup ruled out alternative causes of extraocular muscle enlargement, such as hyperthyroidism, inflammation, or malignancy. As with other cases of CIDP, management involved a combination of immunoglobulin therapy and anti-inflammatory medications. The patient experienced resolution of his symptoms, and radiologic improvement was noted in the muscle enlargement. As many CIDP patients have a favorable treatment response and long-term prognosis, awareness of this rare disease with an early and accurate diagnosis is important.

Support Structures Optimisation for High-Quality Metal Additive Manufacturing with Laser Powder Bed Fusion: A Numerical Simulation Study.

This study focuses on Metal Additive Manufacturing (AM), an emerging method known for its ability to create lightweight components and intricate designs. However, Laser Powder Bed Fusion (LPBF), a prominent AM technique, faces a major challenge due to the development of high residual stress, resulting in flawed parts and printing failures. The study's goal was to assess the thermal behaviour of different support structures and optimised designs to reduce the support volume and residual stress while ensuring high-quality prints. To explore this, L-shaped specimens were printed using block-type support structures through an LPBF machine. This process was subsequently validated through numerical simulations, which were in alignment with experimental observations. In addition to block-type support structures, line, contour, and cone supports were examined numerically to identify the optimal solutions that minimise the support volume and residual stress while maintaining high-quality prints. The optimisation approach was based on the Design of Experiments (DOE) methodology and multi-objective optimisation. The findings revealed that block supports exhibited excellent thermal behaviour. High-density supports outperformed low-density alternatives in temperature distribution, while cone-type supports were more susceptible to warping. These insights provide valuable guidance for improving the metal AM and LPBF processes, enabling their broader use in industries like aerospace, medical, defence, and automotive.

Effects of Acute Triiodothyronine Treatment in Patients with Anterior Myocardial Infarction Undergoing Primary Angioplasty: Evidence from a Pilot Randomized Clinical Trial (ThyRepair Study).

Background: Thyroid hormone has a differential action on healthy and ischemic heart. Triiodothyronine (T3) administration improved postischemic cardiac function while it limited apoptosis in experimentally induced ischemia. Thus, the present study investigated the potential effects of acute liothyronine (LT3) treatment in patients with anterior myocardial infarction. Methods: This study is a pilot, randomized, double-blind, placebo-controlled trial (ThyRepair study). We randomized 52 patients and analyzed data from 37 patients (n = 16 placebo and n = 21 LT3), per prespecified per protocol analysis. We excluded three patients who had died of cardiovascular causes (one in placebo and two in LT3 arm), four with small infarct size below a pre-specified threshold (in the placebo arm), and the rest, who lacked follow-up data. LT3 treatment started after stenting as an intravenous (i.v.) bolus injection of 0.8 µg/kg of LT3 followed by a constant infusion of 0.113 µg/kg/h i.v. for 48 hours. All patients had cardiac magnetic resonance (CMR) at hospital discharge and 6 months follow-up. The primary end point was CMR left ventricular (LV) ejection fraction (LVEF) and secondary endpoints were LV volumes, infarct volume (IV), and safety. Results: The CMR LVEF% at 6 months was 53.6 ± 9.5 for the LT3-treated group and 48.6 ± 11 for placebo, p = 0.15. Acute LT3 treatment resulted in a significantly lower LV end-diastolic volume index (92.2 ± 16.8 mL/m2 vs. 107.5 ± 22.2, p = 0.022) and LV systolic volume index (47.5 ± 13.9 mL/m2 vs. 61.3 ± 21.7, p = 0.024) at hospital discharge, but not at 6 months. There was no statistically significant difference in CMR IV at hospital discharge between the groups (p = 0.24). CMR IV tended to be lower in the LT3-treated group at 6 months (18.7 ± 9.5 vs. 25.9 ± 11.7, in placebo, p = 0.05). Serious, life-threatening events related to LT3 treatment were not observed. A tendency for an increased incidence of atrial fibrillation (AF) was found in the LT3 group during the first 48 hours (19% for T3 group vs. 5% for placebo, p = 0.13). Conclusion: This pilot randomized, placebo-controlled trial study suggests potential favorable effects (acute cardiac dilatation and 6-month IV) as well as potential concerns regarding a higher risk of AF after LT3 administration early after myocardial infarction, which should be tested in a larger scale study.

Tissue plasminogen activator rescues steroid-induced outflow facility reduction via non-enzymatic action.

Purpose: Tissue plasminogen activator (tPA) prevents steroid-induced reduction in aqueous humor outflow facility; however, its mechanism of action at the trabecular meshwork (TM) remains unclear. Enzymatic and non-enzymatic domains allow tPA to function as both an enzyme and a cytokine. This study sought to determine whether cytokine activity is sufficient to rescue steroid-induced outflow facility reduction. Methods: Outflow facility was measured in C57BL/6J mice following triamcinolone acetonide exposure and either transfection of the TM using adenoviral vectors, encoding for enzymatically active and inactive tPA, or administration of the respective proteins. Protein injections were also administered to tPA deficient (PlatKO) and Mmp-9 deficient (Mmp-9KO) mice to determine the potential to rescue reductions in outflow facility and determine downstream mechanisms. Gene expression of matrix metalloproteinases (Mmp-2, -9, and -13) was measured in angle ring tissues containing the TM. Results: Enzymatically active and inactive tPA (either produced after TM transfection or after direct administration) were equally effective in attenuating steroid-induced outflow facility reduction in C57BL/6J mice. They were also equally effective in rescuing outflow reduction in PlatKO mice and causing enhanced expression of matrix metalloproteinases. However, both enzymatically active and enzymatically inactive tPA did not improve outflow reduction in Mmp-9KO mice or increase the baseline outflow facility in naïve C57BL/6J mice. Conclusions: tPA enzymatic activity is not necessary in the regulation of aqueous humor outflow. tPA can increase the expression of matrix metalloproteinases in a cytokine-mediated fashion. This cascade of events may eventually lead to extracellular matrix remodeling at the TM, which reverses outflow facility reduction caused by steroids.

Debate of Percutaneous Coronary Intervention versus Coronary Artery Bypass Grafting in a Multimorbidity Patient with Complex Coronary Lesions.

BACKGROUND: While complete revascularization in coronary artery disease is of high priority, the method of implementation in patients with complex coronary lesions and multiple comorbidities is not directed by published guidelines. Case Presentation. A 53-year-old female with a chronic total occlusion of the right coronary artery and a bifurcation lesion of the left anterior descending artery and the first diagonal branch, presented with non-ST elevation myocardial infarction. Her past medical history concerned thymectomy and prior chest radiation for thymoma, myasthenia gravis, peripheral artery disease, and cervical cancer treated with surgery and radiation. Although SYNTAX score II favored surgical revascularization, the interventional pathway was finally successfully followed. However, it was complicated with vessel perforation and tamponade managed with pericardiocentesis. CONCLUSION: Comorbidities are not all involved in common risk models and require individualization until more evidence comes to light.

The impact of adenotonsillectomy on pediatric asthma.

OBJECTIVE: To determine asthma outcomes in children undergoing adenotonsillectomy (T&A) for treatment of sleep-disordered breathing (SDB). HYPOTHESIS: Asthmatic children will demonstrate improvement in asthma control after T&A compared to asthmatic children not undergoing surgical treatment. STUDY DESIGN: Prospective cohort. PATIENT-SUBJECT SELECTION: 80 children with diagnosed asthma, aged 4-11, undergoing T&A and 62 controls matched to the T&A subjects by age, sex, and asthma severity classification. METHODOLOGY: Parents and children completed the Childhood Asthma Control Test (C-ACT) and the Pediatric Sleep Questionnaire (PSQ). Parents were queried regarding the number of asthma exacerbations, the frequency of the use of systemic steroids, the number of emergency room visits and the number of hospitalizations in the prior 6 months. The identical questionnaires and interviews were completed 6 months after entry. RESULTS: The adjusted mean (95% CI) C-ACT score was 21.86 (20.94-22.68) at entry and 25.15 (24.55-25.71) at follow-up for the T&A group compared with 22.42 (21.46-23.28) and 23.59 (22.77-24.33) for the control group. There was a significant group by time interaction (P < 0.001). Simple effects analysis showed that group means did not differ at entry (P = 1.00) but did differ at follow-up (P = 0.006). Baseline PSQ was a significant predictor of improvement in C-ACT scores. Statistical modeling did not demonstrate significant group by time interactions for any of the asthma clinical outcomes, although these outcomes were very infrequent in both groups. CONCLUSION: Treatment of SDB improves asthma outcomes as measured by the C-ACT.

Effect of initial retinal thickness on outcome of intravitreal bevacizumab therapy for diabetic macular edema.

PURPOSE: To investigate whether eyes with diabetic macular edema (DME) and central retinal thickness (CRT) >400 µm had better visual and anatomical outcomes compared to eyes with a CRT <400 µm when treated with intravitreal bevacizumab in a real-world setting. PATIENTS AND METHODS: Patients undergoing intravitreal bevacizumab therapy for DME were identified from the departmental database of a tertiary referral unit. Following the initial injection, a retreatment was performed for any persistent macular edema, unless there had been no previous response to repeated doses. Recorded parameters included visual acuity, CRT on optical coherence tomography (spectral domain optical coherence tomography [SD-OCT]), and SD-OCT characteristics. Comparisons were made between data at baseline and 12 months after the first injection, and differences were tested for statistical significance using the Student's t-test. RESULTS: In all, 175 eyes of 142 patients were analyzed. Patients in group 2 (CRT >400 µm) had significantly more injections than group 1 (CRT <400 µm) (4.0 versus 3.3; P=0.003). Both groups had similar numbers of eyes with preexisting epiretinal membrane and/or vitreomacular traction at baseline. The reduction in CRT was significantly greater in group 2 when compared to group 1 (P<0.0001). In terms of visual gain between baseline and month 12, each gained significantly by a mean of 0.12 logarithm of the minimum angle of resolution units (P=0.0001), but there was no difference between groups 1 and 2 (P=0.99). CONCLUSION: These results do not support a 400 µm baseline CRT cut-off for treating DME with bevacizumab, in contrast to published data on ranibizumab. Our results also indicate that patients with a thicker CRT require more bevacizumab injections, making treatment less cost-effective for these patients. Our results could be used by practitioners to support the use of bevacizumab in DME without applying a CRT cut-off.

24-hour efficacy of the bimatoprost-timolol fixed combination versus latanoprost as first choice therapy in subjects with high-pressure exfoliation syndrome and glaucoma.

AIM: To compare the 24-h intraocular pressure (IOP) control obtained with the bimatoprost-timolol fixed combination (BTFC) versus latanoprost in newly diagnosed, previously untreated exfoliation syndrome (XFS) or exfoliative glaucoma (XFG) patients with baseline morning IOP greater than 29 mm Hg. METHODS: One eye of 41 XFS/XFG patients who met inclusion criteria was included in this prospective, observer-masked, crossover, comparison protocol. All subjects underwent a 24-h untreated curve and were then randomised to either evening administered BTFC or latanoprost for 3 months and then switched to the opposite therapy. At the end of each treatment period, patients underwent a treated 24-h IOP assessment. RESULTS: 37 patients completed the trial. At baseline, mean untreated 24-h IOP was 31.1 mm Hg. Mean 24-h IOP with BTFC was significantly lower than with latanoprost (18.9 vs 21.2 mm Hg; p<0.001). Furthermore, BTFC reduced IOP significantly more than latanoprost at every time point, for the mean peak and trough 24-h IOP (p<0.001). There was no difference, however, in mean 24-h IOP fluctuation between the two medications (3.8 with BTFC vs 4.2 with latanoprost; p=0.161). Both treatments were well tolerated and there was no statistically significant difference for any adverse event between them. CONCLUSIONS: As first choice therapy in high-pressure, at-risk exfoliation patients, BTFC controlled mean 24-h IOP significantly better than latanoprost monotherapy.

Scanning laser polarimetry in eyes with exfoliation syndrome.

PURPOSE: To compare retinal nerve fiber layer thickness (RNFLT) of normotensive eyes with exfoliation syndrome (XFS) and healthy eyes.
 METHODS: Sixty-four consecutive individuals with XFS and normal office-time intraocular pressure (IOP) and 72 consecutive healthy controls were prospectively enrolled for a cross-sectional analysis in this hospital-based observational study. The GDx-VCC parameters (temporal-superior-nasal-inferior-temporal [TSNIT] average, superior average, inferior average, TSNIT standard deviation (SD), and nerve fiber indicator [NFI]) were compared between groups. Correlation between various clinical parameters and RNFLT parameters was investigated with Spearman coefficient. 
 RESULTS: The NFI, although within normal limits for both groups, was significantly greater in the XFS group compared to controls: the respective median and interquartile range (IQR) values were 25.1 (22.0-29.0) vs 15.0 (12.0-20.0), p<0.001. In the XFS group, all RNFLT values were significantly lower compared to controls (p<0.001). However, they were all within the normal clinical ranges for both groups: TSNIT average median (IQR): 52.8 (49.7-55.7) vs 56.0 (53.0-59.3) µm; superior average mean (SD): 62.3 (6.7) vs 68.8 (8.2) µm; inferior average mean (SD): 58.0 (7.2) vs 64.8 (7.7) µm, respectively. TSNIT SD was significantly lower in the XFS group, median (IQR): 18.1 (15.4-20.4) vs 21.0 (18.4-23.8), p<0.001. There was no systematic relationship between RNFLT and visual acuity, cup-to-disc ratio, IOP, central corneal thickness, Humphrey mean deviation, and pattern standard deviation in either group. 
 CONCLUSIONS: Compared to control eyes, polarimetry-determined RNFLT was lower in XFS eyes with normal IOP. Therefore, close monitoring of RNFLT may facilitate early identification of those XFS eyes that convert to exfoliative glaucoma.

Normal to normal: a method of treatment of coronary aneurysms with deployment of bare-metal stents.

Coronary artery aneurysm (CAA) is defined as a coronary dilatation that exceeds the diameter of normal adjacent segments or the diameter of the patient's largest coronary vessel by 1.5 times. The presence of a CAA is not always without complications. Thrombosis with myocardial infarction, formation of arteriovenous fistulae, vasospasm, and even rupture, may occur especially with very large aneurysms. These complications dictate the need for medical, surgical or percutaneous therapy. The latter consists mainly of the use of polytetrafluoroethylene (PTFE)-covered stents. Compared to PTFE-covered stents, bare-metal stents (BMS) have better flexibility, making implantation in tortuous vessels easier, and permitting access to sidebranches when a bifurcation lesion is involved. Their use in treatment of CAA has rarely been reported. We present three cases with CAA that have been treated with BMS with excellent post-procedure angiographic results and complete exclusion of the aneurysm at mid-term angiographic follow-up.

Thyroid hormone can favorably remodel the diabetic myocardium after acute myocardial infarction.

It has been previously shown that regulators of physiological growth such as thyroid hormone (TH) can favorably remodel the post ischaemic myocardium. Here, we further explored whether this effect can be preserved in the presence of co-morbidities such as diabetes which accelerates cardiac remodeling and increases mortality after myocardial infarction. Acute myocardial infarction (AMI) was induced by left coronary ligation in rats with type I diabetes (DM) induced by streptozotocin administration (STZ; 35 mg/kg; i.p.) while sham-operated animals served as controls (SHAM). AMI resulted in distinct changes in cardiac function and geometry; EF% was significantly decreased in DM-AMI [37.9 ± 2.0 vs. 74.5 ± 2.1 in DM-SHAM]. Systolic and diastolic chamber dimensions were increased without concomitant increase in wall thickness and thus, wall tension index [WTI, the ratio of (Left Ventricular Internal Diameter at diastole)/2*(Posterior Wall thickness)], an index of wall stress, was found to be significantly increased in DM-AMI; 2.27 ± 0.08 versus 1.70 ± 0.05. 2D-Strain echocardiographic analysis showed reduced systolic radial strain in all segments, indicating increased loss of cardiac myocytes in the infarct related area and less compensatory hypertrophy in the viable segments. This response was accompanied by a marked decrease in the expression of TRα1 and TRß1 receptors in the diabetic myocardium without changes in circulating T3 and T4. Accordingly, the expression of TH target genes related to cardiac contractility was altered; ß-MHC and PKCα were significantly increased. TH (L-T4 and L-T3) administration prevented these changes and resulted in increased EF%, normal wall stress and increased systolic radial strain in all myocardial segments. Acute myocardial infarction in diabetic rats results in TH receptor down-regulation with important physiological consequences. TH treatment prevents this response and improves cardiac hemodynamics.

Association of POAG risk factors and the Thr377Met MYOC mutation in an isolated Greek population.

PURPOSE: To characterize the MYOC genotype correlation with phenotypes in an isolated Greek population with a high incidence of glaucoma. METHODS: Five hundred thirty-one villagers were enrolled in the study. Participants underwent a comprehensive ophthalmic examination. All three exons of myocilin were bidirectionally sequenced. Power calculations and measured genotype analysis was conducted using the genetic variance analysis program, SOLAR version 4.2, to account for the relatedness between individuals. RESULTS: The participants, 376 of whom were linked in a single 11-generation pedigree, ranged in age from 10 to 95 years with a mean age of 49. Sixty-five individuals had POAG, and 27 of those carried the Thr377Met MYOC mutation. Both peak intraocular pressure and vertical cup-to dis- ratio were significantly associated with the MYOC Thr377Met variant (P = 9 x 10(-14) and P = 9 x 10(-8), respectively), whereas central corneal thickness showed no significant association (P < 0.7). CONCLUSIONS: This village had a high frequency of glaucoma, with 12% of the participants aged 10 to 95 years having the disease. In this cohort, the Thr377Met MYOC mutation was significantly associated with both high intraocular pressures and high vertical cup-to-disc ratios. No association was found with central corneal thickness.

Myocilin variations and familial glaucoma in Taxiarchis, a small Greek village.

PURPOSE: To initiate a prospective study of glaucoma in a Greek village reported over 30 years ago to have several large families with primary open-angle glaucoma (POAG). METHODS: A random group of 126 villagers from Taxiarchis, Greece was examined in the village community center. The detailed evaluation included ophthalmic and general history, measurement of blood pressure, intraocular pressure (IOP), and central corneal thickness (CCT) as well as evaluation of the optic nerve status. RESULTS: The incidence of glaucoma approached 18% in this small isolated village. Myocilin variants were present in almost half of the individuals screened with Arg76Lys and Thr377Met being the most common finding (25% and 17%, respectively). Over half of the individuals with the Thr377Met mutation were diagnosed with glaucoma. Two of these patients were homozygous for the Thr377Met mutation. Three individuals with the Arg76Lys polymorphism had glaucoma; however, two of these individuals also had the Thr377Met mutation. Only two patients with pseudoexfoliation were identified. CONCLUSIONS: The incidence of glaucoma and the Thr377Met MYOC mutation in this population is much higher than that reported for other European populations.

Thyroid hormone is a critical determinant of myocardial performance in patients with heart failure: potential therapeutic implications.

OBJECTIVE: Previous experimental studies have provided evidence showing that changes in thyroid hormone signaling correspond to alterations in myocardial function in animal models of heart failure. The present study further explores whether thyroid hormone alterations are correlated with the functional status of the myocardium in patients with heart failure. METHODS: In this study, 37 patients with mean ejection fraction (EF%) of 26.2 (8.2) were included. Myocardial performance was assessed by echocardiography and cardiopulmonary exercise testing. Total tri-iodothyronine (T3), thyroxine, and TSH levels were measured in plasma. RESULTS: Total T3 was strongly correlated with VO2max (r = 0.78, P = 2 x 10(-8)). Furthermore, multivariate analysis revealed that total T3 was an independent predictor of VO2max (P = 0.000 005). A weaker but significant correlation was also found between total T3 and EF% (r = 0.56, P = 0.0004), systolic (r = 0.43, P = 0.009) and diastolic (r = 0.46, P = 0.004) blood pressure. CONCLUSIONS: changes in thyroid hormone were closely correlated to myocardial functional status in patients with heart failure. These data probably indicate a possible role of thyroid hormone in the pathophysiology of heart failure and confirm previous experimental reports.

Thyroid hormone attenuates cardiac remodeling and improves hemodynamics early after acute myocardial infarction in rats.

OBJECTIVE: Cardiac remodeling of viable myocardium occurs after acute myocardial infarction (AMI) and further contributes to cardiac dysfunction. The present study explored whether thyroid hormone (TH) administered shortly after AMI in rats can attenuate cardiac remodeling and improve cardiac function. TH regulates important structural and regulatory proteins in the myocardium including myosin isoform expression and calcium cycling proteins. METHODS: AMI was induced in Wistar male rats by ligating left coronary artery (AMI, n=10), while sham-operated rats were used as controls (SHAM, n=10). Animals with acute myocardial infarction were also treated with 0.05% thyroid powder in food (AMI-THYR, n=10). Within 2 weeks, cardiac function was impaired as assessed by echocardiography and under isometric conditions in Langendorff preparations. RESULTS: Ejection fraction (EF%) was 71.5 (SEM, 2.7) in SHAM versus 30.0 (2.0) in AMI, P<0.05. +dp/dt was 3886 (566) in SHAM versus 2266 (206) in AMI hearts, P<0.05 and -dp/dt was 1860 (46) in SHAM versus 1633 (120) in AMI hearts, P=ns. Such changes were associated with alterations in myosin isoform expression in the non-infarcted area; AMI hearts expressed 34% alpha-MHC and 66% beta-MHC versus 52% alpha-MHC and 48% beta-MHC in SHAM, P<0.05, while the expression of SERCA and phospholamban (PLB) remained unchanged. Furthermore, a mismatch of left ventricular size and cardiac mass (2*Posterior Wall thickness/LVIDd was decreased) was observed. After TH treatment, AMI-THYR hearts expressed 71% alpha-MHC and 29% beta-MHC, P<0.05 versus SHAM and AMI and the ratio of SERCA/PLB was increased by 2.0-fold, P<0.05 versus SHAM and AMI. These changes corresponded to a marked improvement in cardiac function; EF% was raised to 45.8 (1.7), P<0.05 versus AMI while +dp/dt and -dp/dt were 3800 (435) and 2600 (200), respectively, in AMI-THYR hearts, P<0.05 versus AMI. The ratio of 2*Posterior Wall thickness/LVIDd was normalized. CONCLUSIONS: Thyroid hormone administration early after infarction attenuates cardiac remodeling and significantly improves myocardial performance.

Time-dependent changes in the expression of thyroid hormone receptor alpha 1 in the myocardium after acute myocardial infarction: possible implications in cardiac remodelling.

The present study investigated whether changes in thyroid hormone (TH) signalling can occur after acute myocardial infarction (AMI) with possible physiological consequences on myocardial performance. TH may regulate several genes encoding important structural and regulatory proteins particularly through the TR alpha 1 receptor which is predominant in the myocardium. AMI was induced in rats by ligating the left coronary artery while sham-operated animals served as controls. This resulted in impaired cardiac function in AMI animals after 2 and 13 weeks accompanied by a shift in myosin isoforms expression towards a fetal phenotype in the non-infarcted area. Cardiac hypertrophy was evident in AMI hearts after 13 weeks but not at 2 weeks. This response was associated with a differential pattern of TH changes at 2 and 13 weeks; T(3) and T(4) levels in plasma were not changed at 2 weeks but T(3) was significantly lower and T(4) remained unchanged at 13 weeks. A twofold increase in TR alpha 1 expression was observed after 13 weeks in the non-infarcted area, P<0.05 versus sham operated, while TR alpha 1 expression remained unchanged at 2 weeks. A 2.2-fold decrease in TR beta 1 expression was found in the non-infarcted area at 13 weeks, P<0.05, while no change in TR beta 1 expression was seen at 2 weeks. Parallel studies with neonatal cardiomyocytes showed that phenylephrine (PE) administration resulted in 4.5-fold increase in the expression of TR alpha 1 and 1.6-fold decrease in TR beta 1 expression versus untreated, P<0.05. In conclusion, cardiac dysfunction which occurs at late stages after AMI is associated with increased expression of TR alpha 1 receptor and lower circulating tri-iodothyronine levels. Thus, apo-TR alpha 1 receptor state may prevail contributing to cardiac fetal phenotype. Furthermore, down-regulation of TR beta 1 also contributes to fetal phenotypic changes. alpha1-adrenergic signalling is, at least in part, involved in this response.