High intensity focused ultrasound in the therapy of benign thyroid nodules-first German bicentric study with long-term follow-up.

PURPOSE: The study evaluated high-intensity-focused ultrasound (HIFU) for benign thyroid nodules in terms of efficiency, complication rate, influence of preablative nodule size, parameters influencing the therapeutic success and hormonal-thyroid-function. METHODS: Seventy-two patients with 75 nodules were treated with HIFU at 2 centers from 2014-2019. Median nodule volume was 4.4 ml (range 0.33-53). The therapeutic ultrasound probe (EchoPulse THC900888-H) generated 80-90 °C in the target tissue with 87.6-320.3 J per sonication. Nodal volume was measured at baseline and over 12 months after therapy in a retrospective bicentric-study with long-term follow-up. Hormonal-thyroid function (TSH, T3, T4) was measured before and after ablation. Complications were assessed. RESULTS: Significant volume reduction (p < 0.05 Wilcoxon-signed-rank test) of thyroid nodules was 38.98% at 3 months, 37.32% at 6 months, 61.54% at 9 months and 60.66% at 12 months. Volume reduction of nodules <3 ml did not differ significantly from nodules >3 ml (p > 0.05 Mann-Whitney test). At 3 months solid nodules had a significant volume reduction of 52.08%, complex nodules of 32.57%, nodules treated under regional anesthesia of 33.07% and under general anesthesia of 49.47%. Hormonal-thyroid function was not influenced significantly by HIFU therapy (p > 0.05 Wilcoxon-signed-rank test). Complication rate was 3.8%. No long-term complications occurred. CONCLUSION: Significant volume reduction of thyroid nodules up to 12 months after HIFU was shown. All complications were reversible. Therapy was more efficient in solid than complex nodules and in nodules treated under general anesthesia than with regional anesthesia. Hormonal-thyroid-function was not affected. TRIAL REGISTRAFTION NUMBER: 2020-1728-evBO. Date of registration: 16.06.2020. Agency: Ethik-Kommission bei der Landesäztekammer Hessen.

Effectiveness of High-intensity Focused Ultrasound (HIFU) Therapy of Solid and Complex Benign Thyroid Nodules - A Long-term Follow up Two-center Study.

PURPOSE: To investigate the effectiveness of high-intensity focused ultrasound (HIFU) of solid and complex benign thyroid nodules. METHODS: Fifty-eight patients with benign thyroid nodules were treated with HIFU at two centers from 2014-2019. The device, EchoPulse (Teraclion, Malakoff, France), heats the nodes to 80-90 °C. Nodal volumes were measured by ultrasound at regular intervals before and up to 12 months after therapy. In a retrospective long-term two-center study, average volume reductions in relation to baseline volume were statistically analyzed by the Wilcoxon signed-rank test. Side effects were documented. RESULTS: In solid nodules, the average percent volume reductions at the 3, 6, 9, and 12-months follow-up were 49.98%, 46.40%, 65.77%, and 63.88%, respectively. The results were significant with p<0.05 in the Wilcoxon signed-rank test at the 3, 6, and 9-months follow-up. In complex nodules, the average percent volume reduction was 35.2% at 3 months, 36.89% at 6 months, and 63.64% at twelve months follow up. The results were significant with p<0.05 in the Wilcoxon signed-rank test at the 3- and 6-months follow-up. The complication rate was 5.2%. All complications occurred in patients with solid nodules. CONCLUSION: The study showed that HIFU is an effective treatment method for both solid and complex nodules. The complication rate is relatively high at 5.2%. No long-term complications occurred. The solid nodules responded better to HIFU than complex nodules.

Effects of Regional and General Anesthesia on the Therapeutic Outcome of Benign Thyroid Nodules Treated with High Intensity Focused Ultrasound (HIFU).

BACKGROUND: The study investigated whether anesthesia performed during high-intensity-focused-ultrasound treatment (HIFU) of benign thyroid nodules influenced the therapy outcome, based on volume reduction and the amount of energy delivered. METHODS: Thirty patients with benign thyroid nodules were treated with HIFU under general or regional anesthesia at two centers from 2014 to 2019. During HIFU, a therapeutic ultrasound probe, EchoPulse (Teraclion, Malakoff, France), heats the focus to 80-90 degrees Celsius. Nodal volumes were measured by ultrasound before and 3 months after therapy. For statistical analysis, the total population was divided into two groups according to the anesthesia performed. In a retrospective long-term multicenter study, volume reduction and the energy delivered were analyzed using the Wilcoxon signed-rank test and the Mann-Whitney test. RESULTS: At three months follow-up, the total study population had an average volume reduction of 39.26% (range 4.03-91.16%, p < 0.001, n = 30), the general anesthesia group of 47.46% (range 13.64-91.16%, p = 0.001, n = 15) and the regional anesthesia group of 31.06% (range 4.03-68.63%, p = 0.001, n = 15). Under regional anesthesia a median energy of 3.16 kJ/cm3 (range: 0.96 - 8.2 kJ/cm3) and under general anesthesia a median energy of 0.88 kJ/cm3 (range: 0.18 - 1.63 kJ/cm3) were delivered. All results were significant with p < 0.05. The complication rate was 6.67%. CONCLUSION: HIFU is an effective method to treat benign thyroid nodules. Comparing anesthesia methods, volume reduction is higher in patients treated under general anesthesia and less energy has to be delivered under general anesthesia. TRIAL REGISTRATION NUMBER: 2020-1728-evBO. AGENCY: Ethik-Kommission bei der Landesäztekammer Hessen.

Comparison between microwave ablation and bipolar radiofrequency ablation in benign thyroid nodules: differences in energy transmission, duration of application and applied shots.

PURPOSE: Comparison between different thermal ablation systems for thyroid nodules regarding their different procedural characteristics such as treatment-time, number of shots and energy transmission in the context of their clinical performance such as complication rate and volume reduction after three months. METHODS: A total of 60 patients with 65 nodules underwent thermal ablation of thyroid nodules with either microwave ablation (MWA) (9 male, 15 female and mean age 57 ± 13 years) or radiofrequency ablation (RFA) (12 male, 24 female and mean age 54 ± 12 years). RESULTS: Mean initial volume (MWA: 23.90 ± 17.35 ml; RFA: 29.44 ± 30.09 ml), energy transmission (MWA: 13.56 ± 10.17 kJ; RFA: 15.12 ± 13.45 kJ), energy transmission per ml (MWA: 0.85 ± 1.01 kJ/ml; RFA: 0.65 ± 0.32 kJ/ml), power (MWA: 22.69 ± 12.32 J/s; RFA: 20.97 ± 7.86 J/s) and duration of ablation (MWA: 618 ± 304 s; RFA: 695 ± 463 s) were not statistically different (p > .05). MWA required significantly less shots (MWA: 3 ± 1; RFA: 6 ± 3) than RFA (p < .05). At three-months follow-up a significant mean nodular volume reduction of 53.54 ± 15.40% after MWA and 51.21 ± 16.58% after RFA (p < .05) was measured. However, mean nodular volume reduction was not significantly different between both systems (p > .05). One patient treated by MWA reported a transient Horner's syndrome, which recovered without any further treatment. Major complications such as nodule rupture, infection or persisting nerve injuries did not occur. CONCLUSION: Both systems are suitable to treat thyroid nodules and show no significant difference in the duration of application, energy transmission and volume reduction. However, MWA requires less shots to treat the whole nodule.

[Influence of glucocorticoid therapy on intratherapeutic biodistribution of 131I radioiodine therapy in Graves' disease]. / Einfluss der Glukokortikoidtherapie auf die intratherapeutische Bio distribution von 131I bei der Radio jodtherapie des Morbus Basedow.

AIM: Radioiodine therapy (RIT) is an important therapeutic method in the definitive treatment of Graves' disease (GD). However, RIT may trigger development of Graves' ophthalmopathy (GO) or exacerbate a pre-existing GO. Therefore, the procedure recommendation of the DGN (German Society of Nuclear Medicine) for RIT of benign thyroid diseases recommends an additional glucocorticoid therapy for patients with pre-existing GO. Aim of this study was to analyze the influence of a protective glucocorticoid therapy on 131I biokinetics during RIT of patients with GD. MATERIAL AND METHODS: In this retrospective analysis 211 patients with GD who underwent RIT without additional thyreostatic medication were examined. To analyze 131I biokinetics the extrapolated maximum uptake (EMU) and the effective half-life of 131I in the thyroid were determined. Patients suffering from GO received glucocorticoids according to a fixed scheme starting one day prior to RIT, patients without GO did not receive glucocorticoids. Subsequently the ratios of values measured during RIT and those measured during radioactive iodine uptake test were compared among the groups. To take into account other factors, the groups were also compared regarding age, weight, TSH, TRAb, TgAb and TPOAb. RESULTS: In patients with additional glucocorticoid therapy, a reduction of the median EMU from 44 % in radioiodine uptake test to 35 % during RIT was observed. The pretherapeutic (47 %) and intratherapeutic (46 %) EMU of the control group without glucocorticoids remained constant. Comparison of the change in the EMU showed a statistically significant difference between both groups (p < 0.001). Comparison of all other parameters including the effective half-life of 131I (p = 0.79) did not show any statistically significant difference. CONCLUSION: The present study suggests that glucocorticoids affect the biokinetics of 131I by reducing its thyroidal uptake. As a result of this study, for patients without antithyroid medication undergoing glucocorticoid therapy, an adjustment of therapeutic 131I activity determined in radioiodine uptake test could be considered.

First clinical use of the EchoTrack guidance approach for radiofrequency ablation of thyroid gland nodules.

PURPOSE: Percutaneous radiofrequency ablation (RFA) of thyroid nodules is an alternative to surgical resection that offers the benefits of minimal scars for the patient, lower complication rates, and shorter treatment times. Ultrasound (US) is the preferred modality for guiding these procedures. The needle is usually kept within the US scanning plane to ensure needle visibility. However, this restricts flexibility in both transducer and needle movement and renders the procedure difficult, especially for inexperienced users. Existing navigation solutions often involve electromagnetic (EM) tracking, which requires placement of an external field generator (FG) in close proximity of the intervention site in order to avoid distortion of the EM field. This complicates the clinical workflow as placing the FG while ensuring that it neither restricts the physician's workspace nor affects tracking accuracy is awkward and time-consuming. METHODS: The EchoTrack concept overcomes these issues by combining the US probe and the EM FG in one modality, simultaneously providing both real-time US and tracking data without requiring the placement of an external FG for tracking. We propose a system and workflow to use EchoTrack for RFA of thyroid nodules. RESULTS: According to our results, the overall error of the EchoTrack system resulting from errors related to tracking and calibration is below 2 mm. Navigated thyroid RFA with the proposed concept is clinically feasible. Motion of internal critical structures relative to external markers can be up to several millimeters in extreme cases. CONCLUSIONS: The EchoTrack concept with its simple setup, flexibility, improved needle visualization, and additional guidance information has high potential to be clinically used for thyroid RFA.

Cooled microwave ablation of thyroid nodules: Initial experience.

OBJECTIVE: To evaluate if internally cooled microwave ablation (cMWA) is a safe and effective method for treatment of benign and malign thyroid nodules. METHODS: 9 patients with 11 symptomatic cold benign thyroid nodules and 1 recurrent thyroid carcinoma ranging in volume from 9.1 to 197ml (mean size 52±â€Š57ml) were treated with cMWA. The mean age of the patients was 59 years. Pain during the treatment was measured on a 10-point scale. Side effects revealed by ultrasound or patients' complaints were documented. Periablative efficacy was measured 24h after cMWA as change (Δ) in serum thyreoglobulin (Tg). Nodule elasticity was measured on a 4-point scale, blood circulation and echogenicity on a 3-point scale. RESULTS: All patients tolerated cMWA well. Median pain intensity averaged 2.1±0.8 (range: 1-3). Postablative hematoma was observed in all cases. In no cases ablation led to hoarseness, superficial burns, nodule ruptures, vagal reactions or dysphagia. cMWA lead to a significant decrease of blood circulation, nodule echogenicity and a significant increase of elasticity (Δ = 1.1 ±â€Š0.33; 0.8 ±â€Š0.4 and 1.1 ±â€Š0.6 points)(p<0.05). An average increase of 4495ng/ml Tg was measured (p<0.05). CONCLUSIONS: cMWA is an effective and secure method for treatment of thyroid nodules.

[131I and 99mTc-Uptake in focal thyroid autonomies. Development in Germany since the 1980s]. / 131I- und 99mTc-Uptake in fokalen Schilddrüsenautonomien. Entwicklung in Deutschland seit den 1980er Jahren.

Germany has developed into a country with a nationwide largely sufficient iodine supply due to improved alimentary iodine supply. The reduction of iodine uptake in focal autonomies induced by reduced iodine avidity was evaluated by Gotthardt et al. 2006, showing a significant decline of pertechnetate uptake up to the year 2004. AIM: This study was intended to carry this investigation forward to the present day to analyze the course of a conjectural stabilization of iodine uptake values. PATIENTS, MATERIAL, METHODS: 283 patients who underwent radioiodine therapy for focal thyroid were analyzed retrospectively. Pertechnetate uptake was measured scintigraphically, thyroid volume sonographically and iodine uptake by iodine uptake test. The uptake percentage in the autonomous volume was correlated with autonomous volume and the resulting values tracked over a time period of seven years. RESULTS: Mean thyroid volume ranged from 24 to 29 ml, autonomous volume from 7.2 to 9.4 ml. Pertechnetate uptake ranged from 0.2 to 0.25%/ml autonomous volume. Iodine uptake values ranged from 3.2 to 4.2%/ml autonomous volume. None of the changes observed were statistically significant (all p>0.05). CONCLUSION: Prophylactic measures towards improvement of the general public´s iodine supply in Germany had led to a decline of pertechnetate and iodine uptake in the thyroid up until the turn of the millennium. The here presented data show a stabilization of 99mTc-Uptake. Our study could also show that actual iodine uptake has stabilized at a steady level over the preceding seven years.

In vivo and ex vivo measurements: noninvasive assessment of alcoholic fatty liver using 1H-MR spectroscopy.

PURPOSE: We aimed to evaluate the ability of 1H-magnetic resonance spectroscopy (1H-MRS) to detect and quantify hepatic fat content in vivo and ex vivo in an experimental rat model of alcoholic fatty liver using histopathology, biochemistry, and laboratory analyses as reference. METHODS: Alcoholic fatty liver was induced within 48 hours in 20 Lewis rats; 10 rats served as control. Intrahepatic fat content determined by 1H-MRS was expressed as the percent ratio of the lipid and water peaks and was correlated with intrahepatic fat content determined histologically and biochemically. Liver enzymes were measured in serum. RESULTS: Fatty liver could be detected in vivo as well as ex vivo using 1H-MRS, in all 20 animals. Histologic analysis showed a fatty liver in 16 of 20 animals. Histology and 1H-MRS results were highly correlated (in vivo, r=0.93, P = 0.0005; ex vivo, r=0.92, P = 0.0006). Also a strong correlation was noted between in vivo 1H-MRS measurements and the fat content determined biochemically (r=0.96, P = 0.0003). Ex vivo results showed a similarly strong correlation between 1H-MRS and biochemistry (r=0.89, P = 0.0011). CONCLUSION: 1H-MRS can be carried out in ex vivo models, as well as in vivo, to detect and quantify intrahepatic fat content in the acute fatty liver.

Improving Drug Penetrability with iRGD Leverages the Therapeutic Response to Sorafenib and Doxorubicin in Hepatocellular Carcinoma.

iRGD is a derivative of the integrin-binding peptide RGD, which selectively increases the penetrability of tumor tissue to various coadministered substances in several preclinical models. In this study, we investigated the ability of iRGD to improve the delivery of sorafenib and doxorubicin therapy in hepatocellular carcinoma (HCC) using established mouse models of the disease. A contrast-enhanced MRI method was developed in parallel to assess the in vivo effects of iRGD in this setting. We found that iRGD improved the delivery of marker substances to the tumors of HCC-bearing mice about three-fold without a parallel increase in normal tissues. Control peptides lacking the critical CendR motif had no effect. Similarly, iRGD also selectively increased the signal intensity from tumors in Gd-DTPA-enhanced MRI. In terms of antitumor efficacy, iRGD coadministration significantly augmented the individual inhibitory effects of sorafenib and doxorubicin without increasing systemic toxicity. Overall, our results offered a preclinical proof of concept for the use of iRGD coadministration as a strategy to widen the therapeutic window for HCC chemotherapy, as monitored by Gd-DTPA-enhanced MRI as a noninvasive, clinically applicable method to identify iRGD-reactive tumors.

Visualization of tissue alterations in thyroid nodules after microwave ablation: sonographic versus scintigraphic imaging.

OBJECTIVE: The aim of this study was to elucidate the potential of B-mode sonography, colour-coded Doppler sonography and scintigraphic imaging as diagnostic methods for the evaluation of treatment success and follow-up of thyroid nodules after microwave ablation. MATERIALS AND METHODS: Thirty-six thyroid nodules in 33 patients were subjected to microwave ablation and were evaluated by means of B-mode sonography, colour-coded Doppler sonography and scintigraphic imaging before and after ablation. B-mode sonography results were characterized by echogenicity that was assigned ultrasound scores (US). Hypoechoic nodules were referred to as US1, isoechoic as US2 and hyperechoic nodules as US3. Colour-coded Doppler sonography was evaluated by a scoring system reflecting the blood flow of ablated nodules. A Doppler score (DS) of 1 was assigned for nodules without blood flow, DS2 for those with an absence of intranodular but presence of perinodular blood flow and DS3 for nodules with intranodular and perinodular flow. Scintigraphic imaging was performed using technetium-99m pertechnetate (99mTc-pertechnetate) for pretherapeutic and post-therapeutic imaging of indifferent nodules and 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) as the tracer for cold nodules. RESULTS: B-mode sonography reflected decreased echogenicity and US [median decrease by Δ=1±0.6 (P<0.01)] after ablation. Colour-coded Doppler sonography showed declined blood flow; median reduction of DS was Δ=1±0.7 (P<0.01). In scintigraphic imaging, tracer uptake reduced by a median 42.5±27.8% (P<0.01). 99mTc-pertechnetate scans recorded tracer uptake reduction by 32.3±17.8%, and 99mTc-MIBI scans showed uptake reduction in ablated regions by 56.1±29.7%. CONCLUSION: B-mode sonography and colour-coded Doppler sonography are easily applicable, providing real-time imaging control for microwave ablation. However, they are limited in accuracy and susceptible to artefacts. Scintigraphic imaging delivers quantifiable, operator-independent results and is promising in the evaluation of treatment success and follow-up.

Detection of hepatocellular carcinoma in transgenic mice by Gd-DTPA- and rhodamine 123-conjugated human serum albumin nanoparticles in T1 magnetic resonance imaging.

Nanoparticle (NP)-based contrast agents that enable high resolution anatomic T1-weighted magnetic resonance imaging (MRI) offer the prospect of improving differential diagnosis of liver tumors such as hepatocellular carcinoma (HCC). In the present study, we investigated the possibility of employing novel non-toxic human serum albumin nanoparticles conjugated with Gd-DTPA and rhodamine 123 (Gd-Rho-HSA-NPs) for the detection of HCC by T1-weighted MRI. In addition, the influence of surface coating of the NPs with poloxamine 908, which alters the absorptive behavior of NPs and changes their distribution between the liver and tumor was examined. MRI of transgenic mice with endogenously formed HCCs following intravenous injection of Gd-Rho-HSA-NPs revealed a strong negative contrast of the tumors. Contrasting of the HCCs by NP-enhanced MRI required less Gd as compared to gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid-enhanced MRI, which currently provides the most sensitive detection of HCC in patients. Immunohistochemical analyses revealed that the Gd-Rho-HSA-NPs were localized to macrophages, which were - similar to HCC in patients - fewer in number in HCC as compared to the liver tissue, which is in agreement with the negative contrasting of HCC in Gd-Rho-HSA-NP-enhanced MRI. Poloxamine-coated NPs showed lower accumulation in the tumor macrophages and caused a longer lasting enhancement of the MRI signal. These data indicate that Gd-Rho-HSA-NPs enable sensitive detection of HCC by T1-weighted MRI in mice with endogenous HCC through their uptake by macrophages. Poloxamine coating of the NPs delayed the tumor localization of the NPs.

Local thyroid tissue ablation by high-intensity focused ultrasound: effects on thyroid function and first human feasibility study with hot and cold thyroid nodules.

OBJECTIVE: The aim of this study was to assess whether high-intensity focused ultrasound (HIFU), a new and promising method for the treatment of benign hot and cold thyroid nodules using thermal ablation, has an impact on thyroid function, and to evaluate its feasibility in outpatient settings. Additionally, a possible difference in the treatment of solid and complex thyroid nodules was evaluated. METHOD: Ten patients with one thyroid nodule each (six cold and four hot nodules) underwent HIFU in January 2014. Four nodules were solid and six nodules were complex. Serum levels of triiodothyronine (T3), thyroxine (T4), thyrotropin (TSH), thyroglobulin (hTg) and additionally antibodies against hTg (TAK), TSH receptors (TRAK) and thyroid peroxidase (TPO) were measured at enrolment and 24 h after the HIFU treatment. The pre- and post-thyroglobulin reduction was measured to evaluate the scale of ablation. In addition, patients' pain was recorded on a numeric rating scale from 0 to 10. RESULTS: The HIFU treatment did not affect thyroid function, since hormone levels stayed stable (p < 0.05). No serious immune reaction was induced. Thyroglobulin serum levels increased significantly (p < 0.05) and were correlated to the total energy emitted by HIFU (p < 0.1). The results of complex thyroid nodules did not differ from solid thyroid nodules. Similarly, the results of hot thyroid nodules did not differ from cold thyroid nodules. All patients tolerated the whole treatment and no severe complications were observed. CONCLUSION: HIFU is a safe and effective method to treat benign, solid, complex, hot and cold thyroid nodules preserving thyroid function. Further developments of the system are needed to gain suitability for daily use.

Biodegradable human serum albumin nanoparticles as contrast agents for the detection of hepatocellular carcinoma by magnetic resonance imaging.

Tumor visualization by magnetic resonance imaging (MRI) and nanoparticle-based contrast agents may improve the imaging of solid tumors such as hepatocellular carcinoma (HCC). In particular, human serum albumin (HSA) nanoparticles appear to be a suitable carrier due to their safety and feasibility of functionalization. In the present study HSA nanoparticles were conjugated with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) using carbodiimide chemistry. The nanoparticles had a uniform spherical shape and a diameter of 235±19nm. For better optical visualization in vitro and in vivo, the HSA-Gd nanoparticles were additionally labeled with rhodamine 123. As shown by confocal microscopy and flow cytometry analysis, the fluorescent nanoparticles were readily taken up by Huh-7 hepatocellular carcinoma cells. After 24h incubation in blood serum, less than 5% of the Gd(III) was released from the particles, which suggests that this nanoparticulate system may be stable in vivo and, therefore, may serve as potentially safe T1 MRI contrast agent for MRI of hepatocellular carcinoma.

Transpulmonary chemoembolization: a novel approach for the treatment of unresectable lung tumors.

This article describes the technique of transpulmonary chemoembolization for the palliative treatment of unresectable lung tumors. Early utilization of this method has resulted in reduction in tumor volume and alleviation of patient symptoms. After superselective catheterization, cytotoxic agents are administered, and the pulmonary arterial supply of the tumor is occluded by injection of microspheres and ethiodized oil. Emerging data suggest that this approach is well tolerated.

PKC-independent signal transduction pathways increase SERCA2 expression in adult rat cardiomyocytes.

Catecholamines seem to play a major role in the initial response of the heart to pressure overload. The mechanisms by which alpha(1A)-adrenoceptor stimulation increases protein synthesis and subsequently cell size have been worked out in the past. However, little is known about the functional consequence of this type of hypertrophy. Recent transgenic work seems to indicate an adaptive character of this response, but mechanistic insights have yet to be established. The present study investigates whether chronic (overnight) exposure of cardiomyocytes to phenylephrine, an alpha-adrenoceptor agonist, modifies the expression of calcium-handling proteins and identifies key elements of signal transduction pathways leading to such alterations. Cardiomyocytes exposed to phenylephrine had elevated expression of SR-calcium ATPase (SERCA), but not of the sodium-calcium exchanger (NCX). SERCA induction persisted in the presence of protein kinase C (PKC) inhibitors, but required an increase in diastolic cell calcium levels via activation of the sodium-proton exchanger (NHE) and the reverse mode of the NCX. Downstream of an increase in resting cell calcium concentrations an activation of the calcineurin/NFAT pathway was found to be responsible for SERCA2 induction. Transfection of cardiomyocytes with decoys directed against NFAT activity inhibited the increase in SERCA2 expression. Decoys did not inhibit the concomitant PKC-dependent increase in hypertrophic growth. In the absence of SERCA up-regulation, hypertrophied cardiomyocytes were unable to maintain normal, load-free cell shortening. In conclusion, our data give mechanistic insights into the adaptional process during alpha-adrenoceptor-dependent myocardial hypertrophy.