scholarly journals Evaluation of ECG time intervals in a rabbit model of anthracycline-induced cardiomyopathy: a useful tool for assessment of cardioprotective agents

2007 ◽  
pp. 251-254 ◽  
Author(s):  
A Potáčová ◽  
M Adamcová ◽  
H Čajnáková ◽  
L Hrbatová ◽  
M Štěrba ◽  
...  

The aim of this study was to analyze the ECG time intervals in the course of the development of chronic anthracycline cardiomyopathy in rabbits. Furthermore, this approach was employed to study the effects of a model cardioprotective drug (dexrazoxane) and two novel iron chelating compounds--salicylaldehyde isonicotinoyl hydrazone (SIH) and pyridoxal 2-chlorobenzoyl hydrazone (o-108). Repeated daunorubicin administration induced a significant and progressive prolongation of the QRS complex commencing with the eighth week of administration. At the end of the study, we identified a significant correlation between QRS duration and the contractility index dP/dt(max) (r = -0.81; P<0.001) as well as with the plasma concentrations of cardiac troponin T (r = 0.78; P<0.001). In contrast, no alterations in ECG time intervals were revealed in the groups co-treated with either dexrazoxane or both novel cardioprotective drugs (SIH, o-108). Hence, in this study, the QRS duration is for the first time shown as a parameter suitable for the non-invasive evaluation of the anthracycline cardiotoxicity and cardioprotective effects of both well established and investigated drugs. Moreover, our results strongly suggest that novel iron chelators (SIH and o-108) merit further study as promising cardioprotective drugs against anthracycline cardiotoxicity.

2007 ◽  
pp. 535-545
Author(s):  
M Štěrba ◽  
T Šimůnek ◽  
O Popelová ◽  
A Potáčová ◽  
M Adamcová ◽  
...  

Anthracycline cardiotoxicity represents a serious risk of anticancer chemotherapy. The aim of the present pilot study was to compare the potential of both the left ventricular (LV) filling pattern evaluation and cardiac troponin T (cTnT) plasma levels determination for the early detection of daunorubicin-induced cardiotoxicity in rabbits. The echocardiographic measurements of transmitral LV inflow as well as cTnT determinations were performed weekly for 10 weeks in daunorubicin (3 mg/kg weekly) and control groups (n=5, each). Surprisingly, no significant changes in LV-filling pattern were observed through the study, most likely due to the xylazine-containing anesthesia, necessary for appropriate resolving of the E and A waves. In contrast to the echographic measurement, the dP/dt(min) index obtained invasively at the end of the study revealed a significant impairment in LV relaxation, which was further supported by observed disturbances in myocardial collagen content and calcium homeostasis. However, at the same time cTnT plasma levels were progressively rising in the daunorubicin-treated animals from the fifth week (0.024+/-0.008 microg/l) until the end of the experiment (0.186+/-0.055 microg/l). Therefore, in contrast to complicated non-invasive evaluation of diastolic function, cTnT is shown to be an early and sensitive marker of anthracycline-induced cardiotoxicity in the rabbit model.


2021 ◽  
Author(s):  
Zuzana Pokorna ◽  
Petra Kollárová-Brázdová ◽  
Olga Lenčová-Popelová ◽  
Eduard Jirkovský ◽  
Jan Kubeš ◽  
...  

Angiotensin-converting enzyme inhibitors (ACEis) have been used to treat anthracycline-induced cardiac dysfunction, and they appear beneficial for secondary prevention in high-risk patients. However, it remains unclear whether they truly prevent anthracycline-induced cardiac damage and provide long-lasting cardioprotection. This study aimed to examine the cardioprotective effects of perindopril on chronic anthracycline cardiotoxicity in a rabbit model previously validated with the cardioprotective agent dexrazoxane with focus on post-treatment follow-up (FU). Chronic cardiotoxicity was induced by daunorubicin (3 mg/kg/week for 10 weeks). Perindopril (0.05 mg/kg/day) was administered before and throughout chronic daunorubicin treatment. After the completion of treatment, significant benefits were observed in perindopril co-treated animals, particularly full prevention of daunorubicin-induced mortality and prevention or significant reductions in cardiac dysfunction, plasma cardiac troponin T levels, morphological damage, and most of the myocardial molecular alterations. However, these benefits significantly waned during 3 weeks of drug-free FU, which was not salvageable by administering a higher perindopril dose. In the longer (10-week) FU period, further worsening of left ventricular function and morphological damage occurred together with heart failure-related mortality. Continued perindopril treatment in the FU period did not reverse this trend but prevented heart failure-related mortality and reduced the severity of the progression of cardiac damage. These findings contrasted with the robust long-lasting protection observed previously for dexrazoxane in the same model. Hence, in this study, perindopril provided only temporary control of anthracycline cardiotoxicity development, which may be associated with the lack of effects on anthracycline-induced and topoisomerase II beta-dependent DNA damage responses in the heart.


Author(s):  
Shuo Zhang ◽  
Frederieke A. M. van der Mee ◽  
Roel J. Erckens ◽  
Carroll A. B. Webers ◽  
Tos T. J. M. Berendschot

AbstractIn this report we present a confocal Raman system to identify the unique spectral features of two proteins, Interleukin-10 and Angiotensin Converting Enzyme. Characteristic Raman spectra were successfully acquired and identified for the first time to our knowledge, showing the potential of Raman spectroscopy as a non-invasive investigation tool for biomedical applications.


Sensors ◽  
2021 ◽  
Vol 21 (3) ◽  
pp. 879
Author(s):  
Robert D. Crapnell ◽  
Ascanio Tridente ◽  
Craig E. Banks ◽  
Nina C. Dempsey-Hibbert

Lactate is widely measured in critically ill patients as a robust indicator of patient deterioration and response to treatment. Plasma concentrations represent a balance between lactate production and clearance. Analysis has typically been performed with the aim of detecting tissue hypoxia. However, there is a diverse range of processes unrelated to increased anaerobic metabolism that result in the accumulation of lactate, complicating clinical interpretation. Further, lactate levels can change rapidly over short spaces of time, and even subtle changes can reflect a profound change in the patient’s condition. Hence, there is a significant need for frequent lactate monitoring in critical care. Lactate monitoring is commonplace in sports performance monitoring, given the elevation of lactate during anaerobic exercise. The desire to continuously monitor lactate in athletes has led to the development of various technological approaches for non-invasive, continuous lactate measurements. This review aims firstly to reflect on the potential benefits of non-invasive continuous monitoring technology within the critical care setting. Secondly, we review the current devices used to measure lactate non-invasively outside of this setting and consider the challenges that must be overcome to allow for the translation of this technology into intensive care medicine. This review will be of interest to those developing continuous monitoring sensors, opening up a new field of research.


2021 ◽  
pp. 201010582110061
Author(s):  
Raja Ezman Raja Shariff ◽  
Hafisyatul Aiza Zainal Abidin ◽  
Sazzli Kasim

Cardiac amyloidosis is a severely underdiagnosed cause of heart failure with preserved ejection fraction. We report a case of highly probable transthyretin (ATTR) cardiac amyloidosis (ATTR-CA) diagnosed through the assistance of non-invasive multimodality imaging. An 81-year-old man presented with worsening dyspnoea, reduced effort tolerance and limb swelling. Examination and bedside investigations demonstrated congestive cardiac failure. On arrival, N-terminal-pro B-type natriuretic peptide was 2400 ng/L, and high-sensitivity troponin T was 78 mmol/L. Echocardiography showed severe left and right ventricular hypertrophy, and a Doppler study revealed diastolic dysfunction. Cardiac magnetic resonance imaging revealed on non-conventional dark blood sequence an abnormal inversion time for nulling myocardium suggestive of infiltrative disease, including amyloidosis. The patient was referred for nuclear-based studies involving technetium-99m pyrophosphate which demonstrated changes highly diagnostic of ATTR-CA. Early diagnosis of ATTR-CA remains paramount due to the increasing availability of disease-modifying therapies. Current guidelines recognise the role of multimodality imaging in confidently recognising the disease without the need for histological evidence in the appropriate context, providing an alternative means of diagnosis.


1974 ◽  
Vol 61 (3) ◽  
pp. 591-598 ◽  
Author(s):  
Joan Smith-Sonneborn ◽  
Michael Klass

The clonal age in paramecia refers to the total number of vegetative divisions a clone has undergone since its origin at autogamy (self-fertilization). As clonal age increases, the interfission time usually increases. The DNA synthesis pattern of cells of different ages was compared by autoradiographic analysis of the DNA synthesis of synchronized cells at various time intervals during the cell cycle (from one division to the next). The study showed that the G1 period (the lag in DNA synthesis post division) was constant, irrespective of interfission time or clonal age; but the duration of the DNA synthesis period increased with increased interfission time or clonal age. Therefore, we have shown for the first time that the G1 period is fixed, and the S period is increased in a eukaryotic unicellular organism as a function of interfission time and clonal age.


2000 ◽  
Vol 345 (3) ◽  
pp. 453-458 ◽  
Author(s):  
Matthew T. FROST ◽  
Barry HALLIWELL ◽  
Kevin P. MOORE

Measurement of nitrotyrosine in biological fluids and tissues is increasingly being used to monitor the production of reactive nitrogen species in vivo. The detection of nitrotyrosine in vivo has been reported with the use of a variety of methods including immunoassay, HPLC and GLC/MS. The validity of HPLC and immunoassays have been questioned with regard to their selectivity and sensitivity limits. In principle, the measurement of nitrotyrosine by GLC/MS permits a highly specific, highly sensitive and fully quantitative assay. The nitration of tyrosine under acidic conditions in the presence of nitrite is well documented. Derivatization for the full quantification of nitrotyrosine by using GLC/MS can lead to the artifactual nitration of tyrosine if performed under acidic conditions in the presence of nitrite. We describe a novel alkaline method for the hydrolysis and derivatization of nitrotyrosine and tyrosine, and demonstrate its applicability to the measurement of plasma concentrations of both free and protein-bound nitrotyrosine and tyrosine. A detection limit of 1 pg for nitrotyrosine and 100 pg for tyrosine has been achieved. Our method allows, for the first time, the analysis of free and protein-bound nitrotyrosine and tyrosine in biological samples. The plasma concentrations (means±S.E.M.) of free tyrosine and nitrotyrosine in eight normal subjects were 12±0.6 μg/ml and 14±0.7 ng/ml respectively. Plasma proteins contained tyrosine and nitrotyrosine at 60.7±1.7 μg/mg and 2.7±0.4 ng/mg respectively.


2021 ◽  
Author(s):  
Shuang Lin ◽  
Yuanjia He ◽  
Meihan Tao ◽  
Aijun Wang ◽  
Qiang Ao

Abstract On account of the poor biocompatibility of synthetic prosthesis, millions of rhinoplasty recipients have been forced to choose autologous costal cartilage as grafts, which suffer from limited availability, morbidity at donor site and prolonged operation time. Here, as a promising alternative to autologous costal cartilage, we developed a novel xenogeneic costal cartilage and explored its feasibility as a rhinoplasty graft for the first time. Adopting an improved decellularization protocol, in which the ionic detergent was substituted by trypsin, the resulting decellularized graft was confirmed to preserve more structural components and better mechanics, and eliminate cellular components effectively. The in vitro and in vivo compatibility experiments demonstrated that the decellularized graft showed excellent biocompatibility and biosecurity. Additionally, the functionality assessment of rhinoplasty was performed in a rabbit model, and the condition of grafts after implantation was comprehensively evaluated. The optimized graft exhibited better capacity to reduce the degradation rate and maintain the morphology, in comparison to the decellularized costal cartilage prepared by conventional protocol. These findings indicate that this optimized graft derived from decellularized xenogeneic costal cartilage provides a new prospective for future investigations of rhinoplasty prosthesis and has great potential for clinical application.


2015 ◽  
Vol 26 (1) ◽  
pp. 109-113

According to available literature data, NAFLD may play crucial role in the pathogenesis of type 2 diabetes and other conditions connected with insulin resistance. In order to study the essence of the NAFLD, we have created an experimental model of the steatohepatosis. The mixed diet for 8 weeks consisting of standard food (47%), sweetened condensed milk (44%), vegetable oil (8%) and vegetable starch (1%) develops non-alcoholic steatohepatosis in the animals undergoing the experiment. The morphological signs of the non-alcoholic steatohepatosis comprised as follows in the hepatocytes of the rats undergoing the experiment: presence of fine-drop fattiness (fine-drop steatosis) and accumulation of fat vacuoles shifting the nucleus towards the cell peripheral. Substantial increase in the liver pulp of the animals undergoing the experiment defined using the ultrasound shear wave elastography technique is indicative of the presence of the non-alcoholic steatohepatosis. The ultrasound shear wave elastography technique can be used as a non-invasive diagnosis marker of the non-alcoholic steatohepatosis. The said diagnosis technique has been recommended for the first time.


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