Full Text Available The aim of the study was to evaluate the possibility of using heart rate (HR as a metric parameter that can be used for the characterisation of behaviour of primitive horses and their relatives, related to reactions to the stress resulting from the contact with humans and adaptation to living in various conditions, including natural environment. This characterisation served the authors to expand the knowledge of such behaviour of primitive horses, and to assess the impact of the environmental and genetic factors. Studies were conducted in three populations of horses: two herds of Polish Konik and one herd of BiÅ‚goraj horses. The studies were performed between 1993 and 2010. They concerned the behaviour of horses during grooming - breeding procedures (hooves clearing, body measurements performed cyclically and the daily observations when HR was monitored continuously. HR results for the respective age categories, during particular grooming - breeding procedures and reserve observations indicate that Polish Konik horses, closely related to the primitive Tarpan breed, are genetically better adapted to living in conditions similar to the natural (reserve than the BiÅ‚goraj horses. They show less stress symptoms, which are evidenced by HR values noted during inhabiting the natural environment.
Regulatory Forum Review*: Utility of in Vitro Secondary Pharmacology Data to Assess Risk of Drug-induced Valvular Heart Disease in Humans: Regulatory Considerations.
Drug-induced valvular heart disease (VHD) is a serious side effect linked to long-term treatment with 5-hydroxytryptamine (serotonin) receptor 2B (5-HT 2B ) agonists. Safety assessment for off-target pharmacodynamic activity is a common approach used to screen drugs for this undesired property. Such studies include in vitro assays to determine whether the drug is a 5-HT 2B agonist, a necessary pharmacological property for development of VHD. Measures of in vitro binding affinity (IC 50 , K i ) or cellular functional activity (EC 50 ) are often compared to maximum therapeutic free plasma drug levels ( fC max ) from which safety margins (SMs) can be derived. However, there is no clear consensus on what constitutes an appropriate SM under various therapeutic conditions of use. The strengths and limitations of SM determinations and current risk assessment methodology are reviewed and evaluated. It is concluded that the use of SMs based on K i values, or those relative to serotonin (5-HT), appears to be a better predictor than the use of EC 50 or EC 50 /human fC max values for determining whether known 5-HT 2B agonists have resulted in VHD. It is hoped that such a discussion will improve efforts to reduce this preventable serious drug-induced toxicity from occurring and lead to more informed risk assessment strategies.
Magnetic Rasonance imaging is a new completely non-invasive diagnostic technique now available even for heart studies. Due to the long time of this examination the main goal for the application to the cardiovascular diagnosis is to obtain the major number of information in a reasonable time for the patient. On the basis of initial experience with this technique a method suitable for the morphological, functional and tissutal characterization in cardiovascular diagnosis is proposed.
Magnetic Rasonance imaging is a new completely non-invasive diagnostic technique now available even for heart studies. Due to the long time of this examination the main goal for the application to the cardiovascular diagnosis is to obtain the major number of information in a reasonable time for the patient. On the basis of initial experience with this technique a method suitable for the morphological, functional and tissutal characterization in cardiovascular diagnosis is proposed
The opening lines of "How the Grinch Stole Christmas!" (Geisel 1957) set the tone for an inspiring change-of-heart story about a grumpy creature that comes to value humanity and the Christmas spirit. Although the book is often considered inspirational for other reasons, the authors were particularly moved by Dr. Seuss's interesting conjectureâ€¦
Full text: Cardiac transplantation has become routine treatment, but not all available donor hearts can be matched. Heterotopic Cardiac Transplantation (the native heart remains in-situ), a technically difficult procedure, was introduced to partly address this limitation. Post-transplantation Gated Blood Pool Scans for these patients presented two challenges - finding the best angle for imaging the transplanted left ventricle, and distinguishing the ECG signals of the native and transplanted hearts. This allowed (a) observation of serial changes in LVEF of both hearts in seven patients, and (b) resolution of the controversy of what happens to native heart function. The transplanted heart was best imaged between LAO 5 deg and RAO 45 deg. By changing ECG limb lead positions or using a wandering V lead, it was usually possible to obtain an upright QRS complex for one heart and a downward complex for the other, allowing appropriate synchronisation of the ECG trigger. The transplant heart LVEF was obtained in 20/23 studies, being always 248%. Native LVEF was obtained in all cases where it was actively sought. Preliminary findings showed that, post-transplant, native LVEF (meanÂ±SD) deteriorated in 6/6 patients (24%Â±12% to 9%Â±4%, p 0.95). One patient's native heart was in intermittent VT making him totally dependent on the transplanted heart. In conclusion this method allowed sequential follow-up of both hearts in these patients and demonstrated that native heart function deteriorates post-heterotopic transplant. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc
Full Text Available Abstract Background Cardiovascular toxicity is a major limiting factor in drug development and requires multiple cost-effective models to perform toxicological evaluation. Zebrafish is an excellent model for many developmental, toxicological and regenerative studies. Using approaches like morpholino knockdown and electrocardiogram, researchers have demonstrated physiological and functional similarities between zebrafish heart and human heart. The close resemblance of the genetic cascade governing heart development in zebrafish to that of humans has propelled the zebrafish system as a cost-effective model to conduct various genetic and pharmacological screens on developing embryos and larvae. The current report describes a methodology for rapid isolation of adult zebrafish heart, maintenance ex vivo, and a setup to perform quick small molecule throughput screening, including an in-house implemented analysis script. Results Adult zebrafish were anesthetized and after rapid decapitation the hearts were isolated. The short time required for isolation of hearts allows dissection of multiple fishes, thereby obtaining a large sample size. The simple protocol for ex vivo culture allowed maintaining the beating heart for several days. The in-house developed script and spectral analyses allowed the readouts to be presented either in time domain or in frequency domain. Taken together, the current report offers an efficient platform for performing cardiac drug testing and pharmacological screens. Conclusion The new methodology presents a fast, cost-effective, sensitive and reliable method for performing small molecule screening. The variety of readouts that can be obtained along with the in-house developed analyses script offers a powerful setup for performing cardiac toxicity evaluation by researchers from both academics and industry.
Absence of Rapid Propagation through the Purkinje Network as a Potential Cause of Line Block in the Human Heart with Left Bundle Branch Block.
Background: Cardiac resynchronization therapy is an effective device therapy for heart failure patients with conduction block. However, a problem with this invasive technique is the nearly 30% of non-responders. A number of studies have reported a functional line of block of cardiac excitation propagation in responders. However, this can only be detected using non-contact endocardial mapping. Further, although the line of block is considered a sign of responders to therapy, the mechanism remains unclear. Methods: Herein, we created two patient-specific heart models with conduction block and simulated the propagation of excitation based on a cellmodel of electrophysiology. In one model with a relatively narrow QRS width (176 ms), we modeled the Purkinje network using a thin endocardial layer with rapid conduction. To reproduce a wider QRS complex (200 ms) in the second model, we eliminated the Purkinje network, and we simulated the endocardial mapping by solving the inverse problem according to the actual mapping system. Results: We successfully observed the line of block using non-contact mapping in the model without the rapid propagation of excitation through the Purkinje network, although the excitation in the wall propagated smoothly. This model of slow conduction also reproduced the characteristic properties of the line of block, including dense isochronal lines and fractionated local electrocardiograms. Further, simulation of ventricular pacing from the lateral wall shifted the location of the line of block. By contrast, in the model with the Purkinje network, propagation of excitation in the endocardial map faithfully followed the actual propagation in the wall, without showing the line of block. Finally, switching the mode of propagation between the two models completely reversed these findings. Conclusions: Our simulation data suggest that the absence of rapid propagation of excitation through the Purkinje network is the major cause of the functional line
This study examined human goodness as lived through the life of Emerson Hynes with a focus on the college years. Emerson Hynes was an ethics and sociology professor at St. John's University during the 1940s and 50s before he became legislative assistant to Senator Eugene McCarthy. He cared deeply about ethics and was a leader in family life,â€¦
We aimed to examine the association between chocolate intake and the risk of incident heart failure in a UK general population. We conducted a systematic review and meta-analysis to quantify this association. We used data from a prospective population-based study, the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort. Chocolate intake was quantified based on a food frequency questionnaire obtained at baseline (1993-1997) and incident heart failure was ascertained up to March 2009. We supplemented the primary data with a systematic review and meta-analysis of studies which evaluated risk of incident heart failure with chocolate consumption. A total of 20,922 participants (53% women; mean age 58Â Â±Â 9 years) were included of whom 1101 developed heart failure during the follow up (mean 12.5Â Â±Â 2.7 years, total person years 262,291 years). After adjusting for lifestyle and dietary factors, we found 19% relative reduction in heart failure incidence in the top (up to 100Â g/d) compared to the bottom quintile of chocolate consumption (HR 0.81 95%CI 0.66-0.98) but the results were no longer significant after controlling for comorbidities (HR 0.87 95%CI 0.71-1.06). Additional adjustment for potential mediators did not attenuate the results further. We identified five relevant studies including the current study (NÂ =Â 75,408). The pooled results showed non-significant 19% relative risk reduction of heart failure incidence with higher chocolate consumption (HR 0.81 95%CI 0.66-1.01). Our results suggest that higher chocolate intake is not associated with subsequent incident heart failure. Copyright Â© 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.