Mechanisms of Cardiac Arrhythmia

Antzelevitch, Charles; Burashnikov, Alexander; Diego, José M. Di

doi:10.1007/978-1-84628-854-8_6

Cited by 4 publications

(4 citation statements)

References 425 publications

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“… 40 Nevertheless, it is possible that NADPH-d reactive nerve fibres have direct influence on the function of the valves, the frequency and force of valve closure and the cardiac contraction; they may play a role in precipitating arrhythmias and premature extrasystoles. 15 , 41 An accurate and full understanding of the precise movements of the valve leaflets and the mechanisms regulating these movements is likely to provide the information to understanding and development of treatment for many different cardiac valve problems, including mitral valve diseases such as prolapse and myxomatous degeneration. 15 …”

Section: Discussionmentioning

confidence: 99%

Distribution of NADPH-diaphorase and AChE activity in the anterior leaflet of rat mitral valve

et al. 2010

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The mitral valve, as an active flap, forms the major part of the left ventricular inflow tract and therefore plays an important function in many aspects of left ventricular performance. The anterior leaflet of this valve is the largest and most ventrally placed of two leaflets that come together during ventricular systole to close the left atrioventricular orifice. Various neurotransmitters are responsible for different functions including controlling valve movement, inhibiting or causing the failure of impulse conduction in the valve and the sensation of pain. Nitric oxide acts as a gaseous free radical neurotransmitter, neuromediator and effective cardiovascular modulator. Acetyl-choline is known to function as a typical neurotransmitter. Histochemical methods for detection of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), as an indirect nitric oxide-synthase marker, and method for detection of acetylcholinesterase (AChE) were used. Both methods were performed on the same valve sample. A widespread distribution of nerve fibres was observed in the anterior leaflet of the mitral valve. The fine NADPH-d positive (nitrergic) nerve fibres were identified in all zones of valve leaflet. AChE positive (cholinergic) nerve fibres were identified forming dense network and fibres organized in stripes. Endocardial cells and vessels manifested heavy NADPH-d activity. Our observations suggest a different arrangement of nitrergic and cholinergic nerve fibres in the anterior leaflet of the mitral valve. The presence of nitrergic and cholinergic activity confirms the involvement of both neurotransmitters in nerve plexuses and other structures of mitral valve.

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Section: Discussionmentioning

confidence: 99%

Distribution of NADPH-diaphorase and AChE activity in the anterior leaflet of rat mitral valve

et al. 2010

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“…During untreated hypothyroidism, the dog showed intense abnormal stimulus of the parasympathetic tone, due to a change in sinus function, in which the frequency was reduced and arrhythmic (Figure 1D). The altered conduction of the sinoatrial node can be impaired or blocked by disease or increase in vagal activity [2], which corresponded to the high values in HF (Table 1). Thus, the intranodal and sinoatrial conductions become slow, leading to bradycardia [2,6], as observed before treatment because of the low values in LF.…”

Section: Discussionmentioning

confidence: 83%

“…The electrodes were positioned in the following precordial leads: location between 5 th and 6 th intercostal spaces on the right (negative electrode) and left (positive electrode) sides; at the junction between the upper and middle 3 rd of the chest, forming the X--axis; in the manubrium region (negative electrode) and xiphoid cartilage region (positive electrode), forming the Y-axis; location between the spinous T7 process (negative electrode) and the opposite ventral aspect (positive electrode), forming the Z-axis. To cover and protect the electrodes, a bandage was applied to the dog's chest, as well as to the digital recording device 2 . The 24 h electrocardiographic tracings were processed using the Cardio Manager S540 software 2 and always reviewed by the same veterinarian.…”

Section: Casementioning

confidence: 99%

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Minimum Dose of Levothyroxine Restored the Autonomic Balance on a Dalmatian Female Dog with Primary Hypothyroidism

Costa

Waller

Rocha

et al. 2020

Acta Scientiae. Vet.

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Background: Hypothyroidism is an endocrine disease that leads to a reduction in the hormones thyroxine (T3) and triiodothyronine (T4), which therapy with levothyroxine restores the clinical signs related to the metabolic rate. Due to the influence of thyroid hormones on the heart, which is under the constant influence of the autonomic nervous system (ANS), dogs with hypothyroidism can develop bradycardia, arrhythmia, and dysautonomia. Heart rate variability (HRV) assesses autonomic modulation by the Holter method, which is scarce in dogs. We aimed to report the cardiac and autonomic effects of the primary hypothyroidism untreated and treated with levothyroxine in a canine case by Holter monitoring.Case: A 7-year-old female Dalmatian, weighing 36 kg, was referred for clinical evaluation due to apathy, weight gain, low hair quality, and lethargy. On physical examination, alopecic lesions on the hind limbs and tail, as well as bradycardia with a heart rate (HR) of 40-50 beats per minute (bpm) were observed, in addition to a 3/6 mitral murmur and 2/6 tricuspid murmur. Given the suspicion of thyroid gland disorder, the blood hormonal measurement revealed an increase in thyroid-stimulating hormone (TSH; 0.65 ng/mL) and a decrease in free T4 (0.11 ng/mL) and total T4 (0.44 ng/mL), confirming primary hypothyroidism. Therapy was started with a minimum dose of levothyroxine (0.913 mg, every 12 h), which clinical signs were restored in five months of treatment, with weight loss, hair growth, and active behavior. To assess the impact of untreated and treated hypothyroidism on the patient’s ANS, a Holter monitoring exam was performed for 24 h before and after therapy. Before treatment, the average HR was 75 bpm, and the HR<50 bpm occurred during 05 h 20 min 36 s. Still, 320 pause events (>2.0s), 1st-degree atrioventricular blocks (AVB), six ventricular ectopias events, and 2nd-degree sinoatrial block (SAB) were also observed. The ANS parasympathetic tone was significantly stimulated, highlighting bradycardia, arrhythmia, and dysautonomia. After five months of treatment with levothyroxine, the average HR was 89 bpm, and the HR<50 bpm occurred during 02 h 06 min 13 s. No ventricular pauses, blocks, or ectopias were observed, showing the stimulation of sympathetic tonus, which restored HR and ANS balance. Still, it was observed that the minimum levothyroxine dose corrected cardiac changes by increasing the low frequency (LF), decreasing the high frequency (HF), and, consequently, increasing the LF/HF ratio, normalizing the frequency conditions in HRV.Discussion: In the frequency index, HF indicates the vagal activity, whereas LF indicates both systems with parasympathetic predominance. Before treatment, the dog had a low LF/HF ratio (0.46), indicating dysautonomia with parasympathetic stimulation. After therapy, the conditions of bradycardia and functional cardiac capacity were corrected, restoring ANS, due to the serum recovery of thyroid hormones. This study reported the cardiac and autonomic effects of primary hypothyroidism untreated and treated with levothyroxine on a dog, that had intense bradycardia and abnormal stimulation of the parasympathetic tone, associated with episodes of 1st-degree AVB, ventricular ectopias, and 2nd-degree SAB. After therapy with a minimum dose of levothyroxine, there was a decrease in parasympathetic activity and an increase in sympathetic stimulus, correcting cardiac changes, and restoring the balance of ANS. As it is a simple, non-invasive, and safe tool that helps the clinician to understand cardiac autonomic modulation, it is recommended to adopt the Holter monitoring exam in cases of hypothyroidism cases to assess sympathetic-vagal balance and check potential cardiac risks.

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Role of Pyk2 in cardiac arrhythmogenesis

Lang

Glukhov

Efimova

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Proline-rich tyrosine kinase 2 (Pyk2) is a nonreceptor protein kinase regulated by intracellular Ca2+, CaMK, and PKC and can be activated by different stress signals involved in heart failure. However, Pyk2 has not been investigated in the human heart, and the functional role of Pyk2 signaling at the whole heart level has not been elucidated. We hypothesize that Ca2+-dependent activation of Pyk2 is involved in cardiac electrophysiology. We examined the expression of Pyk2 in nonfailing versus ischemic and nonischemic failing human hearts ( n = 6 hearts/group). To investigate Pyk2 function, we optically mapped perfused hearts from wild-type (WT; n = 7) and knockout (Pyk2−/−; n = 8) mice during autonomic stimulation. Experiments were done in control mice and after 1 wk of transverse aortic constriction. We used the Illumina beadarray approach for transcriptional profiling of WT and Pyk2−/− mouse ventricles. Western blot analysis revealed a doubling of Pyk2 activation in nonischemic failing versus nonfailing human hearts. In mouse hearts, we observed a much higher probability of ventricular tachyarrhythmia during ACh perfusion in Pyk2−/− versus WT mice. Parasympathetic stimulation resulted in a dose-dependent decrease of atrial action potential duration (APD) in both WT and Pyk2−/− mice, whereas in ventricles it induced APD shortening in Pyk2−/− mice but not in WT mice. Deficiency of Pyk2 abolished ACh-induced prolongation of atrioventricular delay in Pyk2−/− mouse hearts but did not affect heart rate. Lower mRNA and protein levels of sarco(endo)plasmic reticulum Ca2+-ATPase 2 and higher mRNA levels of Na+/Ca2+ exchanger 1 were detected in Pyk2−/− hearts compared with WT hearts. The transverse aortic constriction protocol did not change the phenotype. In conclusion, our results indicate a protective role of Pyk2 with respect to ventricular tachyarrhythmia during parasympathetic stimulation by regulation of gene expression related to Ca2+ handling. We hypothesize that activation of Pyk2 in the human heart during heart failure may contribute to protection against arrhythmia.

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Mechanisms of Cardiac Arrhythmia

Cited by 4 publications

References 425 publications

Distribution of NADPH-diaphorase and AChE activity in the anterior leaflet of rat mitral valve

Distribution of NADPH-diaphorase and AChE activity in the anterior leaflet of rat mitral valve

Minimum Dose of Levothyroxine Restored the Autonomic Balance on a Dalmatian Female Dog with Primary Hypothyroidism

Role of Pyk2 in cardiac arrhythmogenesis

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