Anesthetic Management for Surgical Myectomy in Hypertrophic Cardiomyopathy
Srilakshmi M. Adhyapak, V. Rao Parachuri in Hypertrophic Cardiomyopathy, 2020
Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disease transmitted as an autosomal dominant trait [1]. Cardiomyopathy (CM) involves 14 genes with approximately 1,400 mutations that affect sarcomere protein mutations and results in exuberant left ventricular hypertrophy (LVH) [1–6]. Based on mixed epidemiologic studies, the prevalence of phenotypically expressed HCM in the adult general population is estimated at 0.2% (1,500) [1–5]. The majority of afflicted patients live a near-normal life span but are, nevertheless, susceptible to sudden cardiac death, symptoms secondary to dynamic left ventricular outflow tract obstruction (LVOTO), abnormal diastolic filling, impaired left ventricular systolic function, and atrial fibrillation. Each of these may preclude normal physical activities and impair quality and even duration of life [7].
Past History-Dependence of Myosin Head Performance
Haruo Sugi in Mysteries in Muscle Contraction, 2017
As illustrated in Fig. 123, the sarcomere length versus isometric force relation consists of three parts; (1) the descending limb where the isometric force decreases linearly with increasing sarcomere length from 2.25 to 3.65 µm due to the decrease in the amount of overlap between actin and myosin filaments, i.e., decrease in the number of myosin heads that can interact with actin filaments, (2) the plateau where the isometric force is constant over sarcomere lengths from 2.0 to 2.25 µm (equal to the bare region width), and (3) the ascending limb where the isometric force decreases with decreasing sarcomere length below 2.0 µm due to double overlap of actin filaments and collision of the myosin filament against the Z-line (Gordon, Huxley and Julian, 1966).
Altered Somatosensory Pathways
Golara Honari, Rosa M. Andersen, Howard Maibach in Sensitive Skin Syndrome, 2017
Many downregulated genes are associated with muscle contraction and relaxation process as well as muscle structure. In human facial skin, striated muscle fibers are found in the reticular dermis and subcutis (69), along with smooth muscles accompanying the hair follicles (arrector pili). The sarcomere, a functional unit of muscle, is composed mainly of thick filaments (myosin, slow-type myosin-binding protein C), thin filaments (actin, troponin, alpha tropomyosin 1, nebulin), and elastic components (titin). In the presence of Ca2+ from sarcoplasmic reticulum and ATP, the myosin head binds to the actin that enables the thin filament to slide along the thick filament, allowing for the shortening of the sarcomere (cross-bridge cycling) (70). Actin-bound myosin cross bridges in sensitive skin had more compacted shape than those in nonsensitive skin, indicating more contracted cross-bridge state in sensitive skin tissues (Figure 6.3). Further supporting experiments demonstrated that the decreased expressions of muscle-related genes in sensitive skin were not due to either a sampling bias or differences in anatomical sites. Our results suggest that sensitive skin may be associated with abnormal muscle contraction/relaxation process (29).
Current and emerging pharmacotherapy for the management of hypertrophic cardiomyopathy
Published in Expert Opinion on Pharmacotherapy, 2023
Akiva Rosenzveig, Neil Garg, Shiavax J. Rao, Amreen K. Kanwal, Arjun Kanwal, Wilbert S. Aronow, Matthew W. Martinez
The essential unit of contraction in cardiac myocytes is the sarcomere [20]. Myosin is the molecular motor of the sarcomere that hydrolyzes adenosine triphosphate (ATP) to interact with the thin filament actin. However, for every given contraction, only 10% of myosin molecules are utilized to generate force [21], thus preventing unnecessary energy utilization. During relaxation, paired myosin head domains can interact in either a super relaxed state (SRX), where neither head can interact with actin filaments, or in a disordered state (DRX), where one myosin head is free to hydrolyze ATP and interacts with actin [22]. The predominant myosin isoform, MYH7 (B-myosin heavy chain), and myosin-binding protein C (MYBPC) harbor most of the pathogenic variants in HCM [23]. These pathologic variants increase the proportion of myosin heads in DRX leading to hypercontractility and increased energy expenditure [22]. In these individuals, hypercontractility and impaired diastolic function precede left ventricular hypertrophy [24,25].
Circadian regulation of cardiac muscle function and protein degradation
Published in Chronobiology International, 2023
Proteostasis, including protein synthesis, processing/folding and degradation, is an important cellular mechanism in cardiac muscles (Henning and Brundel 2017; McLendon and Robbins 2015). Compared with non-muscle cells, cardiac muscles are terminally differentiated, must contract throughout lifetime, require robust metabolic/stress responses and involve specialized cellular machineries for electric conductance. The structural and functional unit of striated muscles, including both cardiac and skeletal muscles, is the sarcomere (Martin and Kirk 2020; Ono 2010), which is highly conserved throughout from worms to mammals. Sarcomeres line up sequentially, and tied together by a complex protein assembly called Z-disc to form contractible myofibrils, which in turn are bound in bundles to form cardiomyocytes. The sarcomere consists mainly of the myosin thick filaments and actin thin filaments, with a large number of associated structural and regulatory proteins. Given the heart is the first organ to be formed after birth and must continuously function until death, and that cardiomyocytes are post-mitotic, protein quality control at the sarcomere plays a particularly important role in cardiac proteostasis (Henning and Brundel 2017; Martin and Kirk 2020). Of particular importance is protein degradation mechanisms to remove misfolded or faulty proteins.
Multi-modality management of hypertrophic cardiomyopathy
Published in Hospital Practice, 2023
Shiavax J. Rao, Shaikh B. Iqbal, Arjun S. Kanwal, Wilbert S. Aronow, Srihari S. Naidu
Myosin, the protein that propels the sarcomere and drives muscle contraction, equilibrates between a super relaxed state (with low adenosine triphosphatase [ATPase] activity) and a disordered relaxed state (allowing for interaction with actin) [54]. HCM is characterized by impairment in the energetic and mechanical properties of cardiac myocytes, with recent experimental data suggesting that the resultant hyperdynamic contractility and impaired myocardial relaxation may be due to an imbalance and shift of myosin toward the disordered relaxed state [55–60]. Given these insights, with current limitations of conventional pharmacotherapies and a relatively high threshold for invasive therapies, molecules decreasing the ATPase activity of myosin have emerged as pharmacotherapeutic options targeting the critical pathophysiological mechanism of disease in HCM [61,62].
Related Knowledge Centers
- Actin
- Costamere
- Myofibril
- Myosin
- Myosin Head
- Sarcolemma
- Striated Muscle Tissue
- Myogenesis
- Skeletal Muscle
- Animal Embryonic Development