RESUMO
Muscle contractures that occur after upper motor neuron lesion are often surgically released or lengthened. However, surgical manipulation of muscle length changes a muscle's sarcomere length (Ls ), which can affect force production. To predict effects of surgery, both macro- (fascicle length (Lf )) and micro- (Ls ) level structural measurements are needed. Therefore, the purpose of this study was to quantify both Ls and Lf in patients with cerebral palsy (CP) as well as typically developing (TD) children. Soleus ultrasound images were obtained from children with CP and TD children. Lf was determined and, with the joint in the same position, CP biopsies were obtained and formalin fixed, and Ls was measured by laser diffraction. Since soleus Ls values were not measurable in TD children, TD Ls values were obtained using three independent methods. While average Lf did not differ between groups (CP=3.6±1.2 cm, TD=3.5±0.9 cm; p>0.6), Ls was dramatically longer in children with CP (4.07±0.45 µm vs. TD=2.17±0.24 µm; p<0.0001). While Lf values were similar between children with CP and TD children, this was due to highly stretched sarcomeres within the soleus muscle. Surgical manipulation of muscle-tendon unit length will thus alter muscle sarcomere length and change force generating capacity of the muscle.
Assuntos
Paralisia Cerebral/diagnóstico por imagem , Pé Equino/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Sarcômeros/diagnóstico por imagem , Adolescente , Fenômenos Biomecânicos/fisiologia , Biópsia , Estudos de Casos e Controles , Paralisia Cerebral/patologia , Paralisia Cerebral/fisiopatologia , Criança , Pé Equino/patologia , Pé Equino/fisiopatologia , Feminino , Humanos , Masculino , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Sarcômeros/patologia , Sarcômeros/fisiologia , Tendões/diagnóstico por imagem , Tendões/patologia , Tendões/fisiopatologia , UltrassonografiaRESUMO
The cellular mechanism underlying the Frank-Starling law of the heart is myofilament length-dependent activation. The mechanism(s) whereby sarcomeres detect changes in length and translate this into increased sensitivity to activating calcium has been elusive. Small-angle X-ray diffraction studies have revealed that the intact myofilament lattice undergoes numerous structural changes upon an increase in sarcomere length (SL): lattice spacing and the I(1,1)/I(1,0) intensity ratio decreases, whereas the M3 meridional reflection intensity (I(M3)) increases, concomitant with increases in diastolic and systolic force. Using a short (â¼10 ms) X-ray exposure just before electrical stimulation, we were able to obtain detailed structural information regarding the effects of external osmotic compression (with mannitol) and obtain SL on thin intact electrically stimulated isolated rat right ventricular trabeculae. We show that over the same incremental increases in SL, the relative changes in systolic force track more closely to the relative changes in myosin head orientation (as reported by I(M3)) than to the relative changes in lattice spacing. We conclude that myosin head orientation before activation determines myocardial sarcomere activation levels and that this may be the dominant mechanism for length-dependent activation.
Assuntos
Citoesqueleto de Actina/diagnóstico por imagem , Coração/fisiologia , Cadeias Pesadas de Miosina/química , Miosinas/química , Volume Sistólico/fisiologia , Citoesqueleto de Actina/fisiologia , Animais , Estimulação Elétrica , Masculino , Modelos Animais , Contração Miocárdica/fisiologia , Miocárdio/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Miosinas/metabolismo , Radiografia , Ratos , Ratos Endogâmicos , Sarcômeros/diagnóstico por imagem , Sarcômeros/fisiologia , Difração de Raios XRESUMO
In muscle cells, a complex network of Z-disc proteins allows proper reception, transduction and transmission of mechanical and biochemical signals. Mutations in genes encoding different Z-disc proteins such as integrin-linked kinase (ILK) and nexilin have recently been shown to cause heart failure by distinct mechanisms such as disturbed mechanosensing, altered mechanotransduction or mechanical Z-disc destabilization. We identified core-binding factor ß (CBFß) as an essential component for maintaining sarcomeric Z-disc and myofilament organization in heart and skeletal muscle. In CBFß-deficient cardiomyocytes and skeletal-muscle cells, myofilaments are thinned and Z-discs are misaligned, leading to progressive impairment of heart and skeletal-muscle function. Transcription of the gene encoding CBFß mainly depends on JunB activity. In JunB-morphant zebrafish, which show a heart-failure phenotype similar to that of CBFß-deficient zebrafish, transcript and protein levels of CBFß are severely reduced. Accordingly, ectopic expression of CBFß can reconstitute cardiomyocyte function and rescue heart failure in JunB morphants, demonstrating for the first time an essential role of JunB-CBFß signaling for maintaining sarcomere architecture and function.