The fundamental contractile unit is the sarcomere. Each muscle cell apart from the nucleus,mitochondria and other structures contains parallel fibrils. Sarcomere is a subunit of the fibril. It consists of parallel actin and myosin filaments. The thin actin filaments are attached to its limiting membrane or the Z line and interdigitates with the thicker myosin filaments which are placed centrally. The myosin filaments have flexible heads which can come into contact with the actin filaments. The filaments are propelled past each other by the repeated making and breaking of cross bridges between the actin and myosin filaments. In the resting state when the calcium level is low the myosin binding sites on the actin filament are blocked by tropomyosin which is a regulatory protein. This prevents cross bridge formation. When there is activation and a rise in calcium, the myosin actin binding sites are exposed. The energy required for the cross bridge recycling is provided by adenosine tripshophate (ATP). The number of cross bridges depends on the available calcium molecules. The greater the number of bridges, the more forceful the resulting contraction. During systole there is a 50 fold increase in intracellular calcium concentration.
 |
| Cardiac muscle |
Myocardial Energetics
The oxidation of substrates like free fatty acids (FFA), glucose, lactate and ketone bodies results in the energy of Adenosine triphosphate (ATP) and Creatine phosphate (CP). The substrate used depends on several factors like its level in the blood, level of insulin and catecholamine level. In the resting, fasting state 70-80 per cent of the oxygen consumption can come from the oxidation of FFA. With high glucose levels and resulting high insulin levels the fuel shifts to glucose.
Glucose is phosphorylated to glucose 6 phosphate. It is either synthesized to glycogen or enters glycolysis with pyruvate as the end product. Lactate is used as the major fuel when its level increases with severe exercise. Lactate may leave the myocardium or if acetylated to acetyl coenzyme A enters the tricarboxylic acid cycle. Catecholamines increase lipolysis and thus increase the FFA levels. Normally free fatty acids are the main substrate. In ischaemia the glycolytic pathway is stimulated. This cannot substitute for oxidative phosphorylation and inevitably ischaemia thus leads to a fall in ATP levels. This impairs myocardial function.
Contractility
Myocardial contractility is mostly dependent on the level of sympathetic nerve activity and is also increased by circulating catecholamines and inotropic drugs like dopamine and dobutamine. With increased contractility there is an increased oxygen demand which is out of proportion to the extra work performed. These factors become critical when there is a decrease in oxygen supply as with coronary artery disease.
The oxidation of substrates like free fatty acids (FFA), glucose, lactate and ketone bodies results in the energy of Adenosine triphosphate (ATP) and Creatine phosphate (CP). The substrate used depends on several factors like its level in the blood, level of insulin and catecholamine level. In the resting, fasting state 70-80 per cent of the oxygen consumption can come from the oxidation of FFA. With high glucose levels and resulting high insulin levels the fuel shifts to glucose.
Glucose is phosphorylated to glucose 6 phosphate. It is either synthesized to glycogen or enters glycolysis with pyruvate as the end product. Lactate is used as the major fuel when its level increases with severe exercise. Lactate may leave the myocardium or if acetylated to acetyl coenzyme A enters the tricarboxylic acid cycle. Catecholamines increase lipolysis and thus increase the FFA levels. Normally free fatty acids are the main substrate. In ischaemia the glycolytic pathway is stimulated. This cannot substitute for oxidative phosphorylation and inevitably ischaemia thus leads to a fall in ATP levels. This impairs myocardial function.
Contractility
Myocardial contractility is mostly dependent on the level of sympathetic nerve activity and is also increased by circulating catecholamines and inotropic drugs like dopamine and dobutamine. With increased contractility there is an increased oxygen demand which is out of proportion to the extra work performed. These factors become critical when there is a decrease in oxygen supply as with coronary artery disease.
No comments:
Post a Comment
Note: Only a member of this blog may post a comment.