Contractility in the heart
People experiencing some forms of heart failure have a significant decrease in the contractile ability of muscle cells in the heart (cardiomyocytes). This impaired contractility occurs through a number of mechanisms. Some of the main problems associated with decreased contractility in those with heart failure are issues arising from imbalances in the concentration of calcium. Calcium permits myosin and actin to interact which allows initiation of contraction within the cardiomyocytes. In those with heart failure there may be a decreased amount of calcium within the cardiomyocytes reducing the available calcium to initiate contraction. When contractility is decreased the amount of blood being pumped out of the heart into circulation is decreased as well. This reduction in cardiac output can cause many systemic implications such as fatigue, syncope and other issues associated with decreased blood flow to peripheral tissues. Mechanism of action
cAMP causes increased activation of protein kinase A (PKA). PKA is an enzyme that phosphorylates many elements of the contractile machinery within the heart cell. In the short term this leads to an increased force of contraction. Phosphodiesterases are enzymes responsible for the breakdown of cAMP. Therefore, when phosphodiesterases lower the level of cAMP in the cell they also lower the active fraction of PKA within the cell and reduce the force of contraction. Milrinone is a phosphodiesterase-3 inhibitor. This drug inhibits the action of phosphodiesterase-3 and thus prevents degradation of cAMP. With increased cAMP levels there is an increase in the activation of PKA.
Diabetic gastropathy
Diabetic gastropathy is usually slowly progressive, and can become severe and lethal. Prevalence
Post-infectious gastroparesis, which constitutes the majority of idiopathic gastroparesis cases, affects up to 4% of the American population. Women in their 20s and 30s seem to be susceptible. One study of 146 American gastroparesis patients found the mean age of patients was 34 years with 82% affected being women, while another study found the patients were young or middle aged and up to 90% were women.There has only been one true epidemiological study of idiopathic gastroparesis which was completed by the Rochester Epidemiology Project. They looked at patients from 1996 to 2006 who were seeking medical attention instead of a random population sample and found that the prevalence of delayed gastric emptying was fourfold higher in women. It is difficult for medical professionals and researchers to collect enough data and provide accurate numbers since studying gastroparesis requires specialized laboratories and equipment. References
Further reading
Overview from NIDDK National Institute of Diabetes, Digestive, and Kidney Diseases at NIH
Camilleri M, Parkman HP, Shafi MA, Abell TL, Gerson L (January 2013). "Clinical guideline: management of gastroparesis". The American Journal of Gastroenterology. 108 (1): 18–37, quiz 38. doi:10.1038/ajg.2012.373. PMC 3722580. PMID 23147521. Parkman HP, Fass R, Foxx-Orenstein AE (June 2010). "Treatment of patients with diabetic gastroparesis". Gastroenterology & Hepatology. 6 (6): 1–16. PMC 2920593. PMID 20733935. == External links ==