Acute heart failure--basic pathomechanism and new drug targets.
In view of the high incidence of heart failure and sudden cardiac death, efforts in the development of compounds which target-specific mechanisms such as a reduced expression of SERCA2, the Ca2+ pump of sarcoplasmic reticulum, of hypertrophied cardiomyocytes of pressure-overloaded or infarcted hearts should be strengthened. Lead compounds for correcting a dysregulated gene expression are the carnitine palmitoyltransferase-1 (CPT-1) inhibitors etomoxir and oxfenicine. Since bypassing the CPT-1 inhibition by a medium-chain fatty acid diet had a lesser effect on myosin V1 proportion than on lipid droplet number, one has to infer also other mechanisms such as PPARalpha activation (FOXIB/PPARalpha). In view of the intricate interrelationship between depressed pump function and malignant arrhythmias, stimulation of endogenous antiarrhythmogenic mechanisms linked to an enhanced production of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) could potentially provide alternatives to the administration of 1 g EPA and DHA ethyl esters (minimum 84% EPA + DHA) for secondary prevention of myocardial infarction. The apparently greater efficacy of omega-3 fatty acids in post-myocardial infarction patients (GISSI-Prevention study) compared with ICD patients (SOFA study) can be attributed to the greater ischemia-induced release of membrane-bound EPA and DHA and a better compliance (one vs. four capsules daily).
Rupp
Heinz
H
Molecular Cardiology Laboratory, Department of Internal Medicine and Cardiology, Philipps University of Marburg, 35043, Marburg, Germany. Rupp@staff.uni-marburg.de
Rupp
Thomas P
TP
Alter
Peter
P
Maisch
Bernhard
B
D000208:Acute Disease; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D002303:Cardiac Output, Low / Q000188:drug therapy* / Q000503:physiopathology*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends*; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D006801:Humans
D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D015525:Fatty Acids, Omega-3