Biomaterial Database

Monophosphoryl lipid A induces delayed preconditioning against cardiac ischemia-reperfusion injury. 1998

G T Elliott

Division of Pharmaceutical Development, Ribi ImmunoChem Research Inc., Hamilton, Montana 59840, USA.

Monophosphoryl lipid A represents a novel agent capable of enhancing myocardial tolerance to ischemia/reperfusion injury. This cardioprotective activity of MLA manifests itself as a reduction in infarct size, myocardial stunning and dysrhythmias in multiple animal species. The drug appears to be efficacious in dogs and rabbits at doses of 10-35 micrograms/kg, with larger doses seemingly required in the rat. In the rabbit infarct model, protection appears 6 h following drug administration and lasts for 36 h. Although multifactorial mechanisms of ischemic tolerance may be induced by MLA, current evidence suggests that MLA's cardioprotective effects involve myocardial iNOS enzyme activation with nitric oxide coupled activation of myocardial KATP channels upon ischemic challenge. Monophosphoryl lipid A is presently being evaluated in Phase 2 clinical trials in patients undergoing cardiopulmonary bypass associated with coronary artery bypass engraftment or aortic valve replacement or reconstruction. Severity of lethal and reversible myocardial injury and dysrhythmia are study endpoints. Although further clinical testing will establish the utility of MLA as a cardioprotectant against ischemia/reperfusion injury in the human, presently this agent is proving very useful in expanding our understanding of mechanisms responsible for delayed cardiac preconditioning against ischemia/reperfusion injury.

UI	MeSH Term	Description	Entries
D008050	Lipid A	Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties.
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015428	Myocardial Reperfusion Injury	Damage to the MYOCARDIUM resulting from MYOCARDIAL REPERFUSION (restoration of blood flow to ischemic areas of the HEART.) Reperfusion takes place when there is spontaneous thrombolysis, THROMBOLYTIC THERAPY, collateral flow from other coronary vascular beds, or reversal of vasospasm.	Reperfusion Injury, Myocardial,Injury, Myocardial Reperfusion,Myocardial Ischemic Reperfusion Injury,Injuries, Myocardial Reperfusion,Myocardial Reperfusion Injuries,Reperfusion Injuries, Myocardial
D017322	Clinical Trials, Phase II as Topic	Works about studies that are usually controlled to assess the effectiveness and dosage (if appropriate) of diagnostic, therapeutic, or prophylactic drugs, devices, or techniques. These studies are performed on several hundred volunteers, including a limited number of patients with the target disease or disorder, and last about two years. This concept includes phase II studies conducted in both the U.S. and in other countries.	Drug Evaluation, FDA Phase 2 as Topic,Drug Evaluation, FDA Phase II as Topic,Evaluation Studies, FDA Phase 2 as Topic,Evaluation Studies, FDA Phase II as Topic
D019157	Ischemic Preconditioning, Myocardial	Exposure of myocardial tissue to brief, repeated periods of vascular occlusion in order to render the myocardium resistant to the deleterious effects of ISCHEMIA or REPERFUSION. The period of pre-exposure and the number of times the tissue is exposed to ischemia and reperfusion vary, the average being 3 to 5 minutes.	Myocardial Preconditioning,Myocardial Ischemic Preconditioning,Preconditioning, Myocardial,Preconditioning, Myocardial Ischemic