Postischemic administration of CGX-1051, a peptide from cone snail venom, reduces infarct size in both rat and dog models of myocardial ischemia and reperfusion.
CGX-1051 is a synthetic version of a peptide originally isolated from the venom of cone snails. In the present studies, we tested the potential cardioprotective effect of CGX-1051 in a rat and dog model of myocardial ischemia/reperfusion. CGX-1051 was administered 5 minutes before reperfusion as intravenous bolus doses of 30, 100, and 300 microg/kg. Infarct size (IS) is reported as IS/area at risk (AAR). In the rat, the vehicle control group had an IS/AAR of 59.8+/-2.1%. Postischemic administration of CGX-1051 at doses of 30, 100, and 300 microg/kg resulted in an IS/AAR of 52.6+/-4.2%, 34.6+/-5.6% (P<0.05), and 40.8+/-5.2% (P<0.05), respectively. In the dog, the vehicle control group had an IS/AAR of 18.8+/-1.7%. Postischemic administration of CGX-1051 at doses of 30, 100, and 300 microg/kg resulted in an IS/AAR of 16.9+/-2.5%, 8.4+/-2.9% (P<0.05) and 9.9+/-2.4% (P<0.05), respectively. These results demonstrate that administration of CGX-1051 at a clinically relevant time point results in a dose-dependent reduction in IS in both rats and dogs.
Lubbers
Nathan L
NL
Integrative Pharmacology, Global Pharmaceutical Discovery, Abbott Laboratories, Abbott Park, Illinois 60064-6119, USA. nathan.lubbers@abbott.com
Campbell
Thomas J
TJ
Polakowski
James S
JS
Bulaj
Grzegorz
G
Layer
Richard T
RT
Moore
Jeannine
J
Gross
Garrett J
GJ
Cox
Bryan F
BF
D000818:Animals; D020916:Conotoxins / Q000302:isolation & purification / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000150:complications*; D010455:Peptides / Q000302:isolation & purification / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D020916:Conotoxins; D010455:Peptides; C108818:kappa-conotoxin PVIIA