title: Alpha-human atrial natriuretic peptide, carperitide, reduces infarct size but not arrhythmias after coronary occlusion/reperfusion in dogs.
abstract: Carperitide, a recombinant form of alpha-hANP, possesses potent diuretic, natriuretic, and vasodilatory activity, and inhibits the renin-aldosterone system and sympathetic nervous activity. However, its beneficial effects on ischemic myocardium have not been studied fully. We examined carperitide's effects on infarct size, hemodynamics, and arrhythmia frequency in anesthetized dogs (n = 20) subjected to a 90-min coronary artery occlusion/6-h reperfusion protocol. Intravenous infusion of carperitide (0.2 microg/kg/min) commenced 15 min after occlusion and continued during occlusion/reperfusion. Ventricular fibrillation developed in two of 10 control versus three of 10 treated dogs (p = NS). Hemodynamics, collateral blood flow to the ischemic wall measured 10 min after occlusion, and extent of area at risk were comparable for the two groups. Infarct size/area at risk was smaller in treated than in control dogs (4.5 +/- 2.1% vs. 27.8 +/- 7.8%, respectively; p < 0.05). During occlusion, carperitide tended to increase collateral blood flow (+39%) and significantly decreased left ventricular systolic pressure (-13%) and end-diastolic pressure (-40%) compared with baseline. In control dogs, collateral blood flow tended to decrease (-8.3%), whereas most hemodynamic parameters did not change significantly with respect to baseline. The number of arrhythmias recorded during occlusion/reperfusion was similar in the two groups. Intravenous administration of carperitide limited infarct size, but did not reduce incidence of ventricular arrhythmias after 90-min coronary occlusion/6-h reperfusion in anesthetized dogs. Although the beneficial effects of carperitide may be attributable to concomitant changes in hemodynamics and collateral blood flow, the precise mechanisms require further investigation.
authors.affiliation: First Department of Internal Medicine, Nippon Medical School, Tokyo, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Takagi
authors.forename: K
authors.initials: K
authors.lastname: Kiuchi
authors.forename: T
authors.initials: T
authors.lastname: Endo
authors.forename: T
authors.initials: T
authors.lastname: Yamamoto
authors.forename: N
authors.initials: N
authors.lastname: Sato
authors.forename: J
authors.initials: J
authors.lastname: Nejima
authors.forename: T
authors.initials: T
authors.lastname: Takano
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy* / Q000209:etiology; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D002316:Cardiotonic Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D003097:Collateral Circulation / Q000187:drug effects / Q000502:physiology; D003327:Coronary Disease / Q000150:complications / Q000188:drug therapy*; D006152:Cyclic GMP / Q000097:blood; D004285:Dogs; D005260:Female; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy*; D015425:Myocardial Reperfusion; D010446:Peptide Fragments / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D002316:Cardiotonic Agents; D010446:Peptide Fragments; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP