title: Pretreatment with nicardipine preserves ventricular function after hypothermic ischemic arrest.
abstract: Calcium antagonists have a protective effect on postischemic myocardial function when included in normothermic cardioplegia solutions. This effect varies with the calcium antagonist, but is generally lost under hypothermic conditions. The hypothesis tested was that a calcium antagonist would increase postischemic myocardial performance if given before the onset of hypothermic arrest. Isolated working rat hearts were used with an oxygenated modified Krebs-Henseleit buffer solution as a perfusion media. Rats were pretreated with 1 of 9 doses of a nicardipine solution (0 to 100 micrograms/kg, intraperitoneally) 20 minutes before excision of the heart. Nicardipine is a light-stable, water-soluble calcium antagonist with minimal myocardial depressant effects. The hearts were arrested for 25 minutes at 37 degrees C or 93 minutes at 24 degrees C with 20 mL of cardioplegia solution containing 0.05 mmol/L CaCl2. Postischemic performance and adenosine triphosphate content were used as determinants of efficacy. Eighty-three percent of 101 treated hearts recovered in contrast to a mortality of 50% in the 24 nontreated hearts. Pretreatment with 25 micrograms/kg significantly increased (p less than 0.05) the percent recovery (compared with the nontreated group) of the following variables of cardiac function: systolic pressure, 74% to 96% (37 degrees C), 76% to 90% (24 degrees C); cardiac output, 61% to 90% (37 degrees C), 62% to 84% (24 degrees C); stroke work, 49% to 95% (37 degrees C), 50% to 92% (24 degrees C); and adenosine triphosphate, 76% to 87% (37 degrees C), 58% to 68% (24 degrees C). Progressive increases in postischemic function at 37 degrees and 24 degrees C were seen as the dose of nicardipine was increased from 0 to 25 micrograms/kg and decreased function was seen with a pretreatment dose greater than 25 micrograms/kg of nicardipine. Pretreatment with nicardipine significantly improved postischemic myocardial performance under hypothermic conditions and should be administered or at least not discontinued before cardiac operations.
authors.affiliation: Surgery Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
authors.forename: P S
authors.initials: PS
authors.lastname: Brown
authors.forename: G L
authors.initials: GL
authors.lastname: Parenteau
authors.forename: F W
authors.initials: FW
authors.lastname: Holland
authors.forename: R E
authors.initials: RE
authors.lastname: Clark
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006321:Heart / Q000187:drug effects*; D006324:Heart Arrest, Induced; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009529:Nicardipine / Q000627:therapeutic use*; D011292:Premedication; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D000255:Adenosine Triphosphate; D009529:Nicardipine