The Annals of Thoracic Surgery, Vol 51, 739-746, Copyright © 1991 by The Society of Thoracic Surgeons
Pretreatment with nicardipine preserves ventricular function after hypothermic ischemic arrest
PS Brown Jr, GL Parenteau, FW Holland and RE Clark
Surgery Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.
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.
