The Annals of Thoracic Surgery, Vol 58, 200-206, Copyright © 1994 by The Society of Thoracic Surgeons
Adenosine and AICA-riboside fail to enhance microvascular endothelial preservation
FW Sellke, M Friedman, SY Wang, RN Piana, HB Dai and RG Johnson
Department of Surgery, Beth Israel Hospital, Boston, MA 02215.
Crystalloid cardioplegia may cause coronary microvascular endothelial
dysfunction during cardiopulmonary bypass. The perioperative administration
of either adenosine or AICA-riboside (acadesine, 5-
aminoimidazole-4-carboxamide-1-ribofuranoside) has been associated with
improved myocardial functional preservation and improved coronary blood
flow after ischemic arrest. To examine if this enhanced recovery of
myocardial function and perfusion may be related to improved endothelial
preservation, pigs were placed on cardiopulmonary bypass and the hearts
were arrested with plain cold, hyperkalemic (K+ = 25 mmol/L) crystalloid
cardioplegia, or cardioplegic solution containing either 0.1 mmol/L
adenosine or 50 mumol/L AICA-riboside, which causes the release of
endogenous adenosine. AICA-riboside (375 mg) also was infused over 30
minutes before cardioplegia in the later group. After 1 hour of ischemic
cardioplegia, hearts were reperfused for 1 hour while the pigs were weaned
from cardiopulmonary bypass. Coronary arterioles (90 to 190 microns in
diameter) from both subepicardial and subendocardial regions of the left
ventricle were studied in vitro in a pressurized, no-flow state with
videomicroscopy. After contraction of vessels by 25% to 40% of the baseline
diameter, drugs were applied extraluminally. Relaxation of control
arterioles to serotonin was slightly greater in vessels from the
subendocardial region compared with vessels from the subepicardial region,
and subendocardial arterioles were more affected by cardioplegia than were
subepicardial vessels. In contrast, relaxations of control microvessels to
bradykinin and the calcium ionophore A23187 were similar in the two
transmural myocardial regions. Responses to bradykinin and A23187 were
significantly and similarly reduced after ischemic arrest with plain
crystalloid cardioplegia.(ABSTRACT TRUNCATED AT 250 WORDS)