Effects of ischemic preconditioning on myocardial perfusion, function, and microvascular regulation.
BACKGROUND
Ischemic preconditioning (PC) has been advocated as a method to preserve myocardial function and perfusion during minimally invasive direct coronary bypass (MIDCAB). We examined the effects of PC on indexes of myocardial function, perfusion, and endothelial and beta-adrenergic coronary regulation after 30 minutes of ischemia and 60 minutes of reperfusion (IR).


RESULTS
Five groups of pigs were studied: (1) PC-IR: PC by 3 cycles of 5-minute left anterior descending coronary artery occlusion (CO) and 5-minute reperfusion (Rep) + 30 minutes of CO + 60 minutes of Rep; (2) IR alone: 30 minutes of CO + 60 minutes of Rep; (3) PC alone; (4) PC-IR-glibenclamide (GLIB): PC-IR + infusion of GLIB; (5) control: noninstrumented. Reactivity (in vitro) of coronary arterioles (70 to 150 microns) from the myocardial area at risk was examined with video microscopy. beta-Adrenergic microvascular relaxations to isoproterenol, forskolin, and 8-bromo-cAMP were significantly reduced after IR alone (P < 0.05 versus control, 2-way ANOVA). PC before IR restored these responses to normal (P < 0.05 PC-IR versus IR alone), and GLIB abolished this effect of PC. Subepicardial endothelium-dependent microvascular relaxation to ADP was significantly reduced after IR alone (P < 0.01 versus control) but was preserved in both the PC-IR and PC-IR-GLIB groups (P < 0.05 versus IR alone). The response of vessels to ADP from the subendocardium was significantly reduced in all groups compared with the control response (all P < 0.05 versus control). Nitroprusside elicited a similar response in vessels from all groups. PC before IR did not affect the reduced myocardial percent segmental shortening or left ventricular maximal dP/dt, did not affect myocardial perfusion in the subepicardium or subendocardium, and did not change expression of the inducible or the constitutively expressed isoforms of nitric oxide synthase.


CONCLUSIONS
PC before IR preserves beta-adrenergic signal transduction in coronary smooth muscle through a KATP channel mechanism, whereas PC preserves endothelium-dependent relaxation in the subepicardium through a mechanism not related to KATP channels or the enhanced expression of nitric oxide synthase. Nevertheless, PC does not improve short-term myocardial function or baseline myocardial perfusion after IR. Thus, the short-term beneficial role of PC in myocardial protection during MIDCAB may be limited.
Tofukuji
M
M
Department of Surgery, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Metais
C
C
Li
J
J
Hariawala
M D
MD
Franklin
A
A
Vassileva
C
C
Li
J
J
Simons
M
M
Sellke
F W
FW
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000503:physiopathology; D016228:Endothelial Growth Factors / Q000235:genetics; D005260:Female; D006321:Heart / Q000503:physiopathology; D019157:Ischemic Preconditioning, Myocardial; D008222:Lymphokines / Q000235:genetics; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014661:Vasoconstriction / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III