Effects of intermittent lower limb ischaemia on coronary blood flow and coronary resistance in pigs.
OBJECTIVE
Intermittent limb ischaemia prior to cardiac ischaemia is a cardioprotective stimulus. This study was to investigate whether this peripheral stimulus had any effects on basal coronary blood flow and resistance, and to explore its potential mechanisms by studying the effect of femoral nerve transection and Katp blockade by glibenclamide.


METHODS
Remote ischaemic preconditioning (rIPC) was induced by four 5-min cycles of lower limb ischaemia. Coronary resistance was measured using standard formulae and coronary blood flow in the left anterior descending artery (LAD) by a flow probe. In experiment 1, coronary ischaemia was induced by inflation of a cuff placed around the mid-LAD, and inflated until cessation of flow. Left ventricular (LV) function was assessed using dp/dt and Tau at 1 and 30 min of ischaemia. Experiment 1: 20 pigs were randomized to control (n = 6), rIPC (n = 7) or femoral nerve transection + rIPC (n = 7) groups. The femoral nerve was transected before the rIPC protocol. All data were collected at fixed heart rates of 120 bpm. Coronary resistance was decreased and flow was increased significantly by the rIPC stimulus (P = 0.003, P = 0.016, paired t-test), and these changes were preserved after femoral nerve transection. Experiment 2: 19 pigs were randomized to control (n = 5), rIPC (n = 8) or glibenclamide-treated rIPC (n = 6) groups. Data were collected at baseline, and during incremental pacing between 120 and 180 bpm.


RESULTS
Experiment 1: Coronary resistance was decreased and flow was increased significantly by rIPC stimulus (P = 0.003, P = 0.016, paired t-test), and these changes were preserved after femoral nerve transaction. rIPC was associated with superior LV function (dp/dt(max)) at 30 min, compared with controls and the rIPC + femoral nerve transaction group. Experiment 2: Coronary resistance was significantly lower, and LAD flow was significantly higher in rIPC group (P < 0.0001, P = 0.0008, two-way anova). These effects were reversed in the glibenclamide group.


CONCLUSIONS
The rIPC stimulus leads to reduced coronary resistance and increased flow. This effect, while modified by glibenclamide appears to be a generic effect of remote ischaemia rather than a direct preconditioning effect.
Shimizu
M
M
Division of Cardiology, Hospital for Sick Children, Toronto, ON, Canada.
Konstantinov
I E
IE
Kharbanda
R K
RK
Cheung
M H
MH
Redington
A N
AN
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D003331:Coronary Vessels / Q000502:physiology; D005267:Femoral Nerve / Q000601:surgery; D005905:Glyburide / Q000494:pharmacology; D006614:Hindlimb; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D023421:Models, Animal; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D016277:Ventricular Function, Left / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D005905:Glyburide