Effects of intermittent lower limb ischaemia on coronary blood flow and coronary resistance in pigs M. Shimizu, 1 I. E. Konstantinov, 2 R. K. Kharbanda, 1 M. H. Cheung 1 and A. N. Redington 1 1 Division of Cardiology, Hospital for Sick Children, Toronto, ON, Canada 2 Division of Cardiovascular Surgery, Hospital for Sick Children, Toronto, ON, Canada Received 3 April 2006, revision requested 17 May 2006, final revision received 23 November 2006, accepted 11 December 2006 Correspondence: Prof. Andrew N. Redington, Division of Cardiology, Hospital for Sick Children, 555 University Avenue, Toronto, ON, Canada M5G 1X 8. E-mail: andrew.redington@sickkids.ca Abstract Aim: Intermittent limb ischaemia prior to cardiac ischaemia is a cardio- protective 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 des- cending 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 ¼ 6), rIPC (n ¼ 7) or femoral nerve transec- tion + rIPC (n ¼ 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 ¼ 0.003, P ¼ 0.016, paired t-test), and these changes were preserved after femoral nerve transection. Experiment 2: 19 pigs were randomized to control (n ¼ 5), rIPC (n ¼ 8) or glibenclamide-treated rIPC (n ¼ 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 ¼ 0.003, P ¼ 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, com- pared 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 ¼ 0.0008, two-way anova). These effects were reversed in the glibenclamide group. Conclusion: 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. Keywords coronary resistance, femoral nerve transection, ischaemia, potassium channels, remote ischaemic preconditioning. Acta Physiol 2007, 190, 103–109 Ó 2007 The Authors Journal compilation Ó 2007 Scandinavian Physiological Society, doi: 10.1111/j.1748-1716.2007.01667.x 103