Ketorolac Attenuates the Blood Pressure Response to Plantar Flexion Exercise in Peripheral Arterial Disease Patients


Muller, M., Drew R., Heffernan, M., Blaha C., Sinoway, L. Penn State Hershey Heart and Vascular Institute, Penn State College of Medicine, Hershey, PA

Prostaglandins are produced during skeletal muscle contraction and subsequently stimulate muscle afferent nerves, thereby contributing to the exercise pressor reflex (EPR). Humans with peripheral arterial disease (PAD) have an augmented EPR but the metabolite(s) responsible for this augmented response are not known. Purpose: We tested the hypothesis that intravenous infusion of ketorolac (a non-selective cyclooxygenase inhibitor that reduces prostaglandins) would attenuate the rise in mean arterial blood pressure (MAP) and heart rate (HR) in response to low-intensity plantar flexion exercise in humans with PAD. Methods: Six PAD patients underwent four minutes of one-legged rhythmic plantar flexion (30 contractions/min) in the supine posture. The workload began at 0.5 kg and progressed by 0.5 kg each minute. The leg with more severe PAD was always tested first, followed by a rest period and then the opposite leg. MAP and HR were measured on a beat-by-beat basis; changes from baseline in response to exercise were determined. Rating of perceived exertion (6-20) and leg pain (0-10) were also obtained. Results: Ketorolac did not affect resting MAP (97 ± 3 versus 94 ± 4 mmHg) or HR (58 ± 2 versus 55 ± 2 bpm). During the first 20 seconds of exercise with the most diseased leg, ΔMAP was significantly attenuated with ketorolac (2 ± 2 mmHg) as compared to control (8 ± 2 mmHg, P = 0.017) but ΔHR was similar (7 ± 2 versus 6 ± 1 bpm). During the second and third minutes of exercise, ΔMAP was also significantly attenuated under ketorolac. The less diseased leg displayed similar results. Importantly, subjects rated the exercise bout as “very light” to “fairly light” and average pain ratings were 1 out of 10. Neither perceived exertion nor pain ratings were altered by ketorolac. Conclusions: These data indicate that prostaglandins contribute to the augmented EPR in patients with PAD. Because this response occurred at very low workloads, we speculate that muscle mechanoreceptors are sensitized by cycolooxyegnase products under conditions of chronic limb ischemia.

Supported by NIH P01 HL096570 and UL1 TR000127

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