Reduced effect of ischemic preconditioning against endothelial ischemia-reperfusion injury with cardiovascular risk factors in humans

The extent that clustered CVD risk factors interfere with ischemic preconditioning (IPC) to protect against microvascular endothelial dysfunction with ischemia-reperfusion (I/R) injury in humans is unclear. We hypothesized that adults with a clustered burden of >= 3 CVD risk factors would demonstrate a reduced capacity of IPC to protect endothelial function with I/R injury. Twenty-two (age: 45 +/- 14 year) adults [12 healthy controls; 10 raised risk (10-year FRS risk score similar to 3%)] were studied using a 2 x 2 randomized cross-over design. Pulse arterial tonometry was used to assess microvascular endothelium-dependent vasodilation during reactive hyperemia in response to endothelial I/R injury (20 min brachial artery occlusion/45 min reperfusion) that was preceded by remote IPC (3 x 5 min ischemia/reperfusion) or mock IPC. In both groups, microvascular reactive hyperemia was reduced similar to 20% (both P < 0.01) after endothelial I/R injury without remote IPC. However, in control subjects remote IPC prevented endothelial I/R injury (from baseline reactive hyperemic ratio: 2.1 +/- 0.4 AU to post I/R injury: 2.5 +/- 0.5 AU; P = 0.09). In contrast, the reactive hyperemia ratio in raised risk subjects was significantly reduced from 2.2 +/- 0.6 AU to 1.9 +/- 0.5 AU (P = 0.0087) despite attempts to induce protection by remote IPC, with the magnitude of reduction similar to their mock IPC trial. The magnitude of remote IPC-mediated endothelial protection against I/R injury was inversely related to the number of risk factors. CVD risk factors diminish the effect of IPC to protect the microvasculature from I/R injury in humans. Translating IPC to clinical practice for vasculoprotection will continue to be challenging in patients with increased CVD risk.

Automated summary

This study aimed to investigate the impact of clustered cardiovascular disease risk factors on the ability of ischemic preconditioning (IPC) to protect microvascular endothelial function against ischemia-reperfusion (I/R) injury in humans. The results showed that individuals with a greater burden of cardiovascular disease risk factors demonstrated a reduced capacity of IPC to protect against I/R injury.