Enhanced protection with ischemic preconditioning against endothelial ischemia-reperfusion injury during the luteal phase of the menstrual cycle in premenopausal women

Abstract

PURPOSE: In premenopausal women, we have previously shown that the capacity of remote ischemic preconditioning (IPC) to protect against endothelial ischemia/reperfusion (I/R) injury is diminished during the early follicular phase of the menstrual cycle compared with the late follicular phase. The aim of this research was to extend our initial findings by determining how the luteal phase of the menstrual cycle influences remote IPC to alleviate endothelial I/R injury in a second sample of women. It was hypothesized that the capacity of remote IPC to alleviate endothelial I/R injury will be greater during the luteal phase of the menstrual cycle compared with the early follicular phase. METHODS: Eleven premenopausal eumenorrheic women (age 24±3 yr.) not taking any contraceptive medications were studied. Primary outcomes were the assessment of vascular endothelial function measured during the early follicular (after onset of menses; days 1-6) and at the peak luteal phase (days 21-24 after positive urine progesterone test). Endothelium-dependent vasodilation was assessed by the forearm blood flow (FBF) response to reactive hyperemia using venous occlusion plethysmography with and without endothelial I/R injury (20 min brachial artery ischemia, 15 min reperfusion) when preceded by remote IPC (3×5 min cycles of arm ischemia). RESULTS: Without endothelial I/R injury, peak FBF was similar (P=0.25) between the early follicular (26.6±5.0 ml/100 ml tissue/min) and luteal phases (25.1±3.9 ml/100 ml tissue/min). In contrast, there was a significant main effect (P<0.001) of cycle phase on the capacity of IPC to protect against endothelial I/R injury. During the early follicular phase, peak FBF was significantly (P<0.001) diminished 18% with endothelial I/R injury (from: 26.6±5.0 to 21.8±4.6 ml/100 ml tissue/min) despite remote IPC. As a result, total FBF during reactive hyperemia (area under the curve) was decreased ~25% (P=0.006) after (45.1±10.0) compared with before (59.8±14.1 ml/100 ml tissue) endothelial I/R injury. However, during the luteal phase endothelial I/R injury was prevented with remote IPC. Indeed, in the presence of endothelial I/R injury, peak FBF was well preserved (from: 25.1±3.9 to 27.2±5.7 ml/100 ml tissue/min; P=0.267). As a result, total FBF was similar (P=0.774) after (55.9±13.3) compared with before (51.7±13.8 ml/100 ml tissue) endothelial I/R injury. The level of endothelial protection from I/R injury with remote IPC during the luteal phase was similar (P=0.34) to the late follicular phase in our previous study. CONCLUSIONS: IPC-mediated vascular endothelial protection is robust during the luteal phase of the menstrual cycle but wanes in the early follicular phase. Greater circulating estrogens and perhaps progesterone during the luteal phase may contribute to the protective benefits of IPC in women, and sheds light about how cardioprotection may change with ovarian hormone deficiency with the menopause transition. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.