Blood Flow Restriction Training in Acute Systolic Heart Failure Elicits Muscle Metaboreflex Activation

Blood flow restriction training (BFRT) uses external cuff occlusion to limit blood flow to exercising muscle which reduces the time and exertion required for improved performance, making it a promising alternative to traditional endurance and resistance exercise particularly for patients with heart failure (HF) who often exhibit reduced exercise capacity. Previous studies have demonstrated that the recommended occlusion pressures for BFRT in healthy subjects can activate the muscle metaboreflex (MMR), a pressor reflex originating in the exercising skeletal muscle due to an accumulation of metabolites which stimulate skeletal muscle afferents. In healthy individuals, MMR activation causes substantial increases in mean arterial pressure (MAP) primarily driven by elevated cardiac output due to enhanced ventricular function and central blood volume mobilization. However, in HF, the mechanisms of the reflex pressor response shift towards increased peripheral vasoconstriction. This vasoconstriction occurs even in the coronary vasculature thereby limiting O 2 supply and ventricular function which could elicit ventricular ischemia, arrhythmias and even sudden cardiac death. To date, few studies have evaluated the MMR during a BFRT bout. Furthermore, no study has explored whether MMR is triggered during BFRT in HF using arterial occlusion pressures within the current recommended guidelines. Thus, we explored if the recommended arterial occlusion pressures utilized in BFRT would elicit activation of the MMR in HF and whether there is a safe level of occlusion at which BFRT can be performed in HF without MMR activation. We utilized our chronically instrumented conscious canine model to elicit blood flow restriction training during endurance exercise via graded reductions in hindlimb perfusion pressure at 3.2 km/hr -0% grade before and after induction of acute systolic HF (rapid ventricular pacing;225-250 BPM ~30 days). We explored whether graded levels of arterial occlusion pressure from 60% - 80% would elicit the MMR in HF. We observed that in HF an occlusion pressure of 60% elicited significant MMR mediated increases in both MAP and Heart Rate (HR). Any further increase in occlusion pressure caused progressively larger increases in MAP and HR (slope of MAP-occlusion pressure relationship = -2.1 ± 0.3 mmHg/mmHg, slope of HR = -1.7± 0.6 bpm/mmHg). At 80% occlusion pressure, MAP and HR had risen by 36.3 ± 3.8 mmHg and 29.5 ± 9.4 bpm respectively with little rise in cardiac output (0.5 ± 0.2 L/min HF vs. 2.8 ± 0.6 L/min Control). Since MMR causes substantial increases in sympathetic activity and even frank coronary vasoconstriction in subjects with HF, it is possible that life-threatening cardiac events and potential cardiac damage could occur during strong MMR activation. Thus, our findings highlight the need for caution when implementing BFRT in individuals with cardiovascular disease. We recommend that such patients undertake BFRT only under close medical supervision to mitigate potential adverse events resulting from MMR activation during training. This work was supported by the National Heart Lung and Blood Institute grant HL055473. This work was supported by the National Heart Lung and Blood Institute grant HL055473. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.