Vascular K_ATP channels mitigate severe muscle O₂ delivery-utilization mismatch during contractions in chronic heart...

The vascular ATP-sensitive K⁺ (K_ATP) channel is a mediator of skeletal muscle microvascular oxygenation (PO₂mv) during contractions in health. We tested the hypothesis that K_ATP channel function is preserved in chronic heart failure (CHF) and therefore its inhibition would reduce PO₂mv and exacerbate the time taken to reach the PO₂mv steady-state during contractions of the spinotrapezius muscle. Moreover, we hypothesized that subsequent K_ATP channel activation would oppose the effects of this inhibition. Muscle PO₂mv (phosphorescence quenching) was measured during 180s of 1-Hz twitch contractions (∼6V) under control, glibenclamide (GLI, K_ATP channel antagonist; 5mg/kg) and pinacidil (PIN, K_ATP channel agonist; 5mg/kg) conditions in 16 male Sprague-Dawley rats with CHF induced via myocardial infarction (coronary artery ligation, left ventricular end-diastolic pressure: 18±1mmHg). GLI reduced baseline PO₂mv (control: 28.3±0.9, GLI: 24.8±1.0mmHg, p<0.05), lowered mean PO₂mv (average PO₂mv during the overall time taken to reach the steady-state; control: 20.6±0.6, GLI: 17.6±0.3mmHg, p<0.05), and slowed the attainment of steady-state PO₂mv (overall mean response time; control: 66.1±10.2, GLI: 93.6±7.8s, p<0.05). PIN opposed these effects on the baseline PO₂mv, mean PO₂mv and time to reach the steady-state PO₂mv (p<0.05 for all vs. GLI). Inhibition of K_ATP channels exacerbates the transient mismatch between muscle O₂ delivery and utilization in CHF rats and this effect is opposed by PIN. These data reveal that the K_ATP channel constitutes one of the select few well-preserved mechanisms of skeletal muscle microvascular oxygenation control in CHF.