Acute intermittent hypercapnic hypoxia augments left ventricular contractility

Acute intermittent hypercapnic hypoxia (IHH) evokes persistent increases in vascular sympathetic activity and blood pressure. Whether myocardial contractility is enhanced to contribute to this pressor response is unknown. We hypothesized that IHH would augment left ventricular systolic function. Twenty-four healthy participants (nine females; aged 25 ± 4 years) underwent 40 consecutive 1 min bouts of 40 s of hypercapnic hypoxia ( $P_{\mathrm{ET}{O}_2}$ : 48 mmHg; $P_{\mathrm{ETC}{O}_2}$ : +5 mmHg) and 20 s of normocapnic normoxia. Cardiac, haemodynamic, respiratory and sympathetic measurements were made at rest and during three 5 min stages of progressive lower body negative pressure (LBNP) (-15, -30 and -45 mmHg) before and after IHH. Following IHH, stroke work [Δ: 64 mJ; 95% confidence interval (CI) = 14-113; P = 0.007], longitudinal strain (Δ: -0.9%; CI = -0.1 to -1.7; P = 0.007) and single-beat estimates of preload-recruitable stroke work (PRSW_sb; Δ: 0.9 mJ mL^-1; CI = 0.2-1.5; P = 0.004) were enhanced. Across LBNP stages, IHH further enhanced ejection fraction (Δ: 1.0%; CI = 0.0-2.0; P = 0.041), stroke work (Δ: 44 mJ; CI = 23-66; P < 0.001), longitudinal strain (Δ: -0.5%; CI = 0.0 to -0.9; P = 0.047), end-systolic elastance (Δ: 0.15 mmHg mL^-1; CI = 0.05-0.25; P = 0.004) and PRSW_sb (Δ: 0.60 mJ mL^-1; CI = 0.36-0.85; P < 0.001). Linear end-systolic pressure-volume relationships (+0.13 ± 0.06 mmHg mL^-1, P = 0.024) and preload-recruitable stroke work slopes (+0.83 ± 0.17 mJ mL^-1, P < 0.001) were also increased post-IHH. Ventricular stiffness (E/E' ratio) and relaxation (peak diastolic strain rate) were unaltered by IHH (P > 0.236), whereas the passive/active diastolic filling (E/A) ratio was reduced (P = 0.022), potentially via increased atrial kick contribution (P = 0.068). We demonstrate that increased left ventricular systolic function following acute IHH contributes to the pressor response in addition to the established vasopressor arm in humans. KEY POINTS: Acute intermittent hypercapnic hypoxia evokes persistent sympathoexcitation and increased arterial pressure, known to be mediated by increased vasoconstrictor signalling. Chronic intermittent hypoxia increases cardiac contractility associated with cardiac sympathetic and structural remodelling. However, whether increases in contractility manifest acutely following intermittent hypercapnic hypoxia is unknown. We show increases in indices of cardiac systolic performance at rest and across progressive hypovolaemia following acute intermittent hypercapnic hypoxia. Diastolic relaxation was unchanged, but reductions in the ratio of passive filling to atrial kick during diastole, potentially as a result of increased mitral inflow velocity during atrial filling, suggest that the increases in contractility may extend to the atria.