Sympathetic Activity and Diastolic Dysfunction in HFrEF: Muscle metaboreflex induced changes in left ventricle passive filling pressure
Authors: Mannozzi Joseph , Aoun Kamel , Al-Hassan Mohamed , Alvarez Alberto , Lessanework Beruk , Chung Charles , O'Leary Donal 
Published: May 2023

During exercise, activation of afferents within active skeletal muscle improves cardiovascular performance through reflex increases in cardiac output (CO), ventricular function, and central blood volume mobilization - termed the muscle metaboreflex. In heart failure (HF) ventricular function is depressed and muscle metaboreflex activation (MMA) does little to improve ventricular performance. In HF reflex characteristics shift to from cardio-centric mediated increases in mean arterial pressure via increases in ventricular function and central blood volume mobilization, to profound vasoconstriction of not only the peripheral circulation but also the myocardium which thereby further limits increases in contractility. Impaired increases in CO during MMA in HF are not a result of reductions in preload, but are primarily a result of reduced contractile function via pathology and enhanced negative reflex characteristics. In HF, there are attenuated improvements in the rate of left ventricular relaxation just after the cessation of contraction during MMA vs. that observed in healthy subjects. To what degree MMA also induces alterations in passive left ventricular filling is unknown. We sought to determine if rate of rise in left ventricular passive filling pressure (LVPFR) (an index of ventricular stiffness) during MMA in HF was significantly increased, thus suggesting not only pathological but sympathetically mediated ventricular stiffening. Using conscious, chronically instrumented canines who were observed before and after the induction of HF via rapid ventricular pacing we analyzed 10 ventricular beats in each experiment taken from steady state values at rest, during volitional exercise (3.2 km/hr), and during volitional exercise (3.2 km/hr) with MMA achieved via imposed reductions in hindlimb blood flow by ~ 50%. From these 10 beats the rate of ventricular filling pressure was assessed prior to the atrial kick. We observed in healthy subjects that neither exercise nor MMA significantly altered LVPFR. In HF the LVPFR was significantly increased from rest to exercise (312 ± 54 to 449 ± 76 mmHg/sec) and in response to MMA (449 ± 76 to 726 ± 111 mmHg/sec). The effect of heart failure on LVPFR at rest (217 ± 22 vs 312 ± 54 mmHg/sec P=0.051) and during exercise (288 ± 47 to 449 ± 76 mmHg/sec P=0.059) approached significance, but only reached significance during MMA (385 ± 58 to 726 ± 111 mmHg/sec P= 0.030) when compared to healthy controls. We conclude that in HF, MMA significantly increases the LVPFR thereby indicating reflex mediated increases in ventricular stiffness in addition to those induced as a result of HF. Increases in ventricular stiffness during MMA may be an additional mechanism that limits CO, reducing peripheral perfusion during exercise and potentially leading to sudden cardiac death.

This project was funded by NHLBI grant HL-055473.

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.