(753.2) Direct evidence of a sympathetically-mediated cardio-inotropic response to baroreceptor unloading in rats

Poster Board Number: E427

Liam Stewart (University of British Columbia, University of British Columbia), Liisa Wainman (University of British Columbia, University of British Columbia), Mehdi Ahmadian (University of British Columbia, University of British Columbia), Jennifer Duffy (University of British Columbia, University of British Columbia), Rudi Seethaler (University of British Columbia), Patrick Mueller (Wayne State University), Neil Eves (University of British Columbia), Christopher West (University of British Columbia, University of British Columbia, University of British Columbia)

Rationale: The baroreflex is a cardio-autonomic reflex that is responsible for buffering acute oscillations in blood pressure. Contemporary evidence suggests that, when stimulated, baroreceptors activate a neural reflex arc via two efferent pathways: the vascular-sympathetic arm to control peripheral resistance, and the cardio-vagal arm to control heart rate. However, since sympathetic post-ganglionic fibres innervate both the vasculature and left ventricle (LV) it follows that the heart may also contribute to hemodynamic regulation during baroreceptor unloading through alterations in cardiac inotropy, yet to our knowledge this has not been empirically tested using a load-independent index of LV inotropy.

Aim:  1) To determine whether there is an increase in LV inotropy in response to baroreceptor unloading, and 2) to parse out whether this response occurs via sympathetic activation, parasympathetic withdrawal, or a combination of the two.

Hypotheses: There will be an increase in LV inotropy in response to baroreceptor unloading, and this response will occur via activation of the sympathetic nervous system.

Methods:  10 male Wistar rats were anesthetized (urethane) and instrumented with a LV pressure-volume catheter to measure the maximal rate of pressure generation for a given end-diastolic volume (dP/dtmax–EDV mmHg·s-1·µl-1) as a load-independent metric of cardiac inotropic function. Each rat was then placed in a customized servo-controlled lower-body negative pressure (LBNP) chamber that was programmed to reduce mean arterial pressure (MAP) by 10% for 60s to mechanically unload baroreceptors. The protocol was repeated in the same animal following infusions of lactated ringers (control), esmolol (β1 adrenergic receptor antagonist; blocks cardiac sympathetic transmission), atropine (muscarinic receptor antagonist; blocks cardiac parasympathetic transmission), and esmolol+atropine (full cardiac autonomic blockade). Between-condition differences in LV inotropy were assessed using mixed-models with Bonferroni corrected post-hoc pairwise comparisons.

Results: Under control conditions, dP/dtmax–EDV increased significantly (25.8±4.9 vs 29.9±6.7 mmHg·s-1·µl-1; p=0.002) during unloading. Sympathetic and full cardiac blockade significantly reduced baseline dP/dtmax–EDV (10.8±2.1 and 13.5±3.0 mmHg·s-1·µl-1, respectively; plt;0.001 for both), and abolished the response to baroreceptor unloading (10.6±2.1 and 14.3±4.0 mmHg·s-1·µl-1, respectively; p=0.999 for both). Parasympathetic blockade had no effect on baseline dP/dtmax–EDV (26.1±5.5 mmHg·s-1·µl-1; p=0.999) and the increase in dP/dtmax–EDV during baroreceptor unloading was maintained (30.5±8.3 mmHg·s-1·µl-1; plt;0.001).

Conclusion: These results provide direct evidence of a sympathetically-mediated increase in cardiac inotropic function in response to baroreceptor unloading in rats.

We acknowledge the support of the Natural Sciences and Engineering Research Council of Canada (NSERC), [RGPIN-2020-06240].



Figure 1. Left-ventricular inotropic function at baseline and during baroreceptor unloading following esmolol (18 mg·kg-1·hr-1), atropine (2 mg·kg-1), and complete cardiac autonomic blockade (esmolol+atropine) in the anesthetized rat. dP/dtmax–EDV; maximal rate of pressure generation for a given end-diastolic volume in mmHg·s-1·µl-1.