Spleen Perfusion as an Index of Gender Impact on Sympathetic Nervous System Response to Exercise.

Francesco Lanfranchi,Silvia Chiola,Stefano Raffa,Maria Isabella Donegani,Matteo Bauckneht,Alberto Miceli,Carlo Delucchi,Vanessa Cossu,Michele Pennone,Cecilia Marini,Silvia Morbelli,Sara Maggio,Francesca D'Amico,Gianmario Sambuceti

doi:10.3389/fphys.2021.780713

Abstract

Objective: Sympathetic nervous system (SNS) reaction to exercise is gender dependent. Nevertheless, clinically applicable methods to identify this difference are still missing. An organ largely sensitive to SNS is the spleen whose response to exercise can be easily evaluated, being included in the field of view of myocardial perfusion imaging (MPI). Here, we aimed to verify whether gender interferes with the spleen perfusion and its response to exercise.Methods: For this purpose, we evaluated 286 original scans of consecutive patients submitted to MPI in the course of 2019. Our standard procedure implies a single-day stress-rest sequence with a gap of ≥2 h between the administrations of 180 and 500 MBq of 99mTc-Sestamibi, respectively. Imaging is performed 30 min after radiotracer administration, with scan duration set at 25 and 35 s per view, respectively. Non-gated scans were reconstructed with the filtered back-projection method. A volume of interest was drawn on the spleen and heart to estimate the dose-normalized average counting rate that was expressed in normalized counts per seconds (NCPS).Results: In all subjects submitted to exercise MPI (n = 228), NCPS were higher during stress than at rest (3.52 ± 2.03 vs. 2.78 ± 2.07, respectively; p < 0.01). This effect was not detected in the 58 patients submitted to dipyridamole-stress. The response to exercise selectively involved the spleen, since NCPS in heart were unchanged irrespective of the used stressor. This same response was dependent upon gender, indeed spleen NCPS during stress were significantly higher in the 75 women than in the 153 men (3.86 ± 1.8 vs. 3.23 ± 1.6, respectively, p < 0.01). Again, this variance was not reproduced by heart. Finally, spleen NCPS were lower in the 173 patients with myocardial reversible perfusion defects (summed difference score ≥3) than in the remaining 55, despite similar values of rate pressure product at tracer injection.Conclusion: Thus, exercise interference on spleen perfusion can be detected during MPI. This effect is dependent upon gender and ischemia confirming the high sensitivity of this organ to SNS activation.

Highlights

In patients with coronary artery disease (CAD), the activation of the sympathetic nervous system (SNS) contributes to trigger ischemic episodes during physical effort, since the sudden increase in arterial pressure, heart rate, and cardiac contractility augment myocardial oxygen consumption, possibly leading to an inadequate blood flow supply downstream from a severe coronary stenosis (L’Abbate et al, 1999).The capability to inhibit these SNS effects justifies the wide clinical use of beta-blocking agents in anginal patients
Prevalence of patients with documented CAD and submitted to myocardial perfusion imaging (MPI) to characterize site and severity of myocardial ischemia was distributed between the two stressors
The relevance of the present findings relies on the direct interaction between spleen and heart, that has been found since the late 1940s (Rein, 1949) with the evidence of an improved myocardial contractility in the presence of hypoxia, after stimulation of splenic nerves

Summary

Introduction

In patients with coronary artery disease (CAD), the activation of the sympathetic nervous system (SNS) contributes to trigger ischemic episodes during physical effort, since the sudden increase in arterial pressure, heart rate, and cardiac contractility augment myocardial oxygen consumption, possibly leading to an inadequate blood flow supply downstream from a severe coronary stenosis (L’Abbate et al, 1999).The capability to inhibit these SNS effects justifies the wide clinical use of beta-blocking agents in anginal patients. F., 1999; Wilmot et al, 2015; EUGenMed Cardiovascular Clinical Study Group et al, 2016; Mehta et al, 2016; Bots and Peters, 2017) This difference agrees with the divergent SNS modulation of systemic hemodynamics between women and men that has been observed both in humans (Hinojosa-Laborde et al, 1999; Weitz et al, 2001; Dart and Du, 2002; Hart et al, 2009; Momen et al, 2010; Briant and Charkoudian, 2016) and experimental models (Luksha et al, 2005). It raises the need for a more detailed comprehension of the “gender specificity” of sympathetic response to systemic signals

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Conclusion