Sex Differences in Left Ventricular Stroke Volume During Muscle Metaboreflex Activation
Authors: Boyes Natasha G. , Nelson Michael D. , Elaschuk Cole , Luchkanych Adam M.S. , Khan M. Rafique , Karjala Geoffrey , Olver T. Dylan 
Published: May 2024

Introduction: Muscle metaboreflex activation (MMA) increases blood pressure, possibly by disproportionate increases in left ventricular (LV) stroke volume (SV) in males compared to females due to greater grip strength and metabolite production. The purpose of this study was to determine the effect of sex on SV during isolated MMA using cardiac MRI in young healthy adults. We hypothesized that SV would increase during MMA to a greater degree in males compared to females, and that this effect would be negated by accounting for grip strength. Methods: Ten males [23(2) yrs] and 10 females [26(5) yrs] underwent cardiac MRI during rest, 30% maximal voluntary contraction (MVC) isometric handgrip exercise (6 min), and isolation of MMA with brachial cuff circulatory occlusion (6 min). SV, end-systolic (ESV) and end-diastolic volumes (EDV) were measured by 2- and 4-chamber cine images and indexed (i) to body surface area to account for body size. Heart rate (HR, ECG) and mean arterial pressure (MAP, brachial cuff) were recorded. Cardiac output index (COi) and total peripheral resistance (TPR) were calculated. Analyses included ANOVA (sex × condition), ANCOVA [100% MVC (M=49(13) kg, F=26(7) kg) covariate], and linear regression. Results: SVi decreased from rest to MMA in males [67(8) to 61(5) mL/m2, p=0.0001] but not females [59(9) to 59(7) mL/m2, p=0.998; interaction p=0.002]. Notably, the reduction in SVi during MMA in males ( p=0.002) but not females ( p=0.957) remained with ANCOVA using MVC as the covariate (interaction p=0.021). ESVi increased during MMA in males [39(5) to 48(10) mL/m2, p<0.0001] but not females [32(5) to 36(6) mL/m2, p=0.092; interaction p=0.029]. MMA decreased both EDVi ( p=0.004) and COi ( p=0.045) and increased both MAP ( p<0.0001) and TPR ( p<0.0001) pooled across sex. HR did not change with MMA in either sex (all p≥0.093). Linear regression revealed significant relationships between ΔSVi and ΔESVi in males ( p=0.002, R2=0.709) but not females ( p=0.223, R2=0.179) and between ΔSVi and ΔTPR in males ( p=0.005, R2=0.649) but not females ( p=0.522, R2=0.053). Conclusions: MMA lowers SVi in males but not females, even when accounting for grip strength and despite similar pressor responses in both groups. These findings from gold-standard MRI suggest differential LV responses to MMA between sexes, potentially related to greater sensitivity to increased TPR in males than females. Thus, sex differences in blood pressure control during MMA may be impacted by differences in LV afterload sensitivity. Further, the blood pressure response to MMA may be primarily mediated through TPR and not CO in healthy young adults. Heart and Stroke Foundation of Canada. This is the full abstract presented at the American Physiology Summit 2024 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.