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Impact of castration on changes in left ventricular diastolic pressure-volume relations induced by chronic adrenergic
Bryan Hodson1, Angela J Woodiwiss, Gavin R Norton
1Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Insights
Surgical castration did not prevent left ventricular (LV) dilatation in rats treated with isoproterenol (ISO). This suggests testosterone does not protect against adverse cardiac remodeling from chronic beta-adrenergic activation.
Area of Science:
- Cardiology
- Endocrinology
- Physiology
Background:
- Reduced testosterone levels are linked to heart failure and predict outcomes.
- The protective role of low testosterone against adverse left ventricular (LV) remodeling is unknown.
- Testosterone replacement therapy may offer non-cardiac benefits in heart failure patients.
Purpose of the Study:
- To investigate if surgical castration modifies LV dilatation induced by chronic beta-adrenergic receptor (AR) activation.
- To determine the impact of castration on LV remodeling and systolic dysfunction in response to isoproterenol (ISO).
Main Methods:
- Rats underwent surgical castration or sham operation.
- Rats received daily injections of isoproterenol (ISO) or saline vehicle for 6 months.
- Left ventricular (LV) dilatation was assessed using echocardiography and LV diastolic pressure-volume (P-V) relationships.
- LV systolic chamber function was evaluated using LV endocardial fractional shortening and LV end systolic elastance.
Main Results:
- Chronic beta-AR activation with ISO caused significant LV dilatation in sham-castrated rats.
- Castration did not alter the extent of LV dilatation or the LV volume intercept (V(0)) induced by ISO.
- Chronic beta-AR activation did not impair LV systolic chamber function in either sham-castrated or castrated rats.
Conclusions:
- Castration does not influence the degree of LV dilatation caused by chronic adrenergic activation in this animal model.
- Adverse LV remodeling precedes systolic chamber dysfunction in this model of chronic beta-adrenergic activation.
- The findings suggest testosterone is not a primary protective factor against ISO-induced LV remodeling.
Abstract:
A reduced testosterone concentration characterizes heart failure and independently predicts outcomes. Although testosterone replacement therapy may have non cardiac-related therapeutic benefits in heart failure, whether reduced testosterone concentrations protect against adverse left ventricular remodeling (LV dilatation) is uncertain. We therefore evaluated whether surgical castration modifies LV dilatation after 6 months of daily injections of the β-adrenergic receptor (AR) agonist, isoproterenol (ISO) (0.015 mg·kg(-1)·d(-1)), to rats. The extent of LV dilatation and LV systolic chamber dysfunction were determined using both echocardiography and isolated perfused heart procedures. The extent of LV dilatation was determined from LV diastolic pressure-volume (P-V) relationships. As compared with the saline vehicle-treated group, after 6 months of β-AR activation in sham-castrated rats, a marked right shift in the LV diastolic P-V relationship was noted with an increased LV volume intercept at 0 mm Hg diastolic pressure (LV V(0) in milliliters) (ISO = 0.38 ± 0.02, saline vehicle = 0.30 ± 0.02, P < 0.05). However, chronic β-AR activation did not alter LV systolic chamber function either in vivo (LV endocardial fractional shortening, echocardiography) or ex vivo (LV end systolic elastance). Although castration decreased body weight, castration failed to modify the impact of ISO on the LV diastolic P-V relationships or the LV volume intercept at 0 mm Hg diastolic pressure (LV V(0) in milliliters) (castration ISO = 0.35 ± 0.02, castration saline vehicle = 0.27 ± 0.03, P < 0.05). In conclusion, castration does not influence the extent of LV dilatation induced by chronic adrenergic activation in an animal model, where adverse LV remodeling precedes LV systolic chamber dysfunction.
