Gender Differences in Cardiac Ischemic Injury and Protection—Experimental Aspects

Abstract

This review summarizes some available information on gender differences of myocardial injury with particular attention to experimental approach. It has been observed that significant gender differences exist already in normal heart. They involve among others cardiac growth, contractile function, calcium metabolism and function of mitochondria. Differences, characteristic of the normal myocardium, generate the logical presumption of the different reaction of the male and female heart to various pathogenic factors. Most of the experimental studies confirm the clinical observations: increased resistance of the female heart to ischemia/reperfusion injury was shown in dogs, rats, mice and rabbits. Furthermore, gender differences in the ischemic tolerance of the adult myocardium can be influenced by interventions (e.g. hypoxia) imposed during the early phases of ontogenetic development. The already high tolerance of the adult female heart can be increased by adaptation to chronic hypoxia and ischemic preconditioning. It seems that the protective effect depends on age: it was absent in young, highly tolerant heart but it appeared with the decrease of natural resistance during aging. Both experimental and clinical studies have indicated that female gender influences favorably also the remodeling and the adaptive response to myocardial infarction. It follows from the data available that male and female heart differs significantly in many parameters under both physiological and pathological conditions. Detailed molecular and cellular mechanisms of these differences are still unknown; they involve genomic and non-genomic effects of sex steroid hormones, particularly the most frequently studied estrogens. The cardiovascular system is, however, influenced not only by estrogens but also by other sex hormones, e.g. androgens. Moreover, steroid hormone receptors do not act alone but interact with a broad array of co-regulatory proteins to alter transcription. The differences are so important that they deserve serious consideration in clinical practice in search for proper diagnostic and therapeutic procedures.

Structural Composition of Myocardial Infarction Scar in Middle-aged Male and Female Rats

“…Despite a growing number of clinical observations demonstrating sex-related differences in the cardiac adaptation to postischemic injury (Kwon et al 2009;Ostadal et al 2009;Vaccarino 2010;Vaccarino et al 2011), the experimental findings related to sex-specific alterations during post-MI remodeling and especially scar formation remained obscure. Most of these data were from experiments either exploring the earlier stages of post-MI healing in mice (Cavasin et al 2004;Gao et al 2005;Fang et al 2007;Wang F et al 2007) or analyzing cardiac remodeling and LV functional performance during the chronic post-MI phases in rats (Pfeffer MA et al 1979;Litwin et al 1999;Jain et al 2002).…”

Interaction of Risk Factors, Comorbidities, and Comedications with Ischemia/Reperfusion Injury and Cardioprotection by Preconditioning, Postconditioning, and Remote Conditioning

“…The already high tolerance of the adult female heart can be increased further by ischemic preconditioning. However, it seems that this protective effect of preconditioning in female animals depends on age: it was absent in the young female rat heart but it appeared with the decrease of resistance toward ischemia/reperfusion injury during aging (Ostadal et al, 2009). An increased resistance toward ischemia/reperfusion injury in aged female hearts could also be restored by a PKC«-activator administered before ischemia, and restoration of protection was associated with an enhanced mitochondrial PKC«-translocation (Lancaster et al, 2011).…”

Effect of Tulbaghia violacea on the blood pressure and heart rate in male spontaneously hypertensive Wistar rats

“…The SHR was used in this study as it (i) mimics human HTN remarkably well (ii) allows studies in chronic, stable disease, (iii) produces symptoms which are predictable and controllable, (iv) satisfied economical, technical and animal welfare considerations, and (v) allows measurement of relevant cardiac, biochemical and haemodynamic parameters (Doggrell & Brown, 1998;Nakao et al, 2009). Male animals were preferred to female animals due to the higher prevalence of HTN in male animals compared to females (Iams & Wexler, 1979;Bachmann et al, 1991;Reckelhoff, 2001;Ostadal et al, 2009;Valenti et al, 2009). Young adult rats (aged < 5 months) were also used as haemodynamic properties such as HR, CO, BP and related vascular parameters, have been found to change during the lifetime of rats (Roberts & Goldberg, 1976).…”