Representing Sex and Gender Information in Biomedical Research.

In medicine and biomedical research, sex- and gender-related aspects are ubiquitous. If not considered adequately, a lower quality of research data can be expected together with a lower generalizability of study results with real-world settings. From a translational perspective, a lack of sex- and gender-sensitivity in acquired data can have negative implications for diagnosis, treatment (outcome and side effects), and risk prediction. To establish improved recognition and reward settings we set out to develop a pilot of systemic sex and gender awareness in a German medical faculty, with actions such as implementing equality in routine clinical practice and research, as well as in scientific practice (incl. science education). We believe that the change of culture will have a positive effect on research outcomes, lead to a rethinking in the scientific domain, foster sex- and gender-related clinical studies, and influence the design of good scientific practices.

Rho kinase inhibition mitigates sunitinib-induced rise in arterial pressure and renal vascular resistance but not increased renal sodium reabsorption.

OBJECTIVES: The therapeutic use of the vascular endothelial growth factor (VEGF) antagonist sunitinib is limited by sunitinib-induced hypertension. The hypotheses were tested that sunitinib increases renal vascular resistance (RVR) and renal Na+ reabsorption, and that Rho kinase (ROCK) inhibition blunts sunitinib-induced hypertension. METHODS: Sunitinib actions on human and rat resistance arteries were investigated by myography. The effects of sunitinib alone or in combination with a ROCK inhibitor on arterial pressure and renal function were investigated in rats by radiotelemetry, renal function and metabolism studies accompanied by biochemical, molecular and histological analyses. RESULTS: Sunitinib blunted agonist-induced vasoconstriction and facilitated endothelium-dependent vasodilation. Within 4 days, sunitinib treatment caused arterial pressure and RVR to rise by 30 mmHg and 5 mmHg × ml × min × g kidney weight, respectively, accompanied by reduced glomerular filtration rate and fractional Na+ excretion with unaffected fractional Li+ excretion. ROCK inhibition blunted sunitinib-induced hypertension and prevented the early rise in RVR, but not the decrease in fractional Na+ excretion, which may explain its modest effect on sunitinib-induced hypertension. CONCLUSION: Our data indicate that early sunitinib-induced hypertension is associated with modest alterations in renal vascular function, but markedly increased renal sodium reabsorption, probably due to direct actions of the VEGF antagonist on the collecting duct, suggesting that VEGF receptors regulate renal Na+ absorption.

Applying the Gender Lens to Risk Factors and Outcome after Adult Cardiac Surgery.

BACKGROUND: Applying the gender lens to risk factors and outcome after adult cardiac surgery is of major clinical interest, as the inclusion of sex and gender in research design and analysis may guarantee more comprehensive cardiovascular science and may consecutively result in a more effective surgical treatment as well as cost savings in cardiac surgery. METHODS: We have reviewed classical cardiovascular risk factors (diabetes, arterial hypertension, hyperlipidemia, smoking) according to a gender-based approach. Furthermore, we have examined comorbidities such as depression, renal insufficiency, and hormonal influences in regard to gender. Gender-sensitive economic aspects have been evaluated, surgical outcome has been analyzed, and cardiovascular research has been considered from a gender perspective. RESULTS: The influence of typical risk factors and outcome after cardiac surgery has been evaluated from a gender perspective, and the gender-specific distribution of these risk factors is reported on. The named comorbidities are listed. Economic aspects demonstrated a gender gap. Outcome after coronary and valvular surgeries as well as after heart transplantation are displayed in this regard. Results after postoperative use of intra-aortic balloon pump are shown. Gender-related aspects of clinical and biomedical cardiosurgical research are reported. CONCLUSIONS: Female gender has become an independent risk factor of survival after the majority of cardiosurgical procedures. Severely impaired left ventricular ejection fraction independently predicts survival in men, whereas age does in females.

Cardiac surgery in dialysis-dependent patients: impact of gender on early outcome in single-center experience with 204 consecutive cases.

BACKGROUND: This study evaluates the impact of gender in dialysis-dependent patients undergoing cardiac surgery. METHODS: We retrospectively identified 204 dialysis-dependent patients (68.6% male, aged 66.6 ± 9.9 years) with end-stage renal disease undergoing cardiac surgery and compared them to a propensity-score-pair-matched control collective. RESULTS: A 30-day mortality was 13.2% (14/106) for coronary artery bypass grafting (CABG), 19.3% (6/31) for aortic valve replacement (AVR), and 23.8% (16/67) for combined procedures. Postoperative chest tube output was significantly higher in men (1,007 ± 946 mL) versus women (687 ± 598 mL, p = 0.014). Compared with a propensity-score-pair-matched control collective of 204 patients, we identified significant differences in terms of 30-day mortality: overall mortality revealed 17.6 versus 4.6% (p = 0.0001), 13.2 versus 3.4% (p = 0.014) for CABG, 19.3 versus 0% (p = 0.051) for AVR, and 23.8 versus 9.1% (p = 0.02) for combined procedures. CONCLUSION: Multivariate analysis identified preoperative myocardial infarction, prolonged extracorporeal circulation time, operation time, and surgical reexploration as independent predictors of 30-day mortality. There was a higher occurrence of bleeding complications in men that remained significant even after correction for body surface area.

The Rho kinase inhibitor SAR407899 potently inhibits endothelin-1-induced constriction of renal resistance arteries.

OBJECTIVES: Increased renal vascular resistance contributes to the pathogenesis of hypertension. The new Rho kinase (ROCK) inhibitor SAR407899 more potently lowers arterial pressure than the commercially available ROCK inhibitor Y27623. We tested whether ROCK inhibition more effectively reduced agonist-induced vasoconstriction in renal than in nonrenal resistance arteries and if SAR407899 more potently inhibits agonist-induced vasoconstriction than Y27632. METHODS: The effects of the ROCK inhibitors on endothelin-1 (ET-1) induced vasoconstriction were investigated in isolated renal and coronary arteries from lean, normotensive Dark Agouti and obese, type 2 diabetic Zucker diabetic fatty (ZDF) rats as well as in isolated human resistance arteries from the kidney and thymus. Vascular ROCK mRNA abundance was studied by real-time PCR (RT-PCR). RESULTS: ET-1-induced constriction depended more on ROCK in rat and human renal resistance arteries than in rat coronary or human thymic arteries, respectively. SAR407899 was more effective than Y27632 in reducing ET-1-induced vasoconstriction in ZDF rat renal resistance arteries. Maximum ET-1-induced vasoconstriction in SAR407899-treated and Y27632-treated human renal resistance arteries was 23 ±â€Š5 and 48 ±â€Š6% of control values, respectively. Transcripts of both ROCK isoforms were detected in rat and human renal resistance arteries. In human thymic arteries, only the ROCK2 transcript was found. CONCLUSION: ET-1-induced vasoconstriction is more ROCK-dependent in renal than in nonrenal resistance arteries. SAR407899 causes a greater inhibition of ET-1-induced vasoconstriction in renal resistance arteries from ZDF rats and patients than Y27632. The greater efficacy in renal vessels may contribute to the higher antihypertensive potency of SAR407899 compared with Y27632.