RESUMEN
OBJECTIVES: Prior studies have examined the association between timing of cardiac surgery after coronary angiography with risk of acute kidney injury, but this remains controversial. The purpose of this study was to investigate the association between interval from coronary angiography to urgent coronary artery bypass grafting with acute kidney injury, and to examine this possible effect in patients with preexisting kidney disease. METHODS: Patients from a single institution undergoing urgent, isolated coronary artery bypass grafting within 7 days of coronary angiography were included. Patients were subdivided by chronic kidney disease stage and angiography-to-surgery interval. Locally estimated scatterplot smoothing was used to evaluate the functional relationship of the probability of acute kidney injury and time interval. Adjusted odds ratios were calculated for each time interval group compared against the Day 0 to 1 interval group, controlling for multiple covariates. Analyses were repeated for each chronic kidney disease subgroup. RESULTS: A total of 2249 patients were included in this study. There were 271 (12.0%) patients with postoperative acute kidney injury. Plots demonstrated a decreasing risk of kidney injury from Day 0 to 1 to Day 3 following coronary angiography. Adjusted odds ratios also showed a significant decrease in risk of kidney injury on Day 3 compared with Day 0 to 1. Analyses repeated for each chronic kidney disease stage showed similar trends. CONCLUSIONS: For patients undergoing urgent coronary artery bypass grafting, there is a decreased risk of kidney injury in those having surgery on day 3 after coronary angiography compared with those having surgery on Day 0 to 1, regardless of preexisting kidney disease.
RESUMEN
Previously, we showed that peripheral administration of 6ß-hydroxytestosterone, a CYP1B1 (cytochrome P450 1B1)-generated metabolite of testosterone, promotes angiotensin II-induced hypertension in male mice. However, the site of action and the underlying mechanism by which 6ß-hydroxytestosterone contributes to angiotensin II-induced hypertension is not known. Angiotensin II increases blood pressure by its central action, and CYP1B1 is expressed in the brain. This study was conducted to determine whether testosterone-CYP1B1 generated metabolite 6ß-hydroxytestosterone locally in the brain promotes the effect of systemic angiotensin II to produce hypertension in male mice. Central CYP1B1 knockdown in wild-type (Cyp1b1+/+) mice by intracerebroventricular-adenovirus-GFP (green fluorescence protein)-CYP1B1-short hairpin (sh)RNA attenuated, whereas reconstitution of CYP1B1 by adenovirus-GFP-CYP1B1-DNA in the paraventricular nucleus but not in subfornical organ in Cyp1b1-/- mice restored angiotensin II-induced increase in systolic blood pressure measured by tail-cuff. Intracerebroventricular-testosterone in orchidectomized (Orchi)-Cyp1b1+/+ but not in Orchi-Cyp1b1-/-, and intracerebroventricular-6ß-hydroxytestosterone in the Orchi-Cyp1b1-/- mice restored the angiotensin II-induced: (1) increase in mean arterial pressure measured by radiotelemetry, and autonomic imbalance; (2) reactive oxygen species production in the subfornical organ and paraventricular nucleus; (3) activation of microglia and astrocyte, and neuroinflammation in the paraventricular nucleus. The effect of intracerebroventricular-6ß-hydroxytestosterone to restore the angiotensin II-induced increase in mean arterial pressure and autonomic imbalance in Orchi-Cyp1b1-/- mice was inhibited by intracerebroventricular-small interfering (si)RNA-androgen receptor (AR) and GPRC6A (G protein-coupled receptor C6A). These data suggest that testosterone-CYP1B1-generated metabolite 6ß-hydroxytestosterone, most likely in the paraventricular nucleus via AR and GPRC6A, contributes to angiotensin II-induced hypertension and neuroinflammation in male mice.