Conditioning attenuates kidney and heart injury in rats following transient suprarenal occlusion of the abdominal aorta

Abstract

Suprarenal aortic clamping during abdominal aortic aneurysm (AAA) repair results in ischemiareperfusion injury (IRI) in local (i.e. kidney) and distant (i.e. heart) tissue. To investigate perioperative approaches that mitigate IRI-induced tissue damage, Wistar rats underwent suprarenal aortic clamping either alone or in combination with short cycles of ischemic conditioning before and/or after clamping. Serum analysis revealed significant reduction in key biochemical parameters reflecting decreased tissue damage at systemic level and improved renal function in conditioned groups compared to controls (p < 0.05), which was corroborated by histolopathological evaluation. Importantly, the levels of DNA damage, as reflected by the biomarkers 8-oxo-G, γH2AX and pATM were reduced in conditioned versus non-conditioned cases. In this setting, NADPH oxidase, a source of free radicals, decreased in the myocardium of conditioned cases. Of note, administration of 5-HD and 8-SPT blocking key protective signaling routes abrogated the salutary effect of conditioning. To further understand the non-targeted effect of IRI on the heart, it was noted that serum TGF-β1 levels decreased in conditioned groups, whereas this difference was eliminated after 5-HD and 8-SPT administration. Collectively, conditioning strategies reduced both renal and myocardial injury. Additionally, the present study highlights TGF-β1 as an attractive target for manipulation in this context. Abdominal aortic aneurysm (AAA) is a potentially life-threatening entity, relatively common in routine clinical practice 1. Despite the introduction of endovascular aortic aneurysm repair (EVAR) as well as the significant improvements in surgical techniques, grafts, and perioperative care during the last decades, AAA repair still carries a considerable risk of morbidity and mortality 2. One of the main concerns in vascular surgery over the years

Abdominal Aortic Occlusion and the Inflammatory Effects in Heart and Brain

“…Studies have found that inflammatory cytokines directly released from site of injury can induce injury in distant organs [ 8 ]. In this study, we analyzed proinflammatory factors iNOS, TNF- α , IL-1 β , and IL-6, and anti-inflammatory factors Arg-1, TGF- β 1, IL-4, and IL-10 levels in the serum, hippocampus, and left ventricle at 24 hr after reperfusion.…”

“…Heart. Free radical production is a critical player in tissue destruction caused by reperfusion injury [8]. To determine whether AAO can cause oxidative stress induced by I/R, ROS production was assessed.…”

“…However, in this same study, no pathological changes were found within cardiac tissue [ 7 ]. It has been shown that suprarenal AAO for 30 min results in cellular vacuolization, focal interstitial edema, and hemorrhagic infiltration in cardiac tissue [ 8 ]. Furthermore, prior studies have shown that neurologic tissue is intolerant to ischemia, and the hippocampus in particular is especially sensitive to ischemic conditions [ 9 ].…”

“…During I/R, numerous proinflammatory factors, such as inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF- α ), interleukin-1 β (IL-1 β ), and interleukin-6 (IL-6), were rapidly released [ 12 ]. Upregulation of proinflammatory factors can further aggravate tissue damage [ 8 ]. However, anti-inflammatory factors such as arginase-1 (Arg-1), transforming growth factor- β 1 (TGF- β 1), interleukin 4 (IL-4), and interleukin 10 (IL-10) also reflect the extent of tissue damage [ 16 ].…”

Escape from senescence: molecular basis and therapeutic ramifications

“…The escape‐from‐senescence phenomenon could also be a mechanism contributing to this outcome (see the next section). Ever since GL13 discovery, the spectrum of pathological entities has been expanded to include benign, preneoplastic, and neoplastic lesions, while senescent cells have also been recognised in various experimental and ageing contexts (Table 2) [37,106,107,110–137]. In particular, in clinical settings, skin pathologies (nevi, seborrheic, and actinic keratoses), lung, pancreatic, urothelial and laryngeal precancerous lesions, various types of carcinomas following treatment, sarcomas, haematological malignancies (Langerhans histiocytosis), and a variety of tissues from aged organs were included (Table 2).…”