Application of ultrasound microbubble contrast to evaluate the effect of sitaxentan on renal microvascular perfusion in beagles undergoing cardiopulmonary bypass.

BACKGROUND & OBJECTIVE: We aimed to evaluate the effect of sitaxentan on renal microvascular perfusion via application of ultrasound microbubble contrast. METHODS: Male beagles were randomly divided into: Sham, cardiopulmonary bypass (CPB) and sitaxentan-infused (Sit) groups (n = 6). The ascending slope rate (ASR), area under the curve (AUC), derived peak intensity, and time to peak (TTP) were obtained via ultrasound microbubble contrast before CPB (T1), after 1 h CPB (T2), at end of CPB (T3), and 2 h after CPB (T4). RESULTS: Compared with the Sham group, the CPB group had lower ASR of the renal cortex and medulla at T2 - 4, higher AUC and TTP at T3 - 4, and lower derived peak intensity at T4. The ASR at T2 - 4 in the Sit group was lower, TTP was higher at T2 - 4, and AUC was higher at T3 - 4 (P < 0.05). Compared with the CPB group, the Sit group had higher ASR of the renal cortex and medulla at T3 - 4 and AUC and TTP at T3 - 4 (P < 0.05). Compared with that at T1, the ASR of the renal cortex and medulla at T2 - 4 in the CPB group was lower, and AUC and TTP were higher at T3 - 4. The ASR of the renal cortex and medulla at T2 - 4 in the Sit group was lower, TTP was higher at T2 - 4, and AUC was higher at T4 (P < 0.05). CONCLUSIONS: Ultrasound microbubble contrast could be effectively used to evaluate renal microvascular perfusion peri-CPB in beagles, which was prone to decrease and could be improved via pretreatment with sitaxentan.

Blocking retrograde axonal transport of autophagosomes contributes to sevoflurane-induced neuron apoptosis in APP/PS1 mice.

Autophagy, a crucial pathway for the degradation of proteins in eukaryotic cells, is linked to the development of Alzheimer's disease (AD), and the accumulated autophagosomes in the cells resulting in the death of cells. Sevoflurane can impair spatial learning and memory in mice with AD and lead to the apoptosis of nerve cells; however, the underlying mechanisms remain unknown. We aim to explore the effects and underlying mechanisms of sevoflurane in APPswe/PS1ΔE9 double-transgenic mice. 51 heterozygous APPswe/PS1ΔE9 double-transgenic mice were involved and divided into three groups, including control group, sham group and sevoflurane group. Morris water maze experiment was used to test the learning and memory abilities of mice, flow cytometry was conducted to detect apoptosis and mitochondrial membrane potential of brain cells in mice, transmission electron microscopy was used to observe the number of autophagosomes at the axon in mice, and western blot was carried out to detect the expression of Bax, Bcl-2, LC3II, P62, KIF3B and DIC proteins of brain cells in mice. In our study, we found that significantly longer escape latencies, fewer crossings of the platform and shorter time spent in the target quadrant of the morris water maze experiment in the sevoflurane group. Flow cytometry showed cellular apoptosis was increased and the membrane potential of the mitochondria was reduced of brain cells in the sevoflurane group. Transmission electron microscopy displayed that there was a remarkable upregulation of autophagosomes at the axon of brain cells in mice after treatment of sevoflurane. Western blot demonstrated that the expression of Bax, LC3II, P62 and KIF3B proteins were elevated, and the expression of Bcl-2 and DIC proteins were reduced in the sevoflurane group. Sevoflurane impaired acquisition learning and memory function, promoted the apoptosis of hippocampal neurons in APPswe/PS1ΔE9 double-transgenic mice, and the mechanism might be related to the activation of autophagy along with the disruption of autophagosomes retrograde transport in axons.