Assessment of effects of methylene blue on intestinal ischemia and reperfusion in a rabbit model: hemodynamic, histological and immunohistochemical study

Abstract

Background: Intestinal ischemia-reperfusion (IR) is an important clinical occurrence seen in common diseases, such as gastric dilatation-volvulus in dogs or colic in horses. Limited data is available on the use of methylene blue in veterinary medicine for intestinal ischemia-reperfusion. The present study aimed to compare the hemodynamic, histopathological, and immunohistochemical effects of two doses of methylene blue in two rabbit model groups In one group, 5 mg/kg IV was administered, and in another, 20 mg/kg IV was administered following a constant rate infusion (CRI) of 2 mg/kg/h that lasted 6 h. All the groups, including a control group had intestinal ischemiareperfusion. Immunohistochemical analysis was performed using caspase-3. Results: During ischemia, hemodynamic depression with reduced perfusion and elevated lactate were observed. During reperfusion, methylene blue (MB) infusion generated an increase in cardiac output due to a positive chronotropic effect, an elevation of preload, and an intense positive inotropic effect. The changes in heart rate and blood pressure were significantly greater in the group in which methylene blue 5 mg/kg IV was administered (MB5) than in the group in which methylene blue 20 mg/kg IV dose was administered (MB20). In addition, lactate and stroke volume variations were significantly reduced, and vascular resistance was significantly elevated in the MB5 group compared with the control group and MB20 group. The MB5 group showed a significant decrease in the intensity of histopathological lesion scores in the intestines and a decrease in caspase-3 areas, in comparison with other groups. Conclusions: MB infusion produced improvements in hemodynamic parameters in rabbits subjected to intestinal IR, with increased cardiac output and blood pressure. An MB dosage of 5 mg/kg IV administered at a CRI of 2 mg/ kg/h exhibited the most protective effect against histopathological damage caused by intestinal ischemiareperfusion. Further studies with MB in clinical veterinary pathologies are recommended to fully evaluate these findings.

Methylene Blue to Neonatal Septic Shock treatment in neonate pigs,

“…Leyh et al reported a decrease in cardiac output after the infusion of MB in adults with post-cardiopulmonary bypass-induced norepinephrine-refractory vasoplegia. 30 However, adult animal models did not show the same effect on cardiac output, 31 , 32 consistent with the echocardiographic findings regarding systolic and diastolic ventricular function. MB did not affect the myocardial contractility in the present study.…”

“…The roles of the l-arginine and NO pathways in pediatric and neonatal patients are well documented. 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 Nevertheless, research on MB treatment in these patient age groups is scarce. There is no substantial evidence that contraindicates the use of MB.…”

A novel beneficial role of humanin on intestinal apoptosis and dysmotility in a rat model of ischemia reperfusion injury

“…Image analysis software (ImageJ 1.36b; http://rsbweb.nih.gov/ij ) was used for the estimation of jejunal villus length and width (μm) and area% of caspase-3 and iNOS expressions [ 31 , 51 ]. Quantitative data was evaluated in non-overlapped random different fields in each slide (magnification 100 for villus length and width and magnification 400 for immunohistochemistry).…”

The rationale for methylene blue utility against SARS-CoV-2 infection complications

“…MB also attenuates lung injury induced by hindlimb (Wang et al, 2018) and lungs transplantation (Abreu et al, 2014) ischemia-reperfusion in rats, by inhibiting oxidative stress and inflammation. MB fully protected other organs exposed to ischemic injury namely the pancreas (Weinbroum, 2009), kidneys (Sarac et al, 2015), heart (Cheung et al, 2018), liver (Aksu et al, 2010), and intestine (Morgaz et al, 2020). Protective effects of this compound against other complications induced by xenobiotics or toxics have been examined as well (Chen et al, 2015;Lee et al, 2015).…”