Sodium crocetinate does not alter gut hypercapnic responses or renal energy stores during transient sub-diaphragmatic ischaemia

Abstract

Objectives.

To evaluate the protection afforded by trans-sodium crocetinate against dysoxia in an animal model of recurrent sub-diaphragmatic ischaemia.

Design.

Prospective experimental animal study.

Setting.

University research laboratory

Subjects.

Adult male Sprague-Dawley rats.

Interventions.

Twelve adult male Sprague-Dawley rats (340–510 g) were anaesthetised with sodium pentobarbitone 60 mg/kg i.p. and ventilated with oxygen and isoflurane via tracheostomy. Six 2-min episodes of sub-diaphragmatic hypotension (mean pressure 30 mmHg) were induced using a sling around the proximal aorta. Before the third and sixth episodes, saline 1.5 ml/kg was injected into the aortic cannula. In six rats, this saline contained trans-sodium crocetinate 50 μg/ml.

Measurements and main results.

Ileal luminal PCO₂ and distal aortic pressure were monitored continuously. Following ischaemic episodes trans-sodium crocetinate had no discernible effect on either degree of PCO₂ elevation or the time to peak PCO₂. No effects on renal energy charge or nucleotide concentrations were detected. UV-visible spectroscopy of the crocetinate preparation showed that some cis isomer was present.

Conclusions.

The findings, although limited to one drug dosage in one animal model, bring into question whether trans-sodium crocetinate affects plasma oxygen diffusivity in vivo. Alternative explanations for the negative findings include a TSC-induced exacerbation of arterio-venous oxygen shunting, the brevity of the dysoxic episodes, and the presence of cis isomer.