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 microg/ml. MEASUREMENTS AND MAIN RESULTS: Ileal luminal PCO(2) and distal aortic pressure were monitored continuously. Following ischaemic episodes trans-sodium crocetinate had no discernible effect on either degree of PCO(2) elevation or the time to peak PCO(2). 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.
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 microg/ml. MEASUREMENTS AND MAIN RESULTS: Ileal luminal PCO(2) and distal aortic pressure were monitored continuously. Following ischaemic episodes trans-sodium crocetinate had no discernible effect on either degree of PCO(2) elevation or the time to peak PCO(2). 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.
Authors: M Cross; Z H Endre; P Stewart-Richardson; G J Cowin; J Westhuyzen; R G Duggleby; S J Fleming Journal: Magn Reson Med Date: 1993-10 Impact factor: 4.668