In vitro therapy with dobutamine, isoprenaline and sodium nitroprusside protects vascular smooth muscle metabolism from subarachnoid haemorrhage induced cerebral vasospasm

Background. The cerebrospinal fluid (CSF) from subarachnoid haemorrhage (SA H) patients with cerebral vasospasm stimulates vasoconstriction and oxygen consumption in the porcine carotid artery in vitro. Stimulation of oxygen c onsumption has been used as an in vitro model of vasospasm to assess the re lative benefits of nimodipine, isoprenaline, dobutamine, and sodium nitropr usside (SNP). Method. Samples of human CSF were obtained from SAH patients and applied to de-endothelialised porcine carotid artery. Stimulation of oxygen consumpti on (as an in vitro marker for a stimulation of the vessels) was monitored a nd the effects of SNP, isoprenaline, dobutamine or nimodipine were measured . Findings. The CSF from SAH patients with evidence of vasospasm stimulated o xygen consumption to 0.91 +/- 0.17 (muM O-2/Min/g dry wt, +/- SD p less tha n or equal to 0.01) and CSF from SAH patients without vasospasm did not sig nificantly stimulate oxygen consumption 0.27 +/- 0.02, with 0.23 +/- 0.03 ( muM O-2/min/g dry wt) being an unstimulated rate of respiration for the por cine carotid artery. SNP, isoprenaline or dobutamine significantly (p : 0.0 1) decreased the stimulation of oxygen consumption of the porcine carotid a rtery whereas nimodipine did not. In a cohort of 41 SAH patients who receiv ed nimodipine alone or nimodipine and dobutamine, the in hospital mortality rate of the patients who received only nimodipine was 42% as compared to a n in hospital mortality rate of 17% in the nimodipine plus dobutamine group P less than or equal to 0.076). Interpretation. The in vivo data on the 41 patients is not statistically si gnificant, so further studies are required to determine if the differences are important. SNP, isoprenaline and dobutamine significantly decreased oxy gen consumption of the porcine carotid arteries exposed to CSF from SAH pat ients who had vasospasm whereas nimodipine did not. Our in vitro results su ggest that these compounds require further study in patients with SAH who a re at risk for vasospasm because they may have a direct benefit for the vas ospastic arteries.