Norepinephrine-induced hypertension dilates vasospastic basilar artery after subarachnoid haemorrhage in rabbits
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Vasopressor-induced hypertension is routinely indicated for prevention and treatment of cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH). Mechanisms underlying patients’ clinical improvement during vasopressor-induced hypertension remain incompletely understood. The aim of this study was to evaluate angiographic effects of normovolaemic Norepinephrine (NE)-induced hypertension therapy on the rabbit basilar artery (BA) after SAH.
Cerebral vasospasm was induced using the one-haemorrhage rabbit model; sham-operated animals served as controls. Five days later the animals underwent follow-up angiography prior to and during NE-induced hypertension. Changes in diameter of the BA were digitally calculated in mean µm ± SEM (standard error of mean).
Significant CVS of 14.2% was documented in the BA of the SAH animals on day 5 compared to the baseline angiogram on day 0 (n = 12, p < 0.01), whereas the BA of the control animals remained statistically unchanged (n = 12, p > 0.05). During systemic administration of NE, mean arterial pressure increased from 70.0 ± 1.9 mmHg to 136.0 ± 2.1 mmHg in the SAH group (n = 12, p < 0.001) and from 72.0 ± 3.1 to 137.8 ± 1.3 in the control group (n = 12, p < 0.001). On day 5 after SAH, a significant dilatation of the BA in response to norepinephrine could be demonstrated in both groups. The diameter of the BA in the SAH group increased from 640.5 ± 17.5 µm to 722.5 ± 23.7 µm (n = 12, p < 0.05; ). In the control group the diameter increased from 716.8 ± 15.5 µm to 779.9 ± 24.1 µm (n = 12, p < 0.05).
This study demonstrated that NE-induced hypertension causes angiographic dilatation of the BA in the SAH rabbit model. Based on these observations, it can be hypothesised that clinical improvement during vasopressor-induced hypertension therapy after SAH might be explained with cerebral vasodilatation mechanisms that lead to improvement of cerebral blood flow.
KeywordsSubarachnoid haemorrhage Cerebral vasospasm Triple-H therapy Induced hypertension Norepinephrine
Standard error of the mean
Mean arterial pressure
Delayed ischemic neurological deficits
Cerebral blood flow
Digital subtraction angiography
Haemodilution, hypervolaemia, induced hypertension
This study was supported by the Cerebrovascular Research Fund from the Departments of Neurosurgery and Intensive Care Medicine (Account Nr. 34-160), University of Bern, and from an unrestricted grant from Actelion Ltd, Allschwil, Switzerland. We are grateful to and thank H.R. Widmer, PhD, J. Schmid, RN, and Mr. H. Rohrer from the Departments of Neurosurgery and Neuroradiology, Bern University Hospital, for their professional laboratory support.
Financial disclosure/Conflict of interest
None of the authors has any conflict of interest to declare.
- 3.Egge A, Waterloo K, Sjoholm H, Solberg T, Ingebrigtsen T, Romner B (2001) Prophylactic hyperdynamic post-operative fluid therapy after aneurysmal subarachnoid haemorrhage: a clinical, prospective, randomised, controlled study. Neurosurgery 49:593–605. discussion 605-596. doi: 10.1097/00006123-200109000-00012 PubMedCrossRefGoogle Scholar
- 7.Joseph M, Ziadi S, Nates J, Dannenbaum M, Malkoff M (2003) Increases in cardiac output can reverse flow deficits from vasospasm independent of blood pressure: a study using xenon computed tomographic measurement of cerebral blood flow. Neurosurgery 53(Joseph M, Ziadi S, Nates J, Dannenbaum M, Malkoff M):1044–1051 discussion 1051-1042PubMedGoogle Scholar
- 15.Marbacher S, Neuschmelting V, Graupner T, Jakob SM, Fandino J (2008) Prevention of delayed cerebral vasospasm by continuous intrathecal infusion of glyceroltrinitrate and nimodipine in the rabbit model in vivo. Intensive Care Med 34:932–938. doi: 10.1007/s00134-008-0995-x PubMedCrossRefGoogle Scholar
- 17.Muench E, Horn P, Bauhuf C, Roth H, Philipps M, Hermann P, Quintel M, Schmiedek P, Vajkoczy P (2007) Effects of hypervolaemia and hypertension on regional cerebral blood flow, intracranial pressure, and brain tissue oxygenation after subarachnoid haemorrhage. Crit Care Med 35:1844–1851. quiz 1852. doi: 10.1097/01.CCM.0000275392.08410.DD PubMedCrossRefGoogle Scholar
- 20.Origitano TC, Wascher TM, Reichman OH, Anderson DE (1990) Sustained increased cerebral blood flow with prophylactic hypertensive hypervolaemic haemodilution (“triple-H” therapy) after subarachnoid haemorrhage. Neurosurgery 27:729–739. discussion 739-740. doi: 10.1097/00006123-199011000-00010 PubMedCrossRefGoogle Scholar