Niels-Aage Svendgaard

Subarachnoid Hemorrhage Enhances Endothelin Receptor Expression and Function in Rat Cerebral Arteries.

OBJECTIVEInspired by organ culture-induced changes in the vascular endothelin (ET) receptor population, we investigated whether such changes occur in cerebral arteries in a rat subarachnoid hemorrhage (SAH) model. METHODSSAH was induced with injection of 250 &mgr;l of blood into the prechiasmatic cistern. After 2 days, the middle cerebral artery, basilar artery, and posterior communicating artery were harvested. Pharmacological studies were performed in vitro, and levels of messenger ribonucleic acid (mRNA) were quantified in real-time reverse transcriptase-polymerase chain reaction assays. RESULTSIn the middle cerebral artery and basilar artery from rats with induced SAH, enhanced biphasic responses to ET-1 were observed. The −log(50% effective concentration) value for the high-affinity phase was approximately 12, compared with approximately 8.5 for sham-operated animals. At a concentration of ET-1 of 10−9 mmol/L (approximately equal to the physiological concentration of ET-1 in the plasma), submaximal contractions of 50 to 75% of the contraction obtained through stimulation with 60 mmol/L K+ were now observed. Quantitative mRNA studies with the same arteries demonstrated significant increases in the number of copies of ETB receptor mRNA but not ETA receptor mRNA. Evidence of functional ETB receptors was provided in antagonist studies. The posterior communicating artery did not exhibit significant changes. CONCLUSIONThe altered receptor profile observed may represent the final stage in the series of events leading from SAH to actual spasm of the artery. The pharmacological data for the ETB receptor suggest complex interactions between normally present ETA receptors and up-regulated ETB receptors.

Experimental subarachnoid hemorrhage: cerebral blood flow and brain metabolism during the acute phase in three different models in the rat.

OBJECTIVETo study the cerebral metabolism and its relationship to cerebral blood flow (CBF) acutely after subarachnoid hemorrhage (SAH). METHODSSAH was induced in rats by endovascular perforation of the internal carotid artery, blood injection into the prechiasmatic cistern or the cisterna magna. CBF (measured by laser Doppler flowmetry), cerebral perfusion pressure, O2 tension, and extracellular levels of glucose, lactate, and pyruvate were monitored during 90 minutes after SAH. CBF (assessed by 125I-antipyrine autoradiography), arteriovenous O2 difference, and cerebral metabolic rate of O2 were calculated at 15 or 90 minutes after SAH. RESULTSAfter a transient reduction, cerebral perfusion pressure normalized within 5 minutes after SAH in all groups. There was a transient global decrease in CBF after SAH: its duration depended on the severity of the hemorrhage. CBF of less than 20% of baseline was observed for at least 15 minutes in 25% and 14% of the animals after perforation and prechiasmatic SAH, respectively. In all SAH groups, O2 tension was suddenly reduced to approximately 40% of baseline and gradually increased, reaching 70 to 90% of baseline 90 minutes after SAH. The cerebral metabolic rate of O2 was reduced only at 15 minutes after perforation and prechiasmatic SAH, but arteriovenous O2 difference was normal in all groups. During 30 minutes after perforation SAH, a 50% decrease in glucose and a threefold increase in lactate and pyruvate levels were observed. CONCLUSIONThe data suggest that SAH induced an acute global decrease in CBF together with a depression in the cerebral metabolism. The degree of the changes was related to the severity of the hemorrhage. The metabolic derangements were not always explained by ischemic episodes.

Neuropeptide Y and vasoactive intestinal peptide in experimental subarachnoid hemorrhage: immunocytochemistry, radioimmunoassay and pharmacology

The involvement of noradrenaline (NA), neuropeptide Y, (NPY), 5‐hydroxytryptamine (5‐HT), acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) has been examined in the late phase of spasm after an experimental subarachnoid hemorrhage (SAH) in a rat model. Immunocytochemistry and radioimmunoassay of blood vessels from the circle of Willis did not show significant differences in NPY‐ and VIP‐like immunoreactivity 2 days post SAH as compared to control vessels. The postjunctional effects of NA, NPY, 5‐HT, ACh and VIP were studied two days after SAH using a sensitive in vitro system. NPY induced contractions were significantly (p < 0.01) weaker (lower Emax) in SAH as compared to control rats while the relaxant responses to ACh and VIP were slightly increased after SAH. These observations reveal that in a rat model of SAH, with an approximately 20% in vivo constriction at two days, dynamic changes occur in cerebral artery reactivity despite any obvious change in sympathetic or parasympathetic perivascular nerve networks.