Modulation of the pathophysiology of primate focal cerebral ischaemia by indomethacin.

Harris, Robert J.; Bayhan, M; Branston, Neil M.; Watson, Alan D.; Symon, Lindsay

doi:10.1161/01.str.13.1.17

Cited by 44 publications

(18 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…38 There is evidence to suggest that these dihydropyridine agents may enhance Ca ++ influx for cerebral cells during ischemia and that ischemic edema is worsened by their administration. 15 ' 31 Although not supported by our data, several studies suggest improved flow by these agents during and after ischemia. Overall outcome may well reflect the summation of nimodipine's potential deleterious effect on ischemic cerebral tissue vs its apparent cerebrovascular protective effects.…”

Section: Cerebral Protective Effect Of Nimodipinecontrasting

confidence: 80%

“…In a recent report, Harris et al described the effects of nimodipine, in baboons undergoing MCA occlusion for 90 minutes. 15 Nimodipine did not alter K + or Ca ++ extracellular activity at normal flows. However, when reduced flow states were assessed, K + and Ca ++ activities were altered in the nimodipine treated animals, while ion homeostasis was still preserved in the control group.…”

Section: Cerebral Protective Effect Of Nimodipinementioning

confidence: 78%

“…In Harris et al's study of rCBF in baboons undergoing MCA occlusion in both open and closed skull preparation, 15 treatment was found to improve rCBF after occlusion in the open skull studies. Rats subjected to 15 minutes of forebrain ischemia, pretreated with 0.1 mg kg" 1 of nimodipine, showed patchy areas of increased perfusion admixed with areas of hypoperfusion, yielding a net increase in rCBF.…”

Section: Discussionmentioning

confidence: 96%

See 2 more Smart Citations

Effects of nimodipine on acute focal cerebral ischemia.

Barnett¹,

Bose

Little

et al. 1986

Stroke

View full text Add to dashboard Cite

SUMMARY Nimodipine is a calcium slow channel blocker with several pharmacologlc properties suggesting the potential to favorably modify outcome in focal cerebral ischemia. Thirty adult cats underwent unilateral middle cerebral artery (MCA) occlusion for 4 hours. Seventeen cats were treated with an ipsilateral intracarotid infusion of nimodipine (1 /xg kg" 1 min ~') beginning 15 minutes before MCA ocdusion and continuing throughout the occlusion period. Eight nimodipine treated cats maintaining MAP > 90 mmHg were assigned to a Higher Pressure Nimodipine (HPN) group. The remaining nine treated cats with MAP < 90 mmHg were assigned to the Lower Pressure Nimodipine (LPN) group. Thirteen cats were untreated, receiving an isovolumetric amount of vehicle through the ipsilateral carotid artery. Local cerebral blood flow (1CBF) was continuously monitored using thermal diffusion probes. The brains, assessed for colloidal carbon perfusion, fluorescein and Evans blue staining, electroencephalographic activity (EEG), and histological changes, revealed no significant differences by any of these methods between the HPN and control animals with the exceptions of: 1) HPN treated cats exhibited a preservation of EEG activity at 15 minutes post-occlusion compared to the untreated cats, and 2) Post-iscbemic surface colloidal carbon perfusion was better preserved in the treated cats than hi the untreated cats. Mild hypotension, as demonstrated by the LPN group, negated these two positive effects. Prior to MCA occlusion, 1CBF was bilaterally significantly increased after nimodipine infusion in the HPN group as compared to vehicle infusion. Intra-arterially infused nimodipine did not reduce infarct size.

show abstract

Section: Cerebral Protective Effect Of Nimodipinecontrasting

confidence: 80%

Section: Cerebral Protective Effect Of Nimodipinementioning

confidence: 78%

Section: Discussionmentioning

confidence: 96%

See 1 more Smart Citation

Effects of nimodipine on acute focal cerebral ischemia.

Barnett¹,

Bose

Little

et al. 1986

Stroke

View full text Add to dashboard Cite

show abstract

“…At the end of the experiment, the brain was removed and immersed in kerosene prior to sampling the cortex for brain water determination. [23][24][25] The protocol for group 2 animals was as follows. After basal blood flow determination the mean arerial blood pressure was raised and held steady for 13 ± 3.8 mins.…”

Section: Experimental Protocolsmentioning

confidence: 99%

The effects of a calcium antagonist, nimodipine, upon physiological responses of the cerebral vasculature and its possible influence upon focal cerebral ischaemia.

Harris¹,

Branston²,

Symon³

et al. 1982

Stroke

Self Cite

198

View full text Add to dashboard Cite

SUMMARY The effects of a calcium antagonist, nimodipine, were tested on the response of the cerebral circulation to arterial pC0 2 and blood pressure changes. The effects of reduced blood flow upon oedema formation and extracellular ion homeostasis under nimodipine preloading were studied. Both open and closed skull primate models were used, with alpha-chloralose anaesthesia. Nimodipine infusion increased basal blood flow in the open skull, but not the closed skull animals. Autoregulation to increased blood pressure was little affected. Responses to arterial pC0 2 changes and autoregulation to reduced blood pressure were severely impaired. Residual blood flow after middle cerebral artery occlusion was significantly higher with nimodipine than in controls. The threshold levels of blood flow for the development of cortical oedema and for disturbance of ion homeostasis were, however, increased, suggesting that nimodipine interferes with cellular energy metabolism and increases the susceptibility of tissue to ischaemic damage. Stroke, Vol 13, No 6, 1982 THERE HAS BEEN CONSIDERABLE RECENT DISCUSSION on the mechanism of cell injury in ischaemia, much of which has centred on the role of calcium. 1,2 The hypotheses put forward propose that increased intracellular calcium activity exerts its pathological effects not only by the physical effects of mitochondrial calcium accumulation, 3 but also through stimulation of membrane phospholipid breakdown. 1,2A possible basis for the suggestion that calcium plays a major role in the pathophysiology of ischaemia was provided by Schanne,4 who showed that a range of membrane-active toxins only caused toxic cell death in the presence of normal extracellular calcium activity. When the extracellular calcium activity was reduced to that of normal intracellular activity, the toxins had little effect.Calcium antagonists 5 are supposed to block calcium entry into cells under certain conditions. Their use appeared to be the obvious means to test whether an influx of calcium into the cells is involved in the pathophysiology of ischaemia. Fleckenstein 5 described the action of calcium antagonists as a selective inhibition of the influx of calcium into the cell, by blockade of the so-called slow channels of the cell membrane. Other workers, using a variety of compounds and preparations, have confirmed Fleckenstein's proposal. protect the myocardium from the effects of ischaemia," -15 although the mechanisms of this protection are unclear. Nimodipine has been shown 16 to be one of the most potent calcium antagonists with a selective action on the intracranial vessels. Kazda et al. 16 have shown that nimodipine improves the post-ischaemically impaired flow in cats following 7 minutes total ischaemia, and the same group 17 have shown increased survival rates and functional protection in the same preparation.The present study was designed to test the effects of nimodipine on cerebrovascular physiological responses and on the pathophysiological effects of acute middle cerebral artery occlu...

show abstract

“…Because calcium overload has also been recognized as one of the detrimental factors leading to cell damage during and following brain ischemia (Siesjo, 1981), the use of a calcium antagonist may have potential to diminish brain swelling. However, many calcium antagonists have not been used because they may worsen brain edema by increasing the blood flow instead of im proving the metabolism of damaged cells (Harris et al, 1982;Hossmann et al, 1983) or may further re duce the blood flow in the ischemic area due to the served. Furthermore, PN200-110 diminished the exces sive accumulation of calcium in the MCA area involved.…”

mentioning

confidence: 99%