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Biomedical subjects

J D Wicke

Publications and source records attributed to J D Wicke.

6 recordsLinked to original sources

Angiotensin AT2 receptor stimulation increases survival in gerbils with abrupt unilateral carotid ligation.

Previous studies showed that angiotensin II (AII) infusion increased survival in gerbils subjected to abrupt unilateral carotid ligation. Recently, stimulation of the AII AT2 receptor, reportedly effectively extended the blood pressure (BP) range of cerebral blood flow (CBF) autoregulation. We evaluated the survival of gerbils treated with PD-123319, a ligand of AT2 receptors, to test the hypothesis that restoration of BF to ischemic cerebral tissue produced by AII is mediated through AT2 receptors. Abrupt unilateral carotid ligation was performed on 300 gerbils. In five experimental groups, animals received no drug pretreatment: (a) saline; (b)-(d) PD-123319 1.0, 3.0, and 10 mg/kg; and (e) losartan 10 mg/kg. In three additional experimental groups, animals were pretreated with enalaprilat: (f) saline; (g) PD-123319, 10 mg/kg, and (h) losartan, 10 mg/kg. Survival for 48 h was significantly improved by PD-123319 (10 mg/kg) (p < 0.05) and by losartan (10 mg/kg) (p < 0.05) as compared with animals injected with saline. Pretreatment with enalaprilat neutralized the protective effect of losartan. PD-123319 is an AT2 agonist and improved survival in this animal model of stroke. Losartan, an AT1 antagonist, also improved survival, possibly through renin release and AT2 stimulation by endogenous AII. This effect was neutralized by enalaprilat.

Animals↗

Differences in mortality rate between abrupt and progressive carotid ligation in the gerbil: role of endogenous angiotensin II.

Studies have shown that in comparison to rapid occlusion of a vessel, gradual occlusion produces less severe tissue ischemia due to a more effective development of collateral circulation. As other studies have shown that collateral circulation can be enhanced by stimulation of the endogenous renin-angiotensin II system, it was hypothesized that this system is involved in the mechanism of protection against ischemia that obtains during gradual vascular occlusion. To test this hypothesis, mortality rates were evaluated in gerbils subjected to gradual vascular occlusion by means of progressive carotid ligation while simultaneously infused with inhibitors of the renin-angiotensin II cascade--enalaprilat or saralasin. Groups of animals with either abrupt or progressive carotid ligation infused with saline served as controls. Results showed that (1) in saline-infused animals, there was a significant decrease in the mortality rate of progressive-ligated animals when compared to abrupt-ligated animals, and (2) administration of either enalaprilat or saralasin to progressive-ligated animals resulted in mortality rates that were indistinguishable from those of saline-infused abrupt-ligated animals. These results suggest that the endogenous renin-angiotensin system is indeed involved in an adaptive mechanism that occurs during progressive ligation of the carotid artery, and more specifically, that the relatively benign effect of progressive carotid ligation may be due to the action of angiotensin II to stimulate the development of collateral circulation and reduce the severity of focal brain ischemia.

Angiotensin II↗

The effect of alpha-adrenergic innervation on caudate blood flow.

A thermal diffusion probe, with cannulas for intracerebral microinfusion of drugs and an electrode to monitor electroencephalographic (EEG) activity, was used to examine the local effect of vasoactive amines in a 4 to 5 mm sphere of caudate nucleus in cats. The results demonstrated that it is possible to alter local cerebral blood flow (CBF) without causing any change in systemic blood pressure or heart rate, or in CBF and the EEG in the opposite caudate. One-microliter intracerebral injections, containing varying amounts of phenylephrine, increased local CBF in proportion to dose. The effect was blocked by intracerebral infusion of phentolamine. However, local alpha-adrenergic blockade did not inhibit vascular responses to blood pressure elevation or to metabolic influences on local blood flow.

Adrenergic Fibers↗

On-line statistical detection of average evoked potentials: application to evoked response audiometry (ERA).

An objective method of EP detection in averaged EEG epochs is described which is based on the statistical properties of the averaged EEG in the absence of time-locked EP activity. The statistical properties of the subject's averaged background EEG are summarized by making a set of comparisons between two consecutive EEG epochs immediately preceding each stimulus presentation. After every stimulus presentation, a second set of comparisons is made between the post-stimulus EEG epoch and the immediately preceding pre-stimulus EEG epoch. These two sets of comparisons are then examined to determine whether the latter differ significantly from the former. The technique has been programmed for on-line use on a 12-bit minicomputer, validated on cooperative adult subjects and used for ERA threshold determinations in young children. Using response detection criteria yielding an empirically determined false positive error rate of between 1 and 4%, threshold estimates averaged about 10 dB higher than psychophysical thresholds. The efficiency with which such ERA thresholds may be obtained with this method is substantially greater than that of conventional ERA procedures employing subjective evaluation of averages. Further, the technique allows variation of detection criteria to suit non-audiometric needs and empirical determination of the false-positive error rate under any set of conditions.

Adult↗