Comparative Penetration of Glycopyrrolate and Atropine across the Blood-Brain and Placental Barriers in Anesthetized Dogs

Proakis, Anthony G.; Harris, G. B.

doi:10.1097/00132586-197906000-00020

Cited by 19 publications

(28 citation statements)

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“…This target is comparable to heart rates achieved during cholinergic block in other published work Seifert et al 2010). Glycopyrrolate was chosen as the cholinergic blocking agent because it does not readily cross the blood-brain barrier (Proakis & Harris, 1978) and thus can block muscarinic receptors present on the endothelium of the pial arteries (Elhusseiny et al 1999) without introducing the confound of central cholinergic impairment. After blockade was achieved, OLBNP was applied as above but at an amplitude of only 15 mmHg to mitigate against the augmented blood pressure oscillations resulting from blockade.…”

Section: Protocolsmentioning

confidence: 55%

“…Given that glycopyrrolate does not readily cross the blood-brain barrier (Proakis & Harris, 1978), our data provide evidence for a vascular role of cholinergic control of cerebral perfusion that is independent of possible interactions within the central nervous system. An active cholinergic vasodilatory reflex in balance with sympathetic vasoconstriction in the cerebral circulation has numerous implications for our understanding of cerebrovascular disorders.…”

Section: Discussionmentioning

confidence: 69%

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Cholinergic control of the cerebral vasculature in humans

Hamner

Tan

Tzeng

et al. 2012

The Journal of Physiology

104

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Key points• Cerebral autoregulation maintains cerebral perfusion relatively constant in the face of slow changes in arterial pressure, but is less effective against more rapid changes (i.e. functions as a 'high-pass' filter).• While thought to be maintained mainly through myogenic adjustments to changes in transmural pressure, recent work has highlighted a possibility of active autonomic involvement in cerebral autoregulation.• In this study we examined the cerebrovascular effects of cholinergic blockade on nine healthy volunteers during the application of oscillatory lower body pressure at six frequencies from 0.03 to 0.08 Hz.• Cholinergic blockade impaired autoregulation at frequencies above 0.04 Hz, suggesting a role for active cholinergic vasodilatation in the maintenance of cerebral perfusion.Abstract Despite growing evidence of autonomic nervous system involvement in the regulation of cerebral blood flow, the specific contribution of cholinergic vasodilatation to cerebral autoregulation remains unknown. We examined cerebral and forearm blood flow responses to augmented arterial pressure oscillations with and without cholinergic blockade. Oscillatory lower body negative pressure was applied at six frequencies from 0.03 to 0.08 Hz in nine healthy subjects with and without cholinergic blockade via glycopyrrolate. Cholinergic blockade increased cross-spectral coherence between arterial pressure and cerebral flow at all frequencies except 0.03 Hz and increased the transfer function gain at frequencies above 0.05 Hz. In contrast, gain between pressure and forearm flow increased only at frequencies below 0.06 Hz. These data demonstrate that the cholinergic system plays an active and unique role in cerebral autoregulation. The frequency region and magnitude of effect is very similar to what has been seen with sympathetic blockade, indicating a possible balance between the two reflexes to most effectively respond to rising and falling pressure. These findings might have implications for the role of dysfunction in autonomic control of the vasculature in cerebrovascular disease states.

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Section: Protocolsmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 69%

Cholinergic control of the cerebral vasculature in humans

Hamner

Tan

Tzeng

et al. 2012

The Journal of Physiology

104

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“…Nonetheless, respiratory factors cannot explain the difference between the HF components of P-P and R-R interval variability. Third, it is known that atropine may penetrate the blood-brain barrier and affect the central nervous system (Proakis & Harris, 1978). However, the dose of atropine administered in the present study was as low as to have almost no detectable effect on the central nervous system (Jose & Taylor, 1969).…”

Section: Limitationsmentioning

confidence: 60%

Cardiac parasympathetic outflow during dynamic exercise in humans estimated from power spectral analysis of P–P interval variability

Takahashi

Nakamoto

Matsukawa

et al. 2016

Experimental Physiology

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New Findings r What is the central question of this study?Should we use the high-frequency (HF) component of P-P interval as an index of cardiac parasympathetic nerve activity during moderate exercise? r What is the main finding and its importance?The HF component of P-P interval variability remained even at a heart rate of 120-140 beats min −1 and was further reduced by atropine, indicating incomplete cardiac vagal withdrawal during moderate exercise. The HF component of R-R interval is invalid as an estimate of cardiac parasympathetic outflow during moderate exercise; instead, the HF component of P-P interval variability should be used.The high-frequency (HF) component of R-R interval variability has been widely used as an indirect estimate of cardiac parasympathetic (vagal) outflow to the sino-atrial node of the heart. However, we have recently found that the variability of the R-R interval becomes much smaller during dynamic exercise than that of the P-P interval above a heart rate (HR) of ß100 beats min −1 . We hypothesized that cardiac parasympathetic outflow during dynamic exercise with a higher intensity may be better estimated using the HF component of P-P interval variability. To test this hypothesis, the HF components of both P-P and R-R interval variability were analysed using a Wavelet transform during dynamic exercise. Twelve subjects performed ergometer exercise to increase HR from the baseline of 69 ± 3 beats min −1 to three different levels of 100, 120 and 140 beats min −1 . We also examined the effect of atropine sulfate on the HF components in eight of the 12 subjects during exercise at an HR of 140 beats min −1 . The HF component of P-P interval variability was significantly greater than that of R-R interval variability during exercise, especially at the HRs of 120 and 140 beats min −1 . The HF component of P-P interval variability was more reduced by atropine than that of R-R interval variability. We conclude that cardiac parasympathetic outflow to the sino-atrial node can be estimated better by the HF component of P-P interval variability during exercise and that cardiac parasympathetic nerve activity exists during moderate dynamic exercise.

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“…118 Glycopyrrolate is preferred to atropine because of its limited transplacental passage and resultant effect on fetal heart rate. 114…”

Section: Gastroprotectantsmentioning

confidence: 99%

Pharmacologic Advances in Canine and Feline Reproduction

Wiebe

Howard

2009

Topics in Companion Animal Medicine

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Substantial improvements in therapeutic options for companion animal reproduction and gynecologic emergencies have been made over the last decade. New, alternative drug treatments, with fewer side effects and improved efficacy, are available. This has widened the spectrum of therapeutic possibilities for diseases that were previously treated only by surgical intervention. New drugs are available for estrus induction and pregnancy termination, as well as for the treatment of pyometra. This review summarizes the pharmacology and toxicology of reproductive agents currently in use for contraception, pyometra, dystocia, eclampsia, premature labor, agalactia, mastitis, metritis, and prostatic disorders, and compares their efficacy and safety with newer agents. Drug use and exposure during pregnancy and lactation, and subsequent risks to the fetuses, are also explored, with emphasis on antimicrobials, antifungals, anthelminthics, anesthetics, and vaccinations.

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Comparative Penetration of Glycopyrrolate and Atropine across the Blood-Brain and Placental Barriers in Anesthetized Dogs

Cited by 19 publications

References 0 publications

Cholinergic control of the cerebral vasculature in humans

Cholinergic control of the cerebral vasculature in humans

Cardiac parasympathetic outflow during dynamic exercise in humans estimated from power spectral analysis of P–P interval variability

Pharmacologic Advances in Canine and Feline Reproduction

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