Harvey Cushing and the regulation of blood pressure in giraffe, rat and man: introducing ‘Cushing's mechanism’

Paton, Julian F. R.; Dickinson, C. J.; Mitchell, G.

doi:10.1113/expphysiol.2008.043455

Cited by 89 publications

(86 citation statements)

References 47 publications

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“…8 Consistent with this prediction, there was complete occlusion of the right internal carotid artery and a 50%-60% stenosis of the left in our patient (figure e-3). Intriguingly, PAG stimulation is known to improve cerebral perfusion, at least in the rat.…”

Section: Level Of Evidencesupporting

confidence: 73%

Deep brain stimulation relieves refractory hypertension

Patel¹,

Javed²,

Khan³

et al. 2011

Neurology

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Section: Level Of Evidencesupporting

confidence: 73%

Deep brain stimulation relieves refractory hypertension

Patel¹,

Javed²,

Khan³

et al. 2011

Neurology

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“…138 It has been proposed that triggering of SNA and systemic hypertension in response to inadequate cerebral blood flow is a protective mechanism to maintain perfusion. 16,46,143,144 This warrants further exploration as a potential mediator of human hypertension.…”

Section: Drug-resistant Hypertension-how To Treat?mentioning

confidence: 99%

“…42 Furthermore, both left ventricular hypertrophy and high cardiac SNA promote cardiac arrhythmias, and precipitate sudden cardiac death, particularly when parasympathetic tone is low, when it is in neurogenic hypertension. 43,44 Experimental infusion of noradrenaline can elicit vascular remodelling and increase aortic medial thickening 33 without marked changes in mean blood pressure, 45 while vertebral and basilar artery stenosis have been reported in the pre-hypertensive SHR, 16,46 which may be reversed with angiotensin-converting enzyme (ACE) inhibition. 47,48 Such pathophysiological alterations in the vasculature may be expected to modify the functional properties of the blood vessels.…”

Section: Clinical Implications Of Elevated Snamentioning

confidence: 99%

The sympathetic nervous system and blood pressure in humans: implications for hypertension

2011

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A neurogenic component to primary hypertension (hypertension) is now well established. Along with raised vasomotor tone and increased cardiac output, the chronic activation of the sympathetic nervous system in hypertension has a diverse range of pathophysiological consequences independent of any increase in blood pressure. This review provides a perspective on the actions and interactions of angiotensin II, inflammation and vascular dysfunction/brain hypoperfusion in the pathogenesis and progression of neurogenic hypertension. The optimisation of current treatment strategies and the exciting recent developments in the therapeutic targeting of the sympathetic nervous system to control hypertension (for example, catheter-based renal denervation and carotid baroreceptor stimulation) will be outlined. Keywords: sympathetic nerve activity; neurogenic hypertension; immune-to-brain signalling The sympathetic renaissancePrimary (or essential) hypertension (termed hypertension from here on) accounts for the vast majority of hypertensive cases (B95%).1 Although the aetiology of this condition is incompletely understood, it appears that along with genetic factors, several environmental and behavioural 'hypertensiogenic' factors have been identified, such as obesity, insulin resistance, high-salt intake, low physical activity levels and stress.1 Given the elevated risk of stroke, renal failure, myocardial infarction and coronary heart disease in those afflicted with high blood pressure, the elucidation of the key pathogenic features and optimisation of effective therapeutic strategies are critical.The most common form of hypertension is neurogenic hypertension, defined as high blood pressure with sympathetic overdrive, loss of parasympathetically mediated cardiac variability and excessive angiotensin II (Ang II) activity.2 The importance of the sympathetic nervous system in the short-term regulation of blood pressure via the modulation of peripheral vascular tone and cardiac output is well established, while the role of the sympathetic nerve activity (SNA) in long-term blood pressure control is more controversial. [3][4][5] Although the concept of a potential neurogenic component to hypertension is not new, 4 it has perhaps received less attention than the renin-angiotensin system (RAS), which has been a prominent therapeutic and research target in hypertension over the past few decades. Nevertheless, the activation of the sympathetic nervous system and the RAS in hypertension appears inextricably, and reciprocally, linked. Evidence from studies in both patients and animal models of hypertension strongly implicate the chronic sympathetic neural activation in the aetiology and progression of hypertension (Figure 1). 2,[6][7][8][9] The use of regional surgical sympathectomy to treat hypertension over 50 years ago before the availability of antihypertensive medications that lower sympathetic activity provides an early indication of the clinical appreciation for a significant neurogenic component to hypertension.10 Recent clini...

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“…Of note, there was an increase in systolic blood pressure, which might have been secondary to the transient increase in ICP-although there was no significant decrease in pulse, consistent with Cushing's mechanism. 15 At the end of the experiment, the pigs' brains and spinal cords were harvested and analyzed for the distribution of methylene blue and MTX concentration. In the case of methylene blue, the spectrophotometer was able accurately to measure the concentration of this dye achieved in vivo (Fig.…”

Section: Functional Evaluation Of the Mbp In Vivomentioning

confidence: 99%

Development of the Metronomic Biofeedback Pump for leptomeningeal carcinomatosis: technical note

Chen¹,

Napolitano

Adell

et al. 2015

JNS

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Patients with leptomeningeal carcinomatosis face a particularly grim prognosis. Current treatment consists of intrathecal delivery of methotrexate (MTX) or cytosine arabinoside (Ara-C) via Ommaya reservoir or lumbar puncture. Yet despite these interventions, the median survival after diagnosis is only 4–7 months. To address inherent shortcomings of current treatments and provide a more effective therapeutic approach, the Pharmaco-Kinesis Corporation has developed a novel type of implantable pump capable of delivering intrathecal chemotherapy (i.e., MTX) in a metronomic fashion with electronic feedback. The Metronomic Biofeedback Pump (MBP) consists of 3 components: 1) a 2-lumen catheter; 2) a microfluidic delivery pump with 2 reservoirs; and 3) a spectrophotometer monitoring MTX concentrations in the CSF. Using an animal model of intraventricular drug delivery, the authors demonstrate that the MBP can reliably deliver volumes of 500 μl/min, consistently measure real-time intrathecal MTX concentrations via CSF aspiration, and provide biofeedback with the possibility of instant control and delivery adjustments. Therefore, this novel approach to chemotherapy minimizes toxic drug levels and ensures continuous exposure at precisely adjusted, individualized therapeutic levels. Altogether, application of the MBP is expected to increase survival of patients with leptomeningeal carcinomatosis, and appropriate Phase I and II trials are pending.

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Harvey Cushing and the regulation of blood pressure in giraffe, rat and man: introducing ‘Cushing's mechanism’

Cited by 89 publications

References 47 publications

Deep brain stimulation relieves refractory hypertension

Deep brain stimulation relieves refractory hypertension

The sympathetic nervous system and blood pressure in humans: implications for hypertension

Development of the Metronomic Biofeedback Pump for leptomeningeal carcinomatosis: technical note

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