Incomplete and delayed bioavailability of sublingual nitroglycerin

Noonan, Patrick K.; Benet, Leslie Z.

doi:10.1016/0002-9149(85)90325-x

Cited by 54 publications

(29 citation statements)

References 7 publications

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“…24 To test the possibility that the effect of NTG to reduce the FPW component of AP relates to myocardial contraction/ relaxation, we injected NTG directly into the left coronary circulation at a dose below that observed to generate systemic effects when given intravenously and ≈50-fold lower than that used to achieve systemic effects in the present study (assuming bioavailability of sublingual NTG to be approximate 35%). 25 We observed a significant, albeit less pronounced, effect on AP. This is consistent with an influence of NTG on the FPW component of AP through a direct action on the myocardium to hasten the onset of relation after P1.…”

Section: Discussionmentioning

confidence: 50%

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Augmentation Pressure Is Influenced by Ventricular Contractility/Relaxation Dynamics

Fok

Guilcher

et al. 2014

Hypertension

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A ortic or central pulse pressure (cPP) determines the pulsatile load on the left ventricle, coronary, and carotid arteries and is a major risk factor for adverse cardiovascular events, with at least as strong a relation to such events as peripheral pulse pressure.1-3 cPP is widely assumed to be determined by the interaction of an outgoing forward pressure wave (FPW) generated by ventricular contraction and a backward going pressure wave (BPW) generated by reflections from the periphery of the circulation. 4,5 These components of cPP are separated by the first systolic shoulder of the aortic pulse ( Figure 1). The height of this above diastolic blood pressure (P1) is attributed to the FPW and the height above P1, the augmentation pressure (AP), to the BPW. 6 Augmentation index (AIx), the ratio of AP to cPP, is widely used as a measure of pressure wave reflection. This interpretation has, however, been criticized because of the poor relationship between the magnitude and timing of reflected waves with respect to AP. 7,8 Nitroglycerin (NTG) has a particularly marked action to reduce AP and hence cPP attributed to a change in timing or amplitude of pressure wave reflections. [9][10][11] However, an alternative explanation relates to an influence of nitrovasodilators on contraction-relaxation dynamics of the myocardium, effects observed in isolated myocytes and in vivo. 12,13The aim of the present study was to determine the mechanism by which AP is selectively reduced by NTG. We made simultaneous measurements of aortic pressure and flow and used wave intensity analysis to separate pressure waves into FPW and BPW components.14 Pressure waves were further categorized as compression or expansion (suction). A primary forward compression wave (FCW) arises from the push of the ventricle against the arterial tree and a systolic backward compression wave (BCW) from the push of the arterial tree against the ventricle. A late systolic forward expansion wave (FEW) arises from the braking effect of the ventricle in late systole. 15 These measurements together with cardiac output and the impedance of the arterial tree were obtained at baseline and after systemic administration of NTG. To further distinguish between effects of NTG related to an action on the myocardium and arterial tree, we examined effects of intracoronary infusion of NTG at a dose below the threshold required to produce systemic effects.Abstract-Augmentation pressure (AP), the increment in aortic pressure above its first systolic shoulder, is thought to be determined mainly by pressure wave reflection but could be influenced by ventricular ejection characteristics. We sought to determine the mechanism by which AP is selectively reduced by nitroglycerin (NTG). Simultaneous measurements of aortic pressure and flow were made at the time of cardiac catheterization in 30 subjects (11 women; age, 61±13 years [mean±SD]) to perform wave intensity analysis and calculate forward and backward components of AP generated by the ventricle and arterial tree, respectively. ...

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Section: Discussionmentioning

confidence: 50%

“…25 We observed a significant, albeit less pronounced, effect on AP. This is consistent with an influence of NTG on the FPW component of AP through a direct action on the myocardium to hasten the onset of relation after P1.…”

mentioning

confidence: 50%

Augmentation Pressure Is Influenced by Ventricular Contractility/Relaxation Dynamics

Fok

Guilcher

et al. 2014

Hypertension

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“…While in one study in migraineurs GTN administration did not produce allodynia or hyperalgesia as measured by quantitative sensory testing (Ladda et al, 2006), in contrast, in other studies GTN has been shown to have extracranial effects on nociception in migraineurs, but not in non-migraineurs (Di Clemente et al, 2009; Perrotta et al, 2011; Sandrini et al, 2002) and has been shown to reduce nociceptive thresholds relative to placebo (Thomsen et al, 1996). These latter studies used 0.9 – 1.2 mg GTN, oral or sublingual, which gives rise to plasma levels in the ng/ml range (Noonan and Benet, 1985), similar to that following µg/min intravenous administration (Bogaert, 1994; Imhof et al, 1982). This raises the intriguing possibility that migraine is a more generalized condition, impacting structures outside the head and neck.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms mediating nitroglycerin-induced delayed-onset hyperalgesia in the rat

2016

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Nitroglycerin (glycerol trinitrate, GTN) induces headache in migraineurs, an effect that has been used both diagnostically and in the study of the pathophysiology of this neurovascular pain syndrome. An important feature of this headache is a delay from the administration of GTN to headache onset that, because of GTN’s very rapid metabolism, cannot be due to its pharmacokinetic profile. It has recently been suggested that activation of perivascular mast cells, which has been implicated in the pathophysiology of migraine, may contribute to this delay. We reported that hyperalgesia induced by intradermal GTN has a delay to onset of ~30 min in male and ~45 min in female rats. This hyperalgesia was greater in females, was prevented by pretreatment with the anti-migraine drug, sumatriptan, as well as by chronic pretreatment with the mast cell degranulator, compound 48/80. The acute administration of GTN and compound 48/80 both induced hyperalgesia that was prevented by pretreatment with octoxynol-9, which attenuates endothelial function, suggesting that GTN and mast cell-mediated hyperalgesia are endothelial cell-dependent. Furthermore, A-317491, a P2X3 antagonist, which inhibits endothelial cell-dependent hyperalgesia, also prevents GTN and mast cell-mediated hyperalgesia. We conclude that delayed onset mechanical hyperalgesia induced by GTN is mediated by activation of mast cells, which in turn release mediators that stimulate endothelial cells to release ATP, to act on P2X3, a ligand-gated ion channel, in perivascular nociceptors. A role of the mast and endothelial cell in GTN-induced hyperalgesia suggest potential novel risk factors and targets for the treatment of migraine.

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“…Desventajas: Potencia intermedia, además de sus efectos hemodinámicos conocidos, tiene una biodisponibilidad altamente variable entre los sujetos por su pronunciado metabolismo hepáti-co, pulmonar y placentario 39 .…”

Section: Liberadores De Oxido Nítricounclassified

Untitled

2017

Rev Chil Anest

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AntecedentesLa administración de anestesia para la reparación prenatal del mielomeningocele revela condiciones que están ligadas a esta nueva forma de tratamiento: el bienestar fetal, el contexto quirúr-gico y la perfusión uterina.La descripción, el análisis y la comprensión de las distintas variables que están involucradas permitirá disminuir el elevado riesgo que carga esta cirugía.Objetivo: Esta revisión entrega un enfoque sistemático a los nuevos desafíos que plantea la cirugía fetal. IntroducciónEl estudio comparativo sobre el manejo del mielomeningocele (MMC), tan apropiadamente llamado "MOMS" (Management of myelomeningocele study, por su sigla en inglés), fue publicado por primera vez en el New England Journal of Medicine en Marzo 2011 1 . Los hallazgos de este estudio demuestran los beneficios del tratamiento prenatal y sus conclusiones desplazan las fronteras del conocimiento más allá de los convencionales paradigmas de la terapia en Medicina y abren las puertas a un nuevo desafío para los Anestesiólogos: La Cirugía Fetal.Así como la descripción de Vandam 2 sobre las consideraciones anestésicas para el trasplante renal o la de Aldrete 3 en el trasplante hepáti-co o la reciente publicación de Klein 4 sobre las implicancias anestesiológicas en la inserción de la válvula aortica por cateterismo, el trabajo de Adzick 1 da inicio a una nueva era en el desarrollo de la anestesiología donde deberemos contestar preguntas que no nos habíamos formulado y donde deberemos profundizar en áreas que esta emergente técnica nos obligará a desarrollar.Esta publicación esta basada en la experiencia adquirida en los primeros 29 casos realizados en Chile. Se describen los defectos del tubo neural y se analizan las principales variables a considerar:• El dolor fetal.• La técnica anestésica.• La monitorización.• La relajación uterina.• La reposición de fluidos. Epidemiología de los defectos del tubo neuralEn Chile ocurren alrededor de 250.000 nacimientos por año, con una tasa de natalidad de

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Incomplete and delayed bioavailability of sublingual nitroglycerin

Cited by 54 publications

References 7 publications

Augmentation Pressure Is Influenced by Ventricular Contractility/Relaxation Dynamics

Augmentation Pressure Is Influenced by Ventricular Contractility/Relaxation Dynamics

Mechanisms mediating nitroglycerin-induced delayed-onset hyperalgesia in the rat

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