The influence of basal nitric oxide activity on pulmonary vascular resistance in patients with congestive heart failure

Cooper, Christopher J.; Jevnikar, Frank W; Walsh, Thomas E.; Dickinson, Joanne L.; Mouhaffel, Assad; Selwyn, Andrew P.

doi:10.1016/s0002-9149(98)00400-7

Cited by 64 publications

(40 citation statements)

References 17 publications

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“…In the pulmonary circulation, the endothelium-mediated local control of vasomotility is primarily based on a balanced release of nitric oxide (NO) and ET-1 with the evidence suggesting that raised pulmonary pressure owing to left-sided heart disease is critically sensitive to an imbalance of these two opposing systems 29,30 .…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…Data that supports attenuation or loss of NO-dependent vasodilatation as a basic contributor to pressure elevation have also been provided by recording pulmonary blood flow velocity during intrapulmonary infusion of L-NMMA 29 . In healthy individuals and in patients with LV dysfunction with normal pulmonary vascular resistance, L-NMMA elicited a conspicuous vasoconstrictor response.…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

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Endothelial Dysfunction and Lung Capillary Injury in Cardiovascular Diseases

Guazzi¹,

Phillips²,

Arena³

et al. 2015

Progress in Cardiovascular Diseases

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Cardiac dysfunction of both systolic and diastolic origin leads to increased left atrial pressure, lung capillary injury and increased resistance to gas transfer. Acutely, pressure-induced trauma disrupts the endothelial and alveolar anatomical configuration and definitively causes an impairment of cellular pathways involved in fluid-flux regulation and gas exchange efficiency, a process well identified as stress failure of the alveolarcapillary membrane. In chronic heart failure (HF), additional stimuli other than pressure may trigger the true remodeling process of capillaries and small arteries characterized by endothelial dysfunction, proliferation of myofibroblasts, fibrosis and extracellular matrix deposition. In parallel there is a loss of alveolar gas diffusion properties due to the increased path from air to blood (thickening of extracellular matrix) and loss of fine molecular mechanism involved in fluid reabsorption and clearance. Deleterious changes in gas transfer not only reflect the underlying lung tissue damage but also portend independent prognostic information and may play a role in the pathogenesis of exercise limitations and ventilatory abnormalities observed in these patients. Few currently approved treatments for chronic HF have the potential to positively affect structural remodeling of the lung capillary network; angiotensin-converting enzyme inhibitors are one of the few currently established options. Recently, more attention has been paid to novel therapies specifically targeting the nitric oxide pathway as a suitable target to improve endothelial function and permeability as well as alveolar gas exchange properties.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Section: Accepted M Manuscriptmentioning

confidence: 99%

Endothelial Dysfunction and Lung Capillary Injury in Cardiovascular Diseases

Guazzi¹,

Phillips²,

Arena³

et al. 2015

Progress in Cardiovascular Diseases

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show abstract

“…A basal production of NO, thought to be necessary to keep up the lower pulmonary vascular tone, 10 appears to be deficient in patients with severe heart failure and may contribute to the development of secondary pulmonary hypertension. 11 Severe heart failure is associated with increased ET-1 plasma levels correlating with the degree of heart failure 3 and the extent of pulmonary hypertension. 12 The lungs are an important organ both for the production and elimination of ET-1; 13 a pulmonary spill-over of ET-1 correlating well with the PVR measured in chronic heart failure.…”

Section: Discussionmentioning

confidence: 99%

“…11 Administration of iNO thus substitutes for a physiological mediator in the state of deficient endothelial dependent vasodilation. In addition it may be assumed that iNO therapy not only replaces a diminished pulmonary NO release by exogenous administration but may also modulate the release of endothelins in patients following LVAD implantation.…”

Section: Ii-282 Circulation September 9 2003mentioning

confidence: 99%

Modulation of Circulating Endothelin-1 and Big Endothelin by Nitric Oxide Inhalation Following Left Ventricular Assist Device Implantation

et al. 2003

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Background-Inhaled nitric oxide (iNO) is an established therapy in the treatment of pulmonary hypertension and right ventricular dysfunction following left ventricular assist device implantation. Since it is known that endothelin-1 contributes to pulmonary hypertension, and nitric oxide modulates endothelin-1 synthesis in vitro, we investigated the effects of iNO on circulating endothelin-1 and big endothelin following left ventricular assist device implantation. Methods and Results-On weaning from cardiopulmonary bypass, 15 consecutive patients with secondary pulmonary hypertension after implantation of a left ventricular assist device were treated with iNO. Endothelin-1 and big endothelin plasma levels were measured preoperatively, on cardiopulmonary bypass prior to iNO, 12, 24, and 48 hour postoperatively, and 72 hour after cessation of iNO. Endothelin-1 levels were increased preoperatively (1.05Ϯ0.20 fmol/L), and were highest on cardiopulmonary bypass (1.65Ϯ0.27 fmol/L). During iNO therapy endothelin-1 and big endothelin decreased significantly (endothelin-1: 12 hour 1.24Ϯ0.18, 24 hour 0.93Ϯ0.20, and 48 hour 0.81Ϯ0.14 fmol/L); they were lowest 72 hour post-iNO (endothelin-1: 0.56Ϯ0.09 fmol/L). Plasma endothelin-1 concentrations and iNO dose were inversely correlated (rϭϪ0.657, PϽ0.015). A significant correlation was also found between endothelin-1 versus PA pressures and PVR/SVR ratio, but not with CI and SVR. Conclusions-Since it is known that endothelin-1 mediates pulmonary hypertension, we suggest a 2-fold effect of iNO therapy: firstly, a selective vasodilation of the pulmonary vasculature; and secondly, iNO mediated modulation of endothelin-1.

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“…Inhibition of myogenic contraction by flow-stimulated NO release could also occur with exercise, [92][93][94] explaining why distention of small PAs in this setting does not cause vasoconstriction. In fact, the magnitude of endothelial modulation of myogenic tone could at least partially account for variability in PVR with PVH: Cooper and colleagues, 95 using N Gmonomethyl-l-arginine to inhibit NO production, found that, in adults with PH due to left ventricular noncompliance, those with increased PVR had less baseline NO modulation of PVR than patients with normal PVR. Whether this is due to a limited capacity to generate NO or reduced production for other reasons is unclear, but some patients with PVH and increased PVR show substantial vasodilation with acetylcholine infusion, 28,96 indicating that the endothelium can have the capacity to produce NO but not generate it maximally at baseline.…”

Section: Myogenic Vasoconstrictionmentioning

confidence: 99%

Pulmonary Hypertension Caused by Pulmonary Venous Hypertension

Kulik

2014

Pulm. circ.

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The effect of pulmonary venous hypertension (PVH) on the pulmonary circulation is extraordinarily variable, ranging from no impact on pulmonary vascular resistance (PVR) to a marked increase. The reasons for this are unknown. Both acutely reversible pulmonary vasoconstriction and pathological remodeling (especially medial hypertrophy and intimal hyperplasia) account for increased PVR when present. The mechanisms involved in vasoconstriction and remodeling are not clearly defined, but increased wall stress, especially in small pulmonary arteries, presumably plays an important role. Myogenic contraction may account for increased vascular tone and also indirectly stimulate remodeling of the vessel wall. Increased wall stress may also directly cause smooth muscle growth, migration, and intimal hyperplasia. Even long-standing and severe pulmonary hypertension (PH) usually abates with elimination of PVH, but PVH-PH is an important clinical problem, especially because PVH due to left ventricular noncompliance lacks definitive therapy. The role of targeted PH therapy in patients with PVH-PH is unclear at this time. Most prospective studies indicate that these medications are not helpful or worse, but there is ample reason to think that a subset of patients with PVH-PH may benefit from phosphodiesterase inhibitors or other agents. A different approach to evaluating possible pharmacologic therapy for PVH-PH may be required to better define its possible utility.Keywords: pulmonary hypertension, pulmonary venous hypertension. As a perfect example of how clinical imperative can drive basic physiological investigation, studies of the effect of pulmonary venous hypertension (PVH) on the lung's circulation were in full swing by the very early 1950s, 1 close on the heels of the development of surgical relief of mitral valve stenosis. Cardiac catheterization of patients with mitral valve disease has characterized the physiology of PVH, and histological investigations demonstrated the microvascular changes provoked by PVH. Just as important, the effect of relief of left atrial (LA) hypertension on the circulation has been extensively reported, usually for patients who have had mitral valve intervention. We have learned that the circulatory alterations provoked by PVH share some characteristics with other forms of pulmonary hypertension (PH), such as the idiopathic variety, PH due to chronic alveolar hypoxia, and PH secondary to congenital cardiac shunting lesions. For example, acute "reactivity" to vasodilators may be observed, and there is overlap in the microarchitectural abnormalities seen. On the other hand, the "natural history" of PVH-PH is very different than that of the idiopathic variety or that seen with shunting defects: in the former (as demonstrated with mitral valve disease), PH is likely to largely or completely resolve if PVH is relieved, even with long-standing and severely increased pulmonary vascular resistance (PVR), 2,3 while in the latter two, PH is more likely to inexorably increase. PVH-PH is ther...

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The influence of basal nitric oxide activity on pulmonary vascular resistance in patients with congestive heart failure

Cited by 64 publications

References 17 publications

Endothelial Dysfunction and Lung Capillary Injury in Cardiovascular Diseases

Endothelial Dysfunction and Lung Capillary Injury in Cardiovascular Diseases

Modulation of Circulating Endothelin-1 and Big Endothelin by Nitric Oxide Inhalation Following Left Ventricular Assist Device Implantation

Pulmonary Hypertension Caused by Pulmonary Venous Hypertension

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