Influence of adenosine and prostacyclin on hypoxia‐induced pulmonary hypertension in the anaesthetized pig

Öwall, Anders; Davilén, J.; Sollevi, Alf

doi:10.1111/j.1399-6576.1991.tb03304.x

Cited by 16 publications

(13 citation statements)

References 22 publications

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“…Since the first description of the dilating effects on pulmonary and systemic vessels of intravenous PGH in dogs [1], it has been suc cessfully applied as pulmonary vasodilator in animal models of acute pulmonary hyperten sion [4,5,27,28] and in patients with pulmo nary hypertension of various etiologies [2,29]. At doses effective in reducing PVR, intra venous PGH did, however, induce systemic vasodilation and an increase in cardiac out put.…”

Section: Discussionmentioning

confidence: 99%

“…Prostacyclin (PGI2), an arachidonic acid metabolite, is a potent pulmonary vasodilator [1] , It has been successfully given intrave nously to decrease pulmonary artery pressure (PAP) in primary pulmonary hypertension [2] , in patients with ARDS [3], and in various experimental models of acute pulmonary hy pertension [4][5][6]. The vasodilatory effect of PGF is, however, not restricted to the pulmo nary circulation.…”

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confidence: 99%

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PGI<sub>2</sub> Aerosol versus Nitric Oxide for Selective Pulmonary Vasodilation in Hypoxic Pulmonary Vasoconstriction

Welte

Zwißler

Habazettl³

et al. 1993

Eur Surg Res

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Intravenous prostacyclin (PGI2) is a potent pulmonary vasodilator in pulmonary hypertension. However, dose-dependent systemic vasodilation, an increase in intrapulmonary shunt and hypoxemia limit its clinical application. Recently, inhaled nitric oxide (NO) has been reported to elicit selective pulmonary vasodilation, but its clinical use is restricted by its potential toxicity; furthermore, the feasibility of NO application in clinical practice seems difficult. Therefore, we investigated the effects of PGI2 aerosol on pulmonary and systemic circulation and compared the hemodynamic effects to those of inhaled NO. In 6 dogs, ventilation with a hypoxic gas mixture (F102 0.09–0.11) increased pulmonary vascular resistance (PVR) by 196% (HPV). Aerosolization of a PGI₂ solution at a concentration of 430 ng/ml reduced hypoxia-induced increase of pulmonary artery pressure by 48% and PVR by 52% within 6-10 min without systemic vasodilation. The administered dose of PGI2 was 0.87 ± 0.26 ng/kg/min. In 2 dogs, doubling the PGI2 concentration (860 ng/ml) did not enhance the vasodilatory effect. After termination of PGI₂ inhalation, HPV was restored within 10–15 min. Inhaled NO (50 ppm) decreased the HPV-induced increase in PAP by 76% and in PVR by 73% within 5-10 min. Clinically relevant systemic vasodilation was not observed. It is concluded that inhalation of aerosolized PGI₂ leads to selective pulmonary vasodilation in hypoxia-induced pulmonary hypertension. Aerosolized PGI₂ at a concentration of 430 ng/ml was less potent than NO (50 ppm). However, due to the lack of known toxicity and its uncomplicated mode of application, inhaled PGI₂ may be one alternative to inhaled NO in the treatment of acute pulmonary hypertension.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

PGI<sub>2</sub> Aerosol versus Nitric Oxide for Selective Pulmonary Vasodilation in Hypoxic Pulmonary Vasoconstriction

Welte

Zwißler

Habazettl³

et al. 1993

Eur Surg Res

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“…It has been successfully used in a variety of experimental conditions and patients with pulmonary hypertension (21)(22)(23)(24)(25). The dosis of i.v.…”

Section: Discussionmentioning

confidence: 99%

“…PGI, has been applied in a variety of clinical and experimental conditions with pulmonary hypertension (21)(22)(23)(24)(25). However, vasodilation occurs in both the pulmonary and systemic vessels which might result in systemic hypotension.…”

Section: Inhaled No Versus Pgi In Respiratory Failure 199mentioning

confidence: 99%

Inhaled Nitric Oxide versus Inhaled Prostacyclin and Intravenous versus Inhaled Prostacyclin in Acute Respiratory Failure with Pulmonary Hypertension in Piglets

et al. 1995

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This study was a prospective, randomized design to compare oxygenation and pulmonary hemodynamics between inhaled nitric oxide (NO) and inhaled prostacylcin (PGI,), and between inhaled and i.v. PGI, in acute respiratory failure with pulmonary hypertension. Acute respiratory failure with pulmonary hypertension was induced in 12 piglets weighing 9-12 kg by repeated lung lavages and a continuous infusion of the stable endoperoxane analogue of thromboxane. Thereafter the animals were randomly assigned either for NO or PGI, application. All animals were treated with different concentrations of NO or different doses of PGI, applied i.v. and inhaled in random order. Continuous monitoring included ECG, central venous pressure (CVP), mean pulmonary artery pressure (MPAP), mean arterial pressure (MAP), artertial oxygen saturation (SaO,), and mixed venous oxygen saturation (SvO,) measurements. NO inhalation of 10 ppm resulted in a significant increase in Pao,/fraction of inspired oxygen (FiO,) from 7.5 2 1.34 kPa to 46.1 2 9.7 kPa. MPAP decreased significantly from 5.1 -t 0.26 kPa to 3.7 i 0.26 kPa during inhaled NO of 40 ppm; i.v. infusion of PGI, slightly increased oxygenation parameters. A significant increase in Pao,/ FiO, up to 32.4 2 3.lkPa was observed during PGI, aerosol delivery (11 < 0.01); i.v. PGI, decreased MAP from 11.5 -+ 0.39 kPa to 9.8 2 0.66 kPa ( p < 0.05) and MPAP from 5.8 -+ 0.53 kPa to 4.5 2 0.66 kPa, respectively ( p < 0.05). PGI, aerosol delivery significantly decreased the MPAP to 3.7 2 0.53 kPa ( p < 0.05) without influencing the MAP. It was concluded that inhaled NO and inhaled PGI, act as selective pulmonary vasodilators in acute respiratory Cdilure with pulmonary hypertension In 1987 N O was reported to be an important endotheliumderived relaxing factor (1, 2). NO is synthesized in the vascular endothelial cell from L-arginine by NO synthase. It rapidly diffuses into the vascular smooth muscle cell and acts by stimulation of guanylate cyclase producing cGMP which me-

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“…However, even when NO production was inhibited, there was no role for endogenous prostanoids in the regulation of exercise-induced pulmonary vasodilation. Thus, although the porcine pulmonary conductance and resistance vessels are sensitive to the vasodilator actions of exogenous prostanoids (1,29,33), endogenous prostanoids do not appear to exert a significant vasodilator influence in the pulmonary circulation.…”

Section: Role Of Prostanoids In the Regulation Of Vascular Tonementioning

confidence: 99%

Interaction between prostanoids and nitric oxide in regulation of systemic, pulmonary, and coronary vascular tone in exercising swine

Merkus

Houweling

Zarbanoui

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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. Interaction between prostanoids and nitric oxide in regulation of systemic, pulmonary, and coronary vascular tone in exercising swine. Am J Physiol Heart Circ Physiol 286: H1114-H1123, 2004. First published October 16, 2003 10.1152/ ajpheart.00477.2003.-Prostacyclin and nitric oxide (NO) are produced by the endothelium in response to physical forces such as shear stress. Consequently, both NO and prostacyclin may increase during exercise and contribute to metabolic vasodilation. Conversely, NO has been hypothesized to inhibit prostacyclin production. We therefore investigated the effect of cyclooxygenase (COX) inhibition on exercise-induced vasodilation of the porcine systemic, pulmonary, and coronary beds before and after inhibition of NO production. Swine were studied at rest and during treadmill exercise at 1-5 km/h, before and after COX inhibition with indomethacin (10 mg/kg iv), and in the absence and presence of NO synthase inhibition with N -nitro-Larginine (L-NNA; 20 mg/kg iv). COX inhibition produced systemic vasoconstriction at rest, which waned during exercise. The systemic vasoconstriction by COX inhibition was enhanced after L-NNA, particularly at rest. In the coronary circulation, COX inhibition also resulted in vasoconstriction at rest and during exercise. However, vasoconstriction was not modified by pretreatment with L-NNA. In contrast, COX inhibition had no effect on the pulmonary circulation, either at rest or during exercise. Moreover, a prostanoid influence in the pulmonary circulation could not be detected after L-NNA. In conclusion, endogenous prostanoids contribute importantly to systemic and coronary tone in awake swine at rest but are not mandatory for exercise-induced vasodilation in these beds. Endogenous prostanoids are not mandatory for the regulation of pulmonary resistance vessel tone. Finally, NO blunts the contribution of prostanoids to vascular tone regulation in the systemic but not in the coronary and pulmonary beds. coronary microcirculation; pulmonary microcirculation; peripheral resistance; microspheres THE ENDOTHELIUM PLAYS AN IMPORTANT ROLE in the regulation of vascular tone, by producing both vasodilators [nitric oxide (NO) and prostacyclin] and vasoconstrictors (endothelin). The contribution of these mediators to the regulation of tone varies across vascular beds. Thus, in anesthetized swine, basal pulmonary resistance is strongly influenced by NO and less by prostacyclin, whereas the opposite is true for the systemic vascular bed (1). Prostanoids are produced in skeletal muscle in response to exercise (14,18,23) and in response to increased levels of epinephrine (40). Therefore, prostanoids may contribute to metabolic dilation of the coronary (7, 19) and skeletal muscle vasculature (8, 42), although this is not a ubiquitous finding (4,6,15,34). To date, no study has investigated the contribution of endogenous prostanoids to regulation of vasomotor tone in various regional vascular beds during treadmill exercise. Consequently, the first aim of the present study was...

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Influence of adenosine and prostacyclin on hypoxia‐induced pulmonary hypertension in the anaesthetized pig

Cited by 16 publications

References 22 publications

PGI<sub>2</sub> Aerosol versus Nitric Oxide for Selective Pulmonary Vasodilation in Hypoxic Pulmonary Vasoconstriction

PGI<sub>2</sub> Aerosol versus Nitric Oxide for Selective Pulmonary Vasodilation in Hypoxic Pulmonary Vasoconstriction

Inhaled Nitric Oxide versus Inhaled Prostacyclin and Intravenous versus Inhaled Prostacyclin in Acute Respiratory Failure with Pulmonary Hypertension in Piglets

Interaction between prostanoids and nitric oxide in regulation of systemic, pulmonary, and coronary vascular tone in exercising swine

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