Department of Anesthesiology, University of Hirosaki School of Medicine, Hirosaki 0368562, Japan*Corresponding author
Accepted for publication: March 15, 2000
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Abstract |
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Br J Anaesth 2000; 85: 4602
Keywords: airway, resistance; lung, bronchus; lung, respiratory resistance; equipment, bronchoscope; serotonin (5-hydroxytryptamine)
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Introduction |
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We have previously demonstrated that PGE1 reverses histamine-induced bronchoconstriction dose-dependently.2 A multicentre clinical trial has shown that liposomal PGE1 improved oxygenation, increased lung compliance and decreased ventilator dependency in patients with acute respiratory distress syndrome (see reference 2). These findings suggest that i.v. PGE1 may be effective in airway constriction.
PGE1 has been reported to be useful for treating pulmonary hypertension.3 In addition, several reports suggest that it may reduce experimental pulmonary hypertension4. However, Priebe reported that PGE1 had no beneficial cardiopulmonary effects in a canine model of acute pulmonary hypertension.5 The spasmolytic effects of PGE1 in pulmonary hypertension thus remain controversial.
Serotonin (5-hydroxytryptamine, or 5HT) increases smooth muscle tone via 5HT receptors at low concentrations and via -adrenoceptors at high concentrations.6 Hence it simultaneously produces bronchoconstriction and pulmonary hypertension.
In this study, we examined whether PGE1 reversed 5HT-induced bronchoconstriction and pulmonary hypertension.
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Methods and Results |
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Airway tone was evaluated as bronchial cross-sectional area (BCA) determined by our bronchoscopic method as previously reported.2 7 Briefly, the BCA at the third bifurcation of the right lung was continuously monitored through the bronchoscope, and the area during the end-expiratory pause was measured using image analysis software (NIH Image program written by Wayne Rasband at the US National Institutes of Health). Pulmonary vascular tone was assessed as pulmonary vascular resistance (PVR). Changes in BCA and PVR were expressed as a percentage of the basal value before 5HT infusion.
Bronchoconstriction and pulmonary hypertension were elicited with 5HT infusion (10 µg kg1 +1 mg kg1 h1) via the pulmonary artery catheter. Thirty minutes later, when stable pulmonary hypertension and bronchoconstriction was achieved, seven dogs were subsequently given each dose of PGE1 in the following order: 0 (saline), 0.01, 0.1, 1.0 and 10 µg kg1 (PGE1 group) and four dogs were given saline only (saline group). BCA and PVR were assessed before and 30 min after the 5HT infusion started and 5 min after administration of each dose of PGE1 in the PGE1 group. At least 15 min elapsed between each administration. In the saline group, these variables were assessed before and 30 min after the 5HT infusion started, and 30 and 60 min after saline i.v.
Arterial blood (6 ml) was collected through the femoral artery catheter into syringes containing EDTA simultaneously with BCA and PVR assessment, immediately centrifuged at 3000 r.p.m. (1700 g) for 10 min at 10°C and then the plasma was separated and kept frozen at 70°C until catecholamine assay. Plasma catecholamine concentrations were determined by high performance liquid chromatography with electrochemical detection. The assay coefficients of variation for epinephrine and norepinephrine were 3.31% and 2.93%, respectively.
Data are shown as mean (95% confidence interval) except in Figure 1. Statistical analyses were performed by repeated measure ANOVA followed by Fishers protected least significant difference test. P<0.05 was considered significant.
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5HT did not significantly change systemic haemodynamic variables, while PAP was significantly increased. PGE1 10 µg kg1 significantly decreased the following haemodynamic variables during 5HT infusion: systematic vascular resistance from 4274 (33455202) to 3338 (26084067, P<0.01) dyness cm5 and mean arterial pressure from 127 (90164) to 110 (78143, P<0.01) mm Hg, whereas mean PAP did not change significantly (decreasing from 34 (2839) to 31 (2437) mm Hg).
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Comments |
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In the present study, plasma epinephrine slightly but significantly increased after administration of PGE1 10 µg kg1. This suggests that PGE1-induced systemic vasodilation increases sympathetic activity although PGE1 attenuates arterial baroreceptor reflexes.8 As circulating catecholamine concentration is one of the most important factors controlling airway tone,9 catecholamine release may also be involved in the observed bronchodilation. However, as PGE1 0.1 and 1.0 µg kg1 produced significant bronchodilation without increases in plasma catecholamines, PGE1 may have direct bronchodilatory effects.
PGE1 has been used clinically for the treatment of pulmonary hypertension.3 Fullerton and colleagues10 have also shown a direct relaxant effect of PGE1 on isolated rat pulmonary artery rings. In the present study, PGE1 10 µg kg1 significantly attenuated pulmonary hypertension although at 1.0 µg kg1 PGE1 was ineffective. However, as the catabolism of PGE1 in the lungs of dogs is about six times that in humans,2 clinically relevant doses may not attenuate pulmonary hypertension. Consistent with this, several reports5 suggest that PGE1 does not attenuate pulmonary hypertension by pulmonary vasodilation.
In conclusion, the present study indicates that clinically relevant doses of PGE1 may produce direct bronchodilation, but not pulmonary vasodilation.
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Acknowledgement |
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References |
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2 Hashimoto Y, Otomo N, Hirota K et al. Prostaglandin E1 produces spasmolytic effects on histamine-induced bronchoconstriction in dogs. Crit Care Med 1999; 27: 275559[ISI][Medline]
3 Kunimoto F, Arai K, Isa Y et al. A comparative study of the vasodilator effects of prostaglandin E1 in patients with pulmonary hypertension after mitral valve replacement and with adult respiratory distress syndrome. Anesth Analg 1997; 85: 50713[Abstract]
4 Leeman M, Lejeune P, Mélot C, Naeije R. Pulmonary vascular pressure-flow plots in canine oleic acid pulmonary edema. Am Rev Respir Dis 1998; 138: 3627
5 Priebe HJ. Efficacy of vasodilator therapy in canine model of acute pulmonary hypertension. Am J Physiol 1988; 255: H12329
6 Sanders-Bush E, Mayer S. 5-Hydroxytryptamine (serotonin) receptor agonists and antagonists. In: Hardman JG, Limbird LE eds. Goodman & Gilmans The Pharmacological Basis of Therapeutics, 9th edn. New York: McGraw-Hill, 1996; 24963
7 Otomo N, Hirota K, Hashimoto Y et al. Measurement of bronchodilation using a superfine fibreoptic bronchoscope. Br J Anaesth 1997; 78: 5835
8 Taneyama C, Goto H, Goto K et al. Attenuation of arterial baroreceptor reflex response to acute hypovolemia during induced hypotension. Anesthesiology 1990; 73: 43340[ISI][Medline]
9 Gal TJ. Bronchial hyperresponsiveness and anesthesia: physiologic and therapeutic perspectives. Anesth Analg 1994; 78: 55973[ISI][Medline]
10 Fullerton DA, Agrafojo J, McIntyre RC Jr. Pulmonary vascular smooth muscle relaxation by cAMP-mediated pathways. J Surg Res 1996; 61: 4448[ISI][Medline]