The mechanism of nitrous oxide-induced changes in pulmonary vascular resistance in a dog model of left atrial outflow obstruction

Paul M. Heerdt, Robert William Caldwell

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Nitrous oxide has been reported to increase pulmonary vascular resistance (PVR) in patients with pulmonary hypertension secondary to mitral stenosis. Additional data suggest this response involves sympathetic stimulation because the increase in PVR can be prevented by a-adrenergic and ganglionic blockade. Whether or not active pulmonary vasoconstriction occurs remains unclear. This study was designed to more fully characterize the influence of N2O on pulmonary hemodynamics during left atrial outflow obstruction (LAO). Responses in an in situ blood-perfused lung lobe were compared with those in the remaining intact lung of six dogs anesthetized with pentobarbital, 30 mg/kg, and morphine, 1.5 mg/kg, and prepared for measurement of peak left ventricular (LV) pressure, LV end-diastolic pressure (LVEDP), LV dP/dt, systemic arterial and pulmonary arterial (PA) pressures, and cardiac output (CO). The pulmonary artery branch supplying the left middle lung lobe was cannulated and perfused at a constant rate with warmed blood. LAO was produced by filling the balloon of a Foley catheter positioned in the left atrium (LA) with enough saline to increase PA pressure by 50%; the balloon was subsequently left filled for the entire protocol. Measurements were first obtained during ventilation with 67% N2, and 33% O2. The inspired gas was then changed to 67% N2O and 33% O2 for 10 minutes, and then returned to the N2/O2 mixture. Once baselines had been reestablished (about 10 minutes), phentolamine, 0.75 mg/kg, was administered, and the response to 10 minutes of N2O again observed. N2O did not change vascular resistance in the isolated lobe, but increased intact-lung PVR. The pressure differential across the lung (mean PA pressure - LA pressure) was not altered by N2O in either the isolated or intact lung. CO (pulmonary blood flow) was slightly but significantly reduced by N2O while the perfusion flow rate remained constant. Concomitantly, systemic vascular resistance (SVR) and LVEDP both rose; the increase in LVEDP was not accompanied by an increase in LV dP/dtmax Following phentolamine treatment, N2O did not change hemodynamics in either the intact lung or isolated lobe, nor did it alter CO, SVR, or LVEDP; however, it did produce a fall in LV dP/dtmax This study suggests that under conditions of experimental LAO, nitrous oxide increases PVR primarily by reducing pulmonary blood flow. The findings do not support an active pulmonary arteriolar vasoconstriction by N2O.

Original languageEnglish (US)
Pages (from-to)568-573
Number of pages6
JournalJournal of Cardiothoracic Anesthesia
Volume3
Issue number5
DOIs
StatePublished - Jan 1 1989
Externally publishedYes

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Nitrous Oxide
Vascular Resistance
Dogs
Lung
Cardiac Output
Blood Pressure
Arterial Pressure
Phentolamine
Vasoconstriction
Heart Atria
Hemodynamics
Pressure
Mitral Valve Stenosis
Ventricular Pressure
Pentobarbital
Pulmonary Hypertension
Adrenergic Agents
Morphine
Pulmonary Artery
Ventilation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Anesthesiology and Pain Medicine

Cite this

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title = "The mechanism of nitrous oxide-induced changes in pulmonary vascular resistance in a dog model of left atrial outflow obstruction",
abstract = "Nitrous oxide has been reported to increase pulmonary vascular resistance (PVR) in patients with pulmonary hypertension secondary to mitral stenosis. Additional data suggest this response involves sympathetic stimulation because the increase in PVR can be prevented by a-adrenergic and ganglionic blockade. Whether or not active pulmonary vasoconstriction occurs remains unclear. This study was designed to more fully characterize the influence of N2O on pulmonary hemodynamics during left atrial outflow obstruction (LAO). Responses in an in situ blood-perfused lung lobe were compared with those in the remaining intact lung of six dogs anesthetized with pentobarbital, 30 mg/kg, and morphine, 1.5 mg/kg, and prepared for measurement of peak left ventricular (LV) pressure, LV end-diastolic pressure (LVEDP), LV dP/dt, systemic arterial and pulmonary arterial (PA) pressures, and cardiac output (CO). The pulmonary artery branch supplying the left middle lung lobe was cannulated and perfused at a constant rate with warmed blood. LAO was produced by filling the balloon of a Foley catheter positioned in the left atrium (LA) with enough saline to increase PA pressure by 50{\%}; the balloon was subsequently left filled for the entire protocol. Measurements were first obtained during ventilation with 67{\%} N2, and 33{\%} O2. The inspired gas was then changed to 67{\%} N2O and 33{\%} O2 for 10 minutes, and then returned to the N2/O2 mixture. Once baselines had been reestablished (about 10 minutes), phentolamine, 0.75 mg/kg, was administered, and the response to 10 minutes of N2O again observed. N2O did not change vascular resistance in the isolated lobe, but increased intact-lung PVR. The pressure differential across the lung (mean PA pressure - LA pressure) was not altered by N2O in either the isolated or intact lung. CO (pulmonary blood flow) was slightly but significantly reduced by N2O while the perfusion flow rate remained constant. Concomitantly, systemic vascular resistance (SVR) and LVEDP both rose; the increase in LVEDP was not accompanied by an increase in LV dP/dtmax Following phentolamine treatment, N2O did not change hemodynamics in either the intact lung or isolated lobe, nor did it alter CO, SVR, or LVEDP; however, it did produce a fall in LV dP/dtmax This study suggests that under conditions of experimental LAO, nitrous oxide increases PVR primarily by reducing pulmonary blood flow. The findings do not support an active pulmonary arteriolar vasoconstriction by N2O.",
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T1 - The mechanism of nitrous oxide-induced changes in pulmonary vascular resistance in a dog model of left atrial outflow obstruction

AU - Heerdt, Paul M.

AU - Caldwell, Robert William

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N2 - Nitrous oxide has been reported to increase pulmonary vascular resistance (PVR) in patients with pulmonary hypertension secondary to mitral stenosis. Additional data suggest this response involves sympathetic stimulation because the increase in PVR can be prevented by a-adrenergic and ganglionic blockade. Whether or not active pulmonary vasoconstriction occurs remains unclear. This study was designed to more fully characterize the influence of N2O on pulmonary hemodynamics during left atrial outflow obstruction (LAO). Responses in an in situ blood-perfused lung lobe were compared with those in the remaining intact lung of six dogs anesthetized with pentobarbital, 30 mg/kg, and morphine, 1.5 mg/kg, and prepared for measurement of peak left ventricular (LV) pressure, LV end-diastolic pressure (LVEDP), LV dP/dt, systemic arterial and pulmonary arterial (PA) pressures, and cardiac output (CO). The pulmonary artery branch supplying the left middle lung lobe was cannulated and perfused at a constant rate with warmed blood. LAO was produced by filling the balloon of a Foley catheter positioned in the left atrium (LA) with enough saline to increase PA pressure by 50%; the balloon was subsequently left filled for the entire protocol. Measurements were first obtained during ventilation with 67% N2, and 33% O2. The inspired gas was then changed to 67% N2O and 33% O2 for 10 minutes, and then returned to the N2/O2 mixture. Once baselines had been reestablished (about 10 minutes), phentolamine, 0.75 mg/kg, was administered, and the response to 10 minutes of N2O again observed. N2O did not change vascular resistance in the isolated lobe, but increased intact-lung PVR. The pressure differential across the lung (mean PA pressure - LA pressure) was not altered by N2O in either the isolated or intact lung. CO (pulmonary blood flow) was slightly but significantly reduced by N2O while the perfusion flow rate remained constant. Concomitantly, systemic vascular resistance (SVR) and LVEDP both rose; the increase in LVEDP was not accompanied by an increase in LV dP/dtmax Following phentolamine treatment, N2O did not change hemodynamics in either the intact lung or isolated lobe, nor did it alter CO, SVR, or LVEDP; however, it did produce a fall in LV dP/dtmax This study suggests that under conditions of experimental LAO, nitrous oxide increases PVR primarily by reducing pulmonary blood flow. The findings do not support an active pulmonary arteriolar vasoconstriction by N2O.

AB - Nitrous oxide has been reported to increase pulmonary vascular resistance (PVR) in patients with pulmonary hypertension secondary to mitral stenosis. Additional data suggest this response involves sympathetic stimulation because the increase in PVR can be prevented by a-adrenergic and ganglionic blockade. Whether or not active pulmonary vasoconstriction occurs remains unclear. This study was designed to more fully characterize the influence of N2O on pulmonary hemodynamics during left atrial outflow obstruction (LAO). Responses in an in situ blood-perfused lung lobe were compared with those in the remaining intact lung of six dogs anesthetized with pentobarbital, 30 mg/kg, and morphine, 1.5 mg/kg, and prepared for measurement of peak left ventricular (LV) pressure, LV end-diastolic pressure (LVEDP), LV dP/dt, systemic arterial and pulmonary arterial (PA) pressures, and cardiac output (CO). The pulmonary artery branch supplying the left middle lung lobe was cannulated and perfused at a constant rate with warmed blood. LAO was produced by filling the balloon of a Foley catheter positioned in the left atrium (LA) with enough saline to increase PA pressure by 50%; the balloon was subsequently left filled for the entire protocol. Measurements were first obtained during ventilation with 67% N2, and 33% O2. The inspired gas was then changed to 67% N2O and 33% O2 for 10 minutes, and then returned to the N2/O2 mixture. Once baselines had been reestablished (about 10 minutes), phentolamine, 0.75 mg/kg, was administered, and the response to 10 minutes of N2O again observed. N2O did not change vascular resistance in the isolated lobe, but increased intact-lung PVR. The pressure differential across the lung (mean PA pressure - LA pressure) was not altered by N2O in either the isolated or intact lung. CO (pulmonary blood flow) was slightly but significantly reduced by N2O while the perfusion flow rate remained constant. Concomitantly, systemic vascular resistance (SVR) and LVEDP both rose; the increase in LVEDP was not accompanied by an increase in LV dP/dtmax Following phentolamine treatment, N2O did not change hemodynamics in either the intact lung or isolated lobe, nor did it alter CO, SVR, or LVEDP; however, it did produce a fall in LV dP/dtmax This study suggests that under conditions of experimental LAO, nitrous oxide increases PVR primarily by reducing pulmonary blood flow. The findings do not support an active pulmonary arteriolar vasoconstriction by N2O.

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