Inhibition of nitric oxide synthesis causes systemic and pulmonary vasoconstriction in isoflurane-anesthetized dogs

Peter G Moore, Nguyen D. Kien, John A. Reitan

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The postulate that the hemodynamic changes produced by isoflurane (1.5%) involve release of nitric oxide (NO) was examined. Fifteen dogs were anesthetized with thiamylal (15 mg/kg) and ventilated with isoflurane and oxygen. Catheters were inserted for measurement of aortic pressure, pulmonary artery pressures, and determination of cardiac output. Left thoracotomy was performed and complete heart block was induced by injection of 37% formaldehyde (0.3 mL) into the atrioventricular node; ventricular rate was fixed at 100 beats/min by external pacing. An apical microtransducer was inserted into the left ventricle (LV) via the apex for measurement of left ventricular pressure (LVP) and its first derivative (dP/dt). Flow probes were mounted on the left circumflex (Cx) and anterior descending (AD) coronary arteries. Measurements were obtained before (control period) and during NO inhibition using IV NG-nitro-l-arginine methyl ester (l-NAME) by a 50 mg/kg bolus plus 1 mg/kg/min. Infusion of l-NAME caused immediate and sustained increases in mean arterial pressure to 145 ± 3% (P < 0.001), mean pulmonary arterial pressure to 128 ± 5% (P < 0.001), pulmonary capillary wedge pressure to 144 ± 8% (P < 0.001), coronary perfusion pressure to 163 ± 4% (P < 0.001), systemic vascular resistance to 209 ± 9% (P < 0.001), pulmonary vascular resistance to 142 ± 12% (P < 0.005), anterior descending flow to 115 ± 4% (P < 0.005), and circumflex flow to 113 ± 3% (P < 0.01) of control levels. Decreases in cardiac output to 73 ± 2% (P < 0.001), anterior descending conductance to 71 ± 3% (P < 0.001), and circumflex conductance to 70 ± 3% (P < 0.001) of control, were also observed; LV dP/dt and end-diastolic pressure were unchanged. Inhibition of NO caused systemic and pulmonary vasoconstriction and depression of cardiac output. Responses to NO inhibition unmasked an intense background vasoconstriction during isoflurane, yet coronary blood flow increased due to an increase in perfusion pressure. It is concluded that NO plays a significant role in the systemic and pulmonary vasomotor and cardiac responses during isoflurane anesthesia. On the other hand, the coronary vasomotor effects appear to be mediated indirectly through changes in coronary perfusion pressure (ie, autoregulatory) rather than directly through withdrawal of NO activity.

Original languageEnglish (US)
Pages (from-to)310-316
Number of pages7
JournalJournal of Cardiothoracic and Vascular Anesthesia
Volume8
Issue number3
DOIs
StatePublished - 1994

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Isoflurane
Vasoconstriction
Nitric Oxide
Dogs
Lung
Cardiac Output
Pressure
Arterial Pressure
Perfusion
Vascular Resistance
Heart Ventricles
Thiamylal
Atrioventricular Node
Pulmonary Wedge Pressure
Heart Block
Ventricular Pressure
Thoracotomy
Formaldehyde
Pulmonary Artery
Coronary Vessels

Keywords

  • cardiac output
  • coronary blood flow
  • isoflurane
  • nitric oxide

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Inhibition of nitric oxide synthesis causes systemic and pulmonary vasoconstriction in isoflurane-anesthetized dogs. / Moore, Peter G; Kien, Nguyen D.; Reitan, John A.

In: Journal of Cardiothoracic and Vascular Anesthesia, Vol. 8, No. 3, 1994, p. 310-316.

Research output: Contribution to journalArticle

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abstract = "The postulate that the hemodynamic changes produced by isoflurane (1.5{\%}) involve release of nitric oxide (NO) was examined. Fifteen dogs were anesthetized with thiamylal (15 mg/kg) and ventilated with isoflurane and oxygen. Catheters were inserted for measurement of aortic pressure, pulmonary artery pressures, and determination of cardiac output. Left thoracotomy was performed and complete heart block was induced by injection of 37{\%} formaldehyde (0.3 mL) into the atrioventricular node; ventricular rate was fixed at 100 beats/min by external pacing. An apical microtransducer was inserted into the left ventricle (LV) via the apex for measurement of left ventricular pressure (LVP) and its first derivative (dP/dt). Flow probes were mounted on the left circumflex (Cx) and anterior descending (AD) coronary arteries. Measurements were obtained before (control period) and during NO inhibition using IV NG-nitro-l-arginine methyl ester (l-NAME) by a 50 mg/kg bolus plus 1 mg/kg/min. Infusion of l-NAME caused immediate and sustained increases in mean arterial pressure to 145 ± 3{\%} (P < 0.001), mean pulmonary arterial pressure to 128 ± 5{\%} (P < 0.001), pulmonary capillary wedge pressure to 144 ± 8{\%} (P < 0.001), coronary perfusion pressure to 163 ± 4{\%} (P < 0.001), systemic vascular resistance to 209 ± 9{\%} (P < 0.001), pulmonary vascular resistance to 142 ± 12{\%} (P < 0.005), anterior descending flow to 115 ± 4{\%} (P < 0.005), and circumflex flow to 113 ± 3{\%} (P < 0.01) of control levels. Decreases in cardiac output to 73 ± 2{\%} (P < 0.001), anterior descending conductance to 71 ± 3{\%} (P < 0.001), and circumflex conductance to 70 ± 3{\%} (P < 0.001) of control, were also observed; LV dP/dt and end-diastolic pressure were unchanged. Inhibition of NO caused systemic and pulmonary vasoconstriction and depression of cardiac output. Responses to NO inhibition unmasked an intense background vasoconstriction during isoflurane, yet coronary blood flow increased due to an increase in perfusion pressure. It is concluded that NO plays a significant role in the systemic and pulmonary vasomotor and cardiac responses during isoflurane anesthesia. On the other hand, the coronary vasomotor effects appear to be mediated indirectly through changes in coronary perfusion pressure (ie, autoregulatory) rather than directly through withdrawal of NO activity.",
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N2 - The postulate that the hemodynamic changes produced by isoflurane (1.5%) involve release of nitric oxide (NO) was examined. Fifteen dogs were anesthetized with thiamylal (15 mg/kg) and ventilated with isoflurane and oxygen. Catheters were inserted for measurement of aortic pressure, pulmonary artery pressures, and determination of cardiac output. Left thoracotomy was performed and complete heart block was induced by injection of 37% formaldehyde (0.3 mL) into the atrioventricular node; ventricular rate was fixed at 100 beats/min by external pacing. An apical microtransducer was inserted into the left ventricle (LV) via the apex for measurement of left ventricular pressure (LVP) and its first derivative (dP/dt). Flow probes were mounted on the left circumflex (Cx) and anterior descending (AD) coronary arteries. Measurements were obtained before (control period) and during NO inhibition using IV NG-nitro-l-arginine methyl ester (l-NAME) by a 50 mg/kg bolus plus 1 mg/kg/min. Infusion of l-NAME caused immediate and sustained increases in mean arterial pressure to 145 ± 3% (P < 0.001), mean pulmonary arterial pressure to 128 ± 5% (P < 0.001), pulmonary capillary wedge pressure to 144 ± 8% (P < 0.001), coronary perfusion pressure to 163 ± 4% (P < 0.001), systemic vascular resistance to 209 ± 9% (P < 0.001), pulmonary vascular resistance to 142 ± 12% (P < 0.005), anterior descending flow to 115 ± 4% (P < 0.005), and circumflex flow to 113 ± 3% (P < 0.01) of control levels. Decreases in cardiac output to 73 ± 2% (P < 0.001), anterior descending conductance to 71 ± 3% (P < 0.001), and circumflex conductance to 70 ± 3% (P < 0.001) of control, were also observed; LV dP/dt and end-diastolic pressure were unchanged. Inhibition of NO caused systemic and pulmonary vasoconstriction and depression of cardiac output. Responses to NO inhibition unmasked an intense background vasoconstriction during isoflurane, yet coronary blood flow increased due to an increase in perfusion pressure. It is concluded that NO plays a significant role in the systemic and pulmonary vasomotor and cardiac responses during isoflurane anesthesia. On the other hand, the coronary vasomotor effects appear to be mediated indirectly through changes in coronary perfusion pressure (ie, autoregulatory) rather than directly through withdrawal of NO activity.

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