Isoflurane and the pulmonary vascular pressure-flow relation at baseline and during sympathetic alpha- and beta-adrenoreceptor activation in chronically instrumented dogs.
BACKGROUND
The extent to which isoflurane anesthesia alters systemic vascular regulation has received considerable attention. In contrast, the pulmonary vascular effects of isoflurane have not been elucidated. Our initial objective was to investigate the net effect of isoflurane on the baseline left pulmonary vascular pressure-flow (LPQ) relation compared with values measured in the conscious state. In addition, we assessed the extent to which isoflurane alters the pulmonary vascular responses to sympathetic alpha- and beta-adrenoreceptor activation.


METHODS
Twelve conditioned mongrel dogs were chronically instrumented to measure the LPQ relation. LPQ plots were generated by continuously measuring the pulmonary vascular pressure gradient (pulmonary arterial pressure--left atrial pressure) and left pulmonary blood flow during gradual (approximately 1 min) inflation of a hydraulic occluder implanted around the right main pulmonary artery. LPQ plots were generated at baseline in the conscious and isoflurane-anesthetized states (n = 12). The pulmonary vascular dose-response relation to the sympathetic alpha-adrenoreceptor agonist phenylephrine also was investigated in conscious and isoflurane-anesthetized dogs (n = 6). Finally, after preconstriction with the thromboxane analogue U46619, the dose-response relation to the sympathetic beta-adrenoreceptor agonist isoproterenol was assessed in the conscious and isoflurane-anesthetized states (n = 8).


RESULTS
Compared with values measured in the conscious state, isoflurane anesthesia had no net effect on the baseline LPQ relation. The magnitude of the pulmonary vasoconstrictor response to phenylephrine observed in conscious dogs was not altered during isoflurane anesthesia. In contrast, the pulmonary vasodilator response to isoproterenol was markedly potentiated (P < 0.01) during isoflurane anesthesia compared with that in the conscious state.


CONCLUSIONS
These results indicate that isoflurane does not exert a net vasodilator influence on the pulmonary circulation at baseline. In contrast to the systemic circulation, the pulmonary vasoconstrictor response to sympathetic alpha-adrenoreceptor activation is maintained during isoflurane anesthesia. Surprisingly, the pulmonary vasodilator response to sympathetic beta-adrenoreceptor activation is actually potentiated during isoflurane. Thus, isoflurane anesthesia has differential effects on the canine pulmonary vascular responses to sympathetic alpha- and beta-adrenoreceptor activation.
Lennon
P F
PF
Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
Murray
P A
PA
D000768:Anesthesia, General; D000818:Animals; D001794:Blood Pressure; D004285:Dogs; D006439:Hemodynamics; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014851:Wakefulness
D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D011433:Propranolol; D007530:Isoflurane