Pentobarbital anesthesia alters pulmonary vascular response to neural antagonists

1989 ◽  
Vol 256 (5) ◽  
pp. H1384-H1392 ◽  
Author(s):  
D. P. Nyhan ◽  
H. M. Goll ◽  
B. B. Chen ◽  
D. M. Fehr ◽  
P. W. Clougherty ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Vena Cava ◽  
Cholinergic Receptor ◽  
Conscious Dogs ◽  
Base Line ◽  
Pentobarbital Anesthesia ◽  
Pulmonary Vasodilation ◽  
Receptor Block ◽  
Pentobarbital Sodium Anesthesia ◽  
Line P

We investigated the effects of pentobarbital sodium anesthesia on vasoregulation of the pulmonary circulation. Our specific objectives were to 1) assess the net effect of pentobarbital on the base-line pulmonary vascular pressure-to-cardiac index (P/Q) relationship compared with that measured in conscious dogs, and 2) determine whether autonomic nervous system (ANS) regulation of the intact P/Q relationship is altered during pentobarbital. P/Q plots were constructed by graded constriction of the thoracic inferior vena cava, which produced stepwise decreases in Q. Pentobarbital (30 mg/kg iv) had no net effect on the base-line P/Q relationship. In contrast, changes in the conscious intact P/Q relationship in response to ANS antagonists were markedly altered during pentobarbital. Sympathetic alpha-adrenergic receptor block with prazosin caused active pulmonary vasodilation (P less than 0.01) in conscious dogs but caused vasoconstriction (P less than 0.01) during pentobarbital. Sympathetic beta-adrenergic receptor block with propranolol caused active pulmonary vasoconstriction (P less than 0.01) in both groups, but the magnitude of the vasoconstriction was attenuated (P less than 0.05) during pentobarbital at most levels of Q. Finally, cholinergic receptor block with atropine resulted in active pulmonary vasodilation (P less than 0.01) in conscious dogs, whereas vasoconstriction (P less than 0.01) was observed during pentobarbital. Thus, although pentobarbital had no net effect on the base-line P/Q relationship measured in conscious dogs, ANS regulation of the intact pulmonary vascular P/Q relationship was altered during pentobarbital anesthesia.

AVP-induced pulmonary vasodilation during specific V1 receptor block in conscious dogs

1987 ◽  
Vol 253 (3) ◽  
pp. H493-H499
Author(s):  
D. P. Nyhan ◽  
P. W. Clougherty ◽  
P. A. Murray
Keyword(s):  
Vena Cava ◽  
Cholinergic Receptor ◽  
Receptor Activation ◽  
Conscious Dogs ◽  
Beta Adrenergic ◽  
Pulmonary Vasodilation ◽  
Vasodilator Response ◽  
Pulmonary Vasodilator ◽  
Receptor Block ◽  
Pathway Inhibition

Our objectives were 1) to determine whether exogenously administered arginine vasopressin (AVP) can exert a vasoactive influence on the pulmonary circulation of conscious dogs during specific vasopressinergic-1 (V1) receptor block, and 2) to assess the extent to which the pulmonary vascular response to AVP during V1 receptor block is mediated by either sympathetic beta-adrenergic or cholinergic receptor activation or by cyclooxygenase pathway activation. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by stepwise constriction of the thoracic inferior vena cava to reduce Q. In dogs pretreated with a specific V1 receptor antagonist [d(CH2)5 AVP, 10 micrograms/kg iv], AVP infusion (7.6 ng.kg-1 X min-1 iv) increased (P less than 0.01) Q from 139 +/- 6 to 175 +/- 8 ml.min-1 X kg-1, and decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure: PAP-PCWP) over the entire range of Q studied (140 to 80 ml.min-1 X kg-1). This pulmonary vasodilator response to AVP during V1 block was also observed following sympathetic beta-adrenergic block alone, following combined sympathetic beta-adrenergic and cholinergic block, and following cyclooxygenase pathway inhibition. Thus exogenous administration of AVP during specific V1 receptor block results in active, nonflow-dependent pulmonary vasodilation. This pulmonary vasodilator response is not mediated by reflex activation of sympathetic beta-adrenergic or cholinergic receptors or by metabolites of the cyclooxygenase pathway over a broad range of Q.

Pentobarbital anesthesia modifies pulmonary vasoregulation after hypoperfusion

1988 ◽  
Vol 255 (3) ◽  
pp. H569-H576
Author(s):  
B. B. Chen ◽  
D. P. Nyhan ◽  
H. M. Goll ◽  
P. W. Clougherty ◽  
D. M. Fehr ◽  
...  
Keyword(s):  
Cardiac Index ◽  
Adrenergic Receptor ◽  
Conscious State ◽  
Conscious Dogs ◽  
Mixed Venous Blood ◽  
Vascular Response ◽  
Beta Adrenergic ◽  
Pentobarbital Anesthesia ◽  
Pulmonary Vasoconstriction ◽  
Receptor Block

Our objectives were 1) to investigate the extent to which the pulmonary vascular response to increasing cardiac index after a period of hypotension and hypoperfusion (defined as reperfusion) measured in conscious dogs is altered during pentobarbital sodium anesthesia, and 2) to determine whether pentobarbital anesthesia modifies autonomic nervous system (ANS) regulation of the pulmonary circulation during reperfusion. Base-line and reperfusion pulmonary vascular pressure-cardiac index (P/Q) plots were generated by stepwise inflation and deflation, respectively, of an inferior vena caval occluder to vary Q in conscious and pentobarbital-anesthetized (30 mg/kg iv) dogs. During pentobarbital anesthesia, controlled ventilation (without positive end-expiratory pressure) allowed matching of systemic arterial and mixed venous blood gases to conscious values. Marked pulmonary vasoconstriction (P less than 0.01) was observed during reperfusion in pentobarbital-anesthetized but not in conscious dogs. Both sympathetic alpha-adrenergic receptor block and total ANS ganglionic block attenuated, but did not abolish, the pulmonary vasoconstriction during reperfusion in pentobarbital-anesthetized dogs. Neither sympathetic beta-adrenergic receptor block nor cholinergic receptor block enhanced the magnitude of the pulmonary vasoconstrictor response to reperfusion during pentobarbital anesthesia. Thus, in contrast to the conscious state, the pulmonary vascular response to reperfusion is characterized by active, non-flow-dependent pulmonary vasoconstriction during pentobarbital anesthesia. This response is primarily, but not exclusively, mediated by sympathetic alpha-adrenergic vasoconstriction and is not offset by either sympathetic beta-adrenergic or cholinergic vasodilation. These results indicate, that, compared with the conscious state, pentobarbital anesthesia modifies pulmonary vasoregulation, during reperfusion following hypotension and hypoperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Halothane anesthesia abolishes pulmonary vascular responses to neural antagonists

1992 ◽  
Vol 262 (1) ◽  
pp. H117-H122 ◽  
Author(s):  
B. B. Chen ◽  
D. P. Nyhan ◽  
D. M. Fehr ◽  
P. A. Murray
Keyword(s):  
Entire Range ◽  
Vena Cava ◽  
Cholinergic Receptor ◽  
Conscious State ◽  
Conscious Dogs ◽  
Halothane Anesthesia ◽  
Pulmonary Vasodilation ◽  
Inhalational Anesthetic ◽  
Pulmonary Arterial ◽  
End Tidal

We investigated the effects of the inhalational anesthetic halothane on autonomic nervous system (ANS) regulation of the baseline pulmonary vascular pressure-flow (P/Q) relationship compared with that measured in the conscious state. Multipoint pulmonary vascular P/Q plots were constructed by stepwise constriction of the thoracic inferior vena cava to decrease venous return and Q. P/Q plots were generated in the same dogs in the conscious state and during halothane anesthesia (approximately 1.2% end tidal) in the intact (no drug) condition and after administration of selective ANS antagonists. In conscious dogs, sympathetic alpha 1-adrenoreceptor block with prazosin decreased (P less than 0.01) the pulmonary vascular pressure gradient [pulmonary arterial pressure-pulmonary arterial wedge pressure (PAP-PAWP)] over the entire range of Q studied; i.e., inhibition of endogenous alpha 1-adrenoreceptor activity caused pulmonary vasodilation. In contrast, alpha 1-adrenoreceptor block had no effect on PAP-PAWP at any value of Q during halothane anesthesia. In conscious dogs, sympathetic beta-adrenoreceptor block with propranolol increased (P less than 0.01) PAP-PAWP over the entire range of Q studied; i.e., inhibition of endogenous beta-adrenoreceptor activity resulted in pulmonary vasoconstriction. However, beta-adrenoreceptor block had no effect on PAP-PAWP at any value of Q during halothane anesthesia. Finally, cholinergic receptor block with atropine decreased (P less than 0.05) PAP-PAWP at values of Q greater than 100 ml.min-1.kg-1 in conscious dogs but had no effect on PAP-PAWP at any value of Q during halothane anesthesia. These results indicate that endogenous ANS regulation of the baseline pulmonary vascular P/Q relationship observed in conscious dogs is abolished during halothane anesthesia.

Autonomic nervous system pulmonary vasoregulation after hypoperfusion in conscious dogs

1988 ◽  
Vol 254 (5) ◽  
pp. H976-H983
Author(s):  
P. W. Clougherty ◽  
D. P. Nyhan ◽  
B. B. Chen ◽  
H. M. Goll ◽  
P. A. Murray
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Cardiac Index ◽  
Cholinergic Receptor ◽  
Conscious Dogs ◽  
Base Line ◽  
Beta Adrenergic ◽  
Autonomic Nervous ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasoconstriction

We investigated the role of the autonomic nervous system (ANS) in the pulmonary vascular response to increasing cardiac index after a period of hypoperfusion (defined as reperfusion) in conscious dogs. Base-line and reperfusion pulmonary vascular pressure-cardiac index (P/Q) plots were generated by stepwise constriction and release, respectively, of an inferior vena caval occluder to vary Q. Surprisingly, after 10-15 min of hypoperfusion (Q decreased from 139 +/- 9 to 46 +/- 3 ml.min-1.kg-1), the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) was unchanged over a broad range of Q during reperfusion compared with base line when the ANS was intact. In contrast, pulmonary vasoconstriction was observed during reperfusion after combined sympathetic beta-adrenergic and cholinergic receptor block, after beta-block alone, but not after cholinergic block alone. The pulmonary vasoconstriction during reperfusion was entirely abolished by combined sympathetic alpha- and beta-block. Although sympathetic alpha-block alone caused pulmonary vasodilation compared with the intact, base-line P/Q relationship, no further vasodilation was observed during reperfusion. Thus the ANS actively regulates the pulmonary circulation during reperfusion in conscious dogs. With the ANS intact, sympathetic beta-adrenergic vasodilation offsets alpha-adrenergic vasoconstriction and prevents pulmonary vasoconstriction during reperfusion.

Pentobarbital augments pulmonary vasoconstrictor response to cyclooxygenase inhibition

1989 ◽  
Vol 257 (4) ◽  
pp. H1140-H1146 ◽  
Author(s):  
D. P. Nyhan ◽  
B. B. Chen ◽  
D. M. Fehr ◽  
H. M. Goll ◽  
P. A. Murray
Keyword(s):  
Venous Blood ◽  
Vena Cava ◽  
Blood Gases ◽  
Conscious Dogs ◽  
Mixed Venous Blood ◽  
Base Line ◽  
Pentobarbital Anesthesia ◽  
Vasoconstrictor Response ◽  
Anesthetized Dogs ◽  
Endogenous Metabolites

We utilized multipoint pulmonary vascular pressure-flow (P/Q) plots to investigate the effects of pentobarbital sodium anesthesia on regulation of the pulmonary circulation by endogenous metabolites of the cyclooxygenase pathway. Our specific objective was to characterize the effects of two chemically dissimilar inhibitors of the cyclooxygenase pathway, indomethacin and sodium meclofenamate, on the pulmonary vascular P/Q relationship measured in conscious and pentobarbital-anesthetized dogs. P/Q plots were generated by graded constriction of the thoracic inferior vena cava, which produced stepwise decreases in Q. Controlled ventilation during pentobarbital anesthesia (30 mg/kg iv) allowed the matching of systemic arterial and mixed venous blood gases to conscious values. Pentobarbital had no net effect on the base-line P/Q relationship compared with that measured in conscious dogs. Cyclooxygenase pathway inhibition with either indomethacin (5 mg/kg iv) or meclofenamate (2.5 mg/kg iv) resulted in active, flow-independent pulmonary vasoconstriction (P less than 0.01) in both conscious and pentobarbital-anesthetized dogs. However, the magnitude of the pulmonary vasoconstrictor response to indomethacin was increased (P less than 0.05) over a broad range of Q, and the pulmonary vasoconstrictor response to meclofenamate was increased (P less than 0.05) over the entire range of Q in pentobarbital-anesthetized compared with conscious dogs. Thus regulation of the base-line pulmonary vascular P/Q relationship by endogenous metabolites of the cyclooxygenase pathway in conscious dogs is altered during pentobarbital anesthesia.

Differential effects of general anesthesia on cGMP-mediated pulmonary vasodilation

1992 ◽  
Vol 73 (2) ◽  
pp. 721-727 ◽  
Author(s):  
P. A. Murray ◽  
D. M. Fehr ◽  
B. B. Chen ◽  
P. Rock ◽  
J. W. Esther ◽  
...  
Keyword(s):  
Conscious State ◽  
General Anesthetic ◽  
Halothane Anesthesia ◽  
Pentobarbital Sodium ◽  
Pentobarbital Anesthesia ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasodilator ◽  
Pulmonary Arterial ◽  
End Tidal ◽  
Pentobarbital Sodium Anesthesia

We investigated the effects of an intravenous (pentobarbital sodium) and an inhalational (halothane) general anesthetic on guanosine 3′,5′-cyclic monophosphate- (cGMP) mediated pulmonary vasodilation compared with responses measured in the conscious state. Multipoint pulmonary vascular pressure-flow plots were generated in the same nine dogs in the fully conscious state, during pentobarbital sodium anesthesia (30 mg/kg iv), and during halothane anesthesia (approximately 1.2% end tidal). Continuous intravenous infusions of bradykinin (2 micrograms.kg-1.min-1) and sodium nitroprusside (5 micrograms.kg-1.min-1) were utilized to stimulate endothelium-dependent and -independent cGMP-mediated pulmonary vasodilation, respectively. In the conscious state, both bradykinin and nitroprusside decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary arterial wedge pressure) over the entire range of flows studied; i.e., bradykinin and nitroprusside caused active flow-independent pulmonary vasodilation. Pulmonary vasodilator responses to bradykinin (P less than 0.01) and nitroprusside (P less than 0.05) were also observed during pentobarbital anesthesia. In contrast, during halothane anesthesia, the pulmonary vasodilator responses to both bradykinin and nitroprusside were abolished. These results indicate that, compared with the conscious state, cGMP-mediated pulmonary vasodilation is preserved during pentobarbital anesthesia but is abolished during halothane anesthesia.

Combined neurohumoral block modulates pulmonary vascular P/Q relationship in conscious dogs

1988 ◽  
Vol 255 (5) ◽  
pp. H1084-H1090
Author(s):  
H. S. Geller ◽  
D. P. Nyhan ◽  
H. M. Goll ◽  
P. W. Clougherty ◽  
B. B. Chen ◽  
...  
Keyword(s):  
Inferior Vena ◽  
Vena Cava ◽  
Conscious Dogs ◽  
Vascular Response ◽  
Cyclooxygenase Inhibition ◽  
Pulmonary Vasodilation ◽  
Vascular Regulation ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Vasodilator ◽  
Pathway Inhibition

Our objective was to investigate the integrated pulmonary vascular response of conscious dogs to combined inhibition of the autonomic nervous system, arginine vasopressin (V1) receptors (vasopressinergic V1), and converting enzyme to identify the overall influence of these three major neurohumoral mechanisms in vascular regulation of the pulmonary circulation. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were generated by graded constriction of the thoracic inferior vena cava, which produced stepwise decreases in Q. When compared with the P/Q relationship measured in intact conscious dogs, combined neurohumoral block resulted in active, nonflow-dependent pulmonary vasodilation. A second objective was to assess the extent to which cyclooxygenase pathway inhibition modified both the intact P/Q relationship and the pulmonary vasodilator response to combined neurohumoral block. Cyclooxygenase inhibition alone (either indomethacin or sodium meclofenamate) resulted in active, nonflow-dependent pulmonary vasoconstriction. Moreover, the pulmonary vasodilation in response to combined neurohumoral block was entirely abolished following cyclooxygenase inhibition. Thus the integrated pulmonary vascular response of conscious dogs to combined neurohumoral block is active vasodilation. This response appears to be mediated by metabolites of the cyclooxygenase pathway.

Neurohumoral regulation of the pulmonary circulation during circulatory hypotension in conscious dogs

1993 ◽  
Vol 75 (4) ◽  
pp. 1675-1682 ◽  
Author(s):  
W. P. Peterson ◽  
G. A. Trempy ◽  
K. Nishiwaki ◽  
D. P. Nyhan ◽  
P. A. Murray
Keyword(s):  
Angiotensin Ii ◽  
Muscarinic Receptor ◽  
Arginine Vasopressin ◽  
Pulmonary Circulation ◽  
Vena Cava ◽  
Receptor Activation ◽  
Conscious Dogs ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Vasodilator ◽  
Receptor Block

We investigated the effects of circulatory hypotension (HYPO) on the left pulmonary vascular pressure-flow relationship in chronically instrumented conscious dogs and the role of five neurohumoral mechanisms in either mediating or modulating the response to this stimulus. HYPO was induced by acute (approximately 15-min) inflation of a hydraulic occluder implanted around the thoracic inferior vena cava, which decreased systemic arterial pressure to approximately 55 mmHg. HYPO resulted in active pulmonary vasoconstriction (53–66%; P < 0.01) in intact conscious dogs. Sympathetic alpha 1-adrenoreceptor block reduced (P < 0.01) the magnitude of HYPO-induced pulmonary vasoconstriction by 91–99%. Neither sympathetic beta-adrenoreceptor block nor cholinergic muscarinic receptor block had any significant effect on the magnitude of HYPO-induced pulmonary vasoconstriction. Surprisingly, angiotensin II receptor block increased (P < 0.05) HYPO-induced pulmonary vasoconstriction by 69–91%. In contrast, arginine vasopressin V1-receptor block reduced (P < 0.05) HYPO-induced pulmonary vasoconstriction by 34–41%. These results indicate that the pulmonary circulation of intact conscious dogs is actively regulated by three distinct neurohumoral mechanisms during HYPO. Sympathetic alpha 1-adrenoreceptor activation is the primary mediator of HYPO-induced pulmonary vasoconstriction. Angiotensin II and arginine vasopressin exert opposing pulmonary vasodilator and vasoconstrictor effects during HYPO, whereas sympathetic beta-adrenoreceptor and cholinergic muscarinic receptor activation do not appear to modulate the pulmonary vascular response to HYPO.

Opposing hemodynamic effects of substance P on pulmonary vasculature in rabbits

1985 ◽  
Vol 59 (4) ◽  
pp. 1098-1103 ◽  
Author(s):  
G. S. Worthen ◽  
R. S. Gumbay ◽  
D. T. Tanaka ◽  
M. M. Grunstein
Keyword(s):  
Substance P ◽  
Vena Cava ◽  
Aortic Pressure ◽  
Pulmonary Vasculature ◽  
Base Line ◽  
Epinephrine Infusion ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasoconstriction ◽  
Thromboxane Synthase Inhibitor ◽  
Synthase Inhibitor

Substance P is a peptide implicated in the control of a variety of physiological processes. Although substance P-containing neurons impinge on the pulmonary vasculature, the effects of substance P on the pulmonary circulation have not been systematically investigated. Rabbits were anesthetized with methohexital sodium and paralyzed with pancuronium bromide. Injection of substance P (0.002–0.10 microgram/kg) in the vena cava produced dose-dependent pulmonary vasoconstriction and systemic vasodilation. Pulmonary arterial pressure reached a peak within 15–20 s and declined toward base line over 10 min. Aortic pressure fell rapidly, reaching minimum at 5–10 s. At higher doses cardiac output fell transiently, resulting in a 65% fall in pulmonary vascular conductance. If repeat substance P dosages were administered 15 min apart, there was no tachyphylaxis. Pulmonary vasoconstriction was inhibited by the cyclooxygenase blocker meclofenamate (10 mg/kg) and the thromboxane synthase inhibitor Dazmegrel (UK-38,485) (2 mg/kg). In contrast, vasoconstriction was enhanced by atropine (2 mg/kg). In Dazmegrel-treated animals in whom pulmonary vasoconstriction was established by epinephrine infusion, low doses of substance P produced vasodilation. Our findings indicate that substance P produces pulmonary vasoconstriction via prostaglandin (particularly thromboxane) generation and pulmonary vasodilation via activation of cholinergic pathways.

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