Biomedical subjects

B B Chen

Publications and source records attributed to B B Chen.

At least 19 recordsLinked to original sources

PubMed2000

Structure-activity relationship studies on 1-[2-(4-Phenylphenoxy)ethyl]pyrrolidine (SC-22716), a potent inhibitor of leukotriene A(4) (LTA(4)) hydrolase.

Leukotriene B(4) (LTB(4)) is a pro-inflammatory mediator that has been implicated in the pathogenesis of a number of diseases including inflammatory bowel disease (IBD) and psoriasis. Since the action of LTA(4) hydrolase is the rate-limiting step for LTB(4) production, this enzyme represents an attractive pharmacological target for the suppression of LTB(4) production. From an in-house screening program, SC-22716 (1, 1-[2-(4-phenylphenoxy)ethyl]pyrrolidine) was identified as a potent inhibitor of LTA(4) hydrolase. Structure-activity relationship (SAR) studies around this structural class resulted in the identification of a number of novel, potent inhibitors of LTA(4) hydrolase, several of which demonstrated good oral activity in a mouse ex vivo whole blood assay.

Administration, Oral↗

PubMed2000

[Detection of HPV-DNA and humoral immunity in juvenile laryngeal papilloma].

OBJECTIVE: To study HPV infection route and pathogenesis of juvenile laryngeal papilloma(JLP). METHOD: HPV-DNA of JLP was detected with PCR and PCR product dot blot hybridization. Serum Ig and complement 3(C3) was detected with nephelometry. RESULT: HPV total positive rate in JLP was 95%(19/20). HPV6 was 55%(11/20). HPV11 was 30%(6/20), and HPV6 + 11 was 10%(2/20). Serum IgG, IgA, IgM and C3 of JLP were normal, no significant difference between JLP and the control group(P > 0.05). CONCLUSION: HPV6 infection of JLP was in the majority. And the type was consistent with the type of female genital organ pointed condyloma. Humoral immunity was negligible in HPV infection. Pathologic picture of different HPV type infection was identical.

Child↗

PubMed1998

Electron transfer processes in the reactivity of nonsteroidal anti-inflammatory drugs in the ground and excited states.

The nonsteroidal anti-inflammatory drugs (NSAID), naproxen, sulindac and indomethacin, were shown to donate electrons to nitro blue tetrazolium (NBT) when irradiated with UV light in deoxygenated aqueous buffer solution (pH 7.4, 30 degrees C). The reaction was monitored spectrophotometrically by the appearance of the diformazan reduction product from NBT. The electron transfer process facilitates the decomposition of the drugs. Naproxen in the presence of NBT is photodegraded principally to the alcohol (2-[1-hydroxyethyl]-6-methoxynaphthalene) at a rate approximately 20-fold faster than when irradiated alone in deoxygenated conditions. The photoproduct from naproxen also participates in the electron transfer to NBT but at a much slower rate than naproxen. Irradiation of sulindac or indomethacin in the presence of NBT caused the slow photoreduction of NBT to diformazan. In the absence of NBT, indomethacin and sulindac are essentially unreactive when irradiated in aqueous solution. The ability of a number of NSAID to act as electron donors in their ground state was studied by observing their oxidation by potassium peroxodisulfate in pH 7.0 phosphate buffer at 50 degrees C. The HPLC analysis of the drug remaining showed that the 2-arylpropionic acid NSAID (naproxen, ibuprofen, ketoprofen and suprofen) reacted at a rate equivalent to the thermal decomposition of peroxodisulfate. The major products were the same as detected in the photooxidation of these drugs, resulting from decarboxylation and oxygen addition but also included a dimeric compound. On the other hand, the NSAID that do not contain the propionic acid substituent all reacted more slowly with peroxodisulfate, enabling specific reaction rate constants to be evaluated.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1995

Use of the Pannell-Milstein roller bottle apparatus to produce high concentrations of the CSF-1, the mouse macrophage growth factor.

A simple roller bottle apparatus for growing B cell hybridomas in dialysis tubing yields high concentrations of monoclonal antibodies (Pannell and Milstein, J. Immunol. Methods (1992) 146, 43-48). Here we describe an adaptation of this apparatus for the simple production of high concentrations of the mouse macrophage specific growth factor, CSF-1. This apparatus appears to have general applicability for the production of other secreted cytokines.

Agar↗

PubMed1995

Alternate forms of the Auditory-Verbal Learning Test: issues of test comparability, longitudinal reliability, and moderating demographic variables.

The present investigation examines the alternate-form and longitudinal reliability of two versions of the Auditory-Verbal Learning Test (AVLT) on a large, multiregional, healthy male sample. Subjects included 2,059 bisexual and homosexual HIV-seronegative males recruited from the Multicenter AIDS Cohort Study from centers in Baltimore, Chicago, Los Angeles, and Pittsburgh. The findings revealed no significant differences between forms upon initial or 1-year longitudinal administration, supporting the equivalence of the two versions. However, significant practice effects were noted longitudinally, arguing for the need of appropriate retest normative data. Furthermore, as age, ethnicity, and education were found to significantly affect test performance, it is recommended that normative data be interpreted according to these variables. In addition to providing normative and longitudinal data, this investigation presents information concerning the use and limitations of the alternate forms of the AVLT.

Journal Article↗

PubMed1992

Halothane anesthesia abolishes pulmonary vascular responses to neural antagonists.

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.

Adrenergic alpha-Antagonists↗

PubMed1992

Anesthesia alters pulmonary vasoregulation by angiotensin II and captopril.

We investigated the effects of an intravenous (pentobarbital sodium) and inhalational (halothane) general anesthetic on the pulmonary vascular responses to angiotensin II and angiotensin-converting enzyme inhibition (CEI). Multipoint pulmonary vascular pressure-flow (P/Q) plots were generated in conscious pentobarbital- (30 mg/kg iv) and halothane-anesthetized (approximately 1.2% end-tidal) dogs in the intact (no drug) condition, during angiotensin II administration (60 ng.kg-1.min-1 iv), and during CEI (captopril 1 mg/kg plus 1 mg.kg-1.h-1 iv). In conscious dogs, angiotensin II increased (P less than 0.001) the pulmonary vascular pressure gradient [pulmonary arterial pressure--pulmonary arterial wedge pressure (PAP-PAWP)] over the empirically measured range of Q; i.e., angiotensin II caused pulmonary vasoconstriction. Pulmonary vasoconstriction (P less than 0.01) in response to angiotensin II was also observed during pentobarbital sodium anesthesia. In contrast, angiotensin II had no effect on the P/Q relationship during halothane anesthesia. In conscious dogs, CEI decreased (P less than 0.001) PAP-PAWP over the empirically measured range of Q; i.e., CEI caused pulmonary vasodilation. However, CEI caused pulmonary vasoconstriction (P less than 0.02) during pentobarbital sodium and had no effect on the P/Q relationship during halothane. Thus, compared with the conscious state, the pulmonary vasoconstrictor response to angiotensin II is unchanged or abolished, and the pulmonary vasodilator response to CEI is reversed to vasoconstriction or abolished during pentobarbital sodium and halothane anesthesia, respectively.

Anesthesia, General↗

PubMed1992

Acute and chronic pulmonary vasoconstriction after left lung autotransplantation in conscious dogs.

We investigated the acute and chronic effects of left lung autotransplantation (LLA) on the left pulmonary vascular pressure-flow (LP/Q) relationship in conscious dogs. Continuous LP/Q plots were generated in chronically instrumented conscious dogs 2 days, 2 wk, 1 mo, and 2 mo after LLA. Identically instrumented normal conscious dogs were studied at equal time points post-surgery. LLA had little or no effect on baseline systemic hemodynamics or blood gases. In contrast, compared with normal conscious dogs, striking active flow-independent pulmonary vasoconstriction was observed 2 days post-LLA. The slope of the LP/Q relationship was increased from a normal value of 0.275 +/- 0.021 to 0.699 +/- 0.137 mmHg.ml-1.min-1.kg-1 2 days post-LLA. Pulmonary vasoconstriction of similar magnitude was also observed on a chronic basis at 2 wk, 1 mo, and even 2 mo post-LLA. Pulmonary vasoconstriction post-LLA was not due to fixed resistance at the left pulmonary arterial or venous anastomotic sites. Finally, systemic arterial blood gases were unchanged when total pulmonary blood flow was directed to exclusively perfuse the transplanted left lung. Thus, LLA results in both acute and chronic pulmonary vasoconstriction in conscious dogs. LLA should serve as a useful stable experimental model to assess the specific effects of surgical transplantation on pulmonary vascular regulation.

Animals↗

PubMed1992

Differential effects of general anesthesia on cGMP-mediated pulmonary vasodilation.

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.

Anesthesia, General↗

PubMed1991

Hemodynamic effects and onset time of increasing doses of vecuronium in patients undergoing myocardial revascularization.

Study objectives were (1) to compare the hemodynamic effects of increasing doses of vecuronium, given as a bolus during induction of anesthesia using high-dose fentanyl, in patients undergoing myocardial revascularization; and (2) to determine whether increasing the dose of vecuronium would decrease the onset time to maximal depression of twitch response. Forty patients scheduled for elective coronary artery bypass surgery were randomly assigned to four equal groups to receive either 0.1, 0.2, 0.3, or 0.4 mg/kg of vecuronium. Hemodynamic measurements and neuromuscular blockade were recorded at five time points: A, awake state; B, anesthetized state after the administration of fentanyl, 10 micrograms/kg; C, 2 minutes after vecuronium bolus; D, 5 minutes after vecuronium bolus; and E, after intubation. Increasing the dose of vecuronium from 0.1 to 0.2 mg/kg decreased the onset time from 3.8 +/- 0.3 minutes to 1.8 +/- 0.2 minutes (P less than 0.05). However, higher doses of vecuronium (0.3 or 0.4 mg/kg) did not result in further decreases in onset time. There were no significant differences in any hemodynamic parameter measured among the four groups in the anesthetized baseline state. Compared with the anesthetized state, the administration of vecuronium resulted in few alterations in hemodynamics within the groups studied. There were no changes in any hemodynamic parameter at 2 and 5 minutes following administration of 0.4 mg/kg of vecuronium. There were also no dose-related changes in any hemodynamic parameter. Thus, high doses of vecuronium of up to 0.4 mg/kg may be administered to patients with coronary artery disease with few hemodynamic changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Pulmonary vasoregulation by cyclooxygenase metabolites and angiotensin II after hypoperfusion in conscious, pentobarbital-anesthetized, and halothane-anesthetized dogs.

The authors investigated the extent to which endogenously produced metabolities of the cyclooxygenase pathway and angiotensin II modulate the pulmonary vascular response to increasing pulmonary blood flow after a period of systemic and pulmonary hypotension and hypoperfusion (defined as posthypoperfusion) in conscious, pentobarbital-anesthetized, and halothane-anesthetized dogs. The authors tested the hypothesis that vasodilator metabolites of the cyclooxygenase pathway offset the vasoconstrictor influence of angiotensin II to prevent pulmonary vasoconstriction posthypoperfusion. Baseline and posthypoperfusion pulmonary vascular pressure-cardiac index (P/Q) plots were constructed by stepwise inflation and deflation, respectively, of a hydraulic occluder implanted around the inferior vena cava to vary Q. In intact (no drug), conscious dogs, the pulmonary vascular P/Q relationship posthypoperfusion was not altered significantly compared with baseline. In contrast, after cyclooxygenase inhibition, active flow-independent pulmonary vasoconstriction (12-17%; P less than 0.01) was observed posthypoperfusion, and this response was abolished entirely by angiotensin converting-enzyme inhibition. During pentobarbital anesthesia, significant pulmonary vasoconstriction (27%; P less than 0.01) occurred posthypoperfusion in the no-drug condition. However, the magnitude of the posthypoperfusion vasoconstriction was not increased by cyclooxygenase inhibition, nor was it reduced by converting-enzyme inhibition. During halothane anesthesia, pulmonary vasoconstriction was not observed posthypoperfusion in the no-drug condition, but it was unmasked (8-13%; P less than 0.05) by cyclooxygenase inhibition and attenuated partially by converting-enzyme inhibition. These results indicate that cyclooxygenase metabolites and angiotensin II exert opposing vasodilator and vasoconstrictor effects, respectively, on the pulmonary circulation of conscious dogs posthypoperfusion. These competing mechanisms are active during halothane anesthesia but are abolished during pentobarbital anesthesia.

Anesthesia↗

PubMed1990

Halothane alters the oxygen consumption-oxygen delivery relationship compared with conscious state.

The authors' objectives were as follows: 1) to characterize for the first time the relationship between whole body O2 delivery (DO2) and O2 consumption (VO2) in adult conscious dogs; and 2) to asses the effects of the inhalational anesthetic, halothane, on that relationship. DO2 was varied over a wide range in chronically instrumented dogs by gradual inflation and deflation of a hydraulic occluder implanted around the thoracic inferior vena cava to alter venous return and cardiac output. VO2 was measured at different values of DO2 in dogs in the fully conscious state and again during halothane anesthesia. A "binning" technique indicated that halothane decreased VO2 (P less than 0.01) at any given value of DO2 over a broad range of VO2. A two-line piecewise linear regression analysis technique indicated that halothane decreased (P less than 0.01) the critical O2 delivery (COD) from 20 +/- 3 to 10 +/- 1 ml.kg-1.min-1 and increased (P less than 0.01) O2 extraction at COD from 31 +/- 3 to 40 +/- 2%. However, the DO2-VO2 plots measured in both conscious and halothane-anesthetized dogs did not exhibit a discrete discontinuity but rather were closely fit (correlation coefficient = 0.98) by an exponential equation of the following form: O2 extraction = B1.(1 - exp (-DO2/B2))/DO2, where B1 is the delivery-independent estimate of VO2 and B2 is the "delivery constant," i.e., the DO2 associated with a VO2 equal to 63% of B1. Halothane decreased B1 (P less than 0.01) from 5.3 +/- 0.1 to 3.9 +/- 0.1 ml.kg-1.min-1 and decreased B2 (P less than 0.01) from 5.6 +/- 0.3 to 3.6 +/- 0.3 ml.kg-1.min-1 compared with that measured in conscious dogs. Thus, compared with the conscious state, halothane anesthesia alters the fundamental relationship between DO2 and VO2 and may have a beneficial effect on tissue oxygenation at low values of DO2.

Animals↗

PubMed1990

Halothane anesthesia causes active flow-independent pulmonary vasoconstriction.

We utilized multipoint pulmonary vascular pressure-flow (P/Q) plots to investigate the effects of halothane anesthesia on the pulmonary circulation. Our first objective was to assess the extent to which the P/Q relationship measured in conscious dogs is altered during halothane anesthesia. P/Q plots were constructed by stepwise constriction of the thoracic inferior vena cava to decrease venous return and Q. Compared with conscious dogs, halothane (approximately 1.2% end-tidal) resulted in active, flow-independent pulmonary vasoconstriction (P less than 0.01) at all levels of Q. Halothane also decreased (P less than 0.01) systemic arterial pressure and Q. Thus our second objective was to determine whether the halothane-induced pulmonary vasoconstriction was mediated by reflex neurohumoral activation or by metabolites of the cyclooxygenase pathway. However, the magnitude of halothane-induced pulmonary vasoconstriction was not significantly reduced by sympathetic alpha-adrenoreceptor block, angiotensin converting-enzyme inhibition, combined arginine vasopressin V1 + V2 receptor block, or by cyclooxygenase inhibition. Finally, halothane-induced pulmonary vasoconstriction (P less than 0.01) was also observed when compared with pentobarbital-anesthetized dogs during controlled ventilation. Thus, compared with the conscious state, halothane anesthesia causes active flow-independent pulmonary vasoconstriction that is not mediated by reflex neurohumoral activation, by metabolites of the cyclooxygenase pathway, nor is it due to the effects of general anesthesia and controlled ventilation.

Adrenergic beta-Antagonists↗

PubMed1989

Pentobarbital anesthesia alters pulmonary vascular response to neural antagonists.

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.

Adrenergic alpha-Antagonists↗

PubMed1989

Pentobarbital augments pulmonary vasoconstrictor response to cyclooxygenase inhibition.

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.

Animals↗

PubMed1988

Autonomic nervous system pulmonary vasoregulation after hypoperfusion in conscious dogs.

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.

Adrenergic beta-Antagonists↗

PubMed1988

Pentobarbital anesthesia modifies pulmonary vasoregulation after hypoperfusion.

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)

Acetylcholine↗

PubMed1988

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

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.

Animals↗