Biomedical subjects

P W Clougherty

Publications and source records attributed to P W Clougherty.

6 recordsLinked to original sources

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↗

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↗

PubMed1987

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

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.

Adrenergic beta-Antagonists↗

PubMed1987

Bradykinin actively modulates pulmonary vascular pressure-cardiac index relationships.

Our objectives were to investigate the pulmonary vascular effects of exogenously administered bradykinin at normal and reduced levels of cardiac index in intact conscious dogs and to assess the extent to which the pulmonary vascular response to bradykinin is the result of either cyclooxygenase pathway activation or reflex activation of sympathetic beta-adrenergic and -cholinergic receptors. Multipoint pulmonary vascular pressure-cardiac index (P/Q) plots were constructed during normoxia in conscious dogs by step-wise constriction of the thoracic inferior vena cava to reduce Q. In intact dogs, bradykinin (2 micrograms X kg-1 X min-1 iv) caused systemic vasodilation, i.e., systemic arterial pressure was slightly decreased (P less than 0.05), Q was markedly increased (P less than 0.01), and mixed venous PO2 and oxygen saturation (SO2) were increased (P less than 0.01). Bradykinin decreased (P less than 0.01) the pulmonary vascular pressure gradient (pulmonary arterial pressure-pulmonary capillary wedge pressure) over the entire range of Q studied (140-60 ml X min-1 X kg-1) in intact dogs. During cyclooxygenase pathway inhibition with indomethacin, bradykinin again decreased (P less than 0.05) pulmonary arterial pressure-pulmonary capillary wedge pressure at every level of Q, although the magnitude of the vasodilator response was diminished at lower levels of Q (60 ml X min-1 X kg-1). Following combined administration of sympathetic beta-adrenergic and -cholinergic receptor antagonists, bradykinin still decreased (P less than 0.01) pulmonary arterial pressure-pulmonary capillary wedge pressure over the range of Q from 160 to 60 ml X min-1 X kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗