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Objective: To test the hypothesis that norepinephrine induces a pressor response in the pulmonary vascular bed of the cat and identify the alpha-(1)adrenoceptor subtypes involved in the mediation or modulation of these effects.Design: Prospective vehicle controlled study.Setting: University research laboratory.Subjects: Intact chest preparation, adult mongrel cats.Interventions: In separate experiments, the effects of 5-methyl-urapidil, a selective alpha-(1)A-subtype adrenoceptor antagonist, chloroethylclonidine, an alpha-(1)B-subtype and -(1)D-subtype adrenoceptor antagonist, and BMY 7378, the selective alpha-(1)D-subtype adrenoceptor antagonist, were investigated on pulmonary arterial responses to norepinephrine and other agonists in the pulmonary vascular bed of the cat.Measurements and Main Results: The systemic pressure and lobar arterial perfusion pressure were continuously monitored, electronically averaged, and permanently recorded. In the feline pulmonary vascular bed of the isolated left lower lobe, norepinephrine induced a dose-dependent vasoconstrictor response that was not significantly altered after administration of BMY 7378. However, the responses to norepinephrine were significantly attenuated following administration of 5-methyl-urapidil and chloroethylclonidine.Conclusions: The results of the present study suggest that norepinephrine has potent vasopressor activity in the pulmonary vascular bed of the cat and that this response may be mediated or modulated by both alpha-(1)A-subtype and -(1)B-subtype adrenoceptor sensitive pathways. [ABSTRACT FROM AUTHOR]

Objective: There are extensive data on roles of cyclooxygenase 1 (COX 1) and cyclooxygenase 2 (COX 2) enzymes in temperature, coagulation, and inflammatory modulation. There is little known of the function of these enzymes in regulating tone in pulmonary vasculature. The purpose of this investigation was to elucidate the roles of COX 1 and 2 enzymes in the feline pulmonary vascular bed., Design: Prospective vehicle controlled study., Setting: University research laboratory., Subjects: Intact chest preparation; adult mongrel cats., Interventions: The effects of intravascular administration of U46619, angiotensin II, prostaglandin E1 (PGE1), arachidonic acid, and norepinephrine, were analyzed before and after intravascular administration of selective COX enzyme inhibitors., Measurements and Main Results: Because lobar arterial flow is constant in these experiments, changes in lobar pressure represent changes in pulmonary arterial resistance. Under constant flow conditions, lobar arterial and systemic pressures were continuously monitored, electronically averaged, and recorded. In the isolated left lower lobe of the feline lung bed, U46619, angiotensin II, arachidonic acid, and norepinephrine induced a dose-dependent vasoconstrictor response. PGE1 induced a dose-dependent vasodepressor response. After administration of the COX 1 inhibitor SC 560, the arachidonic acid-induced vasopressor responses were significantly attenuated while U46619, angiotensin II, and norepinephrine-induced vasopressor, and PGE1-induced vasodepressor responses were not significantly altered. After administration of the COX 2 inhibitor nimesulide, both the PGE 1 vasodepressor responses and arachidonic acid-induced vasopressor responses were significantly decreased while the U46619, angiotensin II, and norepinephrine-induced vasopressor responses were not significantly attenuated., Conclusions: The results of the study indicate that PGE1 has potent vasodepressor effects in the feline lung bed and this response is mediated by COX 2 pathways. The data also suggest that arachidonic acid has potent vasopressor activity in the feline pulmonary vascular bed and this response is mediated by both COX 1 and COX 2 sensitive pathways.

The objective of this study was to test the hypothesis that fentanyl induces a depressor response in the pulmonary vascular bed of the cat and to identify the receptors involved in the mediation or modulation of these effects. The authors conducted a prospective vehicle-controlled study at a university research laboratory using intact chest preparation in adult mongrel cats. In separate experiments, the effects of diphenhydramine (histamine receptor blocker), glibenclamide (ATP-sensitive K+ channel blocker), L-N5-(1-Iminoethyl) ornithine hydrochloride (L-NIO) (nitric oxide synthase inhibitor), nimesulide (selective cyclooxygenase [COX]-2 inhibitor), and naloxone (opiate receptor antagonist) were investigated on pulmonary arterial responses to fentanyl and other agonists in the pulmonary vascular bed of the cat. The systemic pressure and lobar arterial perfusion pressure were continuously monitored, electronically averaged, and recorded. In the feline pulmonary vascular bed of the isolated left lower lobe, fentanyl induced a dose-dependent vasodepressor response that was not significantly altered after administration of glibenclamide, L-NIO, and nimesulide. However, the responses to fentanyl were significantly attenuated after administration of diphenhydramine and naloxone. The results of the present study suggest that fentanyl has potent vasodepressor activity in the pulmonary vascular bed of the cat and that this response may be mediated or modulated by both histaminergic and opiate receptor sensitive pathways.

In this investigation we sought to identify the role of remifentanil in the feline pulmonary vascular bed. Using adult mongrel cats in separate experiments, the effects of glibenclamide (adenosine triphosphate-sensitive K+ channel blocker), diphenhydramine (histamine H(1)-receptor antagonist), L-N5-(1-Iminoethyl) ornithine hydrochloride (nitric oxide synthase inhibitor), and naloxone (opioid receptor antagonist) were investigated in pulmonary arterial responses to remifentanil (opioid agonist), pinacidil (adenosine triphosphate-sensitive K+ channel activator), and bradykinin (nitric oxide synthase inducer). Under increased tone conditions in the isolated left lower lobe vascular bed of the cat, remifentanil induced a dose-dependent vasodepressor response that was not significantly altered after administration of glibenclamide and L-N5-(1-Iminoethyl) ornithine hydrochloride. Responses to remifentanil were significantly attenuated after administration of diphenhydramine and naloxone. The results suggest that remifentanil has potent vasodepressor activity in the feline pulmonary vascular bed and that these responses are mediated by histamine and opioid receptor sensitive pathways.

In this investigation, we sought to identify the role of gamma-aminobutyric acid (GABA)(A) and GABA(B) receptors in the feline pulmonary vascular bed. Using adult mongrel cats and in separate experiments, we investigated the effects of l-N(5)-(1-iminoethyl) ornithine hydrochloride (l-NIO) (a nitric oxide synthase inhibitor), glibenclamide (an adenosine triphosphate (ATP)-sensitive K(+) channel blocker), meclofenamate (a nonselective cyclooxygenase inhibitor), bicuculline (a GABA(A) receptor antagonist), and saclofen (a GABA(B) receptor antagonist) on pulmonary arterial responses to pinacidil (an ATP-sensitive K(+) channel activator), bradykinin (a nitric oxide synthase inducer), muscimol (a GABA(A) receptor agonist), and 3-aminopropyl(methyl)phosphinic acid, hydrochloride (SKF-97541; a GABA(B) receptor agonist). Under increased tone conditions in the isolated left lower lobe vascular bed of the cat, muscimol induced a dose-dependent vasodepressor response that was not significantly altered after the administration of l-NIO, glibenclamide, meclofenamate, and saclofen. SKF-97541-induced vasodepression was not significantly attenuated after the administration of l-NIO, meclofenamate, and bicuculline. Responses to SKF-97541 were significantly attenuated after the administration of glibenclamide and saclofen. Responses to muscimol were significantly reduced after the administration of bicuculline. The results suggest that muscimol and SKF-97541 have potent vasodepressor activity in the feline pulmonary vascular bed and that these responses are modulated by, respectively, GABA(A) and GABA(B) receptor-sensitive pathways. Further, SKF-97541-induced vasodepression is mediated or modulated by an ATP-sensitive K(+) channel.

Tissue Doppler Imaging (TDI) provides information on systolic function through its systolic mitral annulus velocity wave (Sm), reflecting the peak velocity of shortening of the myocardial fibers oriented in the longitudinal direction. In this study, we evaluated the effect of load changes on Sm. Forty-two cardiac surgical patients with left ventricular ejection fraction >60% were consecutively evaluated. In 24 patients, load was changed with an IV bolus of phenylephrine (50-100 microg) or nitroglycerine (300-500 microg); in 18 patients, preload was changed with a rapid infusion of 500 mL of a gelatin solution. The sample volume of TDI was placed at the lateral side of the mitral annulus in the mid-esophageal 4-chamber view. Changing loading conditions with phenylephrine or nitroglycerine had no effect on Sm; the increase of preload in 18 patients resulted in a statistically significant increase of Sm (baseline, 8.4 +/- 2.6 cm/s; after increase of preload, 9.6 +/- 2.5 cm/s; P = 0.001). We conclude that Sm is dependent on changes in preload obtained by volume loading and cannot be recommended as an index of ventricular contractile performance in critically ill patients where significant changes in ventricular filling occur.