Pulmonary Vascular Endothelial Responses are Differentially Modulated After Cardiopulmonary Bypass

Nyhan, Daniel; Gaine, Seán; Hales, Mariesa; Zanaboni, Paul; Simon, Brett A.; Berkowitz, Dan E.; Flavahan, Nicholas A.

doi:10.1097/00005344-199910000-00007

Cited by 7 publications

(6 citation statements)

References 30 publications

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“…The function of eNOS has been studied in experimental models of acute but not of chronic lung ischemia. Our results in animals studied 2 d after pulmonary artery ligation are consistent with reports by Serraf and coworkers (18) and Nyhan and coworkers (19) of a selective decrease in receptor-mediated endothelium-dependent pulmonary artery relaxation after acute lung ischemia caused by cardiopulmonary bypass in dogs and pigs. This decrease contrasts with our finding of increased lung eNOS activity after acute ischemia, a result also reported by Lu and coworkers (6), and suggests that acute lung ischemia may cause selective alterations in receptor-mediated eNOS signaling.…”

Section: Discussionsupporting

confidence: 92%

Endothelial Nitric Oxide Synthase Function in Pig Lung after Chronic Pulmonary Artery Obstruction

Fadel

Mazmanian

Baudet

et al. 2000

Am J Respir Crit Care Med

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Because long-term pulmonary artery (PA) obstruction is associated with expansion of the systemic blood supply to the lung, chronic ischemia may not occur, and endothelium nitric oxide synthase (eNOS) function may be preserved in postobstructive pulmonary arteries. To test this hypothesis, we studied piglets 2 d or 5 wk after left PA ligation or a sham operation. We measured left lung ATP and lactate lung concentrations; calcium-dependent and calcium-independent NOS activities and eNOS protein; and left PA relaxations in response to acetylcholine, calcium ionophore, and sodium nitroprusside. Decreases in ATP and increases in lactate concentrations were significantly attenuated after 5 wk PA occlusion (p < 0.05 versus sham and 2-d ligation). Compared with sham and 2-d PA occlusion, calcium-dependent NOS activity and eNOS protein were lower in the long-term PA occlusion group. Calcium-independent NOS activity was unchanged. Acetylcholine and calcium ionophore relaxations were impaired after 5 wk, whereas only acetylcholine relaxation was impaired after 2-d PA occlusion. Relaxation to sodium nitroprusside remained unchanged. In conclusion, despite relative conservation of lung energy metabolism, prolonged PA occlusion decreased eNOS function and protein in postobstructive pulmonary arteries.

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Section: Discussionsupporting

confidence: 92%

Endothelial Nitric Oxide Synthase Function in Pig Lung after Chronic Pulmonary Artery Obstruction

Fadel

Mazmanian

Baudet

et al. 2000

Am J Respir Crit Care Med

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“…A plausible explanation for the increased vascular resistance would be a loss of vasodilator function. Two studies by Nyhan and colleagues (29,30) indicate that cardiopulmonary bypass elicits an increase in pulmonary vascular resistance and attendant pulmonary hypertension by abolishing endothelium-dependent vasodilation. Thus CHX may mimic the high vascular resistance/pulmonary hypertension associated with bypass through similar vasodilator mechanisms, although this theory requires further testing.…”

Section: Discussionmentioning

confidence: 99%

Cyclohexanone contamination from extracorporeal circuits impairs cardiovascular function

Thompson-Torgerson¹,

Champion²,

Santhanam³

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Extracorporeal circulation provides critical life support in the face of cardiopulmonary or renal failure, but it also introduces a host of unique morbidities characterized by edema formation, cardiac insufficiency, autonomic dysfunction, and altered vasomotor function. We tested the hypothesis that cyclohexanone (CHX), a solvent used in production of extracorporeal circuits and intravenous (IV) bags, leaches into the contained fluids and can replicate these clinical morbidities. Crystalloid fluid samples from circuits and IV bags were analyzed by gas chromatography-mass spectrometry to provide a range of clinical CHX exposure levels, revealing CHX contamination of sampled fluids (9.63-3,694 g/l). In vivo rat studies were conducted (n ϭ 49) to investigate the effects of a bolus IV infusion of CHX vs. saline alone on cardiovascular function, baroreflex responsiveness, and edema formation. Cardiovascular function was evaluated by cardiac output, heart rate, stroke volume, vascular resistance, arterial pressure, and ventricular contractility. Baroreflex function was assessed by mean femoral arterial pressure responses to bilateral carotid occlusion. Edema formation was assessed by the ratio of wet to dry organ weights for lungs, liver, kidneys, and skin. CHX infusion led to systemic hypotension; pulmonary hypertension; depressed contractility, heart rate, stroke volume, and cardiac output; and elevated vascular resistance (P Ͻ 0.05). Mean arterial pressure responsiveness to carotid occlusion was dampened after CHX infusion (from ϩ17.25 Ϯ 1.8 to ϩ5.61 Ϯ 3.2 mmHg; P Ͻ 0.05). CHX infusion led to significantly higher wet-to-dry weight ratios vs. saline only (3.8 Ϯ 0.06 vs. 3.5 Ϯ 0.05; P Ͻ 0.05). CHX can reproduce clinical cardiovascular, neurological, and edema morbidities associated with extracorporeal circulatory treatment. ventricular contractility; autonomic nervous system; vasoconstriction; edema EXTRACORPOREAL CIRCULATION [EC; cardiopulmonary bypass, extracorporeal membrane oxygenation (ECMO), hemodialysis, hemofiltration] has become a primary tool in hospitals, providing critical life support in the face of cardiopulmonary or renal failure. However, EC also introduces a host of unique morbidities, including labile blood pressure, depressed cardiac output, ventricular dysfunction, arrhythmias, and major organ edema (1-2, 8, 17-19, 22, 31-33, 40). Although several randomized clinical trials have been conducted to minimize these and other effects of EC treatment (17), EC morbidity rates still remain high and represent a significant barrier to improved patient care, as evidenced by increased time in the intensive care unit (ICU) and on inotropic support.Cyclohexanone [CHX; C 6 H 10 (AO)] is an organic solvent used in the production of polyvinyl chloride (PVC) medical devices, including intravenous (IV) fluid bags and EC circuits. CHX easily migrates from PVC tubing and connections into fluids that come in contact with PVC (10, 12, 35, 37), irrespective of the type of IV fluid. CHX can leach from PVC bags and IV tub...

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“…7,8) Lack of functional vascular endothelium was confirmed by the loss of relaxant response to 3 mM acetylcholine before the experiment began. 9) After the contraction had reached a stable plateau, cumulative concentrations of test compound were added. The vasorelaxant effect was expressed as a percentage of relaxation and the IC 50 (the concentration to produce a 50% maximal relaxation) value was determined from the concentration-response curve by data fitting with computer software GraFit (Erithacus Software, Staines, Middlesex, U.K.).…”

Section: Establishment Of Concentration-contractile Response Curves Omentioning

confidence: 99%

Vasodilatation Produced by Orientin and Its Mechanism Study

Wang

et al. 2005

Biological & Pharmaceutical Bulletin

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Bamboo leaves, Phyllostachys nigra (LODD. ex. lind-1 MUNRO. L), have been used as a Chinese medicament for thousands of years. Theses leaves have anti-free radical activity and are comparable with the leaf of Ginkgo bilabo, which is one potential resource for natural antioxidant and free radical scavenger. 1) Our previous investigation revealed that bamboo leaves have significant effects on protecting myocardial ischemia in rat, restraining blood platelet aggregation of rabbit, increasing coronal flow and have a vasorelaxant effect on rabbit thoracic aortic rings, and also reduce arterial blood pressure. Here, we further investigated the vasorelaxant effect of four flavonoid C-glycosyl compounds ( Fig. 1): Orientin (Luteolin-8-C-glucoside), Isoorientin (Luteolin-6-Cglucoside), Isovitexin (Apigenin-6-C-glucoside), and Vitexin (Apigenin-8-C-glucoside), first isolated from bamboo leaves, all of which are also found in numerous plants. 2,3) It is reported that these flavonoids possess anxiolytic properties 4,5) and that Orientin possesses antioxidative activity, 6) however, there is no information about the vasorelaxant effect of these compounds. In the present investigation, we examined the vasodilatation effects of these flavonoid C-glycosyl compounds and found only Orientin produced a vasorelaxant effect on rabbit aortic rings. The data from the present study suggested that Orientin relaxed thoracic aortic rings by the nitric oxide-guanosine 3,5-cyclic monophosphate (cGMP) pathway, and in the vascular smooth muscle inhibited the contraction induced by the activation of receptor-operating and voltage-dependent Ca 2ϩ channels. Cyclooxygenase pathway, potassium channels, b-receptors and adenosine-3Ј,5Ј-cyclic phosphoric acid (cAMP) pathway, on the other hand, had no apparent roles. The inhibition of both intracellular Ca 2ϩ release and extracellular Ca 2ϩ influx may be one of the main vasorelaxant mechanisms of Orientin. MATERIALS AND METHODS Animal

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Pulmonary Vascular Endothelial Responses are Differentially Modulated After Cardiopulmonary Bypass

Cited by 7 publications

References 30 publications

Endothelial Nitric Oxide Synthase Function in Pig Lung after Chronic Pulmonary Artery Obstruction

Endothelial Nitric Oxide Synthase Function in Pig Lung after Chronic Pulmonary Artery Obstruction

Cyclohexanone contamination from extracorporeal circuits impairs cardiovascular function

Vasodilatation Produced by Orientin and Its Mechanism Study

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