Vascular Tone In Patients Research Articles

FOREARM VASCULAR RESPONSES TO MENTAL STRESS AND DEVICE GUIDED BREATHING ASSOCIATE WITH PLASMA CONCENTRATIONS OF NORMETADRENALINES IN SUBJECTS WITH ESSENTIAL HYPERTENSION

Objective: Forearm vasodilator responses to mental stress (MS) are impaired in hypertensive compared to normotensive individuals by a mechanism that may relate to peripheral alpha-adrenergic activity antagonising that of neuronal nitric oxide. We investigated whether the response to MS may be dependent on the level of basal sympathetic activity as measured by plasma concentrations of normetadrenaline (NM) and how responses to slowing respiratory rate by device guided breathing (DGB, which reduces sympathetic activity) vary according to NM concentrations. Design and method: Subjects with essential hypertension were stratified according to concentrations of plasma NM into those with low NM (< or = 500pmol/L) and high NM (> or = to 750pmol/L). Forearm blood flow (FBF) was measured by venous occlusion plethysmography after 15 minutes of rest, during MS elicited by the Stroop word-colour test and during supervised DGB with breathing rate < 10 breaths/minute. Results: Subjects with high NM (n = 30, 15 men) had greater body mass index than those with low NM (n = 30, 17 men): (mean ± SD) 31 ± 7 vs 27 ± 4 kg/m2 (P < 0.05), but the two groups were similar with respect to age and brachial blood pressure (BP). During MS and DGB, changes in BP were similar in subjects in both low NM and high NM groups. MS increased FBF in both groups but the response in high NM was impaired as compared to subjects with low NM (34 ± 3 vs. 49 ± 3 %, P < 0.05). DGB increased forearm vascular resistance to a lesser extent in subjects with high compared to low NM (1.21 ± 7.95 vs 5.50 ± 6.32 mmHg.100 mL/mL, P < 0.05). Conclusions: These results are consistent with greater sympathetic vascular tone in patients with higher NM that antagonises forearm vascular responses to MS. Circulating concentrations of NM may identify subjects with impaired neuronal nitric oxide signalling.

Vasopressor Therapy in Cardiac Surgery—An Experts’ Consensus Statement

Hemodynamic conditions with reduced systemic vascular resistance commonly are observed in patients undergoing cardiac surgery and may range from moderate reductions in vascular tone, as a side effect of general anesthetics, to a profound vasodilatory syndrome, often referred to as vasoplegic shock. Therapy with vasopressors is an important pillar in the treatment of these conditions. There is limited guidance on the appropriate choice of vasopressors to restore and optimize systemic vascular tone in patients undergoing cardiac surgery. A panel of experts in the field convened to develop statements and evidence-based recommendations on clinically relevant questions on the use of vasopressors in cardiac surgical patients, using a critical appraisal of the literature following the GRADE system and a modified Delphi process. The authors unanimously and strongly recommend the use of norepinephrine and/or vasopressin for restoration and maintenance of systemic perfusion pressure in cardiac surgical patients; despite that, the authors cannot recommend either of these drugs with respect to the risk of ischemic complications. The authors unanimously and strongly recommend against using dopamine for treating post-cardiac surgery vasoplegic shock and against using methylene blue for purposes other than a rescue therapy. The authors unanimously and weakly recommend that clinicians consider early addition of a second vasopressor (norepinephrine or vasopressin) if adequate vascular tone cannot be restored by a monotherapy with either norepinephrine or vasopressin and to consider using vasopressin as a first-line vasopressor or to add vasopressin to norepinephrine in cardiac surgical patients with pulmonary hypertension or right-sided heart dysfunction.

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World Health Organization Pulmonary Hypertension Group 2: Pulmonary hypertension due to left heart disease in the adult—a summary statement from the Pulmonary Hypertension Council of the International Society for Heart and Lung Transplantation

Pulmonary hypertension associated with left heart disease is the most common form of pulmonary hypertension encountered in clinical practice today. Although frequently a target of therapy, its pathophysiology remains poorly understood and its treatment remains undefined. Pulmonary hypertension in the context of left heart disease is a marker of worse prognosis and disease severity, but whether its primary treatment is beneficial or harmful is unknown. An important step to the future study of this important clinical problem will be to standardize definitions across disciplines to facilitate an evidence base that is interpretable and applicable to clinical practice. In this current statement, we provide an extensive review and interpretation of the current available literature to guide current practice and future investigation. At the request of the Pulmonary Hypertension (PH) Council of the International Society for Heart and Lung Transplantation (ISHLT), a writing group was assembled and tasked to put forth this document as described above. The review process was facilitated through the peer review process of the Journal of Heart and Lung Transplantation and ultimately endorsed by the leadership of the ISHLT PH Council.

POSTOPERATIVE VASOPRESSIN AND COPEPTIN LEVELS IN NONCARDIAC SURGERY PATIENTS

Further information on the endogenous arginine vasopressin (AVP) response in patients with postoperative systemic inflammatory response syndrome (SIRS) and vasodilatory shock would provide more insight into the pathophysiology of SIRS-associated cardiovascular failure and help indicate AVP therapy. Patients after uncomplicated abdominal surgery without SIRS (n = 10), critically ill patients after noncardiac surgery with SIRS (n = 9), and patients with SIRS plus vasodilatory shock (n = 22) were included in this prospective trial. Plasma AVP (radioimmunoassay) and copeptin (immunoluminometric assay) concentrations together with clinical parameters were documented daily during the first 7 days postoperative. The AVP response significantly differed between the three groups. Patients without SIRS had lower AVP concentrations than SIRS patients with (P = 0.001) or without shock (P = 0.003). Patients with SIRS and shock had higher AVP levels than patients with SIRS alone (P < 0.001). Arginine vasopressin decreased over time (P = 0.007) in all groups. At day 28, nonsurvivors had higher AVP levels than did survivors (P < 0.001). In SIRS patients without shock, serum osmolarity was indirectly associated with AVP levels, whereas mean arterial blood pressure and serum osmolarity were associated with AVP in SIRS patients with shock. Arginine vasopressin and copeptin correlated significantly with each other (P < 0.001; r = 0.76). In patients without hemofiltration, copeptin levels predicted 28-day mortality with high sensitivity and specificity. The postoperative AVP response in noncardiac surgery patients seems well maintained. The possibility that AVP plays a contributory role in the failure to restore vascular tone in patients with vasodilatory shock cannot be excluded but seems less important than in septic or postcardiotomy shock.

The Effects of Extracellular pH on Vasopressin Inhibition of ATP-Sensitive K+ Channels in Vascular Smooth Muscle Cells

Arginine vasopressin (AVP) inhibits ATP-sensitive potassium (K(ATP)) channels and may help to restore vascular tone in patients with vasodilatory shock. In the present study, we investigated whether extracellular acidification modifies the inhibition of vascular K(ATP) channels by AVP. We used a cell-attached patch-clamp configuration to investigate the effects of extracellular pH (pH(o)) on AVP-K(ATP) channel interaction in rat aortic smooth muscle cells. Bath application of AVP significantly inhibited extracellular acidification (pH(o) = 6.5)-induced K(ATP) channel activity in a concentration-dependent manner, with an half-maximal inhibitory concentration (IC50) value of 16.8 pM. Furthermore, bath application of AVP significantly inhibited pinacidil-induced K(ATP) channel activity at mild (pH(o) = 7.0) and severe (pH(o) = 6.5) extracellular acidification, with IC50 values of 266.7 and 21.4 pM, respectively, but failed to significantly inhibit at normal pH (pH(o) = 7.4) or under alkalosis (pH(o) = 9.0). Augmentation of AVP inhibition of vascular K(ATP) channels during extracellular acidification was eliminated by pretreatment with OPC-21268, a specific blocker of the V1 receptor, but not by a V2 blocker, OPC-31260. AVP-induced inhibition was also suppressed by pretreatment with a protein kinase C inhibitor, calphostin C. Our results suggest that AVP inhibits extracellular acidification-induced vascular K(ATP) channel activity, and that the inhibitory effects of AVP on vascular K(ATP) channels are enhanced by extracellular acidification via the V1 receptor-protein kinase C cell-signaling pathway. The potent inhibition of vascular K(ATP) channels by AVP under acidic conditions may make it suitable for management of vasodilatory shock.

Pitavastatin up-regulates the induction of iNOS through enhanced stabilization of its mRNA in pro-inflammatory cytokine-stimulated hepatocytes

Studies have indicated that protective effects of statins (HMG-CoA reductase inhibitor) are associated with the regulation of endothelial nitric oxide synthase (eNOS) or inducible NOS (iNOS) in heart and liver diseases. Statins have been reported to enhance hepatic NO production and decrease the vascular tone in patients with cirrhosis. However, it is unclear which NOS contributes to the increased NO production. We hypothesized that statins are involved in the up-regulation of iNOS in inflammatory liver, resulting in decreased hepatic resistance. Primary cultured rat hepatocytes were treated with pro-inflammatory cytokine interleukin (IL)-1β in the presence or absence of pitavastatin. Pretreatment of cells with pitavastatin resulted in up-regulation of iNOS induction by IL-1β, followed by increased NO production. Pitavastatin had no effects on the degradation of IκB or activation of NF-κB. However, pitavastatin super-induced the up-regulation of type I IL-1 receptor (IL-1RI), which is essential for iNOS induction in addition to the IκB/NF-κB pathway. Mevalonate and geranylgeranylpyrophosphate blocked the stimulatory effects of pitavastatin on iNOS and IL-1RI induction. Transfection experiments revealed that pitavastatin increased the stability of iNOS mRNA rather than its promoter transactivation. In support of this observation, pitavastatin increased the antisense-transcript corresponding to the 3′-UTR of iNOS mRNA, which stabilizes iNOS mRNA by interacting with the 3′-UTR- and RNA-binding proteins. These findings demonstrate that pitavastatin up-regulates iNOS by the stabilization of its mRNA, presumably through the super-induction of IL-1RI and antisense-transcript. This implies that statins may contribute to a novel potentiated treatment in liver injuries including cirrhosis.

Increased arterial vascular tone during the night in patients with essential hypertension

The time-dependent incidence of cardiovascular events points to an important role of chronobiology for arterial properties. To evaluate arterial properties in patients with essential hypertension, we assessed arterial vascular tone during sleep at night in patients with essential hypertension and normotensive control subjects. Vascular tone was continuously quantified by the reflective index obtained by non-invasive digital photoplethysmography and an algorithm for continuous, investigator-independent, automatic analysis of digital volume pulse. During the first half of the night, the reflective index was significantly higher in 31 patients with essential hypertension compared to 30 normotensive control subjects (30.0+/-0.2 vs 28.8+/-0.2; P=0.001). In patients with essential hypertension, the reflective index significantly increased from 30.0+/-0.2 in the first half (from 2301 to 0230) to 30.7+/-0.2 in the second half (from 0231 to 0600) of the night (n=31; P=0.027). In normotensive control subjects the reflective index also significantly increased from 28.8+/-0.2 in the first half of the night to 30.2+/-0.2 in the second half of the night (n=30; P=0.001). An increase of the reflective index tone indicated systemic vasoconstriction as confirmed by cold pressure tests and a significant correlation between arterial vascular tone and sympathetic nerve activity measured by microneurography from the peroneal nerve. Photoplethysmographic determination of arterial vascular tone demonstrated a significant increase of systemic arterial vascular tone in patients with essential hypertension during the first half of the night compared to normotensive control subjects.

Inducible nitric oxide synthase activity does not contribute to the maintenance of peripheral vascular tone in patients with heart failure

Enhanced iNOS (inducible nitric oxide synthase) activity may contribute to vascular dysfunction in patients with heart failure. In the present study, we aimed to determine whether iNOS activity contributes to the maintenance of vascular tone in patients with symptomatic heart failure with the use of the highly selective iNOS inhibitor 1400W {N-[3-(aminomethyl)benzyl] acetamidine}. Bilateral forearm blood flow was measured using venous occlusion plethysmography in 12 patients with New York Heart Association class II-IV heart failure and eight matched healthy control subjects during intra-brachial infusion of 1400W (0.1-1 micromol/min), L-NMMA (N(G)-monomethyl-L-arginine; a non-selective NOS inhibitor; 2-8 micromol/min) and noradrenaline (control vasoconstrictor; 60-480 pmol/min). In both patients and controls, intra-brachial infusion of L-NMMA and noradrenaline caused a dose-dependent reduction in infused forearm blood flow (P<0.05 for both): peak reduction of 32+/-6% and 37+/-4% during L-NMMA and 52+/-6% and 49+/-5% during noradrenaline respectively (P values were not significant when patients were compared with controls). In contrast, 1400W had no effect on blood flow at 1 micromol/min [-3+/-4% in patients (95% confidence intervals, -11 to 5%) and 3+/-8% in controls; P value was not significant]. In conclusion, we have demonstrated that intrabrachial selective iNOS inhibition does not influence forearm blood flow in patients with heart failure. We conclude that iNOS activity does not contribute to peripheral vascular tone in patients with symptomatic heart failure.

Bradykinin Does Not Contribute to Peripheral Vascular Tone in Patients With Cirrhosis and Ascites

Bradykinin is an endothelium-dependent vasodilator and inflammatory mediator. The aim of the present study was to examine the effects of bradykinin on peripheral vascular tone in patients with cirrhosis and ascites. Forearm blood flow was measured using venous occlusion plethysmography in 8 patients with biopsy-proven alcohol-induced cirrhosis, ascites, and portal hypertension, and 8 age- and sex-matched healthy controls. On 1 occasion, subjects received an intrabrachial infusion of the selective bradykinin antagonist B9340 (1.5-13.5 nmol/min) followed by a control vasoconstrictor norepinephrine (60-540 pmol/min), and on another occasion bradykinin (100-900 pmol/min) followed by the endothelium-independent vasodilator, sodium nitroprusside (SNP, 2-8 microg/min). Bradykinin and SNP caused a dose-dependent vasodilatation (P < 0.001 for both) that did not differ between the 2 groups. Although norepinephrine caused a similar dose-dependent vasoconstriction in both groups (P < 0.001), B9340 had no effect on forearm blood flow in either group (at 13.5 nmol/min in patients; -5%, 95% CI -13-3). Bradykinin does not provide a major contribution to the maintenance of peripheral vascular tone in patients with cirrhosis and ascites. Our findings also suggest that, in contrast to cardiovascular disease, patients with liver cirrhosis do not have marked endothelial dysfunction.

Simvastatin enhances hepatic nitric oxide production and decreases the hepatic vascular tone in patients with cirrhosis

Background & Aims : In cirrhosis, an insufficient release of nitric oxide contributes to increased hepatic resistance and portal pressure and enhances the postprandial increase in portal pressure. We hypothesized that simvastatin, which enhances Akt-dependent endothelial nitric oxide synthase phosphorylation, may increase hepatic nitric oxide release and decrease hepatic resistance in patients with cirrhosis and portal hypertension. Methods : In protocol 1, 13 patients had measurements of the hepatic venous pressure gradient, hepatic blood flow, mean arterial pressure, cardiac output, and nitric oxide products before and 30 and 60 minutes after 40 mg of simvastatin. In protocol 2, 17 patients were randomized to receive placebo or simvastatin (40 mg) 12 hours and 1 hour before the study. After baseline measurements of the hepatic venous pressure gradient, hepatic blood flow, and nitric oxide products, a standard liquid meal was given, and measurements were repeated at 15, 30, and 45 minutes. Results : In protocol 1, acute simvastatin did not modify the hepatic venous pressure gradient but increased the hepatic blood flow (21% ± 13% at 30 minutes; P = 0.01) and decreased hepatic sinusoidal resistance by 14% ± 11% ( P = 0.04). Nitric oxide product levels significantly increased in hepatic venous blood (from 31.4 ± 12.3 nmol · mL −1 to 35.8 ± 10.7 nmol · mL −1; P = 0.04), but not in peripheral blood. Systemic hemodynamics were not modified. In protocol 2, simvastatin pretreatment significantly attenuated the postprandial increase in hepatic venous pressure gradient (mean peak increase, 10% ± 9% vs. 21% ± 6% in placebo; P = 0.01). Hepatic blood flow increased similarly in the 2 groups. Hepatic nitric oxide products increased in the simvastatin group but not in the placebo group. Conclusions : Simvastatin administration increases the hepatosplanchnic output of nitric oxide products and decreases hepatic resistance in patients with cirrhosis.

819-6 Inducible nitric oxide synthase activity does not contribute to the maintenance of peripheral vascular tone in patients with symptomatic congestive heart failure

819-6 Inducible nitric oxide synthase activity does not contribute to the maintenance of peripheral vascular tone in patients with symptomatic congestive heart failure

Selective pulmonary vasodilation in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by a marked maldistribution of pulmonary perfusion in favor of nonventilated, atelectatic areas of the lungs, and it is the main cause of pulmonary right-to-left shunting and hypoxemia. Therapeutic interventions to selectively influence pulmonary perfusion in ARDS became feasible with the introduction of inhaled nitric oxide, which provided a means not only to reduce pulmonary hypertension, but also to improve matching of ventilation to perfusion and, thus, hypoxemia. Clinical studies in ARDS subsequently demonstrated that the combination of inhaled nitric oxide with other interventions, such as positive end-expiratory pressure and prone positioning, yielded beneficial and additive effects on arterial oxygenation. Although the available randomized, controlled trials of this novel concept have so far failed to show an improved outcome in ARDS, inhaled nitric oxide is a clinically valuable option for the treatment of severe refractory hypoxemia in ARDS, and largely promoted the concept of selective pulmonary vasodilation in intensive care practice. Currently, aerosolization of various vasodilators, in particular prostaglandins, is under evaluation in models of acute lung injury and human ARDS. Ongoing research aims to augment the effectiveness of vasodilators with specific inhibitors of phosphodiesterases or by combination with intravenous vasoconstrictors. Consequently, several alternative ways to selectively modulate pulmonary vascular tone in patients with ARDS may be available in the near future. Cost-benefit analysis of these therapeutic options will largely determine their future perspective.

Simvastatin ammeliorates the increased hepatic vascular tone in patients with cirrhosis

Simvastatin ammeliorates the increased hepatic vascular tone in patients with cirrhosis

Altered peripheral vascular responses to exogenous and endogenous endothelin-1 in patients with well-compensated cirrhosis

Plasma endothelin concentrations are elevated in cirrhosis and correlate with disease severity. This study assessed forearm vascular responses to exogenous endothelin-1 (ET-1), and evaluated the contribution of endogenous ET-1 to the maintenance of basal peripheral vascular tone in patients with well-compensated cirrhosis (n = 11) and matched healthy controls (n = 8). Bilateral forearm blood flow (FBF) was measured at baseline and following unilateral, subsystemic, intrabrachial artery infusions of ET-1 (2 and 6 pmol/min); BQ-123, a selective ETA receptor antagonist (3 and 10 nmol/min); and BQ-788, a selective ETB receptor antagonist (0.3 and 1 nmol/min) using venous occlusion plethysmography. Baseline systemic hemodynamics and plasma ET-1 and big ET-1 concentrations were measured using electrical bioimpedance and radioimmunoassay, respectively. Patients and controls had similar baseline FBF, systemic hemodynamics, and plasma ET-1 and big ET-1 concentrations. In both groups, ET-1 and BQ-788 caused significant vasoconstriction (P < .001) and BQ-123 caused significant vasodilatation (P < .001). Compared with controls, cirrhotic patients had attenuated ET-1 responses (P < .001), augmented BQ-123 responses (P < .001), and similar BQ-788 responses (P = .62). Despite normal systemic hemodynamics and plasma ET-1 concentrations, forearm vascular responses to exogenous ET-1 are reduced in cirrhotic patients. The augmented vasodilatation to BQ-123 in cirrhotic patients is consistent with a compensated vasodilated state, and a greater contribution of ET-1 to the maintenance of basal vascular tone acting through the ETA receptor. (HEPATOLOGY 2001;33:826-831.)

Plasma beta-endorphin and adenosine concentration in pulmonary hypertension

To determine whether β-endorphin plays a role in the regulation of pulmonary vascular tone in patients with pulmonary hypertension, we investigated the relations between hemodynamics and β-endorphin and adenosine concentrations in 3 clinical situations: (1) normal hemodynamics (7 subjects, mean pulmonary artery [PA] pressure 18.5 ± 1 mm Hg); (2) moderate pulmonary hypertension secondary to chronic obstructive pulmonary disease (COPD) (8 patients, mean PA pressure 31 ± 3 mm Hg); and (3) severe primary pulmonary hypertension (PPH) (8 patients, mean PA pressure 70 ± 5 mm Hg). Plasma β-endorphin and adenosine were measured in a distal PA and in the femoral artery in room air and during oxygen inhalation. Beta-endorphin levels were similar in the pulmonary and systemic circulations. No difference was observed between patients with COPD and PPH, but relative to controls, both had significantly higher β-endorphin levels. Pulmonary adenosine was significantly lower in patients with pulmonary hypertension than in controls (−60% in COPD [p <0.005] and −70% in PPH [p <0.001]). Pure oxygen administration significantly decreased adenosine and β-endorphin levels, much more so in patients with COPD and PPH. We found a negative correlation between β-endorphin and adenosine concentrations (r = −0.751, p <0.001): the higher the adenosine, the lower the β-endorphin level. These observations suggest that because adenosine release by pulmonary vascular endothelium is reduced in pulmonary hypertension, the resulting worsened hypoperfusion and tissue oxygenation may cause increased β-endorphin release.

Reduced endogenous endothelin-1–mediated vascular tone in chronic renal failure

Endothelin-1 generated by the vascular endothelium contributes to basal vascular tone and blood pressure in healthy humans. Plasma concentrations of endothelin-1, which are elevated in chronic renal failure (CRF), may contribute to increased vascular tone. We investigated the contribution of endogenous and exogenous endothelin-1 to the maintenance of vascular tone in patients with CRF (creatinine > or = 200 mumol/liter) and in age- and sex-matched healthy subjects. In a series of experiments, we measured forearm vascular responses to intra-arterial norepinephrine (30 to 240 pmol/min), endothelin-1 (5 pmol/min), the selective endothelin A (ETA) receptor antagonist BQ-123 (3 mg/hr), the mixed endothelin-converting enzyme and neutral endopeptidase inhibitor phosphoramidon (30 nmol/min), and the selective neutral endopeptidase inhibitor thiorphan (30 nmol/min). The maximum reduction in forearm blood flow (FBF) to norepinephrine in CRF (33 +/- 7%) was similar to that in controls (43 +/- 7%, P = 0.53). Endothelin-1 also produced a similar reduction in FBF in CRF (35 +/- 6%) and controls (36 +/- 5%, P = 0.81). BQ-123 increased FBF in CRF (11 +/- 4%) but significantly less than in controls (44 +/- 10%, P = 0.02). Phosphoramidon increased FBF in CRF (68 +/- 20%), again significantly less than in controls (181 +/- 41%, P = 0.001). Thiorphan reduced FBF similarly in CRF (22 +/- 6%) and controls (14 +/- 6%, P = 0.39). Responses to phosphoramidon were substantially greater than to BQ-123. These studies show that endogenous generation of endothelin-1 contributes to the maintenance of resting vascular tone in patients with CRF, as well as in healthy subjects. Although the contribution of endogenous endothelin-1 to resting vascular tone appears to be reduced in CRF, ETA receptor antagonism, and particularly endothelin-converting enzyme inhibition, should be explored as means by which to reduce vascular tone and blood pressure in patients with CRF.

Regulation of peripheral vascular tone in patients with heart failure: contribution of angiotensin II

ObjectiveTo determine directly the contribution of angiotensin II to basal and sympathetically stimulated peripheral arteriolar tone in patients with heart failure.DesignParallel group comparison.SubjectsNine patients with New York Heart Association grade...

Abnormal vascular responses in human chronic cardiac failure are both endothelium dependent and endothelium independent

ObjectiveTo study underlying vascular responses in chronic heart failure in patients without ACE inhibitor treatment, and to compare them with age matched controls.DesignForearm blood flow was studied using venous occlusion...

Adrenomedullin in patients at high risk for pulmonary hypertension

Background. Adrenomedullin is a newly identified peptide with profound hypotensive effects. We investigated perioperative adrenomedullin levels among patients with congenital heart disease with and without pulmonary hypertension. Methods. Levels of plasma adrenomedullin, endothelin-1, and nitric oxide metabolites were measured in three groups: (1) low pulmonary flow (n = 11); (2) high flow/low pulmonary arterial pressure (less than 60% systemic pressure) (n = 9); and (3) high flow/high pressure (n = 10). Samples were obtained preoperatively, on and off pump, and 3, 6, and 12 hours after bypass. Results. Adrenomedullin levels were highest in the low pulmonary flow group (189.7 ± 15 pg/mL low flow versus 103.1 ± 9.5 pg/mL high flow/low pulmonary and 139 ± 17.5 pg/mL high flow/high pressure at 12 hours; p ≤ 0.05). The arterial pressure/systemic pressure re-mained significantly lower in the high flow/low pulmonary pressure compared with the high flow/high pressure group (0.37 ± 0.08 versus 0.62 ± 0.11; p < 0.005). Perioperative endothelin-1 and nitric oxide levels remained low in the low pulmonary flow group but increased progressively in both high flow groups. Conclusions. Circulating plasma adrenomedullin appears to affect baseline vascular tone in patients with intact endothelial function. It may interact with nitric oxide and endothelin-1 to help regulate blood pressure perioperatively in patients with congenital heart disease.