Increased platelet reactivity and significant changes in coagulation markers after cavopulmonary connection

OBJECTIVE—To evaluate platelet reactivity and coagulation markers after surgical palliation of univentricular hearts.
DESIGN AND PATIENTS—Cross sectional survey of 24 patients, median age 11 (range 4-22) years, at 2 (range 0.5-6) years after a total cavopulmonary connection (TCPC; n = 14) or a bidirectional Glenn anastomosis (Glenn; n = 10).
MAIN OUTCOME MEASURES—Platelet reactivity and/or coagulation markers were measured in 20 patients (four excluded because of anticoagulant treatment) and compared with 33 healthy controls, median age 12 (range 6-16) years.
RESULTS—None of the patients had clinically apparent thromboembolic events. However, increased platelet reactivity was observed ex vivo both after collagen induced platelet aggregation (median 73% (interquartile range 61-84%) in patients, and 61% (47-69%) in controls; p < 0.01), and after ADP induced platelet aggregation (69% (53-77%) in patients, and 56% (40-66%) in controls; p < 0.05). Concentrations of protein S antigen, antithrombin III, and protein C activity were reduced after both TCPC and Glenn. A concomitant decrease was seen in coagulation factor II, VII, X, and factor VII clot activity.
CONCLUSIONS—Several abnormalities in the coagulation system were observed after bidirectional Glenn anastomosis, similar to alterations previously described in Fontan operated and TCPC patients. Antithrombotic treatment in these patients is still an unresolved issue, but aspirin is often recommended. This study shows that such a strategy is rational and the results suggest that antiplatelet treatment may be advantageous, either alone or in combination with oral anticoagulant treatment.


Keywords: Fontan procedure; thrombosis; platelets; coagulatio

Pulmonary and caval flow dynamics after total cavopulmonary connection

Objective—To assess flow dynamics after total cavopulmonary connection (TCPC).
Design—Cross-sectional study.
Setting—Aarhus University Hospital. 
Patients—Seven patients (mean age 9 (4-18) years) who had previously undergone a lateral tunnel TCPC mean 2 (0.3-5) years earlier. 
Interventions—Pressure recordings (cardiac catheterisation), flow volume, and temporal changes of flow in the lateral tunnel, superior vena cava, and right and left pulmonary arteries (magnetic resonance velocity mapping).
Results—Superior vena cava flow was similar to lateral tunnel flow (1.7 (0.6-1.9) v 1.3 (0.9-2.4) l/min*m(2)) (NS), and right pulmonary artery flow was higher than left pulmonary artery flow (1.7 (0.6-4.3) v 1.1 (0.8-2.5) l/min*m(2), p < 0.05). The flow pulsatility index was highest in the lateral tunnel (2.0 (1.1-8.5)), lowest in the superior vena cava (0.8( )(0.5-2.4)), and intermediate in the left and right pulmonary arteries (1.6 (0.9-2.0) and 1.2 (0.4-1.9), respectively). Flow and pressure waveforms were biphasic with maxima in atrial systole and late ventricular systole.
Conclusions—Following a standard lateral tunnel TCPC, flow returning via the superior vena cava is not lower than flow returning via the inferior vena cava as otherwise seen in healthy subjects; flow distribution to the pulmonary arteries is optimal; and some pulsatility is preserved primarily in the lateral tunnel and the corresponding pulmonary artery. This study provides in vivo data for future in vitro and computer model studies.

 Keywords: blood flow dynamics;  total cavopulmonary connection;  congenital heart diseas

Neurohormonal activation late after cavopulmonary connection

OBJECTIVE—To determine whether patients with cavopulmonary connection have higher levels of vasoactive/water-salt regulating hormones and if so, whether hormone levels are related to postoperative haemodynamics and postoperative follow up.
DESIGN—Cross sectional study.
SETTING—University hospital.
PATIENTS—20 patients (New York Heart Association functional class I-II), mean age 11 years (range 4 to 22), were studied at a mean of 2 years (0.5 to 6) after a total cavopulmonary connection (TCPC, n = 12) or a bidirectional Glenn anastomosis (BDG, n = 8).
INTERVENTIONS—Cardiac catheterisation was performed and blood samples were drawn. Control blood samples were drawn from 33 healthy children, mean age 12 years (6 to 16).
MAIN OUTCOME MEASURES—Plasma levels of angiotensin II, renin, aldosterone, arginine, vasopressin, atrial natriuretic factor (ANF), brain natriuretic peptide (BNP).
RESULTS—All neurohormones were significantly increased in both TCPC and BDG patients (p < 0.05), with a fourfold increase in angiotensin II, renin, and aldosterone, and a twofold increase in vasopressin, ANF, and BNP (compared with healthy controls). There was no correlation between haemodynamic variables and hormone levels. Angiotensin II and renin were inversely correlated with time to follow up. All subjects over 15 years (n = 5) had normal neurohormonal levels.
CONCLUSIONS—Neurohormones were raised for years after successful cavopulmonary operations but lower levels were observed with time on follow up. This supports the hypothesis that neurohormonal activation is primarily related to altered postoperative physiology and that adaptation takes place over time.


Keywords: neurohormones; cavopulmonary connection; congenital heart disease; paediatric cardiolog

Inhibition of nitric oxide synthesis improves left ventricular contractility in neonatal pigs late after cardiopulmonary bypass

BACKGROUND—Following neonatal open heart surgery a nadir occurs in left ventricular function six to 12 hours after cardiopulmonary bypass. Although initiated by intraoperative events, little is known about the mechanisms involved.
OBJECTIVE—To evaluate the involvement of nitric oxide in this late phase dysfunction in piglets.
DESIGN—Piglets aged 2 to 3 weeks (4-5 kg) underwent cardiopulmonary bypass (1 h) and cardioplegic arrest (0.5 h) and then remained ventilated with inotropic support. Twelve hours after bypass, while receiving dobutamine (5 µg/kg/min), the left ventricular response to non-selective nitric oxide synthase inhibition (l-N(G)-monomethylarginine (l-NMMA)) was evaluated using load dependent and load independent indices (E(es), the slope of the end systolic pressure-volume relation; M(w), the slope of the stroke work-end diastolic volume relation; [dP/dt(max)](edv), the slope of the dP/dt(max)-end diastolic volume relation), derived from left ventricular pressure-volume loops generated by conductance and microtip pressure catheters.
RESULTS—10 pigs received 7.5 mg l-NMMA intravenously and six of these received two additional doses (37.5 mg and 75 mg). E(es) (mean (SD)) increased with all three doses, from 54.9 (40.1) mm Hg/ml (control) to 86.3 (69.5) at 7.5 mg, 117.9 (65.1) at 37.5 mg, and 119 (80.4) at 75 mg (p < 0.05). At the two highest doses, [dP/dt(max)](edv) increased from 260.8 (209.3) (control) to 470.5 (22.8) at 37.5( )mg and 474.1 (296.6) at 75 mg (p < 0.05); and end diastolic pressure decreased from 16.5 (5.6) mm Hg (control) to 11.3 (5.0) at 37.5( )mg and 11.4 (4.9) at 75 mg (p < 0.05).
CONCLUSIONS—In neonatal pigs 12 hours after cardiopulmonary bypass with ischaemic arrest, low dose l-NMMA improved left ventricular function, implying that there is a net deleterious cardiac action of nitric oxide at this time.


Keywords: ventricular function; nitric oxide; neonatal pigs; cardiovascular surgery; paediatric cardiolog