Fontan circulation leads to contractility-afterload mismatch by means of increased impedance caused by additional connection of the pulmonary vascular bed to the systemic vasculature and by means of deterioration of myocardial contractility. The increased ventriculoarterial coupling ratio and reduced mechanical efficiency predict limited cardiac functional reserve after the Fontan operation.

BD affects coronary circulation by two means: (1) impairment of CBF to decrease in parallel in afterload with consecutive hemodynamic deterioration and (2) severe endothelial dysfunction that may be a contributing factor to posttransplant outcome.

BD induction leads to an initial hyperdynamic reaction followed by hemodynamic instability. The facts that no cardiac dysfunction occurred if loading conditions were kept constant and the ventriculo--arterial coupling ratio and mechanical efficiency remained constant in the intact animal model indicate that decreased contractility reflects to decreased arterial elastance after brain death. Therefore, reduced contractile function after brain death at a decreased afterload may contribute to stroke work optimization.

The aim of this study was to determine the pathophysiological mechanisms of postcardiopulmonary bypass (CPB) intestinal dysfunction using an in vivo canine model of extracorporeal circulation. Six dogs underwent a 90 min hypothermic CPB with continuous monitoring of mean arterial blood pressure (MAP) and mesenteric blood flow (MBF). Reactive hyperemia and vasodilator responses of the superior mesenteric artery to acetylcholine and sodium nitroprusside were determined before and after CPB. Mesenteric lactate production, glucose consumption, creatine kinase (CK) release and venous free radicals were determined. CPB induced a significant fall (p < 0.05) in MAP and MBF. After CPB, reactive hyperemia (-26 +/- 15% versus -53 +/- 2%, p < 0.05) and the response to acetylcholine (-42 +/- 9 versus -55 +/- 6%, p < 0.05) were significantly decreased. Reperfusion increased lactate production (0.8 +/- 0.09 mmol/L versus 0.4 +/- 0.18, p < 0.05) and the CK release (446 +/- 98 U/L versus 5 +/- 19 U/L, p < 0.01). Endothelial dysfunction, conversion from aerobic to anaerobic metabolism, and intestinal cell necrosis seem to be responsible for intestinal complications associated with CPB.

Poly-ADP-ribose synthetase inhibition improves the recovery of myocardial and endothelial function after cardiopulmonary bypass with hypothermic cardiac arrest.

The L-arginine-nitric oxide (NO) pathway plays an important role in ischemia-reperfusion injury. In the present study we investigated the role of NO-precursor L-arginine on cardiac and pulmonary function after reversible hypothermic ischemia. Twelve anesthetized dogs underwent cardiopulmonary bypass. After 60 minutes of hypothermic cardiac arrest, reperfusion was started with application of either saline vehicle (control, n = 6) or L-arginine (40 mg/kg i.v. bolus then 3 mg/kg i.v. infusion during the first 20 minutes of reperfusion, n = 6). The vasodilative response to acetylcholine was significantly higher in the L-arginine group (P < 0.05). The preload recruitable stroke work of the left ventricle decreased significantly after reperfusion, however remained unchanged in the L-arginine group. Arterial blood gas analysis did not show any difference between the two groups. Plasma L-arginine concentration reached peak level at 20 minutes of administration (675.0 +/- 66.6 versus 207.7 +/- 14.5 in the L-arginine group, P < 0.05) and returned to baseline at 40 minutes, while in the control group remained unchanged during ischemia and reperfusion (276.2 +/- 71.6 versus 283.8 +/- 38.5, P< 0.05). Plasma nitrite concentration followed L-arginine changes parallel, however nitrate levels increased slower. Supplementation with L-arginine during reperfusion prevents myocardial and endothelial dysfunction, however does not have any overriding effect on pulmonary function. Considerably rapid elimination of plasma L-arginine was demonstrated during early reperfusion.

We investigated the relationship between coronary perfusion pressure (CPP) and myocardial contractility and the effects of an acute elevation of right atrial pressure (RAP) on this relationship in an experimental model of Fontan circulation in 6 anesthetized open-chest dogs with isolated perfused coronary arteries. The relationship between CPP and Ees could be described by biphasic J-shaped curves which were nearly identical before and under Fontan circulation. While above a "critical" CPP (72 +/- 9 mmHg vs. 81 +/- 8 mmHg, n.s.) the changes of CPP did not affect Ees, below this level the decrease of CPP resulted in a progressive decrease of Ees. Under Fontan circulation, the progressive increase of RAP did not influence Ees at CPP = 100 mmHg, led to a moderate decrease of Ees at CPP = 75 mmHg and severe decrease at CPP = 60 mmHg. Thus, both coronary arterial and venous pressure affect myocardial contractility after Fontan procedure.

L-arginine treatment prevents endothelial dysfunction and improves myocardial performance after BD via enhancement of endogenous nitric oxide synthesis.