C. M. Roos

Inhaled nitric oxide: Selective pulmonary vasodilation in cardiac surgical patients

Background:Inhaled nitric oxide (NO), an endothellum-derlved relaxing factor, is a selective pulmonary vasodilator. The authors investigated whether the pulmonary vasodilation resulting from 20 ppm inhaled NO is related to the degree of pulmonary hypertension or affected by cardiopulmonary bypass (CPB) or the presence of intravenous nitrates. Methods:In patients undergoing cardiac surgery (n=20) or in whom the circulation was supported with a ventricular assist device (VAD; n=5), the lungs were ventilated with 80% O2 and 20% N2 followed by the same gas concentrations containing 20 ppm NO for 6 min. Results:Inhaled NO decreased (P<0.05) the pulmonary artery pressure from 36 ± 3 to 29 ± 2 mmHg and 32 ± 2 to 27 ± 1 mmHg, before and after CPB, respectively, and from 68 ± 12 to 55 ± 9 mmHg in patients with a VAD. Similarly, the pulmonary vascular resistance (PVR) decreased (P<0.05) from 387 ± 44 to 253 ± 26 dyne·cm·s-5 and 260 ± 27 to 182 ±18 dyne·cm·s-5, before and after CPB, respectively, and from 1,085 ± 229 to 752 ± 130 dyne·cm·s-5 in patients with a VAD. Central venous pressure, cardiac output, systemic hemodynamics, and blood gases did not change after inhalation of NO before or after CPB, whereas arterial oxygen tension, mixed venous hemoglobin saturation, and mean arterial pressure increased (P<0.05) in patients supported with a VAD. All hemodynamic and laboratory data returned to control 6 min after discontinuation of NO. The decrease in PVR was proportional to baseline PVR ( PVR=-0.45 PVRb + 39.9) before CPB. The pre- and post-CPB slopes were identical despite possible damage to the endothelium resulting from CPB and the post-CPB presence of intravenous nitroglycerin (17 of 20 patients). Conclusions:This study demonstrates that 20 ppm inhaled NO is a selective pulmonary vasodilator in cardiac surgical patients before and after CPB and in patients in whom the circulation is supported with a VAD. Furthermore, NO-induced pulmonary vasodilation is proportional to PVRb and does not appear to be altered by CPB, the presence of a VAD, or infusion of nitrates.

Direct effects of intravenous anesthetics on pulmonary vascular resistance in the isolated rat lung.

We determined the direct effects of thiopental, ket-amine, midazolam, etomidate, and propofol on pulmonary vascular resistance (PVR), the relationship of the direct effects to the baseline PVR, and the possible interaction with functional endothelium. The intravenous anesthetics were injected randomly into 1) endothelium-intact isolated rat lungs which were either unconstricted or constricted with angiotensin II (n = 10), and 2) lungs with endothelial injury produced by electrolysis (n = 10). In endothelium-intact lungs thiopental (0.5 and 5.0 mg/kg) and etomidate (3.0 mg/ kg) significantly (P < 0.05) increased PVR by 3% ± 1%, 30% ± 7%, and 29% ± 5%, respectively. Ketamine (3.0 and 100 mg/kg) and propofol (20 mg/kg) significantly (P < 0.05) decreased the PVR by 6% ± 1%, 15% ± 1%, and 8% ± 1%, respectively. Midazolam (0.3 and 3.0 mg/kg) and smaller doses of etomidate (0.3 mg/kg) and propofol (2.0 mg/kg) did not affect PVR. These responses did not vary with the baseline PVR over a twofold range. The effects of thiopental, ketamine, etomidate, and midazolam were not altered by endothelial injury. In contrast to the vasodilation produced by propofol in normal lungs, propofol (20 mg/kg) significantly (P < 0.05) increased the PVR by 8% ± 2% after endothelial injury. In conclusion, this study demonstrates that thiopental and etomidate are direct pulmonary vasoconstrictors, ketamine and propofol are direct pulmonary vasodilators, and midazolam has no direct effects in the isolated rat lung. Further, these effects on pulmonary vasculature do not vary with baseline PVR, and only propofol appears to have endothelium-dependent effects.

Nitric oxide modulation of pulmonary vascular resistance is red blood cell dependent in isolated rat lungs

Nitric oxide (NO) or endothelium-derived relaxing factor may play an important role in modulating pulmonary vascular resistance (PVR), although previous studies have produced conflicting results. Endogenous NO inhibition causes an increase in PVR in intact animals but not in saline-perfused isolated lungs. We hypothesized that blood is essential for NO to serve as a modulator of PVR. Therefore, the effects of endogenous NO inhibition (Nomega-nitro-L-arginine methyl ester [L-NAME]) were determined in isolated rat lungs as related to the presence of different blood components under normoxic conditions and after 1 wk of hypoxia (fraction of inspired oxygen [FIO2] = 10%). Exogenously administered inhaled NO was evaluated in isolated lungs from normoxic and hypoxic rats. In normoxic rats, L-NAME (10-100 micro M) caused a dose-dependent increase in PVR in whole (hematocrit [Hct] 40%) and diluted (Hct 12%) blood-perfused lungs. L-NAME (10-800 micro M) had no effect in isolated lungs perfused with a modified salt solution of equal viscosity to blood either alone, or containing plasma (50%) or free oxyhemoglobin (10 micro M). In whole blood perfused lungs, L-NAME (100 micro M) increased PVR more in hypoxic versus normoxic isolated lungs (141% vs 100%). Inhaled NO decreased PVR in isolated lungs from hypoxic rats and partially reversed the effects of L-NAME, but had no effect in normoxic lungs. In conclusion, endogenous and inhaled NO modulate PVR in isolated rat lungs and this role is increased by prolonged hypoxia. The response to inhibition of endogenous NO is dependent on the presence of red blood cells and is independent of the changes in viscosity or the presence of oxyhemoglobin or plasma. (Anesth Analg 1996;83:1212-7)

Fluid restitution and blood volume redistribution in anesthetized rabbits in response to vasoactive drugs.

Vasoactive drugs could alter the fluid restitution from the tissue and redistribute blood volume between the macrocirculation and microcirculation. Methods and ResultsWith bolus injections of vasoactive drugs in anesthetized rabbits, we measured the changes in blood and plasma density for the determination of the volume of restitution and redistribution. Epinephrine 3.5, μg/kg caused a fluid loss to the tissue, leading to a transient decrease in total blood volume by 2.30 mL/kg. Because of blood volume redistribution, the peak volume reduction was accompanied by a volume reduction of 0.81 mL/kg from the macrocirculation and 1.49 mL/kg from the microcirculation. Phenylephrine 70 μg/kg caused a peak reduction in total blood volume of 1.40 mbVkg (with 0.41 mL/kg from macrocirculation and 0.99 mb/kg from microcirculation). Nitroprusside 7 μg/kg increased the blood volume by 1.44 mL/kg (0.83 mb/kg macro and 0.61 mb/kg micro), nitroglycerin 7 μg/kg by 1.48 mL/kg (0.97 mL/kg macro and 0.51 mL/kg micro), and isoproterenol 7 μg/kg by 2.07 mL/kg (0.68 mL/kg macro and 1.39 mL/kg micro). All plasma (or blood) density changes measured for the five drugs (with epinephrine, phenylephrine, and nitroprusside done over a wide dosage range) correlated linearly with the drug-induced changes in arterial pressures. ConclusionsThese results indicate that vasoactive drugs alter total blood volume and the volume of microcirculation and macrocirculation.