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The crystal samples used were from the same batches as those used in other physical studies at Oak Ridge. Precise cell parameters were determined. The Zn2+ion substitutes only in the Al(2) sites, as does Mg2+. The degree of substitution by Zn2+(28.5% from chemical analysis and 29.3% from diffraction analysis) is less than that by Mg2+(33.5% from chemical analysis and 34.9% for the average diffraction result from the three Mg-stabilized β″-aluminas). This implies more Na+vacancies in Zn-stabilized Naβ″-alumina and may explain why it has a higher room-temperature conductivity than Mg-stabilized β″-alumina. Fourier maps of the conducting-ion distributions are presented. The 0(5) ions were treated as disordered in refinement of Mg-stabilized Ag- and Naβ″-aluminas.

Endothelial injury with failure of pulmonary endothelium-dependent vasodilatation has been proposed as a possible cause for the increased pulmonary vascular resistance observed after cardiopulmonary bypass, but the mechanisms underlying this response are not understood. An in vivo piglet model was used to investigate the role of endothelium-dependent vasodilatation in postbypass pulmonary hypertension. The pulmonary vascular responses to acetylcholine, a receptor-mediated endothelium-dependent vasodilator, and nitric oxide, an endothelium-independent vasodilator, were studied in one group of animals after preconstriction with the thromboxane A"2 analog U46619 (n = 6); a second group was studied after bypass with 30 minutes of deep hypothermic circulatory arrest (n = 6). After preconstriction with U46619, both acetylcholine and nitric oxide caused significant decreases in pulmonary vascular resistance (34% +/- 6% decrease, p = 0.007, and 39% +/- 4% decrease, p = 0.001). After cardiopulmonary bypass with circulatory arrest, acetylcholine did not significantly change pulmonary vascular resistance (0% +/- 8% decrease, p = 1.0), whereas nitric oxide produced a 32% +/- 4% decrease in pulmonary vascular resistance (p = 0.007). These results demonstrate a loss of receptor- mediated endothelium-dependent vasodilatation with normal vascular smooth muscle function after circulatory arrest. Administration of the nitric oxide synthase blocker N@c-nitro-l-arginine-methyl-ester after circulatory arrest significantly increased pulmonary vascular resistance; thus, although endothelial cell production of nitric oxide may be diminished, it continues to be a major contributor to pulmonary vasomotor tone after cardiopulmonary bypass with deep hypothermic circulatory arrest. In summary, cardiopulmonary bypass with deep hypothermic circulatory arrest results in selective pulmonary endothelial cell dysfunction with loss of receptor-mediated endothelium-dependent vasodilatation despite preserved ability of the endothelium to produce nitric oxide and intact vascular smooth muscle function. (J THORAC CARDIOVASC SURG 1996;111:1248-56)

Background. Pulmonary dysfunction associated with elevated pulmonary vascular resistance is a significant problem after cardiopulmonary bypass (CPB) and circulatory arrest. Mediators of the pulmonary hypertensive response to CPB have not been fully elucidated. The purpose of this study was to examine the contribution of the endothelium-derived vasoconstrictor endothelin-1 to postbypass pulmonary hypertension. Methods. Twelve 1-month-old piglets were instrumented with left atrial and pulmonary artery (PA) micromanometers and a PA flow probe. Phosphoramidon (Phos, n=6) pigs received a 30 mg/kg bolus of Phos, an endothelin converting enzyme inhibitor. Controls (n=6) received saline solution. All animals were placed on CPB and underwent a 60-minute period of circulatory arrest. The indexed pulmonary vascular resistance (PVRI) was calculated at baseline for controls, both before CPB in both groups. Results. Pre-CPB, mean PA pressure, and PVRI were not different between the control and Phos groups (14.6+/-1.1 versus 14.5+/-1.1 mm Hg and 7322+/-1269 versus 7260+/-947 dyne/sec/kg/cm^-^5 respectively). After CPB mean PA pressure was significantly higher in control than Phos animals (32.1+/-1.1. versus 22.5+/-1.3 mm Hg, p=0.0003). PVRI was also significantly higher in the controls (30896+/-4714 versus 14972+/-1710, dyne/sec/kg/cm^-^5, p=0.02) Conclusions Production of endothelin-1 during CPB and circulatory arrest is a mediator of postbypass pulmonary hypertension.

Background: Endothelin-1 has been shown to be a mediator of pulmonary hypertension after cardiopulmonary bypass and deep hypothermic circulatory arrest. It is not known whether the mechanism is increased production of endothelin-1 or alterations in expression of endothelin-1 receptors in the lung. This study was designed to test the hypothesis that circulatory arrest increases endothelin-1 mRNA levels and endothelin-1 receptor expression in the lung. Methods and results: Twenty-four piglets (7 to 30 days old) were studied randomly either at baseline (controls, n = 12) or after cardiopulmonary bypass with 30 minutes of circulatory arrest (deep hypothermic circulatory arrest, n = 12). Lungs and pulmonary arteries were harvested immediately after hemodynamic data collection. Deep hypothermic circulatory arrest significantly increased pulmonary vascular resistance (p < 0.01). Deep hypothermic circulatory arrest also produced a significant increase in endothelin-1 mRNA levels in the pulmonary arteries (149 +/- 55 pg vs 547 +/- 111 pg, p = 0.007). There was no significant change in the pulmonary parenchymal endothelin-1 mRNA levels (4102 +/- 379 pg vs 4623 +/- 308 pg, p = 0.32). Ligand binding studies of the lung parenchyma revealed a single specific endothelin-1 binding site with an EC"5"0 value (effective concentration causing 50% of the maximum response) of about 1 x 10^-^8 mol/L, consistent with the endothelin B subtype. Deep hypothermic circulatory arrest resulted in a significant increase in the number of endothelin-1 receptors in the lung (109 +/- 6 fmol/mg total protein to 135 +/- 9 fmol/mg total protein, p = 0.02). Conclusions: Deep hypothermic circulatory arrest increases production of endothelin-1 by the pulmonary vascular endothelium. Endothelin-1 production in the pulmonary parenchyma does not change. Expression of endothelin B receptors in the pulmonary parenchyma also increases after cardiopulmonary bypass with deep hypothermic circulatory arrest. This study supports the hypothesis that deep hypothermic circulatory arrest results in pulmonary vascular endothelial activation with increased endothelin-1 mRNA production. (J Thorac Cardiovasc Surg 1997;113:777-83)

Brain death often results in a series of hemodynamic alterations that complicate the treatment of potential organ donors before transplantation. The deterioration of myocardial performance after brain death has been described; however, the pathophysiologic process of the myocardial dysfunction that occurs after brain death has not been elucidated. This study was designed to analyze the function of the myocardial @b-adrenergic receptor and the development of left ventricular dysfunction in a porcine model of experimental brain death. Analysis of the @b-receptor included determination of receptor density and adenylate cyclase activity after stimulation independently at the receptor protein, the G protein, and the adenylate cyclase moiety. Myocardial @b-receptor density did not change after the induction of brain death. A decrease in stimulated adenylate cyclase activity was observed within the first hour after brain death at the level of the @b-receptor, the G protein, and the adenylate cyclase moiety, which suggests the occurrence of rapid desensitization of @b-receptor function. Significant deterioration of myocardial performance also occurred within the first hour after brain death, represented by a decrease in preloadrecruitable stroke work compared with the baseline value. The deterioration of myocardial performance after brain death correlates temporally with desensitization of the myocardial @b-receptor signal transduction system. The mechanism of impairment appears to be localized to the adenylate cyclase moiety itself. (J T HORAC CARDIOVASC SURG 95;110: 51)