Pulmonary hydraulic impedance responses to hypoxia and hypercapnia in newborn pigs.

The purpose of this study was to determine the cumulative effects of brief intervals of hypoxia and hypercapnia on the pulsatile characteristics of the pulmonary arterial circulation of 48-h-old compared with 2-wk-old open-chest Yorkshire pigs while using two different anesthetic regimens: 1) azaperone and ketamine (4 and 12 mg/kg im, respectively) and 2) thiopental sodium (25 mg/kg i.v.). Animals 48 h old were randomly allocated to undergo mild hypoxia (inspired O2 fraction = 0.15), severe hypoxia (inspired O2 fraction = 0.05), or hypercapnia (inspired CO2 fraction = 0.20), whereas animals 2 wk old underwent severe hypoxia or hypercapnia. With use of Fourier analysis, characteristic impedance (Zo), mean input impedance (Zm), impedance moduli, and phase angles were determined. In 48-h-old pigs anesthetized with azaperone-ketamine, neither mild nor severe hypoxia altered Zo, Zm, or pulmonary vascular resistance (PVR), whereas hypercapnia increased Zo by 22% (P < 0.001), which persisted despite a return to normocapnia. In 48-h-old animals anesthetized with thiopental, baseline control Zo and Zm were lower than those in same-age pigs anesthetized with azaperone-ketamine. In thiopental-anesthetized 48-h-old pigs, both severe hypoxia and hypercapnia increased Zm and PVR but Zo was unaltered. In 2-wk-old pigs anesthetized with thiopental, severe hypoxia but not hypercapnia elevated Zm and PVR, whereas Zo was not changed with either stress. Results indicate age- and anesthetic-dependent responses of Zo, Zm, and PVR to severe hypoxia and hypercapnia. The persistent elevation in Zo caused by hypercapnia indicates a prolonged decrease in arterial compliance or a reduction in effective proximal pulmonary arterial radius.

Reduction of conjugated dienes in lung transplantation: effect of BN 52021.

Oxygen-derived free radicals have been identified as the mediators of tissue injury during reperfusion in organ transplantation. Lipid peroxidation of cell membrane polyunsaturated fatty acids, generating conjugated dienes (CD), is a toxicity of oxygen-derived free radicals. The CD structure in fatty acyl moieties was measured by high-pressure liquid chromatography in samples of inferior pulmonary venous blood and pulmonary tissue to assess reperfusion injury and oxygen-derived free radical-mediated damage in a canine model of left lung allotransplantation. The cold ischemic preservation interval was 6 hours and the posttransplantation monitoring period was 6 hours. Twenty-eight size- and weight-matched adult male dogs underwent left lung allotransplantation and were randomized to receive pulmonary artery flush of modified Euro-Collins (EC) (40 mL/kg) or University of Wisconsin (UW) (40 mL/kg) solutions alone or with the addition of the platelet-activating factor antagonist BN 52021 (10 mg/kg). When employed, BN 52021 was administered to donors 30 minutes before harvest and recipients 30 minutes before reperfusion. Left and right inferior pulmonary venous blood samples were obtained at baseline before transplantation and at 1, 2, 4, and 6 hours after transplantation; tissue samples were obtained after euthanasia. Serum and tissue CD levels are expressed as mean fraction of the total hydroperoxide sample +/- standard error of the mean. At 6 hours after transplantation, the EC group's (n = 7) CD fraction was 0.28 +/- 0.03, whereas that of the EC + BN 52021 group (n = 7) was 0.12 +/- 0.03 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Additive myocardial depressant effects of cocaine and ethanol.

Although significant morbidity and mortality have been associated with the combined use of cocaine and ethanol, the cardiovascular effects of this combination are unknown. In this study, the effect of ethanol on cocaine-induced cardiovascular alterations was examined in two groups (n = 8 each) of dogs, which were randomized to receive either ethanol (1.68 gm/kg intravenously) or saline solution and cocaine (2 mg/kg intravenously). Ethanol had no effect on heart rate, mean arterial pressure, or rate-pressure product; but it increased ventricular end-diastolic pressure (p < 0.05), reduced coronary diameter (p < 0.02), and decreased ejection fraction by 16% +/- 4% (p < 0.005) from baseline. Cocaine produced increases in mean arterial pressure, rate-pressure product, and left ventricular end-diastolic pressure that were similar in both groups. After administration of cocaine, left ventricular ejection fraction decreased 16% +/- 2% (p < 0.001) from the baseline value in controls and 32% +/- 5% (p < 0.0002 vs baseline; p < 0.01 vs controls) in the ethanol group. Coronary diameter decreased (p < 0.05) in both groups after administration of cocaine; however, there was no difference between groups in the response of coronary circulation to cocaine. Cocaine and ethanol depress myocardial function, and their effects are additive. Failure of ethanol to enhance cocaine-induced coronary vasoconstriction suggests that the additive myocardial depressant effect of this combination is not related to ischemia but rather to a direct toxic effect of these drugs. Individuals who combine ethanol and cocaine may be at increased risk of hemodynamic compromise.

Platelet activating factor antagonist enhances lung preservation in a canine model of single lung allotransplantation.

Optimal techniques for lung preservation are yet to be defined. Platelet activating factor is a phospholipid released by a variety of cells and produces pulmonary abnormalities similar to posttransplantation pulmonary dysfunction. We investigated the strength of the effect of the platelet activating factor antagonist BN 52021 as compared with that of deferoxamine, an iron chelator previously shown to improve lung preservation. Differential lung function and pulmonary hemodynamics were used to assess preservation after a 6-hour period of cold ischemic storage in a modified canine model of left lung allotransplantation. Thirty size- and weight-matched mongrel male dogs were used for 15 transplant procedures randomized to one of three preservation techniques. The University of Wisconsin solution was used as the basic flush solution for all experimental animals. BN 52021 was added to the flush solution in one group (10 mg/kg, n = 5) and deferoxime in another group (10 mg/kg, n = 5). No additives were used for the control animals (n = 5). BN 52021 and deferoxime were administered to respective donor animals 30 minutes before organ harvesting (10 mg/kg) and to recipient animals 30 minutes before reperfusion (10 mg/kg). The pulmonary artery flush solution was administered (40 ml/kg) over 4 minutes. Recipient animals received double-lumen endotracheal tubes and were monitored with balloon-tipped, flow-directed catheters in both pulmonary arteries and dual-angle ultrasonic flow probes around each pulmonary artery. Solid-state high-fidelity micromanometers were used to measure pressures in the pulmonary artery, the left atrium, and the left ventricle. Systemic arterial, right and left pulmonary venous, and mixed venous blood samples were analyzed at 1, 2, 4, and 6 hours after transplantation. Pulmonary venous oxygen tension of the transplanted lung for the control group was 202 +/- 81 mm Hg versus 282 +/- 53 mm Hg for the BN 52021 group 6 hours after transplantation (p less than 0.05). Pulmonary vascular resistance of the transplanted lung for the control group was 319 +/- 54 dynes.sec.cm-5 versus 149 +/- 71 dynes.sec.cm-5 for the BN 52021 group (p less than 0.05). Proton magnetic resonance spectroscopy was performed on segments of upper and lower lobes of the native and transplanted lung from recipient animals to determine total lung water content. The BN 52021 group had a total lung water content of 57.3% as compared with 51.9% for the deferoxime group (p = not significant) and 88.6% for the control group (p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Platelet activating factor antagonist enhances lung preservation.

Platelet activating factor (PAF) is a potent phospholipid mediator of the immune and inflammatory responses, which causes physiologic effects similar to post-transplant pulmonary dysfunction. This study investigates the hypothesis that the use of a specific PAF antagonist (PAFA), BN 52021, in canine lung transplantation improves lung preservation. Twelve pairs of canines underwent left lung allotransplantation after pulmonary artery flushing with modified Euro-Collins (EC) solution (40 ml/kg). The experimental group (N = 6) received EC with BN 52021 (10 mg/kg). BN 52021 was administered to donors prior to harvest and to recipients prior to reperfusion. The preservation interval was 20 hr and the study period was 12 hr post-transplant. Differential pulmonary function and hemodynamics were monitored, comparing the transplanted left lung and the native right lung. Recipients were ventilated on 100% O2. Administration of the platelet activating factor antagonist, BN 52021, was associated with improvement in transplant lung oxygenation, pulmonary vascular resistance, and compliance. At 12 hr, transplant lung pulmonary venous oxygen tension in the treatment group (EC + BN 52021) was 154 +/- 21 mm Hg versus 87 +/- 10 mm Hg in the control group (EC) (P less than 0.05). Pulmonary vascular resistance of the transplant lung at 12 hr was 146 +/- 24 Dynes.sec.cm-5 in the EC + BN 52021 group as compared to 320 +/- 51 Dynes.sec.cm-5 in the EC group (P less than 0.05). Dynamic pulmonary compliance of the transplant lung at 12 hr was 32 +/- 2.9 ml/cm H2O in the EC + BN 52021 group versus 13 +/- 2.0 ml/cm H2O in the EC group (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)