Physiologic characterization of endothelin A and B receptor activity in the ovine fetal pulmonary circulation.

To determine the potential contribution of endothelin (ET) to modulation of high pulmonary vascular resistance in the normal fetus, we studied the effects of BQ 123, a selective ET-A receptor antagonist, and sarafoxotoxin S6c (SFX), a selective ET-B receptor agonist, in 31 chronically prepared late gestation fetal lambs. Brief intrapulmonary infusions of BQ 123 (0.1-1.0 mcg/min for 10 min) caused sustained increases in left pulmonary artery flow (Qp) without changing main pulmonary artery (MPA) and aortic (Ao) pressures. In contrast, BQ 123 did not change vascular resistance in a regional systemic circulation (the fetal hindlimb). To determine whether big-endothelin-1 (big-ET-1)-induced pulmonary vasoconstriction is mediated by ET-A receptor stimulation, we studied the effects of big-ET-1 with or without pretreatment with BQ 123. BQ 123 (0.5 mcg/min for 10 min) blocked the rise in total pulmonary resistance caused by big-ET-1. CGS 27830 (100 mcg/min for 10 min), an ET-A and -B receptor antagonist, did not change basal tone but blocked big-ET-1-induced pulmonary vasoconstriction. Brief and prolonged intrapulmonary infusion of SFX (0.1 mcg/min for 10 min) increased Qp twofold without changing MPA or Ao pressures. Nitro-L-arginine (L-NA), a selective endothelium-derived nitric oxide (EDNO) antagonist, blocked vasodilation caused by BQ 123 and SFX. We conclude that: (a) BQ 123 causes sustained fetal pulmonary vasodilation, but did not change vascular resistance in the fetal hindlimb; (b) Big-ET-1-induced pulmonary vasoconstriction may be mediated through ET-A receptor stimulation; and (c) ET-B receptor stimulation causes pulmonary vasodilation through EDNO release. These findings support the hypothesis that endothelin may play a role in modulation of high basal pulmonary vascular resistance in the normal fetus.     

Ca2+-Mg2+ ATPase of mouse cardiac sarcoplasmic reticulum is affected by membrane n-6 and n-3 polyunsaturated fatty acid content

White mice, 18-20 g, were fed purified diets containing two weight percent safflower oil plus ten weight percent menhaden, corn, or olive oil for 2 wk. Menhaden oil ingestion resulted in significantly higher levels of 22:6(n-3) and 20:5(n-3), particularly 22:6(n-3), and lower levels of 20:4(n-6) and 18:2(n-6) in cardiac sarcoplasmic reticulum (SR) phospholipids than did corn or olive oil ingestion. These changes in fatty acid composition resulted in a significant decrease in the value of the n-6/n-3 fatty acid ratio of cardiac SR phospholipids. The ratio was 2.8 versus 0.2 in choline phospholipids and 1.9 versus 0.2 in ethanolamine phospholipids in SR of mice fed corn or menhaden oil, respectively. This reduction in the n-6/n-3 fatty acid ratio was associated with a lower relative activity of Ca2+-Mg2+ ATPase, and a lower initial rate of calcium transport and maximum calcium uptake in SR vesicles from mice fed menhaden oil rather than olive or corn oils. The specific activity of NADPH cytochrome C reductase (EC 1.6.2.3) of cardiac SR was not affected by dietary lipids. These data indicate that modification of SR by 22:6(n-3) may change the SR bilayer structure resulting in alteration of the calcium transport properties of SR vesicles. In addition, our results suggest that reduction of calcium flux across cardiac SR following fish oil consumption may also reduce the susceptibility of myocytes to rapid changes in calcium concentrations which may occur during ischemia and reperfusion.     

Acute peripheral arterial and graft occlusion: treatment with selective infusion of urokinase and lysyl plasminogen

Thirty-five patients hospitalized for recent angiographically documented arterial occlusion in the legs (27 femoropopliteal arteries and eight grafts) benefited from local fibrinolytic therapy delivered at the site of the occlusion with a 4- or 5-F catheter. This therapy combined a continuous urokinase (UK) infusion of 1,000 U/kg/hour and a lysyl plasminogen (LYS-PLG) infusion of 15 microkatals every 30 minutes. Angiographically confirmed lysis was obtained in 85% of the cases. Only 3% of the patients had major and 6% had minor groin hematomas. Only two patients had concentrations of fibrinogen as low as 100 mg/dl. Intravascular infusion of UK-LYS-PLG is as effective as streptokinase. Its excellent tolerance makes it a good alternative in the treatment of acute ischemia in the lower limbs.