Reversal of pulmonary capillary ischemia-reperfusion injury by rolipram, a cAMP phosphodiesterase inhibitor

Isoproterenol (ISO) and forskolin, agents that increase adenosine 3',5'-cyclic monophosphate (cAMP) via adenylyl cyclase activation, reverse lung injury associated with increased microvascular permeability. We studied the role of rolipram, a relatively isozyme-selective cAMP phosphodiesterase (PDE) inhibitor, in reversing increased capillary permeability due to ischemia-reperfusion (I/R), a form of oxidant injury in the lung, by using the isolated perfused rat lung model. Rolipram (2 microM) administered after 45 min of ischemia and 45 min of reperfusion reduced I/R-increased permeability as measured by the capillary filtration coefficient to control lung values. Computer image analysis of air space edema and perivascular cuffing, as well as wet-to-dry weight ratios, confirms the permeability reversal by rolipram administration. Rolipram inhibition of cAMP PDE in the lung was assessed by using [3H]adenine prelabeling adapted for the whole lung and perfusate [3H]cAMP accumulation. Rolipram failed to increase perfusate cAMP alone but dramatically increased perfusate cAMP above ISO alone. Dose-response relationships of ISO or rolipram show a close correlation of the half-maximal effective dose (ED50) for injury reversal and perfusate cAMP production. The combination of rolipram and ISO produced synergistic reversal of I/R injury. We conclude that reversal of I/R-induced increased microvascular permeability can be achieved with rolipram and that the mechanism of action of rolipram is probably through PDE isozyme-selective inhibition. The similarity of the ED50 values for cAMP efflux and reversal of permeability increases also supports a close coupling between cAMP accumulation and endothelial cell permeability.     

Hemolytic disease of the newborn due to anti-Di(a): report of one case

In the Diego blood group, the frequency of the Di(a + b +) or Di(a + b -) phenotype among Chinese in Taiwan is estimated to be 3.2%. Here we report a case of severe hemolytic disease caused by anti-Di(a). The baby's total bilirubin elevated to 23 mg/dl at the age of 72 hours. A blood exchange transfusion and phototherapy were performed. We suggest to include Diego positive cell panels in testing antibody specificities that are likely to be encountered in this population.     

Behavioral contingencies modulate tolerance to discriminative stimulus effects of morphine

Experiments examined how learning processes modulate tolerance to discriminative stimulus effects of morphine. Rats were trained to discriminate saline and 3.2 mg/kg morphine, and the doses of morphine required to mimic the training dose were determined before, during and after repeated treatment with saline or high doses of morphine (10 mg/kg, b.i.d.). In one set of experiments, training was either suspended or continued with saline and the original training dose during a 2-week treatment regimen. When training was suspended, high-dose morphine treatment increased the dose of morphine required for stimulus effects approximately 3-fold. Tolerance persisted 2 days after treatment ended, but disappeared within 7 days. In contrast, continued training with saline and 3.2 mg/kg morphine during high-dose treatment both attenuated development of tolerance and transferred control to lower doses. Transfer of control to lower doses appeared conditional upon recent termination of high-dose treatment, as it disappeared within 7 days. Treatment with saline did not change the doses of morphine required for stimulus effects under either training condition. A final experiment examined whether high-dose treatment could transfer control to higher doses of morphine. The treatment dose of 10 mg/kg morphine itself was used as the training dose during a 2-week treatment regimen. The dose of morphine required for stimulus effects increased 2- to 4-fold during treatment, but quickly returned to control values when treatment ended. These results extend previous findings that conditioning and pharmacodynamic processes jointly regulate development of tolerance to discriminative effects of morphine.     

Renal hemodynamics in the rat before and during inhibition of angiotensin II

Renal blood flow (RBF) was measured with a noncannulating electromagnetic flow transducer in anesthetized rats which had been maintained for 3-5 wk on low, normal, or high salt plus deoxycorticosterone diets. After base-line observations, one of two dissimilar inhibitors of the renin-angiotensin system, angiotensin I converting enzyme inhibitor SQ 20881 or the structural analogue [Sar1,Ala8]angiotensin II was administered intravenously. The employed doses of SQ 20881 and [Sar1,Ala8]angiotensin II effectively inhibited the pressor and renal vasoconstrictor responses induced by exogenous angiotensin I and II, respectively, in each dietary group. Both inhibitors vasodilated kidneys in salt-restricted rats; however, neither affected base-line renal hemodynamics in salt-loaded rats. Pressure-flow relationships were evaluated by clamping the aorta to reduce renal perfusion pressure. Renal blood flow was autoregulated between 100 and 140 mmHg with the same efficiency before and during inhibition of angiotensin II in each dietary group. These data indicate that angiotensin II modifies base-line RBF and renal vascular resistance and are consistent with the view that the renin-angiotensin system is not an essential mechanism responsible for autoregulation of RBF in the rat.     

Determination of bone mineral content using CT scanning

The usefulness and accuracy of CT scanning in the determination of bone mineral content is studied. The radius in 31 patients of both sexes and varying ages was examined using both the Norland-Cameron bone mineral analyzer and the CT scanner. There was reasonably good correlation (r=.72). Ten cadaver bones were then examined with CT scanning and were sent to the laboratory for calcium determination. These results indicate excellent correlation (r=.97). It is concluded that CT scanning represents the only practical and accurate in vivo method of bone mineral content determination.     

Relationship of cervical and abdominal vagal activity to lower esophageal sphincter function

The purpose of this study was to compare the effects of electrical stimulation of the abdominal and cervical portions of the vagus on lower esophageal sphincter (LES) pressure in the anesthetized opossum. Unilateral or bilateral abdominal vagotomy gave no significant change in basal LES pressure or in the sphincteric response to swallowing. Electrical stimulation of the peripheral end of the sectioned cervical vagus gave a frequency-related decrease in LES pressure with a maximum reduction of 93.5 +/- 2.5% at 10 HZ, 10 V. Stimulation of the central end of the cervical vagus increased LES pressure, with a maximum response of 34.0 +/- 1.9 mm Hg. Neither peripheral nor central stimulation of the sectioned abdominal vagus had significant effect on LES pressure (P greater than 0.05). Additionally, LES relaxation in response to swallowing or cervical vagal stimulation was intact after bilateral abdominal vagotomy. These studies suggest that whereas the cervical portion of the vagus mediates inhibitory and excitatory changes in LES pressure, the abdominal vagus has no demonstrable role in the control of LES function.