Adenosine pretreatment for prolonged cardiac storage. An evaluation with St. Thomas' Hospital and University of Wisconsin solutions.

Adenosine pretreatment has been shown to be beneficial in several models of ischemia-reperfusion. We wished to evaluate whether adenosine pretreatment is cardioprotective for prolonged cardiac storage and whether the presence of adenosine in the storage media affects the results. Isolated rodent hearts were obtained from Sprague-Dawley rats, mounted on a Langendorff apparatus, instrumented with an intraventricular balloon, and ventricularly paced at 300 beats/min. Four groups of hearts were studied in a 2 x 2 factorial experiment (n = 8 to 12 per group). Hearts were subjected to normal perfusion or to solution supplemented with adenosine 50 mumol/L for 10 minutes followed by adenosine-free perfusion for 10 minutes. Hearts then were stored for 8 hours at 0 degrees C in either University of Wisconsin solution (adenosine 5 mmol/L) or St. Thomas' Hospital II solution (adenosine free). Adenosine pretreatment increased tissue levels of adenosine triphosphate before storage (p = 0.04). Nonfunction was less common after storage (1/19 versus 6/20 hearts, p < 0.05), and diastolic function was better preserved in the adenosine groups in the reperfusion phase (p = 0.01). The beneficial effects of adenosine pretreatment were independent of which storage solution was used. Developed pressure was increased (p < 0.05) and release of creatine kinase and lactate dehydrogenase was reduced (p < 0.0001) in hearts treated with University of Wisconsin solution compared with those treated with St. Thomas' Hospital solution. These studies suggest that adenosine pretreatment improves recovery after prolonged hypothermic storage and that the presence of adenosine in the preservation solution does not alter the results. The experiments provide further evidence that extended myocardial protection is better enhanced with University of Wisconsin solution than with St. Thomas' Hospital II solution.

Dialysis of middle molecules at pulsatile flow.

Pulsatile flow was used in a continuous flow flat-plate dialyzer in order to achieve the more efficient removal of middle molecules. The solutes ranged in the molecular weights from 342 (sucrose) to 1355 (vitamin B-12). The permeability of Cuprophane membrane to sucrose, raffinose and vitamin B-12 were calculated both for pulseless and pulsatile flows. It was found that pulsatile flow is more favorable than steady flow with regard to increase of membrane permeability. However, as the solute molecular weight increases, fluid-phase resistances become relatively less important and the transport rate becomes dominated by the membrane properties.

Problems of competition in charcoal hemoperfusion for the treatment of intoxications.

Both toxic and physiological substances are adsorbed during an extracorporeal hemoperfusion for the treatment of exogenous and endogenous intoxications. Using a closed circuit in vitro, we perfused one liter saline or fresh human plasma with 4425 mumol creatinine, 4854 mumol and 97,086 mumol barbital-Na, 597 mumol bromthalein, 1942 mumol and 29,126 mumol raffinose, and 200 mumol inulin in different combinations over 70 gm of uncoated charcoal with the following results: 1. The adsorptive capacity of other substances is not influenced by preadsorption of the charcoal with a low or middle molecular weight substance; 2. In the low and middle molecular weight range, there is no competition between two substances in a solution; 3. The simultaneous usage of two substances of middle and high molecular weight, or preadsorption with a high molecular weight substance, reduces the rate of adsorption and the capacity of charcoal for middle molecular weight substances, but not for low molecular weight substances.

The distribution time of intravenously injected raffinose and inulin in intact animals and the effect thereon of sex and infusion of oxytocin.

1. In anaesthetized dogs whose renal pedicles were ligated the distribution time for I.V. administered raffinose was noted. In males the plasma concentration of raffinose fell for 7-10 min from the time of injection and in females it fell for 12-15 min; thereafter in both sexes the plasma concentration remained constant. 2. During I.V. infusion of oxytocin 10 mug/kg. min, the distribution time for raffinose was 12-16 min in males and 4-6 min in females. 3. During the period before stabilization of plasma concentration the concentration of raffinose was higher in the femoral artery than in the vein in both sexes. 4. In anaesthetized rats whose renal pedicles were ligated the distribution time for I.V. injected inulin was 7-8 min in males and 5 min in females. 5. Following alpha-adrenoceptor blockade with phentolamine the distribution time in both male and female rats was 14-15 min. 6. The sex differences in distribution time, both in normal and oxytocin-treated dogs, may be related to the state of contraction and differential sensitivity or pre- and post-capillary blood vessels and hence, of capillary pressure.

Reduction of allergic airway eosinophilia by dietary raffinose in Brown Norway rats.

Oral administration of raffinose, a naturally occurring indigestible oligosaccharide, has reportedly ameliorated atopic dermatitis in human subjects although the mechanism is unknown. The present study investigated the effect of dietary raffinose on allergen-induced airway eosinophilia in ovalbumin-sensitised Brown Norway rats as an atopic disease model. Brown Norway rats were immunised by subcutaneous injection with ovalbumin on day 0 and fed either a control diet or the diet supplemented with raffinose (50 g/kg diet). The rats were exposed to aerosolised ovalbumin on day 20, and broncho-alveolar lavage fluid was obtained on the next day. The number of eosinophils in the fluid was significantly lower in the rats fed the raffinose diet than in those fed the control diet. Dietary raffinose significantly reduced IL-4 and IL-5 mRNA levels in lung tissue and tended to lower ovalbumin-specific Ig E levels. Suppression of eosinophilia by dietary raffinose was still observed in caecectomised and neomycin-administered rats, suggesting little contribution by the colonic bacteria to the effect of raffinose. Intraperitoneal administration of raffinose also suppressed eosinophilia. Significant concentrations of raffinose were detected in portal venous and abdominal arterial plasma after the intragastric administration of raffinose. Overall, the findings suggest that dietary raffinose ameliorates allergic airway eosinophilia at least partly via post-absorptive mechanisms in Brown Norway rats.