Oxidative insult associated with hyperoxic cardiopulmonary bypass in the infantile heart and lung.

Cardiopulmonary bypass (CPB) per se alters many factors simultaneously, including free radical generation, which suggests that conventional hyperoxic CPB may produce oxidative injury in the infantile heart and lung. This study tests the hypothesis that CPB provokes oxidative cardiopulmonary changes and pulmonary endothelial dysfunction in immature piglets that can be prevented by free radical scavengers. We studied 15 2- to 3-week-old piglets. Five served as a control without CPB. Ten piglets underwent 60 min of CPB with a membrane oxygenator (Sarns). In 5 of these 10, the bypass prime was supplemented with N-mercaptopropionylglycine (MPG: 80 mg/kg) plus catalase (50,000 U/kg), whereas the others were not treated. Pre- and post-bypass cardiopulmonary function was measured in terms of left ventricular end-systolic elastance [Ees] by a conductance catheter, the arterial/alveolar pO2 ratio (a/A ratio) and static lung compliance. Conjugated dienes (A233 nm/mg lipid) were measured to detect lipid peroxidation in heart and lung tissue, and myocardial antioxidant reserve capacity [malondialdehyde (MDA) production in cardiac tissue incubated with the oxidant t-butyl hydroperoxide (t-BHP)] was assessed to detect oxidative changes. Pulmonary vascular resistance (PVR) and transpulmonary nitric oxide (NO) production were measured to assess pulmonary endothelial injury. Myocardial antioxidant reserve capacity was significantly reduced after 60 min of CPB, compared to control animals (MDA 779 +/- 100 vs 470 +/- 30 nmol/g protein, p < 0.05 at t-BHP 2.0 mmol/L), without evidence of lipid peroxidation or myocardial dysfunction. Pulmonary vascular resistance after CPB was dramatically increased (83 +/- 12 to 212 +/- 30, p < 0.05) without any change in lung function. In parallel to pulmonary vasoconstriction, NO production was significantly decreased after CPB (from 8.8 +/- 1.4 to 2.5 +/- 0.5 mmol/min/kg, p < 0.05). The addition of antioxidants (MPG+catalase) to the prime significantly improved myocardial antioxidant status (MDA: 604 +/- 30 vs 779 +/- 100 nmol/g protein, p < 0.05) and pulmonary vascular resistance (114 +/- 29 vs 212 +/- 30, p < 0.05 vs no-treatment group). In conclusion, the present study confirms that 1) Cardiopulmonary bypass produces substantial oxidative stress in normal immature myocardium, as assessed by reduced antioxidant reserve capacity; 2) CPB impairs pulmonary endothelial function, characterized by NO production, resulting in pulmonary vasoconstriction; and 3) These deleterious effects can be prevented by the addition of antioxidants (MPG/catalase) to the pump prime.

Electroacupuncture and morphine analgesia potentiated by bestatin and thiorphan administered to the nucleus accumbens of the rabbit.

The endogenous opioid peptide enkephalin (EK) is known to be degraded mainly by two enzymes, the dipeptidyl carboxypeptidase 'enkephalinase' and aminopeptidase. Microinjection of the enkephalinase inhibitor thiorphan or the aminopeptidase inhibitor bestatin into the nucleus accumbens of the rabbit produced a dose-dependent analgesic effect. This analgesic effect was totally reversed by the narcotic antagonist naloxone or by antibodies against [Met5]enkephalin (MEK) administered to the same site. Antibodies against [Leu5]enkephalin were not effective. Moreover, microinjection of thiorphan or bestatin into the nucleus accumbens resulted in a marked potentiation of the aftereffect of electroacupuncture (EA) produced analgesia, as well as the analgesia induced by a small dose of morphine. It is concluded that the analgesic effect elicited by EA and morphine is mediated, at least in part, by MEK-like immunoreactive substance(s) in the nucleus accumbens.

[Effect of alpha-mercaptopropionylglycine (alpha-MPG) and sodium dipropylacetate (DPA) on antibody formation (I) (author's transl)].

The humoral immuno-response: A study was carried out to determine the effect of alpha-MPG and DPA on humoral antibody formation. The following results were obtained: The 1st and 2nd immuno-responses in rabbits to bacterial alpha-amylase were potentiated by treatment with both alpha-MPG and DPA given i.p. for 10 days after the 1st immunization, but the treatment after the 2nd immunization did not affect the 2nd immuno-response. Formation of hemolytic plaque forming cells (HPFC) in the spleen of mice immunized with 5 X 10(8) sheep red blood cells (SRBC) was potentiated by the administration of the both drugs given i.p. for 5 days before or after the immunization. No appreciable formation of HPFC was observed by immunization with 5 X 10(6) SRBC, and here alpha-MPG or DPA were without effects. Immunization with more than 5 X 10(7) SRBC resulted in an increase of HPFC in a dose-dependent fashion. Such an increase was further reinforced by treatment with both drugs. HPFC increased with a single dose of alpha-MPG at 48 hr before or 24 approximately 72 hr after the immunization and also increased with that of DPA at 24 hr before or immediately after the SRBC treatment.

[Cystine stone therapy with mercapto-propyonyl-glycine (MPG) (Thiola) (author's transl)]. / Cystinsteintherapie mit Mercaptopropyonylglycin (MPG) (Thiola)

Six patients with recurrent cystine stones and cystinuria were treated with MPG. Three patients were treated for 3 years and 3 patients for 6 months. A relatively high dosage resulted in a reduction of the cytinuria. Since MPG has almost no side effects it represents a valuable aid in the treatment of cystine stones.