Mortality and morbidity from intra-aortic balloon pumps. Risk analysis.

BACKGROUND: The purpose of this study, was to assess the incidence of and predictors for mortality and morbidity in patients who required postoperative intra-aortic balloon pump (IABP) support. METHODS: We have retrospectively estimated 116 patients and data were statistically analyzed, and significant variables were evaluated with multivariate analysis. RESULTS: Mortality rate was 57.8% (67 patients). Nineteen patients (16.3%) had major vascular complications: 12 patients (10.3%) limb ischemia, 1 patient (0.9%) aortic dissection, 6 patients (5.2%) mesenteric infarction. Thirty patients (25.8%) had minor vascular complication: 23 patients (19.8%) bleeding from insertion site, 7 (6%) patients infection of insertion site. Limb ischemia was resolved by IABP removal (10 patients), thrombectomy (2 patients). No patient required limb amputation. Sixty patients (51.7%) had renal insufficiency, of which 40 patients needed dialysis. Fifteen patients (10.3%) had neurological complications, 13 patients (11.2%) thrombocytopenia and 5 patients (4.3%) sepsis. CONCLUSIONS: The incidence of IABP insertion in our institution was 1.5%. Mortality rate is similar to mortality of other studies in which the IABP has been inserted in the postoperative period. We have found that timing of IABP insertion, thrombocytopenia, presence of peripheral vascular disease and the redo intervention are independent predictors of mortality. We also found that female sex, diabetes, history of cigarette smoking and preoperative use of antiplatelet drugs are independent predictors of limb ischemia. The following factors are instead independent predictors of renal insufficiency: postoperative ejection fraction lower than 40% and non use of dobutamine in the postoperative period.

Haemolysis due to active venous drainage during cardiopulmonary bypass: comparison of two different techniques.

To facilitate mini-access for cardiac surgery, two different methods of active venous drainage are used: vacuum assisted drainage and centrifugal pump aspiration on the venous line. The aim of this study was to compare the haemolysis produced using these two techniques. From June to December 1999, 50 consecutive patients were operated on using a ministernotomy. All of these patients had valvular surgery for either valve repair or valve replacement (9 MVRepair, 11 MVR, 29 AVR, 1 AVR + MVR). They were randomized into two groups: Group A, 25 patients who underwent surgery where vacuum assisted drainage was used, and Group B, 25 patients where kinetic asssisted venous drainage with centrifugal pump venous aspiration was used. Patient characteristics of both groups were similar for age, gender, body weight, body surface area, height, cardiopulmonary bypass (CPB) time, aortic crossclamp time, priming volume, cardioplegia volume, haemoglobin concentration, haematocrit, serum creatinine, bilirubin, lactate dehydrogenase (LDH), serum glutamic oxaloacetic transaminase (sGOT), serum glutamic pyruvic transaminase (sGPT), aptoglobin, reticulocytes, and platelet count. We checked all these laboratory parameters preoperatively, at the end of CPB, and 2 and 24 h after operation. We also checked haemoglobinuria at these same time points. We assessed blood loss at 6, 12, and 24 h after the operation and calculated total postoperative bleeding. There was a tendency towards a greater increase in LDH, sGOT and sGPT in Group A more than in Group B, but these data did not reach statistical significance. Platelet count was always lower in Group A and aptoglobin increased in Group A more than in Group B. More patients in Group A had haemoglobinuria. These findings indicate that haemolysis is increased more in patients treated with vacuum assisted drainage, when compared to the rise in haemolysis in those treated with centrifugal pump venous drainage. Total bleeding is also greater in Group A.

Effects of posttraining ethanol on an appetitive task.

The present study examined the effects of posttraining ethanol administration upon retention of an appetitive task using a variety of retention behaviors associated with the task. Male C57BL/6J mice were individually trained to find a cheese pellet placed in the corner of an open field. Five behavioral measures were used including locomotor activity counts, rearings, grooming episodes, approaches to the cheese pellet, and latency to consume the cheese pellet. Immediately after training, mice were injected intraperitoneally with saline or 2.0 g/kg of ethanol and then returned to their home cage in which four "intruder" mice were added for 2 h after training. On subsequent testing days (1, 6, 14, and 51 days posttraining), mice were returned to the original training environment and the five behaviors were measured. Both saline- and ethanol-treated mice habituated to the initially novel test environment at similar rates as indicated by decreased exploratory behavior (locomotor activity and rearings). In contrast, a divergence in the latency to consume the cheese pellet was observed: Saline-treated mice behaved as though the cheese was rewarding (decreased latency to eat the pellet), while the ethanol group behaved as though the cheese was aversive (increased latency to eat the pellet). Taken with previous studies, these results demonstrate that posttraining ethanol can have strikingly different effects on retention depending on the task, the measure of retention used, and the underlying neural structures involved.

Modulation of the stimulus effects of morphine by d-amphetamine.

The stimulus effects of morphine and d-amphetamine coadministration were studied in rats. Place conditioning, drug discrimination, and taste conditioning were employed to assess the rewarding, discriminative, and aversive stimulus properties of both drugs. d-Amphetamine increased the rewarding and morphine-like discriminative stimulus effects of 1.25 mg/kg morphine. d-Amphetamine did not, however, change the aversive effects of 1.25 mg/kg morphine, or any effect of higher (5-20 mg/kg) morphine doses. Because the rewarding/discriminative properties and the aversive properties of a drug are considered the main attributes that regulate (facilitate and weaken, respectively) drug-seeking behavior, the present data are in keeping with clinical reports indicating that amphetamines are sometimes used by opiate abusers in an attempt to increase the effect obtained from poor-quality heroin.

Reversible combined cognitive impairment and severe polyneuropathy resulting from primary hyperparathyroidism.

Central and peripheral nervous systems may be involved in primary hyperparathyroidism (PHP). The efficacy of parathyroidectomy in reversing neurological symptoms is still a matter of controversy. We describe the case of a 71-year-old white male with a 10-year history of PHP who developed progressive cognitive dysfunction and severe sensorimotor axonal polyneuropathy. Successful parathyroidectomy reversed with a different temporal course both the central and peripheral nervous system involvements.

Motivational properties of buprenorphine as assessed by place and taste conditioning in rats.

Buprenorphine, a mixed agonist-antagonist opioid with considerable analgesic activity, is currently indicated as a therapeutic agent with low abuse potential. Nevertheless, buprenorphine abuse has been recently reported from some countries. Thus the present experiments were performed to characterize further the motivational properties of buprenorphine in rats. Rewarding and aversive effects were assessed by place preference and taste aversion conditioning, respectively. It was found that buprenorphine (0.025, 0.050, 0.100 mg/kg s.c.) causes a significant increase in the amount of time spent on the conditioned side, but no significant decrease in saccharin consumption. Therefore buprenorphine data are not consistent with the general finding that psychoactive drugs cause rewarding and aversive effects within a similar dose range.

Food deprivation and motor activity in rats: differences between morphine and clonidine.

The effects of various doses of morphine (0, 1.25, 2.5, 5 mg/kg) and clonidine (0, 1.67, 15, 45 micrograms/kg) on motility were determined in food satiated and in food deprived rats. Food deprivation failed to change the general activity of rats after saline injections. Nevertheless, food-deprived animals tested under morphine were more active than food satiated ones. Clonidine exhibited slight psychomotor stimulant properties that were not increased by food deprivation. The results are discussed in terms of possible mechanisms of deprivation-related hypermotility.

Effects of buprenorphine on motility in chronically morphine treated rats.

The effects of buprenorphine (0.01-0.1 mg/kg) on the activity of nondependent and morphine dependent rats (a 20 mg/kg dose for 28 days) were determined. In naive animals buprenorphine exhibited both depressive and stimulatory actions upon the motility of rats, as repeatedly described for morphine. When buprenorphine was administered to rats chronically treated with morphine, the depressive effect disappeared (cross-tolerance to the inhibitory action); on the contrary the excitatory effect was enhanced (cross-sensitization). The results are discussed in terms of cross-sensitization to the excitatory effects in morphine dependent animals as predictor of morphine-like addictive properties in humans.

Genetically determined differences in the antagonistic effect of pressure on ethanol-induced loss of righting reflex in mice.

Hyperbaric exposure antagonizes ethanol's behavioral effects in a wide variety of species. Recent studies indicating that there are genetically determined differences in the effects of body temperature manipulation on ethanol sensitivity suggested that genotype might also influence the effects of hyperbaric exposure on ethanol intoxication. To investigate this possibility, ethanol injected long sleep (LS)/Ibg (2.7 g/kg), short sleep (SS)/Ibg (4.8 g/kg), 129/J (2.9 g/kg), and C57BL/6J (3.6 g/kg) mice were exposed to one atmosphere absolute (ATA) air or to one or 12 ATA helium-oxygen (heliox) at ambient temperatures selected to offset ethanol and helium-induced hypothermia. Hyperbaric exposure significantly reduced loss of righting reflex (LORR) duration in LS, 129, and C57 mice, but not in SS mice. A second experiment found that hyperbaric exposure significantly reduced LORR duration and increased the blood ethanol concentration (BEC) at return of righting reflex (RORR) in LS mice, but did not significantly affect either measure in SS mice. These results indicate that exposure to 12 ATA heliox antagonizes ethanol-induced LORR in LS, 129 and C57 mice, but not in SS mice. Taken with previous results, the present findings suggest that the antagonism in LS, 129, and C57 mice reflects a pressure-induced decrease in brain sensitivity to ethanol and that the lack of antagonism in SS mice cannot be explained by pressure-induced or genotypic differences in ethanol pharmacokinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Bioavailability of a new controlled-release oral naproxen formulation given with and without food.

The influence of concomitant food intake on the plasma concentration of naproxen given as a new controlled-release (CR) formulation (750-mg tablet) was investigated in a crossover study design. Twelve healthy volunteers received a single tablet of naproxen on two occasions separated by a 3-week washout period:- after an overnight fast and immediately after a standard meal. Plasma naproxen levels were measured through HPLC at intervals suitable for obtaining concentration-time curves of both regimens in the range 1--48 hours. It was found that average plasma AUC values were 1978.7 mcg.hr/ml in fasting participants and 1778.6 mcg.hr/ml in postprandial participants. The confidence interval computed by Westlake's method indicated equivalence of values. Food decreased the peak plasma concentration of CR naproxen by about 14%, but the confidence interval (+/- 22%) barely exceeded equivalence limits. There were no significant differences between fasting versus postprandial values for the mean absorption time, or plasma absorption and disposition half-lifes. It is concluded that the bioavailability of CR naproxen is not substantially altered by the ingestion of food.

Antithrombotic and thrombolytic activity of sulodexide in rats.

We evaluated the ability of sulodexide, an extracted glycosaminoglycan, to prevent thrombus formation and to reduce a stabilized thrombus in a rat venous thrombosis model (vena cava ligature). Injection of sulodexide 10 min before induction of venous stasis, prevented thrombus formation in a dose-dependent manner (median effective dose 0.55 mg/kg). When given to rats with 6-h-old thrombi, sulodexide caused a marked reduction in thrombus size which reached 70% after 2 h with the highest dose tested (2 mg/kg). The effect of sulodexide on established thrombi appears to be due, at least in part, to a fibrinolysis-mediated mechanism, since it was significantly inhibited by epsilon-aminocaproic acid, a well-known antifibrinolytic drug. Treatment with sulodexide did not noticeably affect plasma levels of plasminogen activator and its specific inhibitor. We also showed that fluorescein-labelled sulodexide, when given to animals with 6-h-old thrombi, was present within the thrombi harvested 2 h later, but was then absent from blood. The fluorescence was mainly located in areas filled with amorphous material, that was identified as fibrin by staining with phosphotungstic acid-hematoxylin. No fluorescein-labelled material could be detected in rats treated with fluorescein alone. These findings indicate that, besides preventing venous thrombus formation, sulodexide is able to promote thrombus dissolution by a mechanism that is partly related to local fibrinolysis stimulation.

The relationship between brain temperature during intoxication and ethanol sensitivity in LS and SS mice.

The present study characterized the relationship between brain temperature, rectal temperature, and ethanol sensitivity in the selectivity bred long-sleep (LS) and short-sleep (SS) mice. Radiotelemetric brain probe implanted and nonimplanted LS/lbg and SS/lbg male mice were injected with 2.5 and 4.9 g/kg ethanol, respectively, before exposure to ambient temperatures of 15 degrees C, 22 degrees C, or 34 degrees C. Ambient temperature significantly affected rectal temperature, brain temperature, and ethanol sensitivity, measured by impairment of righting reflex. Brain and rectal temperatures at return of righting reflex (RORR) were highly correlated. In SS mice brain and rectal temperatures at RORR were significantly positively correlated with loss of righting reflex (LORR) duration and significantly negatively correlated with blood ethanol concentration (BEC) at RORR. In LS mice rectal temperature at RORR was significantly negatively correlated with LORR duration, while both brain and rectal temperature at RORR were significantly positively correlated with BEC at RORR. The strength of the correlations and r2 values generated from linear regression analysis indicates that body temperature during intoxication can explain up to 52% of the variability in ethanol sensitivity in SS mice, but only 19% of the variability in ethanol sensitivity in LS mice. The correlational analyses are consistent with previous results based on comparisons between rectal temperature and ethanol sensitivity and extend to direct brain temperature measurement the evidence that decreasing temperature during intoxication decreases ethanol sensitivity in SS mice and increases ethanol sensitivity in LS mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of post-training ethanol and group housing upon memory of an appetitive task in mice.

It has been shown that post-training ethanol's facilitating effects upon memory disappeared if the mice were kept isolated after training. Since ethanol-treated mice were attacked by their cagemates, it has been hypothesized that the improved retention induced by ethanol resulted from an interaction between ethanol and group housing which added aversive information to training. To investigate the correctness of this interpretation, ethanol effects upon memory of an appetitive task were studied. C57BL/6J mice (isolated the day before training) were individually trained to find a cheese pellet placed in a corner of an open-field. Mice were injected intraperitoneally immediately after training with saline, 0.5, 1.5, or 2.0 g/kg of ethanol. They were then returned to their home cage and left alone, with another mouse, or with five other mice for 2 h after training. All mice were tested 24 h later for retention. Reductions in the number of pellet approaches or in the latency to eat the pellet were taken as measures of learning. Post-training ethanol disrupted retention of the appetitive task in a dose-related manner. Moreover disruption was greater in mice group housed after training. The results support the hypothesis that ethanol's post-training facilitating effects upon aversive memory may be due to added aversive information to the stimulus complex, rather than, or in addition, to enhanced storage of memory traces.

Ethanol-induced depression of aggression in mice antagonized by hyperbaric exposure.

The present study investigated the effect of hyperbaric exposure on ethanol-induced depression of aggressive behavior measured by resident-intruder confrontations. Adult male CFW mice (residents) were paired with females and housed together for 26 days. Then, resident mice were intubated with either ethanol (2 g/kg) or water (20 ml/kg) and were exposed to 1 atmosphere absolute (ATA) air, 1 ATA helium oxygen (heliox) or 12 ATA heliox using a within-subjects counterbalanced design. Thirty minutes after intubation an intruder was introduced. Ethanol significantly decreased aggressive behaviors (attack latency, attack bites, sideways threats, tail rattles and pursuit) in 1 ATA-treated animals. Pressure completely antagonized the depression of aggression induced by ethanol. Ethanol alone and pressure alone did not significantly affect nonaggressive behaviors. There were no statistically significant differences between groups in blood ethanol concentrations 50 minutes after intubation. These results suggest that ethanol's effects on aggressive behavior result from the same membrane actions leading to loss of righting reflex, depression of locomotor activity, tolerance and dependence.

Role of repeated exposure to morphine in determining its affective properties: place and taste conditioning studies in rats.

Male Sprague Dawley rats were injected daily with saline (morphine naive rats) or 20 mg/kg morphine (morphine experienced rats), starting at least 12 days before training. Subsequent place and taste conditioning indicated that 2.5 mg/kg morphine caused a significant increase in the amount of time spent on the least preferred side by morphine experienced but not by morphine naive rats; furthermore, saccharin consumption was markedly decreased and slightly increased by 10-20 mg/kg morphine in naive and experienced rats, respectively. It was concluded that morphine experience enhances the reinforcing efficacy of morphine and broadens the conditions under which the drug is reinforcing; thus it possibly increases morphine abuse potential.

Morphine attenuation of a conditioned emotional response in post-dependent rats.

Rats placed in a test chamber where they had received repetitive shocks the previous day significantly reduced their motor activity; this was taken as indicator of a conditioned emotional response. Morphine attenuated this conditioned suppression of motility, possibly due to a reduction of the anxiety associated with the expectation of the noxious stimuli. Previous morphine dependence (20 mg/kg daily for 26 days) did not modify the effect of the opioid on the conditioned suppression of motility. This fact suggests that the action of morphine on pain anticipatory anxiety is similar in non-dependent and in post-dependent rats. Opioids are considered to produce pain relief in part by decreasing the anticipatory anxiety. The present results thus indicate that this important component of the analgesic action of morphine is unchanged in post-addicts.

Pharmacokinetic evaluation of conventional and controlled-release product of naproxen.

The bioavailability and pharmacokinetics of a new controlled-release tablet (CRT) of naproxen (750 mg tablet) have been determined, relative to an equivalent dose of conventional product (CT), by a cross-over study in twenty healthy volunteers. The two dosage forms were bioequivalent in terms of total AUC; however, the Cmax of the controlled-release product was lower, and the Tmax longer than that of the conventional product. The mean residence time and the absorption and elimination half-lives of the CRT were also substantially longer than those of the CT. The pharmacokinetic features offered by the novel formulation suggest that it may be suitable for once-daily dosing.