Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery

The pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass (CPB), resulting in unpredictable postoperative hemodynamic responses to usual doses. The objective of the present study was to investigate the pharmacokinetics of propranolol in patients undergoing coronary artery bypass grafting (CABG) by CPB under moderate hypothermia. We evaluated 11 patients, 4 women and 7 men (mean age 57 ± 8 years, mean weight 75.4 ± 11.9 kg and mean body surface area 1.83 ± 0.19 m²), receiving propranolol before surgery (80-240 mg a day) and postoperatively (10 mg a day). Plasma propranolol levels were measured before and after CPB by high-performance liquid chromatography. Pharmacokinetic Solutions 2.0 software was used to estimate the pharmacokinetic parameters after administration of the drug pre- and postoperatively. There was an increase of biological half-life from 4.5 (95% CI = 3.9-6.9) to 10.6 h (95% CI = 8.2-14.7; P < 0.01) and an increase in volume of distribution from 4.9 (95% CI = 3.2-14.3) to 8.3 l/kg (95% CI = 6.5-32.1; P < 0.05), while total clearance remained unchanged 9.2 (95% CI = 7.7-24.6) vs 10.7 ml min-1 kg-1 (95% CI = 7.7-26.6; NS) after surgery. In conclusion, increases in drug distribution could be explained in part by hemodilution during CPB. On the other hand, the increase of biological half-life can be attributed to changes in hepatic metabolism induced by CPB under moderate hypothermia. These alterations in the pharmacokinetics of propranolol after CABG with hypothermic CPB might induce a greater myocardial depression in response to propranolol than would be expected with an equivalent dose during the postoperative period.

Pharmacokinetic and parasitological evaluation of the bone marrow of dogs with visceral leishmaniasis submitted to multiple dose treatment with liposome-encapsulated meglumine antimoniate

The aim of the present study was to evaluate the impact of a multiple dose regimen of a liposomal formulation of meglumine antimoniate (LMA) on the pharmacokinetics of antimony in the bone marrow of dogs with visceral leishmaniasis and on the ability of LMA to eliminate parasites from this tissue. Dogs naturally infected with Leishmania chagasi received 4 intravenous doses of either LMA (6.5 mg antimony/kg body weight, N = 9), or empty liposomes (at the same lipid dose as LMA, N = 9) at 4-day intervals. A third group of animals was untreated (N = 8). Before each administration and at different times after treatment, bone marrow was obtained and analyzed for antimony level (LMA group) by electrothermal atomic absorption spectrometry, and for the presence of Leishmania parasites (all groups). There was a significant increase of antimony concentration from 0.76 µg/kg wet organ (4 days after the first dose) to 2.07 µg/kg (4 days after the fourth dose) and a half-life of 4 days for antimony elimination from the bone marrow. Treatment with LMA significantly reduced the number of dogs positive for parasites (with at least one amastigote per 1000 host cells) compared to controls (positive dogs 30 days after treatment: 0 of 9 in the LMA group, 3 of 9 in the group treated with empty liposomes and 3 of 8 in the untreated group). However, complete elimination of parasites was not achieved. In conclusion, the present study showed that multiple dose treatment with LMA was effective in improving antimony levels in the bone marrow of dogs with visceral leishmaniasis and in reducing the number of positive animals, even though it was not sufficient to achieve complete elimination of parasites.

New nitric oxide donors based on ruthenium complexes

Nitric oxide (NO) donors produce NO-related activity when applied to biological systems. Among its diverse functions, NO has been implicated in vascular smooth muscle relaxation. Despite the great importance of NO in biological systems, its pharmacological and physiological studies have been limited due to its high reactivity and short half-life. In this review we will focus on our recent investigations of nitrosyl ruthenium complexes as NO-delivery agents and their effects on vascular smooth muscle cell relaxation. The high affinity of ruthenium for NO is a marked feature of its chemistry. The main signaling pathway responsible for the vascular relaxation induced by NO involves the activation of soluble guanylyl-cyclase, with subsequent accumulation of cGMP and activation of cGMP-dependent protein kinase. This in turn can activate several proteins such as K+ channels as well as induce vasodilatation by a decrease in cytosolic Ca2+. Oxidative stress and associated oxidative damage are mediators of vascular damage in several cardiovascular diseases, including hypertension. The increased production of the superoxide anion (O2-) by the vascular wall has been observed in different animal models of hypertension. Vascular relaxation to the endogenous NO-related response or to NO released from NO deliverers is impaired in vessels from renal hypertensive (2K-1C) rats. A growing amount of evidence supports the possibility that increased NO inactivation by excess O2- may account for the decreased NO bioavailability and vascular dysfunction in hypertension.

Effect of cardiopulmonary bypass on the pharmacokinetics of propranolol and atenolol

The pharmacokinetics of some β-blockers are altered by cardiopulmonary bypass (CPB). The objective of this study was to compare the effect of coronary artery bypass graft (CABG) surgery employing CPB on the pharmacokinetics of propranolol and atenolol. We studied patients receiving oral propranolol with doses ranging from 80 to 240 mg (N = 11) or atenolol with doses ranging from 25 to 100 mg (N = 8) in the pre- and postoperative period of CABG with moderately hypothermic CPB (32°C). On the day before and on the first day after surgery, blood samples were collected before β-blocker administration and every 2 h thereafter. Plasma levels were determined using high-performance liquid chromatography and data were treated by pharmacokinetics-modelling. Statistical analysis was performed using ANOVA or the Friedman test, as appropriate, and P < 0.05 was considered to be significant. A prolongation of propranolol biological half-life from 5.41 ± 0.75 to 11.46 ± 1.66 h (P = 0.0028) and an increase in propranolol volume of distribution from 8.70 ± 2.83 to 19.33 ± 6.52 L/kg (P = 0.0032) were observed after CABG with CPB. No significant changes were observed in either atenolol biological half-life (from 11.20 ± 1.60 to 11.44 ± 2.89 h) or atenolol volume of distribution (from 2.90 ± 0.36 to 3.83 ± 0.72 L/kg). Total clearance was not changed by surgery. These CPB-induced alterations in propranolol pharmacokinetics may promote unexpected long-lasting effects in the postoperative period while the effects of atenolol were not modified by CPB surgery.

Rheological behavior and color stability of anthocyanins from Merlot (Vitis vinifera L.) and Bordô (Vitis labrusca L.) grapes in a jam model system

Anthocyanins are the pigments responsible for the color of most red grapes and are easily degraded following various reaction mechanisms affected by oxygen, enzymes, pH, and temperature among other variables. In this study, a jam model system was developed using Merlot and Bordô grape extracts and polysaccharides (xanthan and locust bean gums) and different temperatures (45, 55 and 65 °C). The stability of the anthocyanin pigments and the rheological behavior of the jam model system were studied. For the determination of the stability, the half-life time and first-order reaction rate constants for the anthocyanin pigments were calculated. The rheological behavior was determined through the Power law model. The jam model system produced using a temperature of 45 °C showed the best results for the anthocyanin half-life time. The first-order reaction rate constants for the 45, 55, and 65 °C treatments were not significantly different among each other (p > 0.05). It was observed that with an increase in the jam model system temperature there was an increase in the index of consistency.

Stability of the anthocyanins extracted from residues of the wine industry

Anthocyanins are highly important due to their antioxidant capacity. They are the most important among the phenolic compounds and one of the main natural dyes used in the food industry. In this research, residue of processed grapes was used to investigate the presence of anthocyanins, the possibility of their extraction from the residue, and their stability. The extraction solution consisted of 70 mL of ethanol 70% and 30 mL of HCl 0.1% at pH 2.0. The results found for the processed grapes residue was 26.20 mg.100 g-1. In order to evaluate stability, caffeic acid was added at 0.5:1 w/v; 0.8:1 w/v; and 1:1 w/v concentrations. Anthocyanins extract reached the greatest stability at 0.5:1 w/v concentration, with 82.47% color retention and a half-life period of 15 days. Therefore, the use of this organic acid as a stabilizer for anthocyanins is feasible.

Effects of heat treatment and storage temperature on the use of açaí drink by nutraceutical and beverage industries

This study assesses the storage temperature effect on the anthocyanins of pasteurized and unpasteurized açaí pulp. The data was obtained using a pasteurized and lyophilized pulp (PLP) to evaluate the temperature effect (0, 25, and 40 °C). Part of non-pasteurized frozen pulp (NPP) was pasteurized (NPP-P) at 90 °C for 30 seconds; both pulps were stored at 40 °C. The anthocyanin content reduction in the drink was evaluated from the half-life time (t1/2), activation energy (Ea), temperature quotient (Q10), and the reaction rate constant (k). The t1/2 of the PLP anthocyanins stored at 40 °C was 1.8 times less than that stored at 25 °C and 15 times less than that stored at 0 °C; therefore, the higher temperatures decreased the stability of anthocyanins. The pasteurization increased the t1/2 by 6.6 times (10.14 hours for NPP and 67.28 hours for NPP-P). The anthocyanin degradation on NPP-P followed a first order kinetic, while NPP followed a second order kinetic; thus it can be said that the pasteurization process can improve the preservation of anthocyanins in the pulp.