Mechanisms of pulmonary dysfunction after on-pump and off-pump cardiac surgery: a prospective cohort study

Background  

Pulmonary dysfunction following cardiac surgery is believed to be caused, at least in part, by a lung vascular injury and/or atelectasis following cardiopulmonary bypass (CPB) perfusion and collapse of non-ventilated lungs.     

Treatment of myofascial trigger points in common shoulder disorders by physical therapy: A randomized controlled trial [ISRCTN75722066]

Background  

Shoulder disorders are a common health problem in western societies. Several treatment protocols have been developed for the clinical management of persons with shoulder pain. However available evidence does not support any protocol as being superior over others. Systematic reviews provide some evidence that certain physical therapy interventions (i.e. supervised exercises and mobilisation) are effective in particular shoulder disorders (i.e. rotator cuff disorders, mixed shoulder disorders and adhesive capsulitis), but there is an ongoing need for high quality trials of physical therapy interventions. Usually, physical therapy consists of active exercises intended to strengthen the shoulder muscles as stabilizers of the glenohumeral joint or perform mobilisations to improve restricted mobility of the glenohumeral or adjacent joints (shoulder girdle). It is generally accepted that a-traumatic shoulder problems are the result of impingement of the subacromial structures, such as the bursa or rotator cuff tendons. Myofascial trigger points (MTrPs) in shoulder muscles may also lead to a complex of symptoms that are often seen in patients diagnosed with subacromial impingement or rotator cuff tendinopathy. Little is known about the treatment of MTrPs in patients with shoulder disorders.     

The bioavailability and nonlinear pharmacokinetics of MK-679 in humans

MK-679 (R(?)-3-((3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)(3-(dimethylamino)-3-oxopropyl)thio)methyl)thio(propanoic acid) is a potent and specific LTD₄-receptor antagonist. The disposition of MK-679 was investigated in a three-way crossover study in 12 healthy males receiving single intravenous doses of 75, 250, and 500 mg of MK-679. A greater than proportional increase in the area under the plasma concentration—time curve of MK-679 was observed with increase in dose. The plasma concentration data for each subject fitted well to the differential equations for a two-compartment model with linear tissue distribution and Michaelis-Menten elimination from the central compartment, indicating that the elimination of MK-679 in humans is saturable. In a previous study, the disposition of MK-679 in humans was also dose-dependent when given together with its S(+)-isomer, L-668,018. Thus, the disposition of MK-679 in humans is dose-dependent regardless of the presence of its stereoisomer. Also, the bioavailability of MK-679 was determined in six healthy males receiving simultaneously an oral dose of 250 mg of MK-679 and intravenous infusion of 1 mg ¹⁴C-MK-679. Results of this study indicate that the oral bioavailability of MK-679 is nearly quantitative.     

Role of Tyrosine Kinase in Desflurane-induced Preconditioning

Background: Short administration of volatile anesthetics preconditions myocardium and protects the heart against the consequences of subsequent ischemia. Activation of tyrosine kinase is implicated in ischemic preconditioning. The authors investigated whether desflurane-induced preconditioning depends on activation of tyrosine kinase.

Methods: Sixty-four rabbits were instrumented for measurement of left ventricular pressure, cardiac output, and myocardial infarct size (IS). All rabbits were subjected to 30 min of occlusion of a major coronary artery and 2 h of subsequent reperfusion. Rabbits underwent a treatment period consisting of either no intervention for 35 min (control group, n = 12) or 15 min of 1 minimum alveolar concentration desflurane inhalation followed by a 10-min washout period (desflurane group, n = 12). Four additional groups received the tyrosine kinase inhibitor genistein (5 mg/kg) or lavendustin A (1.3 mg/kg) at the beginning of the treatment period with (desflurane-genistein group, n = 11; desflurane-lavendustin A group, n = 12) or without desflurane inhalation (genistein group, n = 9; lavendustin A group, n = 8).

Results: Hemodynamic values were similar in all groups during baseline (left ventricular pressure, 87 +/- 14 mmHg [mean +/- SD]; cardiac output, 198 +/- 47 ml/min), during coronary artery occlusion (left ventricular pressure, 78 +/- 12 mmHg; cardiac output, 173 +/- 39 ml/min), and after 2 h of reperfusion (left ventricular pressure, 59 +/- 17; cardiac output, 154 +/- 43 ml/min). IS in the control group was 55 +/- 10% of the area at risk. The tyrosine inhibitors had no effect on IS (genistein group, 56 +/- 13%; lavendustin A group, 49 +/- 13%; each P = 1.0 vs. control group). Desflurane preconditioning reduced IS to 40 +/- 15% (P = 0.04 vs. control group). Tyrosine kinase inhibitor administration had no effect on IS reduction (desflurane-genistein group, 44 +/- 13%; desflurane-lavendustin A group, 44 +/- 16%; each P = 1.0 vs. desflurane group).     

S-nitrosoglutathione-containing hydrogel accelerates rat cutaneous wound repair

BACKGROUND: Nitric oxide (NO) plays a key role in wound repair and S-nitrosothiols like S-nitrosoglutathione (GSNO) are well known NO donors. METHODS: Animals were separated in two groups and submitted to excisional wounds on the dorsal surface at the first day. GSNO (100 microm)-containing hydrogels were topically applied on the wound bed in the GSNO group, daily, during the first 4 days. Control group was topically treated with hydrogel without GSNO for the same period. Wound contraction and re-epithelialization were measured. Animals were sacrificed 21 days after wounding. Samples of lesion and normal tissue were formalin-fixed, paraffin embedded for histological analysis. RESULTS: Wound contraction, measured 14 and 21 days after wounding, was greater in the GSNO group than in the control group (P<0.05 for both). The re-epithelialized wound area, measured 14 days after wounding, was higher in the GSNO group than in the control group (P<0.05). A higher amount of inflammatory cells was observed in superficial and deep areas of the granulation tissue of the control group compared to the GSNO group. Twenty-one days after wounding, thin red-yellow collagen fibers arranged perpendicularly to the surface were found in the granulation tissue of the control group, whereas in the GSNO-treated group collagen fibers were thicker and arranged parallel to the surface. Increased number of mast cells was observed in the GSNO group compared with that in the control group. Vascularization and myofibroblast distribution were similar in both groups. CONCLUSION: Topical application of GSNO-containing hydrogel during the early phases of rat cutaneous wound repair accelerates wound closure and re-epithelialization and affects granulation tissue organization.     

Stimulation of choline/Mg2+ antiport in rat erythrocytes by mefloquine.

In non Mg(2+)-loaded and non malaria-infected rat erythrocytes, mefloquine (100 micromol x l (-1)) stimulated choline/Mg2+ antiport without affecting the Na+/Mg2+ antiport. The stimulation of the choline/Mg2+ antiport by mefloquine, found in this study, and by trifluoperazine and fluvoxamine, reported previously [Ebel et al. Biochim Biophys Acta 2004; 1167: 132-40], was associated with CF3 groups attached to the quinoline or benzene ring. The effect of mefloquine on choline/Mg2+ antiport in vitro was not related to the antimalarial action of mefloquine in vivo. In rat erythrocytes, the choline/Mg2+ antiport can be differentiated from the Na+/Mg2+ antiport through the use of cinchonine that inhibited the choline/Mg2+ antiport [Ebel et al. Biochim Biophys Acta 2002; 1559: 135-44], and mefloquine that stimulated the choline/Mg2+ antiport, whereby the Na+/Mg2+ antiport was not affected by either drug at proper concentrations. The Na+/Mg2+ antiport and choline/Mg2+ antiports behave as different molecular entities.     

Distribution of cholinergic neurons in the chick spinal cord during embryonic development. Comparison of ChAT immunocytochemistry with AChE histochemistry.

The location of cholinergic neurons was studied during the development of the chick embryo spinal cord. A comparison between choline acetyltransferase (ChAT) immunocytochemistry and acetylcholinesterase (AChE) histochemistry was performed. ChAT-positive neurons could be detected only from embryonic day 9 (E9) onwards by the FITC technique and from E12 onwards by the PAP technique. These neurons were located mainly in the medial and lateral motor columns in the ventral horn of the gray matter and some of them were observed in the intermediate region of the spinal cord. AChE-containing cell bodies were much more numerous than the ChAT immunoreactive ones and were distributed in the ventral horn of the gray matter, the intermediate gray region and mostly off the apical part of the dorsal horn. ChAT should provide a reliable and specific marker for cholinergic neurons.     

Mild hypothermia during halothane-induced anesthesia decreases resistance to Staphylococcus aureus dermal infection in guinea pigs

Because various immune functions are impaired at temperatures only 1 degrees to 3 degrees C less than normal, we tested the hypothesis that mild hypothermia during anesthesia impairs resistance to dermal infections. Guinea pigs were anesthetized for 6 hours with 1% inspired halothane. Their core temperatures were maintained at either 39 degrees C (normal for guinea pigs, n = 12) or 36 degrees C (n = 12). Two hours after induction of anesthesia, three doses each of Staphylococcus aureus (10(8), 10(7), and 10(6) organisms) were injected intradermally at nine sites on each animal's back. Core temperatures were not controlled after recovery from the anesthetic, and animals in each group were maintained in the same environment. Four days after anesthesia, each injection site was excised to obtain a count of viable bacteria. Subcutaneous oxygen partial pressure values, averaged over time, were 53 +/- 3 mm Hg (mean +/- SEM) in the hypothermic group and 62 +/- 4 mm Hg in the normothermic group (p = 0.06). Capillary perfusion, as assessed by laser Doppler flowmetry, was comparable in the two groups. One day after injection of 10(8) bacteria, the area of induration was 89 +/- 11 mm(2) in the hypothermic group but only 61 +/- 6 mm(2) in the normothermic group (p < 0.05). On postanesthetic day 4, the area of induration was 72 +/- 6 and 59 +/- 6 mm(2) in the hypothermic and normothermic groups, respectively (p > 0.05). After inoculation with 10(8) bacteria, the fraction recovered was 1.0 +/- 0.2 in the hypothermic groups and 0.6 +/- 0.2 in the normothermic group (p < 0.05). After inoculation with 10(7) and 10(6) bacteria, the fraction recovered was less than 0.2, and no difference was found between the hypothermic and normothermic animals. Thus mild hypothermia during halothane-induced anesthesia slightly impairs resistance to dermal infection.