Effect of Propofol With and Without EDTA on Haemodynamics and Calcium and Magnesium Homeostasis During and After Cardiac Surgery

Objective: To determine the effect of the addition of disodium edetate (EDTA) to propofol on haemodynamics, ionised calcium and magnesium serum concentrations, and adverse events during cardiac surgery. Design: Double-blind, randomised, multicenter trial. Setting: Operating room and intensive care unit of 5 academic health centres. Patients: A total of 102 evaluable patients, aged 34 to 85 years, undergoing first-time, elective coronary artery bypass graft surgery. Interventions: Comparison of propofol with EDTA and propofol without EDTA, each in conjunction with the opioid sufentanil, for intraoperative anaesthesia and postoperative sedation. Measurements and Results: There were no significant differences at any time between the two formulations in any clinical chemistry measurements, including ionised calcium, ionised magnesium, total calcium, parathyroid hormone, blood urea nitrogen, creatinine, sodium, potassium, and phosphate. During bypass, the mean concentration of ionised calcium decreased to below the normal range, but the decrease was similar in both groups (propofol with EDTA, 0.98 ± 0.07 mmol/L [N = 51]; propofol, 0.99 ± 0.10 mmol/L [N = 51]; p = NS). Calcium concentration returned to normal after rewarming. Mean ionised magnesium concentrations remained within normal limits in both groups. Similarly, there were no clinically meaningful differences between treatments with respect to haemodynamic variables, efficacy variables, or incidence of adverse events. Conclusions: The inclusion of EDTA in the current formulation of propofol appears to have no significant effects on calcium and magnesium profiles, renal function, haemodynamic variables, or other indicators of safety and efficacy during intraoperative anaesthesia and postoperative sedation in patients undergoing cardiac surgery.     

Synthesis and Antimycobacterial Activity of a Novel Series of Isonicotinylhydrazide Derivatives

A novel series of 14 new isonicotinyl hydrazide derivatives 2a – g , 3a – g containing a 4‐thiazolidinone / 2‐azetidinone nucleus were synthesized by reacting N′‐substituted arylidene / heteroarylidene isonicotinyl hydrazide 1a – g with thioglycollic acid in the presence of dry benzene and with chloroacetyl chloride in the presence of triethylamine, respectively. Structures of all newly synthesized compounds were characterized on the basis of elemental analyses and spectral data (IR and ¹H‐NMR). All the title compounds were tested for their in‐vitro antimycobacterial activity against Mycobacterium tuberculosis H₃₇Rv using Alamar‐Blue susceptibility test, and the activity is expressed as the minimum inhibitory concentration (MIC) in μg/mL. Among the series, compounds 2b , 2g , 3b , and 3g displayed an encouraging antimycobacterial activity profile as compared to that of the reference drugs isoniazid / rifampicin.     

Supervised toothbrushing and oral health education program in Kuwait for children and young adults with Down syndrome

The authors report on the effectiveness of a school-based, supervised toothbrushing program among a group of 112 children with Down syndrome in Kuwait. The study involved 45 boys and 67 girls, who ranged in age from 11–22 years (mean, 14.8 years). The participants had moderate mental retardation and attended one of two special needs schools. Plaque was scored according to the Silness and Loe plaque index and gingivitis according to the Loe and Silness gingival index. Supervised toothbrushing and dental health education sessions were conducted twice a week. The program was evaluated at the end of three months. The mean plaque score decreased from 1.93 to 0.95 (p < 0.001), and the mean gingival score from 2.00 to 0.83 (p < 0.001). This three-month supervised toothbrushing program was effective in reducing plaque and gingivitis scores, but the key to long-term success of the program is sustaining the children's motivation to make oral hygiene a part of their daily life.     

Protein kinase C-alpha and -epsilon modulate connexin-43 phosphorylation in human heart

We have previously demonstrated that protein kinase C (PKC)- alpha expression is significantly elevated in failing human left ventricle, with immunostaining showing increased PKC- alpha localization at the intercalated disks of cardiomyocytes. In the present study we sought to determine, in the failing heart, if PKC- alpha interacted with connexin-43 (Cx-43) both spatially and functionally, and to compare the association of PKC- alpha/Cx-43 with that of PKC- epsilon, a PKC isozyme that does not significantly increase in failing hearts. The possibility of a PKC- alpha or PKC- epsilon/Cx-43 association in non-failing hearts was also investigated. Co-immunoprecipitation of PKC- alpha or PKC- epsilon and Cx-43 in non-failing and failing left ventricle was achieved using antibodies to PKC- alpha or Cx-43. Confocal microscopy confirmed that PKC- alpha distribution within the cardiomyocyte included co-localization with connexin-43 in both failing and non-failing myocardium. In a similar manner, confocal imaging of PKC- epsilon showed cardiomyocyte distribution in both cytosol and membrane, and colocalization of PKC- epsilon with Cx-43. Recombinant PKC- alpha or - epsilon increased PKC activity significantly above endogenous levels in the co-immunoprecipitated Cx-43 complexes (P<0.05). However, phosphorylation of purified human Cx-43 (isolated from failing human left ventricle) by recombinant PKC- alpha or PKC- epsilon resulted in only PKC- epsilon mediated Cx-43 phosphorylation. Thus, in the human heart PKC- alpha, PKC- epsilon, and Cx-43 appear to form a closely associated complex. Whereas only PKC- epsilon directly phosphorylates Cx-43, both PKC isoforms result in increased phosphorylation within the Cx-43 co-immunoprecipitated complex.     

Accuracy of Intraoperative Epicardial Echocardiography in the Assessment of Surgical Repair of Congenital Heart Defects confirmed

Objective:

To determine the accuracy of epicardial echocardiography in detecting residual lesions after surgical repair of congenital heart defects. To determine the sensitivity, specificity, positive predictive valve, negative predictive valve, and false negative and false positive percentage of the same.

Materials and Methods:

One year hospital-based prospective study of epicardial echocardiography in patients undergoing cardiopulmonary bypass for surgical correction of congenital heart defects in children and adults.

Results:

Epicardial echocardiography was done in 158 patients. Residual lesions were detected in 38 patients by epicardial echocardiography. In 28 of these cases the residual lesions were significant. In 24 of them immediate reoperation was done with good outcome. Epicardial echo has high sensitivity, specificity, positive and negative predictive valve, in detecting residual lesion with congenital heart defects.

Conclusion:

Routine use of intraoperative epicardial echocardiography allows detection of majority of residual defects. It has high accuracy. There were no complications associated with use of epicardial echocardiography. The use of transesophageal echocardiography (TEE) can be avoided in small children and neonates undergoing cardiac surgery.     

Aprotinin for Primary Coronary Artery Bypass Grafting: A Multicenter Trial of Three Dose Regimens

Background. High-dose aprotinin reduces transfusion requirements in patients undergoing coronary artery bypass grafting, but the safety and effectiveness of smaller doses is unclear. Furthermore, patient selection criteria for optimal use of the drug are not well defined.

Methods. Seven hundred and four first-time coronary artery bypass grafting patients were randomized to receive one of three doses of aprotinin (high, low, and pump-prime-only) or placebo. The patients were stratified as to risk of excessive bleeding.

Results. All three aprotinin doses were highly effective in reducing bleeding and transfusion requirements. Consistent efficacy was not, however, demonstrated in the subgroup of patients at low risk for bleeding. There were no differences in mortality or the incidences of renal failure, strokes, or definite myocardial infarctions between the groups, although the pump-prime-only dose was associated with a small increase in definite, probable, or possible myocardial infarctions (p = 0.045).

Conclusions. Low-dose and pump-prime-only aprotinin regimens provide reductions in bleeding and transfusion requirements that are similar to those of high-dose regimens. Although safe, aprotinin is not routinely indicated for the first-time coronary artery bypass grafting patient who is at low risk for postoperative bleeding. The pump-prime-only dose is not currently recommended because of a possible association with more frequent myocardial infarctions.