For a better understanding of the persistence of Borrelia burgdorferi sensu lato (s.l.) after antibiotic therapy the kinetics of killing B. burgdorferi s.l. under amoxicillin, doxycycline, cefotaxime, ceftriaxone, azithromycin and penicillin G were determined. The killing effect was investigated in MKP medium and human serum during a 72 h exposure to antibiotics. Twenty clinical isolates were used, including ten strains of Borrelia afzelii and ten strains of Borrelia garinii. The results show that the kinetics of killing borreliae differ from antibiotic to antibiotic. The killing rate of a given antibiotic is less dependent on the concentration of the antibiotic than on the reaction time. Furthermore, the data show that the strains of B. afzelii and B. garinii have a different reaction to antibiotics used in the treatment of Lyme borreliosis and that different reactions to given antibiotics also exist within one species. The B. garinii strains appear to be more sensitive to antibiotics used in therapy. Furthermore, the persistence of B. burgdorferi s.l. and clinical recurrences in patients despite seemingly adequate antibiotic treatment is described. The patients had clinical disease with or without diagnostic antibody titers to B. burgdorferi.

Adolescent↗

PubMedDate not supplied

Inorganic phosphate inhibits contractility and ATPase activity in skinned fibers from human myocardium.

During hypoxic heart failure, inorganic phosphate (Pi) accumulates. We report the effects of Pi on force development and on myofibrillar ATPase-activity of human skinned atrial fibers, both at normal and at reduced levels of Mg-ATP. Pi (10 mM) depressed force production at maximal calcium activation (pCa 4.3) by about 40%. At higher pCa values (pCa 5.6), force inhibition was even more pronounced, but at low concentrations of Mg-ATP (10 microM), Pi was less effective. In contrast to contractile force, myofibrillar ATPase was only inhibited by about 10% at pCa 4.3, whereas it could be inhibited by 40-50% at submaximal calcium activation (pCa 5.6). As Pi inhibited contractile force more than ATPase activity, the ratio of ATPase-activity to force (tension cost) was increased by inorganic phosphate. ATPase-activity and tension cost were significantly reduced by lowering Mg-ATP concentration to 10 microM, whereas contractile force was less affected. Pi did not affect ATPase under these conditions at 10 mM Mg-ATP. Pi also shifted the calcium-force relationship towards higher Ca++ concentrations, that is, it decreased calcium sensitivity. In contrast, the calcium sensitivity of myofibrillar ATPase was less affected. These findings suggest that inorganic phosphate may affect the myocardium by altering crossbridge kinetics rather than the calcium affinity of troponin-C. Because of its inhibitory effect on myofibrillar ATPase, inorganic phosphate may be partly cardioprotective in the hypoxic myocardium. However, this "energy sparing' effect is probably offset by the greater "tension cost' that decreases the "efficiency' of tension maintenance in the presence of inorganic phosphate.

Adenosine Triphosphatases↗

PubMedDate not supplied

The effect of hemodilution on regional myocardial function in the presence of coronary stenosis.

Hemodilution decreases blood viscosity and circulatory input impedance and thus reduces afterload. Its use in treatment of LV power failure has been advocated, but the safe limits of isovolemic hemodilution are not known. Compensation of the reduced O2-capacity of the blood was therefore studied with normal and impaired coronary reserve. In 20 dogs the LAD was stenosed to a degree just not affecting the supplied region and central and coronary hemodynamics were studied. Regional myocardial function was assessed by ultrasound transit time between transducers implanted in the LV wall. Lowering the hematocrit to 15% by isovolumic exchange of blood for Dextran 60 increased CVP (18%), PAP (47%), LAP (64%), LVedP (46%), CO (67%), and flow to the intact area (LCA: 211%). Flow in the stenosed LAD increased slightly. Enddiastolic length (EDL) of LAD dependent muscle segments rose to 120% and their contraction amplitude deltaL was decreased by 46%. Whereas non-ischemic segments showed compensatory rise in deltaL (38%) at almost constant EDL (+9%). After release of the LAD stenosis EDL and deltaL returned to normal. During progressive anemia myocardial O2-demand is not adequately met if coronary reserve capacity is depleted. Reversion of hypokinesia after removal of the stenosis shows unimpaired myocardial function at a hematocrit as low as 15% provided the coronary circulation is intact.

Animals↗

PubMedDate not supplied

Effects of the H2-receptor agonist impromidine in human myocardium from patients with heart failure due to mitral and aortic valve disease.

We determined stimulation rates of cardiac adenylate cyclase activity by isoproterenol and impromidine in particulate sarcolemmal membrane preparations from human papillary muscles resected during open heart replacement of mitral and aortic valves. In addition, specific receptor binding studies with [3H]dihydroalprenolol [( 3H]DHA) to cardiac beta-receptors and [3H]tiotidine [( 3H]TIOT) to cardiac H2-receptors were carried out in the same preparations. Compared with the response in patients with pure mitral valve stenosis, the response of cardiac adenylate cyclase activity to isoproterenol showed a marked decrease (-90%) in patients with combined mitral and aortic valve disease, corresponding to the severity of degree of insufficiency at both valves. Similar changes were observed in receptor binding studies with [3H]DHA, in which the reduction of beta-receptor density was of the same order of magnitude. In contrast, stimulation of the enzyme by impromidine and binding capacity of [3H]TIOT to cardiac H2-receptors were found to be unaltered in the same membrane preparations of all 16 patients. We conclude that treatment with H2-agonists may be a new therapeutic approach to congestive heart failure, especially in patients not responding to beta-adrenoceptor stimulation with beta-sympathomimetic drugs.

Adenylyl Cyclases↗

PubMedDate not supplied

Extracorporeal circulation induced microvascular perfusion injury of the small bowel.

Gastrointestinal complications following cardiopulmonary bypass (CPB) are relatively uncommon, but are associated with a high mortality rate. Impairment of bowel perfusion during and following CPB may serve as a trigger for the development of multiorgan failure. The aim of our study was the development of a new animal model allowing quantitative analysis of small bowel microcirculation during and after CPB. Twelve Landrace pigs served as laboratory animals. A 15-cm loop of the terminal ileum was exteriorized for microscopic observation. In 6 animals, a normothermic, partial left heart bypass (pLHB) was established for 2 h with a flow rate of 2,000 ml/min. Arterioles, collecting venules and the capillaries of the small bowel were recorded for the analysis of the microcirculation. All parameters were recorded prior to, during pLHB and up to 2 h after weaning off the bypass. Six sham operated animals served as controls. Despite unchanged hemodynamics, pLHB leads to microvascular perfusion disturbances of the small bowel. In pLHB animals, blood cell velocity in postcapillary venules (30-70 microm) was significantly decreased during and following bypass. Capillary density was also reduced during bypass and decreased even further after pLHB to only 30% of the control values. With this new large animal model for quantitative assessment of microvascular perfusion of the small bowel during CPB, it could be clearly demonstrated that partial normothermic left heart bypass leads to a significant disturbance of the small bowel microcirculation even under stable hemodynamic conditions.

Animals↗