Changes in [3H]-PK 11195 and [3H]-8-OH-DPAT binding following forebrain ischaemia in the gerbil.

1. A high density of [3H]-PK 11195 binding sites was present in gerbil cortical membranes (Bmax [3H]-PK 11195 1360 +/- 71 fmol mg-1 protein) in comparison to rat cortical membranes (254 +/- 21 fmol mg-1 protein). This effect was species-specific as similar findings were obtained with hippocampal membranes (Bmax 1430 +/- 111 fmol mg-1 protein in gerbil, compared to 196 +/- 31 in rat). 2. RO 5-4864, also a peripheral type benzodiazepine compound, displayed low affinity for the [3H]-PK 11195 site in the gerbil (pKi 6.57 +/- 0.02 and 6.70 +/- 0.12 in hippocampus and cortex respectively) compared to rat (pKi 8.16 +/- 0.07 and 8.48 +/- 0.02). Central benzodiazepine compounds, diazepam and flunitrazepam, also displayed this trend. 3. RO 5-4864 displaced [3H]-PK 11195 binding from gerbil and rat cortical membranes through a competitive interaction with Hill slopes close to unity. In both tissues, saturation isotherms of [3H]-PK 11195 binding indicated that the presence of RO 5-4864 caused changes in Kd without any effect on Bmax. In kinetic experiments, the presence of RO 5-4864 failed to modify the rate of dissociation of [3H]-PK 11195 from equilibrium in both rat and gerbil cortical membranes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cation components of Mueller-Hinton agar affecting testing of Pseudomonas aeruginosa susceptibility to gentamicin

Seven lots of Mueller-Hinton agar were examined for calcium and magnesium contents and their distribution in pools or compartments. Gel disruption and centrifugation yielded the soluble cations, which varied from 9 to 113% of the total calcium and from 76 to 102% of the total magnesium. Throughout the experiments, a standardized disk diffusion test, using Pseudomonas aeruginosa (ATCC 27852) and a 10-μg gentamicin disk, served as an indicator for medium performance. Zone diameters correlated well with the sums of the soluble calcium and magnesium values in the different lots (r = −0.85). Ionized calcium, presumably the biologically active ion, was measured with a calcium-specific electrode. It represented only a fraction of the soluble calcium pool in three lots. Autoclaving resulted in shifts of the cations between the different pools. Addition of magnesium to one medium lot resulted in shifts of soluble and ionized calcium, indicating an interdependence of calcium and magnesium, and zone diameters correlated with soluble magnesium (r = −0.98), soluble calcium (r = −0.96), and ionized calcium (r = −0.96) in this experiment. Manipulation of one medium to match the performance of another showed that excess amounts of both ions were required to obtain similar performance. Satisfactory performance of an individual medium can be obtained by cation supplementation, but simple adjustment will not suffice for all media. The interaction of the other cation pool components must also be evaluated.     

Restoration of normal reflex responses to orthostatic stress during felodipine therapy in congestive heart failure

The mechanisms underlying the abnormal responses to orthostatic stress in congestive heart failure are ill defined and little is known about the effects of specific therapy. In the present study intravascular pressures and plasma noradrenaline levels were measured in nine patients with heart failure subjected to 45 degrees and 90 degrees upright tilt. Studies were repeated during 4 weeks of vasodilator therapy with felodipine and again after felodipine withdrawal. Before the introduction of vasodilator therapy, tilt did not activate orthostatic reflexes despite significant reductions in left ventricular filling pressure and cardiac output. Thus, plasma noradrenaline, heart rate and systemic vascular resistance were unaffected and blood pressure fell. Felodipine resulted in a rapid and sustained improvement in left ventricular function but restoration of orthostatic reflexes was delayed and could be detected only after 48 h therapy. At this time, and during the subsequent 4 weeks, tilt-induced reductions in ventricular filling and cardiac output produced a normal rise in plasma noradrenaline and heart rate. A postural drop in blood pressure, however, was not averted because the direct action of felodipine on vascular smooth muscle prevented adrenergically-mediated increments in systemic vascular resistance. Felodipine withdrawal led to a prompt deterioration in left ventricular function. Orthostatic reflexes, however, were still intact 48 h later when tilt elicited a completely normal pattern of responses. These observations confirm that the abnormal responses to orthostatic stress in congestive heart failure are due principally to impairment of autonomic control mechanisms and are not related to the absence of venous pooling. Importantly the autonomic dysfunction is reversible with felodipine therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Familial neurocardiogenic (vasovagal) syncope

Vasovagal syncope (VSS) is an exaggerated tendency towards the common faint caused by a sudden and profound hypotension with or without bradycardia. The etiology of VVS is unknown though several lines of evidence indicate central and peripheral abnormalities of sympathetic function. Studies however indicate a strong heritable component to the etiology of VVS in over 20% of cases. Here, we report the findings from a family that shows apparently autosomal dominant VVS in at least three generations. Clinical findings included an absence of any discernible cardiac or autonomic abnormalities and reproducible hypotension on tilt table testing in affected family members.