Topologically constrained manganese(III) and iron(III) complexes of two cross-bridged tetraazamacrocycles.

A family of Mn3+ and Fe3+ complexes of 4,11-dimethyl-1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (1) and 4,10-dimethyl-1,4,7,10-tetraazabicyclo[5.5.2]tetradecane (2) has been prepared by the chemical oxidation of the divalent manganese and iron analogues. The ligands are ethylene cross-bridged tetraazamacrocycles derived from cylam and cyclen, respectively. The synthesis and characterization of these complexes, including X-ray crystal structure determinations, are described. The structural evidence demonstrates that the tetradentate ligands enforce distorted octahedral geometries on the metal ions, with two cis sites occupied by labile ligands. Magnetic measurements reveal that the complexes are high spin with typical magnetic moments. Cyclic voltammetry shows reversible redox processes for the Fe3+/Fe2+ couples of the iron(III) complexes, while Mn3+/Mn2+ and Mn4+/Mn3+ couples were observed for the complexes with manganese(III). The manganese chemistry of 1 was studied in depth. The dichloro manganese(III) cation of 1 undergoes facile ligand substitution reactions at the labile, monodentate sites, for example substituting azide for chloride ligands. Air oxidation of the dichloro complex of Mn (1)2+ in basic solution does not give the expected mu-oxo dimeric product common to manganese. Instead, an unusual manganese(III)-OH complex has been isolated from this reaction and structurally characterized. A similar reaction under slightly different conditions gives a putative MnIII(OH)2 complex that metathesizes to MnIII(OMe)2 upon recrystallization from methanol.

The effect of intrathecal sodium nitroprusside on severe chronic vasospasm.

The efficacy of sodium nitroprusside in resolving cerebral vasospasm was evaluated with multicisternal injections. Twelve animals received fresh, unheparinized arterial blood via three injections (15 ml total) into the cisterna magna. Selective vertebral arteriography was performed on Day 0, and blood injections were performed on the second and third days after the first injection. On the seventh day selective arteriography was performed to evaluate the diameter of the basilar artery. In the sodium nitroprusside group, intrathecal injections of the drug were started on Day 4 and continued for two days (25 micrograms/kg/day). The diameter of the basilar artery was reduced 72.98 +/- 11.07% in control experiments. For the animals treated with intrathecal sodium nitroprusside, the mean diameter of the basilar artery was reduced 29.25 +/- 4.54%. The effect of intrathecal sodium nitroprusside on intracranial pressure (ICP), blood pressure (BP) and electrocardiogram (ECG) was also evaluated in 14 animals. There were no prominent changes in ICP, BP, or ECG when sodium nitroprusside was given intrathecally, but BP decreased and ICP and heart rate increased with intravenous doses of sodium nitroprusside. These results support the hypothesis that sodium nitroprusside administered intrathecally is an effective treatment for cerebral vasospasm.

Intracranial pressure reduction by a central alpha-2 adrenoreceptor agonist after subarachnoid hemorrhage.

Pharmacological manipulation of cerebral venous blood volume is a theoretical approach to reduce elevated intracranial pressure (ICP). Microapplication of alpha-2 adrenoreceptor agonists has been shown to constrict pial veins selectively. This report explores the physiological effects of the intravenous alpha-2 agonist xylazine in a canine model of raised ICP after subarachnoid hemorrhage (mean arterial pressure, heart rate, and ICP were measured and compared in five groups: normal saline [n = 4], xylazine [0.05-1.00 mg/kg] [n = 28], tolazoline [a semiselective alpha-2 antagonist, 5 mg/kg] [n = 6], tolazoline [5 mg/kg] plus xylazine [1.0 mg/kg] [n = 7], and phenylephrine [0.008 mg/kg], a selective alpha-1 agonist [n = 3]). Treatment with xylazine produced a significant (P < 0.01), transient, dose-dependent reduction in ICP that was blocked by pretreatment with tolazoline. Treatment with tolazoline alone produced significant (P < 0.01) increases in ICP and mean arterial pressure. Treatment with phenylephrine produced significant (P < 0.01) increases in mean arterial pressure but had no affect on ICP. These results raise the possibility of using an alpha-2 adrenoreceptor agonist for the treatment of elevated ICP after brain injury.

Time course of intraventricular pressure change in a canine model of hydrocephalus: its relationship to sagittal sinus elastance.

Hydrocephalus was induced in adult greyhounds by intracisternal kaolin. Intraventricular pressure (IVP) was monitored in the conscious animal for 2 weeks using a small implantable sensor, and the time-course of IVP change was characterized. Intraventricular pressure increased significantly within 36 h of kaolin infusion and gradually subsided to normal values within 1 week. Enlargement of the lateral ventricles was not observed during the early phase of intracranial hypertension (less than 2 days). Evolving hydrocephalus and intracranial hypertension increased the elasticity (dP/dV) of the sagittal sinus. This effect was statistically significant (p < 0.05) and is possibly reversible in the acute stage. Normotensive hydrocephalus (1 and 2 weeks after kaolin) was associated with an irreversible increase in resistance to outflow (i.e., increased sagittal sinus elasticity). Sagittal sinus venography of animals with obvious ventricular enlargement (at least 1 week after kaolin) showed development of venous collaterals and atypical outflow pathways.

Relationship between intracranial and sagittal sinus pressure in normal and hydrocephalic dogs.

The relationship between intracranial and sagittal sinus pressure in normal and kaolin-induced hydrocephalic greyhounds was examined. In normal dogs there was an average 14 mm Hg pressure difference between the ventricles and the sagittal sinus. Elevations of intraventricular pressure were accompanied by small but consistent elevations in sagittal sinus pressure. In hydrocephalic dogs the average pressure differential was only 2 mm Hg. Also elevations of intraventricular pressure were accompanied by greater elevations in sagittal sinus pressures than those seen in normal dogs. The volume-buffering capacity of the sagittal sinus was decreased, and sinography revealed filling of unusual venous collaterals in hydrocephalic dogs--both suggesting an increased resistance to outflow in the sagittal sinus.

Resistance of the foramen of Monro.

A greyhound dog model was used to study the importance of the foramen of Monro as a resistance element to the flow of cerebrospinal fluid (CSF). Normal dogs had no pressure differential discernible despite the infusion of artificial CSF into one lateral ventricle. When CSF was withdrawn from one lateral ventricle, however, 7 of 10 dogs showed intraventricular pressure differentials at a steady state of 3.28-5.37 mm Hg. All normal dogs undergoing rapid bolus withdrawal of CSF from the ventricles developed pressure differentials. When these experiments were performed on hydrocephalic dogs, no pressure differential could be recorded. The foramen of Monro acts as a valve mechanisms that usually closes in response to CSF withdrawals.

Assessment and resource utilization for cancer patients.

To determine whether rehabilitation counselors and nurses differ in their approaches to using assessment information in care planning, 70 oncology outpatients returning to a comprehensive cancer center for continuing health care were asked to indicate their rehabilitation problems on a checklist. Follow-up consisted of clarifying problems and making relevant resources available to patients. Forty-five patients were followed by a clinic nurse (RN) whose expanded role included assessment and resource utilization functions; 25 were followed by a rehabilitation counselor (RC) whose only role was to perform assessment and resource utilization functions. The RC was found to address a significantly higher proportion of patient problems than the RNs (z = 6.94, p less than .0005). Both the RCs and RNs used many different resources to meet patient needs (43 vs 51). However, RNs used themselves as a resource for 51% of the problems addressed whereas the RC used the RN for 14% of problems addressed (z = -6.01, p less than .0005). Delegation of assessment and resource utilization functions to staff members as a sole responsibility may be an effective way to incorporate rehabilitation into an outpatient oncology setting.