During exercise-induced metabolic acidosis, intravenous administration of bicarbonate increased the buffering capacity of blood and attenuated the decrease in intracellular muscle pH, although there was a small increase in the arterial carbon dioxide pressure.

Infection is a major cause of morbidity following multiple traumatic and head injury. Although immunosuppression has been demonstrated after multiple traumatic injury, the effects of head injury on immune function have not been thoroughly investigated. In a prospective study of 10 severely head-injured patients, in vitro and in vivo parameters of cellular immune activity were assessed. In vitro measurements of lymphocyte surface antigen expression following mitogen stimulation were made serially over a 3-week period in 10 patients with severe head injury. The control group consisted of 20 healthy subjects. Phenotyping of peripheral blood lymphocytes (PBLs) was performed following incubation with and without mitogens. Phenotypes were determined by flow cytometry using monoclonal antibodies (MABs) to T lymphocyte subsets and the alpha subunit of interleukin 2 (IL-2) receptors. In vivo cellular immune function was determined by measuring patient responses to delayed-type hypersensitivity (DTH) skin testing within 24 h of injury. When head-injured patients were compared to controls, PBLs incubated in the presence of phytohemagglutinin (PHA) demonstrated a decrease in cells marking as T cells (p = 0.005), helper-inducer T cells (p = 0.001), and in the number of IL-2 receptor-bearing cells (p = 0.001). The functional ability of these lymphocyte subpopulations to proliferate in the presence of PHA was significantly suppressed within 24 h of injury and normalized within 3 weeks of injury. DTH skin testing to Candida, mumps, trichophyton, and PPD antigens was performed within 24 h of injury and resulted in anergic responses in all 10 patients when measured at 24, 48, and 72 h following administration. The overall infection rate was 60%, with the majority of infections occurring within the first 4 days following injury. The results of this study indicate that severe head injury results in suppression of cellular immune function with a corresponding high rate of infection. The possible significance of the decrease in the percentage of helper-inducer T cells and in the number of cells bearing IL-2 receptors following mitogen stimulation is discussed.

In an effort to determine the value of tissue-type plasminogen activator (TPA) in the treatment of embolic stroke, 17 rabbits were subjected to a model of embolic stroke in which 2-hour-old, tin-impregnated, autologous clots were embolized to the bifurcation of the internal carotid artery at the circle of Willis via retrograde injection into the cannulated external carotid artery. High-resolution digital subtraction radiography was used to localize clots intracranially at the carotid bifurcation. Circulation through the internal carotid artery and intracranial vessels was monitored with serial digital subtraction angiography before and after embolization and during treatment. Disappearance of the tin marker on the digital subtraction radiograph indicated dissolution of clot and was associated with reestablishment of circulation on the digital subtraction angiogram. Experimental animals were treated with human-specific recombinant TPA 30 minutes, 2 hours, or 4 hours after clot embolization. TPA was administered as an intravenous bolus of 0.5 mg/kg followed by an infusion of 1 mg/kg/h for 2 hours. Digital subtraction angiograms were performed every 30 minutes. All clots dissolved, and cerebral circulation was reestablished within 120 minutes of treatment. In control animals treated with saline, embolized clots were stable, and the internal carotid artery remained occluded. At the completion of each study, the animal was perfused with freshly prepared, buffered 2,3,5-triphenyltetrazolium chloride (TTC) for demarcation of cerebral infarction. Control animals demonstrated infarction of 50 +/- 3.6% of the ipsilateral cerebral hemisphere, with an infarct weight of 2.1 +/- 0.2 g.(ABSTRACT TRUNCATED AT 250 WORDS)

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Shunt malfunction is common and its diagnosis may require invasive testing that may be inaccurate or result in complications. Magnetic resonance imaging (MRI) may prove to be a useful noninvasive test of shunt function as it has been shown that MRI is capable of measuring cerebrospinal fluid (CSF) flows from 2 ml/h to 40 ml/h in model systems. Since flows in functioning shunt systems can be less than 2 ml/h, MRI must be sensitive enough to detect flow in this range in order to be a valid test for shunt function. Continuing previous studies, we have studied MRI flow-related enhancement at flow rates from 0 to 2 ml/h. Multiple spin echo scans (TR2000, TE20) were made through a specialized section of tubing in a model shunt system. The intensity of the MRI signal at points known to demonstrate maximal flow-related enhancement was measured. A linear relationship was demonstrated between signal intensity and flow as low as 0.8 ml/h. These results add support to the concept that MRI is sensitive enough to detect the lowest flows present in functioning shunt systems and therefore may be useful as a noninvasive test of shunt function.

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Recombinant tissue plasminogen activator (rTPA) has been more effective in inducing thrombolysis in laboratory studies of intracranial thrombosis than clinical studies of systemic or coronary thrombosis would indicate. To evaluate this discrepancy, 21 rabbits were subjected to embolic occlusion of the right internal carotid artery (ICA) by retrograde injection of a tin-tagged, 2-hour-old autologous clot through the external carotid artery with angiographic monitoring in the same manner as in a previously reported model. The emboli lodged intracranially at the bifurcation of the ICA in 10 animals and in the cervical ICA in 11 animals. Digital subtraction angiography confirmed total occlusion of the ICA in all animals. Treatment started one-half hour after embolization and consisted of a bolus of 0.5 mg/kg of rTPA followed by an infusion of 1 mg/kg/h for 2 hours. All of the animals with intracranial emboli and 6 of the animals with cervical emboli were treated intravenously. The remaining 5 animals with cervical emboli were treated by intracarotid infusion of the same dose of rTPA. In the intravenously treated group, serial digital subtraction angiography documented thrombolysis in 9 of the 10 animals with intracranial emboli and only 1 of the 6 with cervical emboli. Thrombolysis occurred in 4 of the 5 rabbits with cervical emboli treated with intracarotid rTPA. Intravenous rTPA therapy produced a significantly (P less than 0.01) higher rate of thrombolysis in intracranial as compared to cervical thrombus.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimental and clinical studies suggest that the calcium channel blocker nimodipine may reduce cerebral ischemic injury. Using rapid acquisition phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy, we examined the effect of nimodipine on cerebral energy metabolism during severe ischemia in gerbils. High-energy phosphates and intracellular pH were characterized at baseline and at 2-min intervals following bilateral common carotid artery (CCA) ligation. Serial forebrain spectroscopy was continued until phosphocreatine (PCr) and adenosine triphosphate (ATP) resonances disappeared. Controls (n = 10) were compared to gerbils receiving intraperitoneal nimodipine 30 min prior to carotid ligation, at the following doses: 0.5 mg/kg (n = 8), 1.0 mg/kg (n = 10), 2.0 mg/kg (n = 8), or 4.0 mg/kg (n = 4). In the control group, PCr and ATP peaks were undetectable after a mean of 5.4 +/- 0.47 min following CCA ligation. Compared with controls, the mean time for depletion of high-energy phosphates following carotid ligation was prolonged at nimodipine doses of 0.5 mg/kg and 1.0 mg/kg, but the differences did not reach statistical significance. In the 2.0 mg/kg group, however, ATP was preserved until 9.8 +/- 1.0 min following the onset of ischemia, significantly longer than the control group (p = 0.005, Mann-Whitney test). Nimodipine had no effect on the time course or severity of intracellular acidosis. In this model of severe ischemia, relatively high doses of nimodipine slowed the depletion of high-energy phosphates without altering intracellular acidosis. This suggests that nimodipine may provide cerebral protection by directly altering ischemic cellular metabolism.