John P. Kapp

Hyperbaric oxygen and cerebral infarction in the gerbil

The effectiveness of hyperbaric oxygen in reducing the incidence of cerebral infarction during the first 36 hours after occlusion of the right common carotid artery was investigated in gerbils. After carotid ligation, the gerbils were divided into four groups: controls, which breathed air at ambient pressure; group 1, which received hyperbaric oxygen at 1.5 atmospheres absolute pressure (ATA) for 36 hours, with a 5-minute, 1.5-ATA air break each hour; group 2, which received hyperbaric oxygen at 1.5 ATA for 1 hour alternating with 1 hour air at 1 ATA, for 36 hours; and group 3, which received hyperbaric oxygen at 1.5 ATA with hourly 5-minute air breaks for 18 hours, and ambient air for the second 18 hours. Neurological evaluations and staining of the brain with tetrazolium revealed the following results at 36 hours after carotid ligation: 72% of the controls had cerebral infarcts; 26% of the gerbils in group 1 had infarcts, but all animals died at 24-36 hours after beginning hyperbaric oxygen exposure from oxygen toxicity; 44% of the gerbils in group 2 had infarcts; 11% of the gerbils in group 3 had infarcts during the first 18 hours after carotid ligation, and no infarcts developed in the 18 hours that followed. Hyperbaric oxygen reduces the incidence of cerebral infarction after carotid artery ligation, presumably by allowing time for collateral circulation to develop.

Neurological response to hyperbaric oxygen—A criterion for cerebral revascularization

Twenty-two patients with cerebral infarction secondary to occlusion of a carotid or middle cerebral artery were exposed to hyperbaric oxygen at 1.5 atmospheres absolute pressure. Ten of the patients demonstrated improved motor function during hyperbaric exposure. Seven of these patients had successful surgical revascularization and no recurrence of neurological deficit. In 3 patients who were not successfully revascularized, the neurological deficit recurred. It is concluded that response to hyperbaric oxygen may be of use in the selection of patients with neurological deficit who will benefit from surgical revascularization of the brain.

Hyperbaric oxygen after circulatory arrest: modification of postischemic encephalopathy.

Cats were subjected to circulatory arrest of 5 minutes duration by occlusion of the ascending aorta and the superior and inferior venae cavae. After perfusion was re-established by release of the occluding clamps, one group of animals was placed in a hyperbaric chamber and ventilated with oxygen at 1.5 atmospheres absolute pressure for 2.5 hours. Control animals were ventilated with oxygen at ambient atmospheric pressure. The time for electroencephalographic recovery was significantly shortened (P = 0.002) and the cerebrospinal fluid lactate change (2.5-hour value minus the preclamp value) was reduced (P = 0.008) in the animals receiving hyperbaric oxygen. The data indicate that hyperbaric oxygen administered after global cerebral ischemia modifies favorably both postischemic functional impairment and metabolic derangement. Possible mechanisms for the modification of postischemic encephalopathy are discussed.

Effect of intra-arterial cisplatin and 1,3-bis(2chloroethyl)-1-nitrosourea (BCNU) dosage on radiographic response and regional toxicity in malignant glioma patients: proposal of a new method of intra-arterial dosage calculation

SummaryThe frequency of both neurologic toxicity and therapeutic response due to intra-arterial (IA) chemotherapy is decreased by dose reduction. A method to individualize IA drug dosage is needed to provide each patient with the safest, most effective dose. Most trials of IA chemotherapy for malignant glioma have used body surface area (BSA) to calculate dosage; but brain size and arterial distribution do not correlate well with BSA. Fixed doses of cisplatin and BCNU were used in combination to perform 35 IA infusions in 20 malignant gliomas patients. Doses modified by the number of major intracranial vessels supplied by the infused artery were used in 34 infusions in 19 patients. Patients receiving 150 to 200 mg CP and 300 mg BCNU had an incidence of neurologic deficit of 5.6% if ≥ 3 vessels were supplied by the infused artery compared to 42% for those with only 2 vessels. This crude dose modification maintained efficacy while reducing neurologic toxicity. Further refinement is possible using well established intra-arterial pharmacokinetic principles. Intra-arterial dosing based on volume flow at the site of infusion would yield a more reproducible exposure of the infused capillary bed to a drug than methods currently in use. More consistent drug exposure should reduce toxicity due to over dosing and treatment failure due to under dosing.

Cerebral resuscitation with succinate and fructose-1, 6-diphosphate

To test the hypotheses that succinate or fructose-1, 6-diphosphate may have a beneficial effect in global cerebral ischemia, we induced complete global cerebral ischemia for 5 minutes in rabbits by occlusion of the ascending aorta and the superior and inferior vena cavae. Fifteen minutes after restoration of cerebral blood flow, animals received an intravenous bolus of either succinate or fructose-1,6-diphosphate followed by continuous infusion. Another group of animals received fructose-1, 6-diphosphate beginning prior to aortic occlusion. Control animals received intravenous glucose by bolus, followed by infusion. Cerebrospinal fluid lactate levels were measured before occlusion and at 2 1/2 hours after occlusion, when the animals were sacrificed. In all animals electrocortical silence was demonstrated for the 5 minutes of global ischemia. The percent change in cerebrospinal fluid lactate levels in all groups was statistically similar. Only two of seven of the control animals recovered electroencephalogram amplitude during the 2 1/2 hour observation period. Time for recovery of amplitude on the electroencephalogram in animals receiving fructose-1, 6-diphosphate either before or after ischemia was statistically similar to controls. In the succinate treated group, all seven animals regained preocclusion levels of electroencephalogram amplitude within 36 minutes of the restoration of cerebral blood flow. Succinate administered after complete global cerebral ischemia resulted in significantly increased recovery of cerebral electrical activity (Fischers exact test, p less than 0.05).

Systemic heparin in the early management of ruptured intracranial aneurysms: review of 104 consecutive cases and comparison with concurrent controls.

The records of 104 patients treated prophylactically with heparin during gradual carotid ligation after rupture of an intracranial aneurysm, 11 patients, who received heparin after the development of an ischemic neurological deficit during clamp closure, and 46 patients who did not receive heparin during clamp closure were reviewed. The incidence of ischemic neurological deficit, both permanent and transient, was 19.2% in the prophylactic heparin group compared with 38.6% in the control group. The incidence of recurrent intracranial hemorrhage was 9.6% in the heparin group vs. 26.1% in the control group. All differences were statistically significant at or below P less than 0.01 by the Mantel-Haenszel statistical test. Possible mechanisms for the reduction in morbidity and mortality in patients receiving heparin are discussed.

Hyperbaric oxygen As a radiation sensitizer in the treatment of brain tumors

Abstract Rat brain tumor cells grown in a monolayer culture were irradiated in 1.0, 1.5, and 2.0 atmospheres absolute oxygen pressure. Sensitivity of the cells to radiation was not increased by raising oxygen pressure above 1.0 atmosphere absolute during exposure to radiation.

Preservation of brain tumor specimens for drug sensitivity testing.

To examine the feasibility of shipment of brain tumor specimens to a central laboratory for drug sensitivity testing, an experimental gliosarcoma (9L) was grown subcutaneously in rats, harvested, stored, and disaggregated. Growth of the disaggregated tumor cells in monolayer culture was evaluated after storage for various times at 2 to 6 degrees C and 37 degrees C in saline and minimum essential medium. Growth potential was maintained for 24 hours when tumor specimens were stored under refrigerated conditions and was best maintained when specimens were stored in saline. Specimens stored at 37 degrees C grew best when stored in minimum essential medium, but growth potential was lost after 12 hours unless the specimens were refrigerated. Shipment of tumor specimens to a central laboratory for drug sensitivity testing appears to be feasible, since under most circumstances, specimens should reach the laboratory for processing within 24 hours of their removal. Storage and transport of specimens in saline on wet ice appears to be optimal.

Oxygen at 2 atmospheres absolute pressure does not increase the radiation sensitivity of normal brain in rats

Cranial radiation was administered to CD Fisher rats at 1.0, 1.5 and 2.0 atmospheres absolute oxygen pressure. Life span following radiation was recorded. Surviving animals were killed at 28 weeks and the brains were examined independently by two neuropathologists. Survival time was significantly less in animals receiving higher doses of radiation but showed no relationship to the oxygen pressure in the environment of the animal at the time radiation was administered. Microscopic examination of the brain did not reveal any differences in animals radiated in a normobaric or hyperbaric oxygen environment. It is concluded that hyperbaric oxygen does not sensitize the normal brain to the effects of ionizing radiation.