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We have previously implicated uncoupling of oxidative phosphorylation and the associated decreased concentrations of tissue adenosine triphosphate (ATP) in the liver and brain as major factors contributing to death after hypoxia and hypotension. To determine if intravenously administered ATP-MgCl2 complex would result in increased liver and/or brain concentration of ATP, rats were pretreated with intravenous ATP-MgCl2 prior to exposing them to hypoxic-hypotensive stress. In this preliminary work, pretreatment was selected based on the premise that such an experimental design was most apt to demonstrate an effect if such existed. Baseline cerebral cortical and liver ATP and lactate concentrations were obtained immediately after the intravenous infusion of either saline (control group) or ATP-MgCl2 (treated group). ATP and lactate concentrations were again determined after 30 min hypoxic-hypotension and 20 min after resuscitation. ATP-MgCl2 pretreatment resulted in a modest increase in hepatic ATP concentration when measured after 30 min of hypoxic-hypotension. This increase was not evident 20 min later. No increases in cerebral ATP concentrations were noted at any sample time after ATP-MgCl2 pretreatment.

Blunt trauma accounts for 3% to 10% of cervical vessel injuries. Death and severe neurologic impairment have been reported in more than 80% of blunt carotid injuries. In our recent experience, 10 patients sustained 18 blunt cervical arterial injuries: two internal carotid artery (ICA) dissections, three ICA transections with pseudoaneurysm, five ICA thromboses, two vertebral artery dissections, one vertebral artery transection with pseudoaneurysm, one vertebral artery thrombosis, one minimal vertebral artery injury, and three caroticocavernous fistulas. A delay of more than 12 hours in making the diagnosis occurred in seven of the 10 patients. The mental status was initially normal in seven patients. The subsequent development of focal neurologic findings incongruent with CT scanning of the head prompted four-vessel angiography. Treatment was individualized and included supportive management, intravenous heparin, ligation, extracranial-intracranial bypass, and radiologic embolization. We have developed an angiographic classification that may aid management. Early angiography in patients with neurologic findings incongruent with head CT scan or in whom a normal sensorium and hemiparesis are present may permit improved outcomes. We advocate direct operative repair for accessible lesions of recent onset. For surgically inaccessible lesions, those with delayed presentation or in some cases with a fixed neurologic deficit, intravenous heparin can be started and follow-up angiography, head CT scanning, and the patient's clinical status determine further therapy.

Rats were "stressed" by a 30-minute period of breathing 7.5% oxygen combined with hemorrhagic hypotension (x arterial pressure = 25 mm Hg), and then "resuscitated" by restoring the inspired oxygen concentration to 30% and reinfusing the blood previously removed to produce hypotension. We have previously noted in initial return of brain adenosine-triphosphate to normal after this "stress" followed by a progressive decline during the post-resuscitation period. In this study, substrate deficiency was investigated as a possible etiology for the decreased adenosine-triphosphate. Glucose and glucose-6-phosphate concentrations in the brain were measured before "stress" and after resuscitation and were found not to change, indicating no deficiency of substrate.

Rats were subjected to 30 minutes of hypoxic-hypotension and then allocated to one of four treatment groups. Group I was resuscitated by restoration of FIO2 = 30% and reinfusion of shed blood plus an equal volume of additional saline. Group II received in addition nifedipine, 10 micrograms/kg, and groups III and IV received in addition either verapamil, 0.2 mg/kg or 1 mg/kg, respectively. Significantly (P less than 0.01) higher concentrations of creatine phosphate and ATP were present in the brain after nifedipine and after 1 mg/kg verapamil treatment.

Current clinical methods for assessing fetal oxygenation in labor are indirect and remain somewhat imperfect. Since infrared light passes through the cranium and infrared light absorbance by tissues has been shown in adult animals to vary with oxygenation, monitoring of infrared light absorbance may serve as the basis for a new, more direct technique for the assessment of fetal condition. Described here is the application of infrared reflectance spectrophotometry to a fetal sheep model and the precision of the relationship between fetal arterial or venous PO2 and infrared light absorbance at selected wavelengths. A very strong, linear correlation (r = 0.915) was found between fetal arterial PO2 and intracranial infrared light absorbance according to an algorithm developed for selective monitoring of the state of hemoglobin oxygenation in tissue. With further development, this method holds promise for a more direct, noninvasive assessment of fetal condition in labor than is currently available.

The patient with the symptomatic abdominal aortic aneurysm (AAA) presents a management dilemma, ie, emergent, urgent, or elective operation. The mortality for 38 patients with a ruptured AAA prior to 1972 was 61%. That year, a policy of immediate operation was instituted for patients with symptoms that might be referable to a ruptured AAA. It is concluded that an immediate operation on the patient with a symptomatic but intact AAA resulted in an excessively high mortality. Thus, the indications for an immediate operation on these patients should be based on clinical judgment; attempting to differentiate between the patient with the ruptured and the patient with the intact aneurysm. Hemodynamic data (blood pressure hematocrit reading) suggesting a decrease in blood volume dictate an immediate operation. An urgent operation on the well-prepared patient should be performed on all patients with a symptomatic aneurysm in which the clinical and hemodynamic findings do not suggest that it has ruptured.

We studied the effect of nifedipine, a calcium entry blocker, on the recovery of cerebral adenosine triphosphate (ATP), creatine phosphate (CP), and lactate levels following resuscitation from cardiac arrest. Using the cardiac arrest and resuscitation model of de Garavilla, Babbs, and Tacker with an arrest time of eight minutes, 76% of the animals arrested were resuscitated with an average intermittent abdominal compression-CPR time of 3.3 minutes. Rats were assigned randomly to the following groups: nonischemic; eight minutes of arrest without resuscitation; and postresuscitation treatment with either IV normal saline; 3 micrograms/kg nifedipine; 10 micrograms/kg nifedipine; or 30 micrograms/kg nifedipine. Treated animals were sacrificed at either 20 or 120 minutes thereafter. As expected, after eight minutes of cardiac arrest, the levels of ATP and CP dropped to near 0 and rebounded in all resuscitated animals. By 120 minutes after resuscitation, rats given the 10-micrograms/kg dose of nifedipine had levels of ATP equivalent to nonischemic values. Return of CP values to nonischemic levels was seen only at the 3-micrograms/kg dose and was independent of time of measurement. The ATP and CP levels in these nifedipine-treated groups were significantly better when compared to saline-treated controls. There were no treatment-dependent differences in lactate levels. We conclude that clinically appropriate doses of nifedipine had a beneficial effect on the recovery of cerebral high-energy phosphates after cardiac arrest and resuscitation.

The effects of shock as a result of Escherichia coli endotoxin on certain hemodynamic and biochemical parameters and mortality were studied in the baboon. The ability of methylprednisolone succinate (MPS) in massive doses and/or rapid infusion of a buffered electrolyte solution to influence the results was then examined. Shock secondary to Escherichia coli endotoxin was associated with a decrease in RBC 2,3-DPG. This fall in RBC 2,3-DPG was not significantly influenced by MPS. Likewise, MPS did not prevent the changes in oxygen metabolism or systemic hemodynamics, nor was it associated with any decrease in mortality associated with endotoxic shock. Buffered electrolyte solution therapy improved both hemodynamics and mortality, but did not significantly protect against changes in RBC 2,3-DPG.

In view of the increasing frequency in which cardiac output is pharmacologically altered, the endocardial viability ratio was evaluated experimentally in the dog as an additional means by which cardiac function might be monitored. The endocardial viability ratio provided useful information for cardiac function in situations of decreased peripheral resistance. The limitations of the endocardial viability ratio were evident in conditions of acidosis, hypoxia and increased peripheral resistance. Additional work is indicated prior to firmly establishing the endocardial viability ratio as a useful clinical monitor.

Treatment of respiratory insufficiency using continuous positive pressure ventilation (CPPV) with positive end-expiratory pressure (PEEP) is often associated with high airway pressures and large tidal volumes resulting in parenchymal damage and an exacerbation of ventilation/perfusion mismatch. High-frequency jet ventilation and high-frequency oscillation purportedly provide adequate ventilation and might preclude these harmful side effects. Few data exist comparing these methods in a model of respiratory insufficiency. Respiratory insufficiency was produced in three groups of six rabbits by 15 pulmonary lavages with saline (35 ml kg-1) to remove surfactant, following which ventilation for the subsequent 5 hr was as follows: group I, CPPV with a frequency of 60 bpm, and a minute volume of 400 ml min-1 kg-1; group II, oscillatory ventilation with a loudspeaker system delivering a tidal volume of 6-8 ml at a frequency of 5 Hz; and group III, jet ventilation with volumes of 6-8 ml at a frequency of 5 Hz. All groups were ventilated with a PEEP of 10 cm H2O and a FiO2 of 1.0. Arterial blood samples were taken every hour. All three methods provided adequate oxygenation without important differences. The arterial pCO2 rose in all three groups owing to the seriousness of the respiratory insufficiency created. This rise was the highest with oscillatory ventilation. Three of the six rabbits deteriorated after 3 hr of jet ventilation and died with elevated pCO2S with pO2S with bloody edema coming out of the trachea. Because of this apparent damaging effect of jet ventilation and because oscillatory ventilation achieved the same gas exchange but at lower airway pressures as compared to jet ventilation and CPPV, it is thought that oscillatory ventilation is superior over both jet ventilation and CPPV for application in respiratory insufficiency.

Two experiments were conducted to assess the feasibility of near infrared spectrophotometry (niroscopy) to monitor directly the effects of increased intracranial pressure on brain metabolism. ICP was increased in cats by subarachnoid infusion of a "mock" CSF solution. Cytochrome a,a3 redox state, oxyhemoglobin, deoxyhemoglobin and cerebral blood flow were noninvasively and continuously monitored by niroscopy. The results of both experiments indicated that changes in ICP correlated with a reduction in cytochrome a,a3 redox state (p less than 0.01), a decrease in the quantity of oxyhemoglobin and cerebral flow (p less than 0.01) and an increase in deoxyhemoglobin. The study results suggest that niroscopy has the potential for providing noninvasive and continuous data for assessing brain metabolic activity. The correlations obtained with simultaneous measurements of intracranial pressure make this an attractive method for application to those at risk for increased intracranial pressure.

Intracranial pressure was increased in cats by infusing 'mock' CSF intracranially, thus decreasing cerebral perfusion and oxygenation. The cats then randomly received either 50% O2 or 50% O2-5% CO2 by inhalation. As monitored by in vivo near-infrared spectroscopy (NIR), no improvement was noted after 50% O2 whereas 50% O2-5% CO2 resulted in increased perfusion, an oxidation of cytochrome a,a3, an increase in oxyhemoglobin, and reduced quantities of de-oxyhemoglobin (p less than 0.01) despite a further increase in intracranial pressure. The authors conclude that: NIR is a useful means of noninvasively and directly assessing brain metabolism and has advantages over simple ICP monitoring; and continued investigations of CO2 as a possible therapeutic modality after head injury appear warranted.

Intracranial pressure was increased in cats by infusion of "mock" cerebrospinal fluid into the cisterna magna. This condition was then treated by hyperventilation. In addition to direct measurement of intracranial pressure, cerebral metabolism was assessed by near infrared spectrophotometric (niroscopic) measurement of cytochrome a,a3 redox state and the quantity of reduced and oxygenated hemoglobin in the illuminated brain. Cerebral perfusion was assessed by injection of Cardio-Green. Increased intracranial pressure resulted in the expected reduction in cytochrome a,a3,a decrease in HbO2, an increase in Hb, and a reduction of blood flow. The vasoconstriction produced by hyperventilation, while reducing intracranial pressure, produced a further reduction in cytochrome a,a3 and HbO2, with no improvement in blood flow. The data illustrate the fallacy of governing therapy solely by intracranial pressure and demonstrate the need for a direct assessment of brain metabolism. The data also demonstrate the strengths and weaknesses of niroscopy as a noninvasive monitor of the brain metabolism if applied to patients at risk for increased intracranial pressure.

Many trauma victims who have hemorrhagic shock are also intoxicated. Ethanol could worsen the severity of shock and decrease the amount of blood loss necessary to reach or maintain the shock state, perhaps by increasing lactic acidosis. We examined the effect of ethanol on lactic acidosis in a group of rats that were intoxicated, then put in a state of hemorrhagic shock (MAP = 40 mm Hg). These animals were compared to a control group that were in a similar state of hemorrhagic shock but not intoxicated. The volumes of blood necessary to reach and maintain the predetermined model state of shock for two hours in each group were also measured. The animals were paralyzed and placed on controlled ventilation. The ethanol produced an expected baseline lactic acidosis, and it took significantly less blood volume loss to keep the intoxicated group in shock. However, during shock there was no significant difference in the state of lactic acidosis. These results suggest that acute ethanol intoxication made the animals more sensitive to hemorrhage. This effect was not mediated by an increase in lactic acidosis in our model.