Sundt, Thoralf M.

This is a study of 45 patients who underwent angiography and surgery of one or both carotid arteries (56 surgical procedures). All patients had detailed neuro-ophthalmological evaluations including determination of retinal artery pressure (RAP) and scrutiny for emboli in small vessels. Preoperatively, the absolute RAP value has a high correlation with the degree of stenosis of the ipsilateral carotid artery when that stenosis exceeds 80%. The asymmetry of RAP values is greatest when the stenosis is much more severe in one artery than in the other. Both RAP values may show an absolute decrease when the stenosis is severe bilaterally. In these patients, postoperatively there usually is not only an increase in the RAP on the side operated on but also on the side contralateral to the initial procedure. Almost without exception, RAP should be normal after carotid artery surgery. The finding of a subnormal RAP after operation demands immediate investigation.

We have shown the difficulty in producing a reliable model of vasospasm secondary to recurrent subarachnoid hemorrhage from carotid puncture in a squirrel monkey. In this animal, mild systemic hypertension had little or no effect on the clinical status after hemorrhage. The consistent production of a saccular aneurysm on the intracranial arteries was an unexpected result of the arterial puncture and the interruption of the internal elastic membrane. At this time, there is insufficient knowledge regarding the entire subject of vasospasm for correlation with human vessel reaction to injury.

Regional cerebral blood flow (rCBF) measurements with krypton-85 (100 separate determinations) were compared in squirrel monkeys anesthetized with sodium pentobarbital (a cerebral vasoconstrictor) and halothane (a cerebral vasodilator) before, during, and after middle cerebral artery (MCA) occlusion. Prior to MCA occlusion, a normal physiological response to alterations in arterial carbon dioxide tensions (Paco 2 ) was demonstrated in both groups of monkeys; the cerebral vascular resistance was significantly lower in those anesthetized with halothane. During ischemia, there was loss of autoregulation and a failure to respond to alterations in Paco 2 , in both groups. Flow in the ischemic region remained uniform in the barbiturate group but decreased progressively in the halothane group, suggesting a "paradoxical response" to the dilating agent. Reactive hyperemia (luxury perfusion) was demonstrated in both groups after restoration of flow. The use of a beta-emitting isotope ensured that measurements in regions of ischemia accurately reflected rCBF and were free of the artifacts ("look through" and Compton scatter) related to use of a gamma-emitting indicator.

The fluorescence of reduced nicotinamide adenine dinucleotide (NADH) from cerebral cortex was measured before, during, and after middle cerebral artery (MCA) occlusion and then at death of the animal. In normal cortex, NADH remained constant throughout a wide range of variations in blood pressure and Pa co co2 . In ischemic cortex, NADH levels were higher in hypovolemic hypotensive animals than in normotensive normovolemic animals. Neither hypercapnia nor hypocapnia was effective in decreasing NADH in regions of ischemia, but the latter was associated with a degree of hypotension that interfered with interpretation of data. NADH returned to normal with restoration of flow, supporting the reversibility of this degree of ischemia. The high levels of NADH at death, compared to those during ischemia, are consistent with incomplete ischemia in this model of cerebral infarction.

Reduced nicotinamide adenine dinucleotide (NADH) fluorescence was recorded from an avascular area on the squirrel monkey cortex prior to, during, and after focal incomplete ischemia. By using the instrumentation described, stable recordings were obtained free from hemoglobin artifact and with only minimal photodecomposition. Pentobarbital was compared to urethane and halothane as the anesthetic agent and was found acceptable for these types of studies in the dosages used. NADH levels were constant prior to ischemia, increased during ischemia, returned to pre-ischemic levels after restoration of blood flow, and then increased greatly at death produced by anoxia. The use of the infrared microscope for semiquantitative measurements of cortical blood flow throughout the duration of these acute studies was investigated and found to be reliable.

Regional cerebral blood flow (CBF) was measured (intra-arterial injections of 133 Xe) and electroencephalograms (EEG) were recorded periodically before, for two hours during, and for one and one-fourth hours after middle cerebral artery (MCA) occlusion in 20 squirrel monkeys ( Saimiri sciureus ). A CBF-Pa co co2 response curve for these animals under barbiturate anesthesia was created from CBF values prior to MCA occlusion and during the time a steady state was being achieved. The animals were subdivided into four groups (five monkeys in each) on the basis of Pa co co2 values: 20, 36, 40, and 60 mm Hg. CBF values from this study were compared to previous results obtained with 35 Kr. The phenomenon of "look through" and the importance of recognizing this artifact and its significance in analyzing CBF results in areas of focal ischemia are discussed. The present results were correlated with cerebral ATP and lactate concentrations in ischemic regions determined in previous studies using this preparation at these Pa co co2 values and at comparable time intervals before, during, and after MCA occlusion. The EEG appears to reflect the state of ischemic brain accurately. However, CBF measured by the 133 Xe method can be misleading in regard to the true degree of ischemia resulting from occlusion of an intracranial vessel and cannot be relied on to demonstrate accurately "steal" or "reverse steal" due to changes in Pa co co2 .

The effect of large dosages of dexamethasone on the edema of cerebral ischemia and infarction in the squirrel monkey after temporary occlusion of the middle cerebral artery is reported. There was no difference between the ten monkeys treated with dexamethasone and the 11 control animals in clinical course, mortality, morbidity, histological appearance, or amount of edema associated with this ischemic lesion. The differences in the electron microscopic and pathophysiological findings of the edema from ischemia secondary to single major vessel occlusion and in the edema from an intracranial mass lesion are reviewed. The possible therapeutic or pharmacological effects of steroids are considered along with available data on lysosomes in the brain. At the present time, there is no justification for the use of large doses of dexamethasone in the treatment of cerebral infarction.

Previous studies have shown that occlusion of the middle cerebral artery (MCA) of the squirrel monkey results in a consistent large infarct; that in the initial two hours after occlusion of the MCA, blood flow in the central area of ischemia continues at a reduced rate (20% to 50% of normal); and that restoration of normal flow within three hours results in a survival rate of 65% without infarction. In this study, cerebral adenosine triphosphate (ATP), lactate, and pyruvate concentrations were measured at various time intervals after occlusion of the MCA. ATP decreased slowly during a three-hour period to 30% of normal, and lactate, after an initial rapid accumulation, increased slowly to about eight times normal. This compares to the effects of circulatory arrest which, in the dog, results in a reduction of the ATP level to 25% of normal within four minutes and a reciprocal increase in the lactate level. Because the effects of total cerebral anoxia are potentially reversible prior to four minutes, and, therefore, at an ATP concentration above 25% of normal, the slow rate of ATP depletion observed in the ischemic monkey brain supports the view that a significant period exists after occlusion of a major intracranial vessel wherein the ischemic effects are potentially reversible. Using the methods of this study, future investigations should permit a meaningful evaluation of the relative merits of those measures recommended for the treatment of acute cerebral ischemia.

During an 11-month period, 81 endarterectomies under a carefully controlled level of general anesthesia were monitored with continuous electroencephalograms (EEG) and intermittent regional cerebral blood flow (CBF) measurements. There was a high correlation between the CBF (milliliter per 100 gm per minute) during carotid occlusion and alterations in the EEG: no EEG change was seen with the flow above 30 ml/100 gm brain per minute, major changes were not seen with a flow between 18 and 30 ml, and changes invariably occurred with a flow below 17 ml. The degree of EEG change reflected the severity of flow reduction but was always reversible with the placement of a shunt. The EEG at the termination of the surgery corresponded with the patient's neurological state in that all EEG tracings were normal or unchanged as compared to the preoperative tracing and no neurological worsening occurred in any patients studied. The EEG is a valuable monitoring technique that indicates when a shunt is required and informs the surgeon of the state of cerebral function not only during occlusion but also throughout the entire operative procedure.

Background— Previous studies have demonstrated that mitral annulus early diastolic (e′) velocity is increased in constrictive pericarditis (CP) and reduced in restrictive cardiomyopathy. However, those studies did not comprehensively evaluate mitral and tricuspid annular velocities before and after pericardiectomy. Methods and Results— We performed comprehensive echocardiography before and after pericardiectomy in 99 patients with CP, 52 with primary (idiopathic or postpericarditis etiology) and 47 with secondary CP (due to surgery or radiation). Overall, mean±SD mitral medial, mitral lateral, and tricuspid lateral e′ velocities were 12.2±4.2, 10.0±5.4, and 11.6±3.5 cm/s, respectively; annular late diastolic velocities were 10.3±4.3, 12.2±4.9, and 11.7±5.4 cm/s, respectively; and annular systolic (s′) velocities were 7.8±2.8, 8.2±2.1, and 11.2±3.8 cm/s, respectively. Medial e′ was equal to or greater than mitral lateral e′ in 74% of analyzable cases. With the exception of tricuspid s′, there were significant differences in all s′ and e′velocities between primary and secondary CP before pericardiectomy. After pericardiectomy, all annular velocities decreased significantly ( P <0.02 for all comparisons). The reduction in medial e′ velocity was greater than that of mitral lateral e′ velocity ( P <0.0001 and P =0.0004, respectively), and the mitral lateral/medial e′ ratio normalized ( P =0.0002). Conclusions— The mitral lateral/medial e′ ratio is reversed in three fourths of patients with CP. All annular velocities are lower in secondary compared to primary CP before pericardiectomy. After pericardiectomy, there is reduction of all annular velocities and normalization of the mitral lateral/medial e′ ratio.