Profound hypothermia and circulatory arrest with skull base approaches for treatment of complex posterior circulation aneurysms.

OBJECTIVE: Cardiopulmonary bypass with profound hypothermia and circulatory arrest has seen a resurgence as an adjunct technique in neurological surgery. We report our experience with this technique in treating seven complex vertebro-basilar aneurysms. METHODS: Skull base approaches were used in all cases, providing excellent exposure and minimizing brain retraction. There were six basilar artery aneurysms and one giant fusiform vertebro-basilar artery aneurysm. All aneurysms but one had an apparent neck, which could be clipped. The fusiform vertebro-basilar artery aneurysm was trapped, partially resected, and the circulation was reestablished with a saphenous vein graft from the cervical internal carotid artery to the mid-basilar artery. RESULTS: Five patients had an excellent outcome and two had a good outcome at one year or at latest follow up. Two of the patients showed improvement of neurological deficits which were present before the surgical intervention. CONCLUSION: Applying very strict selection criteria in this small series of patients with posterior circulation aneurysms, excellent or good results were achieved using the profound hypothermic circulatory arrest technique.

Cortical brain microdialysis and temperature monitoring during hypothermic circulatory arrest in humans.

OBJECTIVES: Critical vascular surgery of the brain or the heart occasionally requires total cessation of the circulatory system. Profound hypothermia is used to protect the brain from ischaemic injury. This study explores the use of microdialysis to measure metabolic indices of ischaemia: glutamate, lactate, and pH, and cerebral temperature during profound hypothermia and circulatory arrest. METHODS: Effluent from a microdialysis catheter placed in the cerebral cortex of three patients undergoing complete circulatory arrest was continuously sampled. Samples were pooled over 10 minute periods and glutamate and lactate concentrations were measured postoperatively. Brain temperature and pH were measured on line intraoperatively. Electroencephalography and monitoring of somatosensory evoked potentials and brainstem auditory evoked potentials were simultaneously carried out. RESULTS: Patient 1 had normal glutamate and lactate. PH was 6.75 to 6.85 and increased to 6.9 after warming ensued. Patient 2 had raised glutamate and lactate during most measurements. The glutamate concentrations peaked at 305 microM/l at the start of the measurements and fell below 20 microM/l after warming. The lactate concentrations peaked at 680 microM/l before cooling, rose to 1040 microM/l during the cooling process, decreased to 212 microM/l during circulatory arrest, and rose again to 620 microM/l after warming. The pH started at 7.06 and continued a downward course until stabilising at a pH of 6.5 after circulatory arrest. Patient 3 had a transient, mild increase in glutamate and lactate during the cooling and warming period. pH was stable throughout. CONCLUSION: Microdialysis combined with temperature and pH measurements of the cerebral cortex promises to be an important tool in detecting cerebral ischaemia. Further studies are needed to validate our findings and test the feasibility of modifying ischaemic changes.

Combined epidural analgesia and general anesthesia induce ischemia distal to a severe coronary artery stenosis in swine.

Epidural analgesia combined with general anesthesia may improve cardiac function and reduce the work of the heart by decreasing the rate pressure product. However, the effect of this combined technique has not been studied in the presence of severe coronary artery stenosis. Therefore, we investigated epidural analgesia combined with general anesthesia in a swine model with a tight coronary artery stenosis. The coronary stenosis placed around the proximal left anterior descending coronary artery (LAD) allowed normal blood flow at rest but only minimum hyperemia in response to the coronary dilator, adenosine. To accomplish an extensive sympathetic block, we injected enough bupivacaine 0.5% into the lumbar epidural space to reach at least the level of the first thoracic vertebra (T1). Epidural catheter position was verified by fluoroscopy. Hemodynamic changes, LAD myocardial blood flow, and regional myocardial wall thickening were measured. Fifteen minutes after the injection of bupivacaine, systolic and diastolic blood pressure decreased 24.1% and 26%, respectively, cardiac output decreased 25.6%, and mean coronary blood flow decreased 42%, compared to the saline control. Myocardial wall thickening in the LAD bed decreased 31%, although it remained unchanged in the normal myocardium. Epidural bupivacaine added to general anesthesia resulted in moderate hypotension. Distal to the coronary stenosis was a moderate decrease in regional myocardial function and a severe reduction in blood flow.

Postischemic free radical production in the venous blood of the regionally ischemic swine heart. Effect of deferoxamine.

BACKGROUND: We tested the hypothesis that secondarily produced free radicals can be detected in venous coronary effluent without the need for direct exposure of postischemic tissue to the spin trapping agent alpha-phenyl-tert-butylnitrone (PBN). METHODS AND RESULTS: The left anterior descending coronary artery (LAD) of pigs was ligated for 15, 30, 40, or 60 minutes, and the tissue was subsequently reperfused for 60 minutes. Venous effluent (6.5 ml) from the risk area was withdrawn sequentially at 1.5-minute intervals during reperfusion. The effluent blood was immediately infused (4.5 ml/min) with an isotonic saline solution containing 120 mM PBN: Preischemic control effluent samples were collected in an identical fashion. Plasma from each sample was extracted in organic solvent and subsequently analyzed by electron spin resonance (ESR) spectroscopy. Another group of pigs received an infusion of the metal chelator deferoxamine mesylate (25 mg/kg/hr) into the right atrium starting 1 hour before the 40-minute ligation and continuing throughout ligation and reperfusion. We were able to demonstrate the postischemic production of ESR signals for PBN adduct(s) from untreated hearts having spectral characteristics similar to an alkoxyl adduct (PBN-RO.; hyperfine splitting constants for beta-hydrogen [alpha H] = 2.0-2.25 G; nitrogen [alpha N] = 13.5-13.75 G). The reperfusion time course of PBN adduct production had a unique pattern: 1) multiple low-level bursts during the initial 15 minutes of reperfusion, and 2) a prominent PBN adduct signal during a relatively late time (20-25 minutes) of reperfusion. Total postischemic PBN adduct production rose with increasing duration (15-60 minutes) of ischemia and was associated with a progressive elevation of total lactate dehydrogenase in the effluent. Infusion of deferoxamine markedly diminished PBN adduct production as well as total release of lactate dehydrogenase. CONCLUSIONS: These data suggest the potential feasibility of using an ex vivo ESR spin trapping technique in blood-perfused models of cardiovascular injury and that chelatable free iron contributes to the production of alkoxyl radicals.

The effect of arterial pressure alterations during halothane anesthesia on residual flow and infarct size with transient regional ischemia of the dog.

The present study was designed to determine if infarct size under halothane anesthesia could be reduced by increasing the pressure gradient across the collateral vascular bed, thereby increasing flow within the occluded vascular bed. Forty-nine mongrel dogs were anesthetized with halothane under identical physiologic conditions with the exception of systemic arterial blood pressure. The control group of 18 animals anesthetized with halothane was compared to two experimental groups. In one group of 15 dogs, the mean systemic pressure was raised 25% above control with phenylephrine (BP25). In the second group of 15 dogs, systemic pressure was raised 50% above control (BP50). Adjacent marginal branches of the left circumflex coronary artery were ligated for 90 minutes followed by 90 minutes of reflow. The area of the occluded vascular bed was similar in all groups, but the area of infarction as a percentage of the occluded vascular bed was reduced from 47.7 +/- 4.7% to 25.4 +/- 4.3% in the BP25 group (P < or = .05 v control) and to 33.1 +/- 5.0% in the BP50 group. Flow measurements using microspheres showed a larger zone of ischemic tissue receiving adequate residual flow in the BP25 and BP50 groups compared to the control. It is concluded that infarct size during halothane anesthesia in the dog can be reduced by increasing systemic blood pressure with phenylephrine.

Spin trapping of oxygen and carbon-centered free radicals in ischemic canine myocardium.

Oxygen free radical injury has been postulated to occur during myocardial ischemia. We have used Electron Spin Resonance and Spin Trapping techniques to directly demonstrate the production of carbon-centered (R.) and oxygen-centered lipid radical (RO.) in ischemic canine heart. In addition, venous effluent from the ischemic region showed that conjugated dienes (lipid peroxidation products) increased with ischemic duration. Our results suggest that the formation of the oxygen-centered and carbon-centered lipid radical species during ischemia are a consequence of oxy-radical peroxidation of myocardial membrane lipids.

Fentanyl, Na-pentobarbital and halothane influence myocardial infarct size.

We investigated the effects of three anesthetics on the size of myocardial infarction and on blood flow distribution within the myocardial wall. Myocardial infarcts were induced in 34 dogs by ligating a coronary artery for 90 minutes, and permitting reflow for 90 minutes. The anesthetics used were fentanyl, Na-pentobarbital, and halothane. Under halothane the mean blood pressure (BP) during coronary artery ligation was 113 +/- 2/82 +/- 2 mm Hg and the heart rate (HR) was 135 +/- 2/min. Under fentanyl, the BP was 143 +/- 3/91 +/- 2 mm Hg and HR 99 +/- 3/min. Under Na-pentobarbital, BP was 141 +/- 2/104 +/- 2 mm Hg and HR 146 +/- 2/min. A higher mean BP combined with a slower HR, as seen under fentanyl, was associated with the smallest infarct (24 +/- 8%). Low BP and higher HR, as seen under halothane, was associated with the largest infarct (51 +/- 5%). Na-pentobarbital, with a higher BP but also a faster HR, resulted in an infarct size of 32 +/- 5%. We conclude that a higher mean BP combined with a slower HR might favor the preservation of a larger mass of vulnerable myocardial tissue in a totally occluded coronary artery.

Anesthetics influence myocardial infarct size.

This study compares the effect of three anesthetics on infarct size and regional myocardial blood flow. The anesthetics--fentanyl, Na-pentobarbital, and halothane--differ in their effects on such hemodynamic parameters as blood pressure and heart rate. The mean blood pressure during ligation was 144/91 mm Hg with fentanyl, 141/104 mm Hg with Na-pentobarbital, and 113/82 mm Hg with halothane. The heart rate was 98, 146, and 135 beats/min, respectively. The most significant finding of our study following 90 min of reflow was the infarct size of 26 +/- 8% of the occluded vascular bed under the influence of fentanyl; infarct size under Na-pentobarbital and halothane was 32 +/- 5 and 47 +/- 7%, respectively. The regional flow in relation to the zones of the infarction also differed among the groups. Regional flow under Na-pentobarbital was 24 +/- 6% of normal flow at 90 min of occlusion in the infarcted tissue; regional flow under fentanyl and halothane was 9 +/- 2 and 5 +/- 1%, respectively. The flow in the nitroblue-tetrazolium-staining zone of the occluded vascular bed was 69 +/- 11% (fentanyl), 77 +/- 11% (Na-pentobarbital), and 83 +/- 25% (halothane). It is concluded that anesthetics may well influence infarct size and the outcome of a myocardial infarction following a 90-min ischemia. Hemodynamic effects induced by these anesthetics may well be responsible for this outcome and could be determinants of infarct size, possibly by influencing collateral flow.

Pharmacolinetics of fluorocarbon 11 and 12 in dogs and humans.

Blood levels and exhalation bag contents of FC-11 and FC-12 from dogs and humans were used to elucidate the pharmacokinetic model describing the time-course of these agents. The derived pharmacokinetic parameters were in good agreement with the physicochemical properties of these substances. The model was used to estimate the percentage of dose absorbed, which averaged 77 per cent for FC-11 and 55 per cent for FC-12, and to predict the level of FC-11 and FC-12 under a variety of conditions simulating both short- and long-term exposure to the maximum allowable concentrations of these agents. With similar doses, an 8-hour continuous exposure was estimated to produce levels of FC-11 and FC-12 that are much lower than the corresponding levels reported to induce cardiac sensitization in dogs.

Biotransformation and elimination of 14C-trichlorofluoromethane (FC-11) and 14C-dichlorodifluoromethane (FC-12) in man.

Radiocarbon-labeled trichlorofluoromethane (FC-11; 14CC13F) and dichlorodifluormethane (FC-12; 14CC12F2) were separately inhaled by a female subject and a male subject. A predetermined volume of fluorocarbon (1000 ppm; 100 muCi) in air was delivered through a nonrebreating system and a tight-fitting face mask for 7-17 minutes. Total expired gases were collected during fluorocarbon exposure and afterward until no radioactivity was detectable. Expired 14CO2 and 14C-fluorocarbon were assayed. Urine was collected for 72 hours and assayed for nonvolatile radioactivity. Total recoveries of FC-11 were 99.5 and 79.4 per cent in the woman and the man, respectively. Total recoveries of FC-12 were 95.4 and 103.2 per cent. Traces of radioactivity were found in urine (FC-11, 0.07 and 0.09 per cent; FC-12, 0.02 and 0.03 per cent) and in exhaled carbon dioxide (FC-11, 0.13 and 0.10 per cent; FC-12, 0.08 per cent in both subjects). Total metabolites were equal to or less than 0.2 per cent of the administered dose. The amount of radioactivity in urine was insufficient to permit identification of possible fluorocarbon metabolites. The trace of metabolites could be products of radiolabeled impurities. (Key words: Gases, non-anesthetic, dichlorodifluoromethane (Freon 12); Gases, non-anesthetic, trichlorofluoromethane (Freon 11); Pharmacology, fluorocarbons.)