Effects of morphine on coronary and left ventricular dynamics in conscious dogs.

We studied the effects of i.v. 2 mg/kg morphine sulfate (MS) on coronary blood flow and resistance, left ventricular (LV) diameter and pressure (P), rate of change of pressure (dP/dt), and dP/dt/P in conscious dogs. An initial transient reduction in coronary vascular resistance, associated with increases in heart rate, dP/dt, dP/dt/P, and reductions in LV end-diastolic and end-systolic size were observed. This was followed by a prolonged increase in mean coronary vascular resistance, lasting from 5 to 30 min, while heart rate, arterial pressure, and LV end-diastolic diameter returned to control levels and dP/dt/P remained slightly but significantly above control. At 10 min, late diastolic coronary flow had fallen from 44 plus or minus 3 ml/min to a minimum level of 25 plus or minus 3 ml/min, while late diastolic coronary resistance had risen from 1.68 plus or minus 0.10 to 3.04 plus or minus 0.28 mm Hg/ml/min. Morphine also induced substantial coronary vasoconstriction when heart rate was held constant. Neither the MS-induced coronary vasoconstriction nor the positive inotropic response was abolished by bilateral adrenalectomy. The positive inotropic response of MS was reversed after beta blockade, but not the coronary vasoconstriction. Alpha receptor blockade abolished the late coronary vasoconstriction effects of morphine, and only dilatation occurred. In anesthetized dogs MS failed to produce late coronary vasoconstriction. Coronary after a respiratory-depressant dose of morphine, 10 mg/kg i.v. Smaller doses of MS, 0.25 mg/kg every 15 min, produced significant coronary vasoconstriction after a total dose of 0.75 mg/kg in the conscious dogs. The effects of morphine may differ in the normal dog and man and may vary depending upon the presence or absence of coronary artery disease. However, in the normal conscious dog, MS elicits a mild beta adrenergic increase in contractility and an important coronary vasoconstrictor effect, which is mediated through alpha adrenergic receptors.

In vivo human atherosclerotic plaque recognition by laser-excited fluorescence spectroscopy.

Arterial wall perforation and chronic restenosis represent important factors limiting the clinical application of laser angioplasty. Discrimination of normal and atherosclerotic vessels by laser-excited fluorescence spectroscopy may offer a means of targeting plaque ablation, thereby reducing the frequency of restenosis and transmural perforation. In this study, with use of a 325 nm low power helium-cadmium laser, in vivo endogenous surface fluorescence was excited through a flexible 200 microns optical fiber within a 0.018 in. (0.046 cm) guide wire in contact with the intima of 268 vascular interrogation sites from 48 patients either during open heart surgery or during percutaneous catheterization procedures. Fluorescence spectra could be recorded in all patients in bloodless and blood-filled arteries. Endogenous surface fluorescence was analyzed measuring peak intensity, peak position and shape index of the spectra. Compared with normal wall, noncalcified and calcified coronary atheroma showed a 42% (p less than 0.001) and a 58% (p less than 0.001) decrease of peak intensity, and higher shape index (p less than 0.001 and p less than 0.01, respectively). In addition, peak position was shifted to longer wavelengths for noncalcified coronary atheroma (p less than 0.001). Compared with normal aorta sites, aortic plaques demonstrated a 46% decrease of peak intensity, longer peak position wavelengths (p less than 0.05) and a higher shape index (p less than 0.001). Using an atheroma detection algorithm, prospective analysis of aorta and coronary spectra showed a specificity of 100% for identifying normal sites and a sensitivity of 73% for recognizing atherosclerotic sites.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothermia and blood pH. A review.

Management of the hypothermic patient concerns physicians in many specialties. Accidental hypothermia is commonly encountered in the emergency and operating rooms and in the adult and neonatal intensive care units. Intentional induction of hypothermia is used routinely in cardiac surgery to reduce total body metabolism and oxygen consumption, which is beneficial when an increased tolerance to ischemia is required, such as during total circulatory arrest. Hypothermia is associated with such complications as acidosis, impaired myocardial function, altered blood clotting, decreased kidney and liver function, and intracellular swelling. This review summarizes the laboratory, theoretical, and clinical evidence that the management of blood pH during hypothermia may alter the appearance or magnitude of these deleterious effects.

Peroxynitrite releases copper from caeruloplasmin: implications for atherosclerosis.

Peroxynitrite may be formed in the vasculature by the reaction of superoxide with nitric oxide. When the blue copper-containing protein, caeruloplasmin, is incubated with peroxynitrite, copper is released, and ferroxidase activity and the blue colouration are lost. When plasma from normal subjects is incubated with peroxynitrite, the oxidant reacts with numerous plasma constituents but is still able to release copper from caeruloplasmin. As the ferroxidase activity of caeruloplasmin is lost in plasma in the presence of peroxynitrite, a second ferroxidase activity associated with peroxidised lipids, and not inhibited by azide, is formed.

Intermittent hypothermic asanguineous cerebral perfusion (cerebroplegia) protects the brain during prolonged circulatory arrest. A phosphorus 31 nuclear magnetic resonance study.

A system has been developed for the nuclear magnetic resonance spectroscopic evaluation of cerebral high-energy phosphate levels during hypothermic total circulatory arrest and reperfusion by means of cardiopulmonary bypass in large animals. The use of intermittent hypothermic asanguineous cerebral perfusion, termed cerebroplegia, for the preservation of cerebral high-energy phosphates during a 2-hour period of hypothermic total circulatory arrest and reperfusion has been evaluated. Cardiopulmonary bypass was used to achieve deep hypothermia (12 degrees to 15 degrees C) during 2 hours of circulatory arrest and reperfusion. Juvenile sheep were divided into two groups. Group 1 animals (n = 8) (no cerebroplegia) served as the control group. In group 2 animals (n = 7), cerebroplegia was established by intermittent bilateral carotid artery infusion of a hypothermic oxygenated asanguineous cardioplegic solution. Nuclear magnetic resonance spectroscopy recorded changes in cerebral adenosine triphosphate, creatine phosphate, and intracellular pH. Adenosine triphosphate, creatine phosphate, and pH were higher in the group 2 animals for all points during the arrest period and until 60 minutes after reperfusion (p less than 0.05). Electroencephalographic activity returned after 36 minutes of reperfusion in group 2, but it did not return until 117 minutes in group 1 (p less than 0.05). In summary, cerebral high-energy phosphates and pH were maintained and the electroencephalographic signal returned more rapidly during circulatory arrest with the institution of cerebroplegia. These studies suggest that cerebroplegia is protective of the brain during circulatory arrest.

The effect of pH on the hypothermic ventricular fibrillation threshold.

During cardiac operations using hypothermia, the pH measured at 37 degrees C (and corrected to the patient's body temperature) is generally kept at 7.40. However, ectotherms (cold-blooded animals) regulate pH alkaline of 7.40 as temperature falls, e.g., pH 7.58 at 25 degrees C. Hypothermia and acidosis increase the propensity for ventricular fibrillation (VF). This study was undertaken to determine which scheme of pH regulation during hypothermia provided the highest level of cardiac electrical stability. Eleven dogs underwent median sternotomy and implantation of right ventricular and limb electrodes, aortic and central venous pressure catheters, and a probe to measure pulmonary artery blood temperature. To determine the VF threshold, a programmable stimulator was used to find the minimum current needed to produce VF by sweeping the vulnerable period of the cardiac cycle. The animals were divided into two groups for pH management: eight in the clinical scheme (pH 7.4) and seven in the ectothermic scheme, where pH varied with temperature. Control values were recorded prior to cooling and then repeated when core cooling had lowered the temperature to 25 degrees C. In the clinical group, the VF threshold decreased from 23.1 +/- 4.1 mA at 37 degrees C to 17.0 +/- 3.4 mA at 25 degrees C (p = 0.002); in the ectothermic group, the VF threshold was unchanged by hypothermia (23.7 +/- 3.2 to 22.8 +/- 2.8 mA). Heart rate and arterial and central venous pressures were not different between the groups at either temperature. Corrected arterial pH and PCO2 were unchanged from control in the clinical group at 25 degrees C (pH 7.40 +/- 0.01, arterial PCO2 34 +/- 2 torr), whereas arterial PCO2 was maintained at 20 +/- 1 torr to achieve pH 7.59 +/- 0.01 in the ectothermic group. Five of the eight dogs in the clinical group had spontaneous VF while cooling, as compared to one of the seven dogs in the ectothermic group. These studies demonstrate that allowing the corrected pH to rise with hypothermia and remain alkalotic relative to pH 7.4 improves the electrical stability of the heart during hypothermia, as evidenced by the VF threshold at 25 degrees C. Since the ectothermic scheme increases the electrical stability of the heart, it could decrease the incidence of VF during hypothermia and decrease the temperature at which VF occurs during hypothermic cardiopulmonary bypass.

Delayed postoperative cardiac tamponade mimicking severe tricuspid valve stenosis.

A patient developed acute, severe hemodynamic deterioration five days after an aortic valve replacement. Cardiac catheterization revealed a markedly elevated right atrial pressure but a normal right ventricular end-diastolic pressure. Angiography revealed an extrinsic mass causing compression of the right atrium and the tricuspid anulus. A large clot overlying the right atrium and ventricle was found at emergency surgery. Postoperative cardiac tamponade may result in an atypical hemodynamic presentation when there is selective compression of one chamber or of a valve anulus.

Changes in lymphocyte subpopulations as a result of cardiopulmonary bypass. The effect of blood transfusion.

Cardiopulmonary bypass is associated with postoperative humoral and cellular immune changes. Postoperative decrease in T helper (CD4), T suppressor (CD8), and B lymphocyte counts; decrease or reversal of the CD4/CD8 ratio; and poor in vitro response to mitogens have also been observed. Similar changes in lymphocyte number and function have also been noted in patients receiving transfusions. To determine whether observed changes after cardiopulmonary bypass are related to the bypass itself or to associated blood transfusions, we conducted a study of lymphocyte subsets in transfused and nontransfused patients. A flow cytometric analysis of seven lymphocyte subpopulations was conducted in 18 patients undergoing bypass, eight of whom did not receive a transfusion. The transfused group comprised recipients of both homologous (n = 8) and autologous (n = 2) blood. Total lymphocytes and lymphocytes with markers for CD3 (pan-T cells), CD4, and CD8 decreased significantly postoperatively independent of transfusion. B lymphocytes decreased postoperatively in both the autologous transfusion and no transfusion groups. However, this trend was not seen in patients receiving homologous blood, and three of these patients had evidence of T cell activation, suggestive of an immune response to homologous transfusion. Bypass produces significant changes in selected lymphocyte subsets. Furthermore, simultaneous homologous blood transfusion may specifically elicit an immune response in some patients undergoing cardiopulmonary bypass.

Pulmonary artery partition: new method for correction of interrupted aortic arch.

We have successfully corrected interrupted aortic arch with ventricular septal defect by employing deep hypothermia and circulatory arrest, a median sternotomy incision, and a pulmonary arteriotomy. This simplified technique has the advantage of an abbreviated period of cerebral ischemia, with a relatively simple partitioning of the pulmonary artery.

Low-flow hypothermic cardiopulmonary bypass protects the brain.

Cerebral protection during surgical procedures necessitating circulatory arrest or low flow remains the factor that most limits the critical time for repair of lesions. In vivo phosphorus-31 nuclear magnetic resonance spectroscopy was used to assess the metabolic state of the brain during circulatory arrest by measuring the concentration of high-energy phosphate compounds and the intracellular pH. The degree of cerebral protection during deep hypothermic cardiopulmonary bypass at low flow rates was compared with that obtained with a period of circulatory arrest interrupted by intermittent systemic perfusion. Sheep were instrumented with cannulas for cardiopulmonary bypass, and a radiofrequency coil was positioned on the skull. Animals were placed in the bore of a 4.7 Tesla magnet, cooled with the aid of cardiopulmonary bypass to 15 degrees C, and had either circulatory arrest (n = 5) or continuous low flow rates of 5 ml/kg/min (n = 6) or 10 ml/kg/min (n = 7) for 2 hours. A fourth group (n = 5) underwent 1 hour of circulatory arrest, systemic reperfusion for 30 minutes, then another hour of circulatory arrest. Both circulatory arrest and a flow rate of 5 ml/kg/min resulted in severe intracellular acidosis and depletion of high-energy phosphates. A flow of 10 ml/kg/min preserved high-energy phosphates and intracellular pH. Therefore deep hypothermia with cardiopulmonary bypass flows as low as 10 ml/kg/min can maintain brain high-energy phosphate concentrations and intracellular pH for 2 hours in sheep, whereas flows of 5 ml/kg/min or intermittent full-flow systemic perfusion between periods of circulatory arrest offers less protection. Previous studies from our laboratory have shown that improvement in nuclear magnetic resonance parameters positively correlates with improved survival and preservation of neurologic function.

Comparative assessment of chordal preservation versus chordal resection during mitral valve replacement.

Left ventricular function often deteriorates after mitral valve replacement for mitral regurgitation. It has been postulated that disruption of the mitral valve apparatus at operation is a major mechanism of postoperative dysfunction. The hypothesis tested in this investigation was that chordal preservation results in more favorable left ventricular function. Sixty-nine patients with isolated mitral regurgitation who underwent mitral valve replacement were studied before and 6 months after operation by treadmill exercise testing, catheterization, echocardiography, and radionuclide angiography. Nine patients underwent mitral valve replacement with preservation of the entire mitral apparatus and five with preservation of the posterior leaflet and attached chordae. The remaining 55 had mitral valve replacement with complete excision of the native valve. Preoperatively, there were no differences among groups in age, gender, exercise capacity, cardiac index, rest or exercise ejection fraction, fractional shortening, or pulmonary artery pressures. There were four perioperative deaths (7%) and eight late deaths among the 55 patients with chordal resection but no early or late deaths of patients whose chordae were preserved (p = 0.05). In patients in whom the chordae were excised, exercise capacity, left ventricular systolic dimensions, and cardiac index did not improve after mitral valve replacement, and left ventricular function deteriorated, as evidenced by a reduction of both the resting and exercise ejection fractions (from 46% +/- 13% to 31% +/- 13%, p = 0.0001, and from 49% +/- 12% to 37% +/- 14%, p = 0.0007, respectively) and fractional shortening (from 34% +/- 10% to 26% +/- 14%, p = 0.0001). In contrast, exercise capacity improved after mitral valve replacement in patients in whom the entire apparatus was spared (by 4 +/- 3 minutes, p = 0.05), left ventricular systolic dimensions decreased (from 44 +/- 8 to 36 +/- 9 mm, p = 0.03), and left ventricular function was maintained or improved, as evidenced by preservation of the resting ejection fraction (preoperative, 50% +/- 14%; postoperative, 54% +/- 11%; p = no significant difference), exercise ejection fraction (46% +/- 16% versus 52% +/- 9%, p = no significant difference), fractional shortening (from 31% +/- 9% to 28% +/- 9%, p = no significant difference), and an increase in the cardiac index (from 2.0 +/- 0.3 to 2.7 +/- 0.5 L/min/m2, p = 0.05). No statistically significant differences between posterior chordal resection only and preservation of the entire apparatus were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Low-flow cardiopulmonary bypass and cerebral protection: a summary of investigations.

A research program in cerebral ischemia was initiated by our laboratory to determine optimal strategies for cerebroprotection. Four studies relating to cerebroprotection using nuclear magnetic resonance spectroscopy in a sheep model of hypothermic cardiopulmonary bypass are summarized. These showed, first, that low-flow bypass, with a flow as low as 10 mL.kg-1 x min-1, maintained normal cerebral metabolism; second, that hypothermia increases the high-energy phosphate content and the intracellular pH of the brain; third, that hyperglycemia causes a profound intracellular acidosis; and, finally, that barbiturates prevent the normal increase in high-energy phosphates associated with hypothermia.

Late results after triple-valve replacement with various substitute valves.

The purpose of this study was to determine what influence various combinations of mechanical and bioprosthetic valves in the aortic, mitral, and tricuspid positions had on late morbidity and mortality of 40 hospital survivors of triple-valve replacement. At operation the patients ranged in age from 27 to 69 years; 73% were women. The mean postoperative follow-up interval was 8.3 years, with a total follow-up of 331 years (100% complete). At 12 months after operation, functional class decreased from 3.3 to 1.6 (p < 0.05), cardiac index increased from 2.0 to 2.6 L.min-1 x m-2 (p < 0.05), and pulmonary artery pressures decreased from 59/27 to 40/17 mm Hg (p < 0.05). There were no differences in preoperative variables between groups. Actuarial survival for the 40 patients (exclusive of 30-day or in-hospital mortality, which was 31%) was 78% and 74% at 5 and 10 years. At the same milestones, freedom from reoperation was 96% and 54%, freedom from combined thromboembolism and anticoagulant-related hemorrhage was 68% and 56%, and freedom from all late valve-related morbidity and mortality was 64% and 25%. Comparison of the patients with two or more mechanical prostheses with the patients having two or more bioprostheses indicated no significant differences in actuarial freedom from late death, thromboembolic events, or anticoagulant-related hemorrhage. However the actuarial freedom from reoperation in the groups with two or more mechanical valves was lower than that of the groups with two or more bioprosthetic valves (0/10 versus 13/30; p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Relation between choice of prostheses and late outcome in double-valve replacement.

The purpose of this study was to determine if the combination of a mechanical and bioprosthetic valve in the aortic and mitral positions influences late morbidity and mortality when compared with patients who had dual mechanical or dual bioprosthetic valves inserted. We reviewed the course of 89 hospital survivors of combined aortic and mitral valve replacement. The mean postoperative follow-up interval was 6.6 years, with a total follow-up of 583 years (98% complete). At 12 months after operation, mean functional class decreased from 3.1 to 1.7 (p < 0.05) and mean cardiac index increased from 2.1 to 2.5 L.min-1.m-2 (p < 0.05). Actuarial survival for the 89 patients (exclusive of < 30-day or in-hospital mortality, 14%) was 70%, 51%, and 33% at 5, 10, and 15 years. Freedom from reoperation was 93%, 78%, and 68%, and freedom from combined thromboembolism and anticoagulant-related hemorrhage was 82%, 60%, and 50%. These results show that there was no difference in overall survival in patients with dual mechanical valves, dual bioprosthetic valves, or a combination of both types at 15 years. There was, however, a lower reoperation rate in the group with dual mechanical valves as compared with the group with dual bioprosthetic valves (p < 0.05 at 10 years) or with a combination of valves (p < 0.05 at 15 years). The higher the number of mechanical valves the higher the combined risk of thromboembolism and anticoagulant-related hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Ischemic preconditioning protects against paraplegia after transient aortic occlusion in the rat.

BACKGROUND: Paraplegia can result from operations requiring transient occlusion of the thoracic aorta. A rat model of paraplegia with the characteristics of delayed paraplegia and transient ischemic dysfunction was developed to determine whether ischemic preconditioning (IPC) improved neurologic outcome. METHODS: Rats underwent balloon occlusion of the upper descending thoracic aorta. One group (2 minute IPC, n = 19) underwent 2 minutes of IPC and a second group (5 minute IPC, n = 19) had 5 minutes of IPC 48 hours before 10 minutes of occlusion. The control group (n = 31) had no IPC prior to 10 minutes of occlusion. RESULTS: Paraplegia occurred in 68% of the control animals (21 of 31 paraplegic: 6 delayed and 15 immediate paraplegia). Both the 2-minute IPC and 5-minute IPC groups had a decreased incidence of paraplegia when compared to controls (32%, p = 0.011 and 26%, p = 0.009, respectively). CONCLUSIONS: A rat model of spinal cord ischemia demonstrating both delayed paraplegia and transient ischemic dysfunction was characterized. Both 2-minute and 5-minute periods of IPC were found to protect against paraplegia.

Thromboxane A2 receptor-specific antagonism in hypothermic cardiopulmonary bypass.

Using a thromboxane A2 receptor-specific antagonist, SQ 30,741, this study was undertaken to define the role of thromboxane A2 in postischemic myocardial reperfusion injury and in the heparin-protamine reaction. Eighteen heparinized (300 units/kg) sheep were placed on cardiopulmonary bypass (CPB) after complete instrumentation, cooled to 28 degrees C, and had their aortas crossclamped for 1 hour. They were then rewarmed to 36 degrees C and weaned from CPB without inotropic support. Control sheep (n = 6) received a saline infusion throughout the procedure. Bolus animals (n = 6) received 5 mg/kg of SQ 30,741 at 5 minutes after discontinuation of CPB and before protamine sulfate administration. Infusion animals (n = 6) received an SQ 30,741 bolus of 5 mg/kg followed by a continuous infusion of 5 mg.kg-1 hr-1 of SQ 30,741 initiated before CPB. All animals received 5 mg/kg of protamine sulfate over a 15-second period 15 minutes after being weaned from CPB. Control animals exhibited significantly decreased global myocardial function after the 1-hour ischemic interval. Further significant functional decline and increase in pulmonary pressure occurred after protamine sulfate administration. Bolus animals experienced a similar postischemic injury, but had no further decrease in function following protamine infusion. Infusion animals had significantly improved global myocardial function after bypass compared with both other groups and were also protected from the deleterious effects of protamine sulfate administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Metabolism of the heart and brain during hypothermic cardiopulmonary bypass.

The alterations in tissue metabolism induced by hypothermic cardiopulmonary bypass are not completely known. Phosphorus-31 nuclear magnetic resonance spectroscopy was used to determine the effect of hypothermic cardiopulmonary bypass on energy states and intracellular pH of the heart and brain. Sheep were instrumented for cardiopulmonary bypass and had a radiofrequency coil placed over either the heart or skull. The animals were placed in a 4.7-T magnet at 37 degrees C and spectra obtained. The animals were cooled on cardiopulmonary bypass to either 26 degrees C (n = 17) or 18 degrees C (n = 14) for brain studies and to 26 degrees C (n = 12) for heart studies. Hypothermia increased the phosphocreatine/adenosine triphosphate ratio in the heart (2.38 +/- 0.23 versus 3.18 +/- 0.37, 37 degrees versus 26 degrees C, respectively, p = 0.03). The brain phosphocreatine/adenosine triphosphate ratio increased from 1.70 +/- 0.09 at 37 degrees C to 2.00 +/- 0.12 at 26 degrees C (p = 0.009) and 2.10 +/- 0.07 at 18 degrees C (p = 0.0001). Intracellular pH increased during hypothermia (heart: 7.05 +/- 0.02 to 7.18 +/- 0.02, 37 degrees versus 26 degrees C, p = 0.0001; and brain: 7.07 +/- 0.02 versus 7.32 +/- 0.02, 37 degrees versus 18 degrees C, p = 0.0001). The adenosine triphosphate resonance position is known to be sensitive to magnesium binding as well as temperature and was shifted upfield (p less than 0.01) in both the heart and brain. This effect could be totally explained by the temperature dependence of this process.(ABSTRACT TRUNCATED AT 250 WORDS)

Hyperglycemia increases cerebral intracellular acidosis during circulatory arrest.

Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess cerebral high-energy phosphate metabolism and intracellular pH in normoglycemic and hyperglycemic sheep during hypothermic circulatory arrest. Two groups of sheep (n = 8 per group) were placed in a 4.7-T magnet and cooled to 15 degrees C using cardiopulmonary bypass. Spectra were acquired before and during circulatory arrest and during reperfusion and rewarming. Intracellular pH and adenosine triphosphate levels decreased during circulatory arrest. Compared with the normoglycemic animals, the hyperglycemic group was significantly more acidotic with the greatest difference observed during the first 20 minutes of reperfusion (6.40 +/- 0.08 versus 6.08 +/- 0.06; p < 0.001). Intracellular pH returned to baseline after 30 minutes of reperfusion in the normoglycemic group but did not reach baseline until 1 hour of reperfusion in the hyperglycemic animals. Adenosine triphosphate levels were significantly higher in the hyperglycemic group during circulatory arrest. Repletion of adenosine triphosphate during reperfusion was similar for both groups. These results support the hypothesis that hyperglycemia during cerebral ischemia drives anaerobic glycolysis and thus leads to increased lactate production and an increase [corrected] in the intracellular acidosis normally associated with ischemia.

Brain protection during circulatory arrest.

Previous nuclear magnetic resonance studies in this laboratory have shown a beneficial biochemical effect of antegrade cerebroplegia (CP-A) during hypothermic circulatory arrest. This study compared CP-A with other methods of cerebral protection during hypothermic circulatory arrest to assess the clinical utility of this technique. Twenty-three sheep were divided into four groups: systemic hypothermia alone (SYST) and systemic hypothermia combined with external cranial cooling (EXTNL), retrograde cerebroplegia (CP-R), or CP-A. Cardiopulmonary bypass was started, and the sheep were cooled to 15 degrees C and subjected to 2 hours of circulatory arrest. Cardiopulmonary bypass was restarted, and the animals were rewarmed and weaned from cardiopulmonary bypass. Serial neurological examinations were performed and hourly scores assigned until the animals were extubated. Postanesthetic neurological scores improved in all groups throughout the 6-hour recovery period except the CP-R group. The improvement over time for these scores was similar for the EXTNL and CP-A groups and significantly better than for the SYST or CP-R groups (p = 0.004). The CP-A group had 5 of 7 animals with deficit-free survival despite the similarity in recovery of baseline brainstem function. We conclude that both antegrade infusion of cerebroplegia and external cranial cooling confer distinct cerebroprotective effects after a protracted period of hypothermic circulatory arrest when compared with the other methods studied.

Barbiturates impair cerebral metabolism during hypothermic circulatory arrest.

Barbiturates have been used as a method of cerebral protection in patients undergoing open heart operations. Phosphorus 31 nuclear magnetic resonance spectroscopy was used to assess barbiturate-induced alterations in the cerebral tissue energy state during cardiopulmonary bypass, hypothermic circulatory arrest, and subsequent reperfusion. Sheep were positioned in a 4.7-T magnet with a radiofrequency coil over the skull. Nuclear magnetic resonance spectra were obtained at 37 degrees C, during cardiopulmonary bypass before and after drug administration at 37 degrees C and 15 degrees C, throughout a 1-hour period of hypothermic circulatory arrest, and during a 2-hour reperfusion period. A group of animals (n = 8) was administered a bolus of sodium thiopental (40 mg/kg) during bypass at 37 degrees C followed by an infusion of 3.3 mg.kg-1 x min-1 until hypothermic arrest. A control group of animals (n = 8) received no barbiturate. The phosphocreatine/adenosine triphosphate ratio, reflecting tissue energy state, was lower during cardiopulmonary bypass at 15 degrees C in the treated animals compared with controls (1.06 +/- 0.08 versus 1.36 +/- 0.17; p < 0.001). Lower phosphocreatine/adenosine triphosphate ratios were observed throughout all periods of arrest and reperfusion in the barbiturate-treated animals compared with controls (p < or = 0.01). Thiopental prevented the increase in cerebral energy state normally observed with hypothermia and resulted in a decrease in the energy state of the brain during hypothermic circulatory arrest and subsequent reperfusion. These results suggest that thiopental administration before a period of hypothermic circulatory arrest may prove detrimental to the preservation of the energy state of the brain.