Solid and gaseous cerebral microembolization during off-pump, on-pump, and open cardiac surgery procedures.

BACKGROUND: Neurocognitive dysfunction remains a limitation of cardiac surgery with cardiopulmonary bypass. Intraoperative cerebral microembolization is believed to be one of the most important etiologic factors. Using a new generation of transcranial Doppler ultrasonography, we compared the number and nature of intraoperative microemboli in patients undergoing on-pump and off-pump cardiac surgery procedures. METHODS: Bilateral continuous transcranial Doppler monitoring of the middle cerebral arteries was performed in 45 patients (15 off-pump coronary artery bypass grafting, 15 on-pump coronary artery bypass grafting, and 15 open cardiac procedures). All recordings were performed using a multi-range, multifrequency system to allow both measurement of the number and discrimination of the nature of microemboli in the 3 different groups. RESULTS: The median number (interquartile range) of microemboli in the off-pump coronary artery bypass grafting, on-pump coronary artery bypass grafting, and open procedure groups were 40 (28-80), 275 (199-472), and 860 (393-1321), respectively (P <.01). Twelve percent of microemboli in the off-pump coronary artery bypass grafting group were solid compared with 28% and 22% in the on-pump coronary artery bypass grafting and open procedure groups, respectively (P <.05). In the on-pump groups, 24% of microemboli occurred during cardiopulmonary bypass, and 56% occurred during aortic manipulation (cannulation, decannulation, application, and removal of crossclamp or sideclamp). CONCLUSIONS: Cerebral microembolization is significantly reduced with avoidance of cardiopulmonary bypass. The majority of microemboli occurring during cardiac surgery are gaseous, with a higher proportion of solid microemboli in the on-pump group, and may have a different significance for cerebral injury than solid microemboli. The ability to reliably discriminate gas and solid microemboli may have an important role in the implementation of neuroprotective strategies.

Alterations to haemostasis following cardiopulmonary bypass and the relationship of these changes to neurocognitive morbidity.

Cardiopulmonary bypass (CPB) is routinely utilized to provide circulatory support during cardiac surgical procedures. The morbidity of CPB has been significantly reduced since its introduction 50 years ago; however, cerebral injury remains a potentially serious consequence of otherwise successful surgery. The risk of stroke postoperatively is approximately 1-5%. Incidence rates for neurocognitive deficit, however, vary markedly depending on the detection method, although typically it is reported in at least 50% of patients. The aetiology of this cerebral injury remains open to debate, although evidence shows that ischaemia secondary to microembolism may be the principal factor. Emboli originate from bubbles of air, atheroemboli released on aortic manipulation and thromboemboli generated as a result of haemostatic activation. Significant generation of thrombin occurs during CPB resulting in fibrin formation, although the trigger of this activation is not fully understood. Rather than originating from contact activation as previously thought, the primary trigger may be via the activated factor VII/tissue factor pathway of coagulation, with an additional role of contact activation in amplification of coagulation as well as the fibrinolytic response to CPB. Haemostatic activation is inhibited with systemic heparin therapy. The relationship between haemostatic activation and emboli formation during CPB is not known. Interventions to reduce cerebral injury in the context of cardiac surgery depend, in large part, on the minimization of emboli. This review investigates cerebral injury after cardiac surgery and evidence showing that microembolism is the principal causative agent. Fibrin emboli are postulated to be an important source of cerebral embolism. The mechanism of haemostatic activation during CPB is therefore also discussed.

Cardiovascular events associated with different combined oral contraceptives: a review of current data.

Studies of combined oral contraceptive (COC) use and cardiovascular disease have been conducted against a background of low cardiovascular risk in young women, changing COC composition and changing user selection and monitoring. Studies of myocardial infarction have found inconsistent results, possibly because of differences in the prevalence of risk factors (particularly smoking and raised blood pressure) in the populations studied. In the absence of a history of smoking and other conventional risk factors, current users of modern COCs probably do not have an increased risk of myocardial infarction. Neither are former users at risk. Evidence for important differences in the risk of myocardial infarction between formulations is weak and contradictory. Current users of low estrogen dose COCs have a small increased risk of ischaemic stroke although most of the risk occurs in women with other risk factors (notably smoking, hypertension and probably a history of migraine). Former users of COCs do not have an increased risk of ischaemic stroke. There is insufficient information to determine whether major differences in the risk of ischaemic stroke exist between products. Current users appear to have a modestly elevated risk of haemorrhagic stroke, mainly in women older than 35 years; former users do not. Data examining the risk of haemorrhagic stroke in current COC users with other risk factors are very sparse, as are those relating to the haemorrhagic stroke risk associated with particular COCs. Numerous studies have found, with remarkable consistency, an elevated risk of venous thromboembolism among current users of low estrogen dose COCs. The risk is substantially elevated among women with various inherited clotting factor defects. The effects in COC users with other risk factors for venous thrombosis tend to be less pronounced and more inconsistent. A number of studies have found higher relative risks among current users of low estrogen dose COCs containing desogestrel or gestodene, than among users of similar products containing levonorgestrel. A number of explanations, in terms of bias or confounding, have been proposed for these clinically small differences. At best, empirical evidence for these explanations, is weak. The risk of cardiovascular disease of any description is low in COC users. Women can minimise, and possibly eliminate entirely, their arterial risks by not smoking and by having their blood pressure checked before using a COC (in order to avoid its use if raised blood pressure is discovered). Users may decrease their venous thromboembolic risk by their choice of COC preparation although the effects will be modest.

Arch and descending aortic aneurysms: influence of perfusion technique on neurological outcome.

OBJECTIVE: Although cannulation of the femoral artery is used routinely for thoracic aortic operations with hypothermic circulatory arrest, retrograde perfusion through the descending aorta carries the risk of cerebral malperfusion or embolism. We have, therefore, routinely used a central cannulation technique for distal arch and descending aortic operations since 1995. In this study, we compared neurological outcome in consecutive patients undergoing femoral versus ascending aortic perfusion for these aneurysms. METHODS: Between 1987 and 1998, 61 patients underwent aortic resection with circulatory arrest, but without retrograde cerebral perfusion, for lesions of the aortic arch and descending aorta. Thirty-one patients had fusiform true aneurysms, 19 had aortic dissection and 11 had extensive saccular or false aneurysms. Thirty-two patients (52%) were perfused via the femoral artery (group A), and 29 patients (48%) from the ascending aorta (group B). Operative mortality and morbidity, and neurological outcome, were reviewed. RESULTS: There were no differences between the groups in mean age, pathology, abdominal and peripheral vascular disease, net perfusion time, or circulatory arrest time. There were four hospital deaths (three in group A and one in group B; P = 0.61), including one neurological death in group A, group A suffered a higher incidence of neurological events (nine patients: 28%) than group B (two patients: 7%; P = 0.03). Temporary focal neurological deficits occurred in both groups (two patients in group A, 6% and two patients in group B, 7%; P > 0.99), but permanent injury occurred exclusively in group A (seven patients: four with monoplegia, one with hemiplegia, and two with diffuse cerebral injury with one death; P = 0.01). CONCLUSIONS: Anterograde perfusion using a proximal aortic cannula provides a low risk of cerebral embolism and allows extensive aortic resection with low morbidity.

Cerebral injury after cardiac surgery: identification of a group at extraordinary risk. Multicenter Study of Perioperative Ischemia Research Group (McSPI) and the Ischemia Research Education Foundation (IREF) Investigators.

BACKGROUND AND PURPOSE: Cerebral injury after cardiac surgery is now recognized as a serious and costly healthcare problem mandating immediate attention. To effect solution, those subgroups of patients at greatest risk must be identified, thereby allowing efficient implementation of new clinical strategies. No such subgroup has been identified; however, patients undergoing intracardiac surgery are thought to be at high risk, but comprehensive data regarding specific risk, impact on cost, and discharge disposition are not available. METHODS: We prospectively studied 273 patients enrolled from 24 diverse US medical centers, who were undergoing intracardiac and coronary artery surgery. Patient data were collected using standardized methods and included clinical, historical, specialized testing, neurological outcome and autopsy data, and measures of resource utilization. Adverse outcomes were defined a priori and determined after database closure by a blinded independent panel. Stepwise logistic regression models were developed to estimate the relative risks associated with clinical history and intraoperative and postoperative events. RESULTS: Adverse cerebral outcomes occurred in 16% of patients (43/273), being nearly equally divided between type I outcomes (8.4%; 5 cerebral deaths, 16 nonfatal strokes, and 2 new TIAs) and type II outcomes (7.3%; 17 new intellectual deterioration persisting at hospital discharge and 3 newly diagnosed seizures). Associated resource utilization was significantly increased--prolonging median intensive care unit stay from 3 days (no adverse cerebral outcome) to 8 days (type I; P<0.001) and from 3 to 6 days (type II; P<0.001), and increasing hospitalization by 50% (type II, P=0.04) to 100% (type I, P<0.001). Furthermore, specialized care after hospital discharge was frequently necessary in those with type I outcomes, in that only 31% returned home compared with 85% of patients without cerebral complications (P<0.001). Significant risk factors for type I outcomes related primarily to embolic phenomena, including proximal aortic atherosclerosis, intracardiac thrombus, and intermittent clamping of the aorta during surgery. For type II outcomes, risk factors again included proximal aortic atherosclerosis, as well as a preoperative history of endocarditis, alcohol abuse, perioperative dysrhythmia or poorly controlled hypertension, and the development of a low-output state after cardiopulmonary bypass. CONCLUSIONS: These prospective multicenter findings demonstrate that patients undergoing intracardiac surgery combined with coronary revascularization are at formidable risk, in that 1 in 6 will develop cerebral complications that are frequently costly and devastating. Thus, new strategies for perioperative management--including technical and pharmacological interventions--are now mandated for this subgroup of cardiac surgery patients.

[Oral anticoagulation in the secondary prevention of cerebrovascular disease. Long-term follow-up of 169 patients]. / Anticoagulación oral en la prevención secundaria de la enfermedad vascular cerebral. Seguimiento a largo plazo de 169 pacientes.

INTRODUCTION: Although the indications for oral anticoagulation (AO) in the treatment of cerebral vascular disease (CVD) are well established, their potential side effects continue to give cause for worry. OBJECTIVES: To describe the complications and ischemic relapses in patients treated with AO for secondary prevention of CVD of cardiac embolic origin. PATIENTS AND METHODS: We included 169 patients with embologenic cardiopathy who, following an CVD, were treated with AO and followed-up at our medical centre for at least three months. We recorded their past clinical history and risk factors, occurrence of vascular relapses (VR), complications involving hemorrhage (CH), and data regarding course and follow-up. RESULTS: During an average follow-up of 50.3 months of a total of 707.9 patient/years, 20 VR (2.8% per year) were recorded; 15 of these were cerebro-vascular and mainly mild. We recorded 59 CH in 41 patients (8.3% per year) of which 6 were considered to be major. There was a 30% drop-out rate from follow-up at our centre, mainly due to death from other causes or to change of referral centre. CONCLUSIONS: There is a low incidence of relapse and of complications (usually mild) following AO for the secondary prevention of CVD of cardio-embolic origin. Efficacy and security are maintained in the long term.

Cerebrovascular ischemic events with high positive anticardiolipin antibodies.

BACKGROUND AND PURPOSE: The aim of our study was to characterize the patient profile and prognostic value associated with high positive IgG (>100 GPL) anticardiolipin antibodies (aCL). METHODS: We studied the clinical, laboratory, radiological, and prospective historical features of ischemic cerebrovascular disease in patients with >100 GPL titers. From our neurology department, 27 consecutive patients were prospectively identified and followed up (mean follow-up time, 34 months). RESULTS: The mean age of our cohort was 41 years. Lupuslike illness occurred in 3; 23 had primary antiphospholipid syndrome, including 3 who met criteria for Sneddon's syndrome; 1 patient had progressive systemic sclerosis. Cerebral infarcts occurred in 74% and were recurrent in 37%. Systemic ischemic events, most commonly deep vein thrombosis, occurred in 37%. Tobacco use was documented in 85%, hyperlipidemia in 74%, hypertension in 44%, and diabetes mellitus in 7% of patients. A prominent headache history was present in 67%. Lupus anticoagulant (LA) was present in 72%, approximately one half had positive antinuclear antibodies and thrombocytopenia, and one quarter had a false-positive VDRL. We compared mean GPL levels in patients testing positive for specific laboratory features of antiphospholipid syndrome with those testing negative for these parameters. Only the LA(+) group had a significantly higher mean GPL than the LA(-) group (P=0.006). Brain imaging showed nonlacunar infarcts in 73% and lacunes in 12%. Of 19 cerebral angiograms, 5 (26%) showed large-vessel occlusive disease and 6 (32%) branch obstruction. Echocardiograms were abnormal in 75%: thickened left-sided valves in 33% and vegetations in 12%. Recurrent cerebrovascular ischemic events were observed in 96%, with transient events (mean rate, 25%/y) occurring 5 times more frequently than strokes (mean rate, 5%/y). Using a standardized disability scale blinded to aCL titer, neurological impairment was severe in 7%, moderate in 30%, and mild or nonexistent in 63%, and unrelated to mean GPL value (P=0.567). Titers fluctuated greatly for individual patients, and most did not consistently test as highly positive. An analysis of fluctuation in symptom severity with concurrent GPL values did not show a statistically significant correlation. Compared with historical controls having a wide range of positive titers, the presence of high IgG aCL titers did not confer a worse prognosis for disability and recurrent ischemic events. CONCLUSIONS: Our data suggest that cerebrovascular events associated with high positive GPL are frequently multiple and minor (with no disability-titer correlation), present in relatively young patients, and often associated with tobacco abuse, hyperlipidemia, LA, systemic ischemic events, and occult cardiac disease.

S-nitrosoglutathione reduces the rate of embolization in humans.

BACKGROUND: Antiplatelet agents presently used in the secondary prevention of cardiovascular disease fail to prevent the majority of cases of recurrent stroke and systemic embolization. An evaluation of the efficacy of new agents is hampered by a lack of in vivo models in humans. Asymptomatic cerebral embolic signals (ES) may be detected with the use of transcranial Doppler ultrasonography. These signals are particularly common after carotid endarterectomy, and this provides a situation in which new antiplatelet agents can be evaluated. With this model, we determined the effectiveness of S-nitrosoglutathione (GSNO), a nitric oxide donor with relative platelet specificity, in reducing cerebral embolization. METHODS AND RESULTS: Transcranial Doppler ultrasound recordings from the ipsilateral middle cerebral artery were made after carotid endarterectomy in 12 control patients and 12 patients receiving intravenous GSNO from the induction of anesthesia until 2 hours after skin closure. Recording times were 0.5 to 3.5, 6 to 7, and 24 to 25 hours after skin closure. The Doppler signal was recorded onto tape, and analysis for ES was performed, with the investigators blinded to treatment group. All patients received aspirin 300 mg/d before surgery and 5000 IU of heparin during surgery. The median (range) number of ES detected during the initial 3-hour postoperative recording was markedly reduced in the GSNO group compared with the control group: 7.5 (0 to 61) versus 38.5 (1 to 219) (P=0.018). This difference persisted until 6 hours after surgery. CONCLUSIONS: Despite the administration of aspirin and heparin, frequent embolization occurred and was markedly reduced after the administration of GSNO. This demonstrates the potential use of platelet-specific nitric oxide donors in the treatment of thromboembolic disease. This model of cerebral embolism may allow determination of the effectiveness of new antiplatelet agents in humans.

Asymptomatic embolization in subjects with atrial fibrillation not taking anticoagulants: a prospective study.

BACKGROUND AND PURPOSE: Embolism is believed to be the major cause of stroke in patients with nonvalvular atrial fibrillation (NVAF). The detection of asymptomatic embolic signals (ES) in individuals with NVAF might allow identification of patients at high risk of stroke and monitoring of therapy in individual subjects. We determined the frequency of asymptomatic ES in patients with NVAF who were not taking warfarin. METHODS: Bilateral transcranial Doppler recordings were made for 1 hour from the middle cerebral arteries of 111 successive patients with NVAF taking aspirin alone or no antithrombotic or anticoagulant therapy. Adequate recordings could be made in 86 patients. In 79 subjects, recordings were performed on a second occasion to study temporal variability. Recordings for a single hour were also made in 30 age-matched control subjects. RESULTS: ES were detected in 13 (15.1%) of NVAF subjects but in no control subjects (P=0.02). ES were detected both in subjects with symptomatic NVAF (4 of 30 [13.1%], P=0.04 versus controls) and asymptomatic NVAF (9 of 56 [16.1%], P=0.02 versus controls). There was no correlation between the presence of ES and smoking status, diabetes, hypertension, aspirin use, aspirin dose, symptomatic status, left atrial size, left ventricular function, or the presence of left atrial thrombus detected on transthoracic echocardiography. Repeating the recording increased the number of patients with ES to 21 (26.6%). On considering the results of both recordings, again there was no association for either recording between the presence of ES and smoking status, diabetes, hypertension, aspirin use, aspirin dose, age, symptomatic status, left atrial size, or left ventricular function. On repeating the recording, in the symptomatic group only 2 patients (8%) changed status, in contrast to 15 (29%) in the asymptomatic group. CONCLUSIONS: ES can be detected in patients with NVAF at a low frequency. Particularly in asymptomatic patients, ES show marked temporal variability. We found no correlation between the presence of previously reported clinical and echocardiographic markers of increased stroke risk and the presence of ES. This association requires further investigation before the clinical utility of this technique in patients with NVAF is decided.

Further evidence of gaseous embolic material in patients with artificial heart valves.

OBJECTIVE: We undertook this study to evaluate the hypothesis that most microemboli signals in patients with artificial heart valves are gaseous, assuming that microemboli counts in cerebral arteries would progressively decline with increasing distance from the generating heart valve. METHODS: A total of 10 outpatients with CarboMedics (Sulzer Carbomedics Inc., n = 5) and ATS prosthetic heart valves (n = 5) in the aortic (n = 8), mitral (n = 1), or both aortic and mitral positions (n = 1) were recruited. Monitoring was performed simultaneously over the middle and anterior cerebral arteries and the common carotid artery for 30 minutes with the 2 MHZ transducers of a color duplex scanner (common carotid artery) and pulsed-wave Doppler ultrasonography (intracranial arteries). All data were harvested in an eight-channel digital audio tape recorder, and microembolic signal counts were evaluated online by two separate observers. RESULTS: Significantly higher microembolic signal counts were recorded in the common carotid artery (112 [75 to 175]) compared with the middle and anterior cerebral arteries (30 [18 to 36], p < 0.0001). Interobserver variability was satisfactory (k = 0.81). CONCLUSIONS: Our results strongly argue for gaseous underlying embolic material in patients with artificial heart valves because bubbles are bound to implode with time.

Differences in stroke between white, Hispanic, and Native American patients: the Barrow Neurological Institute stroke database.

BACKGROUND AND PURPOSE: Identification of specific features of stroke in minority populations should lead to more effectively focused treatment and prevention. METHODS: We examined 1290 white (WHI), 242 Hispanic (HIS), 83 Native American (NA), and 101 other stroke and transient ischemic attack (TIA) patients hospitalized at the Barrow Neurological Institute from 1990 through 1996. RESULTS: Chi-square analysis detected significant (P<.05) differences as follows: (1) Stroke types--lacunes more prevalent in NA than WHI and HIS (30% versus 16% and 15%); cardioembolic more prevalent in WHI than HIS (16% versus 9%, NA 14%); hemorrhages more prevalent in HIS than WHI and NA (48% versus 37% and 27%); (2) Risk factors--hypertension more prevalent in HIS than WHI (72% versus 66%; NA 71%); diabetes more prevalent in NA than HIS and WHI (62% versus 36% and 17%); cigarette smoking more prevalent in WHI than HIS and NA (61% versus 46% and 41%); cardiac disease more prevalent in WHI than HIS (34% versus 24%; NA 27%); heavier alcohol intake in NA than HIS than WHI (43% versus 24% versus 17%). There were no significant outcome differences between races for any stroke type. ANOVA detected significantly lower mean age at stroke onset in NA than HIS than WHI (56 versus 61 versus 69 years). CONCLUSIONS: There are significant differences in prevalence of risk factors and stroke types between WHI, HIS, and NA in our hospital-based population. Although the three races appear to respond to risk factors similarly, Hispanics may be especially susceptible to hemorrhage. Further evaluation of these observations in community-based studies will be important.

Evidence for improved cerebral function after minimally invasive bypass surgery.

BACKGROUND: Neurological impairment is a major cause of morbidity after cardiac surgery and may be associated with occurrence of cerebral microemboli generated during cardiopulmonary bypass (CPB). This study evaluates cerebral dysfunction following coronary artery surgery on-pump and off-pump. METHODS: Neurological outcome was evaluated in 322 patients with a coronary artery bypass graft (CABG). Conventional CPB was used (on-pump) in 305 patients and in 17 patients no CPB was used (off-pump). Intraoperatively, a pulsed-wave transcranial Doppler with a 2-MHZ probe measured high-intensity transient signals (HITS) by ultrasonic insonnation of the middle cerebral artery indicating the presence of emboli within the vessel lumen. Transcranial near-infrared spectroscopy measured cerebral venous oxygen saturation for adequate perfusion. Postoperatively, all patients were subjected to the antisaccadic eye movement (ASEM) test, a sensitive indicator of neurocognitive deficits secondary to frontal lobe dysfunction. RESULTS: While there was no significant difference in O2 saturation, the number of microemboli HITS generated was significantly higher in the on-pump group than the off-pump group. In the off-pump group, 16 (94%) of 17 patients had perfect scores on the ASEM test, while only 108 (35.4%) of 305 patients achieved a perfect score in the on-pump group (p < 0.01). Furthermore, while all patients in the off-pump group achieved at least 90%, 28% (86/305) in the on-pump group scored "zero" on the ASEM test. CONCLUSION: Cerebral dysfunction as evidenced by ASEM errors is common following coronary bypass on-pump, but rare with off-pump bypass surgery. Cerebral microemboli generated during CPB may account for this difference.

Aortic sinotubular atherosclerotic debris associated with cerebral embolic events can be identified by transthoracic echocardiography.

OBJECTIVE: To evaluate the association between the presence of aortic sinotubular debris (STAD) identified by transthoracic echocardiography (TTE) and embolic strokes. BACKGROUND: The presence of atherosclerotic debris in the ascending aorta or aortic arch detected by transesophageal echocardiography or epiaortic echocardiography has been well established to be correlated with embolic stroke or other thromboembolic events. No data are available on the role of TTE in describing aortic pathology in thromboembolic events. METHODS: We identified 60 transthoracic echocardiographic studies from 11,275 studies, in which STAD was diagnosed. The charts of these patients (group 1; mean age 67 +/- 10 years) were reviewed and compared with those of 57 patients (group 2) without STAD, matched for age, gender and risk factors for advanced atherosclerosis. The results of brain imaging procedures, carotid duplex and coronary angiography were also reviewed. RESULTS: Ischemic stroke was found in 15 of group 1 (25%) and 4 patients of group 2 (7%, odds ratio = 4.4; 95% confidence interval, 1.3-19.4, p = 0.008). The average thickness of STAD was 0.7 +/- 0.2 cm in stroke patients and 0.6 +/- 0.2 cm in patients without stroke (p = n.s.). STAD was associated with

Time course of high-intensity transient signals in patients undergoing elective heart valve replacement: a prospective study.

BACKGROUND AND AIMS OF THE STUDY: This study was performed to evaluate the time course of intracranial high-intensity transient signals (HITS) in patients undergoing elective heart valve replacement. METHODS: Thirty-three patients were enrolled in this study. The examination protocol included serial (before and at one, five, 90 and 180 days after surgery) monitoring sessions with transcranial Doppler and detailed neurological examination. Monitoring was performed bilaterally over the middle cerebral arteries for one hour per session using 2 MHz probes. Microembolic signals were recognized according to standard criteria and stored on a computer for later evaluation. RESULTS: HITS prevalence increased from 3% preoperatively to 41% on the first postoperative day and remained unchanged during the postoperative period. No influence of the intensity of anticoagulation or valve type on HITS counts was evident. Unilateral monitoring provided adequate results in 83.9% of cases. CONCLUSIONS: The causative role of the valve implant in the pathogenesis of HITS appears certain, since their prevalence dramatically increases following valve implantation. Valve type, duration of valve implant or intensity of anticoagulation did not influence HITS counts. Bilateral monitoring is warranted for accurate evaluation of HITS counts in this patient group.

Cerebral microembolic signals during cardiopulmonary bypass surgery. Frequency, time of occurrence, and association with patient and surgical characteristics.

BACKGROUND AND PURPOSE: We sought to determine the number of cerebral microembolic signals (MES) and their time of occurrence during the two most frequent types of cardiopulmonary bypass (CPB) surgery: coronary artery bypass grafting (CABG) and cardiac valve replacement (VR). Furthermore, we sought to examine the association between MES, patient characteristics, and intraoperative parameters. METHODS: Forty-two patients were studied, 15 of whom had CABG and 27 VR. Cerebral MES were detected with the use of transcranial Doppler monitoring of the right middle cerebral artery. RESULTS: Cerebral MES were detected in all patients. The number was significantly higher during VR (median, 1048) than during CABG (median, 82) (P < .001). In VR patients, 85% of the MES were detected when the heart regained effective ejection. During CABG, the highest number was detected when the aorta was cross-clamped (18%) and on release of the side clamp (13%). The numbers of MES during the period when the aorta was cross-clamped and in association with surgical procedures were not significantly different in the two patient groups. The total number of MES was inversely correlated to nasopharyngeal temperature (P < .01). CONCLUSIONS: A significantly higher number of cerebral MES were detected during VR than during CABG. The highest number occurred in VR patients when effective heart ejection was regained and in CABG patients when the aorta was cross-clamped and on release of the side clamp. The total number of MES increased at lower nasopharyngeal temperatures. Transcranial Doppler monitoring may alert the surgical team when emboli enter the cerebral circulation during CPB surgery, thus allowing preventive measures to be taken.

Risk factors and solutions for the development of neurobehavioral changes after coronary artery bypass grafting.

BACKGROUND: As operative mortality for coronary artery bypass grafting has decreased, greater attention has focused on neurobehavioral complications of coronary artery bypass grafting and cardiopulmonary bypass. METHODS: To assess risk factors and to evaluate changes in surgical technique, between 1991 and 1994 we evaluated 395 patients undergoing coronary artery bypass grafting with an 11-part neurobehavioral battery administered preoperatively and at 1 and 6 weeks postoperatively. Patients were instrumented with 5-MHz focused continuous-wave carotid Doppler transducers intraoperatively to estimate cerebral microembolism as an instantaneous perturbation of the velocity signal. Microembolism data were quantitated and compared with surgical technical maneuvers during operation and with neurobehavioral deficit (> or = 20% decline from preoperative performance on two or more neurobehavioral tests) postoperatively. These data and patient demographics were statistically analyzed (chi2, t test) and the results at 2 years (1991 and 1992; group A) were used to influence surgical technique in 1993 and 1994 (group B). RESULTS: Significantly associated with new neurobehavioral deficits were increasing patient age (p < 0.05), more than 100 emboli per case (p < 0.04), and palpable aortic plaque (p < 0.02). Group B patients had a significant decline in the neurobehavioral event rate (group A, 69%, 140/203; versus group B, 60%, 115/192; p < 0.05) of postoperative neurobehavioral deficits at 1 week and at 1 month (group A, 29%, 52/180; versus group B, 18%, 35/198; p < 0.01). The stroke rate was less than 2% in both groups (p = not significant). Modifications of surgical technique used in group B patients included increased use of single cross-clamp technique, increased venting of the left ventricle, and application of transesophageal and epiaortic ultrasound scanning to locate and avoid trauma to aortic atherosclerotic plaques. CONCLUSIONS: Neurobehavioral changes after coronary artery bypass grafting are common and associated with cerebral microembolization. Surgical technical maneuvers designed to reduce emboli production may improve neurobehavioral outcome.

Impact of embolization during coronary artery bypass grafting on outcome and length of stay.

BACKGROUND: Transcranial Doppler ultrasonography detects emboli in most patients during coronary artery bypass grafting. However, the significance of these emboli has not yet been established. METHODS: We monitored 82 patients during coronary artery bypass grafting with this technique and related the numbers of emboli to the outcomes and length of hospital stay. RESULTS: We detected cerebral emboli in all patients. Patients with stroke (n = 4; 4.9%) had a mean of 449 emboli, as compared with 169 emboli in patients without stroke (n = 78) (p = 0.005). Patients with major cardiac complications (n = 7) had a mean of 392 emboli, as compared with 163 in patients without such complications (n = 75) (p = 0.003). The mean hospital stay of survivors was 8.6 days in patients with fewer than 100 emboli (n = 40), 13.5 days in patients with 101 to 300 emboli (n = 23), 16.3 days in those with 301 to 500 emboli (n = 16), and 55.8 days in patients with more than 500 emboli (n = 6) (p = 0.0007). This relation was unchanged when patients with complications were excluded. The correlation between embolization and outcome was independent of the extent of aortic atheroma or age. CONCLUSIONS: Emboli detected during coronary artery bypass grafting are significantly related to major cardiac and neurologic complications and affect length of stay in all patients, even in the absence of such specific complications.

Effect of dietary calcium and milk consumption on risk of thromboembolic stroke in older middle-aged men. The Honolulu Heart Program.

BACKGROUND AND PURPOSE: Evidence suggests that dietary calcium is protective against hypertension. This report examines whether the effect has an influence on thromboembolic stroke. METHODS: Since 1965, the Honolulu Heart Program has followed a cohort of men in a study of cardiovascular disease. This report examines the effect of baseline dietary calcium and milk intake on stroke risk in 22 years of follow-up in 3150 older middle-aged men (55 to 68 years). RESULTS: Men who were nondrinkers of milk experienced stroke at twice the rate (P < .05) of men who consumed 16 oz/d or more (7.9 versus 3.7 per 100, respectively). While the rate of stroke decreased with increasing milk intake (P < .05), the decline in stroke risk with increased consumption was modest for those who consumed under 16 oz/d. Intake of dietary calcium was also associated with a reduced risk of stroke (P < .01), although its association was confounded with milk consumption. Calcium intake from nondairy sources was not related to stroke, suggesting that other constituents or covariates related to milk consumption may be important. CONCLUSIONS: We conclude that an association between milk consumption and a reduced risk of stroke in older middle-aged men cannot be explained by intake of dietary calcium. Since milk is often part of a diverse pattern of dietary intake, it is difficult to determine whether milk consumption has a direct role in reducing the risk of stroke. Data suggest that consumption of milk in older middle age is not harmful, and when combined with a balanced diet, weight control, and physical activity, reductions in the risk of stroke may occur.

Age-related changes in stroke risk in men with hypertension and normal blood pressure.

BACKGROUND AND PURPOSE: Stroke is a major contributor to total morbidity and mortality in older individuals, and hypertension is an important risk factor for stroke. Relatively few data exist on whether this relationship changes with age. METHODS: To examine age-related changes in the relationships between risk of stroke and hypertension, we examined the 6-year incidence of stroke among men aged 45 to 81 years using updated blood pressure data from three examinations of Japanese-American men from the Honolulu Heart Program. RESULTS: Both the prevalence of hypertension (systolic blood pressure > or = 160 mm Hg or diastolic blood pressure > or = 95 mm Hg or the use of antihypertensive medication) and the 6-year incidence of stroke increased significantly with increasing age (P < .01). The increase in thromboembolic stroke incidence with age was more marked in those who were normotensive at baseline (2.7/1000 in those aged 45 to 54 years to 23.9/1000 in those > or = 65 years; P < .001) than in hypertensive men (20.6/1000 in those aged 45 to 54 years to 33.5/1000 in those > or = 65 years; P < .01). The age-related increase in risk of thromboembolic stroke among normotensive men resulted in a decrease in the percentage of strokes attributable to hypertension (50% in those aged 45 to 54 years to 18% in those > or = 65 years; P < .05). Similar trends were seen for hemorrhagic stroke. There were no age-related changes in the relationships of other major atherosclerotic risk factors with stroke. The hypertension/stroke relationships were present after multivariate adjustment for age, smoking, cholesterol, and other factors. CONCLUSIONS: In view of the greater prevalence of hypertension and the proven efficacy of treatment in the elderly, these findings do not negate the value of aggressive screening and treatment of hypertension in this age group. However, it appears that other unidentified factors have an increasing role in the causation of stroke with advancing age.