Protruding aortic arch atheromas: risk of stroke during heart surgery with and without aortic arch endarterectomy.

BACKGROUND: Stroke occurs in 1% to 7% of heart surgery. Aortic arch atherosclerosis is a risk factor for intraoperative stroke, and endarterectomy has been proposed to prevent stroke during heart surgery in patients with arch atheromas. METHODS AND RESULTS: Intraoperative transesophageal echocardiography was performed in 3404 patients undergoing heart surgery between 1990 and 1996. Use of transesophageal echocardiography was unselected and based on equipment availability. Aortic arch atheromas (>/=5 mm, or mobile) were seen in 268 (8%) patients. They were evaluated for intraoperative stroke (confirmed by a neurologist and cerebral infarction on computed tomography or magnetic resonance imaging). Arch endarterectomy was performed in 43 patients as an adjunct to their cardiac procedure in an attempt to prevent intraoperative stroke. The intraoperative stroke rate in all 268 patients with atheromas was high (15.3%). On univariate analysis, age, previous stroke, and arch endarterectomy were significantly associated with intraoperative stroke. On multivariate analysis, age (odds ratio 3.9, P =.01) and arch endarterectomy (odds ratio 3.6, P =.001) were independently predictive of intraoperative stroke. Mortality rate in all 268 patients was high (14.9%). These patients with atheromas also had a long recovery room, intensive care unit, and total hospital length of stay (48 days). CONCLUSIONS: Patients with protruding aortic arch atheromas are at high risk for intraoperative stroke, significant and multiple morbidity, prolonged hospital stay, and death resulting from heart surgery. Aortic arch endarterectomy is strongly associated with intraoperative stroke; its use should be carefully considered in light of these results.

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.

Effect of cannula length on aortic arch flow: protection of the atheromatous aortic arch.

Atheromatous disease in the transverse aortic arch is associated with an increased incidence of perioperative stroke. In addition, tissue erosion in the aortic arch is caused by the high-velocity jet emerging from an aortic cannula during cardiopulmonary bypass (CPB), termed the "sandblast effect". To quantify this phenomenon, flow in the aortic arch was measured intraoperatively by epiaortic ultrasonography in 18 patients undergoing CPB. All were cannulated in the ascending aorta, 10 with a short (1.5 cm) cannula and 8 with a long (7.0 cm) cannula. The peak forward aortic flow velocities (mean +/- standard deviation) measured on the caudal luminal surface of the aortic arch were 0.80 +/- 0.23 m/s off CPB and 2.42 +/- 0.69 m/s on CPB (p < 0.001) for the short cannula and 0.53 +/- 0.20 m/s off CPB and 0.18 m/s on CPB for the long cannula. Thus, during CPB the peak forward aortic flow velocity with the short cannula was significantly greater (p < 0.001) than before CPB, whereas the long cannula produced a lower peak forward aortic flow velocity during CPB. Furthermore, Doppler examination revealed severe turbulence in the aortic arch in all patients with a short cannula. No arch turbulence, however, was seen in 7 patients with a long cannula, and only mild turbulence appeared in the remaining patient with a long cannula. These results show that use of a long aortic cannula results in a significant decrease in peak forward aortic flow velocity and turbulence in the aortic arch during CPB, which may reduce the risk of erosion or disruption of existing atheroma and ensuing embolic complications.

Nimodipine decreases the minimum alveolar concentration of isoflurane in dogs.

Nimodipine is a calcium antagonist that binds with high affinity to neuronal membranes. It is a potent cerebrovasodilator and has been demonstrated also to affect neurotransmitter synthesis and release. Because patients undergoing surgery for intracranial aneurysms are frequently receiving nimodipine, the authors determined the MAC of isoflurane in six dogs before and during three infusion doses of nimodipine (0.5, 1.0 and 2.0 micrograms.kg-1.min-1). MAC was also determined in five dogs before and during infusion of the drug vehicle (10 microliters.kg-1.min-1). Nimodipine produced a reduction in MAC from 1.47 +/- 0.33% to 1.19 +/- 0.18, 1.15 +/- 0.18 and 1.15 +/- 0.09% during infusions of nimodipine 0.5, 1.0 and 2.0 micrograms.kg-1.min-1, respectively (P less than 0.05). Infusion of drug vehicle alone produced no change in MAC (1.39 +/- 0.15%). This reduction in anaesthetic requirement by nimodipine may be due to its effect on neurotransmission. Adjustments in anaesthetic dosage may be necessary in patients receiving nimodipine.

Effect of cardiopulmonary bypass on plasma levels of nifedipine.

Blood levels of many medications are acutely lowered by cardiopulmonary bypass (CPB). Because nifedipine is often used to provide protection from coronary ischemia, a determination of the effect of CPB on plasma nifedipine levels might help to determine the potential clinical benefit of nifedipine during and after bypass. Four samples of blood were drawn from each of eight patients undergoing cardiac surgery: one before, two during, and one after CPB. Although plasma levels of nifedipine declined during and after bypass (P less than 0.05, analysis of variance), the time-course and slope of the decline indicate that this was an effect of normal metabolism of the drug rather than an effect of physiologic changes occurring during CPB. An important additional finding was that the majority of patients had subtherapeutic levels of nifedipine before bypass, suggesting that additional nifedipine given during and after surgery might be of benefit. The effect of the CPB circuit itself was also examined in vitro by mixing nifedipine into a pump prime solution that was then recirculated with 2 U of outdated blood while levels of nifedipine were measured for 3 h. Plasma levels did not change in either a CPB circuit exposed to light or kept in a darkened room.

Flumazenil decreases the minimum alveolar concentration isoflurane in dogs.

Flumazenil is a potent-specific benzodiazepine receptor antagonist that has been shown to reverse CNS depressant effects mediated by benzodiazepine agonists. These agonists are known to affect the interaction of gamma aminobutyric acid (GABA) with its receptor. Because the action of volatile anesthetic agents may be mediated by GABA, the authors determined the MAC of isoflurane in 16 dogs before and after one of three doses of intravenous flumazenil (0.15, 0.3, and 0.45 mg/kg) or the drug vehicle. The flumazenil produced a reduction in MAC from 1.39 +/- 0.15% (mean +/- SD) to 1.23 +/- 0.11% after 0.15 mg/kg (P less than 0.05), from 1.50 +/- 0.35% to 1.08 +/- 0.20% after 0.3 mg/kg (P less than 0.01), and from 1.45 +/- 0.14% to 1.09 +/- 0.08% after 0.45 mg/kg (P less than 0.01). Administration of drug vehicle produced no change in MAC. This reduction in isoflurane requirement by flumazenil may be due to its benzodiazepine receptor agonist action or its analgesic effect.

Uptake of arachidonic acid into membrane phospholipids: effect on chloride transport across cornea.

We demonstrate that arachidonic acid (AA) stimulation of chloride transport across frog cornea is mediated via two independent pathways: (1) stimulation of prostaglandins and cAMP synthesis, and (2) a direct physical change in the membrane produced by substitution of different phospholipid acyl chains. AA is well known as a precursor in the synthesis of prostaglandins, which have been shown to stimulate cAMP synthesis and chloride transport in frog cornea. We show that frog cornea can convert exogenous AA to PGE2, but that in the presence of 10(-5) M indomethacin both the conversion to PGE2 and stimulation of cAMP are completely blocked. However, with indomethacin the action of AA to stimulate chloride transport (as measured by SCC) remains, but peak height of the response is reduced to 57% of that found when AA alone is given. Similarly, we show that propranolol completely blocks cAMP stimulation, but stimulation of SCC is reduced to 45% of the original response. Therefore, cAMP appears to be responsible for roughly half of the observed stimulation in SCC. By gas chromatographic analysis we show that significant quantities of AA can rapidly substitute into membrane phospholipids of corneal epithelium and L929 cells following the addition of AA to the medium. Modification of membrane phospholipid structure can affect membrane viscosity, membrane-bound enzyme activity, and the distribution and lateral mobility of integral proteins. It seems likely that such alterations in the properties of the membrane may modulate the rate of chloride transport, and this may constitute the second mechanism. Upon addition of AA, both mechanisms appear to stimulate chloride transport simultaneously, and are apparently additive. We show that prolonged exposure to AA results in a large incorporation of AA into phospholipid and consequently, a perturbation in the ratio of unsaturated to saturated fatty acids. We also find evidence of a compensatory cellular mechanism that alters the ratio of endogenously synthesized fatty acids and tends to reduce the membrane-perturbing effect of AA.U