Ola Selnes - US grants

DESCRIPTION: (Verbatim from the Applicant's Abstract) In the United States, nearly 650,000 patients undergo coronary artery bypass grafting (CABG) each year. This procedure, although extraordinarily successful in relieving the symptoms of coronary disease, is also associated with a variety of neurologic problems, ranging from stroke to cognitive changes and depression, which remains a major cause of morbidity after surgery. Not only has it been estimated that from 30 and 79 percent of patients show cognitive decline from 2 weeks to 2 months after CABG, but our prior (separately funded) studies showed late decline in certain cognitive domains 1 to 4 years later. The cause of these cognitive changes is unclear: it is generally thought to be related to the use of the cardiopulmonary bypass machine in the operating room, but lack of appropriate control groups has precluded ruling out other causes including the effects of general anesthesia, Alzheimer's disease (AD) or depression. Therefore, newer techniques of "off-pump" coronary artery bypass surgery (OPAL), that are similar to CABG but do not use the cardiopulmonary bypass machine, provide a unique opportunity to determine the role of the bypass machine in the development of cognitive problems. The present proposal prospectively compares cognitive outcome in 3 groups of patients with coronary artery disease:-CABG patients (general anesthesia, use of the cardiopulmonary bypass machine)-OPCAB patients (general anesthesia)-Nonsurgical control patients (no surgery or general anesthesia) To address our overall hypothesis that patients undergoing CABG will show cognitive decline that differs in nature and time course from decline in surgical and nonsurgical controls, the following specific aims are proposed. By examining patients with neuropsychological tests chosen to assess different cognitive domains, and measures of depression preoperatively, at 3 months, at 1 year, at 3 years, aim 1 will compare the incidence of cognitive change up to 1 year in the three groups, to determine if decline is specific to CABG. Aim 2 will determine the incidence of change at 3 years after surgery. Aim 3 will clarify the role of depression on cognitive changes and the development of angina after surgery. Aim 4 will evaluate demographic, medical and genetic risk factors associated with cognitive change. The long-term objective of this proposal is to determine the role of the cardiopulmonary bypass machine in cognitive change after CABG with the ultimate purpose of proposing interventions to overcome these adverse effects.

postoperative state; neuropsychology; coronary bypass; coronary disorder; outcomes research; cognition disorders; depression; patient oriented research; clinical research; human subject; neuropsychological tests;

DESCRIPTION (provided by applicant): Brain injury during cardiac surgery results primarily from cerebral embolism and/or reduced cerebral blood flow (CBF). The latter is of particular concern for the growing number of surgical patients who are aged and/or who have cerebral vascular disease. Normally, CBF is physiologically autoregulated (or kept constant) within a range of blood pressures allowing for stable cerebral O2 supply commensurate with metabolic demands. Cerebral autoregulation is impaired in patients undergoing cardiac surgery who have cerebral vascular disease and in many others due to other conditions. This could lead to brain injury since current practices of targeting low mean arterial blood pressure empirically (usually 50-70 mmHg) during cardiopulmonary bypass may expose patients with impaired cerebral autoregulation to cerebral hypoperfusion. The hypothesis of this proposal is that targeting mean arterial pressure during cardiopulmonary bypass to a level above an individual's lower autoregulatory threshold reduces the risk for brain injury in patients undergoing cardiac surgery. Monitoring of cerebral autoregulation will be performed in real time using software that continuously compares the relation between arterial blood pressure and CBF velocity of the middle cerebral artery measured with transcranial Doppler and with cerebral oximetry measured with near infrared spectroscopy. The primary end-point of the study will be a comprehensive composite outcome of clinical stroke, cognitive decline, and/or new ischemic brain lesions detected with diffusion weighted magnetic resonance (MR) imaging. Autoregulation is mediated by reactivity of cerebral resistance vessels. A secondary aim of this proposal is to evaluate whether near infrared reflectance spectroscopy can be used to trend changes in cerebral blood volume and provide a reliable monitor of vascular reactivity (the hemoglobin volume index). Assessments for extra-cranial and intra-cranial arterial stenosis will be performed using MR angiography to control for this potential confounding variable in the analysis. Finally, an additional aim of the study will be to assess whether preoperative transcranial Doppler examination of major cerebral arteries can identify patients who are prone to the composite neurological end-point. Near infrared oximetry is non-invasive, continuous, requires little care- giver intervention and, thus, could be widely used to individualize patient blood pressure management during surgery. Brain injury from cardiac surgery is an important source of operative mortality, prolonged hospitalization, increased health care expenditure, and impaired quality of life. Developing strategies to reduce the burden of this complication has wide public health implications and is within the mission of the NHLBI. PUBLIC HEALTH RELEVANCE: Neurological complications from cardiac surgery are an important source of operative mortality, prolonged hospitalization, health care expenditure, and impaired quality of life. New strategies of care are needed to avoid rising complications for the growing number of aged patients undergoing cardiac surgery. This study will evaluate novel methods for reducing brain injury during surgery from inadequate brain blood flow using techniques that could be widely employed.

Brain injury during cardiac surgery results primarily from cerebral embolism and/or reduced cerebral blood flow (CBF). The latter is of particular concern for the growing number of surgical patients who are aged and/or who have cerebral vascular disease. Normally, CBF is physiologically autoregulated (or kept constant) within a range of blood pressures allowing for stable cerebral O2 supply commensurate with metabolic demands. Cerebral autoregulation is impaired in patients undergoing cardiac surgery who have cerebral vascular disease and in many others due to other conditions. This could lead to brain injury since current practices of targeting low mean arterial blood pressure empirically (usually 50-70 mmHg) during cardiopulmonary bypass may expose patients with impaired cerebral autoregulation to cerebral hypoperfusion. The hypothesis of this proposal is that targeting mean arterial pressure during cardiopulmonary bypass to a level above an individual's lower autoregulatory threshold reduces the risk for brain injury in patients undergoing cardiac surgery. Monitoring of cerebral autoregulation will be performed in real time using software that continuously compares the relation between arterial blood pressure and CBF velocity of the middle cerebral artery measured with transcranial Doppler and with cerebral oximetry measured with near infrared spectroscopy. The primary end-point of the study will be a comprehensive composite outcome of clinical stroke, cognitive decline, and/or new ischemic brain lesions detected with diffusion weighted magnetic resonance (MR) imaging. Autoregulation is mediated by reactivity of cerebral resistance vessels. A secondary aim of this proposal is to evaluate whether near infrared reflectance spectroscopy can be used to trend changes in cerebral blood volume and provide a reliable monitor of vascular reactivity (the hemoglobin volume index). Assessments for extra-cranial and intra-cranial arterial stenosis will be performed using MR angiography to control for this potential confounding variable in the analysis. Finally, an additional aim of the study will be to assess whether preoperative transcranial Doppler examination of major cerebral arteries can identify patients who are prone to the composite neurological end-point. Near infrared oximetry is non-invasive, continuous, requires little care- giver intervention and, thus, could be widely used to individualize patient blood pressure management during surgery. Brain injury from cardiac surgery is an important source of operative mortality, prolonged hospitalization, increased health care expenditure, and impaired quality of life. Developing strategies to reduce the burden of this complication has wide public health implications and is within the mission of the NHLBI.