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The Bigelow Lecture


Dennis Mangano, a remarkably prolific and insightful critical care anaesthesiologist earned his PhD in mathematics at MIT before entering medical school. His understanding of complexity and extensive research on brain function after cardiopulmonary bypass made him an ideal candidate for the Bigelow Lecture. He has long been a collaborator with Richard Weisel, who introduced him to the audience. Dennis paid significant and respectful homage to Bill Bigelow, reviewing his studies of hibernation, his pursuit of hibernin and his significant contribution of the protective effects of hypothermia during cardiopulmonary bypass. He then reviewed the prevalence of cerebrovascular disease in patients over 65 -- 36% in those who undergo cardiovascular surgery. The cost of postoperative central nervous system complications is staggering -- 1.4 billion dollars per year.

Dennis has led a remarkable number of clinical trials through his network of cardiac colleagues throughout the world. He is the founding President of the Ischemia Research and Education Foundation. He reviewed the precipitating factors in central nervous system complications, demonstrating embolic ischemic changes in the retina and PET scans of the brain, showed us the vascular problems in the aorta and carotid arteries which should be scanned or evaluated prior to cardiopulmonary bypass. During perfusion, hypotension is a common complication based on worldwide studies conducted with his colleagues. The stroke rate is clearly reduced in patients who are maintained with higher mean blood pressure. Macroembolic injury occurs from disturbance of aortic plaques. Microemboli cause small capillary arterial dilations (SCAD). Hyperglycemia during bypass increases progression of ischemic injury and progression to hemorrhage. For each 0.5 degrees centigrade the stroke severity doubled. There is an inflammatory cellular response to bypass via selectins adhesion molecules and inflammatory cytocines. In general there is an incidence of approximately 3.2% of clear cut strokes and an additional 3% who develop encephalopathy with transient global dysfunction. Cognitive dysfunction persists long-term in patients after cardiopulmonary bypass in 5%. Treatment options include retrograde cerebral perfusion, avoidance of aortic and carotid pathology through preoperative or precannulation imaging, intra-aortic filters, temperature management and various pharmacologic interventions. Prominent among these is the use of barbiturates and insulin (1), anti-inflammatories such as steroids, nsaids and protease inhibitors.

Dennis Mangano
Dennis Mangano
Adenosine augmentation is a special interest of Dennis Mangano's. There's clear evidence that adenosine increases in coronary venous blood in response to injury. Augmentation of the protective effects of adenosine decreases mortality, heart failure and stroke. Some novel approaches to the problem of central nervous system injury include the omission of anaesthesia (not a good idea) and exploration of the technology of off-pump cardiac surgery. There are fewer microemboli by doppler and meta-analyses of series of off-pump cases shows a decreased incidence of stroke with omission of the cardiopulmonary bypass. The vascular blood pressure temperature factors still influence postoperative cognitive outcomes. Antithrombotics such as tissue plasminogen activator and heparin have hemorrhagic side effects which limit their usefulness. Recent use of low molecular weight heparin has proven to be helpful in stroke patients.

Dennis left us with the message that the activated platelet which causes microvascular plugging should be a target of therapy. Remarkably low doses of aspirin inactive platelet cyclo-oxygenase and early administration of aspirin in the postoperative period has been proven to decrease strokes, encephalopathy and cerebral death. He concluded by saying we have now better insight into cognitive dysfunction and a very good understanding of what to avoid. The brain suffers from many of the drugs that we have tried, but hypothermia and aspirin work -- the best solution. The rest of the solution still evades us.

In closing, Dennis returned to Bigelow's legacy, having ably illustrated and exemplified Bigelow's wide ranging scientific curiosity and intellectual humility.


(1) Rao V, et al. The Insulin Cardioplegia Trial: Myocardial protection for urgent coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2002;123:928-35.

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