10/10/2018. Pro-Normoxia During Cardiopulmonary Bypass. The Paradigm of Oxygen. Cellular Respiration Under Normal Oxygen Conditions

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Retinopathy of prematurity Tissue damage Neuro-cognitive damage Myocardial tissue damage This is believed to be caused by the

1 The Paradigm of Oxygen Oxygen is Critical to life Current race to find an Oxygen/Water planet Pro-Normoxia During Cardiopulmonary Bypass Joseph Deptula, MS-P, LP, CCP Unfortunately, too much oxygen can cause: Oxidative stress Lung injury and disease Retinopathy of prematurity Tissue damage Neuro-cognitive damage Myocardial tissue damage This is believed to be caused by the creation of Oxygen Free Radicles that could damage biological molecules and tissues 2 Cellular Respiration Under Normal Oxygen Conditions 3 4 1

Cellular Respiration: Food Acetyl CoA Cellular Respiration: Acetyl CoA Citric Acid Cycle

Fatty acids and glycerol Electron transport via NADH and FADH 2 Cell Mitochondrion Cell

Harper s Illustrated Biochemistry, 28 th ed. McGraw-Hill s Access Medicine, 2009.

Murray RK, et al. Harper s Illustrated Biochemistry, 28th ed.

2 Cellular Respiration: Food Acetyl CoA Cellular Respiration: Acetyl CoA Citric Acid Cycle Electron Transport Proteins Carbohydrates Lipids Glucose and other sugars Amino acids Fatty acids and glycerol Electron transport via NADH and FADH 2 Cell Mitochondrion Cell Acetyl-CoA, acetyl-coenzyme A. Reference: Murray RK, et al. Harper s Illustrated Biochemistry, 28 th ed. McGraw-Hill s Access Medicine, NADH, nicotinamide adenine dinucleotide; FADH 2, flavin adenine dinucleotide Reference: Murray RK, et al. Harper s Illustrated Biochemistry, 28th ed. McGraw-Hill s Access Medicine, Mitochondrion Cellular Respiration: Electron Transport System Cellular Respiration: Electrons Are From Citric Acid Cycle 2

Cellular Respiration: Electrons Used to Transport H + Across Membrane Cellular Respiration: Resulting H + Gradient Used to Generate ATP ATP Synthase Cellular Respiration: Electrons Leaving System

3 Cellular Respiration: Electrons Used to Transport H + Across Membrane Cellular Respiration: Resulting H + Gradient Used to Generate ATP ATP Synthase Cellular Respiration: Electrons Leaving System Accepted by Oxygen Cellular Respiration: A Few Electrons Leak and Create ROS Reactive oxygen species (ROS) O 2 O 2- H 2 O 2 HO H 2 O References: 1. Murray RK, et al. Harper s Illustrated Biochemistry, 28 th ed. McGraw-Hill s Access Medicine, McCord JM. Am J Med. 2000;108(8): Mach WJ, et al. Nurs Res Pract. 2011:

Cellular Respiration: During Normoxia, Cell Can Neutralize Most ROS Cellular Respiration During Hyperoxia Reactive oxygen species (ROS) Antioxidants (eg, SOD, GSH, catalase) References: 1.

4 Cellular Respiration: During Normoxia, Cell Can Neutralize Most ROS Cellular Respiration During Hyperoxia Reactive oxygen species (ROS) Antioxidants (eg, SOD, GSH, catalase) References: 1. Murray RK, et al. Harper s Illustrated Biochemistry, 28 th ed. McGraw-Hill s Access Medicine, McCord JM. Am J Med. 2000;108(8): Mach WJ, et al. Nurs Res Pract. 2011: Hyperoxia: Excess O 2 More Electron Leakage Fewer ATP Hyperoxia: More Electron Leakage More ROS HYPEROXIA HYPEROXIA References: 1. Murray RK, et al. Harper s Illustrated Biochemistry, 28 th ed. McGraw-Hill s Access Medicine, McCord JM. Am J Med. 2000;108(8): Mach WJ, et al. Nurs Res Pract. 2011: Turrens. J Physiol. 2003;552(2): References: 1. Murray RK, et al. Harper s Illustrated Biochemistry, 28 th ed. McGraw-Hill s Access Medicine, McCord JM. Am J Med. 2000;108(8): Mach WJ, et al. Nurs Res Pract. 2011: Turrens. J Physiol. 2003;552(2):

Hyperoxia: More ROS with Inadequate Antioxidants Oxidative Stress HYPEROXIA DNA and

transcription Inability cross-linking with proteins Abnormal protein expression

Harper s Illustrated Biochemistry, 28 th ed. McGraw-Hill s Access Medicine, 2009. 2. McCord JM.

18 Proteins and Free Radicles Chain fragmentation Cross-linking with other proteins

5 Hyperoxia: More ROS with Inadequate Antioxidants Oxidative Stress HYPEROXIA DNA and Free Radicles Strand break Mutations, deletions, and translocations occur during transcription Inability cross-linking with proteins Abnormal protein expression Inadequate antioxidants References: 1. Murray RK, et al. Harper s Illustrated Biochemistry, 28 th ed. McGraw-Hill s Access Medicine, McCord JM. Am J Med. 2000;108(8): Mach WJ, et al. Nurs Res Pract. 2011: Proteins and Free Radicles Chain fragmentation Cross-linking with other proteins Altered electrical charge Alterations in activity of enzymes, receptors, and membrane transport Increased membrane permeability

6 Pathologies Linked to Free Radicles Retinopathy Cancer Myocardial Dysfunction Cerebral Injury Hepatic Injury Increase in SIRS Reperfusion Injury Cyanotic Patients Myocardial Damage After Cross Clamp The effects of normoxic versus hyperoxic cardiopulmonary bypass on oxidative stress and inflammatory response in cyanotic pediatric patients undergoing open cardiac surgery: A randomized controlled trial Massimo Caputo, MD, Amir Mokhtari, MRCS, Chris A. Rogers, PhD,a Nayia Panayiotou, MSc, Qiang Chen, PhD, Mohamed T. Ghorbel, PhD, Gianni D. Angelini, Controlled reoxygenation on starting cardiopulmonary bypass is associated with reduced myocardial damage, oxidative stress, and cerebral and hepatic injury compared with hyperoxic bypass and similar whole body inflammatory and stress response in cyanotic children undergoing open cardiac surgery. J Thorac Cardiovasc Surg 2009;138: Summary The main physiological role of oxygen is to accept electrons exiting the electron transport chain During normoxia, a small percentage of electrons leak out of the electron transport system and interact with oxygen to form oxygen free radicles However, the cell produces antioxidants to neutralize most ROS Hyperoxia can damage biological molecules and can lead to cancer and retinopathy Rebuttal

Cardiovascular effects of hyperoxia during and after cardiac surgery A. M. E. Spoelstra-de Man, B. Smit, H. M. Oudemans-van Straaten and Y. M. Smulders High concentrations of oxygen are administered, to prevent cellular hypoxia.

7 Cardiovascular effects of hyperoxia during and after cardiac surgery A. M. E. Spoelstra-de Man, B. Smit, H. M. Oudemans-van Straaten and Y. M. Smulders High concentrations of oxygen are administered, to prevent cellular hypoxia. Extensive evidence from pre-clinical experiments and clinical studies in other patient groups suggests predominant harm, causing vasoconstriction and myocardial injury. Whether these alterations are temporary and benign, or actually affect clinical outcome, remains to be demonstrated. In low-risk patients, higher oxygen compromises cardiovascular function, but does not affect clinical outcome. No data about potential benefits of hyperoxia, such as reduction of gas micro-emboli or post-cardiac surgery infections, were reported. Current evidence is insufficient to specify optimal oxygen targets. Nevertheless, the safety of supraphysiological oxygen is unproven. Anaesthesia 2015, 70, Normoxic and Hyperoxic Cardiopulmonary Bypass in Congenital Heart Disease Amir Mokhtari and Martin Lewis The existence of reoxygenation injury due to a high PaO2 in the field of resuscitation is well established ---This is bad Patients with cyanotic congenital heart defects have severely diminished myocardial protection-no reserves Lower ATP pre surgery Adenosine triphosphate starts low and is reduced under ischemia and increased lactate not only during ischaemia, but also during reperfusion. Oxidative metabolism after ischemia exacerbates reperfusion injury as a mechanism of myocardial damage with cyanotic heart disease Higher release of creatine kinase, LDH, antioxidant levels, in hyperoxic patients. Extracardiac improvements in the normoxic group Hyperoxic patients 57% longer duration of mechanical ventilation BioMed Research - ID , 26 Discussion 27 7

Lesson Overview. Cellular Respiration: An Overview. 9.2 process of cell respiration

Lesson Overview. Cellular Respiration: An Overview. 9.2 process of cell respiration 9.2 process of cell respiration Glycolysis During glycolysis, glucose is broken down into 2 molecules of the 3-carbon molecule pyruvic acid. Pyruvic acid is a reactant in the Krebs cycle. ATP and NADH