1
Q
Ischemia
A
- Conventional: Imbalance between oxygen supply and demand
2
Q
Anoxia
A
- blood flow to tissue but no oxygen delivery
- problem with the release of O2 to the tissues
3
Q
Hypoxia
A
-blood flow to tissue with inadequate oxygen delivery
4
Q
Reperfusion
A
- Restoration of blood flow after ischemic episode
- after cross clamp and every time you deliver cardioplegia
5
Q
reperfusion injury
A
- Reperfusion Injury extends or accelerates the damage from ischemia
- Potential to increase infarct size
- Ischemia sets the stage
- Rate and long-term extent of ischemic injury may be altered by reperfusion conditions/therapy
6
Q
cardiac myocytes (victim of reperfusion injury)
A
- metabolic / functional center of heart
- highest level of oxidative metabolism
- highest rate of ATP turnover
- doesn’t tolerate anaerobic metabolism
7
Q
coronary vascular endothelium (victim of reperfusion injury)
A
- active tissue
- release bunch vasoactive substances
- interface between blood and myocytes
- arterioles / capillaries very sensitive to injury
8
Q
good activators that the vascular endothelium produces
A
- nitric oxide
- adenosine
- prostacyclin
9
Q
bad activators that the vascular endothelium produces
A
- platelet activating factor
- endothelin-1
- superoxide anion
- histamine
- RECRUITMENT OF NEUTROPHILS TO THE AREA (inflammatory process)
10
Q
what factors determine what our myocardial oxygen demand is
A
- Work done by appropriate chamber(s)
- Passive stretch of myocardial cells
- Heart rate
- Inotropic state
- Basal metabolic state
- Reestablishment of ionic homeostasis
- Oxidative energy diverted to myocyte repair
11
Q
how are the concentrations of the ions effected by ischemia
A
-ischemia breaks everything down and doesn’t allow ATP therefore you can’t maintain the ion balance disrupting the ion concentrations
12
Q
how does CPB Affect Myocardial Oxygen Demand?
A
- decrease demand 50% or more
- Myocardial cooling decrease demand by 50% for each 7oC decrease in temperature
- Ventricular decompression
13
Q
Global Myocardial Ischemia (GMI)?
A
- the cross clamp
- No flow to entire heart
- Clamping aorta during bypass (controlled onset)
- 45 min ischemia followed by unmodified reperfusion (reversable damage)
- Right and Left coronary disease
14
Q
Regional Myocardial Ischemia (RMI)?
A
- No flow to part of the heart
- “Off-pump” cases / Coronary blockage (uncontrolled onset)
- 45 min ischemia followed by unmodified reperfusion
- substantial damage
15
Q
Consequences of Myocardial Ischemia?
A
- Decreased global/regional contractile function
- Increased endothelial damage
- Decreased endothelial function
- Decreased global/regional myocardial blood flow
- Neutrophil accumulation
- Apoptosis
16
Q
Apoptosis
A
-Genetically programmed cell death
17
Q
What Determines The Magnitude of Ischemic Injury?
A
- Duration of ischemia
- Collateral blood flow
- Baseline health of tissue
- Influx of calcium
- Intracellular accumulation of sodium and loss of potassium
- Stimulation of other activators
18
Q
What Determines The Time To Onset of Irreversible Damage?
A
- Severity of ischemia
- Myocardial temperature
- Tissue energy demands
- Collateral blood flow
- Appear after 30 minutes of occlusion in working heart
19
Q
what damage can reperfusion injury do?
A
- Potential to extend postischemic injury
- Myocardial stunning
- No-reflow phenomenon
- Reperfusion arrhythmias
- Lethal reperfusion injury
20
Q
Myocardial Stunning
A
-Mechanical dysfunction after reperfusion
21
Q
No-Flow Phenomenon
A
-Inability to reperfuse previously ischemic area
22
Q
Reperfusion Arrhythmias treatments
A
- pacing wires
- drugs
23
Q
Lethal Reperfusion Injury
A
- Several abrupt biochemical and metabolic changes occur – compound injury created by ischemia
- Mitochondrial reenergization
- Generation of reactive oxygen species
- Intracellular calcium overload
- Rapid restoration of physiologic pH
- Inflammation
- Cell death results from opening of mitochondrial permeability transition pore (mPTP) and induction of cardiac myocyte hyper-contraction
24
Q
What Are The Mediators of Lethal Reperfusion Injury?
A
-oxygen-derived free radical
formation (reactive oxygen species (ROS))
-Hugh influx of calcium into the cell
-pH moves from acidic to normal – potentiates many of the changes
-neutrophil activation
-myocradial edema
25
mitochondrial permeability transition pore (mPTP)
- when open, it messes up ion homeostatis
| - results in cell death
26
why do we use blood cardioplegia
-you are not increasing the amount of dissolved oxygen available and blood offers proteins to keep volume in resulting in less edema
27
When Are Oxygen Free Radicals Generated?
- Myocardial ischemia favors oxygen free radical generation
- Tissue stores of endogenous antioxidants depleted during ischemia
- Oxygen not available until reperfusion
- GREATEST RISK (i.e. greatest production) occurres when oxygen returned to myocardium
- hotshot
28
what is in endothelial cells that creates hydrogen peroxide
-xanthine oxidase
29
what two ways to create hydrogen peroxide
- mitochondria
| - NADPH oxidase
30
What Factors Determine The Amount of Oxygen Free Radicals Produced?
- Severity of ischemic injury (duration)
- Activation and recruitment of neutrophils to myocardium
- Level of oxygen in the cardioplegic solution
31
What Changes Are Caused By Oxygen Free Radicals?
-destroys cell membrane
32
What do the oxygen free radicals do?
- Induce opening mitochondrial permeability transition pore
- Act as neutrophil chemoattractants
- Mediate dysfunction of sarcoplasmic reticulum
- Contribute to intracellular calcium overload
- Damage cell membrane by lipid peroxidation
- Induce enzyme denaturation
- Cause direct oxidative damage to DNA
33
What is the Mitochondrial Permeability Transition Pore?
- Nonselective channel (protein) of inner mitochondrial membrane
- When open increases permeability of molecules <1500 Dalton
- When open mitochondrial membrane potential collapses and oxidative phosphorylation is uncoupled
- Closed during ischemia / open during reperfusion
- Opens in response to mitochondrial calcium overload, oxidative stress, restoration of physiologic pH, and ATP depletion
34
How Can We “Attack” The Oxygen Free Radical Problem?
- Administer pharmacological agents that inhibit the formation of oxygen free radicals
- Administer pharmacological agents that scavenge / remove oxygen free radicals
- Administer anti-neutrophil agents
35
What Changes Are Caused
| By Myocyte Calcium Influx?
- Depletion of high-energy phosphate stores
- Accumulation in mitochondria kills ability to produce ATP
- Activation of catalytic enzymes
- Alteration of excitation-contraction coupling of actin-myosin-troponin
36
neutrophil products that act on endothelium
- platelet activating factor
- O2 free radicals
- hypoclorous acid
- proteases
- cytokines
37
What Causes Myocardial Edema?
- Increased intracellular osmotic pressure
- Disruption of electrical potential across cell membrane
- Increased microvascular permeability
- Increased interstitial osmotic pressure
- High cardioplegia delivery pressure
- Hypothermia induced changes to sodium-potassium pump
38
How Can We Target The Perpetrators During Bypass?
- IV administration
| - Cardioplegia
39
How Do We Target The Perpetrators During Off-Pump Cases?
- IV administration
- NO cardioplegia
- NO hypothermia
- MINIMAL cardiac work-load reduction
40
What Clinical Results Do We See As a Result of RPI?
- Dysrhythmias
- Systolic dysfunction
- Diastolic dysfunction (compliance / relaxation)
- Myocardial necrosis
- Endothelial dysfunction
- No reflow phenomenon
41
When Can Myocardial Injury Occur?
- Before bypass
- During cardioplegic arrest
- During reperfusion
42
Pre-bypass / before delivery of cardioplegia – “prebypass window” (myocardial injury)
- Period of unprotected ischemia
- coronary artery or other disease process
- hypotension due to dysrhythmia and/or cardiogenic shock
- coronary spasm
- Reperfusion injury also possible
43
Cross-clamp applied / cardioplegia delivered (myocardial injury)
- Period of protected ischemia
- unresolved coronary stenosis
- obstruction within vascular graft (kink, tight anastomosis, emboli)
- maldistribution of cardioplegia
- inadequate cardioplegia delivery (inadequate pressure or volume, inappropriate composition)
- between infusions of intermittent cardioplegia
- unintentional interruption of continuous cardioplegia
- Reperfusion injury also possible
44
Reperfusion (myocardial injury)
- coronary blood flow restored with unmodified blood after clamp removal
- Ischemic injury also possible
- hypotension post clamp release
- during weaning/termination CPB
- vascular graft thrombosis or mechanical obstruction
- dysrhythmias
- vasospasm of grafted vessel
Perf tech II
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