Topic 9 and 10 Flashcards
1
Q
Ischemia=
A
blood supply problem—wounded
2
Q
Injury=
A
cellular damage
3
Q
Infarction (necrosis)=
A
cell death
4
Q
myocardial ischemia causes
A
not enough blood athersclerosis vasospasm thrombosis embolism
5
Q
myocardial ischemia- ekg
A
depressed ST wave
inverted T wave
6
Q
myocardial infarct- ekg
A
deep Q wave
- Troponin released
7
Q
myocardial injury- ekg
A
elevated ST wave
8
Q
Oxygen Free Radicals/Reactive Oxygen Species (ROS)=
A
Altered O2 molecules created
- -At XC and reperfusion
- -Reactions add unpaired electrons to outer orbit
9
Q
Cardioplegia goal is to protect and
A
create scavengers to make them harmless
–Constantly manufactured and removed
10
Q
What do free radicals do?
A
They attack and steal energy from other cells
11
Q
What creates a free radical?
A
missing electron
–highly reactive
12
Q
Free radical damage:
A
After a cell looses an electron- it creates a chain reaction on the cell membrane. Erosion of the cell membrane then occurs
13
Q
What neutralizes free radicals?
A
antioxidants- it donates an electron to the free radical
14
Q
NADPH+ O2 (n the presence of NADPH oxidase)=
A
Superoxide O2-
15
Q
Superoxide O2- (in the presence of superoxide dismutase)=
A
Hydrogen peroxide H2O2
16
Q
Hydrogen peroxide H2O2 (n the presence of Fe++)=
A
Hydroxyl radical OH-
17
Q
Hydrogen peroxide H2O2 (n the presence of Myeloperoxidase)=
A
Hypochlorite HOCl
18
Q
Hydrogen peroxide H2O2 (n the presence of catalase)=
A
O2 + H2O
19
Q
How Reactive Oxygen Species (ROS) are created: \_\_\_\_\_\_\_\_\_ releases in endothelial cells. Enzyme important in \_\_\_\_\_ breakdown path Catalyze: \_\_\_\_\_\_\_ Process generates \_\_\_\_\_\_\_
A
Xanthine oxidase
purine
hypoxanthine to xanthine to uric acid
hydrogen peroxide (H2O2)
20
Q
How Reactive Oxygen Species (ROS) are created:
Re-energized electron transport chain in
A
myocyte mitochondria
21
Q
How Reactive Oxygen Species (ROS) are created:
Hours later additional released from
A
neutrophil s from NADPH oxidase
22
Q
Anoxia=
A
- Total depletion of O2
- Complete lack of Oxygen
23
Q
Hypoxia=
A
- Lack of oxygen delivered to the tissues
- Insufficient supply of O2
24
Q
Ischemia=
A
- -Restriction in blood supply to an organ
- -Results from a restriction
25
Reperfusion=
Restoration of the circulation
26
Reperfusion can result in
- -Can result in inflammation
| - -Results in oxidative damage through inducing oxidative stress rather than restoration of normal function
27
Reperfusion injury from: Myocyte hypercontracture
- increased intracellular calcium
| - reoxygenation from myocytes
28
Reperfusion injury from: mitochondrial dysfunction
- decreased mitochondrial calcium cencentration
| - decreased ATP and apoptosis
29
Reperfusion injury from: free oxygen radicals
- alters membrane proteins and phospholopids
- increased oxidative stress
- increased inflamation
- leukocyte activation and aggravation
30
Reperfusion injury from: activation of coagulation
- platelet activation
| - complement activation leading to microvascular and endothelial dysfunction
31
Reperfusion injury: Independent mediator of
cardiomyocyte death
| --separate from ischemic injury
32
Reperfusion injury: Abrupt biochemical and metabolic changes occur–(compound injury after ischemia) [5]
```
Mitochondrial re-energization
Generation of reactive oxygen species
Intracellular calcium overload
Rapid restoration of physiologic pH
Inflammation
```
33
Reperfusion injury: Cell death results from opening of
mitochondrial permeability transition pore and induction of cardiacmyocyte hyper-contraction
34
Ionic homeostasis can be disrupted: all designed to keep balance of
electrolytes in the extracellular and intracellular fluids
35
Enzyme system: (2)
```
Antioxidant system (electron donators)
5’ nucleotidase system
```
36
Antioxidant system (electron donators)=
Protect heart from free radicals
- -Superoxide dismutase
- -Catalase
- -Glutathione reductase
37
5’ nucleotidase system=
Converts AMP- > adenosine
| -If adenosine nucleotide pool <50% full recovery is impossible
38
What Are The Mediators of Lethal Reperfusion Injury? (5)
```
Oxygen paradox
Calcium paradox
pH paradox
Inflammation paradox
Myocardial edema
```
39
Oxygen paradox=
Too much of a good thing: oxygen-derived free radical formation (reactive oxygen species (ROS))
40
Calcium paradox=
Large influx of calcium into the cell
41
pH paradox=
pH moves from acidic to normal–potentiates many of the changes
42
Inflammation paradox=
Neutrophil activation
43
Myocardial ischemia favors
oxygen free radical generation
44
Tissue stores of endogenous ______ depleted during ischemia
antioxidants
- -superoxide dismutase
- -catalase
- -glutathione
- -glutathione peroxidase
45
Oxygen not available until reperfusion after
clamp off
46
When Are Oxygen Free Radicals Generated? Greatest risk (i.e. greatest production) occurs when
oxygen returned to myocardium
47
What Factors Determine The Amount of Oxygen Free Radicals Produced? (4)
1. Severity of ischemic injury
2. Activation and recruitment of neutrophils to myocardium
3. Level of O2 in the cardioplegic solution
4. Presence of endogenous scavengers and inhibitors
48
What Changes Are Caused By Oxygen Free Radicals?
1. Peroxidation of lipid components of myocellular membranes (steal electrons from lipid membranes)
2. Impairment of vascular endothelial function (produces vasoactive & antiinflammatory autocoids)
- -autocoids: act like local hormones, act near site of synthesis, short acting
49
Results from Changes Caused By Oxygen Free Radicals?
postischemic dysfunction
dysrhythmias
morphologic injury
necrosis
50
How Do Oxygen Free Radicals Cause Injury?
| Induce opening of
mitochondrial permeability transition pore
51
How Do Oxygen Free Radicals Cause Injury?
| Act as neutrophil
chemoattractants
52
How Do Oxygen Free Radicals Cause Injury?
| Mediate dysfunction of
sarcoplasmic reticulum
53
How Do Oxygen Free Radicals Cause Injury?
| Contribute to intracellular
calcium overload
54
How Do Oxygen Free Radicals Cause Injury?
| Damage cell membrane by
lipid peroxidation
55
How Do Oxygen Free Radicals Cause Injury?
| Induce enzyme
denaturation
56
How Do Oxygen Free Radicals Cause Injury?
| Cause direct oxidative damage to
DNA
57
What is the Mitochondrial Permeability Transition Pore?
Nonselective channel (protein) of inner mitochondrial membrane
58
When the Mitochondrial Permeability Transition Pore it open increases permeability of molecules _____ Daltons
<1500 daltons
59
Mitochondrial Permeability Transition Pore: When open oxidative phosphorylation is uncoupled= Results in
decreased ATP and cell death
60
Mitochondrial Permeability Transition Pore: Closed during ______ / open during ______
```
closed= ischemia
open= reperfusion
```
61
Mitochondrial Permeability Transition Pore Opens in response to
mitochondrial calcium overload
oxidative stress
restoration of physiologic pH
ATP depletion
62
How Can We “Attack” The Oxygen Free Radical Problem? (3)
1. Administer pharmacological agents that inhibit the formation of oxygen free radicals
2. Administer pharmacological agents that scavenge / remove oxygen free radicals
3. Administer anti-neutrophil agents
63
Pharmacological agents that inhibit the formation of oxygen free radicals=
Anesthetic agents and Antiarrhythmics
| --may eliminate hydroxyl radicals, Vit C- >peroxides
64
Pharmacological agents that scavenge / remove oxygen free radicals=
Mannitol
| N-acetylcysteine
65
anti-neutrophil agents do what
Decrease ischemia reperfusion injury
66
What Changes Are Caused By Myocyte Calcium Influx? (4)
1. Depletion of high energy phosphate stores
2. Accumulation in mitochondria kills ability to produce ATP
3. Activation of catalytic enzymes
4. Alteration of excitation-contraction coupling of actin-myosin-troponin
67
What Starts The Activation of Neutrophils?
1. Receptor molecules will be activated / exposed
- -Start attachment process to the endothelium
2. Once bound–Diapedesis
- (blood goes thru capillaries)
68
3 types of receptor molecules
1. selectins (P, L, E)= Initial binding processes with endothelial wall
2. beta2 integrins (CD11/CD18 complex)= Mediate firmer contact with wall
3. immunoglobulin superfamily (ICAM-1)= Mediates final surface adherence
69
What Starts The Activation of Neutrophils?
1. P-selectin (endothelial cells) triggered by proinflammatory mediators
2. Neutrophil recruitment triggered by similar proinflammatory mediators
70
Neutrophil products= (5)
```
Oxygen derived free radicals
platelet activating factor
hypoclorous acid
proteases
cytokines
```
71
What Causes Myocardial Edema? (6)
1. Increased intracellular osmotic pressure
2. Disruption of electrical potential across cell membrane
3. Increased microvascular permeability
4. Increased interstitial osmotic pressure
5. High cardioplegia delivery pressure
6. Hypothermia induced changes to sodium-potassium pump
72
Myocardial edema results=
increased microvasculature resistance
| increased diffusion distance to myofibril
73
How Can We Target The Perpetrators During Bypass?
Cardioplegia
| Ability to modify conditions of reperfusion and the composition of the solution
74
modifiable conditions=
hydrodynamics
temperature
route
75
modifiable compositions=
```
pH
metabolic substrate
hypocalcemia
oxygen
pharmaceuticals
```
76
How Do We Target The Perpetrators During Off-Pump Cases?
IV administration
NO cardioplegia
NO hypothermia
MINIMAL cardiac work -load reduction
77
What Clinical Results Do We See As a Result of RPI?
1. Dysrhythmias
2. Systolic dysfunction
3. Diastolic dysfunction (compliance / relaxation)
4. Myocardial necrosis
5. Endothelial dysfunction
6. No reflow phenomenon
78
When Can Myocardial Injury Occur?
```
Before bypass (think “lines”)
During cardioplegic arrest (think XC ON)
During reperfusion (think XC off)
```
79
Pre-bypass / before delivery of cardioplegia –“prebypass window”=Period of
unprotected ischemia
- -coronary artery or other disease process
- -hypotension due to dysrhythmia and/or cardiogenic shock
- -coronary spasm
80
Cross-clamp applied / cardioplegia delivered=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
81
After cross-clamp removed= period of
Reperfusion
--early phase: <4 hours
--late phase: 4 to 6 hours
--resolution of hypotension / dysrhythmia restores blood flow
--cardioplegia infused at high pressures or with improper
composition
--coronary blood flow restored with unmodified blood after clamp removal
82
Ischemic injury also possible (5)
hypotension post clamp release (think “neo”)
during weaning/termination CPB (do not distend)
vascular graft thrombosis or mechanical obstruction
Dysrhythmias (watch EKG)
vasospasm of grafted vessel
83
Objectives for hypothermic cardioplegia administration (4)
1. immediate/sustained electromechanical arrest
2. rapid/sustained homogenous myocardial cooling
3. maintenance of therapeutic additives in effective concentrations
4. periodic washouts of metabolic inhibitors
84
Goals for Myocardial Protection (4)
1. initiate rapid myocardial arrest
2. keep the heart quiet- no electromechanical activity
3. minimize ischemia
4. control re-perfusion
