Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

ICOM-Cardio > Cardio-Biochem- Ischemia and Reperfusion - Wells > Flashcards

Cardio-Biochem- Ischemia and Reperfusion - Wells Flashcards

1
Q

What is the leading cause of death in patients with cardiovascular disease?

A

ischemia and reperfusion injuries

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the changes ischemia induces in the affected cells?

A

decreased ATP,

accumulation of metabolic precursors,

increased calcium concentration,

increased hydrogen ion concentration (lower pH),

and increased production of reactive oxygen species (ROS)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What underlies many of the metabolic changes that occur with ischemia?

A

A metabolic switch from aerobic respiration to anaerobic glycolysis underlies many of these changes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

During reperfusion, , aerobic metabolism is restored and metabolic precursor levels return to normal, oxygen levels go up/down considerably, calcium levels increase/decrease, pH returns to normal, Caspase-3 (cell death) increases/decreases greatly due to both mitochondrial dysfunction-induced apoptosis and necrosis from oxygen deprivation, decreased/increased calcium handling, and ROS levels spike/decrease due to immune cell activity (clearing dying/dead cells).

A

oxygen levels go up

calcium levels continue to increase

Caspase-3 increases

decreased calcium handling

ROS levels spike

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What occurs as a result of ischemic injury to cardiomyoctes with the switch from aerobic respiration to anaerobic glycolysis to create cellular energy?

A

lactate levels increase,

increased intracellular hydrogen ion levels which decreases pH

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What role does ischemic injury induced decreased pH play on the mitochondrial permeability transition pore (MPTP)?

A

inhibits opening of MPTP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What results from ischemia induced decreased pH inhibition of mitochondrial permeability transition pore (MPTP)?

A

Decreased mitochondrial membrane permeability results, causing intracellular sodium and calcium overload, along with cellular contraction that occurs due to disrupted ion homeostasis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

As concerning Ca+2 levels, what occurs with reperfusion?

A

ischemia results in increased levels as well as reperfusion, leading to Ca+2 overload

(also greatly increases ROS production)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What occurs when the shift to neutral/slightly basic pH with reperfusion once again permits MPTP opening?

A

decreased membrane potential -

cell hypercontraction, increased calcium overload, and increased oxidative stress, followed by cell death via apoptosis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What occurs as the result of neutrophil recruitment after ischemia and reperfusion?

A

clear dead and dying cells via increased expression of ROS, cytoplasmic contents, and adhesion molecules. Neutrophil action involves production of additional ROS to dissolve remaining cell structure, however, even further endangering nearby cells and biomolecules.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

-catalyzed ROS formation is one primary collection of ROS synthesis pathways in cells.

A

Metal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

There are/are not key differences between ROS formation in healthy and I-R injured cells via metabolic and RBC reactions that involve metals, as opposed to the dysregulation that happens with heavy metal poisoning (e.g. lead poisoning).

A

are

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Superoxide (ROS) formed during aerobic respiration includes what additional materials for production?

A

flavin mononucleotide (FMN) cofactor,

iron-sufur group redox cycling,

and quinone ionization cycling.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Lead poisoning, as well as cadmium poisoning, etc., decrease expression of antioxidant proteins and cofactor levels, leading to an imbalance of ROS metabolism. Which reaction is key to resolving heavy metal poisoning?

A

Chelation, binding up free atoms/molecules,

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Why is chelation not a treatment for ischemia-reperfusion injuries?

A

it binds up damaging ROS species but does not address the mitochondrial changes that occur with reperfusion.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

In ROS metabolism, what are the 3 interactive intermediates and antioxidant enzymes?

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is the most prominent protein in blood?

A

albumin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Ischemia modified albumin is a useful for myocardial ischemia

A

biomarker

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

To begin the mechanism of IMA biogenesis, localized ischemia results in

A

acidosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What does the the localized acidic environment of ischemic modified albumin biogenesis release?

A

Cu++ ions from weak binding sites on circulating proteins such as caeruloplasmin.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What protein carries approximately 70% of the total copper in human plasma?

A

Caeruloplasmin and it is synthesized in the liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What happens for free copper II in the prescence of a reducing agent (Vit C) in human plasma and how does that relate to ROS genesis?

A

converted to copper I which can react with oxygen to form copper II and generate superoxide free radicals (O2 •–).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Superoxide free radical is converted to hydrogen peroxide by which enxyme?

A

Superoxide dismutase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What happens to biomolecules (albumin) by hydroxyl radicals released from H2O2 and metals due to ischemia?

A

They are damaged, ischemia modified albumin (IMA produced)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is so damaging about ischemia modified albumin?

A

IMA albumin can’t bind Cu++ and leaves a higher free concentration of copper in the blood which leads to more Hydroxyl creation which causes more IMA and the IMA albumin chain reaction continues.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Which assay is used to determine levels of ischemia modified albumin?

A

◦ Albumin Cobalt Binding assay

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

hydroxyl radicals and other ROS damage other biomolecules other than IMA, namely?

A

phenylalanine, tyrosine, and nucleic acid bases, methionine residues

28
Q

Hydroxyl radicals (ROS) added to phenylalanine, tyrosine, and nucleic acid bases form what?

A

hydroxylated derivatives and crosslinks.

29
Q

Evidence of ROS damage associated with ischemia can leave behind evidence formed by by reaction of H2O2 or HOCl with methionine residues in proteins called:

A

methionine sulfoxide

30
Q

What is formed with the reaction of ROS with carbohydrates?

A

reactive carbonyl compounds that attack proteins, forming adducts and crosslinks (advanced glycation end products; AGEs).

31
Q

Advanced glycation end prducts produced via interaction of carbs and ROS in tissue proteins are increased in what condition?

A

diabetes, and they have been implicated in the development of diabetic complications.

32
Q

What is the process that occurs when the OH • attacks polyunsaturated fatty acid?

A

carbon -centered lipid radical to

conjugated dienyl radical then reacts with ambient O2 to form

hydroperoxyl radical which then takes H+ from neighbor lipid to form

lipid peroxide and regenerates R group that continues to modify PUFA to lipid peroxides until PUFA exhausted or termination reaction occurs

33
Q

What is so damaging about lipid peroxidation caused by ROS reaction with polyunsaturated fatty acids?

A

negatively affects cell membranes, organell membranes, and key driver of cell death from reperfusion injury

34
Q

What stops the lipid peroxide biogenesis with ischemia and reperfusion consequences?

A

Exhaustion of lipid store (polyunsaturated fatty acid) or a termination reaction

35
Q

What main molecule is involved in the termination reaction of the biogenesis of cell damaging/death lipid peroxide?

A

Vitamin E

36
Q

What is the major chain -terminating antioxidant in membranes, reducing both conjugated dienyl and hydroperoxyl radicals, to quench the chain reaction in lipid peroxide biogenesis?

A

Vitamin E

37
Q

Which intermediates of lipid peroxide biogenesis are reduced by Vitamin E and therefore leads to quencing of the reaction?

A

conjugated dienyl and hydroperoxyl radicals

38
Q

What reduces lipid peroxides to form inert lipid alcohols?

A

glutathione peroxidase

39
Q

What occurs with the end products of lipid peroxidase if not reduced by glutathione peroxidase (GPx), to form inert lipid alcohols?

A

LPs decompose to form a range of reactive carbonyl species (F) that react with protein to form advanced lipoxidation end products (ALE): biomarkers of oxidative stress.

40
Q

Lipid peroxidation type reactions can also occur with and

as well as polyunsaturated fatty acids.

A

phospholipids; cholesterol esters

41
Q

What are five key scavenger molecules that bind up ROS within cells?

A

◦ 1 Sentinel methionine residues near anti-ROS enzyme active sites.

◦2 Selenium in antioxidants

3◦ Carotenoids

4◦ Vitamin C

5◦ Vitamin E

42
Q

What do Sentinel methionine residues near anti-ROS enzyme active sites. ◦ Selenium in antioxidants ◦ Carotenoids ◦ Vitamin C ◦ Vitamin E have in common?

A

ROS scavenging compounds

43
Q

How do Sentinel methionine residues act as ROS scavengers

A

Sentinel methionine residues surround enzyme active sites and can be converted to methionine sulfoxide in the presence of ROS, thus acting as a protective buffer to enzyme function under ROS-positive conditions

(methionine sulfoxide then converted back to methionine)

44
Q

In what way does selenium (trace mineral) act as a ROS scavenger?

A

is a part of many antioxidant enzymes

45
Q

What role do cartenoids play as ROS scavengers?

A

proteins that can buffer ROS within cells

46
Q

How do Vitamins E and C act as ROS scavengers (antioxidants)?

A

vitamins C and E are effective, reversible scavengers of ROS

vitamin E recovery involves vitamin C participation as a cofactor.

47
Q

Expression of antioxidant enzymes is under the control of?

A

antioxidant response elements (AREs; DNA sequences) in their gene promoters.

48
Q

A transcription factor, Nrf2, and a carrier protein do what in the presence of ROS?

A

translocate to the nucleus, bind to antioxidant response elements in promoter region in DNA, and activate expression of multiple ROS detoxifying enzymes

49
Q

What are the ROS detoxifying enzymes when speaking of ischemia and reperfusion injuries?

A

◦ Superoxide dismutase

◦ Catalase

◦ Glutathione Peroxidase

◦ Periredoxin

50
Q

How do superoxide dismutase and catalase act as ROS detoxifying enzymes?

A

they react in a redox reaction of oxygen to form water from superoxide.

51
Q

How does Glutathione Peroxidase act as a ROS detoxifying enzyme?

A

it uses energy from NADPH generated by pentose phosphate pathway to detoxify H2O2

52
Q

What are the ROS substrats of Glutathione peroxidase?

A

hydrogen peroxide and lipid peroxides.

53
Q

Unlike cardiomyocytes, RBCs do not use for metabolism and is not involved in .

A

oxygen and phagocytosis

54
Q

Why are ROS formed continuously in RBCs?

A

due to both high O2 tension in arterial blood and high heme iron content.

55
Q

RBC antioxidant defenses include which 4 enzymes?

A

catalase,

superoxide dismutase,

glutathione peroxidase,

and methemoglobin reductase.

56
Q

What is the core concern for ischemia reperfusion tissue damage?

A

◦ ROS overproduction due to increased mitochondrial membrane permeability

57
Q

When are cardioproctective interventions applied to protect against ischemia reperfusion injury?

A

applied just after the ischemic event or during reperfusion

58
Q

How is ischemic conditioning achieved?

A

intermittent occlusion of a coronary vessel either locally or remotely, by inducing reversible ischemia of a distant organ (remote ischemic conditioning), can involve treatment with drugs, small molecules (e.g. a kinase inhibitor), mechanical manipulation, or anesthetics, and it limits myocardial infarct size.

59
Q

What are some of the results of cardioprotective interventions performed just after ischemic event or during reperfusion?

A

◦ Increases levels of pro-survival proteins.

◦ Inhibition of kinase signaling.

◦ Alters Mt membrane permeability

  • decreased mPTP opening; increased mitochondrial kATP opening which

Decreases ROS production and can reduce/prevent tissue damage

60
Q

What metabolites are increased and decreased during myocardial ischemia and myocardial reperfusion injury?

A
61
Q

What is and review this likely sequence of events in myocardial I-R injury:

A
62
Q

When are 3 situations in which ishemia-reperfusion injury can occur?

A

after a heart attack,

after transplantation,

or after cardiovascular surgery.

63
Q
A
64
Q
A
65
Q

What are the key targets in I-R injury conditioning?

A

◦ Kinase signaling and altered mitochondrial membrane permeability

66
Q

Reperfusion injury is mostly associated with which damaging processes?

A

oxygen species generation and ROS actions.

67
Q
A

ICOM-Cardio (32 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions