arrhythmia mechanism

Question 1

Almost all arrhythmias are

Answer 1

acquired:
1. myocardial infarction (MI)
2. ischemia
3. acidosis
4. alkalosis
5. electrolyte abnormalities.

Question 2

Drug toxicity is a common cause of arrhythmia: including

Answer 2

1. cardiac glycosides
2. some antihistamines (astemizole, terfenadine)
3. antibiotics (sulfamethoxazole)

Question 3

Cardiac Arrhythmia Suppression Trial (1989):

Answer 3

post-MI patients treated with flecainide or encainide had a 2-3x >mortality compared to placebo.

Question 4

Consequence of CAST trial:

Answer 4

catheter ablation of ectopic foci and implantable cardioverter- debrillator devices (ICDs) are very often used in place of drugs.

Question 5

Drugs

(1) remain useful in treating some arrhythmias, like ____
(2) are used with_____
(3) would be more useful if we ____

Answer 5

1. supraventricular
2. ICDs to
3. understood the mechanism of action AND molecular targets better

Question 6

The primary targets of antiarrhythmic drugs are:

Answer 6

1.  cardiac Na+ channels
(current = INa) 
2.  cardiac Ca2+ channels
(current = ICa-L)
3. cardiac K+ channels
 (currents = IKs and IKr)
4. B -adrenergic receptors (BAR)

Question 7

direct drug targets

Answer 7

1. Na+ channels
2. Ca2+ channels
3. K+ channels
4. B adrengeric receptors

Question 8

indirect targets of antiarrhythmic drug action.

Answer 8

Via the B adrenergic pathway

Question 9

only ____ have been demonstrated to reduce the incidence of sudden cardiac death

Answer 9

B blockers

Question 10

prolonged ST interval corresponds to

Answer 10

increased AP duration

Question 11

APs in which Ikr channels are partially blocked result in

Answer 11

prolongation of plateau phase

Question 12

at ___% block, ____ are observed.

Answer 12

75%

after-depolarization

Question 13

torsades de pointes

Answer 13

degenerate to ventricular fibrillation

Question 14

Ina is the

Answer 14

cardiac Na+ channel

Question 15

Ica-L is the

Answer 15

cardiac Ca2+ channel

Question 16

INCX is the

Answer 16

electrogenic Na:Ca exchanger

Question 17

Ikr is the

Answer 17

rapidly activated cardiac delayed rectifier K+ channel

Question 18

Iks is the

Answer 18

slowly activated cardiac delayed rectified K+ channel

Question 19

Ik1 is the

Answer 19

hyperpolarization activated K+ channel largely responsible for resting potential in ventricular myocytes

Question 20

Ito is a

Answer 20

very rapidly activated K+ channel that is responsible for phase 1 of the fast response

Question 21

voltage sensor

Answer 21

S4

Question 22

NaV =

Answer 22

voltage- gated Na+ channels

Question 23

familial long QT syndrome results in a

Answer 23

a prolongation of the duration of the cardiac action potential (QT interval) that can lead to ventricular arrhythmia and sudden death

Question 24

In Familial long QT syndrome, prolongation of the plateau phase of the fast response action potential in ventricular myocytes initiates ____

Answer 24

a polymorphic ventricular tachycardia (called torsades de pointes) which can degenerate into ventricular fibrillation followed by syncope and sudden cardiac death.

Question 25

Torsades de pointes is typically triggered by an ____

Answer 25

abrupt increase in sympathetic tone as occurs with emotional excitement, fright, or physical activity.

Question 26

current clinical practice includes treating long QT patients with

Answer 26

β-adrenergic receptor blockers (β-blockers).

Question 27

Thus the autosomal dominant form of long QT syndrome:

Answer 27

Romano-Ward syndrome (RWS), is genetically heterogeneous:

Question 28

In an autosomal recessive form of long QT syndrome,

Answer 28

Jervell-Lange-Nielson syndrome (JLNS),

Question 29

Some of the mutations in cardiac sodium channels and potassium channels that prolong QT interval:

Answer 29

1. a subunit of I-ks
2. a subunit of I-kr
3. a subunit of cardiac sodium channel

Question 30

Long QT mutations in cardiac K+ channel subunits generally

Answer 30

1. reduce the number of K+ channels expressed in the myocyte plasma membrane (loss of function mutations)
2. prolonged plataeu

Question 31

Long QT mutations in the cardiac Na+ channel (INa).

Answer 31

1. prevent Na+ channels from inactivating completely (gain of function mutations)
2. thereby prolonging phase 2 of the fast response.