Physiology 29 Cardiac Performance 3

Front 1

During normoxic beating of the heart, where does energy come from? and where does ATP production take place?

Back 1

This comes from exogenous sources (glucose, lactate, fatty acids, ketone bodies)

and endogenous sources (glycogen and triglycerides)

ATP production takes place in the mitochondria

Front 2

Under normal conditions, what portion of hearts ATP comes from carbohydrates. and what are those sources? (4)

Back 2

30-40%

glycolysis
lactate oxidation
glucose oxidation
glycogen stores

Front 3

under normal conditions, what portion of the hearts ATP comes from fats? what are thoses 3 fat stores?

Back 3

60-70%

TAG lipolysis-Beta oxidation

lipoprotein and CM oxidation

ketone body oxidation

Front 4

What does the randle cycle describe?

Back 4

this is the competition of substrates in the heart, the fasting vs. fed state

Front 5

In the fasting state, what happens with the randle cycle?

Back 5

With low insulin in the fasting state you have:
High lipolysis, high free fatty acids, free fatty acid uptake by the heart
- glucose use is inhibited
FFA=60-70%

Front 6

in the fed state, what happens with the randle cycle?

Back 6

High levels of insulin
-inhibits lipolysis
-increased glucose uptake/use in the heart

Glucose can become up to 100% of the fuel for the heart

Front 7

In the fasting state, how does the Randle cycle prevent glucose use?

Back 7

HIgh insulin and high lipolysis give high levels of Beta Oxidation

This produces lots of Citrate and Acetyl CoA- which inhibit enzymes, which prevents glucose uptake

This increase G-6-P, inhibiting hexokinase

Front 8

What does Citrate inhibit in the cell?

Back 8

PFK activity

Front 9

what does acetyl CoA inhibit?

Back 9

pyruvate dehydrogenase

Front 10

When switching to the Fed state, what molecules are less concentrated, and what enzymes are freed up?

Back 10

citrate - PFK

acetyl coa- pyruvate dehydrogenase

Front 11

What is the problem with high levels of FA being oxidized in the heart?

Back 11

this seriously inhibits Glucose Oxidation, which contributes to LV failure

Front 12

What are the 5 Bad things that high FA metabolism in the heart causes?

Back 12

-Induces arrhythmias
-increases oxygen consumption
-promotes oxygen wasting
-reduces cardiac performance
-leads to heart failure

Front 13

what enzymes do Fatty acids inhibit?

Back 13

FA's inhibit

Na-K ATP as, Ca2- ATPase

Electron transport chain, and krebs cycle

adenine nucleotide traslocase

pyruvate dehydrogenase

glucose oxidation (in general)

Front 14

How is the randle cycle used post surgery, post infarct, and with diabetics?

Back 14

using the randle cycle to lower fatty acid use in the heart improves cardiac performance and outlook for these patients

Front 15

Why is there high FFA level post surgery?

Back 15

the high levels of FFA's come from epinephrine release

Front 16

What is the pharmacological action for inihibit B-oxidation? what drugs do this?

Back 16

Inhibits Ketoacyl CoA Thiolase
(frevents fatty acyl coa from entering Beta Oxidation)

Trimetazidine
Ranolazine

Front 17

what is the pharm action for drugs that inhibit fatty acid uptake into mitochondria? what drugs do this?

Back 17

Inhibits carnitine palmitoyl transferase (carnitine shuttle)

etomoxir
oxfenicine

Front 18

How do drugs that modulate acetyl CoA levels work to lower FFA useage in the heart? What are they?

Back 18

These buffer acetyl CoA levels by turning it into acetylcarnitine (which is transported out of the mitochondria)

this lowers Acetyl CoA levels,
this Disinhibits Pyruvate Dehydrogenase, allowing glyoclysis to occur.

L-carnitine is the drug

Front 19

how do drugs that activate glucose metabolism enzymes work? what drugs this?

Back 19

These stimulate pyruvate dehydrogenase, stimulating glycolysis

Dichloroacetate