Possible ischemic events

1
Possible ischemic events

• Vasospasms-epicardial coronary artery smooth
  muscle contraction, reduces luminal x-sec. area
  Due to overproduction of thromboxane A2,
  serotonin released from platelets alpha
  adrenergic activation by SNS and Epinephrine
• Atherosclerosis may preclude NO release as well

2
Ischemic Cascade

• 1. Stiffening of LV (diastolic dysfunction, less
  filling) 2. Systolic emptying impaired, dec.
  LVEF, SV, and segmental wall motion
  abnormalities 3. Altered repolarization,
  ST-segment depression or elevation, T-wave
  inversion as repolarization changes from ischemic
  and non-ischemic tissue
• Might result in "stunned myocardium" or
  "hibernating myocardium".Life-threatening
  dysrythms may ensue Lead to Acute Coronary
  Syndromes (ACS).

3
Angina Pectoris

• Transient, referred cardiac pain resulting from
  myocardial ischemia Silent Ischemia (no pain)
• Pain located in substernal area, jaw, neck, or
  left arm feeling of pressure, heaviness,
  fullness, squeezing, burning, aching, choking.
  Pain may vary in intensity radiate Usually
  subsides with rest or nitroglycerin

4
Angina (cont)

• Atypical angina-not related with exertion
• Unstable angina-new onset of angina, increasing
  frequency or duration compared to previous stable
  angina, occurring at rest Likely due to
  transient thrombi forming dissolving or
  coronary vasospasms (variant or Prinzmetals
  angina).

5
Coronary Artery Occlusion

• A. Rupture or fissure of plaque with thrombi
  response stops flow of blood-evne in arteries
  lt50 occlusion In seconds, extensive Ischemia
  occurs
• B. 1st 20-40 min, reversible injury to
  subendocardium-first area at-risk. Goal is to
  reperfuse with thrombolytic agents-Tpa,
  streptokinase, Urokinase
• .

6
Occlusion (cont).

• C. Injury leads to necrosis in subendo., injury
  spreads toward epicardium.
• D. 1 hour, necrosis spread over 1/3 of wall
• E. 2 hours, necrosis over 1/2 of wall

7
Phase II

• 3 hours-2/3 affected ST-segment T-wave
  changes-Fig. 29.6
• by 6 hrs, complete or transmural infarction.
• 24-72 hrs, acute inflammation, edema.
• 72 hrs- 2 wks inflammation with proliferation of
  connective tissue. Takes 7 weeks to replace
  necrotic tissue with fibrous connective tissue
  (scar).

8
After Infarction

• Greater chance of deadly dysrhythmias.
• Diastolic stiffening-less preload
• Systolic Hypokinesis-decrease in
  shortheningAkinesis-cessation of
  shorteningdyskinesis-bulging or expansion
  remodeling of ventricular tissue leads to
  dilation may lead to thinning of wall which leads
  to loss of contractility which is congestive
  heart failure

9
Severity of Infarction

• Cardiac enzymes released from necrosis-LDH-II
  normally 21 ratio with LDH-I Levels of LDH-I
  rises with infarction 12-24 hrs after. Best
  marker if patient arrives gt24 hrs after
  suspicious symptoms
• Creatine phosphokinase-MB type found in heart
  tissue-rises 3 hrs after necrosis-peaks 12-24 hrs
  after infarction. Used to be earliest detection.
• Rise in Troponin-T Troponin-I rises in 1st 4-6
  hrs after onset of symptoms. Peaks at 10-24 hrs.
  Trend is to replace LDH as valid marker of heart
  damage.

10
Risk Stratified

• LVEF lt40 or experienced congestive heart failure
  during hospital stay at high risk
• Q-wave infarctions more severe
• Non-Q-wave with high stress levels have high 1-yr
  mortality rates
• Angina Pectoris and low exercise capacity (lt 4
  METs)
• Any new conduction disturbances

11
Chapter 5 LIPOPROTEINS, CHD Exercise

• Textbook demonstrates relationship between CHD
  death rate and serum cholesterol levels. Several
  countries, across cultures, and over 35 years of
  study.
• Source of material for atherosclerotic plaque
  formation. Derived from diet and metabolism.

12
APOLIPOPROTEINS

• Likely give LP there characteristics. Serves to
  activate enzymes and act as receptors on tissue
  membrane.
• See table on handout for type of ApoLP, which LP
  they are found on, and what are their apparent
  mechanisms of action.
• A is antiatherogenic, B is atherogenic.

13
TYPES of LIPIDS/LIPOPROTEINS

• Cholesterol-source from liver diet. Carried by
  all types of lipoproteins.
• Triglycerides- source from diet liver- glycerol
  carries 3 free fatty acids.
• Chylomicrons- packaged triglycerides, cleared
  from circulation by lipoprotein lipase. Removed
  by liver.
• Liver secretes VLDL-C- TG rich, low CHOL.,
  degraded by LPL to IDL-C.

14
LIPOPROTEINS cont.

• IDL-C- circulates, picks up CHOL, and converted
  to LDL-C about 60-70 of all CHOL transported by
  LDL-C. This is likely the most dangerous result.
  CHOL deposited either in liver or in peripheral
  tissues (Coronary arteries).
• HDL-C - the calvary. Reverse CHOL transport.
  Clears CHOL, converts to IDL hopefully taken up
  by liver for removal.

15
LIPOPROTEINS EXERCISE

• Evidence to support role of physical activity in
  improving blood lipid profiles
• 1) Cross-sectional-highly trained have lower
  total chol., LDL-C, and higher HDL-C.
• 2) Greater training state greater the difference.
• 3) dietary,smoking status, alcohol intake may
  confound results.

16
Lipoprotein a

• Similar to LDL-c but has apo a which is similar
  to Plasminogen- may block normal action of
  Plasmin. -anticlotting factor.
• Elevated risk when gt25-30 mg/dl.

17
Role of Lpa CHD

• The Lipid Research Clinics Coronary Primary
  Prevention Trial-effect of Questran to lower CHD
  risk.
• 7-10 yr followup-233 men developed CHD, 390 did
  not.
• Control for age,Chol., Hi BP, smoking,
  obesity-used gt35 mg/dl as Lpa high.

18
Results

• Highest Lpa group had 2 fold greater rate of CHD
  than group with lowest levels (lt3 mg/dl).
• Questran lowered Chol. CHD risk. No significant
  effect on Lpa. Niacin has been only drug to lower
  Lpa, but its success is modest unpredictable.

19
10 week Aerobic Exercise
20
Does Lpa influence progression of atherosclerosis?

• 79 Patients with CHD assesed plaque with
  angiography. One block of gt50 used as criteria.
  Lpa measured at start 2 months later. Rapid
  growth was gt10 new growth or finding of new
  artery occluded.
• 27 patients experienced rapid growth.
• Hi levels of Lpa found in 67 of rapid S.
• 33 of slow patients had hi Lpa.
• Inhibits breakdown of fibrin, found in clots

21
Lpa and fitness level-Israel Article

• Compare active vs. sedentary men women.
• Relate Lpa to other lipids and CV parameters.
• 25 of subjects had high Lpa (gt25 mg/dl)
• Lpa really skewed toward low end .Most subjects
  under 15 mg/dl.
• What did they find??

22
Hubinger (Lpa in middle-aged male runners
controls

• Compare trained runners with sedentary gender,
  age, BMI body mass controls.
• How did these groups differ??

23
Examples of Research-Changes in Lipoproteins

• Cholesterol- -7.0 to -26 reduction
• HDL-c- -1.0 to 18.6 increase
• LDL-c- 16 to -22.6 range
• Triglyc.- 7.4 to -31 range
• Usually those with greatest values show greatest
  changes. Why should normal Lipoproteins change??

24
Resistance Exercise

• 1988- 16 wks W.T. increased HDL-c 13, 5
  reduction in LDL-c, and 8 drop in Chol/HDL-c
  ratio. No Trig. change.
• 1988 10 wks W.T.- No sig. change in Trig., Chol,
  LDL-c No increase in HDL-c.
• 1991-20 wk W.T.-Trig dec. (193 vs 171) Chol dec.
  (231 vs 210) HDL-c (35 vs 36) LDL-c (139 vs
  139).

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Potential Mechanisms

• Lipoprotein Lipase-clears Trig. rich lipoproteins
  from circulation- should lower Trig., Found in
  higher concentrations in aerobic trained
  athletes
• Hepatic Lipase- clears HDL2-c by liver which
  lowers HDL-c levels in blood. Negative
  correlation between HDL2-c Hepatic Lipase.