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Myocardial protection during CPB

By

Dr. Mahmoud Mohammed AbdelAzeem

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Definitions

  • Myocardial protection refers to strategies and techniques used during operation to prevent Ischemic reperfusion injury (IRI).
  • IRI is defined as myocardial damage resulting from restoration of blood flow to ischemic tissue.
  • Reperfusion can produce an array of events such as damage to cellular membrane, oxidative stress, intracellular calcium accumulation and endothelial damage.

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Ischemic preconditioning

  • Ischemic preconditioning is a powerful protective endogenous adaptive response of the myocardium against a prolonged ischemia.
  • A lot of the RIC (Remote Ischemic Conditioning) data have focused on biomarkers of cardiac injury and not outcomes.
  • RIPC was induced by 3 cycles of 5 minutes of arm ischemia/5 minutes of reperfusion in patients undergoing coronary artery bypass surgery. Protection was confirmed by reduced serum troponin I concentrations in patients with RIPC versus control patients.
  • However, the application of ischemic preconditioning requires a temporary stop of the blood supply, which can be difficult to perform in many clinical situations.

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Myocardial protection

  • Myocardial protection during cardiac surgery aims to preserve myocardial function while providing a bloodless and motionless operating field to make surgery easier.
  • Myocardial protection has been achieved by several methods:
  • hypothermia.
  • Cardioplegic solutions.
  • B-adrenergic antagonists.
  • Inhibition of neutrophil inflammatory mediators.
  • Recently applying monoclonal antibodies against inflammatory mediators.

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  • Hypothermia
  • Hypothermia play an important role during myocardial protection and its intensity and duration are determined according to the surgical procedure.
  • However increased hypothermic time seems to have paradoxical effects, worsening myocardial injury induced by ischemia-reperfusion.
  • Deep hypothermia for very long periods may exacerbate intracellular calcium overload and induce the formation of peroxides and oxygen reactive species.

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  • B-adrenergic antagonists
  • B-adrenergic antagonists attenuate the extent of myocardial injury during ischemia and reperfusion, reducing myocardial oxygen consumption and sympathetic tone and stabilizing cell membranes.

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  • Even if most β-blockers have prolonged negative inotropic effects, the ultra-short-acting and cardio selective β-blocker esmolol has a half-life of a few minutes, and its effects are abolished rapidly after cessation of infusion.

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  • inhibition of neutrophil inflammatory mediators
  • Inhibition of neutrophil inflammatory mediators such as : inhibitors of elastase, cyclooxygenase and platelet activating factor has been demonstrated to be promising for the blunting of neutrophil-induced post ischemic injury.

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Cardioplegic solutions

• Cardioplegia solutions have the dual aim of arresting the heart during diastole and minimizing myocardial energy requirements to obtain an adequate balance between the need for a bloodless, motionless operating field and the preservation of the myocardial function.

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  • Cardioplegic arrest is one of the most common myocardial protection strategies. It is used for patients of all ages requiring cardiac surgery in which the heart must be stopped.

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History

  • The early history of cardioplegia can be divided into three different phases with shifting opinions and practice: the birth 1955–1960; the survival years 1960– 1970(So¨ndergaard,the Bretschneider);and international acceptance during the 1970s.
  • Since the first cardiac surgeries with cardiopulmonary bypass (CPB) in 1953 performed by Dr. Gibbon at Massachusetts General Hospital, in the first surgeries, hypothermia was the method used for myocardial protection, but it showed to be insufficient for prolonged periods of ischemia.
  • In 1955,Melrose, Dreyer, Bentall, Baker. used blood as a vehicle for potassium citrate providing myocardial protection with blood cardioplegia, using potassium as a depolarizing solution which is done even today.

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Types of cardioplegic solutions

  • The cardioplegic solutions can be classified into two main groups:-
  • One is based on extracellular components with high potassium, magnesium and bicarbonate levels
  • while the other is based on intracellular electrolytes which mimic the high potassium/low sodium conditions reducing potential concentration gradients across the plasma membrane, thereby halting potassium efflux.
  • The function of the Na+/K+ ATPase channel is reduced in hypothermic conditions, therefore permitting the intracellular concentrations to persist

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Types of cardioplegia

 

HTK

 

University of

Celsior

 

Eurocollins

 

St Thomas’s

 

 

 

Wisconsin

 

 

Solution

Intracellular/extracellular

Extracellular

Intracellular

Extracellular

Intracellular

Extracellular

Na+

10

25

100

 

10

 

120

K+

10

120

15

 

115

 

16

Ca2+

0.015

0

0.25

 

0

 

1.2

Mg2+

4

5

13

 

0

 

16

Cl–

50

20

0

 

15

 

160

Glucose

–

0

0

 

180

 

0

Others

a-KG

Adenosine

0

 

 

 

0

Glucose

0

0

0

 

195

 

0

Impermeant/colloid

 

 

 

 

 

 

 

 

Hydroxyl-Ethyl Starch (g/L)

0

0

50

 

0

 

0

Lactobionate

0

0

100

 

80

 

0

Mannitol

30

0

 

 

60

 

0

Raffinose

0

0

30

 

0

 

0

Buffer

 

 

 

 

 

 

 

 

Phosphate

0

25

0

 

100

 

0

Bicarbonate

0

0

0

 

10

 

10

Histidine

180

0

30

 

 

 

00

Osmolarity (mOsm/L)

310

330

320

 

375

 

320

Anti-oxidants

 

 

 

 

 

 

 

 

Glutothione

0

2

3

 

0

 

0

Allopurinol

0

1

0

 

0

 

0

Tryptophan

2

0

0

 

0

 

0

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Composition of blood cardioplegia

 

Ingredient

Concentration delivered (mixture 4:1 ratio with blood)

Potassium chloride

20 mmol/L

Magnesium chloride

17 mmol/L

Calcium chloride

2 mmol/L

Procaine

hydrochloride

1 mmol/L

Sodium bicarbonate

25 mmol/L

pH

7.35–7.45

​

​

Osmolality

280–300 mOsm

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Composition of Custodiol

Formulation ingredient

Value

Na

15 mmol/L

K

9 mmol/L

Mg

4 mmol/L

Ca

0.015 mmol/L

Histidine

198 mmol/L

Tryptophan

2 mmol/L

Ketoglutarate

1 mmol/L

Mannitol

30 mmol/L

PH

7.02-1.20

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Custodiol

  • Histidine, tryptophane and ketoglutarate are the components of HTK solution.
  • A high histidine content buffers the acidosis caused by the accumulation of anaerobic metabolites during the prolonged ischaemic period
  • Ketoglutarate improves ATP production during reperfusion
  • Tryptophan stabilizes the cell membrane
  • Mannitol decreases cellular oedema and acts as a free-radical scavenger
  • HTK solution is simple to use, safe and practical and administered as one single dose. Moreover, it is considered to confer sufficient myocardial protection up to 3 hours of cardiac arrest.

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Blood Cardioplegia

  • Cold blood cardioplegia is a method which appears to combine the advantages of hypothermia and blood solutions, and appears to complete myocardial recovery after long periods of ischemia in normal hearts.
  • Blood cardioplegia consists of four parts of blood to one part of crystalloid solution. This limits the hemodilution occurring with crystalloid cardioplegia during repeated infusions.

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  • Blood cardioplegia has many benefits over crystalloid solutions.
  • Enhanced oxygen-carrying capacity
  • active resuscitation (warm induction), avoidance of reperfusion damage (hot shot)
  • limitation of haemodilution,
  • Endogenous oxygen free-radical scavengers.
  • Decreases hospital costs.
  • However, a reperfusion injury still occurs with the reintroduction of warm blood when the cross-clamp is removed because the aorta must be clamped to produce a quiet bloodless field for most cardiac surgical procedures leading to myocardial ischemia��

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Modes of cardioplegic adminstration

  • The two most favoured approaches are antegrade route or a combination of antegrade and retrograde route.
  • Antegrade route through the aortic root after aorta is cross-clamped.
  • The retrograde route via a special catheter placed in coronary sinus through a purse-string guarded small opening made in right atrial wall.
  • Pressure in the retrograde cannula was monitored by the side arm of the coronary sinus cannula connected to a manometer ensuring that infusion pressure did not exceed 45 mm Hg to prevent perivascular hemorrhage and edema.

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Retrograde cannulation

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Coronary sinus cannula

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Methods of cold cardioplegia perfusion

Induction

Antegrade delivery

Retrograde delivery

Cold

300 mL/min × 2 min

150 mL/min × 2.5 min

Maintenance

200 mL/min × 1 min

200 mL/min × 1 min

Reperfusion

150 mL/min × 2 min

150 mL/min × 2 min

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Methods of intermittent warm blood cardioplegia

Flow rate

 

Dose

Roller pump (mL/min)

Syringe pump (mL/h)

Duration (min)

[K+]

​

(mEq/L)

First

300

(Push 2 mL

​

then 150)

2

18–20

Second

200

120

2

20

Third

200

90

2

15

Fourth

200

60

3

10

Fifth

200

40

4

6.3

Sixth

200

40

5

6.3

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The optimal temperature for the delivery of blood cardioplegia

  • Hayashida et al. reported a randomized study comparing the�effects of cold (9 C), tepid (29 C) and warm (37 C) blood cardioplegia in patients undergoing coronary artery bypass grafting.
  • Myocardial oxygen consumption,lactate release and acid release were greatest with warm, intermediate with tepid and least with cold cardioplegia.
  • Early postoperative left ventricular function was best�preserved after tepid cardioplegia due to immediate recovery of�cardiac function. �

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  • Adding retrograde perfusion to antegrade cardioplegia
  • improves sub endocardial perfusion.
  • avoids direct ostial cannulation during aortic valve procedures
  • limits repositioning of retractors during mitral procedures
  • Switching from antegrade to retrograde perfusion increases oxygen uptake and lactate washout, confirming that each strategy perfuses different areas. Therefore, both antegrade and retrograde perfusions are often required at least intermittently.

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Assessment

Intraoperative assessment including:

  1. Coming off bypass quality ( arrhythmias)
  2. Use of inotropic support.
  3. Use of D.C.

4. Total bypass time and cross clamp time

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Assessment

    • Post-operative Assesment

All patients will be admitted to the Surgical intensive care unit intubated and mechanically ventilated and will be assessed for:

  1. Period of mechanical ventilation (Hr.).
  2. Arterial blood gases.
  3. Mean arterial blood pressure.
  4. Central venous pressure.
  5. Monitoring of mediastinal and pleural drains to assess the bleeding.
  6. Pre discharge echocardiograghy.

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Assessment

7- ECG and full Laboratory investigations (cardiac enzymes).

8- ICU stay period (day).

9- Hospital stay (day).

10- Complications such as arrthythmias, renal, hepatic, neurological manifestations, bleeding and wound infection.

11- Urine output

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  • Finally, the ideal cardioplegic agent must meet the following requirements:

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  1. Cardiac arrest: rapid and effective induction of cardiac arrest with a relaxed myocardium and minimum ATP consumption
  2. Myocardial protection: protective effects to delay the irreversible cell damage caused by global ischemia and limit the extent of reperfusion injury;
  3. Reversibility: immediate reversal of cardiac arrest with heart rate and contraction force, allowing an early “weaning” from CPB;
  4. Low toxicity: short half-life without toxic effects on other systems or apparatus after CPB withdrawal.

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Pathophysiology of IRI

  • During ischemia, regional oxygen supply is beneath metabolic needs, resulting in depletion of adenosine triphosphate (ATP) cell reserves. There is decreased efficiency of ATP-dependent (Na+),(K+) pumps with increased levels of intracellular Na+.
  • Intracellular (H+) is built up, Nicotinamide adenine dinucleotide )NAD)mitochondrial oxidation inhibition and ATP break down leading to increased H+ for Na+ exchange to maintain cellular PH, increasing intracellular Na+ levels and promoting increased intracellular calcium (Ca2+) levels.

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IRI

  • This reperfusion injury comprises an activation of neutrophils, release of cytokines and proteases triggered by the contact of blood cells with artificial surfaces during CPB finally interacting with the integrity of the endothelium and they have stressed the deleterious of effects of hypothermia on enzymatic system leading to myocardial ischemia.
  • Increased intracellular Ca ++ concentrations during ischemia and early reperfusion resulting in activation of protein kinases with degradation of proteins and phospholipids , Also the production of neutrophils and mitochondria-derived free radicals contributes for proteins and phospholipids degradation.�

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  • The key point in the pathophysiology of reperfusion injury appears to be the extent of damage sustained by the mitochondria, which is related to the degree of opening of the mitochondrial permeability transition pore MPTP

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  • Irreversible myocardial damage and cell necrosis occur when more than 50% of the mitochondria have MPTP open during reperfusion phase

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Factors contributing to myocardial damage during� ischemia/reperfusion

Ischemia

Early reperfusion

Late reperfusion

Hypoxia

Oxygenation

Burst of ROS

 

 

MPTP opening

Depletion of energy

stores

Re-energisation

Hypercontracture

Increased intracellular

Ca++

Massive Ca++

deposits

Cellular dysfunction

Accumulation of

metabolites

Cell membranes

swelling

Membrane disruption/

death

Acidosis

 

 

Hyperosmolarity

 

 

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Thank you