Cardioplegia
Encyclopedia
Cardioplegia is intentional and temporary cessation of cardiac activity, primarily for cardiac surgery
Cardiac surgery
Cardiovascular surgery is surgery on the heart or great vessels performed by cardiac surgeons. Frequently, it is done to treat complications of ischemic heart disease , correct congenital heart disease, or treat valvular heart disease from various causes including endocarditis, rheumatic heart...

.

Overview

The word cardioplegia means cardio-the heart and plegia- paralysis. Technically this means arresting or stopping the heart so that surgical procedures can be done in a still and bloodless field. Most commonly however, the word cardioplegia refers to the solution used to bring about asystole of the heart, or heart paralysis.

The four main goals of hypothermic cardioplegia are:
  1. Immediate and sustained electromechanical quiescence
  2. Rapid and sustained homogenous myocardial cooling
  3. Maintenance of therapeutic additives in effective concentrations
  4. Periodic washout of metabolic inhibitors


The most common procedure for accomplishing asystole
Asystole
In medicine, asystole is a state of no cardiac electrical activity, hence no contractions of the myocardium and no cardiac output or blood flow...

 is infusing cold cardioplegic solution into the coronary circulation
Coronary circulation
Coronary circulation is the circulation of blood in the blood vessels of the heart muscle . The vessels that deliver oxygen-rich blood to the myocardium are known as coronary arteries...

. This process protects the myocardium, or heart muscle, from damage during the period of ischemia.

To achieve this, the patient is first placed on cardiopulmonary bypass. This device, otherwise known as the heart-lung machine, takes over the functions of gas exchange by the lung and blood circulation by the heart. Subsequently the heart is isolated from the rest of the blood circulation by means of an occlusive cross-clamp placed on the ascending aorta proximal to the innominate artery. During this period of heart isolation the heart is not receiving any blood flow, and thus no oxygen for metabolism. As the cardioplegia solution distributes to the entire myocardium the ECG will change and eventually asystole will ensue. Cardioplegia lowers the metabolic rate of the heart muscle thereby preventing cell death during the ischemic period of time.

Physiology

Cardioplegic solution is the means by which the ischemic myocardium is protected from cell death. This is achieved by reducing myocardial metabolism through a reduction in cardic work load and by the use of hypothermia.

Chemically, the high potassium concentration present in most cardioplegic solutions decreases the membrane resting potential of cardiac cells. The normal resting potential
Resting potential
The relatively static membrane potential of quiescent cells is called the resting membrane potential , as opposed to the specific dynamic electrochemical phenomena called action potential and graded membrane potential....

 of ventricular myocytes is approximately -90mV. When extracellular cardioplegia displaces blood surrounding myocytes, the cell depolarizes more readily, i.e. at a less negative membrane potential. The depolarization causes contraction, intracellular calcium is sequestered by the sarcoplasmic reticulum via ATP dependent Ca2+ pumps, and the cell relaxes (diastole). However the high potassium concentration of the cardioplegia extracellular prevents repolarization.
The resting potential on ventricular myocardium is about -84mV at a extracellular K+ concentration of 5.4 mmol/l. Raising the K+ concentration to 16.2 mmol/l raises the resting potential to -60mV, a level at which muscle fibers are inexcitable to ordinary stimuli. When the resting potential approaches -50mV, sodium channels are inactivated resulting in a diastolic arrest of cardiac activity. Membrane inactivation gates, or h Na+ gates, are voltage dependent. The less negative the membrane voltage, the more h gates that tend to close. If partial depolarization is produced by a gradual process such as elevating the level of extracellular K+, then the gates have ample time to close and thereby inactivate some of the Na+ channels. When the cell is partially depolarized, many of the Na+ channels are already inactivated, and only a fraction of these channels are available to conduct the inward Na+ current during phase 0 depolarization.

Interestingly, the use of two other cations, Na+ and Ca2+, also can be used to arrest the heart. By removing extracellular Na+ from perfusate the heart will not beat because the action potential is dependent upon extracellular Na+ ions. However the removal of Na+ does not alter the resting membrane potential of the cell. Likewise removal of extracellular Ca2+ results in a decreased contractile force, and eventual arrest in diastole. An example of a low [K+] low [Na+] solution is HTK (Histidine-tryptophan-ketoglutarate
Histidine-tryptophan-ketoglutarate
Histidine-tryptophan-ketoglutarate, or Custodiol HTK solution is a high-flow, low-potassium preservation solution used for organ transplantation....

). Conversely, increasing extracellular Ca2+ concentration enhances contractile force. Elevating Ca2+ concentration to a high enough level results in cardiac arrest in systole. This unfortunate irreversible event is referred to as "stone-heart" or rigor.

Hypothermia is the other key component of most cardioplegic strategies. It is employed as another means to further lower myocardial metabolism during periods of ischemia. The Van't Hoff equation
Van't Hoff equation
The van 't Hoff equation also known as the Vukancic-Vukovic equation in chemical thermodynamics relates the change in temperature to the change in the equilibrium constant given the standard enthalpy change for the process...

 allow calculation that oxygen consumption will drop by 50% for every 10°C reduction in temperature. This Q10 (temperature coefficient)
Q10 (temperature coefficient)
The Q10 temperature coefficient is a measure of the rate of change of a biological or chemical system as a consequence of increasing the temperature by 10 °C. There are many examples where the Q10 is used, one being the calculation of the nerve conduction velocity and another being calculating the...

 effect combined with a chemical cardiac arrest can reduce myocardial oxygen consumption (MV02) by 97%.

and then cold cardioplegia is given into the heart through the aortic root. Blood supply to the heart arises from the aorta root through coronary arteries. is in diastole thus ensuring that the heart does not use up the valuable energy stores (ATP- adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

) . Blood is commonly added to this solution in varying amounts from 0-100%. Blood acts a buffer and also supplies nutrients to the heart during ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...

.

Once the procedure on the heart vessels (CABG- coronary artery bypass grafting) or inside the heart like valve replacement
Valve replacement
Valve replacement surgery is the replacement of one or more of the heart valves with either an artificial heart valve or a bioprosthesis . It is an alternative to valve repair.There are four procedures:...

 or correction of congenital heart defect
Congenital heart defect
A congenital heart defect is a defect in the structure of the heart and great vessels which is present at birth. Many types of heart defects exist, most of which either obstruct blood flow in the heart or vessels near it, or cause blood to flow through the heart in an abnormal pattern. Other...

 etc. is over the cross-clamp is removed and the isolation of the heart is terminated so that normal blood supply to the heart is restored and the heart starts beating again.

The cold fluid (usually at 4 °C) ensures that the heart cools down to an approximate temperature of around 15–20 °C thus slowing down the metabolism of the heart and thereby preventing damage to the heart muscle. This is further augmented by the cardioplegia component which is high in potassium

When solution is introduced into the aortic root
Aorta
The aorta is the largest artery in the body, originating from the left ventricle of the heart and extending down to the abdomen, where it branches off into two smaller arteries...

 (with an aortic cross-clamp
Aortic cross-clamp
An aortic cross-clamp is a surgical instrument used in cardiac surgery to clamp the aorta and separate the systemic circulation from the outflow of the heart....

 on the distal aorta to limit systemic circulation), this is called antegrade cardioplegia. When introduced into the coronary sinus
Coronary sinus
The coronary sinus is a collection of veins joined together to form a large vessel that collects blood from the myocardium of the heart. It is present in all mammals, including humans...

 it is called retrograde cardioplegia.

Ingredients

  • St. Thomas' Solution
  • Bretschneider Solution
  • University of Wisconsin Solution
  • Custodiol HTK
  • Celsior


There are many cardioplegic solutions of varying additives. The only vital additive in most solutions is potassium chloride in a 20-30 mmol/L concentration range. Other additives such as mannitol, sodium bicarbonate, procaine, et cetera, are of secondary importance. Below are several generic crystalloid cardioplegia solutions.

Induction

Sodium Bicarbonate 8.4% 31.25 mEq

Potassium Chloride 35 mEq

Mannitol 25% 3.75 g

Isolyte-S pH 7.4 133 mL



Add prior to use with induction:

Lidocaine 2% 62.5 mg

Nitroglycerin 500 mcg

Albumin 25% 12.5 g

Reperfusate

Mannitol 20% 37.5 mL

Isolyte-S pH 7.4 291.75 mL

CPD 30 mL

MSA/MSG 0.92M 70 mL



Add prior to use:

Sodium bicarbonate 62.5 mEq (62.5 mL)

Lidocaine 2% 125 mg (6.2 mL)

Nitroglycerin 1000 mcg (0.2 mL)

Ringers

Ringer’s Solution 1000 mL

Potassium Chloride 20 mEq

Magnesium Chloride 32 mEq

Mannitol 20% 10 g

Sodium Bicarbonate 8.4% 6.5 mEq



Add prior to use:

Procaine 10% 2.73 mL

Maintenance

Sodium Bicarbonate 8.4% 125 mEq

Potassium Chloride 25 mEq

Mannitol 25% 15 g

Isolyte-S pH 7.4 802 mL

See also

  • Cardiopulmonary bypass
  • Resting Potential
    Resting potential
    The relatively static membrane potential of quiescent cells is called the resting membrane potential , as opposed to the specific dynamic electrochemical phenomena called action potential and graded membrane potential....

  • Action Potential
    Action potential
    In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...

  • Membrane Potential
    Membrane potential
    Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...

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