Cardioplegia

Last updated
Cardioplegia
ICD-9-CM 39.63
MeSH D006324

Cardioplegia is a solution given to the heart during cardiac surgery, to minimize the damage caused by myocardial ischemia while the heart is paused.

Contents

Overview

The word cardioplegia combines the Greek cardio meaning the "heart", and plegia "paralysis". [1] 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. One of the first physicians to use the term cardioplegia was Dr. Lam in 1957. However his work on the myocardial protection was preceded serendipitously by Sydney Ringer in the late 1800s. At that time Ringer and colleagues noticed that tap water had the ability to increase contractility of the heart, likely due to its high calcium content. Sydney Ringer also commented on the importance of potassium ion concentration on depressing intrinsic heart rhythm. Through a series of experiments performed on frog and canine hearts, reversible arrest was achieved with potassium ions with the consequence of ventricular fibrillation and observed myocardial necrosis. These early experiments started nearly 50 years of work that has led to variety of perfusion strategies available today.

The main goals of hypothermic cardioplegia are:

  1. Immediate and sustained electromechanical quiescence
  2. Rapid and sustained homogeneous myocardial cooling
  3. Maintenance of therapeutic additives in effective concentrations
  4. Periodic washout of metabolic inhibitors [2]

The most common procedure for accomplishing asystole is infusing cold cardioplegic solution into the coronary circulation. This process protects the myocardium, or heart muscle, from damage during the period of ischemia. [3]

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, 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 cardiac 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 of ventricular myocytes is about -90 mV. [4] When extracellular cardioplegia displaces blood surrounding myocytes, the membrane voltage becomes less negative and the cell depolarizes more readily. 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 −84 mV at an extracellular K+ concentration of 5.4 mmol/L. Raising the K+ concentration to 16.2 mmol/L raises the resting potential to −60 mV, a level at which muscle fibers are inexcitable to ordinary stimuli. When the resting potential approaches −50 mV, sodium channels are inactivated, resulting in a diastolic arrest of cardiac activity. [5] 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 is available to conduct the inward Na+ current during phase 0 depolarization. [6]

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 histidine-tryptophan-ketoglutarate. 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 allows calculation that oxygen consumption will drop by 50% for every 10 °C reduction in temperature. This Q10 effect combined with a chemical cardiac arrest can reduce myocardial oxygen consumption (MVO2) by 97%. [7]

Cold cardioplegia is given into the heart through the aortic root. Blood supply to the heart arises from the aortic root through coronary arteries. Cardioplegia in diastole ensures that the heart does not use up the valuable energy stores (adenosine triphosphate). Blood is commonly added to this solution in varying amounts from 0 to 100%. Blood acts a buffer and also supplies nutrients to the heart during ischemia.

Once the procedure on the heart vessels (coronary artery bypass grafting) or inside the heart such as valve replacement or correction of congenital heart defect, etc. is over, the cross-clamp is removed and the isolation of the heart is terminated, so 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 a 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 (with an aortic cross-clamp on the distal aorta to limit systemic circulation), this is called antegrade cardioplegia. When introduced into the coronary sinus, it is called retrograde cardioplegia. [8]

Whilst there are several cardioplegic solutions commercially available; there are no clear advantages of one cardioplegic solution over another. Some cardioplegias, such as del Nido or Histidine-Tryptophan-Ketoglutamate solutions, offer an advantage over blood and other crystalloid cardioplegia as they only require one administration during short cardiac surgeries, compared to multiple doses required by blood and other crystalloid. [9]

Alternatives to cardioplegia

In coronary surgery, there are various alternatives to cardioplegia to perform the operation. One is off-pump coronary surgery where the surgery is done without the need of a cardiopulmonary bypass machine. Another is to use cross-clamp fibrillation whereby the heart fibrillates whilst on cardiopulmonary bypass in order to perform the distal anastomoses. [10]

History of Cardioplegia

Cardiac surgical cases were performed with the aid of a cardiopulmonary pump, without cardioplegia or other means of protecting the heart. High mortality rates due to cardiac injury though, made surgeons to look on how to protect the heart. In 1955 D.G. Melrose suggested ‘’elective cardiac arrest’’, a technique already used for other purposes, in order to protect the heart from ischemia- since cardiac muscle is not working, oxygen demands should be low. In the 1960’s other groups introduced ice slur applied all over the heart’s surface. The rationale was to decrease the temperature of the heart, thus to reduce oxygen demands further. [11]

The next decades many investigators (Bretschneider, Kirch and others) came up with various solutions that could pause the heart without damaging cardiac muscle. In the same period, surgeons found out delivery roots for cardioplegia, other than the commonly used antegrade. Buckberg in North America and Menasche in Europe, introduced retrograde cardioplegia method, via a catheter inserted in Coronary Sinus and thus perfusing the heart in a retrograde fashion. [11]

See also

Related Research Articles

<span class="mw-page-title-main">Coronary circulation</span> Circulation of blood in the blood vessels of the heart muscle (myocardium)

Coronary circulation is the circulation of blood in the arteries and veins that supply the heart muscle (myocardium). Coronary arteries supply oxygenated blood to the heart muscle. Cardiac veins then drain away the blood after it has been deoxygenated. Because the rest of the body, and most especially the brain, needs a steady supply of oxygenated blood that is free of all but the slightest interruptions, the heart is required to function continuously. Therefore its circulation is of major importance not only to its own tissues but to the entire body and even the level of consciousness of the brain from moment to moment. Interruptions of coronary circulation quickly cause heart attacks, in which the heart muscle is damaged by oxygen starvation. Such interruptions are usually caused by coronary ischemia linked to coronary artery disease, and sometimes to embolism from other causes like obstruction in blood flow through vessels.

<span class="mw-page-title-main">Ventricular fibrillation</span> Rapid quivering of the ventricles of the heart

Ventricular fibrillation is an abnormal heart rhythm in which the ventricles of the heart quiver. It is due to disorganized electrical activity. Ventricular fibrillation results in cardiac arrest with loss of consciousness and no pulse. This is followed by sudden cardiac death in the absence of treatment. Ventricular fibrillation is initially found in about 10% of people with cardiac arrest.

<span class="mw-page-title-main">Coronary artery bypass surgery</span> Surgical procedure to restore normal blood flow to an obstructed coronary artery

Coronary artery bypass surgery, also known as coronary artery bypass graft, is a surgical procedure to treat coronary artery disease (CAD), the buildup of plaques in the arteries of the heart. It can relieve chest pain caused by CAD, slow the progression of CAD, and increase life expectancy. It aims to bypass narrowings in heart arteries by using arteries or veins harvested from other parts of the body, thus restoring adequate blood supply to the previously ischemic heart.

<span class="mw-page-title-main">Cardiopulmonary bypass</span> Technique that temporarily takes over the function of the heart and lungs during surgery

Cardiopulmonary bypass (CPB) or heart-lung machine also called the pump or CPB pump is a machine that temporarily takes over the function of the heart and lungs during open-heart surgery by maintaining the circulation of blood and oxygen throughout the body. As such it is an extracorporeal device.

<span class="mw-page-title-main">Cardiac muscle</span> Muscular tissue of heart in vertebrates

Cardiac muscle is one of three types of vertebrate muscle tissues, the others being skeletal muscle and smooth muscle. It is an involuntary, striated muscle that constitutes the main tissue of the wall of the heart. The cardiac muscle (myocardium) forms a thick middle layer between the outer layer of the heart wall and the inner layer, with blood supplied via the coronary circulation. It is composed of individual cardiac muscle cells joined by intercalated discs, and encased by collagen fibers and other substances that form the extracellular matrix.

<span class="mw-page-title-main">Troponin</span> Protein complex

Troponin, or the troponin complex, is a complex of three regulatory proteins that are integral to muscle contraction in skeletal muscle and cardiac muscle, but not smooth muscle. Measurements of cardiac-specific troponins I and T are extensively used as diagnostic and prognostic indicators in the management of myocarditis, myocardial infarction and acute coronary syndrome. Blood troponin levels may be used as a diagnostic marker for stroke or other myocardial injury that is ongoing, although the sensitivity of this measurement is low.

<span class="mw-page-title-main">Cardiac conduction system</span> Aspect of heart function

The cardiac conduction system transmits the signals generated by the sinoatrial node – the heart's pacemaker, to cause the heart muscle to contract, and pump blood through the body's circulatory system. The pacemaking signal travels through the right atrium to the atrioventricular node, along the bundle of His, and through the bundle branches to Purkinje fibers in the walls of the ventricles. The Purkinje fibers transmit the signals more rapidly to stimulate contraction of the ventricles.

Aortic valve replacement is a cardiac surgery procedure whereby a failing aortic valve is replaced with an artificial heart valve. The aortic valve may need to be replaced because of aortic regurgitation, or if the valve is narrowed by stenosis.

<span class="mw-page-title-main">Repolarization</span> Change in membrane potential

In neuroscience, repolarization refers to the change in membrane potential that returns it to a negative value just after the depolarization phase of an action potential which has changed the membrane potential to a positive value. The repolarization phase usually returns the membrane potential back to the resting membrane potential. The efflux of potassium (K+) ions results in the falling phase of an action potential. The ions pass through the selectivity filter of the K+ channel pore.

Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia and tissue death (necrosis).

The intra-aortic balloon pump (IABP) is a mechanical device that increases myocardial oxygen perfusion and indirectly increases cardiac output through afterload reduction. It consists of a cylindrical polyurethane balloon that sits in the aorta, approximately 2 centimeters (0.79 in) from the left subclavian artery. The balloon inflates and deflates via counter pulsation, meaning it actively deflates in systole and inflates in diastole. Systolic deflation decreases afterload through a vacuum effect and indirectly increases forward flow from the heart. Diastolic inflation increases blood flow to the coronary arteries via retrograde flow. These actions combine to decrease myocardial oxygen demand and increase myocardial oxygen supply.

<span class="mw-page-title-main">Amrinone</span> Chemical compound

Amrinone, also known as inamrinone, and sold as Inocor, is a pyridine phosphodiesterase 3 inhibitor. It is a drug that may improve the prognosis in patients with congestive heart failure. Amrinone has been shown to increase the contractions initiated in the heart by high-gain calcium induced calcium release (CICR). The positive inotropic effect of amrinone is mediated by the selective enhancement of high-gain CICR, which contributes to the contraction of myocytes by phosphorylation through cAMP dependent protein kinase A (PKA) and Ca2+ calmodulin kinase pathways.

The sodium-calcium exchanger (often denoted Na+/Ca2+ exchanger, exchange protein, or NCX) is an antiporter membrane protein that removes calcium from cells. It uses the energy that is stored in the electrochemical gradient of sodium (Na+) by allowing Na+ to flow down its gradient across the plasma membrane in exchange for the countertransport of calcium ions (Ca2+). A single calcium ion is exported for the import of three sodium ions. The exchanger exists in many different cell types and animal species. The NCX is considered one of the most important cellular mechanisms for removing Ca2+.

Histidine-tryptophan-ketoglutarate, or Custodiol HTK solution, is a high-flow, low-potassium preservation solution used for organ transplantation. The solution was initially developed by Hans-Jürgen Bretschneider.

The following outline is provided as an overview of and topical guide to cardiology, the branch of medicine dealing with disorders of the human heart. The field includes medical diagnosis and treatment of congenital heart defects, coronary artery disease, heart failure, valvular heart disease and electrophysiology. Physicians who specialize in cardiology are called cardiologists.

<span class="mw-page-title-main">Coronary perfusion pressure</span>

Coronary perfusion pressure (CPP) refers to the pressure gradient that drives coronary blood pressure. The heart's function is to perfuse blood to the body; however, the heart's own myocardium must, itself, be supplied for its own muscle function. The heart is supplied by coronary vessels, and therefore CPP is the blood pressure within those vessels. If pressures are too low in the coronary vasculature, then the myocardium risks ischemia with subsequent myocardial infarction or cardiogenic shock.

Cardiac physiology or heart function is the study of healthy, unimpaired function of the heart: involving blood flow; myocardium structure; the electrical conduction system of the heart; the cardiac cycle and cardiac output and how these interact and depend on one another.

<span class="mw-page-title-main">Cariporide</span> Chemical compound

Cariporide is a selective Na+/H+ exchange inhibitor. Cariporide has been shown to actively suppress the cell death caused by oxidative stress.

<span class="mw-page-title-main">Rottlerin</span> Chemical compound

Rottlerin (mallotoxin) is a polyphenol natural product isolated from the Asian tree Mallotus philippensis. Rottlerin displays a complex spectrum of pharmacology.

Pedro J. del Nido is a Chilean pediatric cardiac surgeon who was the 95th president of the American Association for Thoracic Surgery (AATS), succeeding David J. Sugarbaker and preceding Joseph S. Coselli.

References

  1. ↑ "Definition: Cardioplegia from Online Medical Dictionary". Archived from the original on 2007-12-09. Retrieved 2008-06-19.
  2. ↑ Kaplan J Cardiac Anesthesia. 3rd Edition. W.B Saunders Company. 1993
  3. ↑ "Cold Crystalloid Cardioplegia" Archived 2012-01-07 at the Wayback Machine Hans J. Geissler* and Uwe Mehlhorn, Department of Cardiothoracic Surgery, University of Cologne
  4. ↑ Aaron. "CV Physiology: Membrane Potentials". Archived from the original on 21 November 2016. Retrieved 8 November 2016.
  5. ↑ Hensley F, Martin D. A Practical Approach to Cardiac Anesthesia. 2nd Edition. Little, Brown and Company. 1995
  6. ↑ Berne R, Levy M. Physiology. 3rd Edition. Mosby St. Louis 1993.
  7. ↑ Gravlee G, Davis R, Utley J. Cardiopulonary Bypass Principles and Practice. Williams & Williams Baltimore 1993.
  8. ↑ "Cardioplegia Delivery Systems" Archived September 4, 2006, at the Wayback Machine hosted on Washington University in St. Louis, website
  9. ↑ Reynolds AC, Asopa S, Modi A, King N. HTK versus multidose cardioplegias for myocardial protection in adult cardiac surgery: A meta-analysis. J Card Surg. 2021 Feb 5.
  10. ↑ Ariyaratnam, Priyadharshanan; Cale, Alexander; Loubani, Mahmoud; Cowen, Michael E. (2019-12-01). "Intermittent Cross-Clamp Fibrillation Versus Cardioplegic Arrest During Coronary Surgery in 6,680 Patients: A Contemporary Review of an Historical Technique". Journal of Cardiothoracic and Vascular Anesthesia. 33 (12): 3331–3339. doi:10.1053/j.jvca.2019.07.126. ISSN   1053-0770. PMID   31401206. S2CID   199540471.
  11. 1 2 Kouchoukos et al. 2013, p. 134.

Sources

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