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. 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. 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. 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%. 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. 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. == Alternatives to cardioplegia ==