Hypothermic Cardioplegic Solution Research Articles

Oxygen Nanocarriers for Improving Cardioplegic Solution Performance: Physico-Chemical Characterization.

Nanocarriers for oxygen delivery have been the focus of extensive research to ameliorate the therapeutic effects of current anti-cancer treatments and in the organ transplant field. In the latter application, the use of oxygenated cardioplegic solution (CS) during cardiac arrest is certainly beneficial, and fully oxygenated crystalloid solutions may be excellent means of myocardial protection, albeit for a limited time. Therefore, to overcome this drawback, oxygenated nanosponges (NSs) that can store and slowly release oxygen over a controlled period have been chosen as nanocarriers to enhance the functionality of cardioplegic solutions. Different components can be used to prepare nanocarrier formulations for saturated oxygen delivery, and these include native α-cyclodextrin (αCD), αcyclodextrin-based nanosponges (αCD-NSs), native cyclic nigerosyl-nigerose (CNN), and cyclic nigerosyl-nigerose-based nanosponges (CNN-NSs). Oxygen release kinetics varied depending on the nanocarrier used, demonstrating higher oxygen release after 24 h for NSs than the native αCD and CNN. CNN-NSs presented the highest oxygen concentration (8.57 mg/L) in the National Institutes of Health (NIH) CS recorded at 37 °C for 12 h. The NSs retained more oxygen at 1.30 g/L than 0.13 g/L. These nanocarriers have considerable versatility and the ability to store oxygen and prolong the amount of time that the heart remains in hypothermic CS. The physicochemical characterization presents a promising oxygen-carrier formulation that can prolong the release of oxygen at low temperatures. This can make the nanocarriers suitable for the storage of hearts during the explant and transport procedure.

Nanocarriers Loaded with Oxygen to Improve the Protection of the Heart to be Transplanted.

In the case of serious cardiovascular diseases, such as refractory heart failure, heart transplantation is the only possible intervention. Currently, the modes of organ transport in hypothermic cardioplegic solution do not allow the implantation of the heart beyond 4-5 hours from the explant. The heart being an organ with a greater consumption of oxygen and high metabolism than the brain, its transport in hypothermic cardioplegic solutions presents critical issues in terms of time and conservation. An ambitious goal of many researchers and clinicians is to minimize the hypoxia of the explanted heart and extend the permanence time in cardioplegic solution without damage from hypoxia. Adequately oxygenating the explanted organs may extend the usability time of the explanted organ. This challenge has been pursued for years with approaches that are often expensive, risky, and/or difficult to use. We propose to consider oxygenated nanocarriers releasing oxygen for a long time. In this way, it will also be possible to use organs from distant countries with respect to the recipient, thus exceeding the canonical 4-5 hours tolerated up to now. In addition to the lack of oxygen, the transplanted organ can undergo the accumulation of catabolites due to the lack of perfusion during transport. Therefore, nanocarriers can also be perfused in adequate solution during organ transportation. A better oxygenation improving the postoperative recovery of the transplanted heart will improve the recipient's quality of life.

Does Intermittent Aortic Cross Clamping Decrease the Incidence of Atrial Fibrillation after Coronary Bypass Surgery?

Atrial fibrillation (AF) is the most common arrhythmia after coronary artery bypass grafting (CABG). AF is a vexing problem that causes morbidity, prolongs hospital stay, and increases costs. Numerous factors have been suggested to play a role in the development of AF. The aim of this study was to evaluate the effect of intermittent aortic cross clamping (IACC) compared with hypothermic cardioplegic solution (HCS) in the development of postoperative AF. We evaluated data obtained from 345 patients undergoing CABG with HCS (HCS group, n = 212) and IACC (IACC group, n = 173) between April 2004 and August 2005. Diabetes mellitus was observed more often in the HCS group (P < .05), otherwise both groups had similar preoperative characteristics including sex, age, the number of distal anastomoses, left ventricle ejection fraction, history of myocardial infarction, and use of beta-blocker medication. The only statistically significant difference between the groups was higher postoperative Ca-antagonist use in the HCS group. Rates of postoperative AF, however, were significantly lower in the IACC group (21.52%) than that in the HCS group (11.05%; P < .01). Postoperative Ca-antagonist use in the HCS group and smoking in the IACC group were independent predictors of AF after CABG. The incidence of postoperative AF after CABG with IACC was reduced compared with HCS. IACC with ventricular fibrillation may exert a counteractive effect against AF.

The effect of supplementing hypothermic crystalloid cardioplegia with catalase plus allopurinol in the isolated rabbit heart.

The effect of adding allopurinol and catalase to hypothermic cardioplegia for ischemic-reperfusion injury was investigated in the isolated rabbit heart. Hearts were divided into two groups, namely: Group C (n = 7), which received a hypothermic crystalloid cardioplegic solution alone (4 degrees C), and group T (n = 7), which received the hypothermic cardioplegic solution with allopurinol (148 mumol/L)13 and catalase (37 nmol/L).12 The cardioplegic solution was infused continuously into the isolated hearts, which had been placed in ice-cold saline, during a 12 h preservation. Subsequently, the hearts were mounted on a noncirculating, nonpulsatile perfusion circuit using Krebs-Henseleit buffer solution at 37 degrees C for 1 h at a constant perfusion pressure of 75 mm Hg. The left ventricular developed pressure (LVDP), maximum rate of pressure change (max dp/dt), and percent recovery of coronary flow were higher, while the creatine phosphokinase concentration and left ventricular end diastolic pressure (LVEDP) were lower in group T. The tissue malondialdehyde concentration and water content were similar in both groups. Thus, cardiac function after a 12 h preservation was enhanced by the added combination of allopurinol and catalase to the cardioplegic solution, supporting its role in the prevention of free radical reperfusion injury in cardiac preservation.

Effect of supplementing cardioplegic solution with deferoxamine on reperfused human myocardium

Fourteen randomized patients undergoing myocardial revascularization were divided into group A standard hypothermic cardioplegic solution) and group B (the same cardioplegic solution supplemented with deferoxamine 1000 mg/L). In all patients myocardial biopsy specimens were obtained before ischemia and during reperfusion and were assessed for chemiluminescence (to indirectly determine oxygen-free radical activity) and for electron microscopic studies. Chemiluminescence in group A showed a photoemission of 36.5 +/- 1.5 cpm/mg protein X10(-3) for the preischemia samples and 72 +/- 5.7 cpm/mg protein X10(-3) for the reperfusion samples (p less than 0.01). In the patients who received deferoxime (group B), values for chemiluminescence for preischemia and reperfusion samples were not significantly different. Electron microscopic studies showed a significant increase in grade 4 (severely damaged) mitochondria in reperfusion biopsy specimens from both groups as compared with preischemia samples. However, reperfusion samples from group B showed a better preservation of myocardial cells with marked reduction of grade 4 (severely damaged) mitochondria. These results support the hypothesis that oxygen-free radicals are responsible in part for the production of reperfusion injury in the human heart. They suggest that this mechanism may be at least partially controlled by adding an iron chelating agent such as deferoxime.

The Electrophysiological Effects of Calcium Channel Blockade During Standard Hyperkalemic Hypothermic Cardioplegic Arrest

The addition of calcium channel-blocking agents to a standard hyperkalemic hypothermic cardioplegic solution has been examined both experimentally and clinically. None of these studies, however, have investigated the effect of calcium blockade during cardioplegic arrest on the specialized cardiac conduction tissues and on the subsequent development of arrhythmias after arrest. The present study examined the effect of adding nifedipine to standard cardioplegic solution administered in a canine experimental preparation modeled on routine clinical techniques. The time to and duration of electrical arrest following the administration of cardioplegia and the functional electrophysiological variables before and after arrest were measured using a 32-channel data acquisition system. The addition of nifedipine shortened the time to electrical arrest and prolonged the duration of arrest compared with standard potassium cardioplegic solution alone, without a deleterious effect on conduction function immediately after arrest. The occurrence of low-amplitude electrical activity (LEA) in both atria and ventricles during arrest was significantly reduced by the addition of nifedipine, thereby suggesting a possible correlation between LEA and calcium-mediated conduction occurring under conditions of standard cardioplegic arrest.

The Importance of Monitoring Intramyocardial Temperature during Hypothermic Myocardial Protection

In 50 patients undergoing cardiac operation, hypothermic cardioplegic solution was infused into the root of the aorta immediately after aortic cross-clamping. Cardiac standstill was achieved within 1 to 3 minutes. However, monitoring of intramyocardial temperature with a needle thermistor revealed that such core cooling is unpredictable (the intramyocardial temperature achieved ranged from 7° to 33°C), unstable (this temperature can rise at more than 0.5°C per minute), and uneven (a difference of up to 17°C was observed between the intramyocardial temperature of the anterior and posterior left ventricular sites). The area supplied by the stenotic coronary artery was least protected. Monitoring of intramyocardial temperature enables one to know when supplementary cooling is indicated. We conclude that widespread differences in this temperature during cardiac operation make monitoring advisable for optimal myocardial protection.

Long-term cardiac arrest by cardioplegic coronary perfusion (author's transl)

The Mg++ aspartate-procaine-cardioplegia has been proven in animal experiments as well as from 1970 til 1975 in more than 1000 open-heart-procedures by a myocardial temperature of 32 degrees C and aortic crossclamping time up to 40 minutes superior to all other known procedures of cardiac preservations. To guarantee a safe myocardial protection of the arrested heart for a remarkable longer period of total ischemia, we further developed the cardioplegic technique in the animal lab, and use it now clinically. The arrest is induced by cardioplegia (Mg++ aspartate-procaine), than the arrested heart is cooled down to 15-20 degrees C by cardioplegic coronary perfusion maintaining the oxidative metabolism. The perfusion is stopped. The begin of ischemia is still under normal ATP-levels and continuous cardioplegia. 1. Crossclamping of the aorta; 2. cardioplegic induced cardiac arrest by Mg++ aspartate-procaine (Kirsch); 3. Surface cooling of the heart; 4. Coronary perfusion by hypothermic cardioplegic solution (8-10 min, flow 80-120 ml/min, perfusion pressure maximal 30 mmHg). Perfusate: O2-saturated, erythrocyte free, 6% hydroxyethyl starch solution added 2 mM Mg++ aspartate, 4 mM procaine, 50 mM Na+, 5 mM K+, 0,5 mM Ca++, 25 mM HCO3-, 10 mM glucose, 200 mM mannitol, 250 mg/l 6-methylprednisolone. 84 patients (29 ACVB; 55 valve replacements); crossclamping time: 71 min (SD 22); total time of ischemia: 57 min (SD 18; max 96, min. 27 min); reperfusion time restoring normal excitation-contraction of the heart: 3 min (SD 2); weaning off bypass: 23 min (SD 14). Hemodynamic 12 h postop.: SO2 venous 76% (SD 6). No sympathicomimetics were used. Only 30% of myocardial ATP is splitted after 120 min of cardiac arrest. Electron microscopic findings show only small, reversible alterations of fine structure.