Effects Of Cardioplegic Solutions Research Articles

Impact of Custodiol-N cardioplegia on acute kidney injury after cardiopulmonary bypass.

Myocardial protection during cardiopulmonary bypass (CPB) can be achieved using cardioplegic solutions. Although, acute kidney injury (AKI) is a common complication following CPB, the effects of cardioplegic solutions on AKI have rarely been investigated. Within this study, the effects of the cardioplegic solutions histidine-tryptophan-ketoglutarate (HTK; Custodiol) and HTK-N (Custodiol-N) on AKI in a large animal model were compared. Therefore, Landrace pigs underwent median sternotomy, CPB at 34°C, 90minutes of cardiac arrest and 120minutes of reperfusion. Animals were randomized for single-shot cardioplegia with either HTK (n=10) or HTK-N (n=10). Renal biopsies and sera were analyzed to determine AKI biomarkers and apoptosis. Compared to HTK, HTK-N induced a decreased extent of proximal tubule swelling (48.3±1.6µm vs 52.3±1.1µm, P=.05) and decreased cytochrome c release (0.26±0.04 vs 0.46±0.08, P=.04) without reaching statistical significance due to Bonferroni correction. Comparing baseline and postreperfusion levels, the hemoglobin (Hb) and blood calcium levels were lower in HTK-N (Hbbaseline : 6.0±0.6mmol/L, Hbreperfusion : 6.2±0.7mmol/L, P=.12; Ca2+baseline : 1.36±0.05mmol/L, Ca2+reperfusion : 1.28±0.05mmol/L, P=.16) compared to the HTK group (Hbbaseline : 5.9±0.4mmol/L, Hbreperfusion : 4.7±0.8mmol/L, P<.01; Ca2+baseline : 1.34±0.07mmol/L, Ca2+reperfusion : 1.24±0.06mmol/L, P<.01). The present study showed that HTK-N could positively affect the kidney during CPB. Hb and calcium levels were stabilized. A statistical trend was found showing that AKI-related proximal tubule swelling and cytochrome c release were diminished.

Efficiency of cardioplegic solutions containing L-arginine and L-aspartic acid

In experiments on rats we studied the effects of cardioplegic solutions with L-aspartic acid or L-arginine on functional recovery and metabolism of isolated working heart after 40-min normothermal global ischemia and 30-min reperfusion. After reperfusion of the hearts preventively protected with cardioplegic solution containing L-aspartic acid or L-arginine, coronary flow decreased in comparison with the initial values. As a component of cardioplegic solution, L-arginine was less efficient in recovery of contractility and cardiac output of the hearts in comparison with L-aspartic acid. In hearts protected with L-aspartic acid, the postischemic levels of ATP and phosphocreatine were significantly higher, and the level of lactate was significantly lower than in hearts protected with L-arginine. In comparison with L-arginine, L-aspartic acid is a more efficient component of cardioplegic solution in protection of the heart from metabolic and functional damages caused by global ischemia and reperfusion.

Effects of cardioplegic solutions on the vasoreactivity of the internal mammary artery

Background. During free internal mammary artery grafting, cardioplegia administration can be performed through the internal mammary artery. The present study examined whether cardioplegic solutions produce arterial graft constriction and functional endothelial damage. Methods. Forty internal mammary artery segments from 10 patients were incubated in Krebs solution (n = 10), University of Wisconsin solution (n = 10), Broussais Hospital solution (n = 10), or blood cardioplegia (n = 10). Results. There was a significant difference in sensitivity to norepinephrine between segments in Krebs solution and those in University of Wisconsin solution or Broussais Hospital solution but not segments in blood cardioplegia. There was a significant difference in relaxation to acetylcholine between segments in Krebs solution and those in the three other cardioplegic solutions and between those in blood cardioplegia and segments in University of Wisconsin solution or Broussais Hospital solution. There was no significant difference in relaxation to sodium nitroprusside between segments in any of the solutions. Conclusions. These experiments suggest that storage in the different cardioplegic solutions studied does not preserve the initial vasoreactivity of the internal mammary artery. However, blood cardioplegia appears to be less deleterious in regard to endothelial and myogenic vascular function.

Developmental differences in cytosolic calcium accumulation associated with surgically induced global ischemia: Optimization of cardioplegic protection and mechanism of action

Objective: The effect of cardioplegic solutions with high concentrations of potassium or magnesium (or both) on cytosolic calcium accumulation was investigated with fura-2 in isolated perfused mature ( n = 24) and aged ( n = 24) rabbit hearts. Methods: We compared cytosolic calcium accumulation before ischemia (control), during 30 minutes of ischemia and 30 minutes of reperfusion under global ischemia, or after treatment with potassium (20 mmol/L), magnesium (20 mmol/L), or both. Results: Cytosolic calcium accumulation was increased during global ischemia in the mature heart (from 178.7 ± 24.2 in the control group to 393.6 ± 25.5 nmol/L; p < 0.005) and in the aged heart (from 187.4 ± 18.7 in the control group to 501.0 ± 46.1 nmol/L; p < 0.005). Potassium reduced cytosolic calcium accumulation during ischemia in both the mature and aged hearts (300.9 ± 23.2 and 365.2 ± 27.7 nmol/L, respectively; p < 0.05 vs global ischemia). Magnesium and potassium/magnesium completely controlled cytosolic calcium accumulation in the mature heart (198.7 ± 27.5 nmol/L; p < 0.01 vs global ischemia and p < 0.05 vs potassium: 182.3 ± 22.7 nmol/L; p < 0.05 vs global ischemia and potassium, respectively). Magnesium and potassium/magnesium attenuated cytosolic calcium accumulation in the aged heart (261.3 ± 26.7, 262.3 ± 25.2 nmol/L, respectively; p < 0.01 vs global ischemia). These changes in cytosolic calcium accumulation correlated with improved postischemic ventricular function. To investigate the mechanism(s) of magnesium-supplemented cardioplegic inhibition of cytosolic calcium accumulation, we performed parallel studies ( n = 43) using nifedipine, ryanodine, and dimethylthiourea. Nifedipine with or without ryanodine reduced cytosolic calcium accumulation. Dimethylthiourea did not alter cytosolic calcium accumulation during global ischemia. Our results suggest that cytosolic calcium accumulation during global ischemia was mainly increased via the sarcolemmal 1-type calcium channel and the sarcoplasmic reticulum calcium-release channel. The modulating action of potassium/magnesium cardioplegia on cytosolic calcium accumulation during ischemia would appear to act through the inhibition of the myocardial 1-type calcium channel and the sarcoplasmic reticulum calcium-release channel. Conclusion: Senescent cardiac dysfunction correlates with increased ischemia-induced cytosolic calcium accumulation. Magnesium-supplemented potassium cardioplegia ameliorates this age-related phenomenon at normothermia and may have important implications in myocardial protection in the elderly population. (J T horac C ardiovasc S urg 1996;112:175-84)

Cytotoxic effects of cardioplegic solutions and cytoprotective effects of insulin on immature cardiac myocytes during hypothermic preservation

AbstractThe purpose of this study was to evaluate the functional and biochemical effects of cardioplegic solutions on immature cardiac myocytes incubated under hypothermic conditions. In addition, the effects of insulin as an additive were evaluated in each solution. Cardiac myocytes were isolated from neonatal rat ventricles and cultured for four days; 12.5 x 105myocytes/flask were then incubated at 4 °C for three, six and 12 hours in three types of cardioplegic solutions—glucose-potassium solution (glucose: 50 gm/l, NaHCO3: 20 mEq, KCl: 20 mEq), lactated Ringer's solution (KCl: 20 mEq) and St. Thomas' Hospital solution. After each hypothermic incubation, enzymes were measured in the incubation solutions. The myocytes were then cultured for an additional 24 hours at 37 °C to evaluate the recovery of the myocyte beating rate. In the Ringer's group, the recovery ratio of the myocyte beating rate was complete at three hours, then decreased to 48.8 percent of control (beating rate prior to hypothermic incubation) at 12 hours. The glucose-potassium and St. Thomas' groups had significantly lower recovery ratios than the Ringer's group, beginning at three hours (63.4, 72.9, 95.6 percent, respectively). Release of enzymes (CPK and LDH) in the Ringer's group gradually increased and at 12 hours was 29.0 mIU/flask and 260.0 mIU/flask, respectively. The St. Thomas' group, in contrast, had significantly increased values for CPK at 12 hours to 116.0 mIU/flask, and the greatest increases of both enzymes were observed in the glucose-potassium group at 12 hours (CPK: 115.5, LDH: 1163.9). By addition of 20 IU/l insulin, marked improvements were observed in the Ringer's and glucose-potassium groups both functionally and biochemically. Thus, the lactated Ringer's solution had the least cytotoxic effects that might be suitable for a basic solution of various cardioplegic solutions during the neonatal period, and insulin may have beneficial effects on immature myocardium under hypothermic conditions.

The Effect of Cardioplegic Solution on Coronary Artery

The Effect of Cardioplegic Solution on Coronary Artery

Effects of cardioplegic solutions and their components on human saphenous vein contractility

Cardioplegic solution administration into the vein graft is an established method to ensure cardioplegic distribution beyond coronary artery stenoses. The ultrastructural demonstration of severe endothelial damage after cardioplegic exposure suggests that intravenous cardioplegic administration can contribute to early and late graft thrombosis. The direct effect on human saphenous vein contractility of three cardioplegic solutions and their components was compared. A solution with 30 mmol/L K + and 82 mmol/L Na + produced intense venoconstriction. Lowering the potassium level to 10 mmol/L and increasing the sodium level to 92 mmol/L reduced its vasoconstricting action. A third solution with 16 mmol/L K +, 16 mmol/L Mg 2+, and lidocaine caused venodilatation. Analysis of the single component effects showed that high potassium level, low sodium level, and the addition of lidocaine produced concentration-dependent vasoconstriction. High magnesium concentration resulted in vasodilatation. The present data suggest that cardioplegic solution composition may cause marked vasomotor effects on saphenous vein and thus influence its endothelial integrity. In the search for an “ideal solution” to the cardioplegic controversy, a venoconstrictor infusate should be avoided to improve patency rates of coronary artery bypass grafts.

Microcirculatory dysfunction following perfusion with hyperkalemic, hypothermic, cardioplegic solutions and blood reperfusion. Effects of adenosine.

Cardioplegic solutions have been used to enhance myocardial preservation during cardiac surgery. The benefits derived from preventing myocardial ischemia with cardioplegic solutions may, however, be countered by tissue damage that occurs when the myocardium is reperfused with oxygenated blood. Furthermore, cardioplegia-induced endothelial dysfunction may contribute to depressed myocardial function postoperatively. The endothelium of coronary arteries and vein grafts is damaged by crystalloid cardioplegic solutions. There is less known about the effects of cardioplegic solutions on the microvasculature. The hypothesis that microvascular damage occurs following perfusion with hyperkalemic, crystalloid, cardioplegic solutions and blood reperfusion, leading to decreased blood flow and increased neutrophil accumulation, was tested in a model system. Intravital microscopic observations were performed during a 20-minute perfusion of the hamster cremaster muscle with cardioplegic solutions (10 degrees C) via the femoral artery with the iliac occluded and during a subsequent 2-hour blood reperfusion period (iliac open). Arteriolar vasoconstriction (27% decrease in diameter, p less than 0.05) and a 25% decrease in the density of perfused capillaries (p less than 0.05) occurred during reperfusion in hamsters receiving crystalloid cardioplegic solution (16 meq K+) compared to control hamsters (no cardioplegic solution given). Neutrophils accumulated on venular endothelium in treated animals (250% increase, p less than 0.05) and extravascularly (myeloperoxidase levels 2.0 +/- 0.4 U/g versus 1.3 +/- 0.3 U/g in control, p less than 0.05). The addition of adenosine (10(-4) M) and albumin (2 g%) to the cardioplegic perfusate, accompanied by the administration of adenosine (10(-4) M) during reperfusion, produced arteriolar vasodilation (34% diameter increase, p less than 0.05) and inhibited extravascular neutrophil accumulation (myeloperoxidase level of 1.5 +/- 0.2 U/g, p greater than 0.05 versus control). Capillary perfusion, however, was still significantly diminished (28% decrease, p less than 0.05.) We conclude that injury manifest by decreased microvascular blood flow and increased neutrophil accumulation in tissues occurs after perfusion with hypothermic, hyperkalemic, crystalloid cardioplegic solutions and blood reperfusion. Adenosine seems to partially attenuate this injury by dilating arterioles and decreasing extravascular neutrophil accumulation.

活動電位に対する心筋保護液の影響

活動電位に対する心筋保護液の影響

Effects of cardioplegic solutions on conductive coronary arteries

The effects of two cardioplegic solutions (CPSs) on isolated, superfused, bovine coronary arteries were compared with those produced by changes in composition of standard Krebs medium. High potassium, low sodium content or the addition of albumin produced vasoconstriction; high magnesium, high glucose content or the addition of mannitol led to vasodilatation. In most cases hypothermia slightly reduced vasoconstriction and enhanced vasodilatation. The action of the two CPSs is the result of the interaction of these basic effects. The results suggest that the vasomotor reactions of coronary arteries to CPS may affect the delivery of the CPS to the myocardium and exert a critical influence on successful cardioplegia.