Heterogeneous distribution of cardioplegic solution in pigs

Septal dyskinesia in the left ventricle is detected frequentlyin many patients after open-heart surgery. The present studywas designed to determine whether the antegrade delivery ofcardioplegic solution to the regional wall categorized in echocardiographyis homogeneous, and whether the distribution to the septal walldiffers from that to the lateral wall in the absence of coronaryartery disease. To assess these hypotheses quantitatively, radioactivemicrospheres were mixed into the cardioplegic solution and infusedby an antegrade method in eight normal pigs. The cardioplegicdistribution to the septal wall was significantly less thanto the lateral wall close to the base of the left ventricle(P<0.05). Therefore, antegrade perfusion of cardioplegicsolution was non-uniformly distributed to the regional and transmuralwall of normal pig hearts. Absence of functional correlationwas a limitation of this study. However, these findings suggestthat inadequate protection of the ventricular septum by antegradecardioplegia might be an explanation for the abnormalities ofseptal wall motion after open-heart surgery. Br J Anaesth 2001; 86: 427–30     

Effects of left ventricular venting and distention during heterogenous distribution of cardioplegic solution

The effects of left ventricular venting and distention on myocardial protection during heterogenous distribution of cardioplegic solution remain undefined. This study was undertaken to determine if left ventricular venting enhances and distention impairs myocardial cooling and recovery of global and regional left ventricular function. Twenty-one pigs were placed on cardiopulmonary bypass and subjected to 80 minutes of ischemic arrest with the mid-left anterior descending artery occluded. Hearts were protected with multidose potassium (25 mEq/L) crystalloid cardioplegic solution supplemented with topical (4 degrees C) and systemic (28 degrees C) hypothermia. During arrest, the left ventricle was vented in seven pigs, seven pigs were not vented, and seven others had systemic pump blood infused into the left ventricle to maintain an end-diastolic pressure of 15 mm Hg. Parameters measured included left ventricular temperature, stroke work index, compliance (end-diastolic pressure-end-diastolic volume curves) and wall motion scores (two-dimensional echocardiography). Distended hearts had the lowest mean left ventricular temperature beyond the left anterior descending arterial occlusion (10.1 degrees +/- 1.8 degrees C distended [p less than 0.025 from vented and nonvented groups] versus 14.2 degrees +/- 0.7 degrees C vented versus 15.5 degrees +/- 1.2 degrees C nonvented), the highest postischemic stroke work index (0.78 +/- 0.09 gm-m/kg distended versus 0.62 +/- 0.07 gm-m/kg vented versus 0.66 +/- 0.07 gm-m/kg nonvented at end-diastolic pressure = 10 mm Hg), and the best wall motion scores (0.7 +/- 0.04 distended [p less than 0.025 from vented and nonvented groups] versus 5.5 +/- 1.80 vented versus 4.8 +/- 1.20 nonvented). Postischemic end-diastolic pressure-end-diastolic volume curves were unchanged from preischemic values in each group. We conclude that during heterogenous cardioplegic arrest, left ventricular venting offers no additional myocardial protection and may negate the beneficial effects of moderate (end-diastolic pressure = 15 mm Hg) left ventricular distention.     

Myocardial protection in the neonatal heart. A comparison of topical hypothermia and crystalloid and blood cardioplegic solutions

Myocardial protection achieved during 2 hours of ischemic arrest was evaluated in 45 isolated, blood perfused, neonatal (1 to 5 days) piglet hearts. Comparisons were made among five methods of myocardial protection: Group I, topical cooling; Group II, hyperosmolar (450 mOsm) low-calcium (0.5 mmol/L) crystalloid cardioplegia; Group III, St. Thomas' Hospital cardioplegia; Group IV, cold blood cardioplegia with potassium (21 mmol/L), citrate-phosphate-dextrose (calcium level 0.6 mmol/L), and tromethamine; and Group V, cold blood cardioplegia with potassium alone (16 mmol/L) (calcium level 1.2 mmol/L). Hemodynamic recovery (percent of the preischemic stroke work) after 30 and 60 minutes of reperfusion was 82.9% and 86.7% in Group I, 35.7% (p less than 0.0001) and 43.7% (p less than 0.0001) in Group II, 76.1% and 77.7% in Group III, 67.4% (p less than 0.05) and 60.6% (p less than 0.05) in Group IV, and 110.7% and 100.6% in Group V. Conclusions: Topical cooling is an effective method of myocardial protection in the neonate. Cold blood cardioplegia with potassium alone and a normal calcium level provides optimal functional recovery. The improved protection obtained with both crystalloid and blood cardioplegia with normal calcium levels suggests an increased sensitivity of the neonatal heart to the calcium level of the cardioplegic solution.     

Biventricular distribution of cold blood cardioplegic solution administered by different retrograde techniques

Although retrograde cardioplegia has been shown to provide adequate overall protection to the myocardium, delivery of cardioplegic solution to the right ventricle and septum is poor. We used an animal model of occlusion of the left anterior descending coronary artery to study the effects of modifying the conditions of retrograde cardioplegia administration on delivery to the right and left ventricles. Adult mongrel dogs (n = 12) were each given five retrograde injections of microsphere-labeled cardioplegic solution at 10-minute intervals. Four injections were made directly into the coronary sinus with ostial balloon occlusion at the following dosages and pressures: (1) 10 ml/kg at 30 mm Hg, (2) 20 ml/kg at 30 mm Hg, (3) 10 ml/kg at 50 mmHg, and (4) 20 ml/kg at 50 mm Hg. A fifth dose (20 ml/kg) was given directly into the right atrium at 50 mm Hg. Delivery of cardioplegic solution to the left and right ventricles was significantly reduced when the right atrial route was compared with the coronary sinus route at the same dosage and pressure (for left ventricle, 6.0% +/- 1.4% versus 22.7% +/- 11.4%/100 gm, p less than 0.001; for right ventricle, 0.7% +/- 0.2% versus 4.1% +/- 0.4%/100 gm, p less than 0.001). Septal delivery was less than that to the anterior and posterior left ventricle (10.4% +/- 1.3% versus 30.3% +/- 3.9% and 27.9% +/- 3.1%/100 gm, p less than 0.0001) for all injections. Delivery to the body of the right ventricle was less than that to the inflow and outflow tracts (1.8% +/- 0.2% versus 4.5% +/- 0.7% and 8.4% +/- 1.5%/100 gm, p less than 0.0001). These results indicate that, in this model, (1) the right atrial route provides less overall cardioplegic solution to both ventricles than direct retrograde coronary sinus cardioplegia and (2) regional abnormalities in distribution with direct retrograde coronary sinus cardioplegia are not affected by changes in the dosage or pressure of injection.     

Imidazole-buffered cardioplegic solution. Improved myocardial preservation during global ischemia

Progressive acidosis is a constant finding in global myocardial ischemia and is associated with reduced myocardial contractility after ischemia. The hypothesis tested in these experiments was that imidazole (pKa = 6.7 at 37 degrees C), a commonly used buffer in physiology and microbiology, would provide superior buffering capacity when used in lieu of bicarbonate (pKa = 6.1 at 37 degrees C) in a cardioplegic solution. Twenty-eight isolated, working rabbit hearts were perfused, and preischemic and postischemic determinants of performance were measured. The 30 minute interval of normothermic global ischemia was altered by the injection at 0 and 15 minutes of 2 ml/gm wet weight of a buffered cardioplegic solution. Control hearts received a bicarbonate-buffered cardioplegic solution and experimental hearts received a solution buffered with imidazole. In the imidazole-buffered group, there was a superior recovery of coronary flow, developed left ventricular pressure, peak rate of rise of left ventricular pressure, peak rate of relaxation, and stroke work indices (p less than 0.05). Recovery of mechanical parameters was coincident with an improved acid-base status of the coronary sinus effluent at the end of ischemia. Coronary sinus effluents in the imidazole group had significantly higher pH values and lower partial pressures of carbon dioxide than coronary sinus effluents in the bicarbonate-buffered group (p less than 0.001). The data suggest that improved buffering of the extracellular and possibly intracellular space during global ischemia with a nonbicarbonate buffer is beneficial and provides improved postischemic myocardial recovery.     

Subcellular distribution of protein kinase C isozymes during cardioplegic arrest

BACKGROUND: On the basis of the hypothesis that cardioplegia-associated myocardial depression was due to activation of protein kinase C, we examined whether specific protein kinase C isozymes would translocate to a cellular fraction containing myofilaments. METHODS: Isolated rat hearts were perfused with Krebs-Ringer bicarbonate buffer for 30 minutes and arrested with 4 degrees C St Thomas No. 2 cardioplegic solution for 0 to 120 minutes (n = 5 per group). The 3 fractions of the left ventricle tissue represented the myofibrillar/nuclear fraction (P1), membranes (P2), and cytosol (supernatant). The distributions of protein kinase C isozymes alpha, delta, epsilon, and eta were examined after separation by electrophoresis, immunoblotting/chemiluminescence, and densitometry. RESULTS: A significant increase in protein kinase C-delta in the P1 fraction was detected after 5 minutes of cardioplegic arrest and remained increased for 60 minutes. Increases in P1 protein kinase C-alpha and -epsilon were seen transiently at 5 minutes, and protein kinase C-epsilon demonstrated a secondary increase in P1 at 30 to 60 minutes. There was also a significant relative increase in protein kinase C-alpha and protein kinase C-delta in the P2 fraction after 60 minutes of cardioplegia. CONCLUSIONS: These data are consistent with our hypothesis that activation of protein kinase C isozymes is associated with altered myofilament function after cardioplegic arrest.     

Effects of methylprednisolone in cardioplegic solution during coronary bypass grafting.

The effects of adding 500 mg. of methylprednisolone to each liter of cardioplegic solution were studied in patients undergoing coronary artery bypass grafts. Patients were randomly assigned to control (12 patients) or steroid-treated groups (10 patients). The cardioplegic solution was identical in the two groups except for the added methylprednisolone. Contractile element velocity (VCE and left ventricular end-diastolic pressure (LVEDP) were recorded immediately before and after perfusion in the operating room. There were no differences between the two groups with respect to these two variables or the postoperative courses. Thus this study fails to demonstrate a beneficial effect of methylprednisolone when added to cardioplegic solutions.     

Effect of cold cardioplegic solution and hypothermia on response to acetylcholine in perfused epicardial coronary artery of pig

The effect of cold cardioplegic solution and hypothermia on the response to acetylcholine, a major postganglionic neurotransmitter of the parasympathetic nervous system, was studied using perfused epicardial coronary arteries of pigs. Cold crystalloid cardioplegic solution (5 degrees C) and hypothermia including topical cooling with slushed ice significantly augmented the coronary flow reduction by acetylcholine at one and two hours after rewarming. Cold Krebs-Henseleit solution (5 degrees C) with hypothermia showed similar effects. However, cardioplegic solution at 37 degrees C did not affect the responsiveness. The coronary flow reduction induced by potassium chloride (60 mmol/L) did not change even after the administration of cold cardioplegic solution (5 degrees C) or cold Krebs-Henseleit solution (5 degrees C), indicating that cooling did not necessarily augment the coronary contractile response generally. It is concluded that cooling and subsequent rewarming can potentiate the contractile response of the coronary artery of the pig to acetylcholine. This suggests that cold cardioplegic solution with hypothermia can promote intraoperative coronary spasm upon activation of the parasympathetic nervous system.     

St. Thomas' Hospital cardioplegic solution. Beneficial effect of glucose and multidose reinfusions of cardioplegic solution

The intention of this study was to determine whether glucose is beneficial in a cardioplegic solution when the end products of metabolism produced during the ischemic period are intermittently removed. The experimental model used was the isolated working rat heart, with a 3-hour hypothermic 10 degrees C cardioplegic arrest period. Cardioplegic solutions tested were the St. Thomas' Hospital No. 2 and a modified Krebs-Henseleit cardioplegic solution. Glucose (11 mmol/L) was beneficial when multidose cardioplegia was administered every 30 minutes. Including glucose in Krebs-Henseleit cardioplegic solution improved postischemic recovery of aortic output from 57.0% +/- 1.8% to 65.8% +/- 2.2%; p less than 0.025. The addition of glucose to St. Thomas' Hospital No. 2 cardioplegic solution improved aortic output from 74.6% +/- 1.9% to 87.4% +/- 1.9%; p less than 0.005. Furthermore, a dose-response curve showed that a glucose concentration of 20 mmol/L gave no better recovery than 0 mmol/L, and glucose in St. Thomas Hospital No. 2 cardioplegic solution was beneficial only in the range of 7 to 11 mmol/L. In addition, we showed that multidose cardioplegia was beneficial independent of glucose. Multidose St. Thomas' Hospital No. 2 cardioplegia, as opposed to single-dose cardioplegia, improved aortic output recovery from 57.4% +/- 5.2% to 74.6% +/- 1.9%; p less than 0.025, and with St. Thomas' Hospital No. 2 cardioplegic solution plus glucose (11 mmol/L) aortic output recovery improved from 65.9% +/- 2.9% to 87.4% +/- 1.9%; p less than 0.005. Hence, at least in this screening model, the St. Thomas' Hospital cardioplegic solution should contain glucose in the range of 7 mmol/L to 11 mmol/L, provided multidose cardioplegia is given. We cautiously suggest extrapolation to the human heart, on the basis of supporting clinical arguments that appear general enough to apply to both rat and human metabolisms.     

A new technique for measuring aortic root pressure during infusion of cardioplegic solution

Aortic root pressure is an important factor in determining the distribution of cardioplegic solutions. Previously, in order to measure this parameter, it was necessary to insert a separate catheter into the aortic root during cardioplegic infusion. An alternative method for measuring aortic root pressure is described that is both simple and accurate and obviates the need for a second aortic root catheter.     

Maximal oxygenation of dilute blood cardioplegic solution

The content of dissolved O2 (the major source of O2 for the myocardium) of dilute blood cardioplegic solution (dBCS) varied widely when oxygenated at 4 degrees C by surface flow of O2 in a Bentley BCR-3500 cardiotomy reservoir. We have modified the system to consistently deliver maximally oxygenated dBCS to the heart. Laboratory studies indicated that bubbling O2 through a 16-gauge intravenous catheter in a central Luer-Lok port of the cardiotomy reservoir provided contents of dissolved O2 that were consistently near maximal. We then studied 17 patients in the operating room. The first 6 patients received dBCS oxygenated with 100% O2 with a high dissolved O2 content of 3.2 +/- 0.2 ml/dl. However, the pH of the dBCS became highly alkaline (7.83 +/- 0.11 at 37 degrees C). Therefore, in the remaining 11 patients, 2% CO2 was added to the O2. The dissolved O2 content remained high (3.3 +/- 0.1 ml/dl), and the pH was in a more physiological range (7.35 +/- 0.09 at 37 degrees C). We conclude that consistently maximal oxygenation of a dBCS at a more physiological pH can be achieved by this method.     

Questionable role of glucose-insulin in cardioplegic solution

To evaluate the myocardial protective effect of glucose-insulin (GI) in a cold cardioplegic solution, we compared the effect of a solution not containing GI (solution I) with that of an identical solution containing GI (solution II) under cardiopulmonary bypass in mongrel dogs. After 120 minutes of ischemic arrest, defibrillation was necessary to restore cardiac activity in 12.5% of the solution I group and 42.8% of the solution II group, respectively. No distinct intergroup differences were noted in recovery of left ventricular function, oxygen and lactate extraction of the myocardium during the post-arrest period, the myocardial ultrastructure, and myocardial ATP levels. Although creatine phosphate was less well preserved, glucose-6-phosphate and lactate were more accumulated in the solution II group than in the solution I group. Thus, significant advantages of substrate enhancement by addition of GI to cold cardioplegic solution were not found in spite of multidose cardioplegia and presence of noncoronary collateral blood flow.