The time course of myocardial high-energy phosphate degradation during potassium cardioplegic arrest

Myocardial high-energy phosphate and glucose-6-phosphate levels were determined in the in vivo pig heart model during ischemic arrest and reperfusion to determine the effectiveness of potassium cardioplegia in myocardial protection. Thirty-five pigs were divided into six experimental groups consisting of 2-hour normothermic arrest, 2-hour hypothemic arrest, 2-hour normothermic cardioplegic arrest, and 1-, 2-, and 3-hour hypothermic cardioplegic arrest. Myocardial biopsies from the left ventricle were obtained prior to arrest, every 30 minutes during the arrest interval, and at 30 and 60 minutes of reperfusion. The measurement of adenosine triphosphate and creatine phosphate showed that (1) cardioplegic arrest requires hypothermia to preserve high-energy phosphate levels in myocardial tissue; (2) hypothermia, while not completely protective alone, is more effective than potassium cardioplegia alone in providing myocardial preservation during 2-hour ischemic arrest; (3) the combination of potassium cardioplegia and hypothermia is additive in providing an effective means of maintaining myocardial high-energy phosphate stores during 1, 2, and 3 hours of ischemic arrest; (4) myocardial reperfusion does not allow a return to preischemic adenosine triphosphate (ATP) levels after 2 hours of arrest, except following hypothermic cardioplegia; and (5) extension of the duration of ischemic arrest to 3 hours using hypothermic cardioplegia prevents recovery of high-energy phosphate stores to preischemic levels during reperfusion. Optimal preservation can be achieved during 2 hours of ischemic arrest by using hypothermic potassium cardioplegia. The effects of myocardial reperfusion, however, prevent full ATP and creatine phosphate (CP) recovery following 3 hours of arrest. No other technique studied was as effective in providing myocardial preservation.     

Metabolic enhancement of myocardial preservation during cardioplegic arrest

An experimental study was undertaken to evaluate the relative efficacy of oxygenated versus unoxygenated cardioplegic solutions and to determine if the addition of certain metabolically active substrates to cardioplegic solutions had any effect on myocardial preservation. Sixty-one pigs were divided into seven groups of animals (5 to 15 animals per group). The impact of different cardioplegic vehicles, i.e., crystalloid versus the oxygen-carrying vehicles, blood and Fluosol-DA, on preservation of high-energy phosphates (adenosine triphosphate and creatine phosphate) was examined in the first three animal groups. The influence of Krebs cycle intermediates, i.e., glutamate, malate, succinate and fumarate, on adenosine triphosphate and creatine phosphate preservation was evaluated in the other four animal groups. All hearts underwent 120 minutes of hypothermic cardioplegic arrest at 15 degrees C followed by 60 minutes of normothermic reperfusion. Higher adenosine triphosphate and creatine phosphate levels were maintained during arrest when oxygenated solutions were used as the cardioplegic vehicle and when any of the four intermediates were added to the crystalloid cardioplegic solution, especially succinate and fumarate. During reperfusion, however, adenosine triphosphate levels were uniformly lower than control whereas creatine phosphate levels rose to either control levels or higher in all groups. No significant intergroup difference could be identified during reperfusion. These findings lead to the conclusion that the presence of either oxygen or certain Krebs cycle intermediates enhances the protective effect of hyperkalemic hypothermic cardioplegia on high-energy phosphates during the arrest period only. This enhancement is not maintained during the reperfusion period.     

The effect of temperature and hematocrit level of oxygenated cardioplegic solutions on myocardial preservation

The ideal temperature and hematocrit level of blood cardioplegia has not been clearly established. This study was undertaken (a) to determine the optimal temperature of blood cardioplegia and (b) to study the effect of hematocrit levels in blood cardioplegia. A comparison of myocardial preservation was done among seven groups of animals on the basis of variations in hematocrit levels and temperature of oxygenated cardioplegic solution. The experimental protocol consisted of a 2-hour hypothermic cardioplegic arrest followed by 1 hour of normothermic reperfusion. Group 1 received oxygenated crystalloid cardioplegic solution at 10 degrees C. Groups 2 through 7 received oxygenated blood cardioplegic solution with the following hematocrit values and temperatures: (2) 10%, 10 degrees C; (3) 10%, 20 degrees C; (4) 10%, 30 degrees C; (5) 20%, 10 degrees C; (6) 20%, 20 degrees C; and (7) 20%, 30 degrees C. Parameters studied include coronary blood flow, myocardial oxygen extraction, myocardial oxygen consumption, and myocardial high-energy phosphate levels of adenosine triphosphate and creatine phosphate during control (prearrest), arrest, and reperfusion. Myocardial oxygen consumption at 30 degrees C during arrest was significantly higher than at 10 degrees C and 20 degrees C, which indicates continued aerobic metabolic activity at higher temperature. Myocardial oxygen consumption and the levels of adenosine triphosphate and creatine phosphate during reperfusion were similar in all seven groups. Myocardial oxygen extraction (a measure of metabolic function after ischemia) during initial reperfusion was significantly lower in the 30 degrees C blood group than in the 10 degrees C blood group at either hematocrit level and in the oxygenated crystalloid group, which suggests inferior preservation. The hematocrit level of blood cardioplegia did not affect adenosine triphosphate or myocardial oxygen consumption or extraction. It appears from this study that blood cardioplegia at 10 degrees C and oxygenated crystalloid cardioplegia at 10 degrees C are equally effective. Elevating blood cardioplegia temperature to 30 degrees C, however, reduces the ability of the solution to preserve metabolic function regardless of hematocrit level. Therefore, the level of hypothermia is important in blood cardioplegia, whereas hematocrit level has no detectable impact, and cold oxygenated crystalloid cardioplegia is as effective as hypothermic blood cardioplegia.     

Safety of prolonged aortic clamping with blood cardioplegia. II. Glutamate enrichment in energy-depleted hearts

Cold blood cardioplegic techniques are limited in their ability to protect energy-depleted hearts during aortic clamping. This study extends our previous observations on the benefits of amino acid (L-glutamate) enrichment of blood cardioplegic solutions as well as the added metabolic benefits of normothermic induction of cardioplegic arrest to increase the rate of repair of energy-depleted hearts. The results demonstrate that L-glutamate enrichment of blood cardioplegic solutions significantly improves metabolic recovery (greater oxygen consumption, better anaerobic metabolism) and ventricular performance. Normothermic induction of glutamate-enriched cardioplegia allowed complete recovery of myocardial metabolism and function compared to cold blood cardioplegic technique and may be used as a form of "active resuscitation" of energy-depleted hearts.     

Effect of high-volume cardioplegia on small-amplitude electrical activity during cardioplegia arrest

The effects of high-volume cardioplegia on the presence of small-amplitude electrical activity during cardioplegia arrest were investigated in 19 mongrel dogs. The animals were randomly assigned to receive either high-volume crystalloid cardioplegia (HV-plege) or crystalloid cardioplegia guided by continuous electrical monitoring (V-plege). Cardiac index, left ventricular stroke work index dp/dt, and myocardial oxygen consumption were measured before bypass and following 90 min ischemia and 45 min reperfusion. Biopsies were taken for measurement of adenosine triphosphate (ATP) and examination of myocardial ultrastructure. Nine animals received HV-plege, while the remaining 10 animals received cardioplegia guided by voltage criteria. Small-amplitude electrical potentials were recorded within 10-15 min after the infusion of cardioplegia in all animals receiving cardioplegia guided by voltage criteria. Electrical activity, however, was immediately abolished by reinfusion of cardioplegia. HV-plege reduced the incidence of small-amplitude electrical activity during cardioplegia arrest but did not prevent electrical activity. Left ventricular function and myocardial ultrastructure were better preserved when cardioplegia was guided by electrical monitoring. ATP decreased similarly in both groups following cardioplegic arrest, but myocardial oxygen consumption was significantly higher following the arrest in the V-plege group. Conclusions: HV-plege does not prevent small-amplitude electrical activity and may have adverse effects on myocardial metabolic and functional recovery.     

Induction of cardioplegia with blood and crystalloid potassium solutions during prolonged aortic cross-clamping

Recent controversy concerns the proper vehicle for delivery of potassium cardioplegia. In the present study, adult dogs supported by cardiopulmonary bypass were subjected to 2 hours of multidose, hypothermic potassium cardioplegic arrest with 30 minutes of reperfusion with either autologous blood or crystalloid solution as the cardioplegic vehicle. Preservation of myocardial high-energy nucleotide stores was assessed by serial left ventricular biopsies assayed for adenosine triphosphate (ATP) and creatine phosphate. Preischemic and postischemic ventricular function was assessed by the use of an isovolumic intraventricular balloon. ATP stores were equally maintained at preischemic levels after ischemia and reperfusion by both autologous blood and crystalloid solution. Although creatine phosphate stores significantly declined (P less than 0.01, both groups) after 2 hours of arrest, reperfusion allowed equal restoration of preischemic levels. Maximum first derivative of left ventricular pressure and measured velocity were not depressed by either mode of protection. Similarly, myocardial compliance, as assessed by length-tension curves, showed no change following either autologous blood or crystalloid solution. The data show equal and significant myocardial protection by multidose, hypothermic potassium cardioplegia when both delivery vehicles were used.     

Effects of Delay in Administration of Potassium Cardioplegia to the Isolated Rat Heart

Ischemic injury to the heart in the period between aortic cross-clamping and administration of cardioplegic solution was evaluated in the normothermic rat heart model. After isolation and control perfusion with oxygenated Krebs-Henseleit bicarbonate buffer, the hearts were given lactated Ringer's cardioplegic solution (30 mEq of K⁺ per liter) for 2 minutes at three different intervals following aortic clamping: no delay, 2-minute delay, and 5-minute delay. Thereafter, the hearts were left unper-fused and the time to initiation of ischemic contracture was recorded. Adenosine triphosphate (ATP) and creatine phosphate levels were measured in all groups prior to and at the conclusion of cardioplegia administration.A 2-minute delay in the administration of cardioplegic solution resulted in significantly lower (p < 0.001) ATP levels that were restored after 2 minutes of cardioplegia administration. Contracture times were not significantly altered. A 5-minute delay resulted in significantly shorter (p < 0.001) contracture times and significantly lower (p < 0.001) ATP levels that were not restored to preischemic levels by 2 minutes of cardioplegia administration.The fate of the myocardium may be insensitive to events that occur during the earliest moments of ischemia provided that rapid administration of oxygenated potassium cardioplegia follows the ischemic period and restores preischemic high-energy phosphate stores. However, there is a critical ischemic time during the initial interval before cardioplegia that is associated with an impaired ability of the myocardium to tolerate subsequent ischemia.     

Chronic Hypoxemia Depresses Global Ventricular Function and Predisposes to the Depletion of High-Energy Phosphates during Cardioplegic Arrest: Implications for Surgical Repair of Cyanotic Congenital Heart Defects

Persistence of impaired ventricular function after repair of cyanotic congenital heart defects may be due to previous exposure to chronic hypoxemia or to perioperative ischemic injury. Clarification of this phenomenon was sought in a canine model of cyanotic cardiovascular disease (Group I), in which the left atrium was anastomosed proximal to the banded pulmonary artery. Animals that had pulmonary artery banding alone (Group II) or no prior surgical intervention (Group III) served as controls. All Group I animals became cyanotic during the study period (arterial oxygen tension, 38 ± 4 mm Hg; hematocrit, 55 ± 5%). Radionuclide-determined ejection fractions performed three months after operation showed significant depression of global biventricular function by 16 to 29% (p < 0.05) compared with groups II and III. On cardiopulmonary bypass, all hearts were subjected to 4°C potassium cardioplegic arrest and reperfusion with serial assays for myocardial adenosine triphosphate (ATP) and creatine phosphate (CP) levels. The ATP and CP stores in each ventricle were similar at all sampling intervals, and preischemic levels were comparable in cyanotic and control groups. However, ATP levels were significantly depressed 37 to 43% from preischemic levels (p < 0.02) after arrest and reperfusion in cyanotic dogs, but they were preserved in Groups II and III. During ischemia, CP stores were depleted to 27% of preischemic values in Group I but only to 46 to 63% of preischemic levels in the control groups (p < 0.05). These data indicate that chronic hypoxemia impairs global ventricular function and predisposes to the accelerated depletion of high-energy phosphates during cardioplegic arrest. The formulation of new intracoronary perfusates for the cyanotic myocardium seems warranted.     

A clinical comparative study between crystalloid and blood-based St Thomas' hospital cardioplegic solution.

OBJECTIVE: Myocardial protection with blood cardioplegia during cardiac surgery is increasingly preferred, but few studies have compared the protective effects of crystalloid cardioplegia to the same solution with blood as the only variable. This clinical study compared the protective effects of crystalloid or blood-based St. Thomas' Hospital cardioplegic solution No. 1. METHODS: Fifty higher risk patients undergoing elective coronary artery bypass surgery, with an ejection fraction less than 40%, were randomly allocated to receive cold (4 degrees C) intermittent crystalloid St. Thomas' No. 1 cardioplegia (n = 25), or a similar blood-based solution (n = 25) with a haematocrit of 10-12%. We determined (1) peri-operative and post-operative arrhythmias, (2) left and right ventricular function (24 h) using the thermodilution technique, (3) left ventricular high-energy phosphate content sampled before ischaemia, the end of ischaemia and the end of bypass. RESULTS: Pre-operative haemodynamic data, aortic cross-clamp and bypass times were similar in both groups of patients; there was no mortality. At the end of ischaemia there were no differences in ATP content between groups but creatine phosphate was maintained at a significantly (P < 0.007) higher level in the blood-based St. Thomas' cardioplegia group than the crystalloid St. Thomas' cardioplegia group (20+/-2 (SE) vs. 13+/-1 micromol/g dry wt, respectively). Return to spontaneous sinus rhythm was significantly (P = 0.002) increased in the blood-based St. Thomas' cardioplegia group (96%) compared to the crystalloid St. Thomas' cardioplegia group (60%). Early post-operative ventricular dysfunction occurred in both groups, but normal LV function (stroke work index) recovered significantly (P = 0.043) more rapidly (by 2 h) in the blood-based St. Thomas' cardioplegia group of patients. CONCLUSIONS: In a higher risk (EF < 40%) group of patients undergoing elective cardiac surgery, addition of blood to an established crystalloid cardioplegic solution significantly enhanced myocardial protection by reducing arrhythmias, improving rate of recovery of function and maintaining myocardial high-energy phosphate content during ischaemia.     

Protection of the hypertrophied pig myocardium. A comparison of crystalloid, blood, and Fluosol-DA cardioplegia during prolonged aortic clamping

The myocardial protective effects of crystalloid, blood, and Fluosol-DA-20% cardioplegia were compared by subjecting hypertrophied pig hearts to 3 hours of hypothermic (10 degrees to 15 degrees C), hyperkalemic (20 mEq/L) cardioplegic arrest and 1 hour of normothermic reperfusion. Left ventricular hypertrophy was created in piglets by banding of the ascending aorta, with increase of the left ventricular weight-body weight ratio from 3.01 +/- 0.2 gm/kg (control adult pigs) to 5.50 +/- 0.2 gm/kg (p less than 0.001). An in vivo isolated heart preparation was established in 39 grown banded pigs, which were divided into three groups to receive aerated crystalloid (oxygen tension 141 +/- 4 mm Hg), oxygenated blood (oxygen tension 584 +/- 41 mm Hg), or oxygenated Fluosol-DA-20% (oxygen tension 586 +/- 25 mm Hg) cardioplegic solutions. The use of crystalloid cardioplegia was associated with the following: a low cardioplegia-coronary sinus oxygen content difference (0.6 +/- 0.1 vol%), progressive depletion of myocardial creatine phosphate and adenosine triphosphate during cardioplegic arrest, minimal recovery of developed pressure (16% +/- 8%) and its first derivative (12% +/- 7%), and marked structural deterioration during reperfusion. Enhanced oxygen uptake during cardioplegic infusions was observed with blood cardioplegia (5.0 +/- 0.3 vol%), along with excellent preservation of high-energy phosphate stores and significantly improved postischemic left ventricular performance (developed pressure, 54% +/- 4%; first derivative of left ventricular pressure, 50% +/- 5%). The best results were obtained with Fluosol-DA-20% cardioplegia. This produced a high cardioplegia-coronary sinus oxygen content difference (5.8 +/- 0.1 vol%), effectively sustained myocardial creatine phosphate and adenosine triphosphate concentrations during the extended interval of arrest, and ensured the greatest hemodynamic recovery (developed pressure, 81% +/- 6%, first derivative of left ventricular pressure, 80% +/- 10%) and the least adverse morphologic alterations during reperfusion. It is concluded that oxygenated Fluosol-DA-20% cardioplegia is superior to oxygenated blood and especially aerated crystalloid cardioplegia in protecting the hypertrophied pig myocardium during prolonged aortic clamping.     

Preservation of myocardial function and biochemistry after blood and oxygenated crystalloid cardioplegia during cardiac arrest

We compared the ability of blood cardioplegia and oxygenated crystalloid cardioplegic solutions to maintain regional left ventricle contractility and adenosine triphosphate levels after cardiopulmonary bypass. Ten baboons were subjected to 90-minute cardiopulmonary bypass conducted at 28 degrees C. Hemodynamic measurements were made before and after the bypass procedure, and biopsies for high-energy phosphate determinations were performed at different time intervals during and after bypass. The results showed improved maintenance of myocardial contractility (measured with the regional end-systolic pressure-length relationship) with the oxygenated crystalloid solution. Expressed as a percentage of values before bypass, contractility after bypass averaged 81.69% +/- 4.81% and 80.47% +/- 10.05%, respectively, after 10 and 20 minutes using the oxygenated crystalloid cardioplegia. For blood cardioplegia, the corresponding values were 71.9% +/- 8.73% and 64.99% +/- 8.60% (mean +/- standard error of the mean). The 10- and 20-minute postbypass values between the two groups differed significantly (t test, Welch modification: p = 0.0464 and p = 0.0342). Myocardial adenosine triphosphate level was higher immediately after induction of cardiac arrest when blood cardioplegia was used (blood cardioplegia, 6.82 mol.g wet wt-1; crystalloid cardioplegia, 4.95 mol.g wet wt-1; p = 0.0314), but values subsequently equalized.     

A Comparison of Intermittent and Continuous Arrest for Prolonged Hypothermic Cardioplegia

A study was carried out to evaluate the best method of myocardial preservation in the pig-heart model. Two techniques for employing hypothermic potassium cardioplegia during prolonged ischemic arrest were compared. One entailed three one-hour periods of arrest interrupted with 30-minute intervals of reperfusion (intermittent arrest), and the other involved a single period of continuous hypothermic cardioplegic arrest (continuous arrest) of three hours' duration. In order to evaluate intermittent versus continuous cardioplegic arrest, prearrest and postarrest contractility, compliance, myocardial perfusion, and left ventricular adenosine triphosphate (ATP) and creatine phosphate (CP) levels were compared in 28 animals.The results show significant deterioration in myocardial contractility and compliance following three-hour cardioplegic arrest whether the arrest was intermittent or continuous. However, there were significant differences between the two groups studied. The animal having continuous arrest had less functional impairment than the animal having intermittent arrest. Myocardial perfusion 30 minutes following continuous arrest returned to prearrest levels whereas there was significant depression in perfusion in the group with intermittent arrest. This represented severe coronary vasoconstriction. The ATP level after completion of arrest is significantly higher in the group having continuous arrest and remains higher throughout the final reperfusion period.On the basis of these studies, it is thought that intermittent reperfusion may lead to a reperfusion injury, which is primarily reflected in decreased perfusion, contractility, and compliance. While hypothermic potassium cardioplegia does not optimally protect the myocardium during prolonged (three hour) ischemic arrest, the alternative of intermittent arrest provides poorer myocardial preservation.     

The Effect of Acute Coronary Artery Occlusion during Cardioplegic Arrest and Reperfusion on Myocardial Preservation

A study was undertaken to evaluate the effect of acute occlusion of a coronary artery during cardioplegic arrest on myocardial preservation and to elucidate the influence of reestablishment of flow versus continued occlusion during the phase of myocardial reperfusion. Coronary occlusion was simulated, and myocardial viability was determined by measuring tissue levels of adenosine triphosphate (ATP) and creatine phosphate (CP) in biopsies of the posterior left ventricular wall. Eighteen pigs were divided into three equal groups consisting of animals with (1) patent right coronary arteries during arrest and reperfusion, (2) occluded right coronary arteries during arrest and patent during reperfusion, and (3) occluded right coronary arteries during arrest and reperfusion.The results of ATP and CP measurements showed that while poorer protection was afforded during two-hour arrest when the coronary artery was occluded, the risk of damage was much greater during reperfusion. Failure to restore adequate blood flow by retention of occlusion caused a concurrent decrease in ATP and CP levels below prescribed limits of myocardial tolerance. When occlusion occurs in the clinical setting, impeding cardioplegia and reperfusion, the importance of revascularization is emphasized.     

Surgical revascularization of acute (1 hour) coronary occlusion: blood versus crystalloid cardioplegia

This study compares blood versus crystalloid cardioplegia in restoring contractile function, and high-energy phosphate and tissue water content in a myocardial segment after 1 hour of coronary artery occlusion. Anesthetized dogs underwent instrumentation with the chest open to measure left ventricular and aortic pressures, and systolic shortening in the myocardium perfused by the left anterior descending coronary artery (LAD) was measured with ultrasonic crystals. In 21 dogs, the LAD was occluded for an hour, thereby replacing systolic shortening with passive lengthening averaging -28.7 +/- 6.2% of control shortening in both groups. The dogs were then placed on total bypass, and arrest was achieved with multidose crystalloid (N = 10) or blood cardioplegia (N = 11). The ligatures were released just prior to the second infusion of cardioplegic solution. Postischemic subendocardial levels of adenosine triphosphate were comparably depleted with crystalloid and blood cardioplegia (55.2% and 44.0%, respectively, of control). Subendocardial increases in water content were similar for crystalloid (3.62%) and blood (3.16%) cardioplegia. Recovery of segmental shortening was significantly greater with blood than crystalloid cardioplegia (31.5 +/- 8.2% versus 4.9 +/- 6.6% of control, respectively). We conclude that the composition and the delivery of blood cardioplegia used in this study restore greater postischemic function than crystalloid cardioplegia in acute evolving myocardial infarction.     

Preservation of myocardial high-energy phosphates with vagal stimulation and hypothermic cardioplegia

We examined three methods of inducing hypothermic cardioplegic arrest and related each to preservation of high-energy phosphates. Levels of adenosine triphosphate (ATP) and creatine phosphate (CP) in baseline rat hearts were compared with levels found after vagal stimulation combined with cardioplegia containing 15 mEq of potassium chloride (KCl) per liter, cardioplegia with 15 mEq of KCl per liter alone, and cardioplegia with 30 mEq of KCl per liter alone. Vagal stimulation produced complete electromechanical arrest in a shorter time than either 15 or 30 mEq of KCl alone (p less than 0.001 for both cardioplegic solutions compared with vagal stimulation), with fewer ventricular beats after ischemia than cardioplegic solution containing 15 or 30 mEq of KCl (p less than 0.001 and less than 0.01, respectively). Levels of ATP and CP, although less than baseline levels (p less than 0.01 and less than 0.001, respectively), were greater with vagal stimulation than with either 15 or 30 mEq of KCl (p less than 0.001 and less than 0.05, respectively, for ATP and p less than 0.001 for both CP levels). Furthermore, when all groups were combined, ATP and CP levels were found to correlate negatively with arrest time (r = -0.851 and -0.788, respectively; both r values significant at p less than 0.01) and with the number of ventricular beats after ischemia (r = -0.927 and -0.851, respectively; both r values significant at p less than 0.01). We conclude that electromechanical work quantified as time to arrest after aortic cross-clamping and as number of ventricular beats after ischemia correlates negatively with ATP and CP levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Studies of myocardial protection in the immature heart. V. Safety of prolonged aortic clamping with hypocalcemic glutamate/aspartate blood cardioplegia

This study tests the hypothesis that multidose, hypocalcemic aspartate/glutamate-enriched blood cardioplegia provides safe and effective protection during prolonged aortic clamping of immature hearts. Of 17 puppies (6 to 8 weeks of age, 3 to 5 kg) placed on vented cardiopulmonary bypass, five were subjected to 60 minutes of 37 degrees C global ischemia without cardioplegic protection and seven underwent 120 minutes of aortic clamping with 4 degrees C multidose aspartate/glutamate-enriched blood cardioplegia ([Ca++] = 0.2 mmol/L), preceded and followed by 37 degrees C blood cardioplegic induction and reperfusion. Five puppies underwent blood cardioplegic perfusion for 10 minutes without intervening ischemia to assess the effect of the cardioplegic solution and the delivery techniques. Left ventricular performance was assessed 30 minutes after bypass was discontinued (Starling function curves). Hearts were studied for high-energy phosphates and tissue amino acids. One hour of normothermic ischemia resulted in profound functional depression, with peak stroke work index only 43% of control (0.7 +/- 0.1 versus 1.7 +/- 0.2 gm x m/kg, p less than 0.05). There was 70% depletion of adenosine triphosphate (7.6 +/- 1 versus control 20.3 +/- 1 mumol/gm dry weight, p less than 0.05) and 75% glutamate loss (6.6 +/- 1 versus control 26.4 +/- 3 mumol/gm, p less than 0.05). In contrast, after 2 hours of aortic clamping with multidose blood cardioplegia preceded and followed by 37 degrees C blood cardioplegia, there was complete recovery of left ventricular function (peak stroke work index 1.6 +/- 0.2 gm x m/kg) and maintenance of adenosine triphosphates, glutamate, and aspartate levels at or above control levels adenosine triphosphate 18 +/- 2 mumol/gm, aspartate 21 +/- 1 versus control 2 mumol/gm, and glutamate 25.4 +/- 2 mumol/gm). Puppy hearts receiving blood cardioplegic perfusion without ischemia had complete recovery of control stroke work index. We conclude that methods of myocardial protection used in adults, with amino acid-enriched, reduced-calcium blood cardioplegia, can be applied safely to the neonatal heart and allow for complete functional and metabolic recovery after prolonged aortic clamping.     

氧及红细胞在心肌保护中的作用

３０只白兔等分３组后制务墩体心脏模型。分别以晶体（ＣＲ）、氧全晶体（ＣＯ）、氧合稀释血搏液ｄＢＣ灌注相应各组，停搏１２０ｍｉｎ。每１５重复灌注一次。高压液相色谱（ＨＰＬＣ）测定心肌缺血前、６０．１２０ｍｉｎ及再灌注３０ｍｉｎ的腺苷酸与肌酸磷酸（ＣＰ）含量；于再灌注３０ｍｉｎ时取左室少许心肌制备光、电交易标本。实验结果：Ｃｒ组见轻度线粒体（Ｍｉｔ）改变，ＣＯ组可见心肌内血管改变，而ｄＢＣ组则未见明显     

Diltiazem cardioplegia. A balance of risk and benefit

Calcium channel blockers may prevent myocardial injury during cardioplegia and reperfusion. A prospective, randomized trial was instituted to evaluate the hemodynamic and myocardial metabolic recovery in 40 patients undergoing elective aorta-coronary bypass with either diltiazem in crystalloid potassium cardioplegia (n = 20) or crystalloid potassium cardioplegia (n = 20). In a preliminary trial, doses between 150 and 250 micrograms/kg reduced the period of heart block after cross-clamp removal (90 +/- 110 minutes) from that found with higher doses and improved myocardial metabolism. In the randomized trial, diltiazem cardioplegia (150 micrograms/kg) produced coronary vasodilatation during cardioplegia and produced less reactive hyperemia during reperfusion. Myocardial oxygen extraction was lower and myocardial lactate production was less after diltiazem cardioplegia during reperfusion. Tissue adenosine triphosphate and creatine phosphate concentrations were preserved better after diltiazem cardioplegia. The postoperative creatine kinase MB levels were less (p less than 0.05) after diltiazem cardioplegia, which indicated less myocardial injury. Postoperative volume loading demonstrated that systolic function (the relation between systolic blood pressure and end-systolic volume index) was depressed after diltiazem cardioplegia compared to crystalloid cardioplegia, but cardiac index was higher because afterload (mean arterial pressure) was lower and preload (end-diastolic volume index) was higher. Diltiazem cardioplegia preserved high-energy phosphates, improved postoperative myocardial metabolism, and reduced ischemic injury after elective coronary bypass. However, diltiazem was a potent negative inotrope and produced prolonged periods of electromechanical arrest. Diltiazem cardioplegia may be of value in patients with severe ischemia but should be used with caution in patients with ventricular dysfunction, and a dose-response relation must be established at each institution before clinical use.     

Myocardial protection in the hypertrophied right ventricle.

Hypertrophied right ventricle presents a sensitive state that may not be adequately protected by modern cardioplegic methods. Cardiac metabolism, performance, and ultrastructure were measured in response to 1 hour of cardioplegic arrest in 15 pigs with right ventricular hypertrophy using intermittent hypothermic crystalloid, blood, and Flusol DA 20%-based cardioplegia. Reperfusion time was 1 hour. One hour after a 60-minute cross-clamp period, there were no differences in light microscopy. Total energy stores increased in 4 of 5 animals given blood cardioplegia compared with 1 of 5 for each of the other groups. Cardiac performance data also showed better results for animals treated with blood cardioplegia. After 30 minutes of reperfusion, animals receiving blood cardioplegia recovered 131% +/- 42% of preoperative systolic performance compared with 106% +/- 49% for Fluosol-treated animals and only 82% +/- 27% recovery for the crystalloid-treated group. After 60 minutes of reperfusion, the blood group showed 119% +/- 20% recovery compared with 89% +/- 23% and 85 +/- 50% recovery for Fluosol- and crystalloid-treated hearts, respectively. In conclusion, blood cardioplegia provided better protection than did crystalloid or Fluosol DA 20% cardioplegia when animals with right ventricular hypertrophy underwent 1 hour of cardioplegic arrest. It may have repaired damaged myocardium, leaving better hearts after cross-clamping than before.     

Atrial activity during cardioplegia and postoperative arrhythmias

Cardioplegia provides excellent protection for the left ventricle, but the right atrium may be poorly protected. Myocardial temperatures, right atrial electrical activity, and postoperative arrhythmias were assessed in 103 patients participating in two consecutive randomized trials comparing blood cardioplegia (n = 36), crystalloid cardioplegia (n = 38), and diltiazem crystalloid cardioplegia (n = 29). Both right atrial and right ventricular temperatures were significantly warmer (p less than 0.05) during delivery of the blood cardioplegic solution than during delivery of either the crystalloid or the diltiazem crystalloid cardioplegic solutions; the aortic root temperatures were 9 degrees +/- 2 degrees C with blood cardioplegia and 5 degrees + 1 degrees C with both crystalloid and diltiazem crystalloid cardioplegia. Atrial activity during cardioplegic arrest was greatest with blood cardioplegia (12 +/- 3 beats/min), lower with crystalloid cardioplegia (10 +/- 2 beats/min), and minimal with diltiazem crystalloid cardioplegia (5 +/- 1 beats/min, p less than 0.05). Perioperative ischemic injury (by creatine kinase MB isoenzyme analysis) was greatest with crystalloid cardioplegia (p less than 0.05). Postoperative supraventricular arrhythmias (both treated and untreated) were more frequent after crystalloid cardioplegia (crystalloid, 63%; blood, 40%; diltiazem, 47%; p less than 0.05). Patients in whom supraventricular arrhythmias developed had significantly more postoperative ischemic injury (by creatinine kinase MB isoenzyme analysis, p less than 0.05). Blood cardioplegia reduced supraventricular arrhythmias by reducing ischemic injury despite warmer intraoperative temperatures and more right atrial activity. Diltiazem crystalloid cardioplegia reduced postoperative arrhythmias by improving intraoperative myocardial protection and suppressing intraoperative and postoperative atrial activity. Crystalloid cardioplegia cooled but did not arrest the right atrium intraoperatively, resulted in the most perioperative ischemic injury, and yielded the highest incidence of postoperative supraventricular arrhythmias.