Ischemic myocardial protection. Comparison of nonoxygenated crystalloid, oxygenated crystalloid, and oxygenated fluorocarbon cardioplegic solutions

This study was designed to compare myocardial protection with a nonoxygenated crystalloid solution, an oxygenated crystalloid solution, and an oxygenated fluorocarbon cardioplegic solution. Postischemic ventricular performance was studied in three equal (N = 7) groups of dogs subjected to 120 minutes of global ischemia induced at an average myocardial temperature of 18.5 degrees +/- 1.4 degrees C (range 17.0 degrees to 21.0 degrees C). Left ventricular global and regional function was evaluated by sonomicrometry and micromanometers before ischemia and at 45 and 60 minutes after ischemia. Stroke volume index, left ventricular pressure-minor external diameter loop area, percent shortening, first derivative of left ventricular pressure, mean velocity of circumferential fiber shortening, and the slope of the end-systolic pressure were used to evaluate myocardial contractility. In vitro oxygen content of the three cardioplegic solutions was measured at a mean injection temperature of 8.3 degrees +/- 0.6 degrees C: 0.8 +/- 0.1 vol% (nonoxygenated crystalloid cardioplegia), 3.2 +/- 0.2 vol% (oxygenated crystalloid cardioplegia), and 6.2 +/- 0.2 vol% (oxygenated fluorocarbon cardioplegia). Recovery of global and regional function was significantly (p less than 0.05) better with both oxygenated solutions than with the nonoxygenated solution. Differences between the oxygenated crystalloid and fluorocarbon groups were not significant. We conclude: (1) Compared to nonoxygenated crystalloid cardioplegia, oxygenated crystalloid and oxygenated fluorocarbon cardioplegic solutions gave superior myocardial protection during 2 hours of ischemic arrest; (2) no difference was found in protective effects between an oxygenated crystalloid and an oxygenated fluorocarbon solution.     

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.     

Studies of controlled reperfusion after ischemia. XXI. Reperfusate composition: superiority of blood cardioplegia over crystalloid cardioplegia in limiting reperfusion damage--importance of endogenous oxygen free radical scavengers in red blood cells

Postischemic damage is caused partially by oxygen free radical-mediated injury. This study will show that (1) crystalloid cardioplegia with room air oxygen is deleterious because it is devoid of free radical scavengers and (2) blood cardioplegia limits damage because it contains endogenous free radical scavengers in red blood cells. METHODS: Thirty-two dogs underwent 2 hours of ligation of the left anterior descending coronary artery followed by 20 minutes of regional blood cardioplegic reperfusion on bypass. Ten dogs received only the blood cardioplegic solution (containing its endogenous free radical scavengers); five received initial blood cardioplegia (5 minutes) with endogenous free radical scavengers (catalase and glutathione peroxidase) blocked by aminotriazole and N-ethylmaleimide, respectively; 12 received initial crystalloid cardioplegic solution oxygenated by room air (oxygen tension = 150 mm Hg); seven without and five with exogenous free radical scavengers (superoxide dismutase, catalase, coenzyme Q10); five received initial deoxygenated crystalloid cardioplegic solution (oxygen tension = 6 mm Hg); and five received deoxygenated crystalloid cardioplegic solution. RESULTS: Blood cardioplegia with endogenous free radical scavengers produced the best recovery of systolic shortening (69% systolic shortening) and resulted in the least histochemical damage (11% triphenyltetrazolium chloride nonstaining). The worst recovery and most damage occurred if blood cardioplegia was preceded by oxygenated crystalloid cardioplegia (3% systolic shortening, 48% triphenyltetrazolium chloride nonstaining; p less than 0.05 versus blood cardioplegia) or if free radical scavengers were blocked in the initial period of blood cardioplegia (3% systolic shortening, 41% triphenyltetrazolium chloride nonstaining; p less than 0.05 versus blood cardioplegia). Conversely, deoxygenation or supplementation of oxygenated crystalloid cardioplegic solution with exogenous free radical scavengers restored 60% systolic shortening (p less than 0.05 versus oxygenated crystalloid cardioplegia) and 54% systolic shortening (p less than 0.05 versus oxygenated crystalloid cardioplegia) and reduced damage to 34% and 21% (both p less than 0.05 versus oxygenated crystalloid cardioplegia). CONCLUSION: Blood cardioplegic solutions containing their own endogenous free radical scavengers are superior to crystalloid cardioplegic solutions, because they limit oxygen-mediated perfusion damage and restore contractile function. Initial crystalloid cardioplegic washout negates the salutary effect of blood cardioplegia. Exogenous free radical scavenger supplementation or deoxygenation of the cardioplegic reperfusate is necessary only if crystalloid cardioplegia is used.     

Effect of oxygenated crystalloid cardioplegia on the functional and metabolic recovery of the isolated perfused rat heart

The use of an oxygenated crystalloid cardioplegic solution to improve myocardial preservation during elective cardiac arrest was evaluated with the isolated perfused rat heart used as a model. Experiments were conducted at 4 degrees C and 20 degrees C. The oxygen tension of the nonoxygenated and oxygenated cardioplegic solutions averaged 117 and 440 mm Hg, respectively. At 4 degrees C, the adenosine triphosphate content of hearts subjected to 120 minutes of oxygenated cardioplegia was significantly higher than that of the nonoxygenated cardioplegia group. However, functional recovery during reperfusion was similar for both groups. At 20 degrees C, the myocardial adenosine triphosphate concentration decreased at a significantly faster rate during ischemia in the group receiving nonoxygenated cardioplegia compared with the oxygenated cardioplegia group. Hearts subjected to 180 minutes of ischemia with oxygenated cardioplegia had a normal ultrastructural appearance whereas hearts subjected to 120 minutes of nonoxygenated cardioplegia showed severe ischemic damage. Myocardial functional recovery in the group receiving oxygenated cardioplegia exceeded that of the group receiving nonoxygenated cardioplegia. The use of myocardial adenosine triphosphate concentration at the end of the ischemic period to predict subsequent cardiac output, peak systolic pressure, and total myocardial work showed significant positive correlations.     

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.     

Safety of prolonged aortic clamping with blood cardioplegia. III. Aspartate enrichment of glutamate-blood cardioplegia in energy-depleted hearts after ischemic and reperfusion injury

This study tests the hypothesis that aspartate enrichment of glutamate-blood cardioplegia improves metabolic and functional recovery after ischemic and reperfusion damage. Ischemic and reperfusion damage were produced in 15 dogs by 45 minutes of aortic clamping at 37 degrees C and 5 minutes of blood reperfusion, before 2 more hours of aortic clamping (simulated operation). Six received multidose blood cardioplegia at 4 degrees C. In nine others, the cardioplegic solution was infused at 37 degrees C for the first 5 minutes, followed by multidose infusions at 4 degrees C. Four received 26 mmol glutamate-enriched cardioplegic solution. In five, the glutamate (13 mmol) cardioplegic solution was enriched with aspartate (13 mmol). Oxygen uptake and ventricular function (stroke work index, left atrial pressure) were measured. These data suggest aspartate enrichment produced the highest oxygen uptake (32 +/- 4 versus 17 +/- 2 ml/100 gm for glutamate and 7 +/- 1 ml/100 gm for 4 degrees C blood cardioplegia). Complete functional recovery occurred in aspartate/glutamate-treated hearts (stroke work index 90% +/- 4%, left atrial pressure 12 +/- 2 mm Hg), whereas recovery was incomplete with both glutamate alone (stroke work index 66% +/- 14%, left atrial pressure 20 +/- 3 mm Hg) and 4 degrees C blood cardioplegia at low cardiac outputs. Eight of 10 hearts not receiving aspartate failed at high cardiac outputs. Aspartate enrichment of glutamate-blood cardioplegia improves recovery after severe ischemic/reperfusion damage by improving oxidative metabolism during cardioplegic infusion and during postischemic work.     

Myocardial protection during prolonged aortic cross-clamping. Comparison of blood and crystalloid cardioplegia

We compared the ability of blood and crystalloid cardioplegia to protect the myocardium during prolonged arrest. Twelve dogs underwent 180 minutes of continuous arrest. Group I (six dogs) received 750 ml of blood cardioplegic solution (potassium chloride 30 mEq/L) initially and every 30 minutes. Group II (six dogs) received an identical amount of crystalloid cardioplegic solution (potassium chloride 30 mEq, methylprednisolone 1 gm, and 50% dextrose in water 16 ml/L of electrolyte solution). Temperature was 10 degrees C and pH 8.0 in both groups. Studies of myocardial biochemistry, physiology, and ultrastructure were completed before arrest and 30 minutes after normothermic reperfusion. Biopsy specimens for determination of adenosine triphosphate were obtained before, during, and after the arrest interval. Regional myocardial blood flow, total coronary blood flow, and myocardial oxygen consumption were statistically unchanged in Group I (p greater than 0.05). Total coronary blood flow rose 196% +/- 49% in Group II (p less than 0.005), and left ventricular endocardial/epicardial flow ratio fell significantly in this group from 1.51 +/- 0.18 to 0.8 +/- 0.09, p less than 0.01 (mean +/- standard error of the mean. The rise in myocardial oxygen consumption was not significant in this group (34% +/- 36%, p greater than 0.05). Ventricular function and compliance were statistically unchanged in both groups. In Group II, adenosine triphosphate fell 18% +/- 3.4% (p less than 0.005) after 30 minutes of reperfusion; it was unchanged in Group I. Ultrastructural appearance in both groups correlated with these changes. We conclude that blood cardioplegia offers several distinct advantages over crystalloid cardioplegia during prolonged arrest.     

Retrograde coronary sinus perfusion prevents infarct extension during intraoperative global ischemic arrest

To determine whether continuous infusion of cardioplegia retrograde through the coronary sinus could improve the salvage of infarcting myocardium, 54 pigs were utilized in a region at risk model. All hearts underwent 30 minutes of reversible coronary artery occlusion, and were divided into six groups. Group 1 served as controls and underwent two hours of coronary reflow without global ischemic arrest. The remaining five groups were subjected to 45 minutes of cardioplegia-induced hypothermic arrest followed by two hours of normothermic reflow. Group 2 had a single infusion of crystalloid cardioplegia, and Group 3 received an oxygenated perfluorocarbon cardioplegic solution initially and again after 20 minutes of ischemia. After initial cardiac arrest with crystalloid cardioplegia, all hearts in Groups 4, 5, and 6 underwent a continuous infusion of a cardioplegic solution retrograde through the coronary sinus. Group 4 received a nonoxygenated crystalloid cardioplegic solution, Group 5 received an oxygenated crystalloid cardioplegic solution, and Group 6 received an oxygenated perfluorocarbon cardioplegic solution. With results expressed as the percent of infarcted myocardium within the region at risk, Group 2 hearts, which received only antegrade cardioplegia, had a mean infarct size of 44.8 +/- 6.3%, a 2.2-fold increase over controls (p less than 0.05). While antegrade delivery of oxygenated perfluorocarbon cardioplegia (Group 3) and coronary sinus perfusion with nonoxygenated crystalloid cardioplegia (Group 4) limited infarct size to 33.6 +/- 4.7% and 35.3 +/- 5.4%, respectively, only oxygenated cardioplegia delivered retrograde through the coronary sinus (Groups 5 and 6) completely prevented infarct extension during global ischemic arrest.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Hot shot on recovery after hypothermic ischemia in neonatal lamb heart

BACKGROUND: Terminal warm blood cardioplegia, "Hot shot", is the method for providing an energy replenishment and/or early recovery of aerobic metabolism without electromechanical activity at initial reperfusion. The mechanism of beneficial effects of this Hot Shot is multifactorial. This study was designed to assess the effects of terminal warm blood cardioplegia by comparing with oxygenated terminal warm crystalloid cardioplegia. METHODS: In Group HS-B, n=8 (oxygenated blood; 37 degrees C, Ht: 20%, K+ 20 mEq/l, pH 7.237, PO2 219 mmHg) and in Group HS-C, n=8 (bloodless oxygenated (5% CO2+95%O2) crystalloid, 37 degrees C, K+ 20 mEq/l, pH 7.435, PO2 624 mmHg), terminal warm cardioplegia (20 ml/kg for 5 minutes) was studied in the isolated blood perfused neonatal lamb heart following 2 hr of cardioplegic ischemia. Another eight hearts served as control without any kind of terminal cardioplegia. After 60 min of reperfusion, LV function was measured. Coronary blood flow (CBF), oxygen content, and oxygen consumption (MVO2) were measured and the oxygen extraction ratio was calculated in Group HS-B and HS-C during terminal cardioplegia and/or reperfusion. Results are given as % recovery of preischemic values. RESULTS: HS-B as well as HS-C groups showed better functional recovery in maximum developed pressure (DP: 78.0+/-8.3 in HS-B vs 65.2+/-9.2%; p=0.018), maximum dp/dt (67.3+/-6.2 in HS-B, 65.3+/-7.4 in HS-C vs 55.8+/-5.0%; p=0.003, p=0.02), DP V10 (87.1+/-8.5 in HS-B vs 67.2+/-9.9%; p=0.0001), and peak dp/dt V10 (76.4+/-7.6 in HS-B, 69.8+/-8.1 in HS-C vs 58.6+/-6.9 %; p=0.0001) than the control group. Between the HS-B and HS-C groups, HS-B showed better functional recovery in terms of DP V10 (p=0.01). Oxygen delivery of terminal cardioplegia was almost four times higher in HS-B group (90.4+/-17.7 vs 18.7+/-1.1 mcl/ml), contrarily, HS-C group showed four times higher oxygen extraction ratio compared to HS-B group (0.78+/-0.06 vs 0.18+/-0.11), thus oxygen consumption during hot shot was maintained at the same level in both groups. CBF in the control group was lower than that in the other groups at 60 min of reperfusion. CONCLUSIONS: Reperfusion with both terminal warm cardioplegia including blood and oxygenated crystalloid cardioplegia resulted in better recovery of function and higher levels of CBF with slightly better function in terminal warm blood cardioplegia.     

Improved myocardial recovery after cardioplegic arrest with an oxygenated crystalloid solution

Possible enhancement of myocardial protection by oxygenation of a crystalloid cardioplegic solution was evaluated in a three-part study. In Part I, canine hearts underwent ischemia followed by heterogeneous cardioplegic arrest for 45 to 60 minutes. Oxygenation led to improved recovery in the left anterior descending region (47% versus 86% recovery, p less than 0.05) (15 minutes of ischemia) and in the circumflex region (9.5% versus 52% recovery, p less than 0.05) (30 minutes of ischemia). Part II was a blind prospective randomized study in 12 patients. It examined creatine kinase, myoglobin, and lactate as well as coronary sinus flow, oxygen consumption, and cardiac work 1 hour after aortic cross-clamping during atrial and during ventricular pacing. No significant difference was demonstrable between control and oxygenated solutions. In Part III, 57 coronary bypass patients were protected with a nonoxygenated solution while 94 patients received an identical oxygenated solution. Twelve-hour creatine kinase levels were similar in the nonoxygenated (9.5 +/- 16 IU, +/- standard deviation) and oxygenated (11 +/- 22 IU) groups if the cross-clamp interval was 28 minutes or less. In patients subjected to longer than 28 minutes of arrest, the 12 hour creatine kinase MB levels were more than twice as high in the nonoxygenated group (26.5 +/- 26 IU) compared to the oxygenated group (9.9 +/- 14 IU, p less than 0.05). In this canine model of heterogeneous cardioplegia and in the routine conduct of coronary bypass operations, oxygenated crystalloid cardioplegia is superior to an identical nonoxygenated solution.     

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.     

Studies of controlled reperfusion after ischemia. XX. Reperfusate composition: detrimental effects of initial asanguineous cardioplegic washout after acute coronary occlusion

This study tests whether initial asanguineous washout of potentially toxic substances that accumulate during ischemia improves recovery produced by blood cardioplegic reperfusion and evaluates the role of plasma versus whole blood cardioplegia. METHODS: Twenty-four dogs underwent 2 hours of occlusion of the left anterior descending coronary artery and 20 minutes of blood cardioplegic reperfusion on total vented bypass. In 13 dogs, a 5-minute infusion of either a crystalloid (n = 7) or plasma (n = 6) cardioplegic solution (containing the same pH, calcium potassium, and osmolarity as blood cardioplegia) was given immediately before reoxygenation with blood cardioplegia. Regional oxygen uptake and coronary vascular resistance were measured during controlled reperfusion, and segmental shortening (ultrasonic crystals), tissue water content, and histochemical damage (triphenyltetrazolium chloride stain) were assessed 1 hour after bypass was discontinued. RESULTS: Asanguineous cardioplegic washout before reoxygenation with blood cardioplegic solution resulted in a progressive (+42%) increase in coronary vascular resistances (from 123 to 176 units, p less than 0.05) and low oxygen utilization during 20 minutes of blood cardioplegic reperfusion (29 ml/100 gm, p less than 0.05); coronary vascular resistance remained low throughout blood cardioplegic reperfusion without washout (from 109 to 98 units), and oxygen utilization was 54 ml/100 gm (p less than 0.05). Neither plasma nor crystalloid washout restored substantial regional systolic shortening (3% systolic shortening versus 73% systolic shortening with blood cardioplegia), and asanguineous washout caused more myocardial edema (81.1% +/- 80.9% versus 79.5% water content, p less than 0.05) and produced extensive transmural triphenyltetrazolium chloride damage (48% +/- 41% versus 8% nonstaining in area at risk, p less than 0.05) than initial blood cardioplegic reperfusion. CONCLUSION: Asanguineous cardioplegic washout before blood cardioplegic reperfusion limits oxygen utilization during subsequent controlled reperfusion, restricts early recovery of systolic shortening, allows more myocardial edema, and produces extensive histochemical damage, which may be avoided by initial reoxygenation with blood cardioplegia. The red blood cells appear more important than the plasma components of blood cardioplegia.     

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.     

Right and left ventricular metabolites

Current methods of cardioplegic delivery may delay the recovery of right ventricular metabolism and function. To evaluate right and left ventricular metabolism, we performed biopsies in 37 patients undergoing elective coronary bypass operation with aortic root blood cardioplegia. Right ventricular temperatures were warmer than left ventricular temperatures during cardioplegic arrest (right ventricle: 16.8 degrees +/- 3.8 degrees C, left ventricle: 14.3 degrees +/- 3.7 degrees C, p = 0.02). Adenosine triphosphate concentrations were lower in the right ventricle than in the left ventricle before cardioplegic arrest (right ventricle: 13.8 +/- 7.8 mmol/kg, left ventricle: 21.5 +/- 8.7 mmol/kg, p = 0.02). After reperfusion, right ventricular adenosine triphosphate concentrations fell to low levels (10 +/- 6 mmol/kg). Postoperative left and right ventricular high energy phosphate concentrations (the sum of adenosine triphosphate and creatine phosphate levels) correlated inversely with myocardial temperatures during cardioplegia (r = -0.29, p = 0.048). Aortic root cardioplegia did not cool the right ventricle as well as it did the left ventricle. The lower preoperative high energy phosphate concentrations may have increased the susceptibility of the right ventricle to ischemic injury. Alternative methods of myocardial preservation may improve right ventricular cooling and protection.     

Optimal myocardial protection with fluosol cardioplegia

An oxygenated perfluorocarbon cardioplegic solution was examined, utilizing a blood-perfused canine model. Twenty-one animals were divided into three equal groups, and each animal received Fluosol cardioplegia at one of three infusion temperatures: 20 degrees C, or 4 degrees C. All hearts underwent 90 minutes of ischemia, during which time 150 ml of the cardioplegic solution was infused every 30 minutes. Myocardial oxygen and carbon dioxide tensions (PmO2 and PmCO2) were monitored continually using mass spectrometry, and myocardial oxygen consumption was calculated with each cardioplegic injection. The mean increase in PmO2 was 7.1 +/- 0.9 mm Hg with 20 degrees C Fluosol infusions, 31.1 +/- 4.7 mm Hg with 10 degrees C Fluosol injections, and 22.2 +/- 4.7 mm Hg with infusions of 4 degrees C Fluosol. Average myocardial oxygen consumptioN, expressed as cubic centimeters of oxygen per 100 gm of left ventricle (wet weight), was 21.2 +/- 0.5 with 20 degrees C Fluosol, 22.8 +/- 1.3 for 10 degrees C Fluosol, and 19.6 +/- 1.0 for 4 degrees C Fluosol. Mean myocardial temperatures with infusions of 20 degrees C, 10 degrees C, and 4 degrees C solutions were 21.4 +/- 0.1 degree C, 16.9 +/- 0.4 degree C, and 15.9 +/- 0.5 degree C, respectively. After 45 minutes of reperfusion, maximum rate of rise of left ventricular pressure, expressed as percentage of preischemic control, was 70.9 +/- 3.9% for 20 degrees C Fluosol, 90.9 +/- 3.2% for 10 degrees C Fluosol, and 90.4 +/- 2.3% for 4 degrees C Fluosol (p less than 0.005, 20 degrees C versus 10 degrees C, 4 degrees C Fluosol). In addition, the 10 degrees C and 4 degrees C Fluosol hearts had essentially normal structure by light and electron microscopy. These data demonstrate tht Fluosol cardioplegia results in near optimal myocardial protection when infused at cold temperatures (4 degrees C to 10 degree C). The increases intramyocardial oxygen and myocardial oxygen consumption with each injection demonstrate that there is enhanced oxygen delivery and utilization, which may account for the improved functional recovery observed in these hearts.     

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.     

Oxygenated cardioplegia ameliorates the adverse effects of small amplitude electrical recording of activity on myocardial metabolic and functional recovery

Small amplitude electrical activity has been recorded from the myocardium during cardioplegic arrest in the absence of electromechanical activity. The presence of persistent electrical activity has been associated with impaired myocardial metabolic and functional recovery. To determine whether or not oxygenated cardioplegia would provide sufficient oxygen to support the increased metabolic activity associated with persistent electrical activity during cardioplegic arrest, we randomized 14 adult mongrel dogs to receive either non-oxygenated or oxygenated cardioplegia during 90 min of ischaemia. Cardiac index (CI), left ventricular stroke work index (LVSWI) and dp/dt were measured before bypass and after 90 min of ischaemia and 45 min of reperfusion. Myocardial oxygen consumption (MVO2) and lactate extraction were measured before and after bypass. Intramyocardial voltage was monitored during cardioplegic arrest, and MVO2 was measured during cardioplegia infusion. The onset of small amplitude electrical activity was associated with a rise in intramyocardial voltage and an increase in MVO2. CI, LVSWI and dp/dt were better preserved in those animals receiving oxygenated cardioplegia. MVO2 and lactate consumption following cardioplegia arrest were also higher in this group. Conclusions: (1) small amplitude electrical activity during cardioplegic arrest is associated with a rise in MVO2. (2) Oxygenated cardioplegia increases myocardial protection by providing oxygen for the increased metabolic activity associated with the presence of this small amplitude electrical activity.     

Protection of the hypertrophied myocardium by crystalloid cardioplegia.

Patients with left ventricular hypertrophy (LVH) have a worse outcome after cardiac surgery than those without hypertrophy. We studied protection of hearts with LVH in an isolated rat heart model using multidose, cold, oxygenated cardioplegia. LVH was produced by banding the abdominal aorta in young rats. Six weeks after banding, this produced a 31% increase in the left ventricular dry weight/body weight ratio compared to two age-matched control groups comprising sham-operated and nonoperated animals. The recovery of cardiac output after arrest was higher in LVH (82 +/- 4% of prearrest) than in sham-operated (69 +/- 4%) or nonoperated (66 +/- 3%) control groups. The improved functional recovery in LVH occurred although there were no differences among the groups in myocardial adenosine triphosphate (ATP) and phosphocreatine (PCr) prior to arrest, at the end of arrest, or after reperfusion. Glycogen levels were also similar among the three groups prior to arrest and after reperfusion but were highest in LVH after arrest. Myocardial oxygen consumption (MVO2) and efficiency, expressed as cardiac output/MVO2, were similar among the groups prior to arrest. Myocardial efficiency after reperfusion declined in all groups but was best preserved in LVH. We also compared the sensitivity of hypertrophied and control hearts to the deleterious effects of calcium in cardioplegia. Calcium in the cardioplegia increased myocardial lactate production during arrest in a dose-related fashion and depressed myocardial levels of ATP, PCr, and glycogen at end arrest in all groups. Cardiac output recovery was also depressed by calcium but was still best in LVH. We conclude that the hypertrophied myocardium is well protected by standard cardioplegia and that calcium in cardioplegia does not preferentially depress recovery in LVH.     

Potential deleterious effect of beta-adrenergic stimulation during warm-blood cardioplegia in rabbit hearts.

We hypothesized that beta-adrenergic stimulation with isoproterenol during continuous normothermic cardioplegic arrest would enhance the regenerative and regulatory function of the myocardium, resulting in improved cardiac function. We studied isolated rabbit hearts paced at approximately 200 beats per minute (bpm) and perfused by a support rabbit. We measured ventricular pressure over a range of ventricular volumes to determine maximal elastance (Emax) at baseline and 20 and 45 min after discontinuation of cardioplegia. Myocardial oxygen consumption (MVO2) measurements were performed simultaneously and during cardioplegic arrest. Hearts were prospectively randomized to receive either isoproterenol at 0.1 M or control in blinded fashion for 10 min during a 1-h continuous warm-blood cardioplegic arrest. Compared to control hearts, isoproterenol-treated hearts had trends toward longer time to first spontaneous heartbeat (control 141 +/- 43 vs. isoproterenol 200 +/- 74 s, p = .07), and longer time to capture of atrial pacing (control 214 +/- 52 vs. isoproterenol 288 +/- 91 s, p = .06). There was no difference observed in the MVO2 between isoproterenol-treated and control groups of hearts. MVO2 decreased during cardioplegia (p < .01), but there was no significant change in MVO2 during isoproterenol infusion during cardioplegic arrest. There was a significant reduction in Emax compared to baseline 20 min after discontinuation of cardioplegic arrest in both groups (control 7.3 +/- 1.7 mm Hg/microL vs. 9.0 +/- 1.7 mm Hg/microL, p = .02, isoproterenol-treated 6.8 +/- 2.8 mm Hg/microL vs. 8.2 +/- 2.6 mm Hg/microL, p = .01, respectively), with recovery of Emax by 45 min in control hearts only. We conclude that exposure of hearts to isoproterenol during warm cardioplegic arrest has a deleterious effect that may be mediated through mechanisms independent of increased myocardial oxygen consumption.     

Protection of the neonatal myocardium during hypothermic ischemia. Effect of cardioplegia on left ventricular function in the rabbit

The protective effect of cardioplegia upon neonatal myocardium during ischemia has not been clearly established. This study evaluated the effects of cardioplegia on left ventricular function in isolated working neonatal rabbit hearts (aged 1 week) subjected to 120 minutes of global ischemia at 28 degrees C. Four groups were studied: Group 1, hypothermia alone; Group 2, intermittent washout with an oxygenated noncardioplegic solution; Group 3, multidose cardioplegia; Group 4, single-dose cardioplegia. After ischemia, cardiac output was reduced to 72% +/- 5% (mean +/- standard error of the mean) of control (p less than 0.02) in Group 1 and to 56% +/- 4% in Group 2 (p less than 0.001). In contrast, there was no significant reduction from baseline cardiac output in those animals receiving cardioplegic solution (Group 3, 93% +/- 6%, and Group 4, 97% +/- 4%). Group 2 hearts demonstrated significantly worse recovery of cardiac output and stroke volume than all other groups. After ischemia, the first derivative of left ventricular pressure fell to 73% +/- 13% of control in Group 1 (p less than 0.1) and to 89% +/- 5% in Group 2 (p less than 0.05). However, the first derivative of left ventricular pressure was restored to control values in Group 3 (118% +/- 11%) and Group 4 (114% +/- 9%). When compared to baseline, creatine kinase was higher 30 minutes after reperfusion in Group 1 (40 +/- 8 versus 143 +/- 32 IU/L/gm, p less than 0.05) and in Group 2 (39 +/- 7 versus 163 +/- 33 IU/L/gm, p less than 0.05). Creatine kinase remained unchanged from baseline in Groups 3 and 4. This study demonstrates excellent preservation of left ventricular function in the neonatal rabbit heart protected with cardioplegic solution. In contrast, neither hypothermia alone nor intermittent washout with an oxygenated noncardioplegic solution was effective in preventing myocardial dysfunction. As in adults, the administration of cardioplegic solution preserves ventricular function during ischemia in neonatal hearts.