Inotropic response of the salvaged myocardium after acute coronary occlusion

We determined the response of the reperfused myocardium to inotropic stimulation with dobutamine hydrochloride. The middle part of the left anterior descending coronary artery (LAD) was occluded in 15 greyhounds for 3 hours. Group 1 (N = 8) was reperfused for 3 hours in the beating, working heart. Group 2 (N = 7) was put on cardiopulmonary bypass (CPB) for 1 hour, received 500 ml of potassium cardioplegia in the aortic root and in the area of ischemia through an internal mammary-LAD graft, and the LAD was reperfused off CPB for 3 hours. After 3 hours of reperfusion, dobutamine was given at 10 micrograms/kg/min for 20 minutes. Regional myocardial function was determined with subendocardial ultrasonic crystals in the area of ischemia and in the base of the heart; segmental contractility was determined from the ratio of peak left ventricular pressure to end-systolic segment length; and global contractility was determined by the slope of the ventricular pressure wave at a developed pressure of 40 mm Hg. Measurements were made prior to LAD occlusion (control), at the end of 3 hours of reperfusion (6 hours from the beginning of occlusion), and after 20 minutes of dobutamine infusion. Dobutamine infusion improved segmental function in all animals compared with 3 hours of reperfusion. The study shows that the reperfused myocardium responds favorably to inotropic stimulation after 3 hours of occlusion and 3 hours of reperfusion, and that the contractile response both to reperfusion and to inotropic stimulation is greatly affected by the method of reperfusion.     

Effects of diltiazem cardioplegia on global function, segmental contractility, and the area of necrosis after acute coronary artery occlusion and surgical reperfusion

We investigated the effects of diltiazem cardioplegia on myocardial function and infarct size in the region of the left anterior descending artery after acute occlusion and reperfusion during cardiopulmonary bypass. Sheep (30 kg) were subjected to 1 hour of regional myocardial ischemia by occlusion of the left anterior descending artery and assigned to a control (n = 8) or experimental group (n = 5). Control animals were placed on cardiopulmonary bypass and the heart arrested with potassium cardioplegia. The left anterior descending artery was released and two additional doses of 100 ml of cardioplegic solution were infused during the total cross-clamp time of 30 minutes. The animals were then weaned from bypass after 1 hour and beating, working reperfusion maintained for an additional 4 hours. The experimental group followed the same protocol except that the cardioplegic solution contained diltiazem (1.4 mg/L). Segmental myocardial function was determined by pairs of ultrasonic crystals in the area at risk, control segment, and minor axis. Global contractility was determined from maximum derivative of left ventricular pressure and cardiac output. The area at risk was determined by injecting monastral blue dye into the left atrium with the left anterior descending artery briefly reoccluded, and the area of necrosis was determined by measuring with a planimeter non-triphenyltetrazolium chloride stained areas in the sectioned left ventricle. After 5 hours of reperfusion, not only did the diltiazem group demonstrate better global contractility as defined by the derivative of left ventricular pressure (1853 +/- 292 versus 979 +/- 191, p = 0.05) but, in addition, the systolic shortening in the ischemic area improved significantly when compared with the control group (9.4 +/- 4 versus 2.13 +/- 0.77, p = 0.05). The group receiving diltiazem cardioplegia had an area of necrosis to area at risk ratio of 31.4% +/- 3%, which was significantly better than this ratio in the control group of 60.75% +/- 7% (p = 0.01). Diltiazem cardioplegia results in improved global and segmental contractility and limits the infarct size after occlusion of the left anterior descending artery and surgical reperfusion.     

Controlled reperfusion following regional ischemia

The ability to reverse acute coronary occlusion with fibrinolytic agents and percutaneous transluminal angioplasty has increased interest in the revascularization of ischemic myocardium. This study defines changes in global ventricular function, mass, and compliance during acute coronary occlusion and following reperfusion with blood in the beating and arrested heart. In 17 dogs on cardiopulmonary bypass, the proximal left anterior descending coronary artery was occluded for 45 minutes. In 12 dogs, flow was reestablished by releasing the coronary snare in the beating heart. In the other 5 dogs, the snare was released during a continuous 10-minute infusion of blood potassium cardioplegia in the arrested heart. Coronary occlusion resulted in significant decreases in stroke work index and left ventricular (LV) mass, but compliance was unchanged. Reperfusion in the beating heart increased LV mass compared with the values measured before ischemia (104 +/- 5 versus 95 +/- 5 gm; p less than 0.05) and decreased LV compliance (39 +/- 4 versus 53 +/- 4 ml at LV end-diastolic pressure of 8 mm Hg; p less than 0.05). In contrast, with blood cardioplegia-based reperfusion in the arrested heart, LV mass and LV compliance remained unchanged from control values. We conclude that revascularization of acutely ischemic myocardium in the beating heart further impairs LV function by increasing LV mass and decreasing compliance. This damage can be avoided by reperfusion with blood cardioplegia in the arrested heart.     

Terminal magnesium cardioplegia: protective effect in the isolated rat heart model using calcium accentuated ischemic damage

We have developed a modified isolated working rat heart model to study the effect of potassium and magnesium cardioplegia given just prior to reperfusion, "terminal cardioplegia," on preservation of aortic flow following a standard ischemic insult. The model incorporates a short-term calcium challenge at the beginning of reperfusion to accentuate ischemic injury. All hearts were given initial potassium cardioplegia and subjected to 30 min of normothermic ischemia. Terminal cardioplegia was given for the 2 min prior to reperfusion. Calcium-challenged hearts were reperfused initially with calcium-enriched reperfusate and then switched to standard reperfusate. Aortic flow prior to and 60 min after ischemia was used to determine functional protection. Hearts recovered 82 +/- 3% of preischemic aortic flow when reperfused with normocalcemic reperfusate. When the initial reperfusate was enriched with calcium, aortic flow was only 43 +/- 4% of control. Hearts given terminal magnesium cardioplegia and then challenged with calcium-enriched reperfusate recovered 79 +/- 4% of control aortic flow. Hearts given terminal potassium cardioplegia recovered only 53 +/- 5% of control aortic flow when challenged with calcium-enriched initial reperfusate. Our results indicate that the recovery of aortic flow is significantly reduced by short-term postischemic calcium challenge. This damage is blocked by terminal magnesium cardioplegia, but not by terminal potassium cardioplegia.     

The effect of oxygen free radical scavengers on the recovery of regional myocardial function after acute coronary occlusion and surgical reperfusion

This study investigated the effects of the oxygen free radical scavengers superoxide dismutase and catalase, the peroxide ion inhibitor, in crystalloid potassium cardioplegic solution on infarct size and global and regional myocardial function after occlusion of the left anterior descending artery and surgical reperfusion in young sheep on cardiopulmonary bypass. After 1 hour of occlusion, the animals were randomized to receive either routine potassium cardioplegia or cardioplegia with superoxide dismutase and catalase. Global hemodynamics measured by maximum rate of pressure rise showed significant improvement after 5 hours of reperfusion in the group treated with superoxide dismutase and catalase (1843 +/- 163 versus 979 +/- 191, p less than 0.001). Regional myocardial function was measured by ultrasonic crystals implanted in the ischemic area and in a nonischemic control segment. The percent systolic shortening or bulging was calculated. At end of reperfusion in the animals treated with superoxide dismutase and catalase, there was active shortening in the ischemic area after reperfusion of +9.2% +/- 0.4% versus 2.1% +/- 0.8% in untreated animals (p less than 0.001). Infarct size measured by triphenyltetrazolium chloride staining showed significant difference (p less than 0.001) between animals treated with superoxide dismutase and catalase (0.9% +/- 0.1%) and control animals (61% +/- 70%). Superoxide dismutase and catalase given in the cardioplegic solution before reperfusion of an acutely ischemic area of myocardium enhances recovery of contractile function and results in a significant reduction in infarct size, which suggests improved salvage of the ischemic myocardium.     

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.     

Effects of coenzyme Q10 added to a potassium cardioplegic solution for myocardial protection during ischemic cardiac arrest

To evaluate effects of coenzyme Q10 added to a potassium cardioplegic solution for myocardial protection, 17 mongrel dogs underwent 60 minutes of ischemic cardiac arrest under cardiopulmonary bypass. Cardiac arrest was induced by infusing the cardioplegic solution into the aortic root every 20 minutes. Experimental animals were divided into three groups according to the cardioplegic solution used. In Group 1, we used our clinical potassium cardioplegic solution (K+, 22.31 mEq/L); in Group 2, potassium cardioplegic solution with coenzyme Q10 added (coenzyme Q10, 30 mg/500 ml of solution); and in Group 3, cardioplegic solution with coenzyme Q10 solvent. Exogenous coenzyme Q10 in the cardioplegic solution provided significantly high myocardial stores of adenosine triphosphate and creatine phosphate and a low level of lactate during induced ischemia and reperfusion. Furthermore, percent recovery of the aortic flow in Group 2 was significantly higher than that in the other two groups. Ultrastructures of the ischemic myocardium in Group 2 were better preserved than those in Group 1. Addition of coenzyme Q10 to potassium cardioplegia resulted in improved myocardial oxygen utilization and accelerated recovery of myocardial energy metabolism after reestablishment of circulation.     

吡那地尔预处理对缺血心肌的保护效果

目的观察心肺转流(cardiopulmonory bypass,CPB)下,ATP敏感性钾通道开放剂(KCOs)吡那地尔(pinacidil)预处理分别对常温和低温高钾停跳心肌的保护作用.方法18只犬均分为三组,CPB心脏高钾停跳,全心缺血60 min,恢复灌注30 min.常温吡那地尔组(NP组)、低温吡那地尔组(HP组)CPB前主动脉根部灌注浓度为10 μmol/L的吡那地尔5 min.对比观察阻断主动脉前、后心肌超微结构、丙二醛(MDA)含量、血清心肌酶含量以及血液动力学的变化.结果(1)电镜:HP组除阻断60min外的其他时点心肌的正常线粒体及糖原含量均接近缺血前水平,明显高于C组和NP组;(2)心肌MDA的含量:HP组阻断30 min和开放20 min以及NP组开放20 min与C组有显著性差异;(3)血清心肌酶:HP组,除阻断30 min,CK-MB均明显低于同期C组;(4)血液动力学变化:HP组开放循环后心输出量(CO)、左室搏出功(LVSW)恢复比C组迅速.结论吡那地尔明显增强低温CPB心肌缺血-再灌注期超微结构的保护效果.     

Lidocaine-magnesium blood cardioplegia was equivalent to potassium blood cardioplegia in left ventricular function of canine heart

This study evaluated the effects of lidocaine-magnesium blood cardioplegia on left ventricular function compared with potassium blood cardioplegia. Crystalloid cardioplegia which contains lidocaine has been reported but blood cardioplegia is rare. Thirteen dogs received 60 min of global ischemia under hypothermic cardioplumonary bypass (30 degrees C). Potassium blood cardioplegia was administered every 20 min in group A (n=6), and lidocaine-magnesium blood cardioplegia in group B (n=7). We compared the ratio of Emax obtained during IVC occlusion at pre- and post-global ischemia (%Emax) and LVSW (%LVSV). Cardiac function was evaluated prior to CPB and 60 min after reperfusion. There was no difference in time required for cardiac arrest between the two groups (group A: 78+/-3 s, group B: 89+/-9 s). Percentage maximal elastance was significantly better in group B (group A: 63+/-3%, group B: 76+/-4%, P<0.05). Percentage tissue water content of the myocardium after CPB was significantly lower in group B (group A: 82.3+/-4%, group B: 75.5+/-2%, P<0.05). Lidocaine-magnesium blood cardioplegia was equivalent to potassium blood cardioplegia in systolic left ventricular function and reduced myocardial edema in canine heart.     

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.     

Temperature-response studies of the detrimental effects of multidose versus single-dose cardioplegic solution in the rabbit heart

Both single-dose and multidose cardioplegia are protective in the ischemic adult heart under normothermic and hypothermic conditions, but in the hypothermic neonatal rabbit heart single-dose cardioplegia only is protective, whereas multidose cardioplegia is damaging. The present studies in the isolated perfused working heart from neonatal rabbits (aged 7 to 10 days) were designed to characterize the interrelationships between temperature, frequency of cardioplegic infusion, and tissue protection. Hearts (n = 8/group) were subjected to 1, 1.5, 1.5, 3, 10, 12, or 18 hours of ischemia at 37.0 degrees, 34.5 degrees, 32.0 degrees, 28.0 degrees, 20.0 degrees, 15.0 degrees, or 10.0 degrees C, respectively. These times were selected to achieve approximately 55% to 75% recovery of cardiac output in hearts during normothermic reperfusion when single-dose (2 minutes) St. Thomas' Hospital cardioplegic solution was given at the onset of each ischemic period. Under these conditions actual recoveries of cardiac output were 55.7% +/- 5.6%, 68.5% +/- 6.8%, 73.8% +/- 4.1%, 54.6% +/- 5.3%, 56.3% +/- 7.5%, 59.5% +/- 7.7%, and 81.3% +/- 2.3% of the preischemic control values, respectively. By contrast, with multidose cardioplegia (given every 60 minutes in the 3- to 18-hour experiments and every 30 minutes in the 1- and 1.5-hour experiments) there was a temperature-dependent loss of protection when compared with single-dose cardioplegia; the recoveries of cardiac output were 75.7% +/- 1.5%, 78.4% +/- 4.8%, 65.0% +/- 5.8%, 36.7% +/- 5.8%, 34.6% +/- 7.5%, 25.9% +/- 6.0%, and 9.6% +/- 6.4%, respectively. These results were reflected in other indices of cardiac function and in changes in vascular resistance during cardioplegic infusion and reperfusion. To ascertain whether the progressive loss of protection was related to the degree of hypothermia or the duration of ischemia (which had to be increased as the temperature was lowered to permit a 55% to 75% recovery in the single-dose cardioplegia group), we conducted studies at a fixed temperature (20 degrees C) with variable durations of ischemia (6, 8, 10, and 12 hours). Finally, multidose and single-dose cardioplegia at 10.0 degrees, 20.0 degrees, and 37.0 degrees C were compared with hypothermia alone. We concluded that in the neonatal (in contrast to the adult) rabbit heart the protective properties of multidose cardioplegia relative to single-dose cardioplegia are progressively lost.(ABSTRACT TRUNCATED AT 400 WORDS)     

Myocardial protection by retrograde cardioplegic perfusion in the presence of acute coronary artery obstruction. An experimental study.

To investigate retrograde delivery of cardioplegic solutions as a means of enhancing myocardial protection in the presence of coronary artery occlusion, a two-part experimental model was devised. In part 1 (in vitro) the possibility of retroperfusing the entire myocardium during acute occlusion of the left anterior descending artery (LAD) was assessed. In part 2 (in vivo) acute LAD occlusion was performed in dogs, and during 2 hours of aortic cross-clamping crystalline cardioplegic solution was infused at 20-minute intervals. In group I the infusion was antegrade, via the aortic root, and in group II it was retrograde, via the coronary sinus. Thereafter the LAD snare was released and the dogs were weaned from bypass. Delivery of cardioplegia through the aortic root was associated with depression of ventricular function, poor myocardial cooling and severe cellular damage. With the retrograde procedure there was significantly improved recovery of left ventricular function, uniform myocardial cooling and better preservation of cellular morphology.     

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.     

Pretreatment with lidoflazine, a calcium-channel blocker. Useful adjunct to heterogeneous cold potassium cardioplegia

Ten mongrel dogs were studied to determine if pretreatment with lidoflazine would protect the canine myocardium during aortic cross-clamping when circumflex coronary artery occlusion limits the distribution of cold potassium cardioplegia. A canine right heart bypass preparation was used. Regional function was determined with a sonomicrometer. Twenty minutes before aortic cross-clamping, lidoflazine or solvent was administered in a random, blind fashion. A circumflex artery snare prevented the cardioplegic solution from entering the circumflex artery. A 100 minute arrest period with cardioplegic infusion every 20 minutes was followed by 45 minutes of reperfusion before global and regional function were reevaluated. In the group receiving solvent, postarrest function in the circumflex region recovered to only 30% of prearrest values (p less than 0.05), a marked functional deterioration. In the group protected by lidoflazine, function in the circumflex region returned to 90% of prearrest values (NS). Function in the left anterior descending (LAD) regions of both groups demonstrated full recovery after arrest. Global left ventricular function was well preserved in both groups and failed to reflect the damaged, malfunctioning region in the group receiving solvent. These findings suggest that pretreatment with lidoflazine can improve myocardial protection when delivery of cardioplegia is not homogeneous.     

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.     

A comparison of blood and crystalloid cardioplegia during heart transplantation after 5 hours of cold storage

Four methods of protecting the heart during implantation were compared. All hearts were arrested in situ by perfusing 4 degrees C cardioplegic solution into the aortic root and were stored by a nonperfused cold storage technique for 5 hours at 4 degrees C. The hearts were then transplanted orthotopically with the use of topical iced slush alone or with infusions of either blood cardioplegic solution or one of two crystalloid cardioplegic solutions after each atrial anastomosis. Five dog hearts were included in each group. Biopsy samples to test for adenylates were taken before the arrest, at the end of storage, before cross-clamp removal, and 3.5 hours after cross-clamp removal. The dogs were removed from cardiopulmonary bypass, and with the chest open, left ventricular function curves were measured at 1, 2, and 3 hours after cross-clamp removal. At 3.5 hours of reperfusion time, a full-width section was obtained from the left ventricle for measurement of tissue sodium and water content. No differences in tissue water, sodium, or potassium content were found among the groups. Left ventricular function was significantly better in the blood cardioplegia group than in any other groups. Adenosine triphosphate levels were significantly reduced 3.5 hours after reperfusion in the crystalloid cardioplegia groups but were not significantly depressed at any other measurement time. Excellent early graft function was observed after crystalloid cardioplegic arrest and blood cardioplegic reperfusion during graft implantation.     

Studies of controlled reperfusion after ischemia. XXIII. Deleterious effects of simulated thrombolysis preceding simulated coronary artery bypass grafting with controlled blood cardioplegic reperfusion

This study tests whether simulated thrombolysis before controlled reperfusion (i.e., simulated coronary artery bypass) causes reperfusion injury that obviates the benefits of subsequent controlled reperfusion and results in unnecessary ventricular arrhythmias. Fifteen dogs underwent acute occlusion of the left anterior descending coronary artery. In 10 dogs we simulated thrombolysis after 1 hour of ischemia (delivering 10% to 15% of control flow at 5 ml/min), followed 1 hour later by either normal blood reperfusion at systemic pressure (to simulate percutaneous transluminal coronary angioplasty) in five dogs or regionally controlled blood cardioplegic reperfusion on bypass in five others to simulate coronary bypass. In five dogs ischemia was prolonged to 2 hours, and the initial reperfusate was blood cardioplegic solution on total vented bypass (to simulate primary coronary bypass). All hearts receiving simulated thrombolysis (100%) after 1 hour of ischemia had reperfusion-induced ventricular fibrillation. All hearts treated by simulated angioplasty recovered regional contractility (56% of control systolic shortening), whereas there was no (0%) recovery of spontaneous contractility after subsequent blood cardioplegic reperfusion, and only two (40%) dogs had contractile reserve capacity (6% +/- 49%). Conversely, surgically controlled blood cardioplegic reperfusion without preceding low-flow normal blood reperfusion after 2 hours of ischemia resulted in no ventricular arrhythmias (0%; p less than 0.05 versus simulated coronary artery bypass after simulated thrombolysis), 72% +/- 7% (p less than 0.05 versus simulated coronary artery bypass after simulated thrombolysis) recovery of regional contractility (ultrasonic crystals), and 114% +/- 11% (p less than 0.05 versus simulated coronary artery bypass after simulated thrombolysis) recovery of contractile reserve with calcium chloride stimulation. We conclude that controlled reperfusion (simulating coronary artery bypass) with blood cardioplegic solution produces immediate functional recovery and avoids the ventricular fibrillation that follows simulated thrombolysis despite the need for prolonged ischemic time. Preceding controlled reperfusion by normal blood reperfusion (simulated thrombolysis) shortens the ischemic time but nullifies immediate functional recovery possible by simulated coronary bypass and produces unnecessary arrhythmias.     

A new technique for delivering antegrade/retrograde blood cardioplegia without right heart isolation

We report our updated experience with combined antegrade/retrograde cardioplegia using a self-inflating/deflating balloon cannula that allows rapid transatrial retrograde coronary sinus cannulation (10-15 s) without right heart isolation. This permits routine single venous cannulation and optimizes myocardial protection when combined with antegrade cardioplegia. Two hundred fifty-five consecutive patients underwent antegrade/retrograde cardioplegia. Initial antegrade blood cardioplegia caused immediate arrest (less than 1 min), and the cardioplegic dose was divided equally between antegrade and retrograde delivery. Included are 173 isolated CABG patients (39 with either extending infarction, cardiogenic shock, or ejection fraction less than 20%), and 37 coronary reoperations, 67 with aortic and/or mitral valve procedures, 3 with arrhythmia surgery, and 7 children (VSD, Rastelli, Konno, etc). Septal temperature in patients with LAD occlusion fell to 11.6 degrees C +/- 0.5 after retrograde vs only 16.1 degrees C +/- 3 after antegrade cardioplegia (p less than 0.05). Overall hospital mortality was 2.8% and no complications followed transatrial retrograde coronary sinus cannulation. Antegrade/retrograde cardioplegia allowed retrograde flushing of debris in redo coronary operations, produced immediate arrest with low cardioplegic volumes, improved cardioplegic distribution during IMA grafting, allowed aortic and mitral valve procedures to proceed uninterrupted, and ensured distribution in unforeseen aortic insufficiency. Antegrade/retrograde cardioplegia is now used routinely in all adult and in many pediatric operations because of its speed, safety, and simplicity.     

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)     

Sevoflurane Reduces Myocardial Infarct Size and Decreases the Time Threshold for Ischemic Preconditioning in Dogs

Background: Recent evidence indicates that volatile anesthetics exert protective effects during myocardial ischemia and reperfusion. The authors tested the hypothesis that sevoflurane decreases myocardial infarct size by activating adenosine triphosphate-sensitive potassium (KATP) channels and reduces the time threshold of ischemic preconditioning necessary to protect against infarction.

Methods: Barbiturate-anesthetized dogs (n = 75) were instrumented for measurement of aortic and left ventricular pressures and maximum rate of increase of left ventricular pressure and were subjected to a 60-min left anterior descending (LAD) coronary artery occlusion followed by 3-h reperfusion. In four separate groups, dogs received vehicle or the KATP channel antagonist glyburide (0.1 mg/kg intravenously), and 1 minimum alveolar concentration sevoflurane (administered until immediately before coronary artery occlusion) in the presence or absence of glyburide. In three additional experimental groups, sevoflurane was discontinued 30 min (memory) before the 60-min LAD occlusion or a 2-min LAD occlusion as an ischemic preconditioning stimulus was used with or without subsequent sevoflurane (with memory) pretreatment. Regional myocardial perfusion and infarct size were measured with radioactive microspheres and triphenyltetrazolium staining, respectively.

Results: Vehicle (23 +/- 1% of the area at risk; mean +/- SEM) and glyburide (23 +/- 2%) alone produced equivalent effects on myocardial infarct size. Sevoflurane significantly (P < 0.05) decreased infarct size (13 +/- 2%). This beneficial effect was abolished by glyburide (21 +/- 3%). Neither the 2-min LAD occlusion nor sevoflurane followed by 30 min of memory were protective alone, but together, sevoflurane enhanced the effects of the brief ischemic stimulus and profoundly reduced infarct size (9 +/- 2%).