Does Cardioplegic Arrest Compromise Long-Term Left Ventricular Function?

This study was undertaken to evaluate the chronic, long-term effect of global ischemia produced by cold potassium cardioplegia during cardiopulmonary bypass. Fifteen dogs underwent either control thoracotomy and chronic instrumentation (Group A) or cardiopulmonary bypass and 60 minutes of cold cardioplegic arrest (Group B). With the dogs conscious, hemodynamic variables and left ventricular studies were recorded weekly for 12 weeks postoperatively, both at rest and during volume overload with saline solution. At rest, the heart rate in Group B was 18% higher and stroke volume was 14% lower than Group A. With volume overload, cardiac output and maximum rate of rise of left ventricular pressure in Group B rose only from 3.7 ± 0.6 to 7.1 ± 0.8 liters per minute and 2,410 ± 220 to 2,730 ± 130 mm Hg per second, respectively, compared with 3.9 ± 0.6 to 10.4 ± 0.8 liters per minute and 2,740 ± 230 to 3,890 ± 350 mm Hg, respectively, in Group A (p < 0.01). In Group B, the other variables reached a plateau sooner than in Group A (48 versus 110 seconds). The left ventricular function curve showed a mild decrease in functional capacity and depressed contractility. Therefore, one hour of cardioplegic cardiac arrest caused no depression of function at rest. Mild depression of left ventricular function was demonstrated up to 7 weeks postoperatively during acute volume overload.     

Comparison of Roller Pump versus Pressurized Bag Administration of Potassium Cardioplegic Solution

We sought to determine the relative efficacy of administering cardioplegia by the pressurized bag versus roller pump technique. Fourteen dogs were placed on cardiopulmonary bypass at 30°C and subjected to 2 hours of cardioplegic arrest. Group 1 (7 dogs) was administered cardioplegic solution from a plastic bag under pressure into the ascending aorta every 20 minutes for the 2-hour period, and Group 2 (7 dogs) was given cardioplegia by means of a roller pump.Myocardial temperature decreased in Group 1 to 13.4°C following administration of the cardioplegic solution, and to 13.1°C in Group 2 (not significant). These temperatures were reached in 3.0 minutes in Group 1 and 1.9 minutes in Group 2 (p < 0.03). Aortic root pressures during cardioplegic infusion were 31 ± 2 mm Hg in Group 1 versus 46 ± 2 mm Hg in Group 2 (p < 0.01). No significant differences between groups were noted in myocardial distribution of cardioplegia, myocardial blood flow or metabolism, or left ventricular hemodynamics.We conclude that both methods of administering cardioplegia lowered myocardial temperature adequately and protected the myocardium for a period of 2 hours in these normal hearts. The roller pump method facilitated faster cooling and produced significantly higher aortic perfusion pressures, however, which may be important in hearts with coronary stenosis.     

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)     

Improved myocardial preservation during global ischemia by continuous retrograde coronary sinus perfusion

To investigate whether retrograde continuous low-pressure perfusion of the coronary sinus could deliver cardioplegic solutions with oxygen and substrate beyond stenoses and result in improved myocardial preservation, we subjected 41 canine hearts to 90 minutes of ischemia with an occlusion on the circumflex coronary artery. There were four groups: Group I, antegrade (aortic root) crystalloid cardioplegia every 30 minutes during ischemia; Group II, antegrade plus topical cooling; Group III, continuous retrograde perfusion; Group IV, same as Group III, with an oxygenated perfluorocarbon. All solutions had a PO2 of 400 to 500 mm Hg. Intramyocardial oxygen and carbon dioxide tensions (PO2 and PCO2) and mean myocardial temperatures were monitored during ischemia, and left ventricular (LV) function was assessed before ischemia and after reperfusion. After global ischemia, the circumflex occlusion was released and the hearts reperfused. Following 60 minutes of reperfusion, isovolumic developed pressure returned to 36% +/- 4% and 41% +/- 5% of preischemic levels, respectively, in Groups I and II. By contrast, Groups III and IV (retrograde perfusion) had a significantly greater percent of recovery (78% +/- 5% and 73% +/- 5%). Circumflex area intramyocardial PO2 fell 20 and 25 mm Hg below preischemic levels in Groups I and II during ischemia, whereas in Group III, intramyocardial PO2 in the circumflex region remained near preischemic levels, and in Group IV, it rose 19 mm Hg. Mean myocardial temperature during ischemia in the circumflex area was significantly higher in Group I than in Groups II, III, and IV. Peak intramyocardial PCO2 in the circumflex region was significantly less in the retrogradely perfused hearts. Retrograde coronary sinus perfusion resulted in significant improvement in recovery of LV function, uniform myocardial cooling, normal intramyocardial PO2, and less intramyocardial PCO2 accumulation, despite the presence of a total circumflex coronary artery occlusion.     

Rapid cooling contracture of the myocardium. The adverse effect of prearrest cardiac hypothermia

Hypothermic total circulatory arrest for repair of congenital heart lesions in neonates requires a period of rapid core cooling on cardiopulmonary bypass during which the myocardium is also exposed to hypothermic perfusion. Myocardial hypothermia in the nonarrested state results in an increase in contractility due to elevation of intracellular calcium levels. This study was designed to test the hypothesis that rapid myocardial cooling before cardioplegic ischemic arrest results in damage, with impaired recovery during reperfusion. Two groups of 10 rabbit hearts were perfused on an isolated Langendorff apparatus. Group N (normothermia) was perfused at 37 degrees C before 2 hours of cardioplegic ischemic arrest at 10 degrees C. Group C (cooling) was perfused at 15 degrees C in the unarrested state for 20 minutes before the same cardioplegic arrest conditions as group N. Left ventricular isovolumic pressure measurements, biochemical measurements from right ventricular biopsy specimens, and ventricular necrosis as defined by tetrazolium staining were used to compare the groups at 30 and 60 minutes of normothermic reperfusion. Developed pressure at a constant volume was preserved in group N at 90.7 +/- 4.5 mm Hg versus 76.9 +/- 6.3 in group C after reperfusion (p less than 0.05). Diastolic compliance showed significant deterioration in group C, with marked elevation of diastolic pressure during reperfusion (group N = 6.8 +/- 2.5 mm Hg versus group C = 38.9 +/- 6.1 after reperfusion; p less than 0.001). Adenosine triphosphate levels were significantly higher in group N both at end-ischemia and after reperfusion versus group C (group N = 17.0 +/- 1.1 nmol/mg protein versus group C = 7.7 +/- 1.0 after reperfusion; p less than 0.001). Group N had 0.4% +/- 0.4% necrosis of ventricular mass versus 19.3% +/- 2.2% with prearrest cooling in group C (p less than 0.0001). These results indicate that, when combined with cardioplegic ischemic arrest, rapid myocardial cooling in the unarrested state results in significant damage. The mechanism may be related to the cytosolic calcium loading effect of hypothermia that is not relieved during the subsequent period of cardioplegic arrest. Although hypothermia is an essential component to ischemic preservation, rapid cooling contracture can adversely influence cardioplegic myocardial protection.     

Continuous measurement of intramyocardial pH: relative importance of hypothermia and cardioplegic perfusion pressure and temperature

The continuous measurement of intramyocardial pH was used to follow the progression of ischemia and permit correlation to functional recovery. Adequacy of myocardial preservation following 38 degrees C or 25 degrees C global ischemia alone or with the administration of one or two doses of 38 degrees C, 25 degrees C, or 1 degree C crystalloid cardioplegia at aortic root perfusion pressures of 90 mm Hg or 130 mm Hg was assessed. A new miniature myocardial transducer incorporating fiberoptic technology and dual pH and temperature-sensing capability was placed into the left ventricular free wall and septum of 44 sheep undergoing ischemic arrest during cardiopulmonary bypass. All groups underwent global ischemia until myocardial pH was 6.8. An intramyocardial pH level of 6.8 reliably correlated to similar levels of functional recovery in each group. Aortic root perfusion pressure of 130 mm Hg provided enhanced myocardial protection by increasing the total ischemic time (5 to 10 minutes) with one (p less than 0.01) or two (p less than 0.001) doses of cardioplegic solution until a given functional level of recovery was attained. Aortic root perfusion pressure of 90 mm Hg provided no added benefit in total ischemic time, rate of change of pH, or degree of recovery of function. Hypothermic (25 degrees C) global ischemia alone enhanced myocardial protection by providing increased time (p less than 0.01) until a given functional level of recovery was attained with a slower rate of change of pH (p less than 0.01) compared with normothermic (38 degrees C) global ischemia alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial energetics after thermally graded hyperkalemic crystalloid cardioplegic arrest

Previous studies assessing the efficacy of myoprotective regimens have compared preischemic and postischemic myocardial oxygen consumption within a limited range of cardiac performance. However, recent data suggest that ischemia-induced perturbations in myocardial energetics may occur only when the left ventricle develops physiologic pressures. Therefore, in canine hearts supported by cardiopulmonary bypass, myocardial oxygen consumption (ml oxygen X 10(-2)/beat/100 gm left ventricular weight) was determined during incremental isovolumic pressure-volume loading before and 30 minutes after 2 hours of cardioplegic arrest. The ischemic insult was graded by maintaining myocardial temperature at 12 degrees C (Group I, n = 6), 20 degrees C (Group II, n = 7), or 28 degrees C (Group III, n = 6). Postischemic Starling curves were unchanged in Groups I and II but depressed 53% in Group III hearts (p less than 0.005). In Group I, postischemic myocardial oxygen consumption at specific peak developed pressures was similar to preischemic oxygen consumption. In contrast, postischemic Group II and III hearts consumed 39% more oxygen than preischemically when peak developed pressure exceeded 75 mm Hg (p less than 0.01). Postischemic hearts demonstrated reciprocal changes in arteriovenous oxygen content difference (24%, 30%, and 34% lower than preischemic values for Groups I, II, and III, respectively) and coronary blood flow (156%, 195%, and 192% higher than preischemic values for Groups I, II, and III, respectively). Only in Group II and III hearts did the increased coronary blood flow offset the defect in oxygen extraction such that myocardial oxygen consumption was increased. These data suggest that inefficient utilization of oxygen when the heart is developing physiologic pressures is a sensitive marker for myocardial injury after crystalloid cardioplegic arrest.     

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.     

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.     

Inadequate cardioplegic protection with obstructed coronary arteries.

To determine the contribution of complete cardioplegia to the preservation of left ventricular (LV) function, we put ultrasonic transducers in the anterior and posterior walls of the left ventricle in 18 dog hearts. The dogs were subjected to global ischemia for 60 minutes at 28°C, and the speed of segment shortening (dl/dt) and percent of systolic shortening of the two wall regions before and after ischemic manipulations were measured. When cardioplegic perfusion was uniform, there was no significant difference between the anterior and posterior walls in any of the variables measured, and global LV function (stroke work) was well preserved. However, when the left anterior descending coronary artery was occluded during cardioplegic infusion, there was significant dysfunction after reperfusion of the anterior wall: without perfusion, the anterior segments recovered only 41% (5.9/14.3 mm/sec) of preischemic dl/dt, while the perfused anterior segments retained 78% (11.4/14.6 mm/sec) of control dl/dt (p < 0.05). The experimental anterior regions regained only 36% of preischemic systolic shortening, while the anterior segments in the homogeneously perfused hearts were indistinguishable from internal controls (p < 0.01).Regionally inadequate cardioplegic protection during coronary artery bypass graft operation may contribute to perioperative infarction and LV dysfunction, and appropriate timing of anastomoses to ensure early cardioplegic perfusion of all ischemic myocardium is important.     

Does On‐Pump/Beating‐Heart Coronary Artery Bypass Grafting Offer Better Outcome in End‐Stage Coronary Artery Disease Patients?

OBJECTIVES: The purpose of our study was to evaluate in a cohort of end-stage coronary artery disease (ESCAD) patients the effects of on-pump/beating-heart versus conventional coronary artery bypass grafting (CABG) requiring cardioplegic arrest. We report early and midterm survival, morbidity, and improvement of left ventricular (LV) function. METHODS: Between January 1992 and October 1999, 107 (Group I) ESCAD patients underwent on-pump/beating-heart surgery and 191 (Group II) ESCAD patients underwent conventional CABG requiring cardioplegic arrest. Mean age in Group I was 65.8 +/- 6.5 years (58-79 years); New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) classifications were 3.2 +/- 0.4 and 3.3 +/- 0.5, respectively. LV ejection fraction (LVEF) was 24.8% +/- 4%, LV end diastolic pressure (LVEDP) was 28.2 +/- 3.8 mmHg, and LV end diastolic diameter (LVEDD) was 69.6 +/- 4.6 mm. Mean age in Group II was 64.1 +/- 5 years (57-76 years), NYHA class was 3 +/- 0.6, CCS class was 3.4 +/- 0.4, LVEF was 26.2% +/- 4.3%, LVEDP was 27.2 +/- 3.4 mmHg, and LVED was 68 +/- 4.2 mm. RESULTS: Preoperatively, Group I patients versus Group II patients had a markedly depressed LV function (LVEF, p = 0.006; LVEDP, p = 0.02; LVEDD, p = 0.003; and NYHA class, p = 0.002), older age (p = 0.012), and higher incidences of multiple acute myocardial infarction (AMI; p = 0.004), cardiovascular disease (CVD; p = 0.008), and chronic renal failure (CRH, p = 0.002). Cardiopulmonary bypass (CPB) time was longer in Group II patients (p = 0.028). The mean distal anastomosis per patient was similar between groups (p = NS). Operative mortality between Groups I and II was 7 (6.5%) and 19 (10%), respectively (p = NS). Perioperative AMI (p = 0.034), low cardiac output syndrome (LCOS; p = 0.011), necessity for ultrafiltration (p = 0.017), and bleeding (p = 0.012) were higher in Group II. Improvement of LV function within 3 months after the surgical procedure was markedly higher in Group I, demonstrated by increased LVEF (p = 0.035), lower LVEDP (p = 0.027), and LVEDD (p = 0.001) versus the preoperative data in Group II. The actuarial survivals at 1, 3, and 5 years were 95%, 86%, and 73% in Group I and 95%, 84%, and 72% in Group II (p = NS). CONCLUSIONS: ESCAD patients with bypassable vessels to two or more regions of reversible ischemia can undergo safe CABG with acceptable hospital survival and mortality and morbidity. In higher risk ESCAD patients, who may poorly tolerate cardioplegic arrest, on-pump/beating-heart CABG may be an acceptable alternative associated with lower postoperative mortality and morbidity. Such a technique offers better myocardial and renal protection associated with lower postoperative complications.     

Influence of Potassium Cardioplegia versus Ischemic Arrest on Regional Left Ventricular Diastolic Compliance in Humans

To compare the effects of hypothermic ischemic arrest versus hypothermic potassium cardioplegia, regional left ventricular performance was monitored in 20 adult male patients undergoing saphenous vein bypass operation. Twelve patients received ischemic arrest (Group 1), and 8 received potassium cardioplegia (Group 2). Groups 1 and 2 did not differ in left ventricular ejection fraction (0.62 versus 0.60), number of bypassed vessels (3.7 versus 3.4), mean cross-clamp time (75 versus 63 minutes), or mean cardiopulmonary bypass time (182 versus 170 minutes). Before cardiopulmonary bypass was begun, a pair of ultrasonic crystals was secured in the left ventricular anterior myocardium to measure segment motion and a micromanometer-tipped catheter was placed in the left ventricular chamber. All patients received a saphenous vein bypass graft to a vessel supplying the anterior left ventricular wall in the region of the ultrasonic crystals.Comparison of changes in systolic measurements revealed no significant differences between Groups 1 and 2. After saphenous vein bypass grafting, the left ventricular end-diastolic pressure (11.4 to 17.0 mm Hg) and modulus of left ventricular segment stiffness (0.37 to 0.67, p < 0.02) were elevated in Group 1 but no changes were observed in Group 2 (14.0 to 15.6 mm Hg, and 0.16 to 0.24, respectively).Compared with hypothermic ischemic arrest, hypothermic potassium cardioplegia is not associated with an increased left ventricular diastolic stiffness shortly after saphenous vein bypass grafting in humans.     

The effects of cardioplegic arrest on right atrial function

Atrial electrical and mechanical activity persists during cardioplegic arrest. It has been postulated that atrial ischemia may occur and cause deterioration in atrial function. This study was designed to assess the effect of cardioplegic arrest on right atrial function. Twenty-one pigs were placed on cardiopulmonary bypass (CPB), and the right atrium was isolated from the circulation by snaring both venae cavae and incising the coronary sinus. The tricuspid valve was closed through a small right ventriculotomy, and baseline atrial function was assessed using a compliant balloon in the atrium. Fourteen pigs underwent one hour of cardioplegic arrest (7 with cardioplegia alone [CCA group] and 7 with the addition of topical hypothermia [CCA + TH group]) followed by one hour of normothermic reperfusion. Seven other pigs were placed on CPB for the same period of time (CPB group). Atrial electrical and mechanical activity persisted at 45 beats per minute in the CCA group but was virtually abolished in the CCA + TH group. Cardioplegic arrest caused considerable deterioration in right atrial function (developed pressure, 18.9 +/- 0.8 [baseline] versus 14.1 +/- 0.7 mm Hg; p less than 0.05; first derivative of atrial pressure [dP/dt], 187 +/- 19 versus 134 +/- 25 mm Hg per second; p less than 0.05; 60 minutes of reperfusion and balloon volume of 20 ml). It was not affected by topical cooling. Right atrial developed pressure was maintained, but dP/dt was significantly reduced in the CPB group. This study suggests that cardioplegic arrest does not protect the atrium.     

Right ventricular function: a comparison between blood and crystalloid cardioplegia

Blood cardioplegia resulted in better left ventricular (LV) function than crystalloid cardioplegia after elective coronary artery bypass operations. However, most methods of cardioplegic delivery may not adequately cool and protect the right ventricle, and right ventricular (RV) dysfunction may limit hemodynamic recovery. Therefore, RV and LV temperatures were measured intraoperatively and RV and LV function were evaluated postoperatively in 80 patients with double-vessel or triple-vessel coronary artery disease who were randomized to receive either blood cardioplegia or crystalloid cardioplegia. Myocardial performance, systolic function, and diastolic function were assessed with nuclear ventriculography by evaluating the response to volume loading. Preoperatively the groups were similar. Intraoperatively, blood cardioplegia resulted in significantly warmer LV and RV temperatures (left ventricle: 15.5 degrees +/- 0.2 degrees C with blood cardioplegia and 12.6 degrees +/- 0.3 degrees C with crystalloid cardioplegia [p less than .0001]; right ventricle: 18.3 degrees +/- 0.3 degrees C with blood cardioplegia and 15.1 degrees +/- 0.3 degrees C with crystalloid cardioplegia [p less than .0001]). Postoperatively, blood cardioplegia resulted in better LV performance (higher LV stroke work index at a similar LV end-diastolic volume index [EDVI]) (p = .01), better LV systolic function (similar systolic blood pressures at smaller LV end-systolic volume indexes [ESVI]), (p = .04), and improved LV diastolic function (lower left atrial pressures at similar LVEDVIs) (p = .03).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Comparison of washed blood and oxygenator whole blood as vehicles for sanguinous multidose cardioplegia

The effects of washed blood or oxygenator-traumatized whole blood as vehicles for sanguinous cardioplegia were studied utilizing the isolated blood-perfused dog heart preparation. Hearts were subjected to 2 hr of potassium-induced arrest at 27 degrees C followed by 90 min of normothermic reperfusion. Washed blood cardioplegia (n = 7) contained blood washed thrice with saline while oxygenator blood cardioplegia (n = 6) contained whole blood which had been exposed to an extracorporeal circuit for 30 to 45 min. Cardioplegic solutions were administered at a perfusion pressure of 100 mm Hg every 15 min during arrest. While the arrest-reperfusion sequence caused minor variations in the mechanical, metabolic, and biochemical parameters tested, generally insignificant differences were found to exist between groups. Differences in coronary washout PCO2 appeared to be due to inherent differences between the two cardioplegic solutions. Thus, while washing blood may be thought to be beneficial and whole blood from the extracorporeal circuit may be theorized to have a deleterious effect on the myocardium, excellent recovery of mechanical function was observed with both cardioplegic solutions. The present study suggests that it is unnecessary to wash the sanguinous cardioplegic solution obtained from the cardiopulmonary circuit.     

Protection of the immature heart. Temperature-dependent beneficial or detrimental effects of multidose crystalloid cardioplegia in the neonatal rabbit heart

There are conflicting reports of the detrimental or beneficial effects of hypothermic cardioplegia in the immature heart. We therefore investigated the temperature-dependence of myocardial protection and the ability of single-dose and multidose infusions of cardioplegic solution to protect the immature heart during hypothermic ischemia. Isolated, working hearts (n = 6 per group) from neonatal rabbits (aged 7 to 10 days) were perfused aerobically (37.0 degrees C) for 20 minutes before infusion (2 minutes) with either perfusion fluid (noncardioplegia control) or St. Thomas' Hospital cardioplegic solution and ischemic arrest (for 4, 6, and 18 hours) at various temperatures between 10.0 degrees and 30.0 degrees C. Hearts arrested with cardioplegic solution received either one preischemic infusion only (single-dose cardioplegia) or repeated infusions at intervals of 60 or 180 minutes (multidose cardioplegia). Ischemic arrest with single-dose cardioplegia for 4 hours at 10.0 degrees, 20.0 degrees, 22.5 degrees, 25.0 degrees, 27.5 degrees, and 30.0 degrees C resulted in 96.0% +/- 4.3%, 96.6 +/- 2.5%, 87.0% +/- 3.8%, 71.8% +/- 10.0% (p less than 0.05 versus 10.0 degrees C group), 35.1% +/- 10.3% (p less than 0.01 versus 10.0 degrees C group), and 3.0% +/- 1.9% (p less than 0.04 versus 10.0 degrees C group) recovery of preischemic cardiac output, respectively. With 6 hours of ischemia at 20.0 degrees C, single-dose cardioplegia significantly (p less than 0.01) increased the recovery of cardiac output from 20.9% +/- 13.1% (control) to 76.4% +/- 4.4%, whereas multidose cardioplegia (infusion every 60 minutes) further increased recovery to 97.8% +/- 3.8% (p less than 0.01 versus control and single-dose cardioplegia). In contrast, after 6 hours of ischemia at 10.0 degrees C, cardiac output recovered to 93.4% +/- 1.2% (control) and 92.3% +/- 3.1% (single-dose cardioplegia), whereas multidose cardioplegia reduced recovery to 76.9% +/- 2.2% (p less than 0.01 versus both groups). This effect was confirmed after 18 hours of ischemia at 10.0 degrees C; single-dose cardioplegia significantly increased the recovery of cardiac output from 24.5% +/- 10.9% (control) to 62.9% +/- 13.3% (p less than 0.05), whereas multidose cardioplegia reduced recovery to 0.8% +/- 0.4% (p less than 0.01 versus single-dose cardioplegia) and elevated coronary vascular resistance from 8.90 +/- 0.56 mm Hg.min/ml (control) to 47.83 +/- 9.85 mm Hg.min/ml (p less than 0.01). This effect was not reduced by lowering the infusion frequency (from every 60 to every 180 minutes).(ABSTRACT TRUNCATED AT 400 WORDS)     

Experimental evaluation of secondary blood cardioplegia

Reperfusion damage after ischemia may be evidenced by myocardial cell edema, intracellular calcium accumulation, and limited utilization of oxygen. The need for cardioplegic arrest during initial reperfusion to allow oxygen to be used for reversing ischemic damage rather than for electromechanical activity has been propounded by some researchers. Reports of greater postischemic compliance and performance, low postischemic edema, and greater oxygen uptake at a perfusion pressure of 50 mm Hg or lower have been cited. The present study was conducted on 24 pigs having 2-hr cardioplegic arrest, which of 12 underwent normal reperfusion and 12 experienced secondary cardioplegia followed by normal reperfusion. The results showed that in spite of improved high-energy phosphate preservation, the secondary cardioplegia group had higher myocardial edema, less coronary flow, and poorer contractility and compliance at the end of 1 hr of reperfusion. Because of these findings and contradictory results reported by other groups, caution is urged in the clinical extrapolation of the results of such studies pending further investigations.     

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.     

Core-cooling, heart-perfusion, lung-immersion technique provides successful cardiopulmonary preservation for heart-lung transplantation

Mongrel dogs underwent heterotopic heart-orthotopic left lung transplantation. In Group I (N = 6), donor organs procured following core cooling to 15 degrees C on cardiopulmonary bypass (CPB) with cardioplegic arrest were immediately transplanted. In Group II (N = 6), following cardioplegic arrest without CPB core-cooling, the pulmonary artery was flushed with modified Collins' solution. Heart-lung blocks were immersed in extracellular solution for 6 hours and then transplanted. In Groups III and IV (N = 6 each), following CPB core-cooling to 15 degrees C and cardioplegic arrest, the organ blocks were immersed in extracellular solution (Group III) and the heart was perfused with oxygenated extracellular solution (Group IV). Evaluation of lung function using differences in arterial oxygen tension between the left and right atria demonstrated no differences between groups. However, extravascular lung water and pulmonary vascular resistance were significantly elevated in Group II. Cardiac function assessed by the ratio of end-systolic pressure to end-systolic dimension was significantly better in Group IV than in Groups II and III. Thus, adequate 6-hour hypothermic cardiopulmonary preservation with core cooling plus heart perfusion can be achieved for heart-lung transplantation.