"Directed" cardioplegia: a new approach in myocardial protection in left main coronary artery disease.

"Directed cardioplegia" is a novel approach in myocardial protection in which a certain volume of cardioplegic solution is diverted into a severely diseased coronary artery after surgical occlusion of the other main branches that can be accessed by the surgeon. In this way, the surgeon is able to eliminate the cardioplegic steal from a severely stenosed vessel through other less severely diseased and/or patent arteries during the nonselective antegrade administration of cardioplegia and to protect myocardial regions, which are poorly perfused. We performed this new technique in 2 patients with severe left main coronary artery disease with excellent results.

Pulmonary sequestration of cardioplegia administered via the aortic root during aortocoronary bypass surgery.

UNLABELLED: A semi-quantitative method was devised of tracing blood flow through the heart and lungs at the time of cardioplegia delivery and circulatory arrest of the heart during coronary artery bypass graft surgery (CABG). There were no previous studies confirming or disputing an accepted 'observation' by cardiac surgeons that cardioplegia solution does enter the lung parenchyma during cardiopulmonary bypass (CPB). This study was conducted as part of a larger (n = 142) double-blind, randomised, controlled, clinical research study. OBJECTIVE: The objective was initially to establish the efficacy of measures to prevent cardioplegia entering the lungs and, subsequently, to determine whether cardioplegia indeed circulates through the lung parenchyma or merely accumulates and 'pools'. METHOD: A prospective study on 20 consecutive patients (5 per group) admitted for CABG was made. Technetium (Tc-99m), a radioactive isotope, was added to the cold blood cardioplegia solution prior to cardioplegia delivery in order to track flow of cardioplegia solution. An independent nuclear medicine radiographer measured the samples with the use of a 'Curimentor' dose calibrator for presence and quantity of radiation in the samples. Decay was factored into the results. The Tc-99m tracer samples were also analysed using Gamma Acquisition and Analysis on the Genie 2000vdm Well Counter to confirm the presence and quantity of Tc-99m. RESULTS: In the four groups, it was confirmed that the pulmonary artery (PA) vent is 90-100% effective in retrieving any cardioplegia solution not drained by the atriocaval cannulae. CONCLUSIONS: The PA vent is effective in preventing cold blood cardioplegia solution from entering the lungs. Any cardioplegia that does enter the lung parenchyma during CPB circulates through the lungs and can be retrieved by a vent in the left atrium. This method may be useful in other studies that require investigation.

Heterogeneous distribution of cardioplegic solution in pigs.

Septal dyskinesia in the left ventricle is detected frequently in many patients after open-heart surgery. The present study was designed to determine whether the antegrade delivery of cardioplegic solution to the regional wall categorized in echocardiography is homogeneous, and whether the distribution to the septal wall differs from that to the lateral wall in the absence of coronary artery disease. To assess these hypotheses quantitatively, radioactive microspheres were mixed into the cardioplegic solution and infused by an antegrade method in eight normal pigs. The cardioplegic distribution to the septal wall was significantly less than to the lateral wall close to the base of the left ventricle (P<0.05). Therefore, antegrade perfusion of cardioplegic solution was non-uniformly distributed to the regional and transmural wall of normal pig hearts. Absence of functional correlation was a limitation of this study. However, these findings suggest that inadequate protection of the ventricular septum by antegrade cardioplegia might be an explanation for the abnormalities of septal wall motion after open-heart surgery.

The temperature dependence of cardioplegic distribution in the canine heart.

BACKGROUND: Cold cardioplegic arrest can produce cooling contracture and suboptimal myocardial protection. This study examines whether cooling contracture is associated with maldistribution of cardioplegic solution, particularly subendocardial hypoperfusion, which may impair recovery. METHODS: Canine hearts were arrested by antegrade cold and warm blood cardioplegia in random order. Cardioplegic distribution was measured using radiolabeled microspheres before and just after induction of each period of arrest. RESULTS: With cold cardioplegia, perfusion of left ventricular subepicardial and midwall regions decreased. Subendocardial to subepicardial perfusion ratios increased significantly in the left ventricle as a whole, the anterior and posterior regions of the left ventricular free wall, and the interventricular septum. With warm arrest, transmural flow distribution was not significantly altered from preceding prearrest values. At constant coronary flow, coronary perfusion pressure was initially similar after induction of arrest at both temperatures, but it rose subsequently during warm cardioplegia. CONCLUSIONS: The data suggest that during normothermic arrest, vasomotor tone regulates cardioplegic distribution, and hyperkalemic vasoconstriction is of slow onset. In the absence of beating and with vasomotion inhibited by hypothermia, cardioplegic distribution during cold arrest appears to be primarily dependent on vascular anatomy. There was no evidence of subendocardial underperfusion during cooling contracture.

La solución intracelular de Bretschneider preserva mejor la función miocárdica que la solución extracelular de St Thomas Nº 1 / Superior myocardial protection of the intracellular solution of Bretschneider compared to the extracellular solution of St Thomas Nº 1

Las soluciones de cardioplejia han reducido en forma significativa el daño isquémico del corazón asociado a la cirugía cardíaca. Sin embargo, existe controversia sobre cual es el tipo de solución ideal. En este estudio comparamos la efectividad entre la solución extracelular de St. Thomas Nº 1 (ST) y la solución intracelular de Bretschneider (BT). En ratas Sprague-Dawley se evaluó la función cardíaca in vitro por el método del corazón aislado de Langerdorff. Los corazones fueron perfundidos con (10ml/kg) de la solución ST o BT, los que posteriormente fueron evaluados luego de 0 horas (sham), 1 hora y 4 horas de isquemia preservados a 4ºC. A un grupo control sin isquemia no se perfundió cardioplejia. Las soluciones se compararon evaluando la incidencia de arritmias, el flujo coronario, la contractilidad (pendiente de la relación tensión-elongación sistólica desarrollada), y distensibilidad miocárdica (cambio de volumen diastólico del ventrículo izquierdo en un rango de presión diastólica entre 0 y 25 mmHg). La solución de BT preservó mejor (p<0,05) la contractilidad miocárdica que la solución de ST, tanto a la hora como a las cuatro horas de isquemia. Por otra parte, a las cuatro horas de isquemia la solución de BT preservó mejor (p<0,05) la distensibilidad miocárdica que la solución de ST. No hubo diferencias en la incidencia de arritmias o en el flujo coronario entre los grupos experimentales. Nuestros resultados muestran que la solución de BT preserva mejor la función sistólica y diastólica que la solución de ST luego de 4 horas de isquemia

Assessment of myocardial distribution of retrograde and antegrade cardioplegic solution in the same patients.

OBJECTIVE: In order to clarify intramyocardial delivery and distribution of retrograde cardioplegic solution in humans, we induced both ante- and retrograde methods in the same patients to compare their respective delivery and distribution using myocardial contrast echocardiography during surgery. METHODS: 15 patients consisting of nine patients with valvular heart diseases and six patients with coronary artery diseases (including two patients with myocardial infarcted areas and two patients with areas supplied by coronary collateral situation associated with totally occluded coronary arteries without myocardial infarction). Induction of cardioplegia was initially accomplished antegradely and thereafter retrogradely. RESULTS: In valvular heart disease, retrograde cardioplegic solution was distributed less homogeneously, and was not delivered to the midportion of the interventricular septum in two-thirds of the patients (6/9). The transmural myocardial distribution in the anterior, lateral, and posterior walls in the left ventricle were similar for both ante- and retrograde cardioplegic solution, while delivery to the endocardial halves was better than to the epicardial halves (endo-/epicardial intensity ration in antegrade versus retrograde: 1.31 +/- 0.24 versus 1.29 +/- 0.26; 1.19 +/- 0.05 versus 1.36 +/- 0.23; 1.33 +/- 0.28 versus 1.44 +/- 0.35, respectively (all NS)). For delivery to the right ventricle, the existence of small cardiac vein was important. In patients with small cardiac vein (34% in our study), the delivery to the right ventricular dorsal walls was shown. In coronary heart disease, retrograde cardioplegic solution was well delivered to the areas by coronary collateral situation associated with totally occluded coronary arteries, but antegrade solution was not. Neither ante- nor retro grade solution was delivered to myocardial infarcted areas. CONCLUSIONS: These results have important implications for planning strategies for myocardial protection. We think that it is necessary to fully grasp the coronary arterial and venous anatomy of individual patients and to know how to use either ante- or retrograde cardioplegia properly.

Myocardial distribution of cardioplegia administered by antegrade and retrograde routes to ischemic myocardium.

OBJECTIVE: To study the distribution of a cardioplegic solution delivered by antegrade and retrograde routes to ischemic myocardium. Retrograde administration has been suggested to improve protection of the ischemic myocardium. However, there are insufficient data on perfusion of ischemic and necrotic zones by the retrograde route. DESIGN: A laboratory study in dogs. METHOD: In 12 dogs, 500 mL of hyperkalemic crystalloid cardioplegia containing 0.5 mCi of thallium-201 was injected antegradely or retrogradely through the coronary sinus after 3 hours of occlusion and 2 hours of reperfusion of the left anterior descending coronary artery. Myocardial distribution of the cardioplegic solution was measured by computer planimetry in the normally perfused zone, in the ischemic area and in the necrotic zone. RESULTS: The mean (and standard deviation) area at risk of ischemia (% of the left ventricle) delimited by Evans blue perfusion was smaller in dogs receiving a retrograde injection than in those receiving an antegrade injection (34% [3%] v. 42% [4%], p = 0.15). The infarct size (% of the area at risk indicated by triphenyltetrazolium dye) averaged 25% (11%) and 20% (7%) respectively (p = 0.36). The ratio of thallium-201 activity in ischemic to normal myocardium averaged 76% (13%) in the retrograde and 89 (12%) in the antegrade groups (p = 0.75). The ratio of thallium activity of infarct to normal myocardium averaged 56% (8%) in the retrograde group and 93% (19%) in the antegrade group (p = 0.18). Large areas of hypoactivity in the left ventricular myocardium were noted on scintigraphic imaging in all dogs that received retrograde perfusion. CONCLUSIONS: The retrograde injection of cardioplegia through the coronary sinus does not improve the distribution of cardioplegic solution in the acutely ischemic myocardial area nor in the zone of acute infarction in the dog. Because some cells may remain viable in the border zone and into the necrotic area, retrograde cardioplegia may result in suboptimal protection and incomplete prevention of further damage to the myocardium.

Retrograde cold blood cardioplegia. Obliteration of the posterior interventricular vein in the coronary sinus improves cooling of the left ventricle posterior wall.

The study hypothesis was that obliteration of the posterior interventricular vein in the coronary sinus avoids the back leak of cardioplegia to the right atrium and forces cardioplegia towards the posterior wall of the left ventricle and interventricular septum. A new retrograde cardioplegia cannula with a long balloon (3 cm) was designed which obstructs the posterior interventricular vein in the coronary sinus. The hypothesis was tested by a prospective randomized study in 52 consecutive patients who underwent coronary or aortic valve surgery. In group I (n = 26), the cannula prototype was used, while a standard cannula (balloon length 8 mm) was used in group II (n = 26). The cardioplegic solution was cold blood (14 degrees C). The posterior wall temperature was recorded when the anterior wall temperature reached 15 degrees C. In group I, 91% of patients had the same temperature in the anterior and posterior walls of the left ventricle versus 19% in group II (P < 0.05). The mean of the difference of left ventricular temperatures between anterior and posterior walls was 0.5 degrees C (sigma = 1.7) in group I versus 8 degrees C (sigma= 4.1 ) in group II (alpha < 0.05). In group I, 9.5% of patients had a posterior wall temperature > 20 degrees C versus 81% in group II (P < 0.05). Cooling of the posterior wall of the left ventricle is better in group I than in group II. As cooling and cardioplegia flow are closely linked, obliteration of the posterior interventricular vein in the coronary sinus improves left ventricular distribution of the cardiplegia.

Evidence of improved microvascular perfusion when using antegrade and retrograde cardioplegia.

BACKGROUND: The maximum degree of microvascular distribution of cardioplegic solution is considered important to achieve optimum myocardial protection. This study attempts to demonstrate that the addition of retrograde cardioplegia to antegrade cardioplegia improves overall microvascular perfusion. METHODS: Explanted human hearts (n = 6) were treated with cold cardioplegic arrest and bicaval cardiectomy. Blood cardioplegia (37 degrees C) containing colored microspheres (color A for antegrade, color B for retrograde) was simultaneously infused antegrade at a pressure of 80 mm Hg and retrograde at a pressure of 40 mm Hg for 2 minutes. The ventricular myocardium was then sampled at three sites to determine absolute and relative cardioplegic microvascular flow. RESULTS: Of the total microvascular capillary flow, 27% to 32% was found to be the contribution of retrogradely delivered cardioplegia. CONCLUSIONS: Despite being delivered simultaneously and at a lower pressure, retrograde cardioplegia contributed substantially to overall microvascular perfusion. This suggests that antegrade cardioplegia alone does not perfuse all available myocardial capillaries and that the addition of retrograde cardioplegia enhances overall microvascular distribution and perfusion.

[Left ventricular distribution of retrograde cardioplegia. Should the interventricular posterior vein be occluded in the coronary sinus?]. / Distribution ventriculaire gauche de la cardioplégie rétrograde. Faut-il obturer la veine interventriculaire postérieure dans le sinus coronaire?

Retrograde cardioplegia is still controversial due to the heterogeneous left ventricular flow distribution particularly in the posterior wall. The purpose of this study was to compare retrograde flow distribution delivered through the coronary sinus with two types of cannula. Fifty two patients were prospectively randomized to receive cold blood retrograde cardioplegia with manual inflating long balloon prototype cannula (group I, 26 patients) or with manual inflating short balloon cannula (group II, 26 patients). Left ventricular distribution of the cardioplegic solution was assessed by monitoring the left ventricular wall temperatures (anterior and posterior). The cardioplegic retrograde infusion was stopped as the anterior wall temperature reached 15 degrees C. In group I, 91% of the patients had identical cooling in the anterior and posterior wall of the left ventricle, versus 19% in group II (p < 0.05). The mean temperature difference between anterior and posterior wall was 0.5 degrees C (standard deviation = 1.7) in group I versus 8 degrees C (standard deviation = 4.1) in group II (alpha < 0.05). The cannula with the long balloon allows a better left ventricular distribution of the cardioplegia flow than the short one because it occludes the interventricularis posterior vein in the coronary sinus.

Adequate distribution of warm cardioplegic solution.

Seventy-five patients undergoing coronary artery bypass grafting were randomized to receive warm antegrade (N = 25), warm retrograde (N = 25), or a combination of warm antegrade and retrograde (N = 25) delivery of blood cardioplegic solution. Myocardial oxygen utilization, lactate and acid metabolism, and adenine nucleotides and their degradation products were measured during the operation and cardiac function was assessed postoperatively. Warm retrograde delivery of cardioplegic solution increased lactate and acid release during cardioplegia and reperfusion, decreased left ventricular adenosine triphosphate concentrations, and reduced the washout of adenine nucleotide degradation products from both left and right ventricles. Warm antegrade delivery of cardioplegic solution resulted in less lactate and acid release during cardioplegia but more lactate accumulated in the territory of the left anterior descending artery during the crossclamp period. Intermittent antegrade delivery of the cardioplegic solution during combination cardioplegia washed out lactate and acid, which suggested inhomogeneous delivery of the cardioplegic solution during continuous retrograde cardioplegia. Combination cardioplegia best preserved adenosine triphosphate in the left ventricle and resulted in the best postoperative left and right ventricular function. A combination of intermittent antegrade and continuous retrograde delivery of cardioplegic solution provided better myocardial protection than either antegrade or retrograde delivery of cardioplegic solution alone.

Ventricular effluent of retrograde cardioplegia in human hearts has traversed capillary beds.

BACKGROUND: In human hearts, as much as two thirds of retrograde cardioplegia is shunted through thebesian and arteriosinusoidal channels into the ventricular cavities. This ventricular effluent is believed to have bypassed the myocardial capillary beds and is therefore considered nonnutritive. METHODS: To test this hypothesis, we studied the explanted hearts from 9 cardiac transplant recipients with the diagnosis of idiopathic cardiomyopathy. These hearts were arrested in situ with cold blood cardioplegia and excised with the coronary sinus intact. The left and right coronary ostia and the coronary sinus then were cannulated. Colored microspheres (15 +/- 5 microns) mixed in 37 degrees C blood cardioplegia were administered through the coronary sinus at a pressure of 30 to 40 mm Hg. Effluents from the coronary arteries and ventricular chambers were collected and analyzed for microsphere concentration. RESULTS: Approximately 80% of retrograde cardioplegia solution was recovered in the ventricular chambers. Nearly 40% of this ventricular chambers effluent had traversed capillary beds and, thus, we believe has nutritive properties. Almost all of the coronary artery effluent of retrograde cardioplegia solution had traversed capillary beds. The total nutritive fraction of retrograde warm blood cardioplegia in this explanted human heart model was approximately 55%. CONCLUSIONS: These findings suggest that the ventricular chamber effluent of retrograde blood cardioplegia contributes to the metabolic homeostasis of the arrested human heart.

Retrograde-delivered cardioplegia is not distributed equally to the right ventricular free wall and septum.

Right ventricular myocardial protection during cardiac surgery continues to be a challenge. Retrograde delivery of cardioplegia has been shown to perfuse left ventricular regions subtended by critical coronary stenosis and not adequately protected by antegrade delivery. However, the distribution of cardioplegia from the coronary sinus to the right ventricle remains in question. A reliable means for assessing such flow distribution intraoperatively is provided by contrast echocardiography. It was hypothesized that conventional use of coronary sinus catheters for retrograde cardioplegia delivery does not reliably perfuse the myocardial region subtended by the right coronary artery. Six patients scheduled to undergo elective coronary artery bypass surgery were evaluated with contrast echocardiography to determine the distribution of retrograde-delivered cardioplegia into the right ventricle. Sonicated Renografin-76 (Squibb Diagnostics, Princeton, NJ) was injected during retrograde delivery of cold crystalloid cardioplegia solution and continuous two-dimensional ultrasound imaging of the heart. On-line videodensitometric analysis was performed with a digital ultrasound system. The area under the curve and peak pixel intensity were determined for the anterior septum, the posterior septum, and the right ventricular free wall for each contrast injection. Recorded VHS videotape images of contrast-enhanced perfusion patterns were also reviewed and scored. On-line acoustic-densitometric analysis showed that right ventricular posterior and anterior septal peak pixel intensities were 4.8 +/- 3.2 and 7.3 +/- 1.5, respectively, compared with only 1.6 +/- 1.2 (p < or = 0.05) in the right ventricular free wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial distribution of retrograde cardioplegic solution assessed by myocardial thallium 201 uptake.

Perfusion of the right ventricular myocardium with retrograde infusion of cardioplegic solution through the coronary sinus has been reported to be less than optimal. To study left and right ventricular perfusion during retrograde and antegrade coronary sinus cardioplegia, we added 0.5 mCi of thallium 201 to 500 ml of hyperkaliemic crystalloid cardioplegic solution injected retrogradely into the coronary sinus at low perfusion pressure (20 to 40 mm Hg) in 14 dogs and antegradely in the ascending aorta in seven dogs. The cardioplegic solution was cold (4 degrees C) in eight animals perfused retrogradely and warm (21 degrees C) in 13 animals. After aortic crossclamping, the ascending aorta and the left and right ventricles were vented and cardioplegic solution was injected retrogradely into the coronary sinus. Antegrade injections were performed after aortic crossclamping and venting of the left and right ventricles and of the left and right atrium. After cardioplegic arrest, the heart was harvested, fixed, and scanned with a gamma camera. With cold retrograde cardioplegia, 82% +/- 5% of the injected thallium 201 activity was identified in the myocardium--71% +/- 9% for warm retrograde perfusion and 80% +/- 3% for antegrade perfusion (p > 0.05). Focal areas of hypoactivity in the septum and in the right ventricular free wall were present at scintigraphic imaging in all animals receiving retrograde perfusion. In conclusion, most thallium 201 activity of cardioplegic solution injected retrogradely in the coronary sinus was identified in the myocardium, but focal areas of hypoactivity in the septum and in the right ventricular free wall were present, indicating uneven distribution. Temperature of the crystalloid solution had no effect on the myocardial distribution of the thallium 201 radiotracer in the myocardium.

Importance of the coronary collateral circulation for the distribution of anterograde and retrograde delivered cardioplegic solution in aortocoronary bypass surgery: a haemodynamic study.

The importance of coronary collateral circulation for homogeneous distribution of anterograde and retrograde delivery of cardioplegia was evaluated in 36 patients undergoing myocardial revascularization. All patients had three-vessel coronary artery disease, with a stenosis of the right coronary artery of at least 80%. The patients were randomized into two groups: group A (n = 19) received anterograde delivered cardioplegic solution and group B (n = 17) received retrograde. Both groups were further subdivided depending on the pathology of the right coronary artery, as evaluated on preoperative coronary angiography. In group A1 (n = 8) and group B1 (n = 7) there was no visualization of collateral circulation from the left to the right coronary artery system, whereas in group A2 (n = 11) and group B2 (n = 10) there was retrograde filling of the right coronary artery by collateral circulation. Right atrial pressure increased significantly (P < 0.05) in group A1 and was elevated in group A2, but not significantly (P = 0.07). By contrast, right arterial pressure decreased in groups B1 and B2. Analysis of the individual differences in the right atrial filling pressure showed a statistical significance between the two subgroups (group B1-1.0(0.5) versus group B2-1.8(1.1), P < 0.05), although the individual decrease of the right ventricular stroke work index was not significant. It is concluded that collateral circulation is important for an adequate distribution of anterogradely delivered cardioplegia and is also beneficial in cases of retrograde delivery.

The microvascular distribution of cardioplegic solution in the piglet heart. Retrograde versus antegrade delivery.

The uniform distribution of cardioplegic solution to all areas of the microvasculature is considered critical for myocardial protection. Despite this, little information exists regarding the ability of retrogradely infused cardioplegic solution to perfuse the microvasculature of the heart. In this report, the microvascular distribution of retrogradely delivered cardioplegic solution was studied by means of a technique to quantitatively demonstrate capillary perfusion. Duroc piglet hearts were subjected to either antegrade (n = 4) or retrograde (n = 8) perfusion fixation with 2.5% glutaraldehyde and subsequently perfused with NTB-2 (an intracapillary marker). The results indicate that retrogradely delivered NTB-2 consistently perfused the anterior half of the intraventricular septum and the anterior and lateral free walls of the left ventricle but inconsistently perfused the posterior half of the intraventricular septum, the posterior wall of the left ventricle, and a small paraseptal region of the right ventricle. The remainder of the right ventricle was not perfused. In contradistinction, all regions of the heart were consistently perfused by the antegrade technique. In regions of the heart in which retrograde microvascular perfusion occurred, no statistical difference was found in the quantitative degree of capillary perfusion achieved by either the antegrade or retrograde technique. These results have important implications for planning strategies of myocardial protection and suggest that further investigation concerning the microvascular distribution of retrogradely delivered cardioplegic solution in human beings is merited.