Off-pump versus on-pump coronary bypass in high-risk subgroups.

BACKGROUND: Cardiopulmonary bypass (CPB) has pathophysiologic sequelae that may be more severe in high-risk subsets. We wanted to determine whether off-pump coronary bypass (OPCAB) could optimize outcomes. METHODS: Our database of 242 OPCAB patients undergoing complete revascularization was compared to a base of 483 CABG patients undergoing CPB. Results were compared for the overall series and in the following high-risk subsets: 80 years of age or older, ventricular dysfunction (ejection fraction (EF) < or = 0.25), prior neurologic event or renal failure, chronic obstructive pulmonary disease (COPD), and reoperation. RESULTS: In the overall series, OPCAB significantly reduced the incidence of intraoperative transfusion requirements and showed a trend toward reduced morbidity in terms of postoperative neurologic and renal complications, prolonged ventilator requirement greater than 3 days, and bleeding requiring reexploration. Mortality was less in the OPCAB group (0.4% versus 2.7%, p = not significant). Similar results were achieved in the following high-risk subgroups (n = off-pump/on-pump): 80 years of age or older (n = 28/58), EF less than or equal to 25% (n = 13/26), preoperative neurologic event (n = 25/36), preoperative renal failure (n = 27/46), COPD (n = 33/43), and reoperation (n = 28/76). OPCAB decreased the incidence of prolonged ventilation in COPD patients (0/33 [0%] versus 4/43 [9.3%] p = not significant) and decreased the incidence of renal complications in the elderly (1/28 [3.6%] versus 9/58 [15.5%] p = not significant). Off-pump coronary bypass reduced but did not eliminate neurologic events in the elderly (2/28 [7.1%] versus 8/58 [13.8%] p = not significant). CONCLUSION: Off-pump coronary bypass significantly reduced the incidence of transfusion requirement compared to the CPB counterparts and had a consistent trend in reducing morbidity and mortality overall and in all high-risk subsets. Neurologic events are not eliminated in OPCAB.

Effect of off-pump coronary artery bypass grafting on morbidity.

Three hundred three patients who underwent off-pump coronary bypass were compared with 483 patients who underwent standard on-pump coronary bypass. There was a significant reduction in intraoperative blood transfusion requirements, as well as a significant reduction in the incidence of neurologic, renal, and prolonged ventilatory complications in the off-pump group.

Off-pump obtuse marginal grafting with local stabilization: thoracotomy approach in reoperations.

BACKGROUND: Redo coronary surgery in patients with patent internal mammary artery (IMA) grafts may be hazardous. A thoracotomy approach has been used to graft the circumflex branches to avoid injury from sternal re-entry. Combining this approach with off-pump revascularization techniques may be useful. METHODS: Seven consecutive patients who had undergone prior coronary revascularization developed symptoms attributable to lateral wall ischemia. Five of them had patent IMA grafts. These patients underwent off-pump obtuse marginal grafting using local immobilization techniques via a thoracotomy approach. Inflow was from the descending aorta in 6 patients and splenic artery in 1. RESULTS: Obtuse marginal grafting was successfully performed in all cases without need for cardiopulmonary bypass. CONCLUSIONS: Off-pump obtuse marginal grafting via the thoracotomy route may be useful in redo coronary surgery, particularly in instances of patent IMA grafts.

Technical aspects of total revascularization in off-pump coronary bypass via sternotomy approach.

BACKGROUND: Cardiopulmonary bypass and cardioplegic arrest result in known physiologic inflammatory, coagulopathic, and embolic states that may result in end-organ damage. Interest in off-pump complete coronary revascularization using sternotomy exposure is therefore increasing. METHODS: Using specific surgical and anesthetic techniques, we have been able to achieve total revascularization using off-pump coronary artery bypass grafting procedures (OP-CAB) through a sternotomy approach. Exposure techniques and local stabilization are tailored to individual vessels and cardiac regions. Vascular control is achieved with silicone-elastomer loops, occluders, and shunts. Poor ventricular function, advanced age, and other comorbid conditions, in and of themselves, were not considered contraindications to OP-CAB. Cardiomegaly or situations of small, intramyocardial, or heavily calcified vessels were relative contraindications to OP-CAB. RESULTS: Of 141 sternotomy OP-CAB cases, 132 (93.6%) were completely off-pump. The mean number of OP-CAB grafts per patient in the cases that were completely off-pump was 3.3 (range, 1 to 6). The 30-day operative mortality was 0%. There were four instances of intraoperative cardiac arrest, precipitated by vascular occlusion of the right coronary artery or manipulating a cardiomegalic heart. Advanced age (> or = 80 years) or profound ventricular dysfunction (ejection fraction < or = 0.25) was present in a considerable percentage of patients (10.6% and 9.9%, respectively). CONCLUSIONS: Off-pump coronary artery bypass grafting is successful for total revascularization in large numbers of patients. Anatomic factors, including cardiomegaly and small, intramyocardial, or heavily calcified vessels are possible contraindications to OP-CAB. Patients at highest risk for undergoing cardiopulmonary bypass, including those of advanced age and having ventricular dysfunction, are precisely the ones in whom OP-CAB may be the most useful.

Spontaneous closure of fenestrations in an interatrial Gore-Tex patch: application to the Fontan procedure.

The concept of the partial Fontan procedure, first described with the adjustable atrial septal defect (ASD) and more recently with the fenestrated technique, has become an accepted approach for the management of high-risk patients undergoing the Fontan procedure. Experience with both techniques has shown that a patent ASD placed in a prosthetic interatrial baffle may close spontaneously over a period of weeks to months. The mechanism and timing of spontaneous closure, as well as the effect of antiplatelet therapy on this process, are poorly understood. To better define this process, the interatrial septum of 15 mongrel dogs was excised and replaced with a fenestrated Gore-Tex (W.L. Gore, Flagstaff, AZ) patch. Postoperative echocardiography confirmed the patency of the ASD and left-to-right shunting. Animals were sacrificed 4 to 6 weeks postoperatively, or sooner if infection or other postoperative complications developed. Eight animals underwent no antiplatelet or anticoagulation therapy postoperatively, and 7 received antiplatelet therapy with aspirin. Patches were removed at the end of the study period and analyzed. By 6 weeks, all 2.7-mm and 4-mm holes had closed spontaneously in all animals that had not received antiplatelet therapy. The earliest closure occurred at 1 week. With antiplatelet therapy, hole closure was found to be delayed but not prevented, and was complete by 6 weeks in all but 1 animal. Histologic examination of the explanted patches revealed that closure was accomplished primarily through the ingrowth of fibrous tissue, accompanied by an inflammatory cell infiltrate.(ABSTRACT TRUNCATED AT 250 WORDS)

Girdling effect of nonstimulated cardiomyoplasty on left ventricular function.

The precise hemodynamic effects of latissimus dorsi cardiomyoplasty have not been well characterized. We prospectively studied 11 mongrel dogs using a rapid ventricular pacing model of congestive heart failure. Six dogs received a nonstimulated left latissimus dorsi cardiomyoplasty wrap, and 5 control dogs were paced only. Two-dimensional transthoracic echocardiography was performed on all dogs at baseline and then weekly for 4 weeks. Measurements obtained included left ventricular diameters, lengths, volumes, and ejection fractions. Progressive left ventricular enlargement, increase in volumes, and worsening ejection fractions developed in both groups. However, less left ventricular dilatation and higher ejection fractions were seen in dogs that received a cardiomyoplasty wrap. A nonstimulated cardiomyoplasty wrap significantly attenuated the degree of left ventricular enlargement, increase in left ventricular volumes, and decrease in ejection fraction in a rapid pacing model of congestive heart failure. Apart from its effect on systolic augmentation with a stimulated muscle wrap, cardiomyoplasty may have an important "girdling" effect on the left ventricle that prevents dilatation and deterioration of left ventricular function.

Orthotopic heart transplantation and concurrent coronary bypass.

Lack of donor organ availability is an increasing problem in heart transplantation. Methods to safely increase the donor pool are desperately needed. We report four cases of coronary artery bypass during orthotopic heart transplantation for donor hearts with normal ventricular function and subclinical coronary artery disease. An aggressive approach toward utilizing hearts from older donors with normal ventricular function may expand the donor pool and decrease the waiting period, with its attendant death, for patients awaiting heart transplantation.

Perfluorochemical reperfusion yields improved myocardial recovery after global ischemia.

Reperfusion injury remains a limiting factor in extending ischemic storage time for human heart transplantation. In this study, initial myocardial reperfusion with an oxygenated perfluorochemical (Fluosol) was investigated as a means of limiting such injury. Neonatal piglet hearts were arrested with crystalloid cardioplegia, excised, and stored for 12 hours in saline solution at 0 degrees C. Initial reperfusion (10 minutes) was either with whole blood (n = 6), unmodified perfluorochemical (n = 8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (n = 6), and was followed by an additional 40 minutes of whole blood perfusion. Functional evaluation was then completed, and left ventricular biopsy specimens were taken. A control group (n = 7) was evaluated without an intervening period of ischemia. At a left ventricular end-diastolic pressure of 9 mm Hg, hearts stored in whole blood cardioplegia developed a left-ventricular stroke work index of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean). Under the same conditions, perfluorochemical-reperfused hearts achieved a stroke work index of 14.6 +/- 1.3 x 10(3) erg/g, significantly greater than that of the whole blood group (p < 0.001). Stroke work index for hearts reperfused with aspartate/glutamate-enriched perfluorochemical cardioplegia was 19.8 +/- 1.6 x 10(3) erg/g, significantly increased over that of the nonenriched perfluorochemical group (p < 0.01) and not different from values obtained in controls (19.2 +/- 0.8 x 10(3) erg/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Modified Fontan procedure in patients less than 4 years of age.

BACKGROUND: Initial experience with the modified Fontan procedure in patients < 4 years of age has met with variable success, with early reports showing a high mortality. More recently, improved results with the modified Fontan procedure in younger patients have been achieved. Important advantages of an early Fontan include protection of the pulmonary vascular bed and preservation of ventricular function by reduction in ventricular volume overload and chronic hypoxemia. METHODS AND RESULTS: From 1982 through May 1991, 90 patients < 4 years of age underwent a modified Fontan procedure. The average age was 29 months (range, 7-48 months), and 30 patients were < 2 years of age. Diagnoses included tricuspid atresia in 36, single ventricle in 45, pulmonary atresia intact septum in seven, and hypoplastic left heart syndrome in two patients. An adjustable ASD was placed in 21. Early mortality was 8.9% (eight of 90), which is only slightly higher than our overall Fontan early mortality of 7.4% in 242 patients. The early mortality in the 30 patients < 2 years of age was 6.7% (two of 30). In a mean follow-up of 38 months (range, 7-89 months), there have been three late deaths (3.7%), and one patient has undergone cardiac transplantation. CONCLUSIONS: Early Fontan should be undertaken in patients > 6 months old who present with increasing cyanosis provided good hemodynamics are present. A modified Fontan procedure can be performed safely with good clinical results in patients < 4 years old.

Leukocyte-depleted reperfusion of transplanted human hearts: a randomized, double-blind clinical trial.

Standard methods of myocardial preservation for heart transplantation have generally provided good results. Preservation times beyond 3 hours, however, have been associated with decreased survival. Leukocyte-mediated reperfusion injury is partly responsible for decreased graft function after prolonged graft ischemia. Leukocyte-depleted reperfusion has been shown experimentally to improve cardiac function after cold ischemic arrest. To determine the efficacy and safety of leukocyte-depleted reperfusion, 20 patients were enrolled in a randomized, double-blind clinical trial to be treated with either warm whole blood reperfusion (group I; n = 9) or warm leukocyte-depleted blood reperfusion (group II; n = 11). Reperfusion with leukocyte-depleted blood or whole blood was carried out for 10 minutes, with enriched cardioplegic solution added for the first 3 minutes of reperfusion. The mean donor and recipient age and the ischemic time (142 versus 153 minutes) were not significantly different between the two groups. Coronary sinus release of creatinine phosphokinase-MB 5 minutes after reperfusion was significantly less in group II (1.65 EU/min) than in group I (3.83 units/min; p = 0.05). Thromboxane B2 release was also significantly less (p = 0.05) in group II (33.6 pg/min) than in group I (67.0 pg/min). All hearts functioned adequately in both groups. The duration of inotropic support was shorter in group II than in group I, but the difference was not statistically significant. Postoperative hemodynamics, rejection episodes, and infectious complications were also not significantly different between groups in a mean follow-up of 9 months. Mean ejection fraction 1 month after operation was 65% in both groups. One early death occurred at 66 days secondary to infection; two late deaths occurred in group II, both from rejection. Leukocyte-depleted reperfusion is safe and easily applied in the operating room. Furthermore, leukocyte-depleted reperfusion decreases biochemical evidence of reperfusion injury. Although not influencing postoperative cardiac function when the ischemic time is short, less than 3 hours, leukocyte-depleted reperfusion may prevent significant reperfusion injury and improve posttransplantation graft function when ischemic times are long. Safe extension of the ischemic time would expand the donor pool and allow for better crossmatching.

Management of the left atrioventricular valve in the repair of complete atrioventricular septal defects.

Left atrioventricular valve regurgitation in atrioventricular canal defects is usually due to malalignment of the edges of the cleft or to annular dilatation. Intraoperative assessment and correction of left atrioventricular valve incompetence is critical for successful outcome in the surgical management of complete atrioventricular canal defects. Although some have elected not to suture the cleft in the setting of minimal incompetence, we have found that this often results in significant left atrioventricular valve insufficiency, necessitating reoperation. From January 1982 through December 1990, 105 patients with complete atrioventricular canal underwent definitive repair. Repair was performed with a single pericardial patch technique in 86 patients (82%). Intraoperative assessment of left atrioventricular valve competence was performed in all cases. Ninety-six patients (91%) required suturing of the cleft and 63 (60%) required annuloplasty to establish satisfactory competence of the left atrioventricular valve. The overall early mortality rate was 10.5% (11/105 patients). From 1986 to 1990, the early mortality rate decreased to 7.7% (6/78 patients). In a mean follow-up of 39 months (range 1 to 106 months), late survival was 96% (90/94 operative or early survivors). Reoperation was performed on eleven (11.5%) patients; six (6.3%) for failure of the atrioventricular valve repair, three for patch dehiscence, and two for residual ventricular septal defects. These data demonstrate that routine approximation of the cleft and aggressive use of left atrioventricular valve annuloplasty is safe and results in an excellent outcome with a low incidence of reoperation for failure of left atrioventricular valve repair.

Leukocyte-depleted reperfusion of transplanted human hearts prevents ultrastructural evidence of reperfusion injury.

The present study examines whether leukocyte depletion can prevent postreperfusion ultrastructural injury in transplanted human hearts. Thirty-two patients undergoing orthotopic cardiac transplantation were randomized to receive either enriched, warm, whole blood (Group I; n = 16) or enriched, warm, leukocyte-depleted blood (Group II; n = 16) reperfusion. Donor hearts were arrested with 1 liter of 4 degrees C crystalloid cardioplegia and topically cooled. RV endomyocardial biopsies taken at end-ischemia and following reperfusion were assessed in a blinded fashion and graded according to injury (1 = minimal to 4 = severe). The mean ischemic time (Group I = 142 min, Group II = 153 min) was similar in the two groups. End-ischemic biopsies showed mild-moderate interstitial edema and mild capillary endothelial swelling in both groups with similar injury scores (Group 1 = 1.3 +/- 0.09 (means +/- SEM), Group 2 = 1.25 +/- 0.08). Postreperfusion biopsies in Group I showed nuclear chromatin clumping, moderate mitochondrial swelling, marked capillary endothelial swelling, and marked interstitial edema with a grade of 2.6 +/- 0.14 (P less than 0.001, paired t test). In contrast, postreperfusion biopsies in Group II showed minimal changes with a grade of 1.33 +/- 0.09, P less than 0.0001 in comparison to Group I Leukocyte-depleted reperfusion of human transplanted hearts prevents ultrastructural injury. This may allow safe extension of the ischemic period and result in improved graft function.

Perfluorochemical reperfusion limits myocardial reperfusion injury after prolonged hypothermic global ischemia.

The ability of an oxygenated perfluorochemical (Fluosol) to limit myocardial reperfusion injury following global hypothermic ischemic insult was investigated. Neonatal piglet hearts were arrested with cold crystalloid cardioplegia and stored for 12 hours in 2 degrees C saline. Reperfusion was carried out using an isolated, blood-perfused, working heart preparation. Hearts were initially reperfused (10 minutes) with either whole blood (WB, n = 6), unmodified perfluorochemical (PFC, n = 8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (PFC+, n = 6), prior to institution of whole blood perfusion, functional evaluation and left ventricular biopsy. A control group (C, n = 7) was evaluated without an intervening period of ischemia. At a left ventricular diastolic pressure of 9 mm Hg WB hearts developed a left-ventricular stroke work index (SWI) of 3.8 +/- 2.3 x 10(3) erg/g (mean +/- standard error of the mean). Under similar conditions, PFC-reperfused hearts achieved a SWI of 14.6 +/- 1.3 x 10(3), significantly greater than that of WB (p less than 0.001). SWI for PFC+ hearts was 19.8 +/- 1.6 x 10(3), significantly increased over that of PFC (p less than 0.01), and not different from values obtained for C (19.2 +/- 0.8 x 10(3)). In addition, PFC-reperfused hearts demonstrated superior maintenance (p less than 0.05) of ATP (2.08 +/- 0.16 umole/g), compared to WB (1.50 +/- 0.19), while preservation of ATP in PFC+ hearts (2.99 +/- 0.12), was significantly increased over that of PFC (p less than 0.001), and not significantly different from that for C (2.68 +/- 0.17).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in gamma-glutamyltransferase activity during N-2-fluorenylacetamide-induced rat hepatocarcinogenesis.

Changes in gamma-glutamyltransferase (GGT) activity throughout the course of rat hepatocarcinogenesis induced by brief dietary exposure to N-2-fluorenylacetamide (2-FAA) followed by promotion with dietary phenobarbital (PB) were studied. By examination of changes in total GGT activity and its histochemical localization, the effects of initiator and promoter on this enzyme can be clearly differentiated. Both 2-FAA and PB increase total GGT activity in grossly normal liver, PB causing a tenfold greater increase than that caused by 2-FAA. Although the elevation of GGT activity in livers of rats sequentially treated with 2-FAA-PB was not additive or synergistic, the course of increase was distinct from that of either 2-FAA- or PB-caused changes in activity, suggesting that 2-FAA and PB interact to alter the GGT phenotype of sequentially treated animals. GGT activity in neoplasms induced by either 2-FAA or 2-FAA-PB was highly variable, i.e., from nearly basal levels to those 170-fold greater than basal. Lesions induced by 2-FAA without PB promotion had elevated GGT, indicating that PB is not required to produce GGT-positive neoplasms by this protocol. Histochemically, changes in GGT activity occurred in both hepatocytes and nonhepatocyte cell populations in a characteristic, treatment-dependent manner, well-correlated with total GGT activity. Treatment with 2-FAA, especially that with 2-FAA-PB, induced primarily focal and nodular GGT activity patterns. PB alone produced no GGT-positive foci, but it did cause GGT-positive ductular proliferation. Continued PB exposure produced a GGT activity pattern which clearly defined the interlobular regions of the liver; no similar staining pattern was seen in either 2-FAA-treated or 2-FAA-PB-treated livers. These results indicate that an initiator and one of its promoters, combined and individually, alter GGT activity in a characteristic manner over the course of hepatocarcinogenesis. Moreover, the effects of the promoter on GGT activity are dependent on whether or not prior exposure to initiator has occurred.