Effect of postoperative landiolol administration for atrial fibrillation after off pump coronary artery bypass surgery.

AIM: Atrial fibrillation is one of the most common postoperative arrhythmias following cardiac surgery. Despite many clinical studies, there is still no consensus on the most appropriate prevention strategy for atrial arrhythmia. A randomized prospective trial was conducted to determine the efficacy of intravenous landiolol administration in the early period after off-pump coronary artery bypass grafting (CABG) followed by treatment with carvedilol for prevention of atrial fibrillation. METHODS: Seventy consecutive patients were enrolled in the study prospectively. Patients in the treated group received landiolol intravenously (5 µg/kg/min) in the ICU immediately after surgery. Heart rate was maintained at 60-80 bpm and intravenous landiolol was continued at 0-10 µg/kg/min until oral drug administration was possible. All patients received oral carvedilol (2.5-5 mg/day) after extubation and this was continued postoperatively. The primary endpoint was the overall development of postoperative atrial fibrillation. RESULTS: Postoperative atrial fibrillation occurred in 4 (11.1%) of the 36 patients in the landiolol group, compared with 11 (32.3%) of the 34 patients in the control group, indicating that development of atrial fibrillation was significantly inhibited by landiolol (P=0.042). No major postoperative complications occurred in the landiolol group. CONCLUSION: Postoperative intravenous landiolol therapy followed by oral carvedilol may be more effective than oral carvedilol alone for prevention of atrial fibrillation after off-pump CABG. We also found that intravenous landiolol is well tolerated after cardiac surgery.

Myocardial protection: the efficacy of an ultra-short-acting beta-blocker, esmolol, as a cardioplegic agent.

OBJECTIVE: During myocardial revascularization, some surgeons (particularly in the United Kingdom) use intermittent crossclamping with fibrillation as an alternative to cardioplegia. We recently showed that intermittent crossclamping with fibrillation has an intrinsic protection equivalent to that of cardioplegia. In this study we hypothesized that arrest, rather than fibrillation, during intermittent crossclamping may be beneficial. Because esmolol, an ultra-short-acting beta-blocker, is known to attenuate myocardial ischemia-reperfusion injury, we compared the protective effect of esmolol arrest with that of intermittent crossclamping with fibrillation and conventional cardioplegia (St Thomas' Hospital solution). METHODS: Isolated rat hearts were Langendorff perfused at either constant flow (14 mL/min) or constant pressure (75 mm Hg) with oxygenated Krebs-Henseleit bicarbonate buffer (37 degrees C), and left ventricular developed pressure was assessed. In study 1 (constant flow perfusion) 8 groups (n = 6 hearts per group) were studied: (1) 40 minutes of global ischemia; (2) 2 minutes of St Thomas' Hospital infusion and 40 minutes of ischemia; (3) multidose (every 10 minutes) infusions of St Thomas' Hospital solution during 40 minutes of ischemia; (4) 2 minutes of esmolol infusion and 40 minutes of ischemia; (5) multidose (every 10 minutes) esmolol infusions during 40 minutes of ischemia; (6) continuous infusion of esmolol for 40 minutes during coronary perfusion; (7) intermittent (4 x 10 minutes) ischemia with ventricular fibrillation; and (8) intermittent (4 x 10 minutes) ischemia preceded by intermittent esmolol administration. All protocols were followed by 60 minutes of reperfusion. Further experiments (study 2) examined the esmolol administration method in hearts perfused by constant pressure. RESULTS: An optimal arresting dose of 1.0 mmol/L esmolol was established. In study 1 recovery of left ventricular developed pressure (expressed as percentage of preischemic value) was 7% +/- 4%, 28% +/- 8%, 70% +/- 5%, 8% +/- 1%, 90% +/- 4%, 65% +/- 3%, 71% +/- 5%, and 76% +/- 5% in groups 1 to 8, respectively. Intermittent esmolol arrest with global ischemia provided equivalent myocardial protection to intermittent crossclamping with fibrillation, continuous esmolol perfusion, and multidose St Thomas' Hospital solution. Surprisingly, multidose esmolol infusion was more protective than all other treatments. In further experiments (study 2) optimal recovery was obtained with multiple esmolol infusions (by constant flow or constant pressure), but continuous esmolol infusion (at constant flow) was less effective than constant pressure infusion. CONCLUSIONS: Intermittent arrest with esmolol did not enhance protection of intermittent crossclamping with fibrillation; however, multiple esmolol infusions during global ischemia provided improved protection. Administration (constant flow or constant pressure) of arresting solutions influenced outcome only during continuous infusion. Multidose esmolol arrest may be a beneficial alternative to intermittent crossclamping with fibrillation or conventional cardioplegia.

Sequential grafting of the right gastroepiploic artery in coronary artery bypass surgery.

BACKGROUND: Only a few studies have been done on sequential grafting using the right gastroepiploic artery (GEA). METHODS: Forty patients (35 males, ages 36 to 74 years) who underwent sequential grafting of the GEA were reviewed. Angiography of the GEA was performed preoperatively in all patients. GEAs with a luminal diameter greater than 2 mm at the presumptive distal anastomosis on the angiogram were used. The dissected GEA was led into the pericardial cavity through the antegastric route. We used GEAs to graft 89 branches (2.2 per patient) in the inferoposterior region. RESULTS: In 24 patients who had angiographic examinations, all the GEAs were patent, although luminal narrowing was noted in the segment between the two anastomoses in 3 patients. Eight-year actuarial survival was 92.5% and the cardiac-related event-free rate was 95%. CONCLUSIONS: Sequential grafting of the GEA can be performed effectively in selected patients. Performing preoperative angiography to assess the size of the GEA for sequential grafting is strongly recommended.

Adequacy of flow capacity of bilateral internal thoracic artery T graft.

BACKGROUND: With the T graft configuration, multiple arterial revascularization can be accomplished using bilateral internal thoracic arteries. However, concern remains about the flow capacity of the main stem of the left internal thoracic artery (LITA). METHODS: Forty patients who underwent multiple revascularization of the entire territory of the left coronary system with a T graft were investigated. Six months after the operation, they were examined angiographically. During the same period, dobutamine stress echocardiography was performed to evaluate the adequacy of the myocardial blood supply from the T graft. The T graft revascularized two branches in 5 patients, three branches in 23, four branches in 11, and five branches in 1 of the left coronary system. Other conduits were used if revascularization was required for the right coronary system. RESULTS: Complete revascularization was achieved in the left coronary territory in all patients. The LITA main stem showed a wide lumen in all patients. Luminal narrowing was present in the distal segment of the LITA in 3 patients. The right internal thoracic artery (RITA) was patent in all patients, whereas luminal narrowing was observed in the distal segment of the RITA in 5 patients. No patient exhibited ischemic wall motion abnormality in the anteroseptal, lateral, or posterolateral region of the left ventricle where the T graft revascularized. Eight patients showed ischemic response in the inferoposterior region, that is, the territory of the right coronary artery. CONCLUSIONS: The LITA main stem, forming a T-graft configuration with the free RITA, has an adequate flow reserve to supply at least the entire left coronary arterial system with sufficient blood. Therefore, multiple coronary revascularization using the T-graft technique is feasible.

Experimental study of intermittent crossclamping with fibrillation and myocardial protection: reduced injury from shorter cumulative ischemia or intrinsic protective effect?

OBJECTIVE: During coronary artery revascularization, some surgeons favor intermittent crossclamping with ventricular fibrillation in preference to cardioplegic ischemic arrest for myocardial protection. It is unclear, however, whether intermittent crossclamping with fibrillation is equally protective or whether ischemic injury is reduced as a consequence of shorter cumulative ischemia. METHODS: We used isolated, Langendorff-perfused rat hearts, measured preischemic function (left ventricular developed pressure) with an intraventricular balloon, and then subjected the hearts to either (1) 40 minutes of global ischemia, (2) a 2-minute infusion of cardioplegic solution and 40 minutes of ischemia, (3) multidose (every 10 minutes) infusions of cardioplegic solution during 40 minutes of ischemia, (4) continuous ventricular fibrillation during 40 minutes of ischemia, (5) intermittent (4 x 10 minutes) ischemia with 10 minutes of reperfusion, (6) intermittent (4 x 10 minutes) ischemia preceded by intermittent cardioplegia, (7) intermittent (4 x 10 minutes) ischemia with ventricular fibrillation, (8) continuous (40 minutes) ventricular fibrillation during coronary perfusion, or (9) intermittent (4 x 10 minutes) ventricular fibrillation (with perfusion). All protocols were followed by 60 minutes of reperfusion. RESULTS: After 60 minutes of reperfusion, the percentage recovery of left ventricular developed pressure for groups 1 through 9 was as follows: 32% +/- 2%, 57% +/- 6%, 82% +/- 3%, 19% +/- 3%, 73% +/- 3%, 70% +/- 3%, 78% +/- 4%, 55% +/- 2%, and 57% +/- 3%, respectively. No significant differences were identified among groups 3, 5, and 7, but the percentage recovery of developed pressure in group 3 was significantly higher than that in group 6; the degree of recovery in groups 3 and 5 to 7 was significantly (P <.05) higher than in groups 1, 2, 4, 8, and 9. Early recovery was significantly (P <.05) more rapid in groups 3 and 5 to 9, reaching a plateau (of 55%-80%) by 10 minutes of reperfusion; in groups 1, 2, and 4, the recovery plateau occurred after 50 minutes. Left ventricular end-diastolic pressure was elevated in groups 1, 2, and 4 but was almost unchanged from baseline in the other groups. CONCLUSIONS: A similar level of myocardial protection was achieved with multidose (intermittent) cardioplegia or intermittent crossclamping (with or without fibrillation), indicating that intrinsic preservation by intermittent crossclamping with fibrillation does not exacerbate ischemic injury.

Wavelength and conduction inhomogeneity in each atrium in patients with isolated mitral valve disease and atrial fibrillation.

INTRODUCTION: Patients with mitral valve disease frequently have atrial fibrillation (AF), and the left atrium is presumed to be the primary atrium that develops AF. However, it is still not clear whether the electrophysiologic abnormalities responsible for AF are confined to the left atrium in this subset of patients. METHODS AND RESULTS: To examine the AF vulnerability of each atrium, we measured the wavelength and inhomogeneity of the conduction at the lateral right atrium, lateral left atrium, and Bachmann's bundle after defibrillation of AF in seven patients undergoing the maze procedure and mitral valve surgery for AF and isolated mitral valve disease, respectively (AF group). The data were compared with five coronary surgery patients in sinus rhythm (SR group). The wavelength in the AF group was significantly shorter (P < 0.05) than in the SR group not only at the lateral left atrium (225 +/- 62 vs 285 +/- 36 mm) but also at the lateral right atrium (214 +/- 54 vs 254 +/- 34 mm). The variation coefficient of the local maximum activation phase difference in the AF group (1.9 +/- 0.8 at the right atrium, 2.1 +/- 0.8 at the lateral left atrium, and 2.0 +/- 0.6 at Bachmann's bundle) was significantly greater (P < 0.05) than in the SR group at all atrial regions. CONCLUSION: AF vulnerability was not confined to the left atrium immediately after defibrillation in AF patients with isolated mitral valve disease. Electrical remodeling resulting from perpetuation of AF, pathological changes extending to the right atrium, geometric changes caused by the atrial interactions occurring across the interatrial septum, or a combination of these may explain the results.

"Hexatuple" coronary bypass with in situ arterial grafts.

A fifty-seven year old male patient with severe three-vessel coronary artery disease underwent successful coronary bypass surgery in six vessels utilizing the in situ left internal thoracic and right gastroepiploic arteries. Each arterial conduit was anastomosed sequentially to as many as three coronary vessels respectively. Surgical results were excellent and the patient continues to do very well. A postoperative angiogram showed well-working arterial conduits without any anastomotic problems. Multiple sequential anastomoses of the in situ arterial conduits, although rather technically demanding, can provide better long-term results in patients requiring multiple coronary revascularization. When sequential anastomoses of the right gastroepiploic artery are being considered, the length and caliber of the artery should be evaluated by an angiogram since it varies in size compared to the internal thoracic artery.

The clinical significance of performing preoperative angiography of the internal thoracic artery in coronary artery bypass surgery.

This study was designed to clarify the clinical significance of and indications for performing preoperative internal thoracic artery (ITA) angiography in patients undergoing coronary artery bypass surgery. A total of 300 possible candidates for coronary artery bypass grafting (CABG) underwent ITA angiography during diagnostic catheterization. Semi-selective angiography of bilateral ITAs were performed by injecting contrast medium manually with a 5-F right Judkins coronary catheter. The posteroanterior view of the arteriograms was recorded on a 35-mm cine film or a cut-film. Unusual angiographic findings of the ITAs were observed in nine patients (3%). These findings included: an atrophic ITA in three patients with ipsilateral subclavian artery occlusions; enlarged ITAs giving collaterals to the lower extremities in one patient with extensive aortoiliac occlusive disease; occluded ITAs in one patient with Takayasu's arteritis and two patients with a history of CABG; and a small but nonsclerotic ITA in one patient. Atherosclerotic occlusive ITAs were found in only one patient. Thus, we concluded that routine preoperative angiography of the ITA is not necessary because it is rarely affected by atherosclerosis. However, it should be performed for any of the following reasons: a cervical or supraclavicular bruit; an upper extremity blood pressure difference of greater than 20 mmHg; an extensive aortoiliac occlusion; and certain disorders such as Takayasu's arteritis or Kawasaki disease, or a history of open heart surgery.

Measurement of the upper limit of vulnerability during defibrillator implantation can substitute defibrillation threshold measurement.

We investigated whether defibrillation thresholds (DFTs) could be measured more safely during defibrillator implantation by measuring the upper limit of vulnerability (ULV) without using any special equipment. Nonthoracotomy ICD implantation with endocardial leads was performed in 13 patients, and through the use of the ICD function itself, ULV and DFT were measured using the delayed four-episode up-down algorithm. Myocardial injures caused by high-energy current were assessed by electrocardiograms and serial CPK-MB. ULV was confirmed in all cases, and it strongly correlated with DFT. The average ULV was 5.9 +/- 3.3 J, while the average DFT was 7.9 +/- 4.3 J (r = 0.89, p < 0.0001, DFT = 1.20+1.14x ULV). The average ULV was thus significantly lower (p < 0.01). Although six patients were on amiodarone therapy, the strong correlation between ULV and DFT was also maintained (r = 0.97), p < 0.01) in these patients. In all cases, the CPK-MB failed to increase, and no myocardial injuries were detectable on electrocardiograms. We confirmed that ULV could be easily and safety measured during ICD implantation, and that ULV could be used instead of DFT.

Role of protein tyrosine phosphorylation in etoposide-induced apoptosis and NF-kappa B activation.

When a human myeloid cell line, U937, was incubated with etoposide (10 micrograms/mL), morphologically apoptotic cells first appeared at 3 hr and increased with time to 50% at 6 hr. Pretreatment of U937 cells for 30 min with a potent tyrosine kinase inhibitor, herbimycin A (10 microM), significantly suppressed the appearance of apoptotic morphological changes. Concomitantly, herbimycin A pretreatment prevented both high molecular weight and internucleosomal DNA fragmentation induced by etoposide. Two major bands at 30 and 66 kDa with enhanced tyrosine phosphorylation inhibited by herbimycin A were detectable after 30 min of incubation with etoposide. In addition, herbimycin A prevented etoposide-induced NF-kappa B activation. The expressions of Bcl-2 and Bax, on the other hand, were not affected by herbimycin A pretreatment. Herbimycin A was also found to inhibit 1-beta-D-arabinofuranosylcytosine-induced apoptotic changes and NF-kappa B activation. These results suggest that activation of tyrosine kinase(s) may play an important role in apoptotic processes induced by a variety of anti-cancer drugs.

Simultaneous surgical correction of a common atrium and impure flutter.

We performed surgical correction and treatment of a common atrium and chronic impure flutter using a computerized mapping system in a 49-year-old man. A reentrant circuit was observed to exist around the left atrial appendage. In contrast to the regular activation in the left atrium, the activation sequence of the right atrium was extremely chaotic. Cryolesions were applied to the area of the reentrant pathway. After the operation, sinus rhythm was restored.

Simultaneous subclavian artery reconstruction in coronary artery bypass grafting.

BACKGROUND: Subclavian artery occlusive lesion, although rare, is sufficiently important to consider before coronary artery bypass grafting because it can cause not only symptoms of the lesion per se, but also the postoperative coronary-subclavian steal phenomenon. METHODS: Four patients undergoing coronary artery bypass grafting received simultaneous reconstruction of the subclavian artery. During aortic cross-clamping, an 8-mm ring-reinforced polytetrafluoroethylene graft was attached to the aorta perpendicularly. The prosthetic graft was led to the proximal segment of the axillary artery through the second intercostal space and anastomosed to the inferior surface of the artery. RESULTS: Three patients received unilateral reconstruction of the subclavian artery, whereas another received bilateral reconstruction. There were no complications related to the subclavian reconstruction procedure. Post-operative angiograms revealed excellent patency of the prosthetic grafts. All of the patients have been asymptomatic with follow-up periods ranging from 9 to 50 months. CONCLUSIONS: To perform simultaneous subclavian artery reconstruction along with coronary artery bypass grafting, the aortoaxillary bypass procedure using an 8-mm polytetrafluoroethylene graft may be the method of choice because it has lower potential for complications and is less technically demanding.

Infective endocarditis. Considerations for the timing of surgical intervention and type of infecting microorganism.

To determine the appropriate timing for surgical intervention in infective endocarditis (IE), we evaluated 24 patients (17 males, 6 females, with one included twice) who underwent surgical intervention for IE of native valves (NVE, n = 21) and prosthetic valves (PVE, n = 3) between January 1989 and September 1994. The mean age was 41 +/- 13 years (range 6 to 64 years). The most common infective organisms were Staphylococcus (33% of NVE) and Streptococcus (19% of NVE), with five NVE patients (24%) negative for blood culture. The PVE patients showed a different pattern of infecting organisms, with Enterococcus in one and Pseudomonas in another. From the resected valve culture and pathological findings, 12 patients were in the active stage at operation. Two in-hospital deaths occurred for a mortality rate of 8.7% (2/23). Further, surgical interventions were performed earlier with Staphylococcal infections than with Streptococcal infections, because hemodynamic compromise presented more progressively in the former. Also resected valve cultures and the pathological findings showed that a persistent infectious process existed in many cases of Staphylococcal infection in spite of intensive antibiotic therapy. In conclusion, we suggest that internists make referrals for surgical intervention for patients with NVE or PVE as early as possible in the active stage of infection.

Continuous transoesophageal echocardiography monitoring during weaning from cardiopulmonary bypass in children.

The purpose of this study was to evaluate the effectiveness of transoesophageal echocardiography monitoring during weaning from cardiopulmonary bypass after intracardiac repair in children. The left ventricular ejection fraction, left ventricular end-diastolic volume and left ventricle wall motion were monitored continuously by transoesophageal echocardiography in controls weaned easily from cardiopulmonary bypass (group A, n = 25), and those weaned with difficulty from cardiopulmonary bypass after mechanically assisted circulation (group B, n = 16). In group A, left ventricular ejection fraction and left ventricle wall motion were within normal range, and did not change significantly during weaning after cardiopulmonary bypass when compared with pre-bypass data. In contrast, left ventricular ejection fraction, left ventricular end-diastolic volume and left ventricle wall motion in group B during the first trial of weaning from bypass were significantly worsened. Hence, assisted circulation was performed until the data obtained via transoesophageal echocardiography improved with regard to maintenance of fluid balance, catecholamine dosage and assisted pump flow. All cases in group B were weaned safely from cardiopulmonary bypass despite their critical condition. In conclusion, continuous transoesophageal echocardiography monitoring may be a useful tool in children with severe heart failure for safe weaning from cardiopulmonary bypass after intracardiac repair.

Superior-septal approach for transmitral mapping and cryoablation of ventricular tachycardia.

A superior-septal approach was used for mapping and cryoablation of the left ventricular endocardium over the mitral annulus in a patient with ventricular tachycardia associated with an inferior myocardial infarction without a ventricular aneurysm. This approach provides an excellent view of the mitral valve, and allows safe, adequate mapping and cryoablation of the left ventricular endocardium without the necessity of a ventriculotomy.

Aortic dissection extending from the left coronary artery during percutaneous coronary angioplasty.

A 72-year-old woman with acute aortic dissection as a complication of percutaneous coronary angioplasty was successfully treated. She received a graft replacement of the ascending aorta as well as triple coronary artery bypass grafts. The dissection had extended from the left coronary artery. Although acute aortic dissection is a rare complication of percutaneous coronary angioplasty, physicians and cardiac surgeons should keep its potential occurrence in mind.

Methotrexate inhibits superoxide production and chemotaxis in neutrophils activated by granulocyte colony-stimulating factor.

Treatment of circulating human neutrophils with recombinant human granulocyte colony-stimulating factor (rhG-CSF) for 30 min augmented superoxide generation and chemotaxis induced by N-formylmethionyl-leucyl-phenylalanine (fMLP) in a dose dependent manner. When neutrophils were treated with 1 microM of methotrexate (MTX) for 60 min after incubation with rhG-CSF (10 ng/ml), the effects of rhG-CSF on superoxide generation and chemotaxis were inhibited by approximately 49 and 29%, respectively. Although inhibitory effects of MTX were also seen in neutrophils not pretreated with rhG-CSF, the degree of inhibition was much less. The addition of either hypoxanthine or guanosine at a concentration of 100 microM to the culture medium significantly attenuated the effects of MTX. However, in neutrophils obtained from a patient with Lesch-Nyhan syndrome, which lacked hypoxanthine-guanine phosphoribosyl transferase activity neither hypoxanthine nor guanosine had any rescue effect. These results suggest that MTX inhibits superoxide generation and chemotaxis in rhG-CSF-activated neutrophils, at least in part, by disturbing purine nucleotide biosynthesis.