Use of the MTT assay for rapid determination of chemosensitivity of human leukemic blast cells.

A microcytotoxicity assay employing a tetrazolium salt has been adapted for testing the response of human leukemic blast cells to a variety of chemotherapeutic agents. After exposure to various concentrations of drugs, the viability of fresh leukemic blast cells was measured using a tetrazolium salt, MTT, which is converted to blue formazan crystals by living cells. The amount of formazan produced was quantitated using a microtitre plate spectrophotometer. In the present study, optimal conditions for chemosensitivity testing of human leukemia samples were determined, and the relative chemosensitivity of five patient samples was tested.

Gastroepiploic-coronary anastomosis. A viable alternative bypass graft.

Although increasing use is being made of arterial grafts (the internal mammary arteries) for direct myocardial revascularization, it is frequently not possible to reach the posterior surface of the heart with the internal mammary as either a pedicle or a free graft. Since June 1984 we have used the right gastroepiploic artery in nine patients as a pedicle graft to the distal right coronary artery (four patients), the posterior descending artery (three patients), and the distal circumflex branches (two patients). Eight patients survived the operation. Celiac axis opacification confirmed patency in six and coronary angiography strongly suggested patency in the remaining two. All survivors are functionally in New York Heart Association Class I or II. The early angiographic and clinical results demonstrate the feasibility of using the right gastroepiploic artery as a bypass graft to coronary vessels on the posterior surface of the heart when traditional conduits are unsuitable. If its long-term patency as a living arterial graft is similar to that of the internal mammary arteries, the gastroepiploic artery may become the coronary bypass graft of choice for the distal right coronary and circumflex systems.

A two-year, three institution experience with the Medtronic Octopus: systematic off-pump surgery.

BACKGROUND: The popularity of beating heart coronary artery bypass (CAB) has grown with the development of mechanical stabilizers. Multicenter study offers an opportunity to examine methods and risk relating to this practice. METHODS: The experience since March 1997, utilizing both the original Medtronic Octopus system and the second-generation, retractor-mounted, Octopus II for beating heart CAB (Medtronic, Inc, Minneapolis, MN), was retrospectively reviewed at three institutions. RESULTS: Four hundred fifty-six patients completed Octopus CAB (Medtronic, Inc), performed through left thoracotomy (54), partial (33), or full (374) sternotomy, and epigastric (3) incisions with an average of 1.9 grafts/patient. Morbidities were reviewed: transfusion (20.6%), reoperation for bleeding (1.0%), atrial fibrillation (13.3%), completed stroke (0.2%), perioperative myocardial infarction (0.8%), and new intraaortic balloon pump (IABP) (0.4%), without episodes of deep sternal infection or renal failure. The mortality rate (0.32%), when compared to the Society of Thoracic Surgeons' (STS)-predicted mortality (1.37% and 2.36%) at two institutions, was significantly less (p < 0.05). Twelve nonurgent and one urgent conversion to cardiopulmonary bypass occurred. Six patients have required reintervention on bypassed vessels. CONCLUSIONS: To facilitate lateral and inferior wall grafting, a variety of techniques were utilized, including positioning, sternal and pericardial mobilization, and a new pericardial-based sling retractor, all designed to improve exposure while maintaining hemodynamic stability. The Octopus devices were safely applied with low morbidity and mortality utilizing varied operative approaches at three institutions.

Creative arterial bypass grafting can be performed on the beating heart.

BACKGROUND: To demonstrate that compromise is unnecessary in either the design or performance of beating heart surgery, we report our experience, over 1 year, of total arterial revascularization where composite or creative grafting was utilized. METHODS: We performed 321 off-pump coronary artery bypass operations, of which, 290 (90%) were done with only arterial conduits. The mean number of distal anastomoses was 2.48, with a range of 1 to 5. There were no aortic anastomoses. One hundred eighty-nine patients (65%) were male, and 101 (35%) were female, with a mean age of 67 years. Comorbidities included chronic renal failure (CRF), 21 (7%); diabetes, 92 (32%); obesity, 68 (23%); hypertension, 212 (73%); chronic obstructive pulmonary disease, 189 (65%); cerebral vascular accident (CVA), 39 (13%); smoking, 164 (56%); and hypercholesterolemia, 151 (52%). The mean ejection fraction was 56%, with a range of 21% to 71%. All procedures were performed with external stabilizers with or without vacuum assist. The complete arterial revascularizations included a T-graft (internal thoracic [ITA]/radial arteries [RA]), 130 (45%); a sequential graft (ITA +/- RA), 118 (41%); a U-graft (coronary-coronary graft perfused by the ITA or right gastroepiploic artery), 5 (2%); an I-graft (ITA/RA), 4 (1%); an X-graft (ITA/RA), 2 (12); and a Y-graft (ITA/RA), 31 (10%). RESULTS: The postoperative incidence of atrial fibrillation was 80 of 290 (27%); CVA, 5 of 290 (2%); bleeding resulting in take-back, 5 of 290 (2%); CRF, 8 of 290 (3%); deep sternal infection, 4 of 290 (1%); and readmission (30-day) for angina, 4 of 290 (1%). The observed perioperative (30-day) mortality was 9 of 290 (3.1%), with the STS predicted rate of 3.82%. CONCLUSIONS: Our experience indicates that once the operating surgeon has learned to safely expose the lateral and inferior walls of the heart, the type of conduit and the method of revascularization should be no different than that used with cardiopulmonary bypass. However, we still recommend conventional methods of revascularization (on-pump with saphenous vein conduits) for the ischemic patient.

A review of 1,582 consecutive Octopus off-pump coronary bypass patients.

BACKGROUND: Off-pump coronary bypass may provide a safer form of surgical revascularization by avoiding the unwanted complications of cardiopulmonary bypass, particularly in the increasingly complex patients being referred for operation. This study reviews the entire experience of the Medtronic Octopus System (Medtronic, Minneapolis, MN) for beating heart bypass from 7 surgeons. Demographics, operative procedures, early outcomes, and trends in usage were examined. METHODS: Patients were selected for off-pump procedures by the individual surgeons. Data were entered prospectively into locally maintained databases and then collected for collation and analysis. RESULTS: A total of 1,582 consecutive Octopus patients were entered, representing the entire Octopus experience of each surgeon. Proportions of off-pump procedures relative to standard bypass increased over time, as did the percentage of patients receiving three or more grafts, 24.6% in 1997 and 55.9% in 1999. A total of 3,653 anastomoses were performed, 1,905 to the left anterior descending system, 837 to the circumflex distribution, and 911 to the right coronary territory. Morbidity was low. Few patients required conversion to cardiopulmonary bypass (2.6%; 0.2% urgently). Permanent stroke occurred in 0.6% and myocardial infarction in 1.2%. Operative mortality was 1%. CONCLUSIONS: Octopus off-pump bypass was demonstrated to be a safe procedure with widening applicability. With experience surgeons tend to apply the system to increasing proportions of their patients and are able to revascularize all coronary territories.

Off-pump arterial grafting: 125 cases using the Medtronic-Utrecht Octopus.

OBJECTIVES: The use of arterial grafts in coronary bypass surgery requires a high degree of cardiac stabilization, traditionally achieved with cardiopulmonary bypass and cardioplegic arrest. The Medtronic-Utrecht Octopus has recently been developed as an advanced cardiac stabilization device, based on its unique suction method for regional epicardial immobilization and retraction. The objective of this study was to investigate the feasibility of using this device to enable total arterial revascularization on the beating, working heart. METHODS: From May 1997 to November 1998, off-pump coronary artery bypass using exclusively arterial grafts was performed in 125 selected patients (108 males), aged 2682 years (mean 61.1 +/- 10.5 years). Coronary artery immobilization was achieved with the Octopus, which uses local epicardial suction and avoids cardiac compression. Aortic anastomoses were avoided: both internal thoracic arteries and the right gastroepiploic artery were used as pedicle grafts in all but one case. All radial artery grafts and one right internal thoracic artery were used as Y-grafts from the left internal thoracic artery. There were four surgical approaches: sternotomy (98 patients), left anterior small thoracotomy (20 patients), anterolateral thoracotomy (six patients) and a subxiphoid approach in one patient. RESULTS: Sternotomy: 187 grafts were performed in 98 patients (mean 1.9 grafts per patient). There were 99 grafts to anterior wall vessels, 47 grafts to posterior wall vessels and 41 grafts to lateral wall vessels. Left anterior thoracotomy: 20 patients had a single graft to the left anterior descending artery (LAD). Left anterolateral thoracotomy: three patients had a single graft to a circumflex branch, while three had composite grafts to the LAD and circumflex systems. Subxiphoid: one patient had a single graft to the posterior descending branch of the right coronary artery. There were no peri-operative deaths in any group. No patient required conversion to cardiopulmonary bypass. Three patients required conversion from a limited-access approach to sternotomy. There was one re-operation for bleeding. Postoperative stay was 27 days (mean 3.6 +/- 1.1; median 3 days) for anterior thoracotomy, 3-4 days (mean 3.5 +/- 0.6) for anterolateral thoracotomy, and 378 days (mean 6.6 +/- 8.7; median 4 days) for sternotomy. There were two late deaths in salvage patients; no patient has required cardiac intervention or re-operation. CONCLUSIONS: The Octopus maintains excellent local cardiac immobilization--enabling the routine use of arterial grafts in off-pump coronary surgery. It allows easy access to anterior wall vessels on the heart, and relatively straightforward access to the posterior wall. Circumflex branches are graftable with careful case selection and adjunctive technical maneuvers.

A new surgical technique to correct double chambered right ventricle associated with anomalous left anterior descending coronary artery.

A 42 year old woman with symptomatic double chambered right ventricle had the additional features of an anomalous left anterior descending coronary artery and attachment of the tricuspid valve to the area of subinfundibular stenosis which precluded conventional repair. A non-valved Dacron conduit was used to bypass the obstruction. The patient is asymptomatic two years later.

Total arterial revascularization of the heart: intentional or inevitable.

The impact of left internal mammary to left anterior descending coronary bypass grafting in enhancing long-term patient survival has led to a widespread interest in arterial grafting over the past decade. It is now accepted that the internal mammary artery is a biologically superior coronary bypass graft compared with the traditional saphenous vein. Experience with other arterial grafts--the right gastro-epiploic artery, the inferior epigastric artery and the radial artery--has shown compelling evidence that they share the same biologic advantage. With the judicious use of some or all of these conduits, all regions of the heart can be reached, and total arterial revascularization is a feasible and desirable objective on a routine basis. As long-term results become available, it is inevitable that it will become the operation of choice.

Cardiac tamponade complicating anaesthetic induction for repair of ascending aorta dissection.

A case is described of a 69-year-old woman with dissection of the ascending aorta who developed cardiac tamponade during induction of anaesthesia. The tamponade was diagnosed by a haemodynamic profile showing approximation of the central venous, pulmonary wedge and pulmonary arterial diastolic pressures, and was treated with rapid surgical intervention and drainage of the haemopericardium. Cardiac tamponade and dissecting aneurysms of the ascending aorta are conditions with contrasting anaesthetic considerations and the problems encountered are discussed.

Right gastroepiploic-to-coronary artery bypass. The first decade of use.

BACKGROUND: The right gastroepiploic artery was first used by us as a coronary artery bypass graft (CABG) in June 1984 and has become an accepted alternative conduit for myocardial revascularization. METHODS AND RESULTS: We have now performed this operation in 126 patients (111 of whom were men) aged 32 to 78 years. The right gastroepiploic artery was used as a pedicle graft to the right main coronary artery in 25 patients, to its posterior descending branch in 90, to a left ventricular branch in 2, to branches of the circumflex system in 6, and to the left anterior descending artery in 1. Free (aortocoronary) gastroepiploic grafts were placed to circumflex branches in 2 patients. There were 2 hospital deaths (stroke, arrhythmia), and mean +/- SD postoperative stay was 7.5 +/- 2.0 days. All survivors were symptomatically improved and are functionally in New York Heart Association functional class I or II. There have been 3 late deaths (at 34, 50, and 84 months) in 2 to 120 months of follow-up (mean, 41.4 months). Angiography of bypass grafts and coronary arteries was performed in 44 patients at 7 days to 80 months postoperatively, providing direct evidence of gastroepiploic graft patency in 34 patients and strong indirect evidence in another 6; adequate data could not be obtained in 3 patients for technical reasons, and 1 graft was occluded. CONCLUSIONS: These short-term, intermediate, and long-term results demonstrate the suitability of the right gastroepiploic artery as a CABG. The use of the right gastroepiploic artery as a graft to coronary arteries on the posterior wall of the heart, in conjunction with one or both internal mammary arteries, has the potential to allow complete myocardial revascularization with viable arterial grafts.

Contemporary operative management of pulmonary metastases of colorectal origin.

The management of patients with metastatic disease from primary carcinoma of the colon and rectum is still controversial. To evaluate the results of resection of pulmonary metastases from patients with colorectal primaries, a retrospective study of all patients who underwent such resection was carried out at the teaching hospitals of McGill University and Université de Montréal. A total of 345 patients admitted with pulmonary metastases; 27 of them underwent pulmonary resection with the extent of the resection varying from wedge excision of the metastatic nodule to pneumonectomy. In 25 of the 27 patients the resection was considered curative. Eight of the 27 patients had resection of two metastatic lesions while the remaining 19 patients had resection of solitary lesions. The interval between resection of the primary colorectal malignancy and the resection of the metastatic lesion (disease-free interval) varied from 2 to 77 months with a median interval of 35 months. The five-year survival following resection of pulmonary metastases was 21 percent. A prolonged interval between treatment of the primary and resection of the pulmonary metastasis was associated with a longer survival. This retrospective study demonstrates that prolonged survival can be achieved following resection of pulmonary metastases from colorectal carcinoma.

A possible role for antiphospholipid antibodies in acquired cardiac valve deformity.

We studied the frequency of antiphospholipid antibodies (aPL) in patients undergoing cardiac valve replacement, and present the results in the context of the pathology of the valve lesions. Forty-eight consecutive patients undergoing valve replacement were studied. Of the whole group, 15 (31%) had antibody levels greater than 2 SD above the mean for a control group of healthy persons and 11 (23%) had a level of greater than 3 SD. There was an increased frequency of elevated antibody levels in patients with valves showing fibrocalcific change and a significant association between aPL and valve thrombus. The possible role of these antibodies in the pathogenesis of the valve lesions is discussed.

Simultaneous use of membrane oxygenation and high-frequency jet ventilation in acute pulmonary failure.

A 16-yr-old female suffering acute, rapidly progressive combined respiratory and cardiac failure that was unresponsive to conventional volume-cycled ventilation, was stabilized with the simultaneous short-term use of veno-venous membrane oxygenation and high-frequency jet ventilation. Percutaneously introduced cannulas afforded rapid vascular access for membrane oxygenation, minimal wound problems during the perfusion, and easy decannulation. This is the first reported combined use of high-frequency jet ventilation and extracorporeal membrane oxygenation, and the first reported percutaneous initiation of veno-venous bypass. The patient remained alive and well 4 months after therapy.

Adrenoceptors of the human internal thoracic artery.

Adrenoceptor function in the human internal thoracic artery (ITA) was characterized in vitro using segments of the artery obtained during coronary bypass operations. Specimens were prepared as isolated arterial rings mounted in a tissue bath, and mechanical activity (isometric tension) was measured in response to drugs. The ITA responded to phenylephrine (PE), epinephrine, and norepinephrine with concentration-dependent contractions. The PE-induced contractions were antagonized by phenoxybenzamine, prazosin, and high concentrations of yohimbine. The ITA was not effectively contracted by clonidine in the concentration range normally associated with alpha 2-adrenoceptor stimulation. The beta-adrenoceptor agonist, isoproterenol, had a weak and variable effect on the ITA; samples from 9 out of 12 subjects did not respond to isoproterenol, whereas samples from 3 subjects responded with relaxations of between 33 and 42%. These in vitro studies indicate that the most important adrenoceptors of the human ITA are alpha-adrenoceptors; this may be relevant for the pharmacologic management of patients undergoing coronary bypass surgery using the ITA.

Chemosensitivity testing of small cell lung cancer using the MTT assay.

A simple colorimetric test, the MTT assay, has been adapted for chemosensitivity testing of human small cell lung cancer cell lines, and fresh tumour samples. Optimal conditions for clinical chemosensitivity testing were determined using established SCLC lines. Nineteen different chemotherapeutic agents were tested, and sixteen of them were found to be cytotoxic in this assay system. The drug sensitivity of a panel of 16 SCLC cell lines was measured and compared. There was very little intraexperiment variation, but the interexperiment variation was significant. Cell lines which were derived from patients who had not received chemotherapy at the time the cell line was established were more sensitive (to all but one of the drugs) than lines derived from treated patients, and the differences were statistically significant for two of the drugs. One cell line, NCI-H209, which was derived from an untreated patient, stood out as being the most sensitive or among the most sensitive to all of the drugs tested. Another cell line, H69AR, which is a multidrug resistant subline of the cell line NCI-H69, was the most resistant to many of the natural product drugs tested. Multiple drug chemosensitivity testing was performed on eight fresh tumour samples from SCLC patients (five pleural effusions, one lymph node, and two primary tumours). It was possible to perform chemosensitivity testing on all of the clinical samples in which sufficient tumour cells were available. The drug sensitivity of the clinical samples was, in most cases, within the same range as for the cell lines. Since this assay is very rapid and simple to perform, it may have practical applications in clinical drug sensitivity testing of human tumours.

Thrombelastographic changes in OPCAB surgical patients.

The purpose of this study was to determine whether thrombelastography could detect hypercoagulability in the off-pump coronary artery bypass (OPCAB) patient. Seventeen OPCAB and six cardiopulmonary bypass (CPB) patients were studied pre- and postprocedure, as well as on each of the first three postoperative days (POD). In the OPCAB patients, there was a small reduction in the postprocedure coagulation index (CI). This was followed by an increase in the CI on each of the next three POD, reaching a level exceeding the mean preprocedure CI by 2.32 units, indicative of a state of relative hypercoagulability. The mean CI for the CPB patients decreased significantly in the postprocedure sample. Over the next 72 h, the CI increased to a level that nearly equaled the preprocedure 'baseline'. We concluded that our study identified a state of relative hypercoagulability in the OPCAB patient 72 h after surgery. The mechanism of this hypercoagulation, as well as the clinical significance of this finding, is yet to be determined.