How good is the radial artery as a bypass graft?

The radial artery is being used with increasing frequency to replace the saphenous vein as a coronary artery bypass graft, on the basis of the belief that it will provide improved long-term patency. Innovative techniques in assessing the ulnar collateral circulation to the hand continue to evolve, giving comfort to the surgeon. Several centres have confirmed that the early results of surgery using the radial artery are similar to those using conventional grafts. Few late graft patency results or clinical data have been reported. Unresolved issues, such as the importance of pathological changes in the radial artery, the prevention of spasm, and the hypoperfusion syndrome, lurk in the background. The role of the radial artery continues to evolve.

The road to complete arterial grafting for coronary artery disease.

In 1984, our department moved to the use of single, and subsequently, bilateral internal thoracic artery grafting which, when reviewed after 12 years, suggest the addition of a second internal thoracic artery is beneficial. The 10-year survival using all-cause mortality was 86.9% for bilateral internal thoracic artery grafting compared with 74.2% for the use of a single internal thoracic artery graft. The mortality rate ratio for single versus bilateral internal thoracic artery grafts was 1.4 (P=0.009). In 1995, we entered an era of total arterial grafting using combinations of radial and internal thoracic arteries. There have been no additional early complications in the first 2 years, furthermore the early results show that the postoperative creatinine kinase MB isoenzyme and the myocardial infarction rates were lower in patients receiving at least one radial artery graft compared with those not receiving a radial artery graft. Continued use of internal thoracic and radial arteries to achieve complete arterial revascularisation for patients with coronary artery disease appears justified.

The radial artery as a bypass graft.

The radial artery is being reintroduced into clinical practice to increase the number of arterial grafts for patients undergoing coronary artery bypass surgery. The radial artery is readily available from one or both forearms and removal is safe in patients who have a normal collateral circulation to the hand. Harvesting the radial artery with the adjacent veins using a minimal touch technique and vasodilators will prevent vasospasm and possibly early occlusion. A concern is that subclinical atheroma is present in many patients. The radial artery can be used as a single graft, anastomosed in a "Y" fashion with the internal mammary artery, or used as a sequential graft. The early mortality and complications are low. There are potential cost savings because the need for an incision in the leg is avoided, so that patients may be discharged early. The early results of radial artery grafting are encouraging. Further follow-up is required to determine the late patency and effects on survival of using the radial artery graft.

Homograft replacement of the mitral valve. Graft selection, technique of implantation, and results in forty-three patients.

UNLABELLED: Because of experience gained in reconstructive mitral valve surgery, we have reevaluated the implantation of cryopreserved homografts in the mitral position. Forty-three patients, aged 11 to 69 years (mean 34 years), underwent mitral valve replacement with cryopreserved mitral homografts. The indications for the procedure were acute endocarditis (n = 14), rheumatic stenosis (n = 26), systemic lupus endocarditis (n = 2), and marasmic endocarditis (n = 1). All homografts were obtained from hearts explanted in the course of transplantation and were cryopreserved at -160 degrees C in 10% dimethyl sulfoxide solution without antibiotics. Appropriate sizing was based on morphologic study of the homografts and preoperative echocardiographic assessment of the recipient valve. In 82 homografts analyzed, the height of the anterior leaflet was 25 +/- 3 mm and the distance from the anulus to the apex of the anterior papillary muscle was 21 +/- 3 mm. The morphologic features of the papillary muscles were classified according to four types of increasing complexity. Nine valves with complex (type IV) papillary muscle abnormalities were discarded. Echocardiographic measurements of the valve were matched with those of the homograft identification cards and a slightly larger homograft was selected (measurements + 3 mm). Partial homograft replacement was done in case of a localized lesion (abscess or calcification) (n = 21). Total homograft replacement was undertaken in the presence of diffuse lesions (n = 22). Two hospital deaths occurred as a result of poor cardiac output. One patient required reoperation on the tenth postoperative day after a dehiscence on the valvular suture line. After a mean follow-up of 14 months, there has been one late death caused by a bronchial neoplasm and one reoperation for residual stenosis (partial replacement). The remaining patients were in either New York Heart Association class I (n = 25) or II (n = 13). Thirty-three patients were in sinus rhythm. Follow-up echocardiography has revealed no mitral regurgitation (n = 20), minimal mitral regurgitation (n = 13), and mild mitral regurgitation (n = 5). Surface valve area has been calculated at 2.5 +/- 0.4 cm2 in partial homograft reconstruction and 2.7 +/- 0.3 cm2 in total homograft replacement, with a transvalvular gradient of 3 +/- 4 mm Hg. CONCLUSION: In a selected group of patients, the use of mitral homografts significantly extended the present limitations of reparative surgery of the mitral valve.

Technique of homograft replacement of the mitral valve.

In this paper, we have reviewed previous experiences in the technique of homograft replacement of the mitral valve. Following laboratory studies, we have initiated a clinical program of partial and total homograft replacement of the mitral valve and present our early results in the first 32 patients.

Effect of cardiopulmonary bypass on gastrointestinal perfusion and function.

Gastric mucosal tonometry was used to determine the adequacy of gastrointestinal perfusion in 10 patients undergoing elective myocardial revascularization. Patients were prospectively randomized to receive either pulsatile or nonpulsatile flow during cardiopulmonary bypass. All patients showed a reduction in gastric mucosal perfusion during bypass, manifested by a reduction in the gastric mucosal pH, which occurred independently of variations in the arterial pH. In the group of patients receiving nonpulsatile flow, this reduction was significantly greater (p < 0.05). Cardiopulmonary bypass using nonpulsatile flow is associated with the development of a gastric mucosal acidosis, which may have implications for the development of postoperative complications.

Intractable chest pain in cardiomyopathy: treatment by a novel technique of cardiac cryodenervation with quantitative immunohistochemical assessment of success.

A novel method of cardiac denervation by cryoablation has been developed experimentally. The technique uses liquid nitrogen delivered under pressure to ablate the principal sources of cardiac innervation--namely, the adventitia surrounding the aorta, pulmonary arteries, and veins. The technique has been verified experimentally both in vivo by physiological means and in vitro by quantitative immunohistochemistry and the measurement of myocardial noradrenaline concentrations. A 35 year old woman presented with intractable precordial pain, normal epicardial coronary arteries, and hypertrophic cardiomyopathy. Her symptoms were refractory to maximal medical treatment and she was thought to be unsuitable for either conventional myocardial revascularisation, autotransplantation, or allografting with the concomitant risk of transplant coronary artery disease. She therefore underwent cardiac denervation by the method developed in the laboratory. There was quantitative immunohistochemical evidence of extrinsic cardiac denervation associated with a considerable improvement in her symptoms. This improvement persisted during a follow up period of over 16 months.

Quantitative immunohistochemical assessment of bovine myocardial innervation before and after cryosurgical cardiac denervation.

OBJECTIVE: The aim was to determine the relative distribution and possible origins of peptide containing nerves in the bovine heart before and after functional extrinsic denervation established by cryosurgery. METHODS: A quantitative immunohistochemical technique was used. RESULTS: In the intact heart, myocardial nerve fibres and fascicles displaying immunoreactivity for the general neural marker protein gene product 9.5 had an atrial to ventricular gradient in density. The right atrium was the most densely innervated region and a major proportion of the total myocardial innervation, visualised by protein gene product 9.5 immunoreactive nerves, showed neuropeptide tyrosine (45%) and tyrosine hydroxylase (20%) immunofluorescence staining, while nerves immunoreactive for vasoactive intestinal polypeptide and calcitonin gene related peptide formed relatively minor subpopulations (representing less than 2% and 0.5%, respectively, of the total fluorescent myocardial innervation). Following cryoablation there was a significant reduction in the percentage fluorescent area of protein gene product 9.5 immunoreactive nerves throughout the heart, of greater than 90% of the control values. There were highly significant reductions in the percentage fluorescent area of nerves showing immunoreactivity to neuropeptide tyrosine, tyrosine hydroxylase, and calcitonin gene related peptide, to 1.01, 0.92, and 0.05%, respectively, of the intact myocardial innervation. The distribution of vasoactive intestinal polypeptide immunoreactive nerves was more variable and displayed an equivocal response to cardiac cryoablation. CONCLUSIONS: The majority of nerves showing immunoreactivity to neuropeptide tyrosine, tyrosine hydroxylase, and calcitonin gene related peptide are of extrinsic origin, while vasoactive intestinal polypeptide immunoreactive nerves may have intrinsic as well as extrinsic origins. The distribution and apparent origins of immunohistochemically defined nerves in the bovine heart are similar to those observed in the human heart which suggests that the calf may be an appropriate model for comparative studies.

Physiological consequences of complete cardiac denervation.

The transplanted human heart remains functionally denervated for 5 or more years postoperatively. Denervation has a number of implications for cardiac function, not the least of which is the inability of transplant recipients to experience ischaemic pain. The study of the denervated heart has not only shed light on the physiology of cardiac transplantation but also provided further insights into the functioning of the normally innervated heart.

Regional distribution and regulation of [125I]calcitonin gene-related peptide binding sites in coronary arteries.

Quantitative in vitro autoradiographic techniques were used to localize and characterize 125I-labelled human calcitonin gene-related peptide ([125I]hCGRP) binding sites in sections of bovine left anterior descending coronary artery (LAD). Specific high affinity (Kd 0.4 nM) [125I]hCGRP binding sites were localized to the media of both epicardial and myocardial coronary arteries. Binding site density was greater in distal epicardial and myocardial arteries than in proximal epicardial regions of the LAD. Binding sites exhibited a significantly higher affinity for alpha-hCGRP (Ki 1.1 nM) than for hCGRP-(8-37) (Ki 7.0 nM) and [Cys(ACM)2,7]hCGRP (Ki 27.4 nM). Guanosine-5'-O-(3-thiotriphosphate) inhibited [125I]hCGRP binding in a concentration-dependent manner. Extrinsic denervation of the bovine heart resulted in a depletion of CGRP-like immunoreactive perivascular nerve fibres and an increase in the density of coronary artery [125I]hCGRP binding sites (P = 0.0092). The regional distribution of binding sites in human coronary arteries differed from that observed in bovine and porcine vessels. It is concluded that selective, G protein-coupled, CGRP receptors are present in the media of bovine coronary arteries; there are both regional and species differences in the distribution of CGRP binding sites in coronary arteries and endogenous CGRP may exert a tonic influence on coronary vasomotor tone.

Use of endotracheal silicone stents for relief of tracheobronchial obstruction.

In this article we describe our initial experience with bifurcated and longitudinal silicone stents that can be inserted entirely endoscopically. A total of 10 patients were stented; half had upper airways obstruction resulting from malignant disease and half had anastomotic obstruction after single-lung (3 patients), double-lung (1 patient), or heart-lung transplantation (1 patient). All patients derived immediate relief of life-threatening stridor. Stents were in place for between 5 days and 2 1/2 years (mean, 232.9 days). In the patients with malignant disease, the stents have provided effective relief from stridor for the remainder of their lives. In the transplant recipients, the medium-term results are encouraging, with the stents providing effective relief from stridor, although the longitudinal stents have been associated with distal migration, requiring that the stents be replaced on up to five occasions. The stents have not been associated with infection in the nonimmunosuppressed patients, and during the relatively short follow-up period there has been no tissue reaction to the material.

Simultaneous immunostaining method for localization of bromodeoxyuridine and calcitonin gene-related peptide.

A new simultaneous double immunostaining method has been optimized to localize the DNA synthesis marker bromodeoxyuridine (BrdU) and calcitonin gene-related peptide (CGRP) in endocrine cells of Bouin's-fixed, paraffin-embedded rat lung. Nuclease pre-treatment before immunostaining is compatible with optimal tissue morphology and CGRP antigenicity preservation. Nickel-enhanced development of avidin-biotin-peroxidase staining is used to show CGRP immunoreactivity in black and alkaline phosphatase-anti-alkaline phosphatase is applied to demonstrate incorporated BrdU in red. The present methodology could be useful for studies requiring detection of incorporated BrdU in cells producing regulatory peptides or other labile antigens.

Early and long term results of re-operation for coronary artery disease.

OBJECTIVE: To define the incidence, possible causes, operative procedure, and early and medium term results of patients undergoing reoperation for coronary artery disease. DESIGN: A retrospective analysis of patients undergoing reoperation in one hospital during a 10 year period. SETTING: A regional cardiothoracic centre. PATIENTS: 115 patients had reoperation for recurrent angina, 1-17 years (mean (SD) 7.4 (3.9)) after primary revascularisation. MAIN OUTCOME MEASURES: They received 279 grafts (2.4 grafts per patient); 58% of the grafts were anasatomosed to previously grafted vessels. The internal mammary artery was used in 87% of patients who required grafts to the left anterior descending coronary artery. RESULTS: Reoperation accounted for 8.3% of the total number of patients who underwent coronary bypass grafting. Graft failure alone or in combination with other factors was judged to be the cause of recurrence of symptoms in 87%. 42% of patients had two or more coronary risk factors. The early mortality was 5.2% and the actuarial survival at five and 10 years was 90.4% and 88.4% respectively. 85% of the survivors had initial complete relief of angina and 14% had partial improvement. Freedom from recurrent symptoms at five and 10 years was 66.6% and 34.6% respectively. CONCLUSIONS: Vein graft failure either alone or in combination with progression of native coronary disease is the main cause for symptomatic deterioration after bypass grafting. Reoperation can be performed with slightly increased risk and can give good early and medium term results.

In vitro sensitized autologous tumorocidal lymphocytes to colonic adenocarcinoma.

We report a method of developing a population of tumorocidal lymphocytes by culturing peripheral blood mononuclear cells (PBMC) with live isogenic colorectal tumour cells in a mixed cell culture. When the proportion of PBMC to tumour cells is 100:1, eradication of the tumour cell population results. The proportion of activated lymphocytes in culture increases with cytotoxic activity as demonstrated by the presence of the cytotoxic enzyme serine esterase in the lymphocyte granules.

CGRP-immunoreactive endocrine cell proliferation in normal and hypoxic rat lung studied by immunocytochemical detection of incorporation of 5'-bromodeoxyuridine.

We have tested the suggestion that the reported increase, in hypoxic rats, in the number of lung endocrine cells immunoreactive for the regulatory peptide CGRP is caused by an accumulation of peptide within the cells which renders them more detectable, rather than by a real increase in proliferation. The incorporation of continuously infused 5'-bromodeoxyuridine (BrdU) into nuclei of CGRP-containing cells was studied by immunohistochemistry in the airway and respiratory epithelium of rats kept in a hypoxic (10% O2), normobaric conditions for 7 days and in normoxic, normobaric controls. Some CGRP-immunoreactive cells could also be labelled for BrdU. However, the ratio of the number of cells labelled with both CGRP and BrdU to the number of cells labelled with CGRP alone did not differ significantly between hypoxic and normoxic rats (7.1 +/- 0.7 and 6.1 +/- 1.2, respectively; mean +/- SEM; P = 0.49). These data strongly suggest that CGRP-containing endocrine cells or their precursors do proliferate in adult rat lung, but that the proliferation is not increased significantly in hypoxia.

Cardiac denervation in the calf using cryoablation: functional evidence and regional tissue catecholamine content.

Twenty-six calves were subjected to a technique of cryoablation in order to establish an animal model of complete cardiac denervation. All 26 survived the procedure, and 20 were alive to be re-evaluated 2-4 weeks later. Mean heart rate in the denervated animals rose from 77 +/- 7.8 beats/min to 102 +/- 16.4 (P less than 0.01). Cryoablation abolished the heart rate responses to electrical stimulation of the vagus nerve and thoracic sympathetic trunk. The reduction in myocardial noradrenaline concentrations averaged 99% in the right atrium, 90% in the left atrium, 85% in the right ventricle and 90% in the left ventricle, when compared with tissue obtained from control animals. Cryoablation is a relatively simple means of accomplishing complete functional cardiac denervation in the calf. On the basis of the observed change in heart rate, the calf model appears to be more comparable with human heart transplant recipients than the dog.

Intraabdominal complications after cardiopulmonary bypass.

Thirty-three intraabdominal complications occurred in 27 patients over a 16-year period in 4,629 patients who underwent cardiopulmonary bypass (0.58% incidence). The mortality was 14.8% for the intraabdominal complication group compared with 3.4% for the control group of patients (p less than 0.01). The most common complication was gastrointestinal hemorrhage (n = 20), of which esophagitis (n = 6) was the most common cause. However, patients with duodenal ulcer (n = 4) had the highest mortality; 2 patients who underwent truncal vagotomy and pyloroplasty subsequently died. Two further patients underwent operation for perforated anterior duodenal ulcers without further morbidity. Cholecystitis developed in 5 patients and acute pancreatitis in 4; all were managed nonoperatively with no mortality. Multisystem organ failure developed in 2 patients, of whom 1 died. There was a significant correlation between intraabdominal complications and prolonged bypass time. The mean bypass time was 96.7 +/- 28.6 minutes for the patients with gastrointestinal complications, compared with 81.7 +/- 48.4 minutes for the whole group (p less than 0.01). No correlation was demonstrated for type of operation undergone or the age of the patient. In the last 5 years, 2,145 patients underwent cardiopulmonary bypass, of whom 562 received pulsatile and 1,583 nonpulsatile flow. The incidence of intraabdominal complications was 0.18% (n = 1) in the pulsatile group compared with 0.63% (n = 10) for the nonpulsatile group (p = 0.14). Intraabdominal complications, although of low incidence, carry a significantly high mortality, and the clinician must be alert in the postoperative period to institute early therapy.

Imaging of metastatic colorectal cancer with tumour-activated killer lymphocytes.

Adoptive immunotherapy may be useful for treating or visualising metastatic cancer. Lymphocytes were taken from 6 patients with metastatic colorectal cancer and cultured with cells from the patients primary tumour to produce tumour-activated killer (TAK) lymphocytes. We re-injected each patient with IIIIn-labelled TAK cells in order to visualise metastases. Images were taken with a gamma-camera for up to 48 h after injection. Metastases were revealed as early as 4 h in the lung and as late as 48 h in the abdomen. Liver images produced "cold" spots corresponding to metastatic lesions. Lymph nodes were not visualised. Re-injection of TAK cells raised against autologous colorectal tumours reveals the sites of metastases.