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.

Method of endoscopic esophageal intubation using a rigid esophagoscope.

Endoscopic intubation of malignant esophageal strictures carries a substantial risk of esophageal perforation. We have developed a method of endoscopic intubation that reduces to a minimum the elements of the procedure that have to be performed "blind." The use of this method has been associated with a reduction in perforation rates when compared with other series.

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.

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.

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.

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.

Intraoperative assessment of nodal staging at thoracotomy for carcinoma of the bronchus.

In the staging of operable carcinoma of the bronchus, accurate assessment of mediastinal nodal status is essential in order to determine the feasibility and desirability of resection. In the UK, frozen section analysis is often logistically difficult, and many surgeons rely upon naked-eye assessment. To evaluate the accuracy of this approach, we have reviewed 100 thoracotomies performed for cancer in this unit and compared the naked-eye assessment of nodal staging with the ultimate histological findings. A total of 287 lymph nodes were examined. There were 14 false positives and 10 false negatives. The overall accuracy of naked-eye assessment was 96.1%. On no occasion did an error in naked-eye assessment result in a patient receiving inappropriate treatment. All patients were thought to be pTNM N0 or N1 prior to surgery, yet N2 disease was established in 24 patients. The value of routine mediastinal node dissection at the time of thoracotomy has been established and an important subgroup of patients with microscopic N2 disease has been identified.

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.

Right atrial electrocardiography in placement of central venous catheters.

Right atrial electrocardiography has been used both for the positioning of ventriculoatrial shunts and for the detection and treatment of air embolism during neurosurgical procedures. Its use for the precise placement of central venous catheters for parenteral nutrition is described here. 50 lines were placed in 48 patients. The lines were satisfactorily sited in 48 cases. No false-negative or false-positive traces were obtained. The technique is extremely accurate; failure to obtain the characteristic traces indicates malposition of the catheter tip. The need for on-table radiography is virtually eliminated.

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.

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.

Localization of endothelin binding sites and endothelin-like immunoreactivity in human fetal heart.

The localization of [125I]endothelin-1 ([125I]ET-1) and [125I]endothelin-3 ([125I]ET-3) binding sites, as well as ET-like immunoreactivity, was investigated in sections of human fetal heart, using in vitro autoradiographic and immunohistochemical techniques. High-affinity [125I]ET-1 binding sites showed a tissue-specific distribution pattern, with high-density binding to the atria, ventricles (77-100 amol/mm2), and cardiac valve cusps (120.6 +/- 2.6 amol/mm2). Specific high-density binding of [125I]ET-3 was also exhibited on valve cusps (143.2 +/- 2 amol/mm2), whereas a much lower density of binding was displayed on atria and ventricles (10-15 amol/mm2). Microautoradiographic examination demonstrated binding sites on the wall of the aorta, pulmonary and coronary arteries, myocardium, ventricular conduction system, endocardium, and endothelial lining of valve cusps. Regional differences in the density and affinity of ET binding sites suggest that subpopulations of receptors are present in the human fetal heart. ET-like immunoreactivity was localized to a heterogeneous population of endothelial, endocardial, and epicardial mesothelial cells. The concordant localization of specific binding sites and ET-like immunoreactive cells indicates that locally released peptide might have a paracrine or autocrine role, possibly influencing cardiovascular development and function.