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Biomedical subjects

S J Edmondson

Publications and source records attributed to S J Edmondson.

At least 19 recordsLinked to original sources

Na+/H+ exchanger activity does not contribute to protection by ischemic preconditioning in the isolated rat heart.

BACKGROUND: Despite evidence that pharmacological inhibition of the Na+/H+ exchanger (NHE) is cardioprotective, activation of NHE has been proposed as a protective mechanism of ischemic preconditioning (PC). METHODS AND RESULTS: In isolated rat ventricular myocytes (n=8 to 11 per group) loaded with the fluorescent pH indicator C-SNARF-1, we showed that HOE-642 (HOE) was a potent inhibitor of the sarcolemmal NHE (80% inhibition at 1 micromol/L); such inhibition was readily reversible by washout of the drug. We confirmed that 1 micromol/L HOE produces significant and reversible inhibition of NHE activity in isolated rat hearts as well (n=4), and in this model, we tested (n=8 per group) whether the presence of the drug during (1) the prolonged period of ischemia (40 or 60 minutes) or (2) the preceding brief periods of PC ischemia (3 minutes plus 5 minutes) modulates the protective efficacy of PC. In protocol 1, HOE was infused for 5 minutes immediately before the prolonged ischemic period. With 40 minutes of prolonged ischemia, the postischemic recovery of left ventricular developed pressure (LVDP) was 15+/-2% in controls and was improved to 45+/-7% with HOE (P<.05), 55+/-5% with PC (P<.05), and 68+/-2% with PC+HOE (P<.05 versus all groups). When the prolonged ischemic period was extended to 60 minutes, an additive effect of PC and HOE was readily apparent and LVDP recovery with PC+HOE (66+/-2%) was almost double that observed with HOE (37+/-4%) or PC (34+/-5%) alone (P<.05). In protocol 2, HOE was infused for 3 minutes immediately before each episode of PC ischemia and was subsequently washed out before a 40-minute prolonged ischemic period (HOE+PC). LVDP recovery was 34+/-4% in controls and was improved to 57+/-2% with PC (P<.05) and 55+/-3% with HOE+PC (P<.05). Improved recovery of LVDP was matched by reduced creatine kinase leakage in all cases. CONCLUSIONS: Because coadministration of HOE (at a concentration sufficient to inhibit NHE activity) did not reduce the efficacy of PC in either protocol, we conclude that NHE activity does not contribute to the cardioprotective actions of PC. On the contrary, NHE inhibition during the prolonged ischemic period may enhance the protection afforded by PC.

Animals↗

Na+/H+ exchanger inhibitor HOE-642 improves cardioplegic myocardial preservation under both normothermic and hypothermic conditions.

BACKGROUND: The sarcolemmal Na+/H+ exchanger has been implicated in the pathogenesis of myocardial injury during ischemia/reperfusion. We determined the cardioprotective efficacy of the Na+/H+ exchanger inhibitor HOE-642 (HOE) as an alternative, adjunct, or additive to cardioplegia (CP). METHODS AND RESULTS: In isolated working rat hearts (n=6 per group) subjected to 25 minutes of ischemia at 37 degrees C, the postischemic recovery of aortic flow (AF) was 5+/-3% in controls; this was improved to 18+/-4% by the preischemic infusion of 1 micromol/L HOE (P<.05 versus control) and to 53+/-7% by CP (P<.05 versus control and HOE). In hearts subjected to CP and 35 minutes of ischemia at 37 degrees C, AF recovered to 9+/-3% with CP alone; this was improved to 18+/-3% by the adjunctive administration of HOE during early reperfusion (CP+repHOE, P<.05 versus CP) and to 27+/-4% by the use of HOE as an additive to CP (CP+HOE, P<.05 versus CP and CP+repHOE). With 120 minutes of ischemia at 28 degrees C, AF recoveries were 16+/-3% in CP, 32+/-3% in CP+repHOE (P<.05 versus CP) and to 50+/-4% in CP+HOE (P<.05 versus CP and CP+repHOE). With 300 minutes of ischemia at 7.5 degrees C, the corresponding values were 30+/-4% 45+/-5% (P<.05 versus CP), and 63+/-5% (P<.05 versus CP and CP+repHOE). Improved recovery of pump function was often accompanied by a reduction in creatine kinase leakage during reperfusion. CONCLUSIONS: (i) HOE alone affords significant protection at normothermia but is not a superior alternative to CP, and (ii) the use of HOE as an adjunct or additive to CP provides significant benefit at normothermia, moderate hypothermia, and severe hypothermia.

Animals↗

A surgical approach to coexistent coronary and carotid artery disease.

OBJECTIVE: To assess the early results of combined coronary artery bypass graft surgery and carotid endarterectomy. DESIGN: Retrospective and ongoing analysis of patients who underwent combined coronary artery bypass graft surgery and carotid endarterectomy. SETTING: Cardiothoracic unit in a London teaching hospital. PATIENTS: From June 1987 to March 1995, 64 patients were identified. They were patients who were scheduled to have coronary artery bypass graft surgery or required urgent coronary revascularisation and who were found to have significant coexistent carotid disease. (Unilateral carotid stenosis > 70%, bilateral carotid stenosis > 50%, or unilateral carotid stenosis > 50% with contralateral occlusion.) INTERVENTIONS: Both procedures were performed during one anaesthesia: the carotid endarterectomy was performed first without cardiopulmonary bypass. After completion of carotid endarterectomy, coronary artery bypass graft surgery was performed. MAIN OUTCOME MEASURES: The incidence of stroke, transient ischaemic attack, and myocardial infarction in the early postoperative period was analysed. RESULTS: Myocardial revascularisation was successful in all 64 patients. There were no perioperative infarcts. In three patients (4.7%) a new neurological deficit developed postoperatively: two recovered fully before hospital discharge. CONCLUSIONS: Combined coronary artery bypass graft surgery and carotid endarterectomy were performed safely and with good results.

Aged↗

Dynamics of early postischemic myocardial functional recovery. Evidence of reperfusion-induced injury?

BACKGROUND: The present study was designed to explore the relation between the duration of ischemia and the rate and extent of myocardial functional recovery after reperfusion. METHODS AND RESULTS: Isolated rat hearts were perfused with blood from a support animal for 15 minutes (flow rate, 2.5 mL/min; perfusion pressure, 60.1 +/- 1.3 mm Hg). Control left ventricular developed pressure (LVDP) was measured, and the hearts (six per group) were subjected to 10, 20, 30, 40, 50, 60, 70, or 80 minutes of global ischemia (37 degrees C) and 60 minutes of reperfusion. Pacing (320 beats per minute) was instituted before and after ischemia. In all groups, transient arrhythmias occurred at the onset of reperfusion, to be followed by an early phase of recovery that peaked after 2 to 3 minutes of reperfusion. The relation between the extent of this initial recovery and the duration of preceding ischemia was described by a bell-shaped curve. Thus, the maximum initial mean recovery after 10, 20, 30, 40, 50, 60, 70, or 80 minutes of ischemia was 97%, 108%, 145%, 154%, 118%, 34%, 41%, and 24%, respectively, of preischemic LVDP. Possibly indicative of reperfusion-induced injury, LVDP then declined in all groups so that after 20 minutes of reperfusion, the mean recovery was 63%, 53%, 48%, 50%, 56%, 12%, 9%, and 5%, respectively. In the 10-, 20-, 30-, and 40-minute ischemia groups, there then was a secondary increase in LVDP, possibly indicating the start of recovery from stunning. After 60 minutes of reperfusion, the mean recovery of LVDP was 82%, 65%, 59%, 54%, 47%, 9%, 7%, and 4%, respectively; this second phase of recovery was inversely proportional to the duration of ischemia. To define the early phase of recovery that had been obscured by reperfusion-induced arrhythmias, we repeated the experiments with the inclusion of a cardioplegic infusion (St Thomas' solution for 2 minutes before ischemia). This significantly reduced the incidence of ventricular fibrillation during early reperfusion. The extent of the initial postischemic recovery of LVDP was similar to that observed without cardioplegia; however, the mean secondary recovery was greater in all groups. Again, the relation of early transient (2 to 5 minutes) recovery to the duration of ischemia was represented by a bell-shaped curve, whereas the secondary recovery was inversely related. CONCLUSIONS: Although the results of the present study confirm the protective properties of cardioplegia, they also shed some light on the nature of reperfusion-induced injury and myocardial stunning and their complex relation to the severity of the preceding ischemia.

Animals↗

Dobutamine echocardiography and thallium-201 imaging predict functional improvement after revascularisation in severe ischaemic left ventricular dysfunction.

OBJECTIVES: To evaluate the concordance between thallium-201 uptake and echocardiographic wall thickening, which are both indicators of potentially reversible myocardial dysfunction, in patients with chronic ischaemic left ventricular failure and to assess their relative contribution to predicting improvement in regional function after revascularisation in a subgroup. PATIENTS AND METHODS: 45 patients with chronic ischaemic left ventricular dysfunction (mean (SD) ejection fraction 25 (8)%) underwent echocardiography before and after dobutamine infusion (10 micrograms/kg/min). Of these, 22 patients underwent rest echocardiography at a mean (SD) of 9 (1) weeks after revascularisation. 201Tl imaging was performed during dobutamine echocardiography and at rest, 1, and 4 h after treatment with sublingual glyceryl trinitrate on two separate days. Potentially reversible dysfunction was thought to be present when a myocardial segment contained a Tl score of > or = 3 (ascending score 1-4), or showed improved wall thickening of a dysynergic segment during dobutamine stimulation. RESULTS: Of the 201Tl protocols, the redistribution scan 1 h after treatment with glyceryl trinitrate best demonstrated myocardial viability. Concordance between 201Tl and dobutamine induced wall thickening was 82% (kappa = 0.59) for detecting potentially reversible myocardial dysfunction before revascularisation (n = 45). Regional function improved in 18 of 22 patients after revascularisation. There were 168 dysynergic segments before intervention. The sensitivity of echocardiography and 201Tl imaging for detecting "recoverable" or viable segments after revascularisation was 87% and 92% respectively and specificity was 82% and 78% respectively (P = NS). CONCLUSIONS: Dobutamine echocardiography and 201Tl imaging may be used to predict mechanical improvement in dysynergic segments after revascularisation in patients with chronic ischaemic left ventricular dysfunction.

Adult↗

Surgery for radiation-induced valvular disease.

The effects of radiation on the heart have been well described including acute and chronic pericarditis, myocardial fibrosis, accelerated arteriosclerosis of the coronary arteries. However, valvular dysfunction secondary to mediastinal irradiation has received less attention. We report two cases who developed valvular dysfunction associated with coronary artery disease possibly caused by mediastinal irradiation and a review of the literature regarding surgery for radiation induced valvular disease. Both patients underwent aortic valve replacement and coronary artery bypass graft surgery. With increasingly prolonged survival following mediastinal irradiation, we believe that long term follow up in patients who receive mediastinal irradiation is indicated.

Angina Pectoris↗

Coronary artery anastomotic contour--a method for individual surgeons to assess their suture techniques.

A method is described whereby individual surgeons may monitor their coronary graft suturing techniques. The coronary artery anastomotic contour is measured quantitatively in corrosion resin cast models made of anastomoses between long saphenous vein and the left anterior descending coronary artery of a pig's heart. The relevant parameter assessing the contour is the mean anastomotic narrowing expressed as a percent (MAN%). To provide an example of the potential of the method, a single surgeon compared a continuous suture technique (n = 30) with an interrupted one (n = 30) using corrosion resin models. There was significantly less (P < 0.05) narrowing of the anastomotic contour with the interrupted technique (mean MAN% = 0.3 +/- 2.9) than with the continuous (mean MAN% = 10.5 +/- 3).

Anastomosis, Surgical↗

Significance of plasma fibrinogen in coronary arterial disease: marker or causative risk factor for arterial thrombosis?

The relationship between fibrinogen and severity of disease was measured in patients with coronary arterial disease (n = 301) prior to surgical coronary revascularisation. Platelet reactivity (shear-induced haemostasis) was measured from non-anticoagulated blood, in vitro. Coagulation was assessed by the clotting time of flowing native blood (dynamic) and by the conventional (stagnant) tube tests. Significantly enhanced platelet reactivity to shear-stress was observed when patients with one-vessel disease were compared to those with two- or three-vessel disease (P = 0.003). Neither coagulation nor fibrinogen were significantly related to the severity of disease. Furthermore, patients who had myocardial infarction (n = 144) showed enhanced platelet reactivity (P = 0.02) as compared to those who had not (n = 157). Again, neither coagulation nor fibrinogen discriminated between these groups of patients. Relationship between plasma fibrinogen and platelet reactivity was also investigated in vitro. Identical blood samples with normal (220-280 mg/dl) and elevated plasma fibrinogen (approximately 500 mg/dl) were compared by measuring platelet reactivity and coagulation from native blood and platelet aggregation in whole blood. The in vitro studies suggested that plasma fibrinogen and platelet reactivity are inversely associated. Furthermore, increased fibrinogen prolonged dynamic coagulation. These findings do not support the assertion that elevated plasma fibrinogen is a true causative factor for coronary arterial disease and arterial thrombosis.

Blood Coagulation↗

Contamination of underwater seal drainage systems in thoracic surgery.

The incidence of bacteriological contamination of drainage fluid (water constituting the underwater seal plus drainage effluent) was studied in 38 patients (50 chest drains), up to 6 days after thoracotomy. No bacteriological contamination was demonstrated in any of the samples taken during this period of time. We conclude that the underwater seal drainage system may be left for up to 6 days postoperatively without change of any of its components and without risk of contamination.

Drainage↗

Quantitative measure of small vessel anastomotic contour using corrosion resin cast models: an aid to surgical training.

A surgeon who had not previously carried out a small vessel anastomosis performed 20 consecutive anastomoses between human long saphenous vein and the left anterior descending artery of a pig's heart. Corrosion resin cast models were made of the anastomoses and subjected to a quantitative analysis of the anastomotic contour. A trend of improvement in contour parameters was found with increasing experience. This model may be useful for surgeons in training.

Animals↗

Modified technique of internal mammary artery harvest.

A simple method of internal mammary artery harvesting is described. Hydrostatic pressure is used as an aid to dissection of the tissues including the internal mammary artery from the chest wall. The technique minimizes trauma to the mammary artery and allows for a rapid harvest.

Dissection↗

Bullet pulmonary embolus and the role of surgery.

A case report is described of a 33-years-old male who suffered a bullet pulmonary embolus following an abdominal gunshot injury. The literature of this rare occurrence is discussed together with the role of surgery in its treatment. Operative removal is advocated in all cases and the optimal time for removal is 1-2 weeks following the initial embolus to allow pulmonary induration, which can prevent peroperative embolus migration.

Abdominal Injuries↗

Giant thymic carcinoid.

Thymic carcinoid is a rare tumour. It may present with ectopic endocrine secretion or with symptoms of compression as a result of its size. A case is reported which presented with symptoms of compression where the size of the tumour was uniquely large such as to warrant the term giant thymic carcinoid. The typical histological features are described, together with its possible origin and its likely prognosis.

Carcinoid Tumor↗

Extensive endocardial resection for recurrent ventricular tachyarrhythmias.

Twenty-two consecutive patients underwent elective map-guided extensive endocardial resection (EER) for recurrent ventricular tachyarrhythmias (VT) of whom 20 were male. The ages ranged from 43 to 74 years (mean 57). All arrhythmias were ischaemic in origin. The mean ejection fraction was 29%. The presenting arrhythmias were ventricular tachycardia in 14, ventricular fibrillation (VF) alone in 1 and ventricular tachycardia and VF in 7. Useful additional intraoperative mapping was obtained in 19 patients. Under cardioplegic arrest, the scarred left (22) and where indicated right (4) ventricular endocardium was extensively resected. Resection of scarred papillary muscles was avoided and where indicated, localised cryoablation was performed: 21/22 had concomitant aneurysmectomy and/or coronary artery bypass grafting. There was 1 (4.5%) operative death. All survivors (95.5%) underwent postoperative electrophysiological studies at around 1 week. None had inducible arrhythmias. There were 3 (13.5%) late cardiac deaths, all due to primary cardiac failure without recurrence of arrhythmia. Of 17 (77%) long-term survivors, 16 (94%) are VT-free on no anti-arrhythmic medication at a mean follow-up of 37.2 months. One developed a new arrhythmia at 1 year which is controlled on medication. EER offers a high rate of success in ablating VT in association with a low operative mortality and good prospect of VT-free long-term survival.

Adult↗

Blunt traumatic rupture of the thoracic oesophagus.

A man with a crush injury of his upper abdomen developed bilateral pulmonary empyema after repair of tears of the oesophagus and liver. Attempts to withdraw chest drains led to recurrent septicaemia, treated by reinsertion of the drains plus administration of antibiotics. The communication of the empyema space with both the bronchial tree and the oesophagus was managed successfully with intermittent positive pressure ventilation and with a double lumen endobronchial tube isolating the right lung for 10 days. Traumatic rupture of the thoracic oesophagus carries a high mortality and prompt repair is vital.

Adult↗

Isolated atrial amyloid contains atrial natriuretic peptide: a report of six cases.

Twenty five specimens of the human right atrial appendage were examined for immunoreactivity to alpha human atrial natriuretic peptide. In the electron microscope characteristic amyloid fibrils were identified around small blood vessels and adjacent to atrial muscle cells in eight of the surgical cases and in two necropsy cases. In six cases, four surgical and two necropsy, these fibrils contained immunoreactive alpha human atrial natriuretic peptide. Amyloid is known to occur in peptide secreting endocrine tumours and immunoreactive peptide may be incorporated in the amyloid matrix. The demonstration of atrial amyloid containing immunoreactive alpha human atrial natriuretic peptide suggests that some deposits of cardiac amyloid are of a type analogous to that found in other endocrine organs.

Adult↗