Myocardial rewarming during normothermic cardiopulmonary bypass.
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Biomedical subjects
Publications and source records attributed to G D Angelini.
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Intimal thickening is an important cause of late coronary vein graft occlusion, which no variation of surgical technique or pharmacologic intervention has been shown to reduce. We used a recently developed quantitative organ culture of human saphenous vein to investigate whether surgical preparative injury promotes neointima formation. We also investigated the effects on neointima formation of the lipid-soluble cyclic nucleotide analogs, 8-Br-cyclic adenosine monophosphate and 8-Br-cyclic guanosine monophosphate, and the phosphodiesterase inhibitor, isobutylmethylxanthine. These agents are pharmacologic mimetics of endothelium-derived prostacyclin and nitric oxide, which elevate vascular smooth muscle cyclic adenosine monophosphate and cyclic guanosine monophosphate concentrations, respectively, and may normally suppress neointima formation. Surgical preparation was found to promote intimal thickening and neointimal smooth muscle cell proliferation by 42% and 48%, respectively. 8-Br-cyclic adenosine monophosphate, 8-Br-cyclic guanosine monophosphate, or isobutylmethylxanthine (which elevated endogenous cyclic adenosine monophosphate concentrations) inhibited intimal thickening by 80%, 40%, and 72%, respectively, at a concentration of 0.1 mmol/L. The results imply that surgical techniques that avoid preparative injury and vasodilator drugs that act by elevating cyclic adenosine monophosphate or cyclic guanosine monophosphate concentrations may reduce neointima formation in vein grafts.
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A prospective study of 100 patients undergoing coronary artery bypass surgery was performed to demonstrate the effectiveness of a posterior pericardiotomy in reducing the incidence of pericardial effusions and, consequently, reducing the incidence of supraventricular arrhythmias in the post-operative period. Pericardial effusion occurred in 4 of 50 patients following a posterior pericardiotomy, whereas effusion occurred in 20 of 50 patients in whom a pericardiotomy was not created (P < 0.0005). Supra-ventricular arrhythmias occurred in 4 patients in the pericardiotomy group and 18 in the group treated without pericardiotomy (P < 0.005). No complications resulted from this procedure. We conclude that pericardiotomy is a simple, safe and effective method for reducing the incidence or pericardial effusion and thereby post-operative supra-ventricular arrhythmias.
BACKGROUND: The demand for open heart surgery has driven current practice towards early postoperative discharge and interhospital transfer to maximise patient throughput. The extent to which this redirects morbidity to other healthcare providers is unknown. OBJECTIVE: To define the incidence of inhospital and early postoperative morbidity within 6 weeks of primary hospital discharge after cardiac surgery. DESIGN: Prospective inhospital data for 322 consecutive adult patients undergoing cardiac surgery were compared with retrospective information obtained by postal questionnaire. RESULTS: Mean (SD) primary postoperative hospital stay was 8.3 (3.1) days. There were 13 inhospital deaths (4%), and three patients died within 6 weeks of primary discharge. Retrospective information was obtained from 297 patients (96%). Of these, 77% patients were discharged home directly, while 23% were transferred to other hospitals for continued medical care. Mean (SD) hospital stay after transfer was 12 (8.4) days and required 741 additional hospital bed days. Thirty nine patients (13%) were readmitted to hospital, requiring a further 275 hospital bed days. The readmission rate was lower in patients sent home directly (10%), than in those who were transferred (22%; P < 0.001). CONCLUSIONS: Inhospital audit underestimates early morbidity after cardiac surgery. The burden transferred to other healthcare providers is considerable and has important financial implications for purchasers.
BACKGROUND: The recent introduction of normothermic cardiopulmonary bypass (CPB) perfusion has raised concerns regarding the associated risk of renal dysfunction through its potential to exacerbate the systemic inflammatory response and end-organ injury. This study was designed to investigate the influence of CPB perfusion temperature on renal function. METHODS: A prospective, randomized, controlled trial of CPB perfusion temperature (28 degrees C, 32 degrees C, and 37 degrees C) was performed in 30 patients undergoing routine coronary artery bypass grafting with normal preoperative renal function. Creatinine clearance was measured before induction of anesthesia, during CPB, and during every 12-hour period thereafter for 48 hours postoperatively. Glomerular and tubular function were assessed further by measurement of urinary creatinine, albumin, total protein, and retinol binding protein levels preoperatively, during CPB, and on days 1 and 3 postoperatively. RESULTS: Creatinine clearance increased on CPB by 51% (28 degrees C), 185% (32 degrees C), and 112% (37 degrees C) (all p < 0.01 versus preoperative values) and returned to preoperative values by 24 hours postoperatively in all three groups. Urinary albumin/creatinine ratios rose significantly from a mean of 0.4 +/- 0.1 (standard deviation) to 10 +/- 12.5 (28 degrees C), from 0.55 +/- 0.3 to 5.2 +/- 4.9 (32 degrees C), and from 0.96 +/- 0.8 to 7.8 +/- 7.0 (37 degrees C) during CPB (all p < 0.001) but decreased gradually thereafter. Also, urinary total protein/creatinine ratios rose significantly from a mean of 0.009 +/- 0.007 to 0.034 +/- 0.02 (28 degrees C), from 0.01 +/- 0.006 to 0.026 +/- 0.01 (32 degrees C), and from 0.011 +/- 0.008 to 0.033 +/- 0.02 (37 degrees C) during CPB (all p < 0.005); however, there was a further increase by 24 hours, and ratios decreased gradually thereafter. Similarly, urinary retinol binding protein/creatinine ratios rose significantly in all three groups during CPB (all p < 0.0001) and increased further by 24 hours. There was no statistically significant difference between the renal markers in the three temperature groups in any of the observations. CONCLUSION: These data suggest that cardiopulmonary bypass perfusion temperature does not influence renal function in patients undergoing coronary artery bypass grafting.
In order to clarify the role of thrombolytic therapy for the treatment of left sided prosthetic valve thrombosis, a composite analysis of 158 cases reported in the English literature was undertaken. Complete success of therapy was achieved in 68.4% of patients, and the results were better in patients with aortic compared to mitral valve prostheses (p < 0.01), in those presenting in lower NYHA class (p < 0.01), and with acute rather than chronic symptoms (p < 0.05). A successful outcome was seen more frequently with tilting disc than bileaflet valves (p < 0.001). Overall mortality during therapy was 7%. Cerebral embolic events were observed in 9.5% of patients, and irreversible neurological injury occurred in 4.4%. The rethrombosis rate was 17% and the incidence of late death was 6.3%. Thrombolysis may be a useful therapeutic alternative for left sided prosthetic valve thrombosis in patients with a perceived contraindication to surgery. The risks of systemic clot embolization along with incomplete resolution of valve leaflet motion or rethrombosis limits any recommendation for more widespread use.
OBJECTIVES: Earlier research on human skeletal and cardiac muscle has shown a fall in the intracellular free amino acid pool, particularly the non-essential amino acids, during surgery. Surgical preparation of the human saphenous vein for coronary artery by pass grafting has been shown to provoke metabolic damage and may therefore induce changes in cellular amino acids which may have long-term implications for the performance of the grafted vein. This work investigates the hypothesis that surgical preparation of saphenous vein induces changes in amino acids. METHODS: Changes in the intracellular free amino acid pool were monitored, using high-performance liquid chromatography (HPLC), in both freshly isolated and surgically prepared human saphenous veins during coronary artery bypass grafting. In order to asses the extent of metabolic damage incurred by surgical preparation, adenosine triphosphate (ATP) levels were also measured. RESULTS: A substantial fall in intracellular free amino acid was associated with surgical preparation of human saphenous vein for coronary artery bypass grafting (190.8 +/- 25 to 106 +/- 18 mumol.g-1 protein, n = 10, P < 0.05). Although the fall was seen in most amino acids detected, it was marked and statistically significant (P < 0.05) for taurine (30.6 +/- 3.1 to 9.0 +/- 2.2 mumol.g-1 protein), glutamate (43.6 +/- 5.6 to 18.2 +/- 4.5 mumol.g-1 protein), glutamine (12.8 +/- 1.6 to 3.3 +/- 1.2 mumol.g-1 protein) and asparagine (9.6 +/- 1.6 to 4.1 +/- 1.0 mumol.g-1 protein). The fall in tissue taurine which would be largely due to transport showed a strong positive correlation with the fall seen in glutamate, glutamine and asparagine. ATP levels significantly decreased as a result of surgical preparation (279 +/- 44 to 96 +/- 21 nmol.g-1 wet weight, P < 0.05). The fall in ATP was accompanied by an increase in alanine/glutamate ratio which may reflect increased glutamate-alanine transaminase activity and therefore metabolic changes. CONCLUSIONS: The metabolic damage associated with surgical preparation of human saphenous vein for coronary artery bypass grafting is accompanied by a fall in the intracellular free amino acid pool which is marked and statistically significant for glutamate, taurine, glutamine and asparagine. The fall is likely to be due to transport metabolism may also contribute. This may have important implications for the functional recovery of the grated vein.
BACKGROUND AND AIM OF STUDY: Aprotinin is widely used during high risk cardiac surgery to reduce blood loss. Concern has been expressed about the safety of aprotinin in association with hypothermic circulatory arrest for surgery of the thoracic aorta and aortic valve. METHODS: A consecutive series of 19 patients undergoing surgery of the ascending aorta and/or the aortic arch using hypothermic circulatory arrest (15 - 20 degrees C) in conjunction with the use of aprotinin were studied prospectively from January 1993 to October 1994. The indications for operation were aortic dissection (n = 15) (11 acute) or annuloaortic ectasia (n = 4); 11 were emergency procedures. Ten patients underwent aortic valve replacement as part of a composite aortic root replacement and in seven patients aortic valve resuspension was possible. RESULTS: Mean total chest tube drainage was 878 +/- 548 ml (range 300 - 2,000 ml) with a mean usage of homologous blood of 2,328 +/- 1,600 ml. All but one patient survived (mortality 5.3%). None of the survivors experienced any adverse cardiac or neurological events. Serum creatinine rose significantly from a mean of 102 +/- 17 micromol/L preoperatively, to a mean of 172 +/- 100 micromol/L postoperatively (p<0.05), however, none of the patients became anuric or required dialysis and all values returned to preoperative levels by six weeks after surgery. Median intensive care stay was two days (range 1 - 20 days) and the median postoperative hospital stay was 11 days (range 6 - 50 days). CONCLUSION: These data suggest that aprotinin in conjunction with hypothermic circulatory arrest for surgery of the thoracic aorta and aortic valve has no adverse effect on early survival. However, significant though transient postoperative renal dysfunction was commonly observed in our experience.
Coronary artery disease is a common finding, responsible for substantial morbidity and mortality in the elderly. Despite this, there is a general reluctance to refer elderly patients for further investigation as the perceived risks are thought to outweight any potential benefit. This is not however borne out by the available evidence, which suggests that revascularisation procedures carry little additional risk in appropriately selected elderly patients. Chronological age per se should, therefore, no longer be a bar to myocardial revascularisation.
Transesophageal echocardiography is becoming increasingly popular as a method of intraoperative monitoring because it can be performed continuously, does not transgress the sterile operative field, and provides data with regard to valve function, ventricular volumes, and contractility. Recently it was suggested that it can be used to measure cardiac output; however, controversy remains regarding its accuracy. Cardiac output was measured simultaneously by transesophageal echocardiography (using a 5-MHz pulse-wave Doppler, single-plane viewing probe) and by the thermodilution method in 21 patients undergoing open heart operations. The cardiac outputs measured by thermodilution correlated poorly (r = 0.45) with the transesophageal values derived from the left ventricular cross-sectional area, and the mean difference was 0.47 +/- 2.17 (standard deviation) L.min-1, giving limits of agreement of from -3.87 to +4.81 L.min-1. Cardiac outputs measured by thermodilution correlated well (r = 0.95) with transesophageal Doppler values derived from pulmonary artery flow velocity, with a mean difference of 0.12 +/- 0.45 L.min-1 and narrow limits of agreement of from -0.78 to +1.02 L.min-1. Based on our findings, transesophageal Doppler echocardiographic determination of cardiac output using pulmonary artery flow measurements can provide accurate hemodynamic data in patients undergoing cardiac operations.
Thyroid function is depressed during and after cardiopulmonary bypass surgical procedures, and this may adversely affect myocardial performance. There is known to be a high prevalence of thyroid abnormalities in the elderly population, and many patients undergoing cardiac operations fall into this category. We have assessed thyroid function in 116 patients admitted for elective open heart procedures to determine the value of preoperative testing. Abnormalities in thyroid function were present in 13 (11.2%) of the patients studied, 3 of whom were receiving thyroxine therapy. One patient who had overt hypothyroidism died postoperatively of a large cerebral infarct; 11 had elevated thyrotropin levels with normal serum thyroxine levels; and 1 who had overtreated hypothyroidism suffered fast atrial fibrillation postoperatively. No other complications were observed. These findings indicate that thyroid function should be assessed preoperatively in patients already on thyroxine therapy. Whether thyroid function should be evaluated routinely in all patients before operations involving cardiopulmonary bypass is not clear. Although there is a high incidence of abnormal laboratory results, there were no apparent adverse effects on the surgical outcome.
Cross-sectional and M-mode echocardiography were used to review 33 patients 6-28 months (mean 19 months) after open heart surgery. Eleven patients had had echocardiographic signs of pericardial effusion during the first week after open heart surgery (Group A), and 22 had not (Group B). At review, pericardial effusion was found in 73% of subjects in Group A compared with 18% of those in Group B (P < 0.01). On average, posterior effusions were small (mean dimension in systole 0.9 cm) but they were detected reproducibly (interobserver agreement 97%). Anterior echo-free spaces (< 0.5 cm) were found frequently, but interobserver variation in their detection was high (agreement in 68%). Symptoms did not correlate with the presence of a late post-operative effusion but the groups were not matched for rhythm or ventricular function. Five patients in Group A had developed atrial fibrillation in association with their early post-operative effusion, and four of these had persisting atrial fibrillation at this review. These results suggest that echo-free spaces around the heart, suggestive of small pericardial effusions, may persist for many months after open heart surgery.
OBJECTIVE: The aim was to test the hypothesis that platelet derived growth factor (PDGF) is synthesized in intact coronary arteries and that it is associated with cell proliferation in atherosclerotic plaques. METHODS: Segments of human coronary artery obtained from heart transplant recipients were cultured in serum-free media for 24 h. Tissue viability was assessed by ATP concentration. Cell proliferation was determined by incorporation of [3H] thymidine, autoradiography, and proliferating cell nuclear antigen (PCNA) immunostaining. Coronary artery conditioned media were tested for mitogenic activity using a fibroblast proliferation bioassay. Reverse transcription polymerase chain reaction (RT-PCR) for PDGF A and B was subsequently performed in order to confirm the endogenous nature and isoform of this mitogen. RESULTS: Tissue viability remained unchanged during culture, and cell proliferation was detected by incorporation of [3H] thymidine. Autoradiography and PCNA immunostaining showed proliferating cells within the intimal and medial layers. Coronary artery conditioned media produced significant stimulation of cell growth [127(SEM 29)%, n = 15] above that caused by culture medium alone. This mitogenic activity was inhibited by 42(8)% (n = 8) with a polyclonal neutralising antibody to PDGF. The endogenous nature of this mitogenic activity was confirmed by detection of PDGF-A and PDGF-B mRNA expression using RT-PCR and the identity of the amplified products confirmed by DNA sequencing. CONCLUSIONS: The data provide evidence for active PDGF production and gene expression within cells of the vessel wall. They also suggest that endogenously produced PDGF may play a role in controlling vascular smooth muscle cell proliferation in human coronary arteries.
Saphenous vein graft failure remains a significant clinical and economic burden. Although increased use of arterial conduits has improved long-term outcome, the majority of bypass procedures continue to use saphenous vein. Early vein graft patency is maximized by avoiding damage at the time of implantation, meticulous surgical technique, and appropriate use of antithrombotic therapy. No surgical technique or pharmacological intervention, however, has been shown to prevent late occlusion, which results from the progression of intimal vascular smooth muscle cell proliferation and superimposed atheromatous changes. Over the last few years, there has been a dramatic increase in our understanding of the biology of the vessel wall and the cellular and humoral influences on the process of intimal vascular smooth muscle cell proliferation. This has been possible principally through the advancement and application of molecular biological techniques. Although pharmacological therapies to prevent intimal hyperplasia continue to be evaluated, it is again the new series of strategies made possible by molecular biology that provide the most exciting prospects for treatment. Development of specific antibodies, antisense oligonucleotides, and vascular gene transfer represent potentially effective therapies, not only for the prevention of vein graft failure but also for a whole range of cardiovascular diseases.
OBJECTIVE: To assess current clinical practice in coronary artery bypass surgery and compare it with a previous survey conducted five years ago. SETTING: United Kingdom. DESIGN: Postal questionnaires were sent in March 1993 to 120 consultant cardiac surgeons currently performing coronary artery bypass surgery. 104 (87%) were returned by May 1993. RESULTS: The 104 surgeons who returned the questionnaire performed an estimated total of 25,234 coronary artery bypass operations in 1992 with an average case load per surgeon similar to that in 1987 (243 v 214, NS). The internal mammary artery was regarded as the conduit of choice by 101 surgeons (97%) and was used in 93% of bypass grafts to the left anterior descending coronary artery compared with 73% in 1987 (p < 0.001) but only in 7% of grafts to the circumflex and right coronary systems. There was also a significant increase in the number of surgeons using both internal mammary arteries (88% v 59%, p < 0.01) but only a small increase in those using the internal mammary artery as a sequential graft (55% v 44%, NS). The age of the patient remains one of the main contraindications to the use of the internal mammary artery (40%), together with insufficient mammary flow (42%), endarterectomy (22%), and unstable angina (17%). The right gastroepiploic and inferior epigastric arteries were used only occasionally (3%) when the internal mammary artery or the saphenous vein were not available. Most surgeons (96%) still advocate the use of aspirin to enhance graft patency, with 87% of surgeons continuing treatment indefinitely, compared with 50% in the previous survey (p < 0.001). As for methods of myocardial protection, 72% of surgeons used cardioplegic arrest whereas 28% preferred intermittent aortic cross clamping and fibrillation. CONCLUSIONS: It is the consensus among British cardiac surgeons that the internal mammary artery is the graft conduit of choice. Its use has been significantly extended over the past five years (1987 to 1992) suggesting a quick response to advancing scientific knowledge. The use of alternative arterial conduits is still limited, perhaps as a reflection of the relative lack of information on their long-term performance. The recently advocated technique of retrograde cardioplegia and continuous warm cardioplegia is not yet popular.
Coronary artery disease and its complications remain the leading cause of death in Western society. With an ageing population there is an increasing number of patients with severe multilevel atherosclerosis. Atheromatous disease affecting the coronary, carotid, abdominal aorta and peripheral vasculature may co-exist, and vascular surgical reconstruction is commonly indicated to more than one site. The investigation and sequence of surgical interventions to minimize morbidity and mortality in this group of patients are discussed.