Nitroglycerin tolerance in human vessels: evidence for impaired nitroglycerin bioconversion.

BACKGROUND: The basis for progressive attenuation of the effects of organic nitrates during long-term therapy (nitrate tolerance) remains controversial; proposed mechanisms include impaired nitrate bioconversion resulting in decreased release of nitric oxide (NO) from nitrates and/or increased NO clearance through a reaction with incrementally generated superoxide (O(2)(-)). METHODS AND RESULTS: Patients undergoing elective coronary artery bypass were randomized to receive 24 hours of intravenously infused nitroglycerin (NTG; nitrate group) or no nitrate therapy (control group). Discarded segments of the internal mammary artery and saphenous vein were used to examine (1) vascular responsiveness to NTG, sodium nitroprusside, and the calcium ionophore A23187; (2) bioconversion of NTG to 1,2- and 1,3-glyceryl dinitrate; and (3) the generation of O(2)(-). Responses to NTG were reduced 3- to 5-fold in vessels from the nitrate group compared with control vessels (P:<0. 01 for both types of segments), whereas responses to sodium nitroprusside and A23187 were unchanged. Tissue content of 1, 2-glyceryl dinitrate was lower (P:=0.012) in the saphenous veins from the nitrate group than in those from the control group. O(2)(-) generation was greater (P:<0.01) in internal mammary artery samples from the nitrate group than in those from the control group. However, incremental O(2)(-) generation induced by an inhibitor of superoxide dismutase did not affect NTG responses. CONCLUSIONS: NTG tolerance in patients with coronary artery disease is nitrate-specific and is associated with evidence of impaired NTG bioconversion. Tolerance was associated with incremental O(2)(-) generation, but short-term elevation of O(2)(-) did not affect NTG responsiveness, suggesting increased NO clearance by O(2)(-) has a minimal contribution to tolerance.

Thirty years experience with heart valve surgery: isolated aortic valve replacement.

BACKGROUND: Thirty years have elapsed since the commencement of open-heart surgery in South Australia. A retrospective study was performed to evaluate mortality and complication rates and to identify factors associated with poor outcomes in all patients who underwent prosthetic aortic valve replacement during this period. METHODS: Questionnaires and personal contact have been used to generate a combined database of pre-operative and post-operative information and long-term follow-up on 1322 patients who underwent isolated prosthetic aortic valve replacement at the Cardio-Thoracic Surgical Unit of the Royal Adelaide Hospital between 1963 and 1992. RESULTS: Complete survival follow-up data were obtained for 94% (1241) of the patients. The Bjork-Shiley valve was used in 66% (875) of the patients, a Starr-Edwards prosthesis in 31% (412), a St Jude prosthesis in 2% (26), and only 0.7% (9) bioprosthetic valves were inserted. The hospital mortality rate for the 30-year period was 2.9%. Progressively older and less fit patients have undergone surgery in recent years. The long-term survival of patients with aortic stenosis and aortic incompetence was not significantly different. Long-term survival was significantly shorter for patients with higher New York Heart Association (NYHA) functional classifications, and for patients in pre-operative atrial fibrillation. Pre-operative dyspnoea was significantly improved following aortic valve replacement. The rates of postoperative haemorrhagic and embolic complications were low by comparison with other published series. CONCLUSIONS: Aortic valve replacement can be performed with low hospital mortality and complication rates, and significant symptomatic improvement can be expected. Aortic valve recipients have a favourable prognostic outcome compared with an age- and sex-matched population, and risk factors that determine long-term survival can be identified pre-operatively.

Thirty years experience with heart valve surgery: isolated mitral valve replacement.

BACKGROUND: Thirty years have elapsed since the commencement of open-heart surgery in South Australia. A retrospective study was performed to evaluate mortality and complication rates and to identify factors associated with poor outcomes in all patients who underwent prosthetic mitral valve replacement during this period. METHODS: Questionnaires and personal contact have been used to generate a combined database of pre-operative and post-operative information and long-term follow-up on 938 patients who underwent isolated prosthetic mitral valve replacement at the Cardio-Thoracic Surgical Unit of the Royal Adelaide Hospital between 1963 and 1993. RESULTS: Complete survival follow-up data were obtained for 92% (865) of the patients. The Starr-Edwards valve was used in 95% (891) of the patients, a Bjork-Shiley prosthesis in 2.5% (23) of the patients, and only 24 (2.5%) other valves were inserted. The hospital mortality rate for the 30-year period was 4.7%. The mean age of the patients who underwent surgery was greater in each of the three successive decades. A long-term survival advantage was observed for patients with mitral stenosis, however, survival was significantly shorter for patients with higher New York Heart Association (NYHA) functional classifications and for patients in pre-operative atrial fibrillation. Pre-operative dyspnoea was significantly improved following mitral valve replacement. The rates of postoperative haemorrhagic and embolic complications were low by comparison with other published series. CONCLUSION: Mitral valve recipients do not regain a normalized life expectancy, but risk factors that determine long-term survival can be identified pre-operatively to aid appropriate patient selection.

Longitudinal study of molecular epidemiology of small round-structured viruses in a pediatric population.

Small round-structured viruses (SRSV), recently designated members of the family Caliciviridae, can now be readily subtyped by amplification of a defined portion of their genome by reverse transcription-PCR and then by identification of the amplicons with specific probes by Southern blotting. A longitudinal survey (from 1991 to 1995) was conducted to determine the genotypes of the SRSV present in pediatric stool specimens from patients with sporadic cases of gastroenteritis. It was found that almost all viruses were of the G-2 genotype, and on probing, the subtype P2-B was predominant but the frequencies of the different subtypes varied from year to year. A survey of the genotypes of SRSV from community outbreaks from 1995 showed that the G-2 genotype was also predominant and that the distribution of its subtypes was similar to that seen in sporadic cases of diarrhea in pediatric patients over the same time period. It was concluded that there is a succession of subtypes of SRSV in our pediatric population over time. This distribution of genotypes in sporadic cases of pediatric gastroenteritis may reflect the distribution in community outbreaks occurring at the same time.

A 4-year experience with the Björk-Shiley Monostrut valve.

We reviewed 314 consecutive patients in whom a Björk-Shiley Monostrut aortic valve prosthesis was inserted by our cardiothoracic surgical unit from June 1982 through June 1986. The group comprised 220 males (70%) and 94 females (30%), with a mean age of 60 years (range, 5 to 83 years). Two hundred ninety-six patients (94%) received an aortic prosthesis alone, and the other 18 (6%) received both an aortic Monostrut valve and a Starr-Edwards mitral valve prosthesis. In each case, preoperative data were collected prospectively, and a questionnaire was sent at the time of follow-up. The median follow-up period was 23 months (range, 0 to 46 months); 6 (2%) of the patients were lost to follow-up. In the remaining 308 cases, there were 20 deaths (6.5%), 8 of which occurred within approximately 1 month after operation. There were no known instances of valve failure. One death occurred in the group that underwent double-valve replacement. Valve endocarditis accounted for 2 late deaths. With respect to preoperative dyspnea, 59 (19%) of the patients were in New York Heart Association functional Class I, 74 (24%) were in Class II, 138 (45%) were in Class III, and 37 (12%) were in Class IV. Postoperatively, there were 247 patients (80%) in Class I, 43 (14%) in Class II, 15 (5%) in Class III, and 3 (1%) in Class IV (p < 0.0001). All of the patients received postoperative anticoagulant therapy; 3.4% per year were subsequently readmitted for bleeding problems. Thromboembolic events necessitating hospitalization occurred in 3.0% of the patients per year. On the basis of these results, our early experience with the Björk-Shiley Monostrut valve in the aortic position has been satisfactory, with an acceptable rate of complications and no documented valve failures.

The costs of coronary artery surgery to the community.

The possible benefits obtained both for the community and patients following coronary artery bypass grafting (CABG) have been examined in 4001 patients (mean age 54 years, 14.8% female) who underwent CABG from 1971 to 1982 in the Cardiothoracic Surgical Unit of the Royal Adelaide Hospital. Assessment followed a fixed response format questionnaire sent to all patients with a total follow-up of 98.8%. The hospital mortality was 1.4% for the 10 year period with a fall from 4% in 1973 to 0.9% in 1981. Shifts in employment were assessed in survivors. At follow up, 548 patients who were previously employed had ceased full-time or part-time employment. This decrease in employment was attributed mainly to age. Analysis of retirement curves for the general male population and male patients showed a similar pattern but downward translation of 4% for the pre-operative group. A similar downward shift occurred following surgery. For female patients, performance of home duties improved from 159 patients on full home duties pre-operatively to 292 post-operatively. Visits to the doctor dropped in 50% of surviving patients. CABG has a low mortality. The community benefits by helping to maintain productivity and decreased cost for ongoing medical care.

Cardiac tamponade following infarction: management with pericardiocentesis and surgery.

Four patients with cardiac tamponade following myocardial infarction are presented. Diagnostic clinical features and the role of echocardiography are discussed. Pericardiocentesis resulted in rapid improvement in clinical state but frequently tamponade recurred. Surgery was undertaken in three patients and two have survived long term. If promptly recognised, tamponade following myocardial infarction may be treated.

Twelve years of coronary artery surgery in South Australia.

Twelve years' results of coronary artery bypass surgery in South Australia have been reviewed. The preoperative assessment parameters and operative profiles of 4001 patients who underwent isolated coronary artery grafting between 1970 and 1982 have been examined. In addition, all surviving patients received a follow-up questionnaire; only 48 patients have remained untraced. Survival curves for the patient group have been calculated and compared with those for the Australian population. The risk factors which influenced long-term survival have been identified. Surviving patients described their anginal symptoms as diminished in 93% of cases at the time of review. When recurrent angina was described, 58% of patients experienced it within 12 months of the operation. Postoperative activity was improved in 71% of patients; 8% described a deterioration. A second operation was performed in 2.1% of patients. This study provides a comprehensive review of the efficacy of coronary artery bypass surgery both in the short and in the medium term.

Anomalous right subclavian artery arising proximal to a postductal thoracic aortic coarctation.

Approximately 1% of patients with postductal thoracic aortic coarctation have an associated anomalous right subclavian artery. Previous reports indicated that the aberrant right subclavian vessel arose distal to the coarctation site. The case of a patient is presented in whom the anomalous right subclavian artery originated proximal to the postductal coarctation. We believe this to be among the first reports of this entity. The embryological development pathway and clinical implications of this congenital defect complex are discussed.

Coronary artery surgery in South Australia: second report.

This is the second report on the results of coronary artery grafting in South Australia. Symptomatic relief after grafting has continued at a high level (at five years, the conditions of 90.3% of surviving patients are improved as assessed by their cardiologists), and, in patients with significant symptoms, the operation can be recommended with a high degree of safety on these grounds alone. In addition, an attempt has been made to ascertain whether grafting alters longevity and, although more information is required on this point, the initial results are most encouraging with the five-year survival rate for operated patients being 92%, a figure which compares favourably with any large, medically treated group of patients. The operative mortality rate has continued to fall and is 2.2% for the entire series.

Coronary artery surgery in South Australia 1970-1976.

The South Australian population of approximately 1,245,000 is 9.2% of the total Australian population. The Cardio-Thoracic Surgical Unit of the Royal Adelaide Hospital is the only one such unit in the State which is equipped for open heart surgery, and coronary artery grafting was first undertaken there in December, 1970. From that time until the end of December, 1976, 701 patients underwent coronary artery grafting with an overall hospital mortality of 3.0%, and a late mortality of 3.2%. The principal indication for operation was incapacitating angina, and of the 628 patients who have been followed-up after operation for a minimum period of six months, 78.6% were judged by their cardiologist to be completely relieved of this symptom. A further 8.9% of patients were considered to be significantly improved. Coronary artery surgery has rapidly assumed a dominant role in our Unit so that, in 1976, of the 435 open heart operations which were performed, 267 (61%) were procedures which necessitated coronary artery grafting. The rate of increase has slowed considerably over the past 18 months, and it is expected that, with current operative indications, the proportion of coronary artery cases will not rise much above 60% of the open heart work load of the Unit.

The results of surgical treatment of coarctation of the thoracic aorta.

A retrospective study of the results of surgical treatment in 124 cases of coarctation of the thoracic aorta is presented. The diagnosis was based on clinical findings alone in 90% of cases. Aortography and/or cardiac catheterization were performed if the diagnosis was in doubt or if other cardiac abnormalities were suspected. Surgical treatment involved either resection with end-to-end anastomosis (114) or some form of grafting procedure (10). The results of treatment have been analysed in terms of operative mortality, late mortality, relief of hypertension, and the incidence of re-stenosis.