Release of adenosine from human hearts during angina induced by rapid atrial pacing.

This study was designed to determine whether human hearts release adenosine, a possible regulator of coronary flow, during temporary myocardial ischemia and, if so, to examine the mechanisms involved. Release of adenosine from canine hearts had been reported during reactive hyperemia following brief coronary occlusion, and we initially confirmed this observation in six dogs hearts. Angina was then produced in 15 patients with anginal syndrome and severe coronary atherosclerosis by rapid atrial pacing during diagnostic studies. In 13 of these patients, adenosine appeared in coronary sinus blood, at a mean level of 40 nmol/100 ml blood (SE = +/-9). In 11 of these 13, adenosine was not detectable in control or recovery samples; when measured, there was concomitant production of lactate and minimal leakage of K(+), but no significant release of creatine phosphokinase, lactic acid dehydrogenase, creatine, or Na(+). THERE WAS NO DETECTABLE RELEASE OF ADENOSINE BY HEARTS DURING PACING OR EXERCISE IN THREE CONTROL GROUPS OF PATIENTS: nine with anginal syndrome and severe coronary atherosclerosis who did not develop angina or produce lactate during rapid pacing, five with normal coronaries and no myocardial disease, and three with normal coronaries but with left ventricular failure. The results indicate that human hearts release significant amounts of adenosine during severe regional myocardial ischemia and anaerobic metabolism. Adenosine release might provide a useful supplementary index of the early effects of ischemia on myocardial metabolism, and might influence regional coronary flow during or after angina pectoris.

Ventricular arrhythmias after coronary artery bypass graft surgery: incidence, risk factors and long-term prognosis.

The incidence, risk factors and long-term prognosis of complex ventricular arrhythmias after coronary artery bypass graft surgery are not known. Complex ventricular arrhythmias are defined as Lown grades 4a (couplets), 4b (ventricular tachycardia) and 5 (R on T phenomenon). Ninety-two patients with normal left ventricular function who underwent elective coronary artery bypass graft surgery were prospectively evaluated. Ventricular arrhythmias were documented by predischarge 24 hour ambulatory electrocardiographic monitoring; 43% of patients had no or simple ventricular arrhythmias (Lown grades 1 to 3) and 57% had complex ventricular arrhythmias. Risk factors analyzed included age, sex, diabetes, hypertension, smoking, preoperative digoxin or propranolol therapy, cardiopulmonary bypass time, aortic cross-clamp time, number of vessels bypassed, peak creatine kinase (CK) elevation and pericarditis. No risk factor identified patients at higher risk for complex ventricular arrhythmias. Patients were followed up for 6 to 24 months (mean 16). Patients with complex ventricular arrhythmias did not have a higher incidence of sudden death, cardiac death, syncope, angina, myocardial infarction or cerebrovascular accident. It was concluded that: Complex ventricular arrhythmias are common after coronary artery bypass graft surgery. None of the risk factors considered identify high risk patients. Complex ventricular arrhythmias after coronary artery bypass graft surgery do not indicate a poor prognosis in patients with normal left ventricular function.

Release of nucleosides from canine and human hearts as an index of prior ischemia.

During ischemia, myocardial adenosine triphosphate is degraded to adenosine, inosine and hypoxanthine. These nucleosides are released into coronary venous blood and may provide an index of ischemia; adenosine may also participate in the autoregulation of coronary flow. In dogs, the temporal relations between reactive hyperemic flow and nucleoside concentrations in regional venous blood were correlated after brief occlusions of a segmental coronary artery. Reactive hyperemia and adenosine release peaked together in 10 seconds, persisted for 10 to 30 seconds and then decreased in a pattern consistent with the hypothesis that they are related. During initial reflow after 45 seconds of ischemia, mean concentrations of adenosine, inosine and hypoxanthine increased, respectively, to 52, 67 and 114 nmol/100 ml plasma; after 5 minutes of ischemia, the respective levels increased to 58, 1,570 and 1,134 nmol and fell quickly. In nine patients there was a similar release of nucleosides into coronary sinus blood during reperfusion after 59 to 80 minutes of ischemic arrest during cardiac surgery. With initial reflow, adenosine, inosine and hypoxanthine levels reached 65, 655 and 917 nmol/100 ml of blood, respectively. Inosine and hypoxanthine concentrations remained high for 5 to 10 minutes after cardiac beating resumed, often when production of lactate had decreased. The results indicate that postischemic release of nucleosides reaches significant levels in man as well as animals, is parallel with the duration of ischemia, is temporary and may be a useful supplement to measurement of lactate as an index of prior myocardial ischemia.

Chylothorax as a manifestation of rheumatic mitral stenosis: its postoperative management with a diet of medium-chain triglycerides.

Chylothorax occurred as a manifestation of severe congestive heart failure resulting from rheumatic mitral stenosis. Following replacement of the mitral valve, chylothorax recurred and was treated by thoracocentesis initially and then resolved during six months of therapy with a diet of medium-chain triglycerides. Ultimately, the patient resumed a regular diet with no further accumulation of pleural fluid.

Durability of measured mitral annuloplasty: seventeen-year study.

This report describes the technique and results of measured mitral annuloplasty performed in 196 patients having isolated mitral valve disease during the 17 years between January, 1961, and January, 1978. These patients represent 35% of all of those operated upon for isolated mitral valve disease during this period. Ages ranged from 3 to 70 years. Annuloplasty was performed in 115 patients and both commissurotomy and annuloplasty in another 81 patients. The operative mortality rate was 4.5% and the late mortality rate 8.7%. There were six arterial embolic episodes during the 17 years. Reoperation was required in 8% with another repair of the valve being possible in one third of them. This study suggests that measured repair of mitral regurgitation resulted in lower operative mortality, late mortality, and incidence of embolization when contrasted with mitral valve replacement. This operation appears to be the preferred procedure for certain subsets of patients (1) who require operation during infancy or childhood, including during active carditis; (2) who require operation during the childbearing age; and (3) in whom anticoagulation poses a severe threat to life or quality of life.

Predictors, prevention, and long-term prognosis of atrial fibrillation after coronary artery bypass graft operations.

Multiple trials have suggested the use of digoxin, digoxin and propranolol, or timolol to prevent atrial fibrillation after coronary artery bypass grafting. No trial has evaluated the efficacy of digoxin verus propranolol. Furthermore, the predictors of postoperative atrial fibrillation and the long-term consequence of atrial fibrillation that reverts to sinus rhythm have not been established. One hundred fifty patients were randomized to receive no drug, propranolol (20 mg every 6 hours), or digoxin (0.5 mg followed by 0.25 mg daily). Twenty-seven patients were excluded from data analysis. In the remaining 123 patients, no preoperative parameter (age, sex, diabetes, hypertension, smoking, electrocardiographic p wave morphology, or preoperative digoxin or propranolol therapy), intraoperative parameter (bypass time, aortic cross-clamp time, or number of vessels bypassed), or postoperative parameter (peak creatinine kinase, congestive heart failure, or pericarditis) by univariate or multivariate analysis predicted patients at risk for atrial fibrillation. Sustained atrial fibrillation developed in 37.5% of control and 32.6% of digoxin-treated patients. Only 16.2% of propranolol-treated patients had sustained atrial fibrillation (p less than 0.03). There were no in-hospital complications in those patients with atrial fibrillation. After 26 +/- 7 months follow-up, those patients with postoperative atrial fibrillation had no increased incidence of angina, cerebral vascular accident, myocardial infarction, or sudden death. Therefore, in this select population, propranolol prophylaxis is effective but discretionary.

Cystic thymoma simulating contrictive pericarditis. The role of echocardiography in the differential diagnosis.

A case is presented of a 60-year-old woman with fatigue, dyspnea, and chest pain. A chest x-ray film revealed an abnormal cardiac silhouette. Echocardiography revealed a large, echo-free area with well-demarcated, discrete borders adjacent to the right heart border. This structure decreased in size with inspiration and did not show pulsatile cardiac motion. Cardiac catheterization confirmed the extracardiac nature of the lesion and also showed a "constrictive" pattern with equalization of diastolic pressures. Surgical exploration revealed a large cystic thymoma. With removal of the tumor, intracardiac pressures returned to normal.

Experience with the Mitroflow aortic bioprosthesis.

From October 1985 to May 1990, the Mitroflow bovine pericardial valve was placed in the aortic position in 168 patients (97 men, 71 women) with a mean age of 69.7 years. Eighty-nine patients had isolated aortic valve replacement, and 79 had aortic valve replacement and additional procedures. Follow-up over 7 1/2 years includes 781 patient years (426 for isolated aortic valve replacement). Mean follow-up time is 56 months. Peak-to-peak gradients (in millimeters of mercury) measured in the intraoperative period averaged 11.0 +/- 8.7, 11.8 +/- 10.8, and 8.6 +/- 8.2 for 19 mm, 21 mm, and 23 mm valves, respectively. Hospital mortality was 7.3% (14 patients); all deaths were non-valve related. Late mortality of 20.1% in 31 patients resulted from cardiac failure (n = 8), sepsis (n = 4), valve reoperation (n = 1), non-cardiac causes (n = 15) and sudden, unknown causes (n = 3). Fifteen thromboembolic episodes occurred, but only three late thromboembolic episodes occurred in isolated aortic valve replacement without other risk factors. Four early and four late episodes of endocarditis occurred. Seven patients had clinical valve dysfunction, and five others required reoperation for structural deterioration, with one death. At 94 months, overall survival was 64% +/- 5%. Freedom from thromboembolic episode was 87% +/- 3% and 90% +/- 4% for isolated aortic valve replacement. Freedom from combined reoperation or clinical dysfunction was 75% +/- 8%: 64% +/- 15% for those under 70 years of age, and 87% +/- 7% for those 70 years of age and older. The valve has favorable hemodynamics. Durability begins to decline during the sixth year after implantation, possibly at a slower rate in patients older than 70 years of age.

Immediate-early gene expression in human saphenous veins harvested during coronary artery bypass graft operations.

Saphenous vein graft occlusion is a common late complication of coronary bypass grafting. Intimal smooth muscle cell hyperplasia is a component of this pathobiology, but the underlying molecular events are poorly understood. Immediate-early genes are activated shortly after growth stimulation and subserve cellular functions, which may contribute to intimal smooth muscle cell accumulation. In the present study, human saphenous vein grafts were harvested with minimal manipulation during coronary bypass and processed for isolation of total ribonucleic acid to examine change in immediate-early gene expression of messenger ribonucleic acid by Northern blotting techniques. Thirty saphenous vein grafts were incubated at 4 degrees C in Dulbecco's modified Eagle media from 30 minutes to 10 hours. The messenger ribonucleic acids for immediate-early genes c-fos and c-myc were weak or undetectable in controls but were increased (> 10 times controls) within 1 hour (c-fos) and persisted for at least 6 hours (c-myc) after harvest. Our results demonstrate, for the first time in human vascular tissue, incipient immediate-early gene induction. This information may lead to molecular therapies to control saphenous vein graft disease.

Results of combined valvular and myocardial revascularization operations.

A total of 105 patients underwent combined coronary artery and valvular operations. Sixty-six had combined coronary artery bypass grafting (CABG) and aortic valve replacement (AV), 28 had CABG and mitral valve operations (MV), and 11 patients had CABG and double or triple valve operations (DTV). An average of 3.0 bypasses was done, range one to seven. These patients were compared to a similar group of patients who underwent valve replacement(s) only, without CABG. Bypass time was increased for the combined groups, as was ischemic cross-clamp time. Early mortality was 3.0% AV, 3.5% MV, and 9.1% DTV in the combined groups and 1% in the valve only groups. The higher mortality for the combined groups was almost entirely due to the 23% mortality in women over 70 years of age. Perioperative myocardial infarction (MI) was higher in the combined groups (5% MI, 9% probable MI versus 2.9% MI, 4.1% probable MI). All survivors were in improved clinical condition and free of angina. Mortality and improvement were unrelated to perioperative infarction. The small increase in risk compared to the significant improvement from the combined approach has led to the following principles: coronary arteriography on all adult patients requiring valvular operations; bypass of all significant coronary lesions; restoration of valvular function and hemodynamics; and myocardial preservation with cold cardioplegia during a single period of cross clamping, topical cold, and systemic hypothermia.

Infective endocarditis. An analysis of 54 surgically treated patients.

One hundred seventy-seven patients were admitted to the New York University Medical Center from 1970 through 1975 with infective endocarditis. Fifty-four of these patients required surgical treatment. The over-all mortality rate was 28 per cent. Two thirds of the deaths were early (10 patients) and one third late (5 patients). The mortality rate was 90 per cent in 10 patients treated for 4 to 6 weeks in whom the infection was uncontrolled and the clinical condition was deteriorating. However of the 12 patients with uncontrolled infection who were operated upon promptly within 10 days, 83 per cent survived. The fact that fungal and gram-negative infections responded poorly to medical therapy suggests the need for prompt, early surgical intervention. The mortality rate in the 32 patients operated upon in whom the infection was controlled was 12.5 per cent. It is our conclusion that all patients with infective endocarditis who develop progressive congestive failure, recurrent embolization, or progressive sepsis, despite treatment, shold have prompt valve replacement within 7 days of the institution of appropriate antimicrobial therapy.

Measured tricuspid annuloplasty: a rapid and reproducible technique.

A technique for repairing the tricuspid valve that involves principles successfully used in operative repair of the mitral valve is described. A measured orifice produces competence but not obstruction and eliminates the trial-and-error aspects of annuloplasty. The procedure can be performed with the heart beating, though it can be transiently fibrillated so that the suture may be tied without tension.

Repair of coronary sinus rupture secondary to retrograde cardioplegia.

Coronary sinus injuries related to retrograde cardioplegia administration are uncommon, but can be a lethal complication of this technique. This report describes a major coronary sinus disruption during retrograde cardioplegia administration and details a method of repair with suggestions for possible prevention of this complication.

Early postoperative spasm in left internal mammary artery bypass grafts.

Two patients with early postoperative spasm of a left internal mammary artery bypass graft are described. To our knowledge, this entity has not been reported previously. Both patients were characterized by vasomotor collapse secondary to intractable spasm responsive only to local application of vasodilator agents. Although the mechanism of graft spasm is not clear, prophylactic nifedipine therapy in appropriate dose may be of some value. The profound hemodynamic effect of internal mammary artery spasm in the immediate postoperative period may allow no time for anything other than emergency reoperation to assess the nature of the problem and treat it appropriately.

Simplified method for reoperation on the mitral valve.

Reoperation on the mitral valve is becoming more common because of the degeneration of bioprosthetic valves, endocarditis, and malfunction or thrombosis of mechanical valves. We advocate a technique that transforms a technically difficult operation into one that is much less tedious, time-consuming, and dangerous than reopening a sternal-split operative site the second, third, or fourth time. Favorable experience in 11 patients using right anterolateral thoracotomy without aortic or right atrial cannulation and without aortic cross-clamping or cardioplegia is presented.

Safety and efficacy of autologous blood donation before elective aortic valve operation.

Although the use of preoperative autologous blood donations for patients undergoing elective cardiac operations has increased dramatically in recent years, patients awaiting elective aortic valve replacement have traditionally been denied access to preoperative autologous blood collection programs. We report our experience with 79 patients, each of whom donated 1 to 3 units of autologous blood before an aortic valve operation. All patients had serious aortic valve disease as evidenced by symptoms and preoperative catheterization data. The patients collectively made 129 blood donations. One patient had a syncopal episode within 2 hours of donation and recovered without difficulty. Of the patients who gave autologous blood preoperatively, 68% avoided any homologous blood donor exposure during their subsequent hospitalization for aortic valve replacement. In contrast, in a group of 298 patients who did not give autologous blood preoperatively, only 31% avoided homologous blood exposure during aortic valve replacement (p < 0.0001). Our experience suggests that preoperative autologous blood donation by patients awaiting elective aortic valve replacement is both safe and effective. Patients with aortic valve disease should not be routinely excluded from preoperative blood services.

NF-Y activates mouse tryptophan hydroxylase transcription.

Tryptophan hydroxylase catalyses the rate-limiting step in the biosynthesis of serotonin, a neurotransmitter which has been implicated in the etiologies of clinically important psychiatric illnesses. Tryptophan hydroxylase is expressed in a tissue-specific manner, but little is known about its transcriptional regulation. By analysing transcriptional activities of a set 5'-deletion constructs of promoter-reporter plasmids in P815-HTR mastocytoma cells, we found that transcription was activated by sequences between nucleotides -343 and -21. DNase I footprint analysis, using nuclear protein extracts from P815-HTR cells, revealed a protein-DNA interaction between nucleotides -77 and -46. A double stranded oligonucleotide, representing this binding site, specifically bound nuclear protein in a gel shift assay. Methylation interference analysis of this complex revealed that nuclear protein interacted with an inverted GGCCAAT element, which is a high-affinity binding motif for the transcription factor NF-Y (also known as CP1 or CBF). An NF-Y specific antibody abolished protein binding in a gel shift assay. Mutagenesis of specific base pairs abolished protein binding in vitro, and mutagenesis of the same base pairs in a reporter gene construct resulted in a 65% decrease in transcriptional activity. Our results suggest that the transcription factor NF-Y binds to a GGCCAAT motif in the tph proximal promoter and activates transcription.

Coexisting carotid stenosis in patients undergoing cardiac surgery: indications and guidelines for simultaneous operations.

The coexistence of critical carotid stenosis with coronary artery or valvular heart disease occurs in a small percentage of patients requiring open heart surgical procedures. Recognition of such combined lesions by noninvasive carotid testing identifies patients at risk for neurologic events. Our experience with 62 patients having combined simultaneous carotid and cardiac operations among 2,400 open heart surgery patients was compared with the results in 110 patients with only carotid endarterectomy operations. The outcomes indicated that carotid endarterectomy can be performed simultaneously with open heart surgical procedures with morbidity and mortality rates similar to those of isolated cervical artery operations. Thus, patients with significant coexisting carotid artery disease defined with specific criteria and coronary artery disease need not be exposed to cerebral ischemic events or to myocardial infarctions that often accompany staged operations.

The influence of diabetes and hypertension on the results of coronary revascularization.

The effects of diabetes and hypertension on the early postoperative course of patients undergoing coronary revascularization were studied by reviewing the records of 177 patients operated upon in 1972. There were 121 nondiabetic, nonhypertensive; 32 hypertensive; ten diabetic; and 14 diabetic-hypertensive patients. The incidence of postoperative low cardiac output, renal insufficiency and arrhythmia was significantly higher in the hypertensive patient. Operative mortality ranged from 0 in diabetic patients, to 0.8 per cent in nondiabetic, nonhypertensives, to 7.1 per cent in diabetic-hypertensives and 12.5 per cent in hypertensive patients, suggesting an increased risk for the hypertensive patient. The one- to two-year follow-up results documented symptomatic improvement in 90.7 per cent of patients with little adverse effect apparent from diabetes or hypertension. Pre- and postoperative coronary angiography was carried out in 103 patients between 1968 and 1973 with a mean elapsed time between operation and postoperative angiogram of 9.3 months. The progression of atherosclerosis was graded on a 0-4 basis in both grafted and ungrafted coronary arteries. While hypertension appeared to contribute to disease progression, the incidence of vein graft and internal mammary artery bypass occlusion was not significantly affected by either diabetes or hypertension. This study has shown that while hypertension contributes to increased morbidity and mortality in the early postoperative period and an increased rate of progression of atherosclerosis, neither diabetes nor hypertension appeared to influence the one- to two-year results of coronary revascularization.

Prevention of ventricular fibrillation after aortic declamping during cardiac surgery.

Ventricular fibrillation is common after aortic declamping during cardiac surgery, and the metabolic demands of such fibrillation, or its treatment by means of countershock, may contribute to myocardial injury. To determine the effects of administering intravenous lidocaine just before aortic declamping, we randomly divided 194 cardiac surgery patients into 2 groups. One hundred patients (group A) received lidocaine, 200 mg intravenously, 3 minutes before aortic declamping; and 94 patients (group B) received no medication before declamping. Multiple baseline variables, including clamp times, medications, electrolyte values, ventricular function, and the extent and type of surgery, were similar for both groups. After aortic declamping, 31 of the 100 patients in group A had ventricular fibrillation, as did 57 of the 94 patients in group B (p < 0.001). Of those who fibrillated, the group-A patients required a mean of 1.76 countershocks, whereas the group-B patients required a mean of 2.68 countershocks (p < 0.05). Serum potassium level also affected the incidence of ventricular fibrillation, independently of lidocaine. Elevated serum potassium levels were associated with a lower incidence of ventricular fibrillation. Although lidocaine was independently protective at all potassium levels, the combination of lidocaine and a high serum potassium level had the greatest effect in preventing fibrillation. In patients who had potassium levels higher than 5.1 mEq/l and who were also given lidocaine, the incidence of ventricular fibrillation was lower than 15%.