Joseph W. Rubin

cGMP Accumulation and Gene Expression of Soluble Guanylate Cyclase in Human Vascular Tissue

Gene expression of soluble guanylate cyclase (sGC) and cGMP accumulation in response to sodium nitroprusside (SNP) were studied in cultured human vascular cells and freshly harvested vascular tissue. As revealed by reverse transcriptase‐polymerase chain reaction, cultured smooth muscle and endothelial cells, as well as freshly isolated human vascular tissue, express mRNA for the α3 and β3 subunits but not for the α2 or β2 sGC. In cultured human cells, expression of the α3 and β3 subunits is evident even in the absence of increased cGMP accumulation in response to SNP. cGMP accumulation in cultured human cells from different vascular beds typically increased two‐ to fivefold (maximum of 11.4‐fold) over baseline following stimulation with 100 μM SNP. Bovine, murine, canine, and avian vascular smooth muscle cells accumulated similar or lower amounts of cGMP than human cells, whereas porcine, rat, and rabbit smooth muscle cells accumulated greater amounts of cGMP. In freshly harvested human vessels, cGMP accumulation in response to SNP was found to increase fifteenfold over baseline. In contrast to the SNP‐induced cGMP accumulation, cGMP levels in response to the particulate guanylate cyclase activator atriopeptin II were equal or greater in cultured human cells than in fresh human vascular tissue. We conclude that human vascular cells (fresh and cultured) express the mRNA for both a large (α3) and a small (β3) sGC subunit and that fresh human cells are more sensitive to SNP stimulation.

Two Decades of Experience with Modified Heller's Myotomy for Achalasia

We reviewed the hospital records of 36 patients who underwent modified Hellers myotomy for achalasia between January, 1961, and December, 1982. There were 18 male and 18 female patients ranging between 17 months and 75 years old. The most frequent symptom was dysphagia, followed by regurgitation of ingested food and weight loss. Modified Hellers myotomy was performed through a transthoracic incision in 35 patients and a transabdominal incision in 1. An antireflux procedure in addition to esophagomyotomy was performed in 20 patients. There was 1 postoperative death. Thirty-three patients were followed up for periods ranging from 9 months to 21 years. The results were considered good in 27, fair in 2, and poor in 4. One of the 4 underwent repeat esophagomyotomy 71/2 years after the initial operation with a good result. The remaining 3 had an antireflux procedure at the time of esophagomyotomy. Because of recurrence of symptoms, esophagogastrostomy was performed in 1 and colon interposition in 2. These results suggest that an antireflux procedure should not be added to modified Hellers operation in the treatment of achalasia.

Thirteen year experience with aortic valve replacement

Abstract Two hundred forty-one patients (163 male, 78 female) underwent isolated aortic valve replacement at the Medical College of Georgia from 1963 to 1976. The mean age was 46 years (range 12 to 72). Thirty-seven percent had aortic stenosis, 39 percent aortic regurgitation and 24 percent mixed valve lesions. One hundred ninety-eight were in New York Heart Association functional class III or IV. Forty-three were in functional class I or II and underwent surgery for endocarditis, severe regurgitation with rapidly increasing heart size or appearance of angina or electrocardiographic signs of ischemia. The long-term clinical characteristics of five models of Starr-Edwards valves (1000, 1200, 2300, 2310 and 2320) and the Bjork-Shiley prosthesis were defined by rates of survival, complications and rehabilitation. In 212 patients who survived operation, the annual valve-related cardiac mortality rate calculated by the life table method was 4.8 percent for those with model 1000, 3.6 percent for those with model 1200, 7.1 percent for those with model 2300, 6.1 percent for those with model 2310, 3.7 percent for those with model 2320 and 4.0 percent for those with the Bjork-Shiley prosthesis. Complications were most frequent among patients with models 2300 and 2310. The model 2320 valves have posed the greatest embolism risk (7.1 episodes/100 patient years compared with 3.3/100 for the entire group). One hundred twelve current survivors (90 percent) are in functional class I or II. No patient in class IV preoperatively survived the full study period. Thirty-nine percent of those in class III and 91 percent of those in classes I and II preoperatively survived 13 years. Successful management of patients with an aortic valve prosthesis is based upon knowledge of the natural history of individual prostheses. Longevity and rehabilitation depend upon aortic valve replacement before severe myocardial decompensation occurs plus meticulous management to avoid lethal complications inherent in individual prostheses. Assessment of functional durability of hemodynamically adequate valve designs requires long-term evaluation.

Esophageal mucocele: a complication of blind loop esophagus

Mucocele of the bypassed esophagus is an unusual complication of esophageal replacement and has been described only in isolated references. This report is based on our experience with 6 patients in whom a mucocele developed following esophageal replacement. Esophageal replacement was performed on 37 patients over a 10-year period at the Medical College of Georgia Hospital. A symptomatic mucocele requiring excision developed in 3 patients with achalasia, 1 with congenital tracheoesophageal fistula, 1 with esophageal atresia, and 1 with inflammatory stricture. Conduits used included stomach (4), reversed gastric tube (1), and colon (1). Our experience indicates that conversion of a closed-loop esophagus into a symptomatic mucocele is more likely in the presence of functioning, chronically irritated mucosa. The clinical features were referable to the mucocele itself or respiratory embarrassment therefrom. Thoracic roentgenograms and computed tomographic scans were diagnostic in verifying the presence of the esophageal mucocele. All five mucoceles arose from squamous epithelium. One of 3 patients with achalasia in whom a mucocele developed following esophageal replacement had premalignant changes in the mucosa. Based on this experience, our treatment of choice is early, complete excision of the mucocele.

Disc Immobilization of Björk-Shiley and Medtronic Hall Valves during and Immediately after Valve Replacement

During the last fourteen years, 377 unileaflet tilting-disc prosthetic valves (Björk-Shiley and Medtronic Hall) have been used for single or multiple valve replacements with and without concomitant coronary artery by-pass grafting. In the past five years, five instances of disc immobilization (three in the mitral and two in the aortic position) occurred either at the time of weaning from cardiopulmonary bypass or immediately thereafter. When the implanted site of the prosthetic valve was the mitral position, reexploration in 2 patients revealed chordal remnants in the subannular area stuck between the disc occluder and the valve ring, thereby immobilizing the disc. In the third instance, the free movement of the disc was impeded by the left ventricular myocardium. In the aortic position, an unraveled suture impacted between the disc occluder and the valve ring immobilized the disc in 1 patient. In the other patient, the cause of the malfunction could not be determined at the time of reexploration. The 1 death among these 5 patients was directly related to the malfunction of the prosthesis. The mechanism, recognition, treatment, and prevention of this catastrophic malfunction of tilting-disc valves are discussed.

Aortic valve rheumatoid nodules producing clinical aortic regurgitation and a review of the literature.

The majority of cardiac involvement in rheumatoid arthritis (RA) is an incidental finding at postmortem, as less than 3% of patients with RA have clinical cardiac signs or symptoms. Most cardiac involvement in RA involves the pericardium and has been known since Charcot first described an RA patient with pericarditis in 1881. Cardiac involvement takes two different forms: non-specific inflammatory changes and specific granuloma formation. Specific rheumatoid nodules in the heart are an infrequent complication of RA. This is the first case report of a surgically excised heart valve with rheumatoid nodules. A 74-year-old RA patient with a high seropositive rheumatoid factor presented with severe aortic regurgitation and underwent a valve replacement. The native aortic valve showed significant stenosis with multiple, classic rheumatoid nodules.

Congenital Absence of Pericardium: An Unusual Cause of Atypical Angina

Congenital defects of the pericardium are unusual. Patients may experience exertional chest pain, cardiac arrhythmias, syncope, sudden death, or incarceration of myocardium, or they may be entirely asymptomatic. We describe the case of a symptomatic pericardial herniation diagnosed by echocardiography and confirmed by cineangiography. Successful repair was accomplished using a polytetrafluoroethylene soft-tissue prosthesis.

Experimental determination of optimum performance of counterpulsation assist pumping under computer control

Abstract Intra-aortic balloon pumping (IABP), a currently popular method for assisting a failing left ventricle, has a fundamental clinical problem that the effectiveness of the device is significantly affected by the method of controlling the timing settings. An experimental procedure is presented for the determination of the optimum control of a counterpulsation-type assist device such as IABP. Initial experiments with the method are reported with IABP under computer control. Determination of optimum heart assist pumping was considered based on performance indices defined as mean coronary artery flow, left ventricular stroke work, end-diastolic aortic pressure, cardiac output, and tension-time index. Weighting factors were chosen for each index. Data are presented in the form of computer-generated plots showing the effect of balloon pump timing (delay and duration) on each variable measured. The results show that the optimum setting of the timing settings is a compromise between several factors and that an on-line controller is indicated to continuously monitor and control the timing settings. In particular, inflation of the balloon earlier than the closing of the aortic valve and deflation of the balloon before the receipt of an ECG trigger may be beneficial.

Permanent Cardiac Pacemakers: Twelve-Year Experience with 287 Patients

Our total pacemaker experience was evaluated to determine survival, complications, effectiveness of follow-up techniques, and future goals for surveillance. A retrospective review of 287 patients with 570 pulse generators revealed 164 alive and 104 dead; 3 recovered normal conduction, 14 transferred care, and 2 have been lost to follow-up. Average age at initial implantation was 67 years. Overall mean generator life has been 22 months. The one-, three-, five-, and ten-year survival is 84, 71, 60, and 39%, respectively. The 738 operations performed averaged 2.6 procedures per patient. Of the total survivors, 108 (66%) had no complications; 56 (34%) have had at least one complication, 70% during the first year of the initial implantation. Fifty episodes of premature interruption of pacing service were detected. Ninety-one patients (32% of the group) have required an operative procedure on their pacemaker system more frequently than every two years. Of the replacements, 89 (29%) were for reasons other than end of generator life; 66 (63%) of the deaths occurred before replacement of the first generator. Mortality in the first two years was 23%. Once survival exceeded two years the average annual death rate was 3.7% (expected, 3.2%). Survival in our series compares favorably with that of other groups who report by the actuarial method. These data suggest that some deaths, reduced patient productivity, and the high cost to health care providers may be due in part to inadequate follow-up after the first pacemaker implantation. If follow-up observation is done frequently during the first year after initial implantation and once minimum generator longevity has passed, the goals of pacemaker therapy may be achieved.

Twelve-year experience with mitral valve replacement.

Between 1962 and 1974, 203 mitral prostheses were implanted in 201 patients. Of the 102 survivors, 29 have Beall, 25 Kay-Shiley, 22 Starr-Edwards (SE) 6000, and 27 SE 6320 valves. Full rehabilitation was achieved in 25 patients with Beall and 23 with SE 6320 valves. Sixteen with SE 6000 valves remain normally active. Only 8 with Kay-Shiley prostheses have resumed normal activities. Systemic embolization occurred with the following frequencies per 1,000 patient-months: 13.7 for those receiving the Kay-Shiley valve; 7.2 in the SE 6000 group; 4.3 after SE 6320 implantations; and 3;1 for the Beall group. Other prosthesis-related complications that were much less frequent included detachment (10), bacterial endocarditis (5), and hemolysis (10). Three Kay-Shiley valves malfunctioned. Life table analyses reveal the following survival rates: 33% after 11 years in the SE 6000 patients, 50% after 7.5 years in the Kay-Shiley group, 69% 2.5 years after SE 6320 implantation, and 65% 3.5 years after replacement with a Beall valve. Evidence is presented to support the extension of operative treatment to patients with less advanced valvular heart disease. Postoperative anticoagulation remains an unresolved issue despite lower rates of thromboembolism. More cumulative analyses of survival and morbidity and follow-up hemodynamic data are needed to assess the Beall and SE 6320 prostheses now employed in our valve replacement program.