Bleomycin-induced diffuse interstitial pulmonary fibrosis in baboons.

Pulmonary fibrosis was induced in eight baboons with bleomycin; five untreated animals were controls. After 45-65 U/kg of bleomycin, lung volumes and diffusing capacity were reduced, and static lung pressure-volume curves were shifted to the right. Right middle lobes were resected at this time in five bleomycin-treated and two control animals. Compared to controls, right middle lobes from bleomycintreated animals had increased weight and contained increased amounts of total protein, collagen, elastin, and DNA; synthesis of collagen and noncollagen protein were also elevated. Occasional alveolar septae were edematous and infiltrated by mononuclear inflammatory cells; a slight increase in collagen was demonstrable histologically. Four of six treated animals died with extensive diffuse interstitial fibrosis after 95 U/kg of bleomycin. Biochemical analyses revealed significantly elevated lobar contents of dry weight, protein, elastin, and collagen. Two animals survived 95 U/kg of bleomycin and were terminated 6 mo after treatment. In these animals, physiologic studies were indicative of restrictive lung disease, but lung histology was nearly normal. Lung weight, total protein, and DNA had returned to control values, but collagen and elastin were increased in amount and concentration. Bleomycin induces an intense inflammatory response in the lung. During this inflammation, connective tissue proliferation occurs in concert with proliferation of other tissue components. Cessation of bleomycin treatment is followed by resolution of inflammation manifested by decreases in tissue mass, cellular content, and nonconnective tissue protein. Collagen and elastin deposited during inflammation are less successfully removed during resolution, leading to a stage characterized by increased concentrations of these proteins. A similar sequence of tissue alterations may occur in idiopathic diffuse interstitial fibrosis of man in response to various lung injuries.

Complement localization and mediation of ischemic injury in baboon myocardium.

We sought to determine whether the third component of complement (C3) is localized in ischemic baboon myocardium after coronary artery ligation. Furthermore, we assessed the effects of prior C3 depletion on myocardial necrosis. We studied seven control baboons (group I) and seven C3-depleted (group II) baboons that were killed 24 h after ligation of the anterior descending coronary artery. Multiple tissue samples were obtained from infarct, intermediate, and normal myocardial sites as defined by serial unipolar epicardial ECG mapping. In group I baboons, myocardial creatine kinase content from infarct sites was reduced as compared with normal sites (12.6+/-0.92 [SE] vs. 24.4+/-0.75 IU/mg protein, P < 0.001). The intermediate sites from group I contained more creatine kinase (19.0+/-1.25 IU/mg protein) than infarct sites (P < 0.001), but less (P < 0.025) than normal sites. In group II, intermediate sites showed no significant reduction in creatine kinase from normal sites and there was significantly less creatine kinase depletion in infarct sites when compared with group I animals (33.7+/-4.6 and 51.4+/-1.8% depletion, respectively, P < 0.001). In all seven group I baboons, uniform C3 localization was observed in infarct sites by direct immunofluorescence but appeared in mosaic patterns in intermediate sites. C3 was not demonstrated in any normal sites, nor in any site from group II baboons. Additional studies on baboons killed at earlier times after ligation indicated that C3 was localized focally on swollen myocytes in infarct sites as early as 4 h after coronary ligation. These results strongly implicate the active participation of the complement system of inflammatory proteins in the pathogenesis of myocardial tissue injury following coronary occlusion.

Percutaneous transluminal angioplasty of saphenous vein grafts for medically refractory unstable angina.

OBJECTIVES: We attempted to answer the question, Is balloon angioplasty a reasonable alternative to repeat coronary artery bypass graft surgery in patients with previous coronary bypass graft surgery, medically refractory unstable angina and vein graft lesions? BACKGROUND: Patients with medically refractory unstable angina need revascularization. Patients with previous coronary artery bypass graft surgery and medically refractory angina are at "high risk" for adverse outcomes with repeat coronary bypass graft surgery. Conversely, patients with angioplasty of old vein grafts are also at "high risk" for adverse outcomes. METHODS: Balloon angioplasty of 89 lesions in saphenous vein grafts was performed in 75 consecutive patients with medically refractory unstable angina. Of these 75 patients, 24 (32%) had myocardial infarct within 30 days, 23 (31%) had left ventricular ejection fraction < 0.35, and 50 (67%) had major comorbidity. Patients underwent standard balloon angioplasty with aggressive use of intravenous and intracoronary heparin, urokinase, nitroglycerin, oral aspirin, calcium channel blocking agents and coumadin. RESULTS: Angiographic success (reduction of stenosis < or = 50% without major complication) was seen in 84 of 89 lesions. Clinical success (angiographic success plus hospital discharge without major complication) was seen in 70 of 75 patients. During index hospitalization, two patients (3%) died, two (3%) had nonfatal infarcts, and one (1%) had emergency reoperation (coronary bypass graft surgery). In late follow up (3 to 66 months), 14 (20%) patients were lost to follow-up, 17 (23%) had repeat percutaneous transluminal coronary angioplasty, 2 (3%) had late bypass graft reoperation, 18 (25%) had late death, and 1 (< 1%) had a heart transplant. Of the 41 patients alive after one or more angioplasties, 25 have little or no angina, and 16 have occasional or more angina. We compared long-term survival rate in these 75 patients with a cohort of patients with high risk, unstable angina from the Veterans Affairs Surgical Registry (2,570 patients). The 30-day survival rate was better in patients with coronary angioplasty (97% vs. 92%, p < 0.05), but by 6 months there was no difference, and by 5 years a trend toward a higher survival rate with coronary artery bypass graft surgery was seen. CONCLUSIONS: Balloon angioplasty of saphenous vein grafts with aggressive adjunctive pharmacotherapy is a reasonable alternative to repeat coronary bypass graft surgery in patients with medically refractory unstable angina, previous coronary bypass graft surgery and saphenous vein narrowing.

Outcomes 15 years after valve replacement with a mechanical versus a bioprosthetic valve: final report of the Veterans Affairs randomized trial.

OBJECTIVES: The goal of this study was to compare long-term survival and valve-related complications between bioprosthetic and mechanical heart valves. BACKGROUND: Different heart valves may have different patient outcomes. METHODS: Five hundred seventy-five patients undergoing single aortic valve replacement (AVR) or mitral valve replacement (MVR) at 13 VA medical centers were randomized to receive a bioprosthetic or mechanical valve. RESULTS: By survival analysis at 15 years, all-cause mortality after AVR was lower with the mechanical valve versus bioprosthesis (66% vs. 79%, p = 0.02) but not after MVR. Primary valve failure occurred mainly in patients <65 years of age (bioprosthesis vs. mechanical, 26% vs. 0%, p < 0.001 for AVR and 44% vs. 4%, p = 0.0001 for MVR), and in patients > or =65 years after AVR, primary valve failure in bioprosthesis versus mechanical valve was 9 +/- 6% versus 0%, p = 0.16. Reoperation was significantly higher for bioprosthetic AVR (p = 0.004). Bleeding occurred more frequently in patients with mechanical valve. There were no statistically significant differences for other complications, including thromboembolism and all valve-related complications between the two randomized groups. CONCLUSIONS: At 15 years, patients undergoing AVR had a better survival with a mechanical valve than with a bioprosthetic valve, largely because primary valve failure was virtually absent with mechanical valve. Primary valve failure was greater with bioprosthesis, both for AVR and MVR, and occurred at a much higher rate in those aged <65 years; in those aged > or =65 years, primary valve failure after AVR was not significantly different between bioprosthesis and mechanical valve. Reoperation was more common for AVR with bioprosthesis. Thromboembolism rates were similar in the two valve prostheses, but bleeding was more common with a mechanical valve.

Prediction of operative mortality after valve replacement surgery.

OBJECTIVES: We sought to develop national benchmarks for valve replacement surgery by developing statistical risk models of operative mortality. BACKGROUND: National risk models for coronary artery bypass graft surgery (CABG) have gained widespread acceptance, but there are no similar models for valve replacement surgery. METHODS: The Society of Thoracic Surgeons National Cardiac Surgery Database was used to identify risk factors associated with valve surgery from 1994 through 1997. The population was drawn from 49,073 patients undergoing isolated aortic valve replacement (AVR) or mitral valve replacement (MVR) and from 43,463 patients undergoing CABG combined with AVR or MVR. Two multivariable risk models were developed: one for isolated AVR or MVR and one for CABG plus AVR or CABG plus MVR. RESULTS: Operative mortality rates for AVR, MVR, combined CABG/AVR and combined CABG/ MVR were 4.00%, 6.04%, 6.80% and 13.29%, respectively. The strongest independent risk factors were emergency/salvage procedures, recent infarction, reoperations and renal failure. The c-indexes were 0.77 and 0.74 for the isolated valve replacement and combined CABG/valve replacement models, respectively. These models retained their predictive accuracy when applied to a prospective patient population undergoing operation from 1998 to 1999. The Hosmer-Lemeshow goodness-of-fit statistic was 10.6 (p = 0.225) for the isolated valve replacement model and 12.2 (p = 0.141) for the CABG/valve replacement model. CONCLUSIONS: Statistical models have been developed to accurately predict operative mortality after valve replacement surgery. These models can be used to enhance quality by providing a national benchmark for valve replacement surgery.

Percutaneous coronary intervention versus coronary artery bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: a multicenter, randomized trial. Investigators of the Department of Veterans Affairs Cooperative Study #385, the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME).

BACKGROUND: Percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) are being applied to high-risk populations, but previous randomized trials comparing revascularization methods have excluded a number of important high-risk groups. OBJECTIVES: This five-year, multicenter, randomized clinical trial was designed to compare long-term survival among patients with medically refractory myocardial ischemia and a high risk of adverse outcomes assigned to either a CABG or a PCI strategy, which could include stents. METHODS: Patients from 16 Veterans Affairs Medical Centers were screened to identify myocardial ischemia refractory to medical management and the presence of one or more risk factors for adverse outcome with CABG, including prior open-heart surgery, age >70 years, left ventricular ejection fraction <0.35, myocardial infarction within seven days or intraaortic balloon pump required. Clinically eligible patients (n = 2,431) underwent coronary angiography; 781 were angiographically acceptable; 454 (58% of eligible) patients consented to random assignment between CABG and PCI. RESULTS: A total of 232 patients was randomized to CABG and 222 to PCI. The 30-day survivals for CABG and PCI were 95% and 97%, respectively. Survival rates for CABG and PCI were 90% versus 94% at six months and 79% versus 80% at 36 months (log-rank test, p = 0.46). CONCLUSIONS: Percutaneous coronary intervention is an alternative to CABG for patients with medically refractory myocardial ischemia and a high risk of adverse outcomes with CABG.

Independent association between acute renal failure and mortality following cardiac surgery.

PURPOSE: To determine whether there is an independent association of acute renal failure requiring dialysis with operative mortality after cardiac surgery. PATIENTS AND METHODS: The 42,773 patients who underwent coronary artery bypass or valvular heart surgery at 43 Department of Veterans Affairs Medical Centers between 1987 and 1994 were evaluated to determine the association between acute renal failure sufficient to require dialysis and operative mortality, with and without adjustment for comorbidity and postoperative complications. Crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were derived from logistic regression analysis. RESULTS: Acute renal failure occurred in 460 (1.1%) patients. Overall operative mortality was 63.7% in these patients, compared with 4.3% in patients without this complication. The unadjusted OR for death was 39 (95% CI 32 to 48). After adjustment for comorbid factors related to the development of acute renal failure (surgery type, baseline renal function, preoperative intraaortic balloon pump, prior heart surgery, NYHA class IV status, peripheral vascular disease, pulmonary rales, left ventricular ejection fraction below 35%, chronic obstructive pulmonary disease, systolic blood pressure, and the cross-product of systolic blood pressure and surgery type), the OR was 27 (95% CI 22 to 34). Further adjustment was made for seven postoperative complications (low cardiac output, cardiac arrest, perioperative myocardial infarction, prolonged mechanical ventilation, reoperation for bleeding or repeat cardiopulmonary bypass, stroke or coma, and mediastinitis), that were independently associated with operative mortality. The OR adjusted for comorbidity and postoperative complications associated with acute renal failure was 7.9 (95% CI 6 to 10). CONCLUSIONS: Acute renal failure was independently associated with early mortality following cardiac surgery, even after adjustment for comorbidity and postoperative complications. Interventions to prevent or improve treatment of this condition are urgently needed.

Mechanism of inferior electrocardiographic ST-segment depression during acute anterior myocardial infarction in a baboon model.

Controversy exists concerning the mechanism of electrocardiographic (ECG) ST-segment depression in leads remote from an area of acute myocardial infarction. Thus, 13 baboons were studied during ligation of the distal third of the left anterior descending coronary artery. The morphologic pattern of the ECG limb leads in the supine baboons resembled that of an asthenic human and did not change when the chest was opened. The visually apparent infarct area of the distal anterior wall was confirmed by epicardial ECG mapping 30 minutes after ligation, and by tissue creatine kinase and histologic study at 24 hours. All 13 baboons had ST depression in leads III and aVF of 0.1 to 1.2 mV at 30 minutes, and 11 of 13 had similar changes in lead II. Also, all 13 baboons had ST elevation in lead aVL (n = 10) or aVR (n = 11), suggesting that the ST vector from the infarct area was directed away from the inferior leads. In no baboon did inferoposterior wall ventricular epicardial mapping show evidence of myocardial ischemia, and mean creatine kinase content from the infarct sites was markedly lower than that from posteroinferior sites (12.7 +/- 2.8 vs 20.6 +/- 2.1 IU/mg protein, p less than 0.01). In addition, the inferoposterior myocardium was normal histologically. In conclusion, acute myocardial infarction often results in reciprocal ST depression at sites distant from the area of acute necrosis and need not represent "ischemia at a distance."

Effectiveness of percutaneous transluminal coronary angioplasty for patients with medically refractory rest angina pectoris and high risk of adverse outcomes with coronary artery bypass grafting.

This study was undertaken to test the hypothesis that percutaneous transluminal coronary angioplasty (PTCA) is a reasonable alternative to coronary artery bypass grafting (CABG) for some high-risk patients with medically refractory rest angina. Over a 5-year period, 1 operator at a tertiary Veterans Affairs Medical Center performed angioplasty on 624 patients, of whom 441 had unstable angina. Of these 441 patients, 288 had rest angina and 225 had medically refractory rest angina. Medically refractory unstable angina was defined as reversible myocardial ischemia occurring at rest in an intensive care unit setting with low flow oxygen despite the following medications: (1) oral aspirin, intravenous heparin, or both; (2) some combination of beta blocker, calcium blocker, and/or nitrate so that resting heart rate is < 70 beats/min or resting blood pressure < 140 mm Hg, or both. There were 207 patients with medically refractory rest angina who had > or = 1 of the following characteristics predictive of a more than twofold increased risk of operative death at CABG: age > 70 years, prior CABG, recent myocardial infarct, need for intravenous nitroglycerin, need for intraaortic balloon pump, and left ventricular ejection fraction < 0.35. Of these 207 patients, 11 died (5%) during index hospitalization, 196 (95%) were discharged, and 186 (90%) went home angina free. There were 2 emergency CABGs and 9 acute myocardial infarctions. At follow-up (3 to 60 months, average 24), there were 27 late deaths (for a total of 38 [18%]), 8 (4%) late CABGs, and 44 (21%) late PTCAs (with 17 [8%] late myocardial infarctions). The 2-year mortality of 18% for this cohort is comparable to a 21% 2-year mortality observed in a group of 1,073 "high-risk" patients who underwent CABG in the Veterans Affairs Medical Center from 1987 to 1988. These data support the hypothesis that PTCA provides an alternative to CABG in some high-risk patients with medically refractory rest angina.

Mild renal failure is associated with adverse outcome after cardiac valve surgery.

The present study was performed to ascertain whether the presence of mild renal failure (defined as a serum creatinine concentration of 1. 5 to 3.0 mg/dL) is an independent risk factor for adverse outcome after cardiac valve surgery. An extensive set of preoperative and postoperative data was collected in 834 prospectively evaluated patients undergoing cardiac valve surgery at 14 Veterans Affairs Medical Centers. Univariate and multivariable analyses were performed to determine whether an independent association of mild renal dysfunction with adverse outcomes was present. Patients with mild renal failure had significantly greater 30-day mortality rates (P = 0.001; 16% versus 6%) and frequency of postoperative bleeding (P = 0.023; 16% versus 8%), respiratory complications (P = 0.02, 29% versus 16%), and cardiac complications (P = 0.002; 18% versus 7%) than patients with normal renal function (serum creatinine <1.5 mg/dL) when controlling for multiple other variables. The presence of a serum creatinine concentration of 1.5 to 3.0 mg/dL is significantly and independently associated with adverse outcomes after cardiac valve surgery.

The role of CT and MRI in staging of the mediastinum.

Lung Cancer Study Group (LCSG) Protocol 883, the comparative study of the results of magnetic resonance imaging (MRI) and computerized tomography (CT) for staging of tumor, nodal, and selected metastatic sights in patients with surgically staged lung cancer was activated in August 1988 but was not completed because of termination of LCSG funding. A literature review was therefore undertaken to determine the results of other studies that were performed to evaluate the relative efficacy of MRI and CT in the staging of patients with lung cancer. These studies determined that CT and MRI are approximately equal in the staging of N2 disease with a sensitivity of 70 to 90%, a specificity of 60 to 90%, and an accuracy of 66 to 90% depending on the criteria used for determining positive nodes and the compulsiveness of surgical staging. Magnetic resonance imaging is probably better in the assessment of superior sulcus tumors, tumors involving the aorta-pulmonary window, hilar nodes, in assessing chest wall or diaphragmatic invasion, and in evaluating patients whose CT findings are equivocal. Computed tomography and MRI reveal adrenal abnormalities in 10 to 20% of patients but only one third of these have metastases. Mediastinoscopy has a sensitivity of 85 to 90%, a specificity of 100%, and an accuracy of about 95% and is therefore the gold standard for N2 staging. If the CT examination reveals no N2 disease, one can proceed directly to thoracotomy with approximately a 15% chance of finding N2 disease. It was concluded that because CT is much cheaper, it should therefore be used for the noninvasive staging of patients with lung cancer unless the above-noted special circumstances are present that have been shown to favor MRI. Because of the limited accuracy of CT and MRI, however, positive findings must be confirmed by biopsy specimens and pathologic study.

Clinical science research.

Clinical science research incorporates the fields of clinical investigation and health services research. With a focus on the use of either human specimens or subjects, clinical investigation research projects translate knowledge gained from basic science research based on animal models for disease. The goal of clinical investigation is to develop new prevention, intervention, and therapeutic approaches to improve patient clinical outcomes. In contrast, health services research focuses on the improvement of the efficacy, cost-effectiveness, and outcomes of care. Health services research projects examine options to improve the health care delivery system, organization, financing, and reimbursement mechanisms in place today. The purpose of this article is to review common terminology and methodologic approaches that are used in clinical science research. The process of designing a research project is reviewed. Beginning with the development of a research question and hypothesis, the steps for successful completion of the project are discussed. Different study design approaches are presented with their respective strengths and weaknesses. The challenges associated with conducting a clinical research study are discussed, including the development of an appropriate sampling strategy, the designing of data collection, instruments, and the assurance of study data integrity. Possible threats to study validity and generalizability are assessed.One the major advantages of clinical research is that it offers an opportunity to study clinical questions in the clinical setting without the expenses of a basic research laboratory and basic science technology. Thus important clinical questions related to patient care, new technology assessment, clinical practice management, health care administration, or health policy may be addressed.

Objective evaluation of the efficacy of various venous cannulas.

Six venous cannulas (USCI No. 32, USCI No. 40, USCI No. 44, Sarns No. 40, Sarns two-stage cavoatrial, and Ferguson Argyle No. 40) were tested for efficiency of venous flow during cardiopulmonary bypass, with and without aortic cross-clamping. Each cannula was tested six times in dog models (twice in each of three dogs) and the data were averaged. The tip of the cavoatrial Sarns catheter was positioned as recommended. Two No. 32 USCI caval cannulas were placed either with or without caval snaring. The other cannulas were placed in the right atrium. Arterial flow was constant at 80 ml/kg/min, and aortic pressure averaged 84 mm Hg. Central venous pressure and the right ventricle excluded from the pulmonary artery so that blood which was not drained via the venous cannula was measured. Each single atrial cannula decompressed the right atrium (right atrial pressure 0 to 1 mm Hg) better than two caval cannulas (right atrial pressure 0 to 2 mm Hg). Caval snaring did not empty the right atrium (right atrial pressure 2 to 5 mm Hg) as well as any single cannula. The cavoatrial Sarns catheter did not empty the right atrium as well (right atrial pressure 2 to 4 mm Hg), but drained blood from the inferior vena cava (central venous pressure 0 mm Hg) better than other atrial cannulas (central venous pressure 1 to 5 mm Hg). All of the atrial cannulas performed equally well. The right ventricular vent flow varied between 63 and 70 ml/min with each of the atrial cannulas but rose to 85 ml/min with the cavoatrial Sarns catheter and 190 and 74 ml/min during caval cannulation with and without snaring, respectively. Aortic cross-clamping eliminated coronary sinus flow and decreased right ventricular vent flow. Therefore, a single atrial cannula is more efficient in draining blood from the right side of the heart than are two caval or a cavoatrial cannula. This advantage is negated by aortic cross-clamping.

Management of penetrating lung injuries in civilian practice.

Recent reports of military thoracic injuries have advocated early thoracotomy and aggressive management of pulmonary injuries with resection as opposed to the more conservative and traditional treatment with chest tube thoracostomy. A retrospective study was therefore performed to determine the incidence of thoracotomy and lung resection in civilian injuries and to evaluate the effectiveness of treatment of these injuries. Between 1973 and 1985, in a series of 1,168 patients, there were 384 gunshot wounds and 784 stab wounds to the thorax. Two hundred eighty-three patients with a gunshot wound (74%) and 602 with a stab wound (77%) were treated with chest tubes alone. Sixty-eight patients (6% of the total) required operative repair of pulmonary hilar or parenchymal injury. Pulmonary resection was necessary in only 18 patients (nine with a gunshot wound and nine with a stab wound), and 10 patients had repair of hilar injuries (nine with a gunshot wound and one with a stab wound). Of patients requiring pulmonary resection, nine required wedge or segmental resection, six required lobectomy, and three patients required pneumonectomy. Mortality for all thoracic injuries was 2.3%: for those treated with chest tube alone, 0.7%; for pulmonary hilar injuries, 30%; for pulmonary parenchymal injuries, 8.6%; and for injuries necessitating lung resection, 28%. Most civilian lung injuries can be treated by tube thoracostomy alone. Although relatively few patients with primary pulmonary injury require thoracotomy, those that do are at significant risk and may require lung resection to control bleeding or hemoptysis or to remove destroyed or devitalized lung tissue.

Intrapericardial diaphragmatic hernia after subxiphoid epicardial pacemaker insertion: case reports.

The first two cases of intrapericardial diaphragmatic hernia following a subxiphoid epicardial pacemaker insertion are reported. Factors deemed responsible for this rare complication in one case were previous gastrectomy with a resulting paucity of omentum, and entrance into the peritoneal cavity during the pacemaker procedure.

Effects of systemic hypothermia on myocardial metabolism and coronary blood flow in the fibrillating heart.

Ventricular fibrillation during normothermic cardiopulmonary bypass is deleterious to the myocardium. This study was undertaken to determine if moderate systemic hypothermia would protect the myocardium during ventricular fibrillation. Fourteen mongrel dogs were subjected to 1 hour, 15 minutes of total cardiopulmonary bypass. Ventricular fibrillation was induced by a continuous electrical alternating current applied at the beginning of bypass and lasting for 1 hour. Six animals were maintained at normothermia (Group I), and eight were cooled to 30 degrees C. for 1 hour (Group II). The hypothermic group (Group II) demonstrated lower myocardial oxygen consumption and metabolism, decreased coronary blood flow, and less myocardial lactate production during ventricular fibrillation than did Group I. It is concluded that hypothermia does offer some protection, although not complete, against the deleterious effects of ventricular fibrillation described previously.

Effective control of refractory pulmonary hypertension after cardiac operations.

OBJECTIVES: Inhaled nitric oxide is a promising therapy to control pulmonary hypertension. However, pulmonary hypertension caused by valvular heart disease is often refractory to inhaled nitric oxide. The objective of this study was to determine whether the combination of inhaled nitric oxide plus dipyridamole will cause a response in patients with pulmonary hypertension undergoing cardiac operations who had not responded to inhaled nitric oxide alone. METHODS: Responses in 10 patients (62 +/- 7 years) with pulmonary hypertension caused by aortic or mitral valvular disease (mean pulmonary artery pressure, > or = 30 mm Hg) were studied in the operating room after valve replacement. The effect of inhaled nitric oxide alone (40 ppm) on pulmonary vascular resistance, mean pulmonary artery pressure, cardiac output, and mean arterial pressure was determined. Inhaled nitric oxide administration was then stopped and patients were given dipyridamole (0.2 mg/kg intravenously); the effect of inhaled nitric oxide plus dipyridamole was then examined. RESULTS: Dipyridamole effected a response in patients who had not responded to nitric oxide. Pulmonary vascular resistance and mean pulmonary artery pressure were significantly reduced and cardiac output was increased without change in mean arterial pressure. CONCLUSIONS: Patients with refractory pulmonary hypertension in whom inhaled nitric oxide alone fails to cause a response may respond to combined therapy of inhaled nitric oxide plus dipyridamole. This therapy may be particularly valuable in patients with dysfunction of the right side of the heart as a result of pulmonary hypertension because of its effective lowering of right ventricular afterload.

Pulmonary sling. Case report and collective review.

The eighteenth survivor of correction of an anomalous left pulmonary artery arising from the right pulmonary artery is reported. This is the first case in which postoperative angiography demonstrated patency of the left pulmonary artery. The onset of symptoms in infancy, predominance of expiratory rather than inspiratory stridor, anterior indentation of the esophagus, and lethal progression of symptoms during the first year of life are peculiar to this anomaly. Operation through a left thoracotomy is advocated, with division of the proximal left pulmonary artery and implantation into the main pulmonary artery posterior to the phrenic nerve. Previously reported cases are collectively reviewed.

Does lower systemic temperature enhance cardioplegic myocardial protection?

This study was performed to determine if systemic temperature affects the rate of cooling and rewarming of the myocardium between infusions of cold potassium cardioplegic solution and if it alters the degree of myocardial protection. Twenty-one dogs underwent cardiopulmonary bypass and 3 hours of ischemic arrest produced by infusing 0 degrees to 4 degrees C potassium cardioplegic solution every 20 minutes. The animals were perfused at different systemic temperatures--Group A, 23 degrees C; Group B, 30 degrees, C; and Group C, 37 degrees C. Myocardial temperature decreased to 11 degrees C in Groups A and B as compared with 13 degrees C in Group C immediately after infusion of the potassium cardioplegic solution (p < 0.0007). Myocardial temperature increased to 19 degrees, 21 degrees, and 26 degrees C in Groups A, B, and C (p < 0.000005) 20 minutes after infusion. Myocardial adenosine triphosphate (ATP) concentration significantly decreased, from 6.69 to 3.56 mumoles/gm (p < 0.0003) in Group B and from 4.99 to 2.80 (p < 0.005) in Group C at the end of 3 hours of cardioplegic arrest. Myocardial glycogen levels also significantly decreased, from 1.156 to 446 mg% (p < 0.003) in Group B and from 811 to 439 mg% (p < 0.04) in Group C. Myocardial ATP and glycogen did not decrease significantly in Group A during the period of arrest. Myocardial lactate values increased more in Groups B and C during the arrest period than in Group A. 12.6 versus 6.5 mumoles/gm (p < 0.03). Moderate systemic hypothermia, therefore, appears to enhance the myocardial protection of potassium cardioplegia.

Carcinoma of the esophagus. An aggressive one-stage palliative approach.

We reviewed the records of 44 consecutive patients with advanced esophageal carcinoma treated at either a Veterans Administration or a city-country hospital. The patients, 38 men and six women, ranged in age from 27 to 72 years and had been referred for operative management. The average duration of dysphagia was 5 months. All patients underwent a one-stage esophagogastrectomy with esophagogastrostomy. The last 34 patients also had a modified fundoplication. Lesions at the gastroesophageal junction were approached via a low left thoracotomy and the others via a simultaneous right thoracotomy and laparotomy. All patients had preoperative enteral or parenteral hyperalimentation. Seven patients died within 30 days after operation (operative mortality 16%). Twenty-six patients lived from 3 to 28 months postoperatively (average 11.5 months). Eleven are alive at present (average 10 months). Postoperative complications were as follows: anastomotic leak, three patients (two died); respiratory failure, four (two died); stricture, three; myocardial infarction, two (two died); cholecystitis, one; and pulmonary embolus, one (patient died). Thirty-four patients had modified fundoplication, and an inconsequential anastomotic leak developed in one. In contrast, two of the 10 patients who did not have modified fundoplication died as a result of anastomotic leak. Preoperative hospital stay ranged from 10 to 28 days (average 18); postoperative stay ranged from 10 to 40 days (average 16). Except for the three patients in whom stricture developed, all patients (92%) had continuous relief of dysphagia. We conclude that one-stage esophagogastrectomy with esophagogastrostomy is applicable in most cases and is associated with both satisfactory long-term palliation and a reasonable period of hospitalization. The addition of a modified fundoplication results in a relatively low rate of anastomotic leak.