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Chronic thromboembolic pulmonary hypertension occurs when acute thromboemboli fail to dissolve completely. The resulting fibrotic scar tissue within the pulmonary arteries is obstructive and eventually leads to right heart failure. Medical therapy for this condition is supportive, but surgery with pulmonary artery endarterectomy is curative, and carries a low mortality at experienced centers.

Reperfusion lung injury is a postoperative complication of pulmonary thromboendarterectomy that can significantly affect morbidity and mortality. Studies in other postoperative patient populations have demonstrated a reduction in acute lung injury with the use of a low-tidal volume (Vt) ventilation strategy. Whether this approach benefits patients undergoing thromboendarterectomy is unknown.We sought to determine if low-Vt ventilation reduces reperfusion lung injury in patients with chronic thromboembolic pulmonary hypertension undergoing thromboendarterectomy.Patients undergoing thromboendarterectomy at one center were randomized to receive either low (6 ml/kg predicted body weight) or usual care Vts (10 ml/kg) from the initiation of mechanical ventilation in the operating room through Postoperative Day 3. The primary endpoint was the onset of reperfusion lung injury. Secondary outcomes included severity of hypoxemia, days on mechanical ventilation, and intensive care unit and hospital lengths of stay.A total of 128 patients were enrolled and included in the analysis; 63 were randomized to the low-Vt group and 65 were randomized to the usual care group. There was no statistically significant difference in the incidence of reperfusion lung injury between groups (32%, n=20 in the low-Vt group vs. 23%, n=15 in the usual care group; P=0.367). Although differences were noted in plateau pressures (17.9 cm H2O vs. 20.1 cm H2O, P0.001) and peak inspiratory pressures (20.4 cm H2O vs. 23.0 cm H2O, P0.001) between the low-Vt and usual care groups, respectively, mean airway pressures, PaO2/FiO2, days on mechanical ventilation, and ICU and hospital lengths of stay were all similar between groups.In patients with chronic thromboembolic pulmonary hypertension undergoing pulmonary thromboendarterectomy, intra- and postoperative ventilation using low Vts (6 mg/kg) compared with usual care Vts (10 mg/kg) does not reduce the incidence of reperfusion lung injury or improve clinical outcomes. Clinical trial registered with www.clinicaltrials.gov (NCT00747045).

Pulmonary endarterectomy, which 25 years ago was only performed at the University of California, San Diego (UCSD), is now widely recognized as an effective way of treating pulmonary hypertension as a result of chronic thromboembolic disease. The operation is carried out using cardiopulmonary bypass to achieve profound hypothermia and circulatory arrest, which results in the bloodless field necessary for the visibility required for this delicate operation.

Background Obesity is a common comorbidity of patients with chronic thromboembolic pulmonary hypertension referred for pulmonary thromboendarterectomy, yet the effect of obesity on pulmonary thromboendarterectomy outcomes has not been well described. Methods We conducted a retrospective cohort study in which 476 consecutive operations over a 3.5-year period were examined to determine the effects of obesity on outcomes. Patients were grouped into four categories based on body mass index (BMI): less than 22 kg/m 2 , 22 to 30 kg/m 2 , 30 to 40 kg/m 2 , and more than 40 kg/m 2 . Results There were important differences in baseline pulmonary hemodynamics, with obese patients having significantly lower pulmonary vascular resistances than nonobese patients. All patients achieved a significant reduction in pulmonary vascular resistance, although the improvement was greatest in the lower BMI groups. The overall in-hospital mortality was 0.8%, and there were no differences in risk among BMI groups. Among the BMI groups, there were no differences in incidence of postoperative complications, including atrial fibrillation (overall 24.8%), reperfusion lung injury (overall 23.1%), and surgical site infection (overall 4.4%) or in median lengths of stay (including ventilator days, intensive care unit days, and postoperative length of stay). Conclusions Pulmonary thromboendarterectomy outcomes have continued to improve, and this surgery can safely be completed in obese patients, previously deemed to be at high risk for poor outcomes.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a known sequela of acute pulmonary embolic disease and yet remains underdiagnosed. Although nonsurgical options for patients with CTEPH have become increasingly available, including pulmonary artery hypertensive medical therapy, surgical endarterectomy provides the most appropriate intervention as a potential cure for this debilitating disorder. This article summarizes the most recent outcomes of pulmonary endarterectomy at a single institution over the past 12 years, with emphasis on the surgical approach to segmental-level chronic thromboembolic disease.More than 2,700 pulmonary endarterectomy operations have been performed at the University of California, San Diego Medical Center. Because of recent changes in the patient population and in surgical results, 1,500 patients with symptomatic chronic thromboembolic disease who underwent pulmonary endarterectomy between March 1999 and December 2010 were analyzed. The outcomes for the more recent 500 patients, compared with the previous 1,000 were studied.In-hospital mortality for the cohort of 1,000 patients (group 1) was 5.2% compared with 2.2% for the last 500 operations (group 2) (p0.01). There was no mortality in the last 260 consecutive patients undergoing isolated pulmonary endarterectomy. More patients presented with segmental type III disease in the more recent 500 patients (21.4% versus 13.1%; p0.001). Between the 2 patient groups, there was a comparable decline in pulmonary vascular resistance (PVR) (group 1: 861.2 ± 446.2 to 94.8 ± 204.2 dynes/sec/cm(-5); group 2: 719.0 ± 383.2 to 253.4 ± 148.6 dynes/sec/cm(-5)) and mean pulmonary artery (PA) pressures (group 1: 46.1 ± 11.4 to 28.7 ± 10.1 mm Hg; group 2: 45.5 ± 11.6 to 26.0 ± 8.4 mm Hg) after endarterectomy.Despite a patient population with more distal disease, results continue to improve. Pulmonary endarterectomy for patients with CTEPH results in significant pulmonary hemodynamic improvement, with favorable outcomes achievable even in patients with distal segmental-level chronic thromboembolic disease.

Pulmonary vascular remodeling occurs in patients with chronic thromboembolic pulmonary hypertension (CTEPH). One factor contributing to this vascular wall thickening is the proliferation of pulmonary artery smooth muscle cells (PASMC). Store-operated Ca2+ entry (SOCE) and cytosolic free Ca2+ concentration ([Ca2+]cyt) in PASMC are known to be important in cell proliferation and vascular remodeling in pulmonary hypertension. Rapamycin is widely known for its antiproliferative effects in injured coronary arteries. Although several reports have suggested favorable effects of rapamycin in animal models of pulmonary hypertension, no reports have been published to date in human tissues. Here we report that rapamycin has an inhibitory effect on SOCE and an antiproliferative effect on PASMC derived from endarterectomized tissues of CTEPH patients. Cells were isolated from endarterectomized tissues obtained from patients undergoing pulmonary thromboendarterectomy (PTE). Immunohistochemical analysis indicated high deposition of platelet-derived growth factor (PDGF) in tissue sections from PTE tissues and increased PDGF receptor expression. PDGF transiently phosphorylated Akt, mammalian target of rapamycin (mTOR), and p70S6 kinase in CTEPH cells from CTEPH patients. Acute treatment (30 min) with rapamycin (10 nM) slightly increased cyclopiazonic acid (10 μM)-induced Ca2+ mobilization and significantly reduced SOCE. Chronic treatment (24 h) with rapamycin reduced Ca2+ mobilization and markedly inhibited SOCE. The inhibitory effects of rapamycin on SOCE were less prominent in control cells. Rapamycin also significantly reduced PDGF-stimulated cell proliferation. In conclusion, the data from this study indicate the importance of the mTOR pathway in the development of pulmonary vascular remodeling in CTEPH and suggest a potential therapeutic benefit of rapamycin (or inhibition of mTOR) in these patients.

Pulmonary hypertension as the result of chronic pulmonary thromboembolic disease is a serious condition with poor long-term prognosis. The condition is one of the more common cardiovascular diseases affecting Americans, yet it is severely underdiagnosed. Pulmonary thromboendarterectomy is the definitive treatment for chronic pulmonary hyper-tension as the result of thromboembolic disease; however. it is an uncommon procedure, primarily because of lack of recognition on the part of the clinicians. Patients affected by chronic thromboembolic pulmonary hypertension (CTEPH) may present with a variety of debilitating cardiopulmonary symptoms. However, once diagnosed, there is no curative role for medical management, and surgery remains the only option. Palliation therapy with medical management in order to delay surgery carries the risk of prolonging the disease and irreversibly damaging unaffected pulmonary vasculature.

OBJECTIVES: Pulmonary arterial hypertension causes right ventricular remodeling; that is, right ventricular dilatation, hypertrophy, and leftward ventricular septal bowing. We studied the effect of pulmonary endarterectomy on the restoration of right ventricular remodeling in patients with chronic thromboembolic pulmonary hypertension by magnetic resonance imaging.METHODS: In 17 patients with chronic thromboembolic pulmonary hypertension, before and at least 4 months after pulmonary endarterectomy, and in 12 healthy controls, right ventricular and left ventricular end-diastolic and end-systolic volumes (milliliters) and mass (grams per meter squared) and leftward ventricular septal bowing (1 divided by the radius of curvature in centimeters) were determined by magnetic resonance imaging.RESULTS: Before pulmonary endarterectomy, right ventricular volumes, left ventricular end-diastolic volume, right ventricular mass, and leftward ventricular septal bowing differed significantly between patients with chronic thromboembolic pulmonary hypertension and healthy control subjects. After pulmonary endarterectomy, pulmonary hemodynamics improved, and right and left ventricular volumes and leftward ventricular septal bowing normalized; right ventricular mass decreased significantly (46 +/- 14 to 31 +/- 9 g x m(-2), P< .0005), but did not completely normalize. The change in total pulmonary resistance correlated with the change in right ventricular ejection fraction (r = 0.50, P < .05), right ventricular mass (r = 0.63, P < .01), and leftward ventricular septal bowing (r = 0.50, P < .05).CONCLUSIONS: Right ventricular remodeling was observed in patients with chronic thromboembolic pulmonary hypertension and restored almost completely after a hemodynamically successful pulmonary endarterectomy. Magnetic resonance imaging is a valuable tool to evaluate cardiac remodeling and function in patients with chronic thromboembolic pulmonary hypertension, both before and after pulmonary endarterectomy.

Background Pulmonary endarterectomy is the accepted therapy for thromboembolic pulmonary hypertension. A recognized complication of this surgery is the postoperative development of reperfusion edema, a potentially fatal cause of respiratory failure. Because reperfusion edema can be a reversible process, temporizing support measures may be life saving. Methods We retrospectively reviewed our experience with venovenous extracorporeal life support (V-V ECLS) from July 1990 to February 2006, in 20 adult patients (mean age 50.5 ± 14.5 years) presenting with potentially reversible respiratory failure after pulmonary endarterectomy. This subset of patients comprised 1.12% of our total pulmonary endarterectomy experience during that time (1,790 cases). Results Overall in-hospital survival was 30.0% for patients requiring ECLS support after pulmonary endarterectomy versus 94.2% for patients who underwent pulmonary endarterectomy alone during the same timeframe. V-V ECLS was instituted at a mean of 86.8 hours after surgery. The mean duration of V-V ECLS was 123.4 ± 71.3 hours. The most common cause of death in ECLS patients after pulmonary endarterectomy was pulmonary hemorrhage. Survival was greater in patients cannulated within 120 hours of surgery (46.2% survival; 6 of 13 patients) compared with those cannulated after 120 hours (0 of 7 patients). Multiple logistic regression identified long duration of mechanical ventilation pre-ECLS and severity of preoperative pulmonary hypertension together as predictors of mortality. Conclusions A small subset of patients undergoing pulmonary endarterectomy develop temporary life-threatening respiratory failure secondary to severe reperfusion edema. In those patients with satisfactory hemodynamic outcome, V-V ECLS is a therapeutic option when all other conventional strategies have been exhausted.

The vascular response to intravenous thiopental in patients on cardiopulmonary bypass during deep hypothermia was examined.This was a prospective observational study.A university teaching hospital.Twenty-one consecutive adult patients undergoing pulmonary thromboendarterectomy during which deep hypothermic circulatory arrest was instituted.Immediately before circulatory arrest, each patient was administered a 500-mg dose of thiopental intravenously. Arterial blood pressure was monitored and recorded by using a femoral artery catheter and serum electrolytes, acid-base status and arterial hematocrit were determined immediately before the administration of thiopental.Thiopental was associated with a dose-related increase in mean arterial pressure of 32 +/- 11 mmHg (p0.0001). Thiopental also resulted in an increase in arterial pH of 0.08 +/- 0.03. A positive correlation between the magnitude of the pH change and the magnitude of the hypertensive response was suggested but did not reach statistical significance (p = 0.066). Of the other factors investigated, only serum-ionized calcium had a statistically significant association with the vascular response in that higher ionized calcium was associated with less hypertensive response (p = 0.014).The administration of thiopental to deeply hypothermic patients during cardiopulmonary bypass is associated with a dramatic increase in mean arterial blood pressure. The mechanism responsible for this vasoconstrictive response may involve thiopental's potentiation of the effects of norepinephrine in the peripheral vasculature.

Chronic thromboembolic pulmonary hypertension has emerged as one of the leading causes of severe pulmonary hypertension. This disease is estimated to occur in approximately 1 to 5% of all patients who have previously developed an acute pulmonary embolism, although the true prevalence is suspected to be much higher. Chronic thromboembolic pulmonary hypertension is characterized by intraluminal thrombus organization, fibrous stenosis, and vascular remodeling of pulmonary vessels. Pulmonary endarterectomy is an operation that is considered curative for thromboembolic pulmonary hypertension and is therefore superior to transplantation for this condition. This article focuses on the surgical outcomes of patients undergoing pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension and discusses the currently known factors that affect survival after this operation.

Pulmonary endarterectomy is the definitive treatment for chronic pulmonary hypertension as the result of thromboembolic disease. Although significant progress has been made over the last decade in recognition, diagnostic modalities, and treatment of this disease, chronic thromboembolic pulmonary hypertension (CTEPH) continues to be severely underdiagnosed and as a consequence pulmonary endarterectomy remains an uncommon procedure. Patients with CTEPH may present with a variety of debilitating cardiopulmonary symptoms. However, once diagnosed, there is no curative role for medical management, and surgery remains the only option. Medical management in these patients is only palliative, and surgery by means of transplantation for this type of pulmonary hypertension is an inappropriate use of resources with less than satisfactory results. In this article we describe the technical advances of pulmonary endarterectomy and the current procedure as it is performed at University of California-San Diego Medical Center.

This article provides a historical perspective for our current understanding of chronic thromboembolic pulmonary hypertension and surgery for this disease. It chronicles the developments in surgical techniques that have made pulmonary endarterectomy the procedure of choice for obstruction of pulmonary vessels by organized thromboemboli and secondary vessel wall thickening.

ObjectivePulmonary endarterectomy is the operation of choice for thromboembolic pulmonary hypertension. As the largest referral center for thromboembolic pulmonary hypertension in the world, we are frequently asked whether patients with extreme pulmonary hypertension (pulmonary artery systolic pressure >100 mm Hg) can safely undergo this operation with therapeutic benefit.MethodsTo determine whether patients with pulmonary artery systolic pressures of greater than 100 mm Hg have favorable outcomes after pulmonary endarterectomy, we reviewed the outcomes of 743 patients who underwent this operation between 1999 and 2004. We compared hemodynamic and outcome parameters of 65 patients (group 1: 26 male and 39 female patients; mean age, 49.5 years) who had preoperative pulmonary artery systolic pressures of greater than 100 mm Hg with 678 patients (group 2: 314 male and 364 female patients; mean age, 50.3 years) with preoperative pulmonary artery systolic pressures of less than 100 mm Hg.ResultsGroup 1 patients had a greater overall diminution in pulmonary vascular resistance (mean decrease: 926.7 ± 511.1 vs 546.4 ± 365.1 dynes·sec·cm−5, P < .01) and reduction in pulmonary artery systolic pressure (mean decrease: 50.5 ± 18.7 vs 27.2 ± 18.6 mm Hg, P < .05), with similar improvement in cardiac output (mean increase: 1.53 ± 1.47 vs 1.55 ± 1.58 L/min) compared with values seen in group 2 patients. Although length of hospital stay was similar for the 2 groups, overall perioperative survival was slightly lower in group 1 patients (89.2% [58/65] for group 1 vs 96.5% [654/678] for group 2). Patients with extreme pulmonary hypertension manifest a higher rate of postoperative reperfusion edema, leading to longer days of intubation compared with group 2 patients.ConclusionsPulmonary endarterectomy can be performed safely in patients with severe thromboembolic pulmonary hypertension. The magnitude of preoperative pulmonary artery systolic pressure or pulmonary vascular resistance is not a contraindication for surgical intervention. Indeed, patients with extreme pulmonary hypertension might benefit the most from this operation.

Objectives The aim of this research was to test whether constitutive expression of hypoxia-inducible factor 1-alpha (HIF-1α) influences infarction size and cardiac performance after myocardial infarction. Background A major question in clinical medicine is whether infarction size and border zone remodeling of the heart can be influenced by the overexpression of specific genes in the peri-infarction region. Methods We investigated the role of constitutive HIF-1α expression in acute myocardial infarction using a transgenic model. Transgenic mice containing the HIF-1α gene under the control of the α-myosin heavy chain promoter were constructed. Myocardial infarction was produced by coronary ligation in HIF-1α transgenic mice and control animals. Extent of infarction was then quantitated by two-dimensional and M-mode echocardiography as well as by molecular and pathologic analysis of heart samples in infarct, peri-infarct, and remote heart regions at serial time points. Results Constitutive overexpression of HIF-1α in the murine heart resulted in attenuated infarct size and improved cardiac function 4 weeks after myocardial infarction. Significantly, we found an increase in both capillary density as well as vascular endothelial growth factor and inducible nitric oxide synthase expression in peri-infarct and infarct regions in the hearts of constitutive HIF-1α–expressing animals compared to control animals. Conclusions These observations suggest the involvement of HIF-1α in myocardial remodeling and peri-infarct vascularization. Our results show that supranormal amounts of this peptide protect against extension of infarction and improve border zone survival in myocardial infarction.

Although brucellosis is a common zoonotic disease worldwide, infection with Brucella canis is rare and often difficult to diagnose. We describe the clinical and epidemiological aspects of a case of B. canis peritonitis.

This pilot study investigated the hemodynamics of a yogic breathing technique claimed "to help eliminate and prevent heart attacks due to abnormal electrical events to the heart," and to generally "enhance performance of the central nervous system (CNS) and to help eliminate the effects of traumatic shock and stress to the CNS."Parameters for (4) subjects were recorded during a preexercise resting period, a 31-minute exercise period, and a postexercise resting period.Parameters for subjects were recorded in a laboratory at the University of California, San Diego.Parameters for 3 males (ages 44, 45, 67) and 1 female (age 41) were recorded. One (1) subject (male age 45) had extensive training in this technique.This yogic technique is a 1 breath per minute (BPM) respiratory exercise with slow inspiration for 20 seconds, breath retention for 20 seconds, and slow expiration for 20 seconds, for 31 consecutive minutes.Fourteen beat-to-beat parameters were measured noninvasively and calculated for body surface area to yield: stroke index (SI), heart rate (HR), cardiac index, end diastolic index, peak flow, ejection fraction, thoracic fluid index, index of contractility, ejection ratio, systolic time ratio, acceleration index, and systolic, diastolic, and mean arterial pressures (MAPs). Left stroke work index (LSWI) and stroke systemic vascular resistance index (SSVRI) were calculated.We report on SI, HR, MAP, LSWI, and SSVRI and how they can help to describe hemodynamicstate changes. This technique induces dramatic shifts in all hemodynamic variables during the 1 BPM exercise and can produce unique changes in the postexercise resting period after long-term practice that appears to have a unique effect on the brain stem cardiorespiratory center regulating the Mayer wave (0.1-0.01 Hz) patterns of the cardiovascular system.Preclinical studies are warranted to examine the possible long-term effects of this technique that appear to reset a cardiorespiratory brain-stem pacemaker. We postulate that this effect may be the basis for the purported yogic health claim.

Objectives Because pulmonary thromboendarterectomy (PTE) can result in an immediate reduction in pulmonary artery (PA) pressure, we sought to evaluate the effect of PTE on severe tricuspid regurgitation (TR) without tricuspid annuloplasty. Background Few data exist regarding the frequency and magnitude of functional TR improvement after reduction in PA pressure. Methods We identified 27 patients with severe TR, defined by a regurgitant index (RI) >33%, who underwent PTE. The RI, tricuspid annular diameter (TAD), apical displacement of leaflet coaptation, and estimated PA systolic pressure were determined on pre- and post-PTE echocardiograms. Patients were stratified based on resolution (RI ≤33%) or persistence (RI >33%) of severe TR. Results Comparing pre- and post-PTE echocardiography results, severe TR resolved in 19 of 27 (70%) patients. This group had a more effective PA systolic pressure reduction after PTE (49 ± 20 mm Hg vs. 32 ± 16 mm Hg by echocardiography, p = 0.075, and 37 ± 16 mm Hg vs. 16 ± 13 mm Hg by catheter measurement, p = 0.004). No difference was observed in TAD, apical displacement of the tricuspid valve, or other features compared with the group with persistent severe TR. There was a trend toward longer hospital stays in the group with persistent severe TR (19 ± 15 days vs. 14 ± 9 days; p = 0.55). Conclusions After significant PA pressure reduction by PTE, severe functional TR with a dilated annulus may improve without annuloplasty despite dilated tricuspid annulus diameters.

Objectives: To determine the femoral-to-radial arterial pressure gradient, as well as the factors associated with them, in patients receiving cardiopulmonary bypass (CPB) with profound hypothermia and circulatory arrest. Design: Retrospective automated hemodynamic record review. Setting: University hospital. Participants: Patients undergoing pulmonary thromboendarterectomy with deep hypothermic circulatory arrest. Measurements and Main Results: The automated hemodynamic records of 54 consecutive patients undergoing pulmonary thromboendarterectomy with deep hypothermic circulatory arrest were reviewed, comparing the femoral and radial arterial pressures throughout the intraoperative period. In 20 of the patients, the hemodynamic data from the first 16 postoperative hours were also studied. Forty-one of 54 (76%) of the patients exhibited a mean arterial gradient of at least 10 mmHg either during or after CPB, femoral being higher. Clinically significant gradients were noted throughout the CPB period and the post-CPB period in these patients. In the 54 patients studied, the systolic blood pressure (SBP) gradient was 32 ± 19 mmHg after CPB (95% confidence limits 28.2 mmHg, 39.0 mmHg), and the mean arterial pressure (MAP) gradient was 6.3 ± 4.9 mmHg (95% confidence limits 5.5 mmHg, 8.6 mmHg). The duration of clinically significant SBP (>10 mmHg) and MAP (>5 mmHg) gradients in the postoperative period were 5.2 ± 5.7 hours and 5.8 ± 7.2 hours, respectively. Advanced age correlated with high post-CPB pressure gradients in this population and was associated with prolonged postoperative resolution of the gradients. Conclusions: The femoral-to-radial arterial pressure gradients, particularly systolic, after CPB, were greater and of longer duration in these patients undergoing deep hypothermic circulatory arrest than gradients previously reported for routine CPB. Central arterial pressure monitoring is recommended for patients undergoing deep hypothermic circulatory arrest, being valuable both for intraoperative and postoperative care.

Pathophysiological findings in chronic thromboembolic pulmonary hypertension (CTEPH) have suggested that a secondary small vessel arteriopathy may contribute to the haemodynamic impairment observed in these patients. It was hypothesised that this element of the elevated vascular resistance may be responsive to continuous intravenous epoprostenol therapy. Retrospectively, the clinical and haemodynamic responses to continuous intravenous epoprostenol were evaluated in nine CTEPH patients who subsequently underwent pulmonary thromboendarterectomy (PTE). Cardiopulmonary haemodyamics were determined prior to the initiation of epoprostenol, while on epoprostenol, prior to PTE, and after PTE. Six patients, treated for 2-26 months prior to PTE, experienced either clinical stability or improvement that was associated with a mean reduction in pulmonary vascular resistance (PVR) of 28% (median 33%,,, range 0-46%). Three patients, treated for 3-9 months, experienced clinical deterioration during epoprostenol administration, with a significant increase in PVR in two patients. Subsequent PTE resulted in a highly significant improvement of cardiac index, mean pulmonary artery pressure and total pulmonary resistance. To conclude, selected patients with chronic thromboembolic pulmonary hypertension may benefit clinically and haemodynamically from continuous intravenous epoprostenol treatment prior to pulmonary thromboendarterectomy. Factors predictive of a beneficial response, and whether this intervention influences either morbidity or mortality associated with pulmonary thromboendarterectomy, remain to be established

Background The incidence of pulmonary hypertension resulting from chronic thrombotic occlusion of the pulmonary arteries is significantly underestimated. Although medical therapy for the condition is supportive only, surgical therapy is curative. Our pulmonary endarterectomy program was begun in 1970, and 188 patients were operated on in the subsequent 20 years. With the increased recognition of the disease and the success of operative therapy, however, more than 1,400 operations have been done since 1990 at our center. Methods The safety and efficacy of the operation was assessed with changes made through increased experience. We examined in detail the results of our last 500 consecutive patients. Results Median sternotomy, cardiopulmonary bypass, profound hypothermia, and circulatory arrest were found to be essential to the success of the operation. All occluding material could be removed at operation. We currently believe that there is no degree of embolic occlusion within the pulmonary vascular tree that is inaccessible and no degree of right ventricular impairment or any level of pulmonary vascular resistance that is inoperable. With shorter cardiac arrest periods and the use of a cooling jacket to the head, cerebral impairment has been eliminated. The pulmonary artery pressures and pulmonary vascular resistance in a recent cohort of 500 patients is examined. The mortality rate for the operation has been reduced steadily, and was 22 of the last 500 patients operated on (4.4%). Conclusions The operation is considered curative and therefore greatly superior to transplantation for this condition. Current techniques of operation make the procedure relatively safe.

The eSVS Mesh (Kipps Bay Medical, Minneapolis, MN USA) Mesh (Kipps Bay Medical, Minneapolis, MN USA) is a new concept in improving saphenous vein graft patency for coronary bypass grafting. This is a nitinol-based external support device that maintains external support of the graft and prevents detrimental expansion when exposed to arterial pressure. The implanting technique is critical to outcomes and is described in this article. Clinical testing in the United States is pending.

Objective: We sought to determine whether type and location of thromboembolic disease in the pulmonary vascular tree predicts the hemodynamic result and clinical outcome in patients undergoing pulmonary endarterectomy. Methods: From 1998 to 2000, 202 patients with pulmonary hypertension and pulmonary vascular resistance ranging from 194 to 2950 dynes-s-cm−5 underwent pulmonary endarterectomy. Preoperative and postoperative tricuspid valve function, pulmonary artery pressure, and pulmonary vascular resistance were determined by means of transthoracic echocardiography and measurements with a Swan-Ganz catheter (Edwards Lifesciences, Irvine, Calif), respectively. Patients underwent intraoperative classification of thromboembolism as follows: type 1 (76 patients), fresh thrombus in the main-lobar pulmonary arteries; type 2 (81 patients), intimal thickening and fibrosis proximal to the segmental arteries; type 3 (38 patients), disease within distal segmental arteries only; and type 4 (7 patients), distal arteriolar vasculopathy without visible thromboembolic disease. Results: Overall perioperative mortality was 4.5% (9/202 patients). By means of univariate analysis, patients with type 3 or 4 disease (distal pulmonary vasculopathy) had more residual postoperative tricuspid regurgitation (P

Inhaled nitric oxide (INO) has been shown to improve oxygenation and decrease intrapulmonary shunt and pulmonary hypertension in various lung diseases. In this study we report a patient with end-stage idiopathic pulmonary fibrosis and pulmonary hypertension who received INO after coronary artery bypass surgery, with significant improvement in arterial oxygenation and pulmonary arterial pressure. Using a pulsing delivery system, the patient continued to receive outpatient INO for 30 months while waiting for lung transplantation. Exercise study and two-dimensional echocardiogram, after 3 months of inhaled NO, demonstrated continued benefits of INO for improvement of arterial oxygenation, pulmonary arterial pressure and exercise tolerance.

Patients with pulmonary hypertension due to chronic thromboembolic disease benefit from pulmonary thromboendarterectomy. A subset of these patients present with concomitant coronary or valvular disease.From July 1990 to July 2000, 90 patients (68 males, 22 females, mean age 68 years) with pulmonary vascular resistance (PVR) ranging from 297 to 2261 dynes x sec x cm(-5) underwent pulmonary thromboendarterectomy in conjunction with coronary bypass grafting (59 patients), coronary artery bypass grafting/foramen ovale closure (24 patients), tricuspid annuloplasty (3 patients), mitral valve repair (2 patients), and aortic valve replacement (2 patients). The perioperative and hemodynamic outcomes of these patients were compared with the cohort of 1,100 isolated pulmonary thromboendarterectomies performed at our institution during this time.Overall perioperative survival (93.3%; 84 of 90 patients) and mean diminution in PVR (521 dynes x sec x cm(-5)) for patients undergoing combined operations were similar to those undergoing pulmonary thromboendarterectomy alone (94.2% survival; 1034 of 1100 patients; 547 dynes x sec x cm(-5) mean PVR reduction). Although patients undergoing combined operations were older (mean age 68 vs 50 years, p0.0001), had longer hospital stays (median 14 vs 9 days), and had worse left ventricular function (mean preoperative cardiac output 3.1 vs 4.4, p0.0001), there was no difference in cross-clamp time, resolution of tricuspid regurgitation, or postoperative systolic function between these two groups.Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension may be performed safely in conjunction with other cardiac operations. Older patients evaluated for pulmonary thromboendarterectomy should be screened for concomitant coronary and valvular disease.

Objective: A consistent pathologic feature seen in lungs of patients with pulmonary hypertension from thromboembolic disease is hyperplasia of the media of pulmonary arterioles. The molecular factors responsible for these vessel wall changes are unknown. Angiopoietin-1 is a gene responsible for the formation of the media of blood vessels in utero. We hypothesized that aberrant expression of the angiopoietin-1 gene in the adult lung would be a major contributing factor in the development of pulmonary hypertension. Methods: From April 1999 to March 2000, a total of 35 patients (18 men, 17 women, mean age 52 years) with pulmonary hypertension and pulmonary vascular resistance ranging from 407 to 2006 dynes · sec · cm –5 underwent pulmonary endarterectomy at our institution. Before cardiopulmonary bypass, lung biopsy specimens were taken from each patient. Biopsy specimens were also obtained from 10 patients (5 women, 5 men, mean age 55 years) undergoing lung resection for causes other than pulmonary hypertension. All specimens were blindly scored by a pathologist for degree of medial hyperplasia. Quantitative reverse transcriptase–polymerase chain reaction, Western blot, and immunohistochemistry were used to quantitate angiopoietin-1 messenger RNA and protein in each sample. Results: Lung specimens from all patients with pulmonary hypertension demonstrated up-regulation of angiopoietin-1 at the messenger RNA level. The degree of angiopoietin-1 transcription was directly proportional to the preoperative pulmonary vascular resistance and medial wall hyperplasia/hypertrophy in each patient. By immunohistochemistry, angiopoietin-1 protein was confined to the media of pulmonary arterioles. Lung biopsy specimens from patients without pulmonary hypertension had no detectable expression of angiopoietin-1 at the messenger RNA or protein level. Conclusion: Angiopoietin-1, a gene responsible for vessel development in the embryonic lung, is up-regulated in the lung parenchyma of patients with pulmonary hypertension. The level of expression of angiopoietin-1 at messenger RNA and protein levels correlates to the severity of pulmonary hypertension in patients with thromboembolic disease and serves as a target for strategies to treat this disease. J Thorac Cardiovasc Surg 2001;122:65-73

Objective: Stenosis of the left main coronary artery is a recognized complicating feature of supravalvular aortic stenosis. We have retrospectively identified three anatomic subtypes of left main coronary obstruction in patients with supravalvular aortic stenosis, each necessitating a distinct surgical approach. Methods: From 1991 to 1998, 9 patients underwent surgical repair of supravalvular aortic stenosis and left main coronary stenosis. Five patients (group 1) had obstruction from near-circumferential thickening of the left main ostium, 2 patients (group 2) had restricted coronary flow due to fusion of an aortic valve leaflet to the supravalvular ridge, and 2 patients (group 3) had diffuse narrowing of the left main coronary artery. Group 1 patients were treated with patch aortoplasty encompassing the left main ostium and supravalvular aortic stenosis. Group 2 patients were treated with excision of the fused leaflet from the aortic wall and patch aortoplasty. Group 3 patients were treated with bypass grafting and aortoplasty. Results: Surgical strategy was determined by coronary angiography and intraoperative assessment of coronary anatomy. There was 1 early death. All surviving patients underwent echocardiography with or without postoperative catheterization. The mean postoperative supravalvular gradient for 7 patients was 8 mm Hg (range 2-15 mm Hg). One patient required reoperation for a residual aortic gradient as a result of aortic arch involvement. No evidence of left main coronary artery stenosis was seen in groups 1 and 2; bypass grafts were patent in group 3 patients at a mean follow-up of 54.8 months. Conclusion: Three subtypes of left main coronary stenosis with supravalvular aortic stenosis are described. Each anatomic type mandates an individual surgical approach. Favorable surgical outcomes are achievable with each category. (J Thorac Cardiovasc Surg 2000;120:1040-6)

Pulmonary thromboendartectomy (PTE) for chronic thromboembolic pulmonary hypertension may be complicated by reperfusion lung injury. This has previously been demonstrated to be neutrophil-mediated. We postulated that blocking selectin-mediated adhesion of neutrophils to the endothelium with Cylexin (CY-1503) would prevent reperfusion lung injury in this patient population. In this double-blind, randomized, placebo-controlled, parallel study, 26 patients received Cylexin the day of surgery and 25 received placebo. Significantly fewer patients in the treated group (31%) compared with the placebo group (60%) developed lung injury (p = 0.036). However, the average number of days of mechanical ventilation, days in the intensive care unit (ICU) and hospital, as well as mortality were not significantly different between the treatment groups. Those with reperfusion lung injury had significantly elevated percent neutrophils, total protein, and soluble P-selectin in bronchoalveolar lavage fluid compared with those without lung injury. We conclude that reperfusion lung injury after PTE is a high-permeability lung injury and its incidence can be reduced by the administration of Cylexin on the day of surgery.

When the myocardium is deprived of blood, a process of ischemia, infarction, and myocardial remodeling is initiated. Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator of vascular endothelial growth factor (VEGF) and is critical for initiating early cellular responses to hypoxia. We investigated the temporal and spatial patterns of expression of the alpha subunit of HIF-1 (HIF-1alpha) and VEGF in specimens of human heart tissue to elucidate the early molecular responses to myocardial hypoxia.Ventricular-biopsy specimens from 37 patients undergoing coronary bypass surgery were collected. The specimens were examined by microscopy for evidence of ischemia, evolving infarction, or a normal histologic appearance. The specimens were also analyzed with the reverse-transcriptase polymerase chain reaction for HIF-1alpha and VEGF messenger RNA (mRNA) expression and by immunohistochemical analysis for the location of the HIF-1alpha and VEGF proteins.HIF-1alpha mRNA was detected in myocardial specimens with pathological evidence of acute ischemia (onset,48 hours before surgery) or early infarction (onset,24 hours before surgery). In contrast, VEGF transcripts were seen in specimens with evidence of acute ischemia or evolving infarction (onset, 24 to 120 hours before surgery). Patients with normal ventricles or evidence of infarction in the distant past had no detectable levels of either VEGF mRNA or HIF-1alpha mRNA. HIF-1alpha immunoreactivity was detected in the nuclei of myocytes and endothelial cells, whereas VEGF immunoreactivity was found in the cytoplasm of endothelial cells lining capillaries and arterioles.An increase in the level of HIF-1alpha is an early response to myocardial ischemia or infarction. This response defines, at a molecular level, one of the first adaptations of human myocardium to a deprivation of blood. HIF-1alpha is a useful temporal marker of acutely jeopardized myocardium.

Chronic thromboembolic pulmonary hypertension is substantially more prevalent than is generally recognized. Most patients affected with this disorder are severely symptomatic, but in the early stages, the diagnosis may be hard to make. Despite an estimated incidence of 2500 to 25,000 cases annually in the United States alone, these patients continue to be misdiagnosed. The condition results in pathologic arterial changes (in both affected and unaffected vessels) due to chronic pulmonary embolism. The disease carries a poor prognosis and a high mortality rate. Medical therapy is limited to anticoagulants, diuretics, vasodilators, and inotropes; however, because the disease is caused by fixed obstructive lesions, no medical treatment is considered curative. In general, medical treatment only transiently relieves symptoms and is ineffective in altering the prognosis. The condition is treated with pulmonary transplantation in a number of centers. Pulmonary endarterectomy has many advantages, however, including a lower operative mortality rate, excellent long-term results, and no need for chronic immunosuppression; it is now widely accepted as the most appropriate therapeutic option. With successive improvements in technique and in the postoperative management of these patients over the past decade, we can now offer this procedure to patients because there is an acceptable incidence of death and excellent anticipation of clinical improvement. Although the procedure is offered to some severely ill patients with poor risk factors, the mortality rate of this procedure at our institution remains in the range of 5% to 7%. Underrecognition remains the primary barrier to care. It is hoped that with more awareness of the efficacy of surgical treatment, more patients will be given the opportunity to be relieved of this disease.

Optimal reduction in pulmonary vascular resistance caused by chronic pulmonary embolism is obtained by bilateral pulmonary thromboendarterectomy with removal of occlusive material in all bronchopulmonary segmental arteries that are partially or completely obstructed. The most effective way to obtain this goal is the use of median sternotomy with cardiopulmonary bypass, deep hypothermia, and intermittent periods of circulatory arrest. During circulatory arrest, thromboendarterectomy is performed by specially designed dissectors that allow simultaneous dissection and removal of blood from the surgical field. The operative mortality rate for pulmonary thromboendarterectomy at the University of California, San Diego, between 1990 and 1998 was 9.2% in 1,049 patients.

Models of transplantation of the heart and lung in the rat have been important in determining the mechanisms of rejection and their treatment. Reviewed here are several important milestones contributing to the current state of the art of clinical heart and lung transplantation.

Patients with sickle cell disease have been reported to have an increased risk of thromboembolism and pulmonary hypertension. Some of these patients may benefit from pulmonary thromboendarterectomy (PTE), a procedure that requires profound hypothermia, cardiopulmonary bypass, and periods of circulatory arrest, factors that may potentially increase the risk of sickling. Two patients with sickle cell disease (sickle-thalassemia [Hb S/beta+] and Hb SS) presented to the Pulmonary Vascular Center of UCSD Medical Center with significant shortness of breath and limitation of daily activities. Both of these patients were found to have surgically accessible chronic thromboembolic disease with pulmonary hypertension. PTE was performed in both patients using exchange transfusion, with avoidance of anemia, hypoxia, and acidosis. A successful outcome with resolution of pulmonary hypertension was achieved in both cases. To our knowledge this is the first report of patients with sickle cell disease who successfully underwent PTE for chronic thromboembolic pulmonary hypertension.

Predictors of survival were evaluated among 74 patients selected for a lung transplantation program. Each patient received the quality of well-being scale, a utility-based outcome measure that gives a score on a continuum ranging from 0 (for dead) to 1.0 (for optimum function), and a measure of depressive symptoms (Beck depression inventory). Over the course of follow-up, 24 patients died (ranging from listing date, 3 to 1, 110 d). Of the 49 patients who received lung transplantation, 13 died. In a multivariate analysis, the most significant predictor of survival was quality of well-being (relative risk = 0.454, p0.05). Lung transplant status, when entered as a time-dependent covariate (a function of how long the patient waited for surgery) was not a significant predictor of survival (relative risk = 0.942, p0.05). Depression was not a significant predictor of survival (relative risk = 0.961, p0.05). We conclude that health-related quality of life is a significant predictor of survival for patients with serious lung diseases.

We developed a dextran-glucose-based extracellular perfusion solution (DGX) that supports limited aerobic metabolism to maintain cellular integrity of an inflated donor lung during long-term ischemia and a storage temperature of 10 degrees C. In a dog model, we compared respiratory and hemodynamic function of orthotopically transplanted left lungs preserved using this method (DGX, group I, n = 6) with function of those preserved with EuroCollins solution (EC) stored at a temperature of 4 degrees C (group II, n = 6). All lungs were inflated with room air and stored for 12 hr. Pulmonary function was monitored for 5 hr of reperfusion. Values expressed below are group means with standard deviation. Statistical significance was calculated using a two-tailed t test. For PO2 (mmHg) (FiO2 = 0.4), group I (EC): control = 193 +/- 8, 30 min p.o. = 87 +/- 20*, 300 min p.o. = 174 +/- 13*; and group II (DGX): control = 217 +/- 28, 30 min p.o. = 184 +/- 46*, 300 min p.o. = 248 +/- 5*. For pulmonary vascular resistance (dynes), group I: control = 389 +/- 22, 30 min p.o. = 1209 +/- 301, 300 min p.o. = 1025 +/- 204*; and group II: control = 401 +/- 31, 30 min p.o. = 522 +/- 129, 300 min p.o. = 458 +/- 137* (*P < 0.05 DGX vs. EC). Gas analysis performed on air samples taken from the ischemic donor lung immediately after harvest and after 12-hr storage showed (calculated as group means) a significant decrease of PO2 and a significant increase of PCO2, respectively. Histology of the lungs after 5 hr of reperfusion showed essentially normal-appearing lungs in the DGX group, whereas lungs in the EC group showed thickening of the intra-alveolar septi, marked cellular infiltration, and accumulation of protein-like material in the alveoli. In this study, preservation with DGX resulted in satisfactory respiratory and hemodynamic function of the transplanted lung even after 12 hr of ischemia. It does not cause an increase of pulmonary vascular resistance as seen after preservation with EC. Data from the intrabronchial air analysis of the donor lung suggest that aerobic metabolism continues even under preservation conditions.

Pulmonary artery tumors are rare and a frequently overlooked cause of pulmonary artery occlusion. The presentation is one of progressive pulmonary dysfunction and right ventricular failure. The diagnosis seldom is made preoperatively. We report 6 cases of primary sarcoma of the pulmonary artery identified at operation, which were treated surgically. Resection with or without adjuvant therapy currently offers the only chance for survival. Emphasis must be placed on earlier identification of these tumors.

Although xenografts can be rejected by humoral or cellular mechanisms, the relative contribution of each remains unknown for any given recipient-donor combination. Moreover, the cells involved in cell-mediated events, as well as the mechanisms by which these cells recognize xenoantigens, remain controversial. It would be advantageous to have a model in which either, as well as various parts of either, could be investigated in the absence of the other, as well as in the absence of events taking place during organ engraftment. In the present report, rejection of rat skin xenografts was monitored after adoptive transfer of unique populations of highly purified lymphoid cells to previously transplanted immunodeficient C.B17 Scid/Scid mice. Purified T cells and, unexpectedly, purified CD4+ T cells alone and purified CD8+ T cells alone rejected rat xenografts. Alternatives that may explain these findings are discussed.

Background We sought to determine the efficacy and safety of perioperative treatment with methylprednisolone on the development of lung injury after pulmonary thromboendarterectomy. Methods This was a randomized, prospective, double-blind, placebo-controlled study of 98 adult patients with chronic thromboembolic pulmonary hypertension who were undergoing pulmonary thromboendarterectomy at a single institution. The patients received either placebo (n = 47) or methylprednisolone (n = 51) (30 mg/kg in the cardiopulmonary bypass prime, 500 mg IV bolus following the final circulatory arrest, and 250 mg IV bolus 36 h after surgery). The primary end point was the presence of lung injury as determined by two independent, blinded physicians using prospectively defined criteria. The secondary end points included ventilator-free, ICU-free, and hospital-free days and selected levels of cytokines in the blood and in BAL fluid. Results The incidence of lung injury was similar in both treatment groups (45% placebo, 41% steroid; P = .72). There were no statistical differences in the secondary clinical end points between treatment groups. Treatment with methylprednisolone, compared with placebo, was associated with a statistically significant reduction in plasma IL-6 and IL-8, a significant increase in plasma IL-10, and a significant reduction in postoperative IL-1ra and IL-6, but not IL-8 in BAL fluid obtained 1 day after surgery. Conclusions Perioperative methylprednisolone does not reduce the incidence of lung injury following pulmonary thromboendarterectomy surgery despite having an antiinflammatory effect on plasma and lavage cytokine levels.

Chronic thromboembolic pulmonary hypertension results from repeated or unresolved emboli in the pulmonary circulation, and occurs in 3–4% of patients suffering acute pulmonary embolism. Pulmonary thromboendarterectomy is an endarterectomy of the entire pulmonary vascular tree, and is the preferred treatment for chronic thromboembolic pulmonary ­hypertension. The most common presenting symptom of chronic thromboembolic pulmonary hypertension is exertional dyspnea. The diagnosis is confirmed with echocardiography, right-sided cardiac catheterization, and pulmonary angiogram. Patients with chronic thromboembolic pulmonary hypertension, when left untreated, develop a small-vessel vasculopathy that mimics idiopathic pulmonary hypertension. Monitoring includes femoral and radial arterial ­pressures, processed EEG, pulmonary artery pressures, and transesophageal echocardiography. Anesthetic induction and maintenance are tailored to hemodynamic stability, right ventricular coronary perfusion pressure, and right ventricular support. Factors that lead to increased pulmonary vascular resistance, such as light anesthesia, acidosis, and hypoxemia, should be avoided. Pulmonary vasodilators such as nitric oxide and milrinone are generally ineffective in chronic thromboembolic pulmonary hypertension, but should be available for management of patients with small-vessel vasculopathy.