Lower Pulmonary Artery Pressure Research Articles

Adenosine A 2A receptor activation reduces inflammation and preserves pulmonary function in an in vivo model of lung transplantation

Reperfusion injury continues to significantly affect patients undergoing lung transplantation. Isolated lung models have demonstrated that adenosine A 2A receptor activation preserves function while decreasing inflammation. We hypothesized that adenosine A 2A receptor activation by ATL-146e during the initial reperfusion period preserves pulmonary function and attenuates inflammation in a porcine model of lung transplantation. Mature pig lungs preserved with Viaspan (Barr Laboratories, Pomona, NY) underwent 6 hours of cold ischemia before transplantation and 4 hours of reperfusion. Animals were treated with (ATL group, n = 7) and without (IR group, n = 7) ATL-146e (0.05 microg kg -1 . min -1 ATL-146e administered intravenously for 3 hours). With occlusion of the opposite pulmonary artery, the animal was maintained for the final 30 minutes on the allograft alone. Recipient lung physiology was monitored before tissue evaluation of pulmonary edema (wet-to-dry weight ratio), myeloperoxidase assay, and tissue tumor necrosis factor alpha by means of enzyme-linked immunosorbent assay. When the ATL group was compared with the IR group, the ATL group had better partial pressure of carbon dioxide (43.8 +/- 4.1 vs 68.9 +/- 6.3 mm Hg, P < .01) and partial pressure of oxygen (272.3 +/- 132.7 vs 100.1 +/- 21.4 mm Hg, P < .01). ATL-146e-treated animals exhibited lower pulmonary artery pressures (33.6 +/- 2.1 vs 47.9 +/- 3.5 mm Hg, P < .01) and mean airway pressures (16.25 +/- 0.08 vs 16.64 +/- 0.15 mm Hg, P = .04). ATL-146e-treated lungs had lower wet-to-dry ratios (5.9 +/- 0.39 vs 7.3 +/- 0.38, P < .02), lower myeloperoxidase levels (2.9 x 10 -5 +/- 1.2 x 10 -5 vs 1.3 x 10 -4 +/- 4.0 x 10 -5 DeltaOD mg -1 . min -1 , P = .03), and a trend toward decreased lung tumor necrosis factor alpha levels (57 +/- 12 vs 96 +/- 15 pg/mL, P = .06). The ATL group demonstrated significantly less inflammation on histology. Adenosine A 2A activation during early reperfusion attenuated lung inflammation and preserved pulmonary function in this model of lung transplantation. ATL-146e and similar compounds could play a significant role in improving outcomes of pulmonary transplantation.

Pulmonary hypertensive responses of broilers to bacterial lipopolysaccharide (LPS): evaluation of LPS source and dose, and impact of pre-existing pulmonary hypertension and cellulose micro-particle selection

Previous studies demonstrated that bacterial lipopolysaccharide (LPS, endotoxin) triggers pulmonary vasoconstriction leading to pulmonary hypertension (PHS, ascites) in broilers. The lungs of broilers are constantly challenged with LPS that can trigger pulmonary vasoconstriction. Among broilers from a single genetic line, some individuals respond to LPS with large increases in pulmonary arterial pressure (PAP), whereas others fail to exhibit any response to the same supramaximal dose of LPS. In the present study we evaluated the impact of a variety of factors on the magnitude of the PAP response of male broilers to LPS, including: (1) the role of the initial PAP (low vs. high initial PAP); (2) the source of the LPS (Salmonella typhimurium vs. Escherichia coli); (3) the dose of LPS (0.02, 0.1, and 0.5 mg/kg of BW); and (4) the role of micro-particle selection for improved pulmonary vascular capacity (cellulose survivors vs. saline-injected controls). Broilers in the low initial PAP group (21 +/- 0.34 mmHg, mean +/- SEM) did not differ in their pulmonary hypertensive response to LPS compared with broilers in the high initial PAP group (29 +/- 0.55 mmHg, mean +/- SEM). Lipopolysaccharide from S. typhimurium elicited pulmonary hypertensive responses qualitatively similar to those elicited by E. coli LPS. A detailed evaluation revealed that an LPS dose of 0.1 mg/kg of BW elicits a maximal pulmonary hypertensive response in male broilers, and broilers selected by micro-particle injection for a robust pulmonary vascular capacity did not differ in their pulmonary hypertensive response to LPS compared with unselected broilers. This research confirms that the variable pulmonary hypertensive responses among broilers cannot be attributed to the source or dosage of LPS, or to differences in the baseline pulmonary arterial pressure or micro-particle selection before injecting LPS. These findings are consistent with the hypothesis that innate rather than acquired variability may influence the profile of chemical mediators released during the inflammatory cascade.

Endothelin-1 Receptor Antagonist BQ123 Prevents Pulmonary Artery Hypertension Induced by Low Ambient Temperature in Broilers

Evidence has indicated that endothelin-1 is related to the pathogenesis of hypertension. To characterize the role of endothelin-1 (ET-1) in the development of pulmonary hypertension syndrome in broilers, the blockade effect of ETA receptor (ET(A)) antagonist, BQ123, on blood pressure in experimental models of pulmonary hypertension was examined. Birds were locally anesthetized and instrumented with venous catheters for pulmonary arterial pressure (PAP) and right ventricular pressure (RVP), followed by packed cell volume (PCV) and Ascites heart index (AHI) measured, after exposed to low ambient temperature for 7 or 14 d. In treated groups, BQ123 (0.4 or 2.0 microg each time, 2 times a day), administered in abdominal cavities for 7 or 14 d during birds kept in low ambient temperature, prevented both PAP and RVP increasing, especially the high dose BQ123 lowered PAP and RVP to normotensive levels as that in control under normal temperature, whereas significant increases (p<0.05) were found in the two parameters of broilers in both untreated and saline treated group under low ambient temperature compared with those of birds in control. Furthermore, there was also a reduction in low ambient temperature-induced right ventricular hypertrophy in the groups administered BQ123. The preventive effect of BQ123 suggests that ET-1 is associated with the development of broilers' pulmonary hypertension, which leads to the development of ascites, and BQ123 can prevent the occurrence of pulmonary hypertension.

High-Altitude Pulmonary Edema in Children With Underlying Cardiopulmonary Disorders and Pulmonary Hypertension Living at Altitude

Pulmonary hypertension has not been described as a predisposing risk factor for high-altitude pulmonary edema (HAPE) in children. Previous studies have shown an association of HAPE with abnormally increased pulmonary vasoreactivity to hypoxia but generally normal pulmonary artery pressure (PAP) after recovery. To describe HAPE of relatively rapid onset and its management in a series of children residing at moderate to high altitudes, all of whom had underlying pulmonary hypertension. From 1997 to 2003, 30 children came to our center with high-altitude illness. Of these, 10 children (aged 4-18 years; male-female ratio, 8:2) living at moderate to high altitudes (1610-3050 m) underwent cardiac catheterization after recovery from HAPE, and all were found to have chronic pulmonary hypertension (mean PAP, 38 +/- 9 mm Hg; pulmonary vascular resistance, 8.6 +/- 2.8 U x m2). Increases in PAP and pulmonary vascular resistance to hypoxia (16% oxygen) suggest that these children have a reactive pulmonary pressor response and hence are susceptible to HAPE. Six of the 10 patients had predisposing cardiopulmonary abnormalities, and 5 of these 6 patients did not receive a diagnosis prior to the onset of HAPE. Long-term treatment with calcium channel blockers, bosentan, sildenafil citrate, and/or oxygen lowered PAP, improved symptoms, and prevented the recurrence of HAPE. Children living at altitude who develop HAPE should undergo screening for diagnosis of underlying cardiopulmonary abnormalities including pulmonary hypertension.

Pulmonary preservation effect of nitroglycerine in isolated rat lung reperfusion model

Purpose Though nitric oxide has many favorable protective effects on donor lungs, it may also have cytotoxic side effects. In this regard, we investigated whether administration of nitroglycerine, a nitric oxide donor, could minimize ischemia-reperfusion injury in an isolated rat lung reperfusion model. Materials and methods Thirty-five Sprague-Dawley rats were used for this experiment. The nitroglycerine (NTG) group ( n = 18) received the drug intravenously and the 17 control group hosts were treated with the same amount of normal saline. The heart-lung block was retrieved, weighed, and maintained in University of Wisconsin solution for 24 hours at 10°C. Reperfusion was performed using human blood diluted in Krebs-Hensleit solution for 60 minutes. Peak inspiratory pressure, pulmonary artery pressure, and blood gas analysis were performed. After 60 minutes of reperfusion, the amount of protein in bronchoalveolar lavage (BAL) fluid and the myeloperoxidase (MPO) activity in the lung were measured. Results There were no major statistical differences between the two groups in peak inspiratory pressure and pulmonary artery pressure, but the NTG group maintained lower pulmonary artery pressure during the whole period of reperfusion. Oxygen tension in the NTG group was significantly higher, whereas there were no differences in carbon dioxide tension, BAL fluid, protein, or MPO activity. Conclusion Administration of NTG before donor lung preservation resulted in better lung protection, a possible strategy for clinical application.

Higher not lower systolic blood pressure is independently associated with improved survival in heart failure

Background: Increase in systolic blood pressure (SBP) is independently and incrementally associated with risk of developing of heart failure (HF). The relationship between SBP and prognosis in patients with pre-existing HF has not been systematically investigated. Methods: This study analyzed 1879 systolic HF patients (age 52±13, LVEF 22±7, 60% NYHA IV) referred to a single university center for HF management and heart transplant evaluation between 1983 and 2003. Blood pressure and other hemodynamic variables were prospectively recorded after implementation of HF medical therapy. Patients were analyzed by quartiles of SBP. Results: Patients with higher SBP were older, had significantly higher left ventricular ejection fraction (LVEF) and cardiac index, and lower pulmonary artery and pulmonary capillary wedge pressure (PCW). The higher SBP quartiles were associated with higher sodium, hemoglobin, and total cholesterol levels, history of hypertension and diabetes, and therapy with ACE inhibitor and statins. SBP quartiles were similar in terms of gender, coronary artery disease, BMI, beta-blocker therapy, and levels of TnI, BNP, and Cr. Higher quartiles of SBP were associated with significantly improved 1-yr survival (Figure). The hazard ratio for Q1 (SBP<92 mmHg) relative to Q4 (SBP>112 mmHg) was 2.48 (95% CI 1.79–3.43). After adjustment for sex, age, coronary artery disease, LVEF, ACE inhibitor use, PCW, and cardiac index, relative risk of death at 1 year per each 10 mmHg increase was 0.80 (p<0.0001). Conclusions: Higher not lower SBP is associated with improved HF survival independent of ventricular function, invasive hemodynamic parameters, and other prognostic factors. The optimal, target SBP for HF patients requires further study.

Fistulous connection between internal mammary graft and pulmonary vasculature after coronary artery bypass grafting: a rare cause of continuous murmur

A 58-year-old male who had undergone coronary artery bypass grafting (CABG) using left internal mammary artery and a sequential saphenous vein graft 2 years ago presented with new onset angina. His initial physical examination revealed an unexpected continuous murmur over the left sternal border, and two-dimensional echocardiography has failed to identy the cause. Cardiac catheterization then performed and revealed patent left internal mammary artery and saphenous vein grafts. Besides, selective injection of the left internal mammary artery graft also showed a fistula formation between left internal mammary artery graft and pulmonary vasculature of the left upper lobe. He was managed conservatively because of the severely diseased left anterior descending artery distal to internal mammary artery anastomosis and low pulmonary artery pressure. The development of fistulous connection between internal mammary artery and pulmonary vasculature is an extremely rare complication following CABG. Patients with such fistulae usually present with chest pain due to coronary steal syndrome. A new heart sound, especially a continuous murmur, may be detected during physical examination. Surgical correction is indicated in the event of refractory angina, growing fistula causing heart failure or endarteritis. Otherwise, a conservative approach with instruction of the patient for prophylactic precautions of subacute bacterial endocarditis may be recommended for asymptomatic patients.

Cardiothoracic transplantation for congenital heart disease in teenagers and adults

Since 1980, 194 patients aged between 10–52 years have undergone cardiothoracic transplantation for congenital heart disease (CHD) at our institution. Sixty underwent heart transplantation, 129 heart-lung transplantation, and 5 bilateral lung transplantation with repair of the underlying defect. This represented 4%, 27% and 3 % of all patients undergoing heart, heart-lung and bilateral lung transplantation respectively. Patients undergoing heart transplantation either had complex abnormalities with low pulmonary artery pressure (n = 37) or myocardial failure after previous reparative operations (n = 23). Fourteen patients undergoing heart-lung transplantation had complex pulmonary atresia and 115 had CHD with pulmonary hypertension. The type of operation has been modified during the period under review to take account of the increasing scarcity of donor organs. Operative techniques are adapted according to the complexity of the underlying anatomy. In-hospital mortality was 20/60 (33%) for hearts, 41/115 (36%) in heart-lung transplantation for CHD and pulmonary hypertension and 12/14 (85%) for complex pulmonary atresia. There were no deaths in the five patients undergoing bilateral lung transplantation and repair. Major risk factors for early death in the heart-lung transplant group were complex pulmonary atresia, previous lateral thoracotomy and age greater than 35 years at transplant. Actuarial survival in the heart transplants was 60%, 54% and 46% at 1 year, 5 years, and 10 years respectively and 61%, 45% and 36% at 1 year, 5 years and 10 years respectively for heart-lung transplant patients with CHD and pulmonary hypertension. It is concluded that risk of early death is greater in patients with complex CHD undergoing heart transplantation than in patients with acquired heart disease. Thereafter survival in patients with CHD is similar to other patients undergoing heart or heart-lung transplantation.

Therapeutic Treatments of Phosgene-Induced Lung Injury

A series of studies was performed to address treatment against the former chemical warfare edemagenic gas phosgene. Both in situ and in vivo models were used to assess the efficacy of postexposure treatment of phosgene-induced lung injury using clinically existing drugs. The degree of efficacy was judged by examining treatment effects on pulmonary edema formation (PEF) as measured by wet/dry weight (WW/DW) ratios, real-time (in situ) lung weight gain (LWG), survival rates (SR), odds ratios, and glutathione (GSH) redox states. Drugs included N-acetylcysteine (NAC), ibuprofen (IBU), aminophylline (AMIN), and isoproterenol (ISO). Using the in situ isolated perfused rabbit lung model (IPRLM), intratracheal (IT) NAC (40 mg/kg bolus) delivered 45–60 min after phosgene exposure (650 mg/m3) for10 min lowered pulmonary artery pressure, LWG, leukotrienes (LT) C4/D4/E4, lipid peroxidation, and oxidized GSH. We concluded that NAC protected against phosgene-induced lung injury by acting as an antioxidant by maintaining protective levels of GSH, reducing both lipid peroxidation and production of arachidonic acid metabolites. Also in IPRLM, administration of AMIN (30 mg/kg) 80–90 min after phosgene exposure significantly reduced lipid peroxidation and perfusate LTC4/D4/E4, reduced LWG, and prevented phosgene-induced decreases in lung tissue cAMP. These data suggest that protective mechanisms observed with AMIN involve decreased LTC4/D4/E4 mediated pulmonary capillary permeability and attenuated lipid peroxidation. Direct antipermeability effects of AMIN-induced upregulation of cAMP on cellular contraction may also be important in protection against phosgene-induced lung injury. Posttreatment with ISO in the IPRLM by either combined intravascular (iv; infused into pulmonary artery at 24 μg/min infused) + IT (24 μ g bolus) or IT route alone 50–60 min after phosgene exposure significantly lowered pulmonary artery pressure, tracheal pressure, and LWG. ISO treatment significantly enhanced GSH products or maintained protective levels when compared with results from phosgene-exposed only rabbits. These data suggest that protective mechanisms for ISO involve reduction in vascular pressure, decreased LTC4/D4/E4-mediated pulmonary capillary permeability, and favorably maintained lung tissue GSH redox states. For in vivo male mouse (CD-1, 25–30 g) studies IBU was administered ip within 20 min after a lethal dose of phosgene (32 mg/m3 for 20 min) at 0 (saline), 3, 9, or 15 mg/mouse. Five hours later, a second IBU injection was given but at half the original doses (0, 1.5, 4.5, and 7.5 mg/mouse); therefore, these treatment groups are now referred to as the 0/0, 3/1.5, 9/4.5, and 15/7.5 mg IBU/mouse groups. SRs and odds ratios were calculated for each dose at 12 and 24 h. The 12-h survival was 63% for 9/4.5 mg IBU and 82% for the 15/7.5 mg IBU groups, compared with 25% for saline-treated phosgene-exposed mice. At 24 h, those survival rates were reduced to 19%, 19%, and 6%, respectively. In the 15/7.5 mg IBU group, lung WW/DW ratios were significantly lower than in saline-treated mice at 12 h. Lipid peroxidation was lower only for the 9/4.5 mg IBU dose; however, nonprotein sulfhydryls (a measure of GSH) were greater across all IBU doses. The odds ratio was 5 for the 9/4.5 IBU group at 12 h and 13 for the 15/7.5 mg IBU group, compared with 3.5 for both groups at 24 h. IBU posttreatment increased the survival of mice at 12 h by reducing PEF, lipid peroxidation, and GSH depletion. In conclusion, effective treatment of phosgene-induced lung injury involves early postexposure intervention that could reduce free radical species responsible for lipid peroxidation, correct the imbalance in the GSH redox state, and prevent the release of biological mediators such as leukotrienes, which are accountable for increased permeability.

Angiographic and hemodynamic predictors for successful outcome of transcatheter occlusion of patent ductus arteriosus in infants less than 8 kilograms.

Transcatheter occlusion of patent ductus arteriosus (PDA) using Gianturco coils (GCs) has been performed for the past decade. However, little has been written regarding anatomical and hemodynamic predictors for successful occlusion of the PDA in infants. This report is to evaluate the outcome of transcatheter occlusion of PDA in symptomatic infants less than 8 kg and to assess predictors of successful occlusion. Retrospective review of catheterization charts and cineangiograms of 42 symptomatic infants who underwent cardiac catheterization for attempted transcatheter occlusion of their PDA was conducted. The hemodynamic and angiographic data evaluated included the length/diameter (L/D) ratio, defined as the length divided by the narrowest diameter of the ductus arteriosus, and preocclusion pulmonary artery pressures. Thirty-one out of 42 patients (74%) had successful occlusion. Twenty-nine out of 42 infants had an L/D ratio > 3. Of these, 26 (90%) had successful occlusion of their PDA. Thirteen out of 42 patients had an L/D ratio < or = 3. Of these, 8 (62%) had unsuccessful occlusion. Complications encountered were transient loss of femoral arterial pulse (n = 6), coil embolization (n = 5), hemolysis (n = 2), and mild left pulmonary artery obstruction (n = 2). No permanent loss of femoral arterial pulse was noted. These complications resulted in no mortality and minimal morbidity. The L/D ratio was the strongest predictor of successful outcome, with an L/D ratio greater than 3.0 being more amenable to transcatheter occlusion (odds ratio of 4.6). Other predictors for success included lower preocclusion systolic, diastolic, and mean pulmonary artery pressure and smaller ductal diameter. Our conclusion was that infants less than 8 kg with an L/D ratio > 3.0 can safely and successfully undergo transcatheter occlusion of their PDA using transcatheter coils.

Association of intraoperative hypotension and pulmonary hypertension with adverse outcomes after orthotopic liver transplantation

Background Various preoperative, surgical, and postoperative markers of impaired outcome after orthotopic liver transplantation have been reported, but the influence of intraoperative hemodynamic aberrations has not been thoroughly investigated. Setting University Hospital. Study design Retrospective cohort analysis. Methods The authors retrospectively reviewed computerized anesthesia records to determine associations between occurrences of abnormally low or high mean pulmonary artery pressure (MPAP), cardiac output, heart rate, systolic arterial pressure, diastolic arterial pressure, and mean arterial pressure (MAP) with negative surgical outcome. Negative surgical outcome was defined as poor early graft function, primary graft nonfunction, or death attributable to hemodynamic causes. Results Of 789 patients, 142 (18.0%) had negative surgical outcome. Controlling for the influence of United Network for Organ Sharing (UNOS) status > 1, long operation time, cold donor organ ischemia time, and donor age, the only hemodynamic parameters that were independently associated with negative surgical outcome were MAP < 40 mmHg at least once during the procedure (odds ratio [OR] 2.39, p = 0.0016) and MPAP > 40 mmHg at least 3 times during the procedure (OR 2.2, p = 0.035). The occurrence of MAP < 40 mmHg was temporally associated with donor graft reperfusion. Hepatic artery thromboses were not associated with hemodynamic aberrations. Conclusions Hemodynamic events are independently associated with adverse outcomes after orthotopic liver transplantation.

Successful Fontan procedure for asplenia with pulmonary atresia and major aortopulmonary collateral arteries

Asplenia with a single ventricle and major aortopulmonary collateral arteries (MAPCAs) is a rare congenital cardiac anomaly. In this patient group achievement of the Fontan procedure depends on ample rehabilitation of the pulmonary arteries to secure sufficient pulmonary vascular beds and the prevention of progressive pulmonary vascular obstructive disease. Here we report a successful 1-stage bilateral unifocalization of the pulmonary blood supply followed by a staged Fontan procedure in a patient with a univentricular heart and MAPCAs. Clinical Summary The patient was given a diagnosis of asplenia, univentricular heart (right ventricular type), common atrioventricular orifice, pulmonary atresia, bilateral superior vena cavas, total anomalous pulmonary venous connection (intracardiac type), and MAPCAs on the basis of echocardiography and cardiac catheterization. His neonatal aortography showed a small central pulmonary artery (3 mm in diameter) and bilateral multiple MAPCAs (Figure 1, A). The patient’s arterial oxygen saturation (Sa O2) was around 80%, and his pulmonary/systemic blood flow ratio (Qp/Qs) was 1.6 with stable hemodynamics. Subsequent cardiac catheterization at 6 month of age revealed a good-sized central pulmonary artery (Figure 1, B) and 5 large MAPCAs. His SaO2 was approximately 87%, and his Qp/Qs had increased to 3.7. At 1 year of age, he underwent a primary complete unifocalization of his bilateral pulmonary arteries, total anomalous pulmonary venous connection repair for progressive pulmonary venous obstruction (Figure 2), and a left modified Blalock-Taussig shunt (polytetrafluoroethylene [PTFE],* 5 mm). The postoperative course was uneventful except for transient bilateral phrenic nerve palsy. He subsequently did well, while becoming increasingly cyanotic. A catheterization at 2 years of age revealed peripheral pulmonary stenosis, low pulmonary vascular resistance (1.2 Wood units), and normal pulmonary blood flow (Qp/Qs 1.0). The patient then underwent a bilateral bidirectional cavopulmonary shunt and take down of his left modified Blalock-Taussig shunt without cardiopulmonary bypass. This postoperative course was also uneventful, with an SaO2 of 85% and superior vena caval pressure of 10 mm Hg. Eight months after the bilateral bidirectional cavopulmonary shunt, a cardiac catheterization was performed, demonstrating good-shaped pulmonary arteries (Figure 3), low pulmonary vascular resistance (1.4 R*U), low pulmonary artery pressure (mean, 10 mm Hg), and low pulmonary blood flow (Qp/Qs 0.8). Two weeks before definitive surgical intervention, he underwent balloon angioplasty for peripheral pulmonary stenoses and coil embolization of aortopulmonary collateral arteries. At 3 years of age, a fenestrated modified Fontan procedure was performed. An 18-mm PTFE tube graft with a 4-mm PTFE tube graft anastomosed in end-to-side fashion was used for the extracardiac total cavopulmonary connection. The 4-mm PTFE tube graft was anastomosed to the common atrium as a fenestration. The patient was hemodynamically stable intraoperatively, with superior vena caval and inferior vena caval pressures of 11 mm Hg, a common atrial pressure of 4 mm Hg, and an SaO2 of 94%. The patient returned to the cardiovascular intensive care unit in stable condition and was extubated 3 hours after the operation. His postoperative course was uneventful. He was transferred to the general ward on the first postoperative day and discharged home 13 days later without any complications. Three months after the Fontan procedure, another cardiac catheterization was performed, demonstrating a spontaneously occluded tube graft fenestration, an Sa O2 of 96%, low pulmonary artery pressure (mean, 12 mm Hg), and excellent Fontan circulation.

Is cardiac catheterization a prerequisite in all patients undergoing bidirectional cavopulmonary anastomosis?

Traditionally, all patients undergo cardiac catheterization before bidirectional cavopulmonary anastomosis (BCPA). The purpose of this study was to determine if preoperative catheterization is necessary when echocardiographic parameters appear favorable. A retrospective review was performed of all patients who underwent BCPA (n = 142) between February 1996 and May 2001. Echocardiographic criteria defining a favorable BCPA candidate included good ventricular function, moderate or less atrioventricular and semilunar valve regurgitation, absence of ventricular outflow tract obstruction, normal proximal branch pulmonary artery (PA) size, and low PA pressures estimated by PA band gradient or systemic PA shunt velocity. The median age at operation was 7 months (range: 2-11) and weight was 6.2 kg (range: 2.7-7.1). There were 73 unfavorable candidates. Patients with hypoplastic left heart syndrome (n = 23) and pulmonary atresia with intact septum (n = 15) predominated among the unfavorable group. All patients were catheterized. This provided additional information on PA pressures in 3 patients in the favorable group but did not defer operation or influence outcome (no mortality, prolonged pleural drainage, or longer intensive care department stay). All 3 patients are alive at a mean follow-up of 51 months. The 30-day mortality was 2% (4 of 151 patients), all in the unfavorable group. Overall, 20 patients (13%) required arterioplasty of PAs at the time of BCPA. BCPA can be performed with a low risk of morbidity and mortality in a wide range of patients. By using commonly acquired echocardiographic parameters, a low-risk subgroup of patients can be identified who can safely avoid preoperative cardiac catheterization.

Low molecular weight heparin and unfractionated heparin are both effective at accelerating pulmonary vascular maturation in neonatal rabbits.

Creation of a bi-directional cavopulmonary shunt after the Norwood procedure for hypoplastic left heart syndrome is delayed to allow pulmonary vascular resistance to fall with maturation of the pulmonary vascular bed. We hypothesized that unfractionated heparin (UFH) and low molecular weight heparin (LMWH), which promote angiogenesis and inhibit smooth muscle cell growth, could accelerate this process. Fifty-six newborn rabbits were randomly selected to receive UFH 225U/kg (n=12), LMWH 1 mg/kg (n=14), LMWH 10 mg/kg (n=16), or saline (n=14) by subcutaneous injection every 12 hours for 14 days. Treatment with heparin reduced mean pulmonary artery (PA) pressure by 12% to 16% relative to controls [9.0+/-0.2 (UFH), 9.4+/-0.1 (LMWH 1 mg/kg), 9.2+/-0.2 (LMWH 10 mg/kg) versus 10.7+/-0.2 mm Hg (saline), P=0.0001]. Lower PA pressures were associated with reduced alveolar:arterial ratio consistent with enhanced pulmonary angiogenesis in heparin treated animals [8+/-1 (UFH), 13+/-2 (LMWH 1 mg/kg), 12+/-2 (LMWH 10 mg/kg) versus 23+/-5 (saline), P<0.03]. Reduced PA medial wall thickness and muscularization, two additional features of pulmonary vascular maturation, were also more evident in heparin treated animals. Mean PA pressures in 14-day-old rabbits treated with heparin were lower than those measured in control rabbits less than 7 weeks of age suggesting that heparin shortens the pulmonary vascular maturation process by over 60%. These results indicate that both UFH and LMWH are effective at accelerating pulmonary vascular maturation in newborn rabbits. This raises the possibility that administration of heparin to children after the Norwood procedure might allow for earlier conversion to a bi-directional cavopulmonary shunt.

Effect of a surgical aortocaval fistula on monocrotaline-induced pulmonary hypertension.

Increased pulmonary blood flow is believed to contribute to the development of pulmonary hypertension. We investigated the effect of overcirculation via an aortocaval fistula, on the development of monocrotaline-induced pulmonary hypertension in rats. Monocrotaline was administered 1 wk after the creation of an aortocaval fistula. Randomized, controlled study. Research laboratory of an academic institution. Male Sprague-Dawley rats. Overcirculation was induced by pneumonectomy and by surgical creation of aortocaval fistula. Pulmonary artery hypertension was induced by administration of monocrotaline. Aortic blood flow, Pao(2), and pulmonary arterial pressure were measured 4 wks later. A blinded investigator quantified pulmonary arterial neointimal formation in small pulmonary arteries. Compared with animals that received monocrotaline and/or underwent pneumonectomy but did not undergo aortocaval fistula, the presence of a surgical aortocaval fistula was associated with increased aortic blood flow (p <.001), increased Pao(2) (p <.001), and lower mean pulmonary arterial pressure (p <.001). In addition, rats with aortocaval fistula had less pulmonary arterial neointimal formation than matched animals without an aortocaval fistula (p =.034). The presence of a surgical aortocaval fistula attenuates, rather than worsens, the development of monocrotaline-induced pulmonary hypertension in rats.

Predictors of Severe Right Ventricular Failure After Implantable Left Ventricular Assist Device Insertion: Analysis of 245 Patients

Insertion of an implantable left ventricular assist device (LVAD) complicated by early right ventricular (RV) failure has a poor prognosis and is largely unpredictable. Prediction of RV failure after LVAD placement would lead to more precise patient selection and optimal device selection. We reviewed data from 245 patients (mean age, 54+/-11 years; 85% male) with 189 HeartMate (77%) and 56 Novacor (23%) LVADs. Ischemic cardiomyopathy predominated (65%), and 29% had dilated cardiomyopathy. Overall, RV assist device (RVAD) support was required after LVAD insertion for 23 patients (9%). We compared clinical and hemodynamic parameters before LVAD insertion between RVAD (n=23) and No-RVAD patients (n=222) to determine preoperative risk factors for severe RV failure. By univariate analysis, female gender, small body surface area, nonischemic etiology, preoperative mechanical ventilation, circulatory support before LVAD insertion, low mean and diastolic pulmonary artery pressures (PAPs), low RV stroke work (RVSW), and low RVSW index (RVSWI) were significantly associated with RVAD use. Elevated PAP and pulmonary vascular resistance were not risk factors. Risk factors by multivariable logistic regression were preoperative circulatory support (odds ratio [OR], 5.3), female gender (OR, 4.5), and nonischemic etiology (OR, 3.3). The need for circulatory support, female gender, and nonischemic etiology were the most significant predictors for RVAD use after LVAD insertion. Regarding hemodynamics, low PAP and low RVSWI, reflecting low RV contractility, were important parameters. This information may lead to better patient selection for isolated LVAD implantation.

Histomorphometric analysis of pulmonary vessels in single ventricle for better selection of patients for the Fontan operation

Objective: In cases of single-ventricle physiology, the Fontan procedure often fails even when the usual selection criteria are strictly respected. We analyzed specimens from intraoperative open lung biopsies performed on 40 patients with single-ventricle physiology who were considered to be good candidates for the Fontan procedure. Histomorphometric study was performed to determine histologic factors predictive of failure of the Fontan procedure. Methods: Histomorphometric studies were performed on samples from 40 patients aged 6 months to 23 years with single-ventricle physiology, either tricuspid atresia (n = 14) or univentricular heart (n = 26). The preoperative pulmonary arterial pressure was 18 mm Hg or less in 35 cases and greater than 18 mm Hg in 5 cases. Eighteen patients underwent total cavopulmonary connection, 16 patients underwent partial cavopulmonary connection, and 6 underwent a palliative procedure, as determined according to clinical and hemodynamic findings. Results: Lung biopsy specimens from all 5 patients with pulmonary arterial pressure greater than 18 mm Hg appeared abnormal, whereas they appeared abnormal only 51% of the time in the low pulmonary arterial pressure group. The most frequent histologic abnormality observed was extension of smooth muscle cells in the wall of distal intra-acinar pulmonary arteries. Of the 18 patients who underwent the Fontan procedure, 9 had normal distal pulmonary arteries and good surgical results (except 1 with the Fontan circulation taken down for an anatomic reason). The remaining 9 had thick-walled distal intra-acinar pulmonary arteries with poor results of the Fontan procedure, and 6 died. The mean percentage wall thickness of small intra-acinar pulmonary arteries was significantly greater among the patients with bad results than among those with good results of the procedure (P < .01). Conclusions: Lung biopsy specimens were abnormal in 51% of patients with low pulmonary arterial pressure, there was no relationship between preoperative pulmonary arterial pressure and outcome, and extension of muscle in peripheral arteries was always present in cases of failure of the Fontan procedure. Histomorphometric study is therefore a useful adjunct to the usual selection criteria for surgical decision making in cases of single-ventricle physiology.

Cierre quirúrgico de la comunicación interauricular antes o después de los 25 años de edad. Comparación con la evolución natural en pacientes no operados

Surgical closure of an atrial septal defect (ASD) before the age of 25 years has been demonstrated to reduce complications during adulthood. However, the outcome for patients operated after the age of 25 is still debated. In a retrospective study we examined the outcome of early and late surgical repair of ASD in adults, as compared with the natural evolution of unoperated patients. The study population was 280 patients (mean age 40 18 years) with non-restrictive ASD: 102 patients (group 1) underwent surgery before the age of 25 years, 90 patients (group 2) underwent surgery after the age of 25 years, and 88 unoperated patients were older than 25 years at the time of study (group 3). The variables analyzed were left ventricular systolic function, left atrial dimensions, systolic pulmonary pressure, right ventricular dimensions, the degree of mitral and tricuspid regurgitation, and the prevalence of late atrial fibrillation. Left ventricular systolic function and the degree of mitral regurgitation were not statistically different between groups. Compared with the patients in group 2, the patients in group 1 had a significantly lower systolic pulmonary arterial pressure (p < 0.001) and less dilated right ventricle (p < 0.001) and left atrium (p < 0.001). The degree of tricuspid regurgitation (p < 0.001) and prevalence of atrial fibrillation (p < 0.001) were significantly higher in the patients of group 2. Compared with group 3, the patients in group 2 had a significantly lower systolic pulmonary arterial pressure (p < 0.001) and less dilated right ventricle (p < 0.001). However, the left atrial dimensions, degree of tricuspid regurgitation, and prevalence of atrial fibrillation did not differ in a statistically significant way between the two groups. Surgical repair of an atrial septal defect in patients over 25 years of age does not fully prevent hemodynamic deterioration and the development of atrial arrhythmias. Therefore it seems that the surgical closure of ASD before adulthood should be strongly recommended.

Airway pressure release ventilation in the acute respiratory distress syndrome following traumatic injury.

Respiratory insufficiency that occurs following a traumatic injury is due to both mechanical and physiological disruption of pulmonary integrity. Although an overall decrease in pulmonary compliance (Δ V/Δ P) is a component of acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS)*, this may not be a homogeneous process. Changes in compliance may actually occur at varying degrees throughout the lung parenchyma in a heterogeneous fashion. Attempting to open or recruit collapsed alveoli without causing lung injury by overdistention or stretch of alveoli with more normal compliance remains a clinical challenge. Airway pressure release ventilation (APRV) is a ventilator mode that incorporates features that optimize the spectrum of alveolar mechanics present in ARDS/ALI. In the past, the focus on ventilator support was on conforming the patient to the ventilator; alternatively, APRV accommodates the patient's breathing pattern and superimposes ventilation onto a pressure framework to support spontaneous breathing, 1 - 3 and thereby conforms the ventilator to the patient. APRV differs from other modes of positive-pressure ventilation in that it delivers a continuous positive airway pressure (CPAP) that releases periodically to augment CO 2 exchange. The patient's breathing is spontaneous and unrestricted throughout the entire ventilator cycle, allowing infinite inspiratory/expiratory ratios. Studies have shown that APRV can augment ventilation with lower pulmonary artery pressures and improved efficiency compared to traditional modes of ventilatory support; these elements may reduce the risk of ventilator-associated lung injury while improving oxygenation. After a brief review of the incidence and outcome of traumatic ARDS, we will present basic concepts of ventilator management with APRV and then will address the use of APRV in the patient with respiratory failure secondary to trauma.

Vital capacity inhalation induction with sevoflurane: An alternative to standard intravenous induction for patients undergoing cardiac surgery

Objective: To determine the respiratory and cardiovascular effects of a high concentration vital capacity induction with sevoflurane compared with an intravenous induction with etomidate in patients scheduled for elective coronary artery bypass graft (CABG) surgery. Design: Prospective, randomized, double-blind, controlled clinical trial. Setting: Cardiothoracic unit at a university hospital referral center. Participants: Twenty-two patients undergoing elective CABG surgery. Interventions: The study group (group S) received a vital capacity gaseous induction with sevoflurane 8% (n = 12) and the control group (group E) were given etomidate, 0.2 to 0.3 mg/kg (n = 10). Anesthesia was supplemented with fentanyl, 8 μg/kg, and vecuronium, 0.1 mg/kg, in both groups. Measurements and Main Results: The speed of induction of anesthesia was comparable between the groups. There was a significant increase in minute ventilation after induction of anesthesia in both groups. This increase was associated with a small reduction in PaCO2. There were no clinically significant changes in pH and PaO2. The incidence of breath-holding and the need for an oropharyngeal airway were similar between the groups. Both groups had similar reductions in mean arterial pressure and cardiac output during the study period; however, a downward trend in mean pulmonary artery pressure was noted in group S, whereas in group E it remained unchanged. Absolute plasma epinephrine and norepinephrine values were low during the precardiopulmonary bypass period in both groups. Conclusions: The technique of vital capacity inhalation induction with 8% sevoflurane offers a rapid onset of anesthesia, satisfactory airway control, and a good hemodynamic profile. Consideration should be given to the benefits of single-agent anesthesia and lowered pulmonary artery pressure during the precardiopulmonary bypass period. In addition to CABG surgery, this technique could be considered in patients with coronary artery disease undergoing noncardiac surgery, particularly for procedures in which spontaneous ventilation is preferred. Copyright © 2001 by W.B. Saunders Company