Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates.

In vitro and in vivo studies have suggested that human complement component C5a plays a key role in neutrophil injury in the adult respiratory distress syndrome (ARDS). First, using leukocyte aggregometry, we demonstrated that the addition of a recently developed rabbit anti-human polyclonal antibody to C5a des arg to endotoxin-activated plasma prevented leukocyte aggregation in vitro. We then administered the anti-C5a des arg antibody to septic primates (Macaca fascicularis). Three groups of primates, control, septic, and anti-C5a antibody treated septic, were studied (n = 4 in each group). A 30-min infusion of Escherichia coli (1 X 10(10)/kg) resulted in severe sepsis and ARDS. Primates were killed 4 h after completion of the E. coli infusion. Septic animals not treated with anti-C5a antibody had 75% mortality (3/4), decreased oxygenation, severe pulmonary edema, and profound hypotension. Septic primates treated with anti-C5a antibodies did not die and did not develop decreased oxygenation (P less than 0.05) or increased extravascular lung water (P less than 0.05). They also had a marked recovery in their mean arterial blood pressure (P less than 0.05). This study demonstrates that treatment with rabbit anti-human C5a des arg antibodies attenuates ARDS and some of the systemic manifestations of sepsis in nonhuman primates.

Port-access mitral valve replacement in dogs.

OBJECTIVE: The objective was to assess mitral valve replacement in a minimally invasive fashion by means of port-access technology. METHODS: Fifteen dogs, 28 +/- 3 kg (mean +/- standard deviation), were studied with the port-access mitral valve replacement system (Heartport, Inc., Redwood City, Calif.). Eleven dogs underwent acute studies and were sacrificed immediately after the procedure. Four dogs were allowed to recover and then were sacrificed 4 weeks after operation. Cardiopulmonary bypass was conducted by femoral cannulation with an endovascular balloon catheter for aortic occlusion, root venting, and antegrade delivery of cardioplegic solution. Catheters were inserted in the jugular vein for pulmonary artery venting and retrograde delivery of cardioplegic solution. Through the oval port, a prosthesis (St. Jude Medical, Inc., St. Paul, Minn., or CarboMedics, Inc., Austin, Texas) was inserted through the left atrial appendage and secured to the anulus with sutures. Deairing was performed. RESULTS: Cardiopulmonary bypass duration was 114 +/- 24 minutes and aortic crossclamp time was 68 +/- 14 minutes. All animals were weaned from cardiopulmonary bypass in sinus rhythm. Cardiac output and pulmonary artery occlusion pressure were unchanged (2.8 +/- 0.7 L/min and 7 +/- 3 mm Hg before operation vs 2.6 +/- 0.6 L/min and 9 +/- 4 mm Hg after operation). There was no mitral regurgitation according to left ventriculography in 13 of 15 dogs. In two dogs there was interference with prosthetic valve closure by residual native anterior leaflet tissue. Pathologic examination otherwise showed normal healing without perivalvular discontinuity. Microscopic studies showed no damage to the valve surfaces. Transthoracic echocardiography of the four dogs in the long-term study showed normal ventricular and prosthetic valve function 4 weeks after the operation. CONCLUSION: Mitral valve replacement with a minimally invasive method has been demonstrated in dogs. A clinical trial is in progress.

Port-access coronary artery bypass grafting: a proposed surgical method.

Minimally invasive surgical methods have been developed to provide patients the benefits of open operations with decreased pain and suffering. We have developed a system that allows the performance of cardiopulmonary bypass and myocardial protection with cardioplegic arrest without sternotomy or thoracotomy. In a canine model, we successfully used this system to anastomose the internal thoracic artery to the left anterior descending coronary artery in nine of 10 animals. The left internal thoracic artery was dissected from the chest wall, and the pericardium was opened with the use of thoracoscopic techniques and single lung ventilation. The heart was arrested with a cold blood cardioplegic solution delivered through the central lumen of a balloon occlusion catheter (Endoaortic Clamp; Heartport, Inc., Redwood City, Calif.) in the ascending aorta, and cardiopulmonary bypass was maintained with femorofemoral bypass. An operating microscope modified to allow introduction of the 3.5x magnification objective into the chest was positioned through a 10 mm port over the site of the anastomosis. The anastomosis was performed with modified surgical instruments introduced through additional 5 mm ports. In the cadaver model (n = 7) the internal thoracic artery was harvested and the pericardium opened by means of similar techniques. A precise arteriotomy was made with microvascular thoracoscopic instruments under the modified microscope on four cadavers. In three other cadavers we assessed the exposure provided by a small anterior incision (4 to 6 cm) over the fourth intercostal space. This anterior port can assist in dissection of the distal internal thoracic artery and provides direct access to the left anterior descending, circumflex, and posterior descending arteries. We have demonstrated the potential feasibility of grafting the internal thoracic artery to coronary arteries with the heart arrested and protected, without a major thoracotomy or sternotomy.

Minimally invasive cardiopulmonary bypass with cardioplegic arrest: a closed chest technique with equivalent myocardial protection.

Thoracoscopic cardiac surgery is presently under intense investigation. This study examined the feasibility and efficacy of closed chest cardiopulmonary bypass and cardioplegic arrest in comparison with standard open chest methods in a dog model. The minimally invasive closed chest group (n = 6) underwent percutaneous cardiopulmonary bypass and cardiac venting, as well as antegrade cardioplegic arrest through use of a specially designed percutaneous endovascular aortic occluder and cardioplegic solution delivery system. The control group (n = 6) underwent standard sternotomy and conventional open chest cardiopulmonary bypass, aortic crossclamping, and antegrade cardioplegia. Ischemic arrest time was 1 hour in each group. Ventricular pressures and sonomicrometer segment lengths were recorded before bypass and at 30 and 60 minutes after bypass. Left ventricular function did not differ significantly between the two groups, as demonstrated by measurements of elastance and end-diastolic stroke work. Also, the preload recruitable work area was 69% and 60% of baseline at 30 and 60 minutes after bypass in the minimally invasive group versus 65% and 62% in the conventional control group (p = not significant); the stroke work end-diastolic length relationship was 78% and 71% of baseline in the minimally invasive group at these intervals versus 77% and 74% in the conventional control group (p = not significant). Myocardial temperatures were similar throughout bypass in the two groups, and ultrastructural examination of prebypass and postbypass biopsy specimens showed no differences between groups. These results demonstrate that minimally invasive cardiopulmonary bypass with cardioplegic arrest is as feasible, safe, and effective as conventional open chest cardiopulmonary bypass. Thus current technology may allow wider clinical application of closed chest cardiac surgery.

Minimally invasive right heart operations: techniques for bicaval occlusion and cardioplegia.

Peripheral cardiopulmonary bypass with cardioplegia has facilitated minimally invasive coronary artery bypass grafting and mitral valve replacement. The cardiopulmonary bypass system was modified to allow bicaval occlusion for right heart operations. In 4 canine studies, three variants of bicaval cannulation techniques were successfully used for atrial septal defect repair via a right minithoracotomy.

Port-access cardiac operations with cardioplegic arrest.

BACKGROUND: A less invasive approach to cardiac surgery has been propelled by recent advances in video-assisted surgery. Previous obstacles to minimally invasive cardiac operations with cardioplegic arrest included limitations in operative exposure, inadequate perfusion technology, and inability to provide myocardial protection. METHODS: Port-access technology allows endovascular aortic occlusion, cardioplegia delivery, and left ventricular decompression. The endoaortic clamp is a triple-lumen catheter with an inflatable balloon at its distal end. Antegrade cardioplegia is delivered through a central lumen, which also acts as an aortic root vent, a second lumen is used as an aortic root pressure monitor, and a third lumen is used for balloon inflation to provide aortic occlusion. RESULTS: Experimental and clinical studies have demonstrated the feasibility of port-access coronary artery bypass grafting and port-access mitral valve procedures. Endovascular cardiopulmonary bypass using the endoaortic clamp was effective in achieving cardiac arrest and myocardial protection to allow internal mammary artery to coronary artery anastomosis in a still and bloodless field. Intracardiac procedures, such as mitral valve replacement or repair, have been successfully performed clinically. CONCLUSION: The port-access system effectively achieves cardiopulmonary bypass and cardioplegic arrest, thereby enabling the surgeon to perform cardiac procedures in a minimally invasive fashion. This system provides for endovascular aortic occlusion, cardioplegia delivery, and left ventricular decompression.

Closed-chest cardiopulmonary bypass and cardioplegia: basis for less invasive cardiac surgery.

BACKGROUND: We developed a method of closed-chest cardiopulmonary bypass to arrest and protect the heart with cardioplegic solution. This method was used in 54 dogs and the results were retrospectively analyzed. METHODS: Bypass cannulas were placed in the right femoral vessels. A balloon occlusion catheter was passed via the left femoral artery and positioned in the ascending aorta. A pulmonary artery vent was placed via the jugular vein. In 17 of the dogs retrograde cardioplegia was provided with a percutaneous coronary sinus catheter. RESULTS: Cardiopulmonary bypass time was 111 +/- 27 minutes (mean +/- standard deviation) and cardiac arrest time was 66 +/- 21 minutes. Preoperative cardiac outputs were 2.9 +/- 0.70 L/min and postoperative outputs were 2.9 +/- 0.65 L/min (p = not significant). Twenty-one-French and 23F femoral arterial cannulas that allowed coaxial placement of the ascending aortic balloon catheter were tested in 3 male calves. Line pressures were higher, but not clinically limiting, with the balloon catheter placed coaxially. CONCLUSIONS: Adequate cardiopulmonary bypass and cardioplegia can be achieved in the dog without opening the chest, facilitating less invasive cardiac operations. A human clinical trial is in progress.

Port-Access coronary artery bypass grafting with the use of cardiopulmonary bypass and cardioplegic arrest.

BACKGROUND: To reduce surgical trauma, we performed minimally invasive Port-Access (Heartport Inc, Redwood City, CA) coronary artery bypass grafting with cardiopulmonary bypass and cardioplegic arrest. METHODS: Thirty-six men and 6 women with a median age of 59 years (range, 31 to 75 years) and isolated lesions of the left anterior descending branch of the coronary artery underwent Port-Access coronary artery bypass grafting. A small (6- to 9-cm) incision was made parasternally on top of the fourth rib. The left internal thoracic (mammary) artery was dissected and taken down through the minithoracotomy either alone or using an additional thoracoscopic approach. Cardiopulmonary bypass was instituted through femoral cannulation, and an additional endoarterial balloon catheter (Heartport Inc) was introduced into the ascending aorta for aortic occlusion, aortic root venting, and the delivery of cold antegrade crystalloid cardioplegia. After cardioplegic arrest, the left internal mammary artery was anastomosed to the left anterior descending artery under direct vision. RESULTS: The median left internal mammary artery takedown time was 49.5 +/- 21.9 minutes, the duration of cardiopulmonary bypass was 59.5 +/- 32.8 minutes, the aortic occlusion time was 28.5 +/- 7.9 minutes, the intensive care unit stay was 1.0 +/- 3.2 days, and the total hospital stay was 5.0 +/- 2.5 days. Intraoperative angiograms were done in the first 10 patients and showed patent left internal mammary artery grafts without anastomotic complications in all cases. Two arterial dissections, including one aortic dissection, were observed in patients with preexisting peripheral vascular disease. The other complications were minor. All but 1 patient recovered well, with no major limitations in their daily activities. CONCLUSIONS: Using this minimally invasive method, sternotomy-related complications can be avoided, the hospital stay can be reduced, and a safe coronary artery bypass grafting procedure can be performed with the advantage of cardiopulmonary bypass and cardioplegic arrest as are used routinely in conventional coronary artery operations.

Port-access coronary artery bypass with cardioplegic arrest: acute and chronic canine studies.

BACKGROUND: Our goal is to perform minimally invasive coronary artery bypass grafting without sacrificing the benefits of myocardial protection with cardioplegia. METHODS: Twenty-three dogs underwent acute studies and 4 dogs underwent survival studies. The left internal mammary artery was taken down using a thoracoscope. Cardiopulmonary bypass was conducted via femoral cannulas and using an endovascular balloon catheter for ascending aortic occlusion, root venting, and delivery of antegrade blood cardioplegia. Pulmonary artery venting was achieved with a jugular vein catheter. An internal mammary artery-to-coronary artery anastomosis was performed using a microscope through a 10 mm port. RESULTS: All animals were weaned from cardiopulmonary bypass in sinus rhythm without inotropes. Cardiopulmonary bypass duration was 104 +/- 28 minutes and aortic clamp duration was 61 +/- 22 minutes. Cardiac output and pulmonary artery occlusion pressure were unchanged. The internal mammary artery was anastomosed to the left anterior descending artery (25) or the first diagonal (2) with patency shown in 25 of 27. One dog in the survival study had a very short internal mammary artery pedicle under tension and was euthanized for excessive postoperative hemorrhage. Three weeks postoperatively the remaining dogs had angiographically patent anastomoses, normal transthoracic echocardiograms, and histologically normal healing and patent grafts. CONCLUSIONS: Endovascular cardiopulmonary bypass using a balloon catheter is effective in arresting and protecting the heart to allow thoracoscopic internal mammary artery-to-coronary artery anastomosis.

Minimally invasive mitral valve surgery.

Because of advances in video-assisted general and thoracic surgery, minimally invasive cardiac surgery has been successfully performed experimentally and clinically. Recently described techniques of less invasive mitral valve surgery include limited right thoracotomy, parasternal incision, and partial sternotomy. These methods have been coupled to video-assisted thoracoscopy to further decrease the incision size. Cardiopulmonary bypass (central or peripheral) and either hypothermic fibrillatory arrest or cardioplegic arrest are used. The Port-Access approach is a catheter-based system that provides effective cardiopulmonary bypass, cardioplegic arrest, and ventricular decompression. At Stanford University, 10 Port-Access mitral valve procedures were performed between May 1996 and January 1997. The mean age of the patients (eight men and two women) was 54 +/- 7 (SD) years. Nine patients had severe mitral regurgitation from myxomatous degeneration, and one suffered from severe mitral regurgitation and moderate mitral stenosis from a rheumatic etiology. Five patients underwent mitral valve replacement, and five underwent mitral valve repair. There was no operative mortality. The mean incision length was 8.1 +/- 2.5 cm. The aortic "cross-clamp" time was 99 +/- 22 minutes, and the cardiopulmonary bypass time was 151 +/- 52 minutes. The total hospitalization averaged 4.3 +/- 1.4 days. One patient developed third-degree atrioventricular block, requiring a prolonged stay in the intensive care unit and pacemaker placement; the same patient was found to have a perivalvular leak on follow-up, requiring reoperation at 3 months. Port-Access mitral valve procedures can be performed safely with satisfactory outcome. Greater clinical experience and long-term follow-up are necessary to fully assess these less invasive techniques of mitral valve surgery.

Port-access cardiac surgery with cardiopulmonary bypass and cardioplegic arrest.

In the past decade, laparoscopic and thoracoscopiC technology have significantly and irreversibly altered the approach to many general and thoracic surgical diseases. With advances in laparoscopy and thoracoscopy, the concept of a minimally invasive approach to cardiac surgery has been realized.

Shared knowledge about infants among fathers and mothers.

Evidence for the exchange of parenting information between low-income White mothers and fathers of infants was found. Mothers had more accurate expectations for normative development than fathers, but more accurate fathers had spouses who were also more accurate--even when education was controlled. Though few significant differences were evident in help-seeking behavior when infant problems were encountered, fathers turned to fewer helpers than mothers and were somewhat more likely to rely solely on their spouse. These data indicate that researchers must consider the exchange of information between spouses, particularly when studying the socialization of parenting among fathers at this stage in the life cycle of the family.

Social support, locus of control, and parenting in three low-income groups of mothers: black teenagers, black adults, and white adults.

Mother's social support, their instrumental use of extended family members and of professionals for help, and their sense of personal control were examined as predictors of parenting skill in 3 groups of low-income women. Separate regression models were generated for black adult mothers, white adult mothers, and black teen mothers, all of whom had at least 1 infant. Black teen and white adult mothers who sought help with child-rearing problems from extended family members were more skillful parents. Among white mothers, use of professionals for help with child-rearing problems and mothers' sense of internal control were also significant predictors. Black adult mothers' parenting skill was predicted only by locus of control. These prediction models suggest that in 2 of the groups, social ties to significant others were the linkages through which child-rearing information flowed to affect parenting behavior.

The status of transplantation of the human lung.

Transplantation for end-stage pulmonary disease is now established as an effective therapy for selected patients. Initially, combined heart and lung transplantation was the only therapeutic option for these patients. Recent developments that include improved immunosuppression, preservation of grafts and technical advances and markedly decreasing bronchial anastomotic complications have made unilateral pulmonary transplantation a clinical reality.

Extracorporeal circulation for port-access cardiac surgery.

Minimally invasive techniques for cardiac surgery are a new approach in performing some cardiac operations. Minimally invasive surgery may minimize patient discomfort, length of stay in the hospital and postoperative rehabilitation. These procedures utilize a small thoracotomy for direct visualization of the heart. However, without the use of cardiopulmonary bypass, this approach is limited to some epicardial procedures such as coronary bypass grafting, where the heart rate is pharmacologically reduced. Port-access cardiac surgery is a new approach which provides all the benefits of minimally invasive surgery without sacrificing the advantages of cardiopulmonary bypass and myocardial preservation. Port-access cardiac surgery uses an anterior mediastinotomy and thoracic ports in conjunction with a specially designed set of endovascular catheters. These catheters provide a mode to arrest, preserve and vent the heart through an endoaortic occlusion balloon positioned in the ascending aorta. A pulmonary artery vent and coronary sinus cardioplegia catheter can also be used. These endovascular catheters, integrated with a modified heart-lung machine, provide complete cardiopulmonary support through extrathoracic cannulae inserted in a femoral artery and vein. Maintenance and monitoring of this endovascular cardiopulmonary bypass system requires the use of a kinetic pump in the venous drainage line to augment return to the heart-lung machine. Special guidelines and management parameters exist to optimize bypass with this catheter system. Using this system, port-access, minimally invasive surgery can be applied to a wider range of both epicardial and intracardiac procedures.

The Type A behavior pattern and carotid artery atherosclerosis.

The Type A behavior pattern has been identified as an important precursor of coronary atherosclerosis. However, atherosclerosis is a disease process that occurs throughout the arterial system. The present research examined the hypothesis that the Type A pattern may also be related to disease in other arteries such as the carotid arteries. Men (n = 21) and women (n = 23) from 40 to 65 years of age were examined for carotid artery atherosclerosis using doppler ultrasonography. Subjects also completed the Jenkins Activity Survey (JAS) to measure the Type A pattern. The results indicated that the diseased individuals were more likely to be classified as Type A (71%) than as Type B (29%), Z = 2.08, p less than 0.05. The nondiseased individuals were not more likely to be Type A (53%) than Type B (47%). The results are consistent with the hypothesis that atherosclerosis in Type A individuals is not limited to the coronary arteries but the disease is likely to occur throughout the arterial system.

Analysis of optokinetic and eye tracking data on normal subjects.

This study was undertaken to determine the incidence of abnormal eye tracking patterns in normal subjects and to compare the optokinetic (OPK) response of normal subjects using a nystagmographic gonioscope (Nystagmotrac) and Coats's type of OPK drum. Eye movement was recorded by means of an electronystagmographic (ENG) recorder, and the speed of the slow component was computed for the OPK response. The eye tracking test showed a high rate of abnormality among our subjects. Optokinetic testing revealed highly symmetrical responses for all subjects.