The effect of modified ultrafiltration on angiopoietins in pediatric cardiothoracic operations.

BACKGROUND: Cardiopulmonary bypass subjects patients' blood to hemodilution and nonphysiologic conditions, resulting in a systemic inflammatory response. Modified ultrafiltration (MUF) counteracts hemodilution and has also been postulated to improve outcomes by proinflammatory cytokine removal. The objective of this study was to investigate whether the benefits of MUF include the removal of proinflammatory mediators, such as angiopoietin-2 (angpt-2). We hypothesize that some of the clinical benefits of MUF are related to the preferential removal of angpt-2. METHODS: We performed a prospective cohort study in children 18 years old or younger undergoing cardiopulmonary bypass. Serum samples were obtained from each patient preoperatively, after cardiopulmonary bypass, and on intensive care unit admission. A fluid sample from the MUF effluent was also analyzed. Angpt-1, angpt-2, interleukin-8, and interleukin-10 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Thirty-one patients were enrolled. Angpt-1 levels significantly decreased across all time points (p<0.01). Angpt-2 concentrations were significantly elevated at intensive care unit admission when compared with both preoperative and post-cardiopulmonary bypass levels (p<0.01). The angpt-2:1 ratio significantly increased after cardiopulmonary bypass to intensive care unit admission (p<0.01). There was no significant difference between the angpt-2 or angpt-1 percentage of extraction within MUF effluent. Interleukin-8 and interleukin-10 significantly increased from preoperative to intensive care unit admission (both p<0.01). CONCLUSIONS: The results of this study demonstrate that MUF removes both proinflammatory and antiinflammatory mediators equally. This study suggests that the clinical benefits of MUF cannot be attributed to the removal of larger quantities of proinflammatory mediators such as angpt-2 and interleukin-8.

Right ventricle-sparing heart transplantation effective against iatrogenic pulmonary hypertension.

BACKGROUND: Right heart failure is the predominant cause of death following heart transplantation, occurring with disturbingly high frequency in patients with severe antecedent pulmonary hypertension. We have recently reported a novel technique of heart transplantation that spares the recipient right ventricle, excising only the recipient left ventricle. The resulting model has 2 right hearts and 1 left heart. The aim is to preserve the recipient's right ventricle, which is already conditioned to pulmonary hypertension. The hope is that, in this way, death due to right heart failure can be prevented in humans. Our prior report was a feasibility study in normal dogs. This study challenges this new technique by creating iatrogenic pulmonary hypertension in the recipient animals. METHODS: Iatrogenic pulmonary hypertension was created in 4 recipient canines by intravenous injection of the pulmonary toxin monocrotaline pyrrole (single bolus of 3.5 to 4.5 mg/kg intravenously [i.v.]). RESULTS: Within 6 weeks of monocrotaline administration, relative pulmonary hypertension occurred (mean pulmonary artery [PA] pressure 20 mm Hg vs 10 mm Hg for controls [p < 0.01]) (pulmonary vascular resistance [PVR] 4.2 vs 1.5 Wood units [P < 0.01]), and right ventricular (RV) hypertrophy developed (RV thickness 11 mm vs 2 mm [P < 0.04]). Histologic examination confirmed severe muscle infiltration and thickening of the media of the pulmonary arterioles. RV-sparing heart transplantation was performed successfully in all 4 animals with pulmonary hypertension. In all cases, the animals were weaned without difficulty from cardiopulmonary bypass, despite the ambient pulmonary hypertension, on low-dose epinephrine, maintaining systolic blood pressure of 104 mm Hg at right atrial pressure of 7 mm Hg. Both right hearts contracted well without dilation or strain. A single "control" traditional orthotopic transplant experiment in an animal with monocrotaline-induced pulmonary hypertension resulted in immediate death from right heart failure. CONCLUSIONS: Right ventricle-sparing heart transplantation ("one-and-one-half heart model") can handle pulmonary hypertension without difficulty. This evidence adds impetus for further pursuing of right ventricle-sparing heart transplantation to decrease the incidence of death from right heart failure in recipients with severe antecedent pulmonary hypertension.

Novel technique for isolated accessory right heart transplantation for congenital heart disease.

BACKGROUND: Our prior laboratory work has permitted adding a whole donor heart to a preserved recipient right heart, producing a heart-and-a-half preparation able to cope with pulmonary hypertension in the recipient. The experiments in the present study explore the feasibility of the converse operation: adding an isolated donor right heart to an entire preserved heart. METHODS: Eight adult mongrel dogs (4 donors and 4 recipients) were used in 4 transplant operations performed through a right thoracotomy without cardiopulmonary bypass (using side-biting control of recipient vessels). The donor heart underwent resection of the left atrium and left ventricle, leaving an isolated donor right heart. Blood supply to the donor right ventricle was preserved from the donor ascending aorta. Through a right thoracotomy, the donor right heart was transplanted in parallel to the native right heart of the recipient by using the following anastomoses: (1) donor superior vena cava to recipient superior vena cava (end-to-side anastomosis); (2) donor pulmonary artery to recipient pulmonary artery (end-to-side anastomosis); (3) donor ascending aorta to recipient aorta (through a great vessel [end-to-end anastomosis] to provide arterial inflow to donor coronary arteries). Animals were euthanized within 1 hour after completion of transplantation. RESULTS: Isolation of the right ventricle by excision of the left chambers was technically feasible. Transplantation without cardiopulmonary bypass was feasible in all cases. The isolated right heart beat well after transplantation in all animals, demonstrating sinus rhythm. Three of 4 animals were able to sustain good hemodynamics on support with epinephrine. Bleeding from the septum or aortic valve of the donor (now open to the pericardial space) was not problematic. Mean arterial pressure was 85 mm Hg (mean) at a right atrial pressure of 6 mm Hg (mean). In 2 animals the recipient superior vena cava was ligated to obligate upper body flow to pass through the accessory ventricle; hemodynamics were preserved under these circumstances. CONCLUSION: Transplantation of an isolated right heart is feasible. Such a technique has potential as a novel therapeutic alternative for obstructive or hypoplastic lesions of the right heart in human children.