Twenty-four hours postoperative results after orthotopic cardiac transplantation in swine.

BACKGROUND: In-vivo explants in pigs are well-established to investigate myocardial function directly after transplantation. However, there is no functional data available for a longer time period after transplantation. We have established a pig model to investigate myocardial function 24 hours after orthotopic transplantation. MATERIALS AND METHODS: Orthotopic cardiac transplantations (HTx) in pigs were performed with a postoperative observation period of 24 hours (n = 6). To analyze myocardial function after transplantation, hemodynamical parameters (Swan-Ganz- and impedance-catheter data) as well as tissue and blood samples were obtained. Regional myocardial blood flow (RMBF) was assessed using fluorescent microspheres. RESULTS: The impedance-catheter parameters demonstrated a preserved contractility in both ventricles 24 hours post-transplantation. In contrast, cardiac output 24 hours after HTx was diminished by 50% as compared to the preoperative value. Conversely, pulmonary vascular resistance increased significantly. The RMBF was increased in both ventricles. Metabolic and histological analyses indicate myocardial recovery 24 hours after HTx with no irreversible damage. CONCLUSIONS: For the first time, we were able to establish a porcine model to investigate myocardial function 24 hours after heart transplantation. While the contractility of the transplanted hearts was well-preserved, impaired cardiac output was going along with an increase in pulmonary vascular resistance. Using this clinical relevant model, improvements of human cardiac transplantation and post-transplant contractile dysfunction, especially, could be investigated.

Anatomical study on the surgical technique used for xenotransplantation: porcine hearts into humans.

BACKGROUND: The pig heart is an ideal graft for orthotopic cardiac xenotransplantation regarding its physiological attributes and ready availability. Although single clinical attempts have been performed since the 1960s, details concerning the surgical technique of pig-to-human transplantation have never been reported. The present investigation should verify which anatomical differences between humans and pigs require special care in cardiac xenotransplantation. MATERIAL AND METHODS: We transplanted four pig hearts into human thoraces after autopsy. Implantation was performed using both the biatrial (modified Shumway) and bicaval techniques. The implanted hearts were not perfused. RESULTS: The four-legged walk of the pig implies a more transverse heart position and therefore a different outflow-angle of the great vessels. Accordingly, the thin-walled pulmonary artery and the superior vena cava (in bicaval technique) tend to kink and narrow. A special feature of porcine anatomy is the left azygous vein that empties into the coronary sinus. It must be ligated before the implantation. CONCLUSIONS: Keeping the porcine anatomical particularities in mind, technical problems in pig-to-human heart transplantation can be avoided. The anastomosis of the pulmonary artery requires special care. By using the biatrial technique surgeons can prevent imminent stenoses of the caval vein anastomoses.

Improved durability of the HeartMate XVE left ventricular assist device provides safe mechanical support up to 1 year but is associated with high risk of device failure in the second year.

BACKGROUND: Life-threatening device failure of the HeartMate VE due to biologic inflow valve incompetence or motor failure is a major drawback of long-term mechanical support when using this left ventricular assist device (LVAD). The new XVE model is the result of recent technical improvements. The aim of this study was to compare the clinical performance and durability of the new and earlier HeartMate versions. METHODS: We analyzed the incidence of device failure and of other device-specific complications (infections, bleeding) in 9 VE and 17 XVE patients. Explanted pumps were examined and biologic valve damage classified according to a score ranging from 0 (no visible damage) to 3 (severe destruction). RESULTS: Mean support time was 145 +/- 92 and 267 +/- 195 days in the VE and XVE groups, respectively (difference not significant [NS]). Survival was 89% (VE) vs 75% (XVE). The incidence of device failure requiring urgent heart transplantation or device replacement was 44% (VE) vs 31% (XVE) (NS). Device failure occurred significantly later in the XVE group (200 +/- 34 vs 487 +/- 53 days, p < 0.01). Causes of device failure were inflow valve incompetence (n = 6) and motor failure (n = 3). Acute device failure caused 1 death in the XVE group. One XVE patient has been on mechanical support for > 483 days. Macroscopic inflow valve damage score after explantation of the devices was 2.2 +/- 1.1 in the VE group and 2.0 +/- 0.8 in the XVE group (NS). CONCLUSIONS: The novel HeartMate XVE offers greater durability and provides reliable mechanical support in the first year. However, there is a high risk of life-threatening device failure in the second year. Further technical refinements are necessary to meet the challenges of safe long-term circulatory assistance.

Implantable left ventricular assist device for treatment of pulmonary hypertension in candidates for orthotopic heart transplantation-a preliminary study.

OBJECTIVES: Elevated pulmonary vascular resistance (PVR) unresponsive to pharmacological intervention is a major limitation in heart transplantation (HTX). The post-operative course of these patients is associated with an increased risk of life-threatening right heart failure. We evaluated the efficiency of an implantable left ventricular assist device (LVAD) to decrease PVR by unloading the left ventricle and to lower the risk of later orthotopic HTX. METHODS: Six patients with end-stage heart failure (NYHA class IV) and 'fixed' pulmonary hypertension (PVR 5.7+/-0.7, range 4.4-6.5 Wood units) were analyzed. Despite maximal pharmacological intervention at initial evaluation (oxygen inhalation, nitrates, alprostadil infusion) PVR could not be reduced to under 2.5 Wood units. Four patients received a TCI Heartmate, one patient a Novacor, and one patient a Jarvik 2000. RESULTS: All patients survived the LVAD implantation, four patients could be discharged from hospital. Cardiac index and pulmonary artery pressure values returned to normal during the early post-operative phase. After a mean support time of 191+/-86 days PVR had fallen to 2.0+/-1.2 (range 0.8-3.6) Wood units. All patients could be bridged to transplantation, one patient died 3 months after transplant, five patients are still alive after a mean follow-up of 16.2+/-10.5 months. CONCLUSIONS: Mechanical support using an implantable LVAD is a very efficient approach with an acceptable risk to treat severe pulmonary hypertension in end-stage heart failure patients before HTX. Adequate reduction of PVR can be expected within 3-6 months. Subsequent HTX is associated with a good outcome.

Transgenic and transmural revascularization: regional myocardial tissue pressure during chronic ischemia.

Channel patency and a cavito-myocardial pressure gradient are prerequisites for one potential mechanism of transmyocardial laser revascularization (TMLR), namely indirect (non-coronary) myocardial perfusion. We assessed the effect of TMLR combined with vascular endothelial growth factor (VEGF) on the myocardial tissue pressure (MTP) in chronic ischemia questioning firstly, whether transmural pressure allows perfusion of laser channels, and secondly, whether additional application of VEGF improves channel patency. One week after creation of an operative left anterior descending artery stenosis (2nd operation), pigs were designated to untreated ischemia (n=7), TMLR (n=8) or TMLR+VEGF-cDNA (2 mg intramyocardially, n=6). MTP and left ventricular pressure (LVP) were recorded simultaneously in the endo-, mid-, and epimyocardium before and after stenosis (1st operation), before and after therapy (2nd operation), and 12 weeks later (3rd operation). Myocardial samples were subjected to immunohistochemistry. Endo- and epimyocardial MTP exceeded LVP in all groups throughout the study, whereas midmyocardial MTP was constantly below LVP (P<0.05). Immediately after combined TMLR+VEGF, the endo-MTP decreased from 246.5+/-44.2 to 176.7+/-20.7 mmHg (P=0.043), remaining higher than LVP. After 12 weeks, it increased to 225.6+/-31.8 mmHg (P=0.04), but did not reach baseline values (P=0.04). Histological examination revealed occluded channels with surrounding vascular proliferation in both treatment groups. Additional VEGF-cDNA application in the vicinity of TMLR channels does not improve long-term patency. Direct blood flow from the cavity into the myocardium is impossible due to the high endomyocardial pressure. This limitation might be overcome by implantation of endomyocardial stents.

Myocardial viability twenty-four hours after orthotopic heart transplantation from non-heart-beating donors.

OBJECTIVES: Using a new preservation strategy, we investigated the performance of hearts from non-heart-beating donors during an observation period of 24 hours after orthotopic heart transplantation in a pig model. METHODS: In the control group (n = 6) beating donor hearts were harvested with Bretschneider's HTK solution and transplanted orthotopically without reperfusion modifications. In the non-heart-beating donor group (n = 6) hearts were perfused with leukocyte-depleted blood cardioplegia after 30 minutes of normothermic ischemia. Blood cardioplegia was supplemented with a sodium-hydrogen exchange inhibitor and adenosine. After transplantation, a second controlled reperfusion with blood cardioplegia was performed. RESULTS: Preload recruitable stroke work of the left ventricle 24 hours after transplantation in the control versus non-heart-beating donor group was 108% +/- 24% versus 103% +/- 18% of baseline values. Myocardial blood flow of the left and right ventricle was increased to 146% +/- 32% and 176% +/- 51% in the control group versus 176% +/- 29% and 194% +/- 27% in the non-heart-beating donor group. Myocardial oxygen consumption was 11.2 +/- 2.1 versus 12.8 +/- 2.2 mL/100 g per minute at baseline and 11.6 +/- 2.6 versus 13.2 +/- 3.1 mL/100 g per minute after 24 hours (not significant). Histologic examination with Luxol fast blue staining revealed that 2.6% +/- 4.8% of myocytes in the control group versus 1.8% +/- 1.9% in the non-heart-beating donor group were damaged irreversibly. CONCLUSIONS: Recovery of donor hearts from non-heart-beating donors is comparable with recovery of organs harvested from heart-beating donors if the above-mentioned preservation technique is used. These results could encourage the use of marginal donor hearts and help to expand the limited donor pool.

Blood cardioplegia filtration.

The introduction of blood cardioplegia has been proven to limit ischaemia and reperfusion injury in cardiac surgery. But the presence of activated neutrophils in the capillary bed may cause further damage. Leukocyte filters have been shown to be very effective in reducing the leukocytes in blood cardioplegia to less than 10%. Leukocyte depletion of blood cardioplegia provides an excellent approach to minimizing myocardial injury, predominantly in high-risk cardiac surgery.

Percutaneous aortic valve replacement: an experimental study. I. Studies on implantation.

OBJECTIVE: The purpose of this preliminary study was to devise a new surgical procedure for minimally invasive aortic valve implantation with a transluminal technique. METHODS: The new collapsible heart valve was prepared by mounting a porcine aortic valve, taken from a freshly slaughtered pig, into a self-expandable nitinol stent by means of a suture technique. The outer diameter of the valved stent ranged from 15 to 23 mm, and the length ranged from 21 to 28 mm. Before implantation in vivo, these valved stents were tested in an in vitro circulatory system. Only in vitro-tested valved stents with a pressure gradient of less than 7 mm Hg and regurgitation of I degrees or less were used for transluminal aortic valve implantation in vivo. Six of these valved stents were implanted in the descending aorta and 8 in the ascending aorta of anesthetized pigs. The catheter delivery system (22F) was extraperitoneally inserted through the left iliac artery or the infrarenal aorta. Measurements for transvalvular gradient, valvular opening and closure, blood-flow characteristics, regurgitation, and macroscopic analysis were performed at baseline and after the observation period (164 +/- 48 minutes). RESULTS: This preliminary study contained 14 animals. One animal died of ventricular fibrillation. Technical failure occurred in 2 pigs as a result of stent twisting. At the end of the observation period, the 11 successfully implanted valved stents demonstrated low transvalvular gradients (mean end-systolic Deltarho(max) of 5.4 +/- 3.3 mm Hg for the descending aorta group, 5.4 +/- 1.2 mm Hg for the supracoronary group, and 5.4 +/- 1.1 mm Hg for the subcoronary group), which did not differ from their in vitro gradients. Two-dimensional echocardiography demonstrated complete valvular closure and opening in 5 of 5 cases. Angiography indicated only a physiologic jet of regurgitation (0 degrees ) in 8 animals and mild (I degrees ) regurgitation in 3 animals. Color Doppler ultrasonography indicated no regurgitation in 5 of 5 cases and minor paravalvular leakage in 1 case. CONCLUSION: Aortic valved stents can be successfully implanted without thoracotomy by using a transluminal catheter technique. Long-term function of the valves remains to be established.