Cardioprotective effects of tetrahydrobiopterin in cold heart preservation after cardiac arrest.

BACKGROUND: It has recently been shown that tetrahydrobiopterin (BH4), an essential cofactor of nitric oxide synthase (NOS), reduces ischemia-reperfusion myocardial injury. The aim of this study was to determine if supplementation with BH4 after cardiac arrest followed by cold heart preservation would exert a cardioprotective effect against ischemia-reperfusion injury. MATERIALS AND METHODS: Isolated perfused rat hearts were subjected to 4 degrees C cold ischemia and reperfusion. Hearts were treated with cold cardioplegic solution with or without BH4 just before ischemia and during the first 5 min of reperfusion period. Effects of BH4 on left ventricular function, myocardial contents of high-energy phosphates, and nitrite plus nitrate were measured in the perfusate, before ischemia and after reperfusion. Moreover, the effect of BH4 on the cold-heart preservation followed by normothermic (37 degrees C) ischemia was determined. RESULTS: BH4 improved the contractile and metabolic abnormalities in reperfused cold preserved hearts that were subjected to normothermic ischemia. Furthermore, BH4 significantly alleviated ischemic contracture during ischemia, and restored the diminished perfusate levels of nitrite plus nitrate after reperfusion. CONCLUSION: These results demonstrated that BH4 reduces ischemia-reperfusion injury in cold heart preservation. The cardioprotective effect of BH4 implies that BH4 could be a novel and effective therapeutic option in the preservation treatment of donor heart after cardiac arrest.

Autologous peripheral blood mononuclear cell implantation for patients with peripheral arterial disease improves limb ischemia.

BACKGROUND: Implantation of bone marrow mononuclear cells, including endothelial progenitor cells, into ischemic limbs has been shown to improve collateral vessel formation. In the present study the safety and feasibility of autologous peripheral blood mononuclear cells (PBMNCs) implantation after granulocyte-colony stimulating factor (G-CSF)-induced mobilization was investigated in patients with severe peripheral arterial disease. METHODS AND RESULTS: Six cases were enrolled: 5 of thromboangitis obliterans and 1 of arteriosclerosis obliterans. Following administration of G-CSF (10 microg . kg(-1) . day(-1)), PBMNCs were harvested and injected intramuscularly (5 legs and 1 arm) for 2 days for the patients with ischemia of the legs. No serious adverse events related to G-CSF administration, harvest or implantation were observed during this study period. Improvement in the ankle - brachial pressure index (ABI: >0.1) was seen in 4 patients at 4 weeks and ischemic ulcers improved in 3 of 3 patients. The mean maximum walking distance significantly increased from 203 m to 559 m (p=0.031) at 4 weeks and was sustained for 24 weeks. Significant improvement was seen in physiological functioning subscale of Short Form-36. CONCLUSION: Implantation of PBMNCs collected after G-CSF administration could be an alternative to therapeutic angioplasty in patients with severe peripheral arterial disease.

The tumor suppressor WARTS activates the Omi / HtrA2-dependent pathway of cell death.

Drosophila tumor suppressor WARTS (Wts) is an evolutionally conserved serine / threonine kinase and participates in a signaling complex that regulates both proliferation and apoptosis to ensure the proper size and shape of the fly. Human counterparts of this complex have been found to be frequently downregulated or mutated in cancers. WARTS, a human homolog of Wts, is also known as tumor suppressor and mitotic regulator, but its molecular implications in tumorigenesis are still obscure. Here, we show that WARTS binds via its C-terminus to the PDZ domain of a proapoptotic serine protease Omi / HtrA2. Depletion of WARTS inhibited Omi / HtrA2-mediated cell death, whereas overexpression of WARTS promoted this process. Furthermore, WARTS can enhance the protease activity of Omi / HtrA2 both in vivo and in vitro. Activation of Omi / HtrA2-mediated cell death is thus a potential mechanism for the tumor suppressive activity of WARTS.

Graft for mycotic thoracic aortic aneurysm: omental wrapping to prevent infection.

Nine cases of mycotic thoracic aortic aneurysm were treated surgically between July 1995 and March 2003. The aneurysms were located in the ascending aorta in 1 patient, the descending thoracic aorta in 5, and the thoracoabdominal aorta in 3. Preoperatively, 3 patients were in shock due to rupture of the aneurysm. All patients underwent aneurysmectomy and in-situ graft placement. In 5 patients, the graft was covered with a pedicled omental flap to prevent postoperative graft infection. There were 2 hospital deaths: one patient died of multi-organ failure, and the other died from intrathoracic bleeding. After discharge, one patient died from intrathoracic bleeding 3 months after surgery. These 3 patients had not received omental wrapping. Postoperative graft infection did not occur in the 6 surviving patients during a mean follow-up period of 4.0 +/- 3.1 years. It was concluded that covering the prosthetic graft with a pedicled omental flap may help prevent postoperative graft infection and improve the surgical results.

Improvement of liver function after surgery for Budd-Chiari syndrome.

PURPOSE: We evaluated the relationship between liver histology and postoperative improvement of liver function after surgery for Budd-Chiari syndrome (BCS). METHODS: Over a period of 23 years, we operated on 46 patients with BCS by reconstructing the occluded inferior vena cava (IVC) and reopening as many occluded hepatic veins as possible. We divided the patients into a liver cirrhosis group (group I, n = 30) and a hepatic fibrosis or liver congestion group (group II, n = 16), and compared the ages, duration of illness, preoperative liver function, changes in liver function, and changes in esophageal varices (EV). RESULTS: There were no hospital deaths. In group I the patients were older, and the duration of illness was longer. The group I patients also had a lower thrombotest percentage and a higher serum ammonia. The indocyanine green clearance (ICG) test showed more remarkable improvement in liver function in group II. The rate of disappearance of EV was also higher in group II. CONCLUSION: Surgery during the early stage of BCS is important in improving postoperative liver function.

Malignant fibrous histiocytoma of the heart complicated by factor XI deficiency in a Jehovah's Witness patient.

We describe a 16-year-old girl with malignant fibrous histiocytoma (MFH) of the heart complicated by factor XI deficiency. The preoperative diagnosis was left atrial myxoma. We decided to perform the operation owing to a normal bleeding time. Operative findings suggested a malignant tumor. The patient was a Jehovah's Witness, and extensive excision was not performed because blood transfusion was not allowed. We resected as much of the tumor and left atrial appendage as possible. The pathologic diagnosis was MFH. Excessive bleeding was not observed during the operation. Bleeding time helps to determine whether a surgical procedure is indicated in patients with factor XI deficiency.

The prevention of nerve injury in aortic arch aneurysmal surgery.

In a case of aortic arch aneurysm associated with adhesion to the surrounding structures, we devised an operative technique to avoid nerve injury during the surgical procedure. By preserving the adventitial layer of the aortic arch aneurysm to which the phrenic and recurrent nerves were attached, injury to the nerves was avoided, and the aneurysmectomy was completed with the distal anastomosis being performed intraluminally.

Diaphragmatic plication in adult patients with diaphragm paralysis after cardiac surgery.

OBJECTIVE: We investigated the benefit of diaphragmatic plication for weaning from mechanical ventilation in these adult patients. PATIENTS AND METHODS: Four patients underwent diaphragmatic plication for difficulty of weaning from mechanical ventilation due to diaphragmatic paralysis. They were all men with an average age of 70.5 +/- 6.3 years. Three of the patients had undergone cardiac surgeries for coronary artery bypass grafting and one patient ascending aortic replacement for pseudoaneurysm after coronary revascularization. Right diaphragmatic plication (muscle sparing procedure) was performed between 30 to 61 days after cardiac surgery. RESULTS: The mean forced tidal volume improved dramatically from 216 to 415 ml after plication in all patients, and it was possible to discontinue mechanical ventilation from 2 to 12 days after plication. One patient with obstructive respiratory dysfunction died from aspiration pneumonia 15 days after plication. However, postoperative tidal volume in this patient improved to 420 ml and he was able to be weaned from ventilatory support five days after plication. The other three patients were discharged between 26 to 58 days after plication and continue to do well without symptoms. CONCLUSION: Diaphragmatic plication is a useful procedure for treatment of diaphragmatic paralysis in adults as well in children.

Direct cannulation of the common carotid artery during the ascending aortic or aortic arch replacement.

OBJECTIVE: To evaluate cerebral perfusion using direct cannulation into the common carotid artery. A new technique is needed to protect brain ischemic injury during ascending aortic or aortic arch replacement. METHODS: This technique was evaluated for patients who would have difficulty maintaining adequate cerebral perfusion during surgery. The procedure was performed when patients had the following diagnoses: pseudoaneurysm formation in contact with the sternum with the risk of aneurysmal rupture (n = 5), acute aortic dissection with compression of the true lumen of the innominate artery by the pseudolumen (n = 3), or a large volume of thrombus in the lumen of the aneurysm with the risk of cerebral thromboembolism if standard extracorporeal circulation was used (n = 2). The perfusion catheter was cannulated into one side of the common carotid artery (right side: n = 6, left side: n = 4) and mean perfusion flow rate was found to be 175 mL/min. The operative procedures consisted of ascending aortic and aortic arch replacement with coronary artery bypass grafting in six patients, ascending aortic replacement in 2 patients, and innominate artery reconstruction/innominate artery and right subclavian artery reconstruction in one patient. RESULTS: No cerebral accidents or deaths occurred while patients were hospitalized. We have followed up patients for a mean of 2.1 years (maximum 3.6 years), with no complications noted from the surgical procedure. CONCLUSIONS: Direct cannulation of the common carotid artery is a simple, safe, and acceptable cerebral protection for patients undergoing aortic or aortic arch replacement procedures in the patients with these specific conditions.

Type B dissection complicated with subacute visceral ischemia.

A 63-year old man presented with back pain and abdominal pain that worsened after eating. Contrast-enhanced computed tomography revealed type B aortic dissection. Arteriography 20 days after dissection revealed celiac trunk stenosis and the superior mesenteric artery did not arise from the true lumen. Saphenous vein bypass grafting from the right common iliac artery to the superior mesenteric and gastroduodenal arteries was performed. The postoperative course was uneventful and the abdominal symptoms completely disappeared.

Two cases of ventricular tachycardia with congenital left ventricular malformation in an adult.

Two patients without any risk factors for coronary artery disease presented with symptomatic, recurrent, nonsustained ventricular tachycardia. They were found to have a postero-lateral left ventricular aneurysm and diverticulum. Coronary angiography revealed normal coronary arteries. The 12-lead electrocardiogram showed sinus rhythm with frequent premature ventricular contractions. Their nonsustained ventricular tachycardias were reproduced by programmed electrical stimulation and was unresponsive to procainamide, mexiletine, and disopyramide. Aneurysmal resection and cryoablative surgery were performed. The pathological examination of the aneurysmal wall revealed focal defect of muscle fibers in case 1. On the other hand, the wall of case 2 was formed by all three cardiac layers. After surgery, ventricular programmed stimulation was negative, and premature ventricular contraction had disappeared.

Selective visceral perfusion during thoracoabdominal aortic aneurysm repair.

PURPOSE: To evaluate the effectiveness of selective visceral perfusion during repair of an thoracoabdominal aortic aneurysm (TAAA), we compared the postoperative renal and hepatic functions (blood urea nitrogen, serum creatinine, total bilirubin, glutamate pyruvate transaminase) between the two groups with and without perfusion. PATIENTS AND METHODS: We operated on 52 patients with TAAA. Among them, the visceral vessels were reconstructed in 22 patients with selective visceral perfusion and in 12 patients without perfusion. The average selective perfusion time was 49.5+/-25.5 min. in the celiac and superior mesenteric arteries and 32.8+/-18.8 min. in the renal arteries. The average perfusion flow rate per each visceral vessel was 155.4+/-97.4 ml/min. RESULTS: There were five hospital deaths. There was no significant difference between the groups in the postoperative value of four factors. The selective perfusion time for vessel reconstruction in the selective visceral perfusion group was significantly longer than the arterial clamp time for vessel reconstruction in the non-perfusion group (49.5+/-25.5 min. vs. 25.6+/-13.4 min.). CONCLUSION: Our selective visceral perfusion method is not only beneficial for organ protection, but also provides us with the necessary time to reimplant the visceral as well as intercostal or lumbar arteries.

Acute postoperative paraplegia complicating with emergency graft replacement of the ascending aorta for the type a dissection.

Postoperative paraplegia complicating with type A dissection is extremely rare. We describe a case of acute paraplegia after emergency graft replacement of the ascending aorta for type A dissection. A 63 year-old hypertensive man presented to hospital with chest pain. A chest computed tomography demonstrated an aortic dissection of the ascending aorta with mild pericardial effusion. Under deep hypothermic circulatory arrest with concomitant antegrade selective cerebral perfusion, the ascending aorta was replaced. The patient regained consciousness six hours after operation, however, he was complicated with paraplegia. All sensation was lost below the level of Th12. The cause of the paraplegia was assumed to be a thrombotic occlusion of costal arteries, which originated from the false lumen. Spinal fluid was drained for three days. Hyperbaric oxygenation therapy was started four days after onset of paraplegia. Fortunately, our patient recovered gradually, and he was doing well and was walking independently at one-year follow-up. (Ann Thorac Cardiovasc Surg 2003; 9: 330-3)

Prevention of postoperative paraplegia during thoracoabdominal aortic surgery.

BACKGROUND: We present data showing the impact of sequential multisegmental aortic clamping accompanied by reimplantation of as many segmental arteries as possible on the prevention of postoperative paraplegia or paraparesis during thoracoabdominal aortic graft replacement. METHODS: Since 1987 we have performed graft replacements in 51 individuals undergoing thoracoabdominal aortic surgery using the technique of normothermic partial bypass with sequential multisegmental aortic clamping. The procedure was performed emergently in 10 patients and electively in 41 patients. The patients ranged in age from 22 to 82 years (mean, 57.6 +/- 13.8 years). Indications for surgery included dissecting thoracoabdominal aortic aneurysm (n = 19) and nondissecting thoracoabdominal aortic aneurysm (n = 32). The extent of aneurysm was Crawford type I in 19 patients, type II in 7 patients, type III in 12 patients, and type IV in 13 patients. Along the entire extent of aneurysm to be replaced, we reimplanted as many of the patent segmental arteries as feasible. RESULTS: Five patients died during hospitalization, for an in-hospital mortality rate of 9.8%. The number of aortic clampings per patient ranged from one to five (median, three). A total of 124 segmental arteries were reimplanted in 44 (86.3%) of 51 patients. Of the 124 arteries, 90 (72.6%) were distributed between T9 and L2. Postoperative paraplegia or paraparesis did not develop in any of the patients. CONCLUSIONS: Our results demonstrate that extensive reimplantation of segmental arteries using sequential multisegmental aortic clamping, accompanied by adequate intraoperative distal aortic perfusion, is effective in preventing spinal cord ischemia.

Pannus formation in aortic valve prostheses in the late postoperative period.

We present three patients who underwent repeat aortic valve replacement for prosthetic valve dysfunction caused by tissue ingrowth in the late postoperative period. These patients (three women aged 48-51 years, mean 49.3 +/- 1.53 years) underwent operations for restriction of prosthetic valve leaflet movement by pannus in the left ventricular outflow tract. The interval from the previous operation ranged from 8.0 to 9.6 years (mean 9.6 +/- 2.0 years). The symptoms of the patients were New York Heart Association functional class I, II, and IV in one patient each. Diagnosis was made by cinefluoroscopy in two patients and aortography in one patient. The operative procedures consisted of aortic valve replacement ( n = 1) and aortic valve replacement with mitral valve replacement ( n = 2). Pannus was found at the left ventricular aspect of the prosthetic valve in all patients. In two patients, the pannus directly restricted movement of the leaflet and also severely narrowed the inflow orifice of the prosthetic valve. In the other patient, the pannus had grown at a distance of 7 mm from the valve and narrowed the left ventricular outflow tract circularly. The postoperative course was uneventful and all three patients were discharged in a good condition. One patient died of pneumonia 8 months after surgery and the other two patients have remained well and have been followed up for one and a half years. In conclusion, there may be a discrepancy between the clinical symptoms and the grade of subvalvular stenosis caused by pannus. Therefore, it is essential for satisfactory operative results that early diagnosis be made by various means.

Pulseless hematochezia: Takayasu's arteritis associated with ulcerative colitis.

A 36-year-old woman with ulcerative colitis presented with fever, chest and back pain, and fatigue sensation of the arm. Her upper limb pulses were absent. Angiography showed multiple aneurysms of the aorta and its branches, consistent with Takayasu's arteritis. She showed HLA-B35 but no B52, which is the typical haplotype among the coexistence cases of both diseases. Prednisolone was effective. The possible pathogenic association of the disorders is discussed.

Intraoperative transesophageal echocardiographic assessment of myocardial protection in a redo ascending-arch aortic operation.

In a redo operation of the ascending aortic arch, transesophageal echocardiography was useful in confirming antegrade infusion flow of cardioplegia solution into the left main coronary artery.

Experimental study on changes in energy metabolism and urine outflow with nonpulsatile low blood-flow perfusion in the canine kidney.

OBJECTIVE: Renal artery perfusion is useful to prevent renal ischemic injury during thoracoabdominal aortic aneurysm repair, and this study was designed to clarify the relationship between the perfusion flow rate and the renal function. METHODS: Canine left renal arteries were perfused at selective low flow rates (10% of native flow in Group I, 25% in Group II, and 50% in Group III) using a roller pump for 2 h, and thereafter reperfused with native flow for 2 h. At the end of perfusion and reperfusion, the energy metabolites were measured. The urinary output was measured for 30 min during selective perfusion and reperfusion. Thus, the renal function was evaluated using energy metabolites and urine outflow. RESULTS: Adenosine triphosphate levels decreased significantly after perfusion in all groups and were recovered after reperfusion in Group II and in Group III. Inorganic phosphate and lactic acid levels increased after perfusion in Group I and in Group II and decreased after reperfusion. Changes in the perfusion pressure and in the urine outflow, and histologic findings were found to be correlated with the changes in energy metabolite levels. CONCLUSIONS: Renal function was impaired depending on the degree of low perfusion flow and the function was restored after reperfusion at a flow rate of 25% or more of native flow.

Myocardial protective effect of hypothermia during extracorporeal circulation -- by quantitative measurement of myocardial oxygen consumption -.

OBJECTIVE: To evaluate the effect of systemic temperature on myocardial protection during extracorporeal circulation, we quantitatively evaluated the relationship between myocardial oxygen consumption and rectal temperature. MATERIALS AND METHODS: Myocardial oxygen consumption during cardiac arrest was calculated via blood gas analysis of venous blood samples collected from the coronary sinus. The rectal temperatures of the patients during extracorporeal circulation ranged from 16.0 degrees C to 33.5 degrees C. The patients were classified into three groups according to their rectal temperature: group I (n=10; rectal temperature: 20.3+/-1.80 degrees C), group II (n=24; rectal temperature: 29.4+/-0.97 degrees C), and group III (n=29; rectal temperature: 31.7+/-0.72 degrees C). The myocardial oxygen consumption of each group was then compared. RESULTS: The average of the myocardial oxygen consumption of all cases was 62.5+/-64.0 O(2) ml/min/100 mm(3) left ventricle volume, and the averages of the individual groups were 26.9+/-28.8 in group I, 72.2+/-71.8 in group II, and 69.3+/-62.6 in group III. There was a significant difference in the oxygen consumption between group I and the other two groups. There was a positive correlation between the rectal temperature and myocardial oxygen consumption, as reflected in the following formula: Y=-0.3 x X +1.10 x X(2)-0.02 x X(3) (Y, myocardial oxygen consumption; X, rectal temperature; R(2)=0.533; P<0.0001). CONCLUSION: This study suggested that rectal temperature below 22.5 degrees C is advantageous due to the resultant myocardial protection such hypothermia affords.