A key role for the subunit SUR2B in the preferential activation of vascular KATP channels by isoflurane.

BACKGROUND AND PURPOSE: It has been postulated that isoflurane, a volatile anaesthetic, produces vasodilatation through activation of ATP-sensitive K+ (KATP) channels. However, there is no direct evidence for the activation of vascular KATP channels by isoflurane. This study was conducted to examine the effect of isoflurane on vascular KATP channels and compare it with that on cardiac KATP channels. EXPERIMENTAL APPROACH: Effects of isoflurane on KATP channels were examined in aortic smooth muscle cells and cardiomyocytes of the mouse using patch clamp techniques. Effects of the anaesthetic on the KATP channels with different combinations of the inward rectifier pore subunits (Kir6.1 and Kir6.2) and sulphonylurea receptor subunits (SUR2A and SUR2B) reconstituted in a heterologous expression system were also examined. KEY RESULTS: Isoflurane increased the coronary flow in Langendorff-perfused mouse hearts in a concentration-dependent manner, which was abolished by 10 microM glibenclamide. In enzymically-dissociated aortic smooth muscle cells, isoflurane evoked a glibenclamide-sensitive current (i.e. KATP current). In isolated mouse ventricular cells, however, isoflurane failed to evoke the KATP current unless the KATP current was preactivated by the K+ channel opener pinacidil. Although isoflurane readily activated the Kir6.1/SUR2B channels (vascular type), the volatile anesthetic could not activate the Kir6.2/SUR2A channels (cardiac type) expressed in HEK293 cells. Isoflurane activated a glibenclamide-sensitive current in HEK293 cells expressing Kir6.2/SUR2B channels. CONCLUSION AND IMPLICATIONS: Isoflurane activates KATP channels in vascular smooth muscle cells and produces coronary vasodilation in mouse hearts. SUR2B may be important for the activation of vascular-type KATP channels by isoflurane.

[Is the quality of off-pump coronary artery bypass grafting equivalent to that of conventional coronary artery bypass grafting].

We analyzed 44 patients undergoing coronary artery bypass grafting (CABG) from November 2001 to March 2003. Of 44 patients, 40 patients (29 men and 11 women; mean age 68.1 +/- 9.2 years) underwent off-pump CABG (OPCAB) [90.9%]. The mean number of bypass grafts was 2.53 +/- 0.78. In-hospital mortality was none and major complications except for one case of reexploration for bleeding were not seen. The early patency rate of over-all grafts was 94.6%. The quality of OPCAB was considered to be equivalent to conventional CABG.

[Inferior vena cava cannulation using Forgaty catheter for partial cardiopulmonary bypass].

Partial cardiopulmonary bypass is adopted in operation for aneurysm of descending aorta or DeBakey IIIb dissection. Cannulation from left common femoral vein to inferior vena cava (IVC) is often difficult because of operative position and anatomical relation of iliac veins to IVC. In this paper, IVC cannulation using Forgaty catheter is reported to be easy and safe for prevention of IVC perforation.

Prediction of improvement in regional left ventricular function after coronary artery bypass grafting: quantitative stress-redistribution 201Tl imaging in detection of myocardial viability.

BACKGROUND: This study investigated the usefulness of quantitative assessment of Thallium-201 stress redistribution myocardial scintigraphy combined with quantitative assessment of regional left ventricular function using the centerline method for predicting of recovery regional left ventricular function following myocardial revascularization. METHODS: Twenty patients with chronic total obstruction of the proximal portion of left anterior descending artery and/or right coronary artery were studied. Percent Tl-uptake method was used to evaluate myocardial viability before CABG. Regional LV function was evaluated before and after CABG with the centerline method. The territory of LAD was defined by chords 10 to 58 and that of RCA was defined by chords 59 to 80 in the centerline method. The parameter of regional left ventricular function was the mean (SF-Av.)/SD of each LAD and RCA territory. RESULTS: In cases showing a % uptake value under 50%, the preoperative value of (SF-Av.)/SD was -3.18+/-0.74 and postoperative value was -2.63+/-0.8 1. The difference between these values was not significant. When the %uptake value over 50%, the preoperative value of (SF-Av.)/SD was -2.80+/-0.49 and the postoperative value was -2.27+/-0.28. The postoperative value was significantly higher than the preoperative value(p=0.007). CONCLUSIONS: Even in cases of severe left ventricular dysfunction, regional left ventricular function improved if the value of % uptake in the redistribution Thallium imaging was 50% or over. Quantitative analysis of myocardial scintigraphy combined with quantitative analysis of left ventriculography is a useful method for predicting recovery of regional left ventricular function following myocardial revascularization.

[Total arch replacement using prior selective cerebral perfusion].

Prior selective cerebral perfusion is the method whereby selective cerebral perfusion and systemic perfusion start almost simultaneously, and the arch vessels are clamped. Cerebral circulation is isolated from systemic circulation to avoid cerebral embolization owing to detachment of atherosclerotic material from the aorta, caused by the "sandblasting" effect of high-velocity jets of blood exiting the aortic canula. Twenty-seven consecutive patients underwent total arch replacement for degenerative aortic arch aneurysm using prior selective cerebral perfusion from 1992 to 2001. Surgical death (within 1 month after operation) was 2 cases (7.4%), in-hospital death was 5 cases (18.5%). Systemic circulatory arrest time is almost equal to the time which distal anastomosis takes. The time was 81.4 +/- 24.3 minutes. Selective cerebral perfusion time was 194.9 +/- 30.9 minutes. Extracorporeal circulation time was 280.6 +/- 55.3 minutes. The time for emergence from anesthesia was 6.0 +/- 2.7 hours. Permanent neurologic dysfunction which was thought to occurred within 48 hours after surgery was noted in 1 case (3.7%). Postoperative survival at 8 years was 73.3%. There was 1 arch aneurismal related accident. Prior selective cerebral perfusion may be useful for avoiding cerebral embolization.

Surgical treatment for chronic pulmonary thromboembolism under cardiopulmonary bypass with selective cerebral perfusion.

The median sternotomy approach for the treatment of chronic pulmonary thromboembolism was recently improved by Daily, Jamieson, and coworkers who adopted it for use under cardiopulmonary bypass with intermittent circulatory arrest; however, we have sometimes found that the circulatory arrest time was too short to complete thromboendarterectomy. Therefore, we attempted to perform a selective cerebral perfusion technique to extend the endarterectomy time. Although we noted slight back-bleeding from the bronchial arteries, we were able to extend the endarterectomy time without causing any postoperative delirium. We conclude that the median sternotomy approach using cardiopulmonary bypass with selective cerebral perfusion may be the best option for extending the thromboendarterectomy time.

[A combination of reoperation for pseudoaneurysm following the Cabrol procedure and total aortic arch replacement in a patient with Marfan syndrome--a case with an aberrant right subclavian artery].

A 44-year-old male with Marfan's syndrome had undergone an initial operation for DeBakey type I acute aortic dissection with annulo-aortic ectasia. He had undergone replacement of the ascending aorta and aortic valve with a composite graft and reconstruction of the coronary artery by the Cabrol procedure. At 5 years after the initial surgery he experienced chest pain and was subsequently examined. Computed tomography revealed a pseudoaneurysm in the ascending aorta and the residual aortic dissection. The maximum diameter of the pseudoaneurysm was 85 mm and the maximum diameter of the aortic arch was 55 mm. The aortic arch was associated with an aberrant right subclavian artery. Angiography revealed that the pseudoaneurysm was caused by leakage at the coronary ostium-graft anastomoses. We repaired the anastomoses and performed total aortic arch replacement with reconstruction of four arch branches. The postoperative course was uneventful without any complications. We report this case because there have been few reports regarding arch replacement in cases with an aberrant right subclavian artery.

Separate-hypothermia retrograde cerebral perfusion.

We have developed a technique of cerebral protection in which the blood for the retrograde cerebral perfusion from the superior vena cava cannula is cooled down to 10 degrees C, while the core temperature is maintained at moderate hypothermia. We performed graft replacement of the ascending and aortic arch in 2 patients with dissecting aneurysm using this method. This technique may provide excellent cerebral protection without coagulation disorder.

[Surgical treatment of traumatic rupture of the aortic valve].

Rupture of the aortic valve after a blunt chest trauma is rare. A 63-year-old man was injured in an automobile accident and was hospitalized elsewhere due to acute respiratory failure 4 days after the accident. On admission, he was intubated immediately. The patient did not respond to available medical treatments and was therefore transferred to our hospital. His condition was diagnosed as severe left heart failure, and an emergency operation was performed. The right coronary and non-coronary cusps were perforated and the commissure between the right coronary and non-coronary cusps was torn. The aortic valve was excised and a SJM 25 AEC prosthetic valve was inserted. The patient recovered well postoperatively.

[A case report of a successful Redo Bentall operation].

An initial Bentall operation was performed on a patient aged 38 years with annuloaortic ectasia and aortic regurgitation. An echocardiogram and RI angiogram revealed a perigraft aortic aneurysm on the same patient aged 45 years. The aneurysm gradually developed and the maximum diameter reached 90 mm in size. The Redo-Bentall operation (Piehler modification) was successfully done once again on the same patient aged 56 years. The anastmosis between the right coronary orifice and the graft was detached on all sides. The anastmosis between the left coronary orifice and the graft was detached two thirds of all sides.

[Selection of the surgical methods and surgical outcome of the distal arch aneurysm].

Between January, 1985, and December, 1993, 20 patients (18 males, 2 females; median age 65 years) underwent repair of aneurysms of the distal arch. fourteen patients had sacciform aneurysms and 6 patients had fusiform aneurysms. The approaching methods to the aneurysms were left thoracotomy in 3 patients and median sternotomy in 17 patients, including the so-called "door open method" in 2 patients. The supportive methods during surgery were left heart bypass using a centrifugal pump in 3 patients cardiopulmonary bypass with selective cerebral perfusion in 11 patients, and cardiopulmonary bypass with retrograde cerebral perfusion in 6 patients. The operative methods were patch closure in 4 patients, graft replacement using the inclusion technique in 13 patients, and total arch replacement using the exclusion technique in 3 patients. One patient who underwent left heart bypass died intraoperatively from intractable bleeding, one who had undergone selective cerebral perfusion died postoperatively of rupture of the distal anastomosis and two patients, who were supported with retrograde cerebral perfusion, died postoperatively because of perioperative myocardial infarction or rupture of the dissection arising from the aneurysm. There were three cases with cerebral complications postoperatively. These three patients were supported with selective cerebral perfusion. Graft exclusion technique using a prosthetic graft with three branches under the retrograde cerebral perfusion shortened cardiopulmonary bypass time and heart and brain ischemic time, so that this technique might reduce cerebral complications and should be a promising surgical treatment for the distal arch aneurysm.

[A successful repair of the aortic dissection (DeBakey type I) with ischemic complications of the kidney and lower extremities].

A 65-year-old male was referred to our institution under diagnosis of aortic dissection which passed 1 month after the onset. An aortography revealed DeBakey type I aortic dissection with the left renal artery involvement and the very narrow true lumen of the abdominal aorta compressed by the pseudolumen, especially at the orifice of the right renal artery. On the 3rd day of admission, the patient manifested SVC syndrome, oliglia and pulselessness of the femoral artery bilaterally, that indicated ischemia of the kidney and the lower extremities. An emergency operation was performed, and the ascending aorta was replaced using open distal anastomotic technique for the distal site of the aorta under deep hypothermia and retrograde cerebral perfusion method. The ischemic symptoms and SVC syndrome were disappeared promptly after operation. Postoperative CTscan showed the narrow true lumen of the abdominal aorta expanded remarkably. The postoperative course was uneventful and the patient discharged on the 54th postoperative day.

Retrograde cerebral perfusion with hypothermic blood provides efficient protection of the brain: a neuropathological study.

Retrograde cerebral perfusion is a method that is recently being used for protection of the brain during operations on the aortic arch. This method is useful but is said to provide a limited time for protecting the brain. We designed an experiment in dogs to investigate neuropathologically the effect of protecting the brain for 120 minutes under: (1) circulatory arrest (CA); (2) retrograde cerebral perfusion with moderately cooled blood (RCPMC); and (3) retrograde cerebral perfusion with deeply cooled blood (RCPDC). We calculated the number of the abnormal cells of 400 hippocampal neurons per dog light microscopically. The number was 199 +/- 23 (mean +/- 1 SD) in the CA group, 149 +/- 50 in the RCPMC group, and 72 +/- 33 in the RCPDC group. The difference between the CA group and the RCPMC group was not statistically significant (p < 0.05), but there was a significant difference between the RCPMC and RCPDC groups (p < 0.05). The degree of cerebral protection provided by retrograde cerebral perfusion for 120 minutes is not sufficient when using moderately cooled blood. If we use deeply cooled blood at a temperature of about 10 degrees C, we should obtain a sufficient degree of protection of the brain.

[Successful mitral valve plasty for mitral regurgitation combined with dilated cardiomyopathy in Noonan's syndrome].

We have experienced a mitral valve plasty for mitral regurgitation combined with dilated cardiomyopathy in a 21-year-old male patient with Noonan's syndrome, who had suffered from recurrent congestive heart failure. In echocardiography, severe mitral regurgitation and prolapse of the posterior mitral leaflet were noted. The left ventricle was dilated and the function was severely deteriorated. The plasty consisted of plication of the prolapsed posterior leaflet and annuloplasty with Carpentier ring. Intraoperative biopsy of the myocardium of the left ventricle showed an appearance consisting with dilated cardiomyopathy. Postoperatively the mitral regurgitation disappeared and the patient returned to his ordinary life.

[Surgical treatment of aortico-left ventricular communication due to infective endocarditis].

A 51-year-old woman was referred to our institute for surgical treatment from an other hospital where she was diagnosed as having a mycotic aneurysm located at the aortic annulus due to infective endocarditis. The aneurysm communicated with the left ventricle, with aortic stenosis and regurgitation, mitral stenosis and tricuspid regurgitation caused by rheumatic fever. On admission to our institute, the infective endocarditis was at the healed stage. The mycotic aneurysm was located at the aortic annulus of the right coronary cusp, and was closed using a prosthetic patch with mattress sutures. Aortic valve replacement with a 19-mm St. Jude Medical prosthesis was then performed on this patch. The mitral and tricuspid valves were also replaced with 27-mm and 29-mm St. Jude Medical prostheses, respectively. The patient is doing well 1 year after surgery.

Medium-term results after surgery for aortic arch aneurysm with hypothermic cerebral perfusion.

We have used two techniques of hypothermic cerebral perfusion (CP) for the surgical treatment of aortic arch aneurysm in the last 10 years. Between March 1985 and December 1993, 83 patients underwent surgery for aortic arch aneurysm. Fifty-one cases had aortic dissection (AD) in the transverse arch and/or its branches, and 32 cases showed true aneurysm (TA) of the aortic arch. In those 83 patients, 37 cases received antegrade CP and 46 cases underwent retrograde CP. Surgical results were compared among the groups by Kaplan-Meier actuarial method and Cox-Mantel statistical analysis. The early mortality after surgery for aortic arch aneurysm was 11.8% in the AD group and 21.9% in the TA group. The early mortality was 21.6% with antegrade CP and 10.9% with retrograde CP. The 6-year actuarial survival rate was 71.7% in the TA group and 67.1% in the AD group. In the AD group, the 3-year survival rate was 93.9% with retrograde CP and 61.1% with antegrade CP (P < 0.005). In the TA group, the 3-year survival rate was similar for antegrade CP (73.3%) and retrograde CP (69.2%). These results suggest that current surgical results of aortic arch aneurysm with hypothermic CP are acceptable and the retrograde CP technique might be recommended, especially for surgery of aortic arch aneurysm with AD.

[Transcranial Doppler measurement of middle cerebral artery blood flow during continuous retrograde cerebral perfusion].

This is the first report of cerebral blood flow measurement with transcranial Doppler (TCD) during aortic arch reconstruction using continuous retrograde cerebral perfusion (CRCP) with deep hypothermia. Cerebral blood flow velocity was measured in 6 patients. CRCP was performed via the superior vena cava (SVC) at 30 cmH2O of internal juglar vein pressure and at 18 degrees C or lower of minimum bladder temperature. During the operation, the flow velocity of the middle cerebral artery (MCA) was continuously measured with TCD fixed on the temple. The cerebral blood flow during CRCP was different in each of the 6 patient. The retrograde MCA flow could be measured during CRCP in 3 patients, and the flow velocity was 11-60% of the MCA flow velocity before cardiopulmonary bypass. In the other 3 patients, retrograde MCA flow could not be detected during CRCP, but antegrade MCA flow could be found after antegrade perfusion was resumed. The antegrade flow velocity right after CRCP became more than the MCA flow before CRCP, which was regarded as a reaction due to cerebral ischemia. All the patients awoke within several (2-9) hours after operations and had no permanent neurological complications. But 2 patients developed drowsiness for several days after the operations; their CRCP times were 127 and 131 minutes. It is concluded that CRCP is a simple technique for brain protection, but the cerebral blood flow during CRCP is a simple technique for brain protection, but the cerebral blood flow during CRCP is different in each patient.(ABSTRACT TRUNCATED AT 250 WORDS)

[Rescue effect of 15-deoxyspergualin for acute rejection on heart transplantation--using a rat model].

15-Deoxyspergualin (DSG) attracts a lot of attention as an immunosuppressive drug which has less side effects these days. In the present study, we researched the rescue effect of DSG for acute rejection on heart transplantation (HTX) by using rat models. We performed 40 heterotopic heart transplantation models. We injected them DSG (group A: 5 mg/kg/day, group B: 10 mg/kg/day) intravenously through 3 days, starting from the 3rd day the 4th day, and the 5th day after HTX. Our previous study showed the pathology on the 3rd day after HTX corresponded to mild rejection, the 4th day to moderate rejection, and the 5th day to severe rejection. One day after the injection was completed, the recipients were sacrificed. The rescue effect was histopathologically assessed by H-E stain, and the action mechanism of DSG was considered by immunohistochemical stain using monoclonal antibodies, which were against CD4 positive cells, CD8 positive cells, and macrophages. In result, the rescue effect of DSG was significant in all groups, in comparison with controls, which had no immunosuppression. And the rescue effect of group B was superior to group A. We also found using a immunohistochemical technique, that DSG inhibited the accumulation of CD4 and CD8 positive cells. We concluded the rescue effect of DSG for acute rejection on HTX was significant, especially in 10 mg/kg/day even in the severe rejection. And the suppression of helper and cytotoxic T cells accumulation might be one of the action mechanisms of DSG.

[Effect of retrograde cerebral perfusion in preserving cerebral function during circulatory arrest].

The efficacy of retrograde cerebral perfusion (RCP) method was evaluated in 26 patients who underwent aortic arch reconstruction. Surgical procedures were; ascending-proxymal arch replacement involving Bentall type procedures (17 cases), total arch replacement (4 cases), and distal arch replacement (5 cases). The RCP were performed through selective cannulation on the superior vena cava at 18.4 degrees C of the average rectal temperature. The perfusion pressure was 28.3 (+/- 5.9) cmH2O and flow was 360 (+/- 15.4) ml/min. RCP time was 74.1 (+/- 26.2) min. Twenty-four patients survived among 26 patients and 2 patients died after operation. Postoperative consciousness was confirmed in 25 patients. Postoperative neurological complications were 1) delayed arousal 5 cases, 2) delirium 3 cases, 3) respiratory disorders 5 cases, 4) double vision 2 cases, 5) cerebral infarction (CI) 1 case. These complications except-CI were resolved in early postoperative period. And regarding effective time period of RCP, incidence of neurological complications were significantly higher in cases which received RCP over 80 min. Therefore we consider that 80 min is a safety time period. In conclusion, RCP is a useful step for preserving the brain during the operation of graft replacement of aorta involving aortic arch.