Senri Miwa

Adrenomedullin Infusion Attenuates Myocardial Ischemia/Reperfusion Injury Through the Phosphatidylinositol 3-Kinase/Akt-Dependent Pathway

Background—Infusion of adrenomedullin (AM) has beneficial hemodynamic effects in patients with heart failure. However, the effect of AM on myocardial ischemia/reperfusion remains unknown. Methods and Results—Male Sprague-Dawley rats were exposed to a 30-minute period of ischemia induced by ligation of the left coronary artery. They were randomized to receive AM, AM plus wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor), or saline for 60 minutes after coronary ligation. Hemodynamics and infarct size were examined 24 hours after reperfusion. Myocardial apoptosis was also examined 6 hours after reperfusion. The effect of AM on Akt phosphorylation in cardiac tissues was examined by Western blotting. Intravenous administration of AM significantly reduced myocardial infarct size (28±4% to 16±1%, P <0.01), left ventricular end-diastolic pressure (19±2 to 8±2 mm Hg, P <0.05), and myocardial apoptotic death (19±2% to 9±4%, P <0.05). Western blot analysis showed that AM infusion accelerated Akt phosphorylation in cardiac tissues and that pretreatment with wortmannin significantly attenuated AM-induced Akt phosphorylation. Moreover, pretreatment with wortmannin abolished the beneficial effects of AM: a reduction of infarct size, a decrease in left ventricular end-diastolic pressure, and inhibition of myocardial apoptosis after ischemia/reperfusion. Conclusions—Short-term infusion of AM significantly attenuated myocardial ischemia/reperfusion injury. These cardioprotective effects are attributed mainly to antiapoptotic effects of AM via a PI3K/Akt-dependent pathway.

Effect of Different Methods of Internal Thoracic Artery Harvest on Pulmonary Function

BACKGROUND In several clinical studies, internal thoracic artery (ITA) grafting for myocardial revascularization has been identified as increasing the risk of postoperative pulmonary complications. This study was designed to determine whether the technique used to harvest the ITA has an effect on postoperative pulmonary function. METHODS Seventy-nine consecutive patients undergoing coronary artery bypass grafting using the left ITA were compared with patients undergoing coronary artery bypass grafting using saphenous vein grafts only. Two methods of ITA harvesting were used: (1) incision of the endothoracic fascia dissected off the ITA as a skeletonized vessel (group 1, n = 33) and (2) mobilization of the ITA as a wide musculofascial pedicle (group 2, n = 46). Thirty-two patients underwent coronary artery bypass grafting using saphenous vein grafts only (group 3). Pulmonary function tests were performed between postoperative days 20 and 30. RESULTS The postoperative values of forced vital capacity were reduced in patients in all groups (p < 0.0001). The ratios of postoperative to preoperative forced vital capacity were 84% in group 1, 77% in group 2, and 84% in group 3. The reduction in group 2 was significant compared with group 1 (p < 0.05) and group 3 (p < 0.05). CONCLUSIONS Postoperative pulmonary dysfunction was significantly greater in patients who underwent wide musculofascial pedicle dissection of the ITA compared with skeletonization of the artery. Thus, of the two techniques, the latter may be the method of choice with regard to lowering the incidence of postoperative pulmonary dysfunction.

Mycotic aneurysm of the left coronary artery.

We report a 24-year-old man with mitral valve endocarditis complicated by acute myocardial infarction due to coronary embolism. Percutaneous transluminal coronary angioplasty and subsequent mitral valve replacement were performed. Postoperative coronary angiography revealed formation of a mycotic aneurysm of the left anterior descending coronary artery at the site of balloon inflation. The patient then underwent successful resection of the aneurysm with coronary artery bypass grafting.

Coronary Revascularization in Patients With Liver Cirrhosis

BACKGROUND Liver cirrhosis is a major risk factor for cardiac surgery using cardiopulmonary bypass. However, percutaneous coronary intervention (PCI) or off-pump coronary artery bypass graft surgery (OPCABG) may be a less invasive alternative strategy. METHODS Among the 9,877 patients undergoing first PCI or CABG enrolled in the CREDO-Kyoto Registry (a registry of first-time PCI and CABG patients in Japan), 332 patients diagnosed with liver cirrhosis were entered into the study (age 67.1±9.4 years; 246 male). Liver cirrhosis was diagnosed by liver biopsy or signs of portal hypertension with characteristic morphologic liver and spleen changes. RESULTS A total of 233 patients received PCI, 58 conventional on-pump CABG (CCABG), and 41 OPCABG. Median follow-up was 3.3 years. The PCI group included less complex coronary lesions such as triple vessel and left main disease (p<0.01 each). Propensity score adjusted in-hospital mortality after CCABG or OPCABG was higher than that after PCI; however, the differences were not significant (odds ratio [95% confidence interval]: 6.84 [0.52 to 90.8], p=0.14 for CCABG versus PCI; and 1.86 [0.08 to 45.8], p=0.71 for OPCABG versus PCI). Adjusted overall mortality after CCABG or CABG was lower than that after PCI, but the differences were not significant (0.66 [0.31 to 1.40], p=0.28; and 0.64 [0.28 to 1.49], p=0.31, respectively). Approximately two thirds of patients died of noncardiovascular morbidities (malignancies, including hepatocarcinoma, or hepatic decompression). CONCLUSIONS Because overall noncardiovascular mortality is high among patients with liver cirrhosis, complete revascularization may not be associated with better survival outcomes. Further study is warranted to determine the impact of a coronary revascularization strategy for liver cirrhosis patients.

Visualization of intramuscular left anterior descending coronary arteries during off-pump bypass surgery

In off-pump coronary artery bypass surgery, an appropriate method for intraoperative evaluation of grafts and vessels has been awaited. We report the usefulness of a 15-MHz linear transducer for this purpose. A 15-MHz linear transducer with a SONOS 5500 (Philips Medical Systems, Best, Netherlands) was applied epicardially in off-pump coronary artery bypass surgery patients. Vascular anatomy was easily discerned when the transducer was applied in an appropriate way. In 6 patients, intramuscular coronary arteries were easily detected, and in all of these patients, anastomoses were successful. The shapes of the anastomoses were very clearly shown, and the flow and its phase in the bypass graft or coronary artery were measured with synchronization of electrocardiograms in all patients. The total left internal thoracic artery (LITA) flow (28.4 +/- 6.8 mL/s) and the pattern of the flow was dominantly diastolic in all patients. The 15-MHz linear transducer system (Philips) is very useful for detecting intramuscular left anterior descending coronary arteries and may become one of the standard tools for intraoperative evaluation in off-pump coronary artery bypass surgery.

Effect of edaravone, a novel free radical scavenger, supplemented to cardioplegia on myocardial function after cardioplegic arrest: in vitro study of isolated rat heart

Cardioplegic arrest has been the main mechanism of myocardial protection during open-heart surgery; however, it causes myocardial injury during ischemia-reperfusion. Free radical scavengers are widely known to attenuate ischemia-reperfusion injury in various settings. We investigated the effects of edaravone, a novel free radical scavenger that was originally used for cerebral protection, on myocardial function during ischemia-reperfusion after cardioplegic arrest. Rat hearts were excised and perfused using Langendorff apparatus. The hearts were cardioplegically arrested for 90 min using St. Thomas’ Hospital cardioplegic solution (ST solution) at 4°C every 45 min and then reperfused for 20 min. The hearts were divided into 4 groups (n = 13 in each group). In Group ST, the hearts were arrested using the ST solution alone. In Groups L, M, and H, the hearts were arrested using the ST solution supplemented with a low-dose (1 μM), moderate dose (10 μM), and high dose (100 μM) of edaravone, respectively. Left ventricular function (+dp/dtmax) and the levels of the cardiac enzymes released were measured before and after cardioplegic arrest. At the end of the study, the water content and the tissue oxidative stress (8-hydroxy-2′-deoxyguanosine) of the heart were measured. During reperfusion, the edaravone-treated groups showed a greater functional recovery with regard to the +dp/dtmax (P < 0.05). The lactate level was the lowest (P < 0.01) in Group M. The water content of the hearts in the edaravone-treated groups was significantly lower (P < 0.05) than that in Group ST. Oxidative stress was significantly lower (P < 0.01) in the edaravone-treated hearts than in Group ST, and it was the lowest in Group M. The addition of edaravone to the cardioplegic solution ameliorates the impairment in myocardial function by reducing the oxidative stress after cardioplegic arrest. In this study, the maximum improvement in the myocardial function was achieved by addition of a moderate dose (10 μM) of edaravone.

Topical Application of a Biodegradable Disc With Amiodarone for Atrial Fibrillation

BACKGROUND Amiodarone is a potent anti-atrial fibrillation (AF) agent; however, its systemic administration induces serious side effects such as interstitial pneumonia. To avoid such effects, we developed a local sustained-release system for amiodarone. METHODS A biodegradable, cross-linkable dextran disc was developed as a sustained-release carrier for amiodarone. Under general anesthesia, Japanese white rabbits underwent median sternotomy and the biodegradable disc with or without amiodarone (30 mg) was implanted onto the surface of the right atrium. Three days after implantation, we measured tissue amiodarone concentrations (n = 5), the AF threshold, and the atrial effective refractory period of the left atrium by using the Langendorff apparatus. The incidences of induced AF evoked by rapid pacing were measured and compared. RESULTS The right atrial concentration of amiodarone was far higher than that in the lungs, ventricles, or other organs (p < 0.01). The blood concentration of amiodarone was below detectable levels. The amiodarone biodegradable disc significantly increased the AF threshold (amiodarone group, 6.9 ± 4.6 mA versus control group, 0.5 ± 0.6 mA; p < 0.01) and the effective refractory period (amiodarone group, 53.9 ± 8.9 milliseconds versus control group, 43.9 ± 9.5 milliseconds; p = 0.035) of the left atrium, indicating the electrophysiologic effect of the amiodarone biodegradable disc on the left atrium. Further, the amiodarone group was significantly less likely to experience AF, as compared with the control group (p < 0.01). CONCLUSIONS This approach may be a less invasive and effective therapeutic option for preventing postoperative AF.

Living-donor lobar lung transplantation with sparing of bilateral native upper lobes: a novel strategy.

A 44-year-old man became wheelchair-bound due to sever bronchiolitis obliterans caused by peripheral blood stem cell transplantation for acute myelogenous leukemia. His lung donors, his sister and his wife, were 17 cm shorter than him. He successfully underwent living-donor lobar lung transplantation with sparing of the bilateral native upper lobes to address the size mismatch. Ten months after the transplantation, the patient has returned to a normal lifestyle without supplemental oxygen.

Pulmonary arterioplasty for the remaining arterial stump of the donor and the arterial cuff of the donor graft in living-donor lobar lung transplantation

In living-donor lobar lung transplantation (LDLLT), donor surgeries are conducted in ways that ensure proper dissections for both donors and recipients. We report a case of LDLLT, in which pulmonary arterioplasties with autopericardial patch were performed on both a donor and a recipient. Since excision of the lingular branch of the pulmonary artery was carried out far lower than that of the upper segment of the left lower lobe branch, pulmonary arterioplasty was performed to avoid potential stricture of the remaining lingular branch. Also, because of the oblique stump of the graft pulmonary artery, pulmonary arterioplasty with autopericardial patch was required in the recipient.

Effects of two inhibitors of renin-angiotensin system on attenuation of postoperative remodeling after left ventricular aneurysm repair in rats.

Abstract We reported that the initial beneficial effects of left ventricular repair (LVR) surgery for LV aneurysm after myocardial infarction (MI) did not persist because of postoperative LV remodeling in a rat model. The renin‐angiotensin system (RAS) plays an important role in postinfarction LV remodeling. Inhibition of RAS may be useful to preserve LV function by preventing remodeling. We studied the effects of two inhibitors of RAS in an attempt to improve the operative results of LVR. LV aneurysms were created in rats after ligating the left anterior descending artery. These rats underwent LVR by plicating the LV aneurysm and were treated by three methods: no treatment, treatment with angiotensin‐converting enzyme inhibitor (ACE‐I) (lisinopril 10 mg/kg per day), and treatment with angiotensin II receptor blocker (ARB) (candesartan 5 mg/kg per day). One week after LVR, echocardiography revealed smaller LV size and better LV motion than before surgery. Four weeks after LVR, LV size returned to the preoperative value in the untreated group, but not as much in the treated groups. Cardiac catheterization revealed lower LV end‐diastolic pressure and higher E‐max in the treated groups. There was no difference between ACE‐I and ARB groups except for systolic blood pressure. LVR decreased LV size and improved systolic function only in the early phase. Adjuvant therapy of ACE‐I or ARB‐attenuated LV remodeling and maintained LV function at the same level after LVR. This probably indicates that tissue RAS is associated with postoperative remodeling. Concomitant use of RAS inhibitors may make LVR a longer‐lasting procedure for LV aneurysm. (J CARD SURG 2003;18 (Suppl 2):S61‐S68)