[Acute Aortic Dissection Complicated by IgA Deficiency].

Immunoglobulin A (IgA) deficiency is the most common type of primary immunodeficiency. When a patient receives a blood product transfusion, anti-IgA antibodies are formed. Second transfusion may sometimes cause an anaphylactic reaction, thus caution is necessary. Reported here is a case of Stanford type A acute aortic dissection performed in the patient with IgA deficiency with a history of blood transfusion. Red blood cells and platelet were washed and prepared, and flesh frozen plasma from IgA deficient donors was obtained. Thereafter, the surgery was safely performed.

[Lipomatous Hypertrophy of Interatrial Septum in Patient with Venous Thrombus:Report of a Case].

A 64-year-old female underwent a computed tomography (CT) examination of the chest because of pneumonia, which revealed lipomatous hypertrophy of the atrial septum. During medical treatment for pneumonia, venous thrombus of the superior vena cava occurred and then disappeared following apixaban administration. The patient refused surgery at that time, thus follow-up examinations include CT scans were conducted at the outpatient clinic. Two years later, the tumor became larger, and this time she accepted surgery. Under total cardiopulmonary bypass with beating heart a 5.0×3.5 cm tumor was resected. Because of its location very close to superior vena cava, upper area of the right atrium was augmented using a bovine pericardium. Following surgery, sick sinus syndrome developed and pacemaker implantation was performed. Thereafter, the patient had a smooth recovery and no recurrence is noted one year since.

[Off-pump Coronary Artery Bypass Grafting in Jehovah's Witness Patient on Hemodialysis;Report of a Case].

Cardiac surgery in Jehovah's witnesses is challenging due to their refusal of blood transfusion. Furthermore, dialysis patients often suffer from anemia and are also prone to bleeding. We performed offpump coronary artery bypass grafting (CABG) [OPCAB] on a Jehovah's witness male patient on hemodialysis. His preoperative hemoglobin level was around 10.0 g/dl. We used cell saver-collected blood as much as possible during operation. His postoperative course was uneventful with the lowest hemoglobin level of 7.2 g/dl using iron supplements and erythropoietin. This case indicates that intraoperative blood salvage and perioperative management of anemia make OPCAB without blood transfusion possible even in Jehovah's witness hemodialysis patients, when their preoperative hemoglobin levels are maintained greater than 10.0 g/dl.

[Acute Type B Aortic Dissection Complicated with Malperfusion of Celiac Artery Alone;Report of a Case].

Malperfusion of the superior mesenteric artery(SMA) in acute type B aortic dissection is potentially fatal. Revascularization should therefore be aggressively considered in a proactive way. However, this is not the case with the celiac artery malperfusion. We present a case of malperfusion of isolated malperfusion of the celiac artery due to acute type B aortic dissection. Although the collateral blood flow from the SMA via the pancreatic arcade was identified, ischemic gastric ulcer and pancreatitis developed later on. At present, there is a general agreement that catheter intervention is the 1st treatment of choice for complicated acute type B aortic dissection. In the present case, however, even a guide wire did not pass through the orifice of the celiac artery and revascularization was not successful.

[Emergency Mitral Valvoplasty for Papillary Muscle Rupture].

We experienced 2 emergency surgical cases of severe mitral valve regurgitation due to papillary muscle rupture. Case 1:a 69-year-old man presented with respiratory and cardiac failure due to mitral regurgitation. He had no history of myocardial infarction. Mitral valve repair with artificial cords was performed. The papillary muscle of the anterior leaflet was ruptured. The postoperative course was uneventful. Case 2:a 80-year-old man came to our hospital with cardiac arrest. Emergency coronary intervention was performed to the right coronary and intraaortic balloon pumping was inserted. However his condition remained unstable. Severe mitral regurgitation was found by teansesophageal echo cardiography, and he underwent emergency mitral valve repair and single coronary bypass grafting. His cardiac function recovered quickly, but severe brain damage remained.

Increased severity of reperfusion arrhythmias in mouse hearts lacking histamine H3-receptors.

We had previously reported that activation of histamine H(3)-receptors (H(3)R) on cardiac adrenergic nerve terminals decreases norepinephrine (NE) overflow from ischemic hearts and alleviates reperfusion arrhythmias. Thus, we used transgenic mice lacking H(3)R (H(3)R(-/-)) to investigate whether ischemic arrhythmias might be more severe in H(3)R(-/-) hearts than in hearts with intact H(3)R (H(3)R(+/+)). We report a greater incidence and longer duration of ventricular fibrillation (VF) in H(3)R(-/-) hearts subjected to ischemia. VF duration was linearly correlated with NE overflow, suggesting a possible cause-effect relationship between magnitude of NE release and severity of reperfusion arrhythmias. Thus, our findings strengthen a protective antiarrhythmic role of H(3)R in myocardial ischemia. Since malignant tachyarrhythmias cause sudden death in ischemic heart disease, attenuation of NE release by selective H(3)R agonists may represent a new approach in the prevention and treatment of ischemic arrhythmias.

Ectonucleotidase in sympathetic nerve endings modulates ATP and norepinephrine exocytosis in myocardial ischemia.

We recently reported that ATP, coreleased with norepinephrine (NE) from cardiac sympathetic nerves, increases NE exocytosis via a positive feedback mechanism. A neuronal ectonucleotidase (E-NTPDase) metabolizes the released ATP, decreasing NE exocytosis. Excessive NE release in myocardial ischemia exacerbates cardiac dysfunction. Thus, we studied whether the ATP-mediated autocrine amplification of NE release is operative in ischemia and, if so, whether it can be modulated by E-NTPDase and its recombinant equivalent, solCD39. Isolated, guinea pig hearts underwent 10- or 20-min ischemic episodes, wherein NE was released by exocytosis and reversal of the NE transporter, respectively. Furthermore, to restrict the role of E-NTPDase to transmitter ATP, sympathetic nerve endings were isolated (cardiac synaptosomes) and subjected to increasing periods of ischemia. Availability of released ATP at the nerve terminals was either increased via E-NTPDase inhibition or diminished by enhancing ATP hydrolysis with solCD39. P2X receptor blockade with PPADS was used to attenuate the effects of released ATP. We found that, in short-term ischemia (but, as anticipated, not in protracted ischemia, where NE release is carrier-mediated), ATP exocytosis was linearly correlated with that of NE. This indicates that by limiting the availability of ATP at sympathetic terminals, E-NTPDase effectively attenuates NE exocytosis in myocardial ischemia. Our findings suggest a key role for neuronal E-NTPDase in the control of adrenergic function in the ischemic heart. Because excessive NE release is an established cause of dysfunction in ischemic heart disease, solCD39 may offer a novel therapeutic approach to myocardial ischemia and its consequences.

Norepinephrine release from the ischemic heart is greatly enhanced in mice lacking histamine H3 receptors.

We previously reported that histamine H(3) receptors (H(3)Rs) are present in cardiac sympathetic nerve endings (cSNE) of animals and humans, where they attenuate norepinephrine (NE) release in normal and hyperadrenergic states, such as myocardial ischemia. The recent creation of a transgenic line of mice lacking H(3)R provided us with the opportunity to assess the relevance of H(3)R in the ischemic heart. We isolated SNE from hearts of wild-type (H(3)R(+/+)) and knockout (H(3)R(-/-)) mice and found that basal NE release from H(3)R(-/-) cSNE was approximately 60% greater than that from H(3)R(+/+) cSNE. NE exocytosis evoked by K(+)-induced depolarization of cSNE from H(3)R(+/+) mice was attenuated by activation of either H(3)R or adenosine A(1) receptors (A(1)R). In contrast, NE release from cSNE of H(3)R(-/-) was unaffected by H(3)R agonists, but it was still attenuated by A(1)R activation. When isolated mouse hearts were subjected to ischemia for 20 min, NE overflow into the coronaries was 2-fold greater in the H(3)R(-/-) hearts than in those from H(3)R(+/+) mice. Furthermore, whereas stimulation of H(3)R or A(1)R reduced ischemic NE overflow from H(3)R(+/+) hearts by 50%, only A(1)R, but not H(3)R activation, reduced NE release in H(3)R(-/-). Our data demonstrate that NE release from cSNE can be modulated by various heteroinhibitory receptors (e.g., H(3)R and A(1)R) and that H(3)Rs are particularly important in modulating NE release in myocardial ischemia. Inasmuch as excessive NE release is clinically recognized as a major cause of arrhythmic cardiac dysfunction, our findings reveal a significant cardioprotective role of H(3)R on cSNE.

Activation of a renin-angiotensin system in ischemic cardiac sympathetic nerve endings and its association with norepinephrine release.

We had reported that in the ischemic heart, locally formed bradykinin (BK) and angiotensin II (Ang II) activate B2- and AT1-receptors on sympathetic nerve terminals (SNE), promoting reversal of the norepinephrine (NE) transporter in an outward direction (i.e., carrier-mediated NE release). Although both BK and Ang II contribute to ischemic NE release, Ang II is likely to play a more important role. Since BK is formed by ischemic SNE, we questioned whether cardiac SNE also contribute to local Ang II formation, in addition to being a target of Ang II. SNE were isolated from surgical specimens of human right atrium and incubated in ischemic conditions. These SNE released large amounts of endogenous NE via a carrier-mediated mechanism, as evidenced by the inhibitory effect of desipramine on this process. Moreover, two renin inhibitors, pepstatin-A and BILA 2157 BS, the ACE inhibitor enalaprilat and the AT1-receptor antagonist EXP3174 prevented ischemic NE release. Western blot analysis revealed the presence of renin in cardiac SNE. Renin abundance increased more than three-fold during ischemia. Thus, renin is present in cardiac SNE and is activated during ischemia, eventually culminating in Ang II formation, stimulation of AT1-receptors and carrier-mediated NE release. Our findings uncover a novel autocrine mechanism, by which Ang II, formed at SNE in myocardial ischemia, elicits carrier-mediated NE release by activating prejuntional AT1-receptors.

Ischemia promotes renin activation and angiotensin formation in sympathetic nerve terminals isolated from the human heart: contribution to carrier-mediated norepinephrine release.

We recently reported that in the ischemic human heart, locally formed angiotensin II activates angiotensin II type 1 (AT(1)) receptors on sympathetic nerve terminals, promoting reversal of the norepinephrine transporter in an outward direction (i.e., carrier-mediated norepinephrine release). The purpose of this study was to assess whether cardiac sympathetic nerve endings contribute to local angiotensin II formation, in addition to being a target of angiotensin II. To this end, we isolated sympathetic nerve endings (cardiac synaptosomes) from surgical specimens of human right atrium and incubated them in ischemic conditions (95% N(2,) sodium dithionite, and no glucose for 70 min). These synaptosomes released large amounts of endogenous norepinephrine via a carrier-mediated mechanism, as evidenced by the inhibitory effect of desipramine on this process. Norepinephrine release was further enhanced by preincubation of synaptosomes with angiotensinogen and was prevented by two renin inhibitors, pepstatin-A and BILA 2157BS, as well as by the angiotensin-converting enzyme inhibitor enalaprilat and the AT(1) receptor antagonist EXP 3174 [2-N-butyl-4-chloro-1-[2'-(1H-tetrazol-5-yl)biphenyl-4-yl] methyl]imidazole-5-carboxylic acid]. Western blot analysis revealed the presence of renin in cardiac sympathetic nerve terminals; renin abundance increased ~3-fold during ischemia. Thus, renin is rapidly activated during ischemia in cardiac sympathetic nerve terminals, and this process eventually culminates in angiotensin II formation, stimulation of AT(1) receptors, and carrier-mediated norepinephrine release. Our findings uncover a novel autocrine/paracrine mechanism whereby angiotensin II, formed at adrenergic nerve endings in myocardial ischemia, elicits carrier-mediated norepinephrine release by activating adjacent AT(1) receptors.