Tetsuo Hadama

Actions of Mibefradil, Efonidipine and Nifedipine Block of Recombinant T- and L-Type Ca2+ Channels with Distinct Inhibitory Mechanisms

We compared detailed efficacy of efonidipine and nifedipine, dihydropyridine analogues, and mibefradil using recombinant T- and L-type Ca²⁺ channels expressed separately in mammalian cells. All these Ca²⁺ channel antagonists blocked T-type Ca²⁺ channel currents (I_Ca(T)) with distinct blocking manners: I_Ca(T) was blocked mainly by a tonic manner by nifedipine, by a use-dependent manner by mibefradil, and by a combination of both manners by efonidipine. IC₅₀s of these Ca²⁺ channel antagonists to I_Ca(T) and L-type Ca²⁺ channel current (I_Ca(L)) were 1.2 µmol/l and 0.14 nmol/l for nifedipine; 0.87 and 1.4 µmol/l for mibefradil, and 0.35 µmol/l and 1.8 nmol/l for efonidipine, respectively. Efonidipine, a dihydropyridine analogue, showed high affinity to T-type Ca²⁺ channel.

Occurrence of peptic ulcer in the gastric tube used for esophageal replacement in adults

Reported in this paper are two cases of peptic ulcer which developed in the gastric tube used for esophageal replacement following esophagectomy for esophageal tumors in adults. The results of our cases suggest that acid secretion from the mucosa of the gastric tube, in spite of truncal vagotomy and the state of the tube, seems to play important roles in the pathogenesis of peptic ulcer of the gastric tube after esophageal replacement, even though circulatory disturbances, due to postoperative irradiation and gastric tube formation, have been suspected as the cause. Therefore, in those cases of gastric tube stasis, surgical drainage of the gastric tube should be performed.

Acute myocardial infarction due to left main coronary artery occlusion. Therapeutic strategy.

OBJECTIVE Acute myocardial infarction due to left main coronary artery occlusion remains catastrophic and mostly fatal due to severe cardiogenic shock and arrhythmia. METHODS We studied 13 patients undergoing coronary artery bypass grafting for acute myocardial infarction due to left main coronary artery occlusion to clarify the optimal management of these difficult patients. RESULTS In-hospital mortality was 46.2% (6/13). Revascularization was achieved by catheter intervention followed by bypass surgery in 7, and bypass surgery alone in 6. Two bypass surgery patients without catheter intervention had collateral flow to the left coronary artery, with the right coronary artery dominant. The time from onset to recanalization in the survival group was significantly shorter than in the early death group. CONCLUSIONS Emergency intervention to preserve left ventricular function or right coronary artery dominant and collateral blood flow to left coronary arteries is important for improving the prognosis of patients with acute myocardial infarction due to left main coronary artery occlusion. If residual left main coronary artery stenosis is significant or other proximal coronary stenosis exists after catheter intervention, early coronary bypass surgery may improve long-term survival.

Limb ischemia and reperfusion during abdominal aortic aneurysm surgery

PurposeAbdominal aortic aneurysm (AAA) surgery involves ischemia and reperfusion of the lower extremities, but assessing the pathophysiological changes is difficult. We evaluated the extent and time course of ischemia–reperfusion injury of the lower extremities during AAA surgery.MethodsTo monitor oxygen metabolism, two near-infrared spectroscopy (NIRS) probes were positioned on each calf muscle of nine patients undergoing AAA surgery. Lactate and pH were also measured in both iliac veins.ResultsNear-infrared spectroscopy signals responded sensitively to aortic cross-clamping and declamping. Lactate increased gradually and exponentially during aortic cross-clamping, and reconstruction of the first iliac artery resulted in a further but transient increase in ipsilateral venous lactate. The time course of the pH level after declamping was almost a mirror image of that of lactate. Reconstruction of the first iliac artery did not affect the contralateral NIRS signals, lactate, or pH.ConclusionsNear-infrared spectroscopy may be useful for monitoring limb ischemia during AAA surgery. The transient increase in lactate and the transient decrease in pH after first declamping may contribute to the mechanism of declamping shock. The fact that first declamping did not affect measurements on the other side shows that contralateral ischemia progresses steadily after reconstruction of the first iliac artery. Therefore, reconstruction of the second iliac artery should be done as soon as possible.

LAPAROSCOPIC CHOLECYSTECTOMY IN PATIENTS UNDERGOING ANTICOAGULANT THERAPY

We recently performed a laparoscopic cholecystectomy on three patients receiving preoperative oral anticoagulant therapy. The patients requiring anticoagulants for pre-existing cardiac conditions have the following risks at surgery: thromboembolism, hemorrhage, endocarditis, and cardiopulmonary dysfunction. In patients receiving anticoagulant therapy, one must thus maintain a balanced international normalized ratio of the prothrombin time to prevent thromboembolism or hemorrhage. Warfarin sodium was discontinued preoperatively in all patients. Heparin sodium was individualized according to each patient’s risk of thromboembolism. As a result, these patients all underwent a laparoscopic cholecystectomy without complications. Attention was paid to achieve hemostasis in the operative field and the trocar inserted sites during the procedure. The administration of warfarin sodium was resumed on the first postoperative day in all patients. Restarting warfarin sodium early also helps to simplify postoperative management. A broad spectrum of antibiotic therapy was also used to reduce the risk of endocarditis. Each patient’s cardiopulmonary function was carefully monitored. The minimal invasion experienced during a laparoscopic cholecystectomy may thus facilitate the management of gallstones in patients receiving systemic anticoagulation treatment based on the findings of this limited series.

Stented elephant trunk method for multiple thoracic aneurysms

Stent-grafting and open graft replacement was introduced to reduce the complications of suture anastomosis in the descending aorta. We applied this technique in the treatment of a patient with multiple thoracic aneurysms. The elephant trunk procedure was used for thromboexclusion. A single branched graft was placed easily without twisting. In patients with aneurysms at both the proximal and distal thoracic aorta, combined stent-grafting and open graft replacement is an excellent approach.

Structural differences in the cytoarchitecture and intercalated discs between the working myocardium and conduction system in the human heart

Abstract. Working and specialized cardiac myocytes and their intercalated discs in adult human hearts without history of cardiac disease were examined by scanning electron microscopy. The NaOH/ultrasonication treatment of cardiac tissues resulted in the digestion of connective tissue and separation of intercellular junctions. Auricular and ventricular working cardiac myocytes were quasi-cylindrical in shape, bifurcated, and connected end-to-end at the intercalated discs. The intercalated discs in the working cardiac myocytes showed a stair-like profile, consisting of steps (plicate segments) and corresponding risers (interplicate segments). The ventricular myocytes, in particular, had many steps and risers. The plicate segments were filled with numerous finger-like microprojections. The strands of the myocytes in the sinoatrial node were oriented linearly, while those in the atrioventricular node formed a reticular network. The intercalated discs in both nodal cells were underdeveloped, having few microprojections. Myocytes in the atrioventricular bundle (His) and the right limb were arranged in parallel, and were characterized by the presence of slender branches. Purkinje cell strands formed reticular networks. The intercalated discs in the His-Purkinje system were irregular in appearance, and the microprojections were larger in size and smaller in number than those of working myocytes. The myocytes in the crista terminalis and surrounding the fossa ovalis resembled cells in the His-Purkinje system rather than auricular working myocytes in morphology, and may act as the internodal pathway. It is concluded that morphological differences in both the cytoarchitecture and intercalated discs were closely related with contraction and impulse propagation in the various regions of the human heart.

Detection of acute cardiac rejection by analysis of heart rate variability in heterotopically transplanted rats

BACKGROUND A less-invasive method for cardiac allograft surveillance than endocardial biopsy is needed. We analyzed heart rate variability of heterotopically transplanted rat hearts as a method of detecting rejection of rat cardiac allografts. METHODS Two kinds of heterotopic transplants were performed: 1) Brown-Norway rats received Brown-Norway rat isografts, and 2) Lewis rats received Brown-Norway rat allografts. The electrocardiogram (ECG) of the grafts were serially recorded under non-anesthetized and non-restricted conditions using a telemetric ECG transmitter implanted in the recipients abdomen. Frequency domain analysis of the ECGs was performed using a fast Fourier algorithm. RESULTS Total power of the heart rate variability in the isograft heart was reduced to 1.1%, compared to normal subjects without transplantation (p < .001). In the allograft heart, it was also reduced to 1.0% on days 1.5 (rejection score 0 to 1), but gradually increased thereafter up to 185% on day 6 (rejection score 3.75+/-0.50). The increase in spectral power was frequency-dependent (i.e., changes in the power in lower frequency range [LF, 0.04 to 0.67 Hz] were significantly higher than other ranges). This increase was reversible when immunosuppressive therapy was performed with the use of cyclosporine A. In the allograft group, peak-to-peak amplitudes of the QRS complex and heart rate were significantly decreased on day 5.5 or later, whereas the power of the LF was significantly increased by day 3.5 or later. CONCLUSIONS Our data suggest that heart rate variability analysis is a promising noninvasive marker for early detection of cardiac allograft rejection. This method may also provide a sensitive means of assessing the effects of immunosuppressive therapy.

Aortic valve replacement and splenectomy in a patient with chronic idiopathic thrombocytopenic purpura—preoperative management with high-dose γ-globulin

SummaryWe report the management of a patient with chronic idiopathic thrombocytopenic purpura and severe aortic valvular disease. Preoperative intravenous high-dose γ-globulin administration was employed, and aortic valve replacement combined with splenectomy were performed during the same operation. The platelet count at admission was 34,000/mm3 and increased to 146,000/mm3 after the γ-globulin therapy. Platelet transfusion at the end of the cardiopulmonary bypass was considered no longer necessary in the postoperative period, because the platelet count increased quickly after the procedure. The post-operative course was uneventful. We believe that open heart surgery and splenectomy can successfully be performed simultaneously in a patient with chronic idiopathic thrombocytopenic purpura treated with high-dose γ-globulin therapy.

Effect of Prostaglandin E1 on Ischemia–Reperfusion Injury During Abdominal Aortic Aneurysm Surgery

ObjectiveAbdominal aortic aneurysm (AAA) surgery subjects the lower extremities to ischemia and reperfusion. Although it is not extensive or prolonged, ischemia of the lower extremities during aortic cross-clamping is gradually and steadily induced. We studied the effects of prostaglandin E1 (PGE1) on ischemia–reperfusion injury of the lower extremities during AAA repair.MethodsDuring AAA surgery, two near-infrared spectroscopy probes were positioned on each calf muscle to monitor oxygen metabolism in the lower extremities. We also measured lactate concentration in both iliac veins.ResultsNear-infrared spectroscopy signals responded sensitively to aortic cross-clamping and declamping. Lactate increased time-dependently during aortic cross-clamping. The continuous venous administration of PGE1 (20 ng/kg per minute) inhibited the accumulation of lactate during aortic cross-clamping. Declamping of the first iliac artery resulted in a further but transient increase in ipsilateral venous lactate, which may be one component in the mechanism of declamping shock. Prostaglandin E1 eliminated the transient increase in ipsilateral lactate. The administration of PGE1 inhibited the contralateral accumulation of lactate after first declamping, and the lactate level decreased gradually before the second declamping.ConclusionsProstaglandin E1 seems to have a protective effect against ischemia–reperfusion injury of the lower extremities during AAA surgery.