Nobuhiko Hayashida

Obstruction of st jude medical valves in the aortic position: histology and immunohistochemistry of pannus

OBJECTIVE This study aims to reveal the morphological, histological, and immunohistochemical mechanism of pannus formation using resected pannus tissue from patients with prosthetic valve dysfunction. METHOD Eleven patients with prosthetic valve (St Jude Medical valve) dysfunction in the aortic position who underwent reoperation were studied. We used specimens of resected pannus for histological staining (hematoxylin and eosin, Grocotts, azan, elastica van Gieson) and immunohistochemical staining (transforming growth factor-beta, transforming growth factor-beta receptor 1, alpha-smooth muscle actin, desmin, epithelial membrane antigen, CD34, factor VIII, CD68KP1, matrix metalloproteinase-1, matrix metalloproteinase-3, and matrix metalloproteinase-9). RESULTS Pannus without thrombus was observed at the periannulus of the left ventricular septal side; it extended into the pivot guard, interfering with the movement of the straight edge of the leaflet. The histological staining demonstrated that the specimens were mainly constituted with collagen and elastic fibrous tissue accompanied by endothelial cells, chronic inflammatory cells infiltration, and myofibroblasts. The immunohistochemical findings showed significant expression of transforming growth factor-beta, transforming growth factor-beta receptor 1, CD34, and factor VIII in the endothelial cells of the lumen layer; strong transforming growth factor-beta receptor 1, alpha-smooth muscle actin, desmin, and epithelial membrane antigen in the myofibroblasts of the media layer; and transforming growth factor-beta, transforming growth factor-beta receptor 1, and CD68KP1 in macrophages of the stump lesion. CONCLUSIONS Pannus appeared to originate in the neointima in the periannulus of the left ventricular septum. The structure of the pannus consisted of myofibroblasts and an extracellular matrix such as collagen fiber. The pannus formation after prosthetic valve replacement may be associated with a process of periannular tissue healing via the expression of transforming growth factor-beta.

Usefulness of a multidetector-row computed tomography scanner for detecting pannus formation

BACKGROUND Prosthetic valve dysfunction (PVD) as a result of pannus or thrombus formation is an infrequent but serious complication. Currently available diagnostic tools, however, are insufficient to detect a minute pannus and thrombi. The use of a more advanced diagnostic image, multidetector-row computed tomography scanner, may enable us to determine the anatomic and functional causes of PVD. METHODS Patients who underwent aortic valve replacement with a St. Jude Medical valve were examined by transthoracic echocardiography and cineradiography to diagnose PVD. Sixteen patients with PVD (PVD group) and 12 patients with normal prosthetic valve function (control group) were studied using the multidetector-row computed tomography scanner. The multidetector-row computed tomography findings in 2 patients with PVD were validated by the observations during reoperation. RESULTS In 13 of 16 patients (81%) in the PVD group and 3 of 12 patients (25%) in the control group, multidetector-row computed tomography demonstrated that an abnormal small tissue, regarded as pannus, was found to extend from the left ventricular septum into the pivot guard. These findings were confirmed by the observations during reoperation in 2 patients in the PVD group. CONCLUSIONS Multidetector-row computed tomography can be a useful diagnostic technique for anatomic and functional evaluation of PVD as a result of pannus formation.

Effects of minimal-dose aprotinin on coronary artery bypass grafting

OBJECTIVE To evaluate the effects of minimal-dose aprotinin in patients undergoing coronary artery bypass grafting, we conducted a prospective randomized study. METHODS A total of 167 patients were randomized to receive no aprotinin treatment (control, n = 57), minimal-dose aprotinin (1.0 x 10(6) KIU; n = 55), or low-dose aprotinin (2.7 +/- 0.5 x 10(6) KIU; n = 55). Blood loss and transfusion requirements, parameters of clotting and fibrinolysis, renal function, and early graft patency rates were assessed. RESULTS Postoperative blood loss and transfusion requirements were significantly (p = 0.01) lower in both the minimal-dose and low-dose groups than in the control group. The increase in D-dimer level after cardiopulmonary bypass was significantly (p < 0.05) less marked in the low-dose group than in the control group. The alpha 2-plasmin inhibitor and plasminogen activator inhibitor-1 levels were significantly (p < 0.05) greater in the minimal-dose and low-dose groups than in the control group after bypass, suggesting the prevention of fibrinolysis by both aprotinin doses. No statistically significant differences in postoperative renal function and early vein graft patency rates were noted (control group, 93.8%; minimal-dose group, 95.5%; low-dose group, 92.3%; p = 0.25). CONCLUSIONS Aprotinin was not associated with a significant increase in the prevalence of renal dysfunction or early vein graft occlusion. Minimal-dose aprotinin inhibited enhanced fibrinolytic activity and reduced blood loss and transfusion requirements after bypass equivalently to low-dose aprotinin. The dose of 1 x 10(6) KIU added to the pump prime may be acceptably effective in reducing blood loss in patients undergoing primary coronary operations.

Inhibitory Effect of Milrinone on Cytokine Production After Cardiopulmonary Bypass

BACKGROUND It has been suggested that cyclic adenosine monophosphate-elevating agents suppress cytokine production. To evaluate the effects of milrinone, a phosphodiesterase III inhibitor, on cytokine production after cardiopulmonary bypass, we conducted a prospective randomized study. METHODS Twenty-four patients undergoing coronary artery bypass grafting were randomized to receive either milrinone treatment (milrinone, n = 12) or no milrinone treatment (control, n = 12). Administration of milrinone (0.5 microg x kg(-1) x min(-1)) was started after induction of anesthesia and was continued for 24 hours. Blood samples for determination of plasma cyclic adenosine monophosphate, tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, and interleukin-8 levels were collected perioperatively. RESULTS No significant differences were observed in tumor necrosis factor-alpha and interleukin-8 levels between the groups. Interleukin-1beta and interleukin-6 levels after cardiopulmonary bypass were significantly (p < 0.05) lower in the milrinone group than in the control group. Plasma levels of cyclic adenosine monophosphate increased significantly (p < 0.05) after the administration of milrinone and the levels correlated inversely (r = -0.55, p < 0.01) with interleukin-6 levels. CONCLUSIONS The results indicate that milrinone suppresses cytokine production by elevating cyclic adenosine monophosphate levels in patients undergoing cardiopulmonary bypass. With its positive inotropic and vasodilator activities, milrinone may have antiinflammatory effects.

Optimal flow rates for retrograde warm cardioplegia

Retrograde delivery of warm blood cardioplegia may improve nutrient cardioplegic flow beyond coronary obstructions, but may not adequately perfuse the right ventricle and the posterior left ventricle. To determine the optimal flow rate for warm retrograde cardioplegia, we assessed 62 patients undergoing elective coronary artery bypass in two studies. In the low flow study, administration of 50 ml/min (n = 9), 75 ml/min (n = 11), or 100 ml/min (n = 7) was associated with high lactate production and oxygen extraction during cardioplegic administration. At 50 minutes of cardioplegic arrest, the coronary venous effluent pH was low in all groups. In the high flow study, 30 patients all received flow rates of 100, 200, and 300 ml/min in randomized order during the crossclamp period. In addition, five patients received cardioplegia at a rate of 500 ml/min for the duration of the crossclamp period. Administration of 200 ml/min or higher minimized lactate production and maintained coronary venous pH within the physiologic range, but flows of 300 ml/min or higher did not increase oxygen use or reduce lactate or acid production. Patients in the low flow groups had significantly greater myocardial lactate release during cardioplegic infusion and after removal of the crossclamp than the high flow group. Warm retrograde cardioplegia should be delivered at flow rates of at least 200 ml/min during elective coronary artery bypass operations.

Obstruction of St Jude Medical Valves in the Aortic Position: A Consideration for Pathogenic Mechanism of Prosthetic Valve Obstruction:

Between 1995 and 2000, 8 patients with St. Jude Medical (SJM) valves in the aortic position required 9 redo valve replacement for prosthetic valve obstruction. Obstruction of the prosthetic valve was diagnosed by simultaneous echocardiography and cineradiography, and process of restricted leaflet movement that progressed to hemodynamic impairment was observed by serial studies in three recent patients. An oral anticoagulation was considered to be adequate in all patients except one patient who had withdrawal of warfrain. Pannus was the sole cause of valve obstruction in seven events in 6 patients, and both thrombus and pannus in 2 patients. Pannus overgrowth was found on the inflow aspect of the SJM valve, and involved the ends of the straight edge of the leaflets over pivot guards. These results suggest that pannus might play the primary role in development of obstruction of aortic SJM valves in patients on adequate oral anticoagulation.

Minimally diluted tepid blood cardioplegia.

BACKGROUND To evaluate the effects of minimally diluted tepid blood cardioplegia, a prospective, randomized study was undertaken. METHODS Thirty-seven patients undergoing isolated primary coronary artery bypass grafting were randomized to receive standard 4:1 diluted tepid blood cardioplegia (4:1 group, n = 18) or minimally diluted tepid blood cardioplegia (Mini group, n = 19). Cardioplegic solution was delivered in an intermittent antegrade fashion in both groups. Myocardial oxygen and lactate metabolism, release of the MB isoenzyme of creatine kinase and thiobarbituric acid reactive substances, and cardiac function were measured during and after the operation. RESULTS Myocardial oxygen consumption was significantly greater and lactate release was significantly lower in the Mini group than in the 4:1 group during cardioplegia. Minimally diluted blood cardioplegia resulted in more prompt resumption of lactate extraction, lower levels of release of the myocardial-specific isoenzyme of creatine kinase and thiobarbituric acid reactive substances during reperfusion, and better postoperative left ventricular function compared with the standard 4:1 cardioplegia. CONCLUSIONS Minimally diluted tepid blood cardioplegia may provide superior myocardial protection than the standard 4:1 dilution technique by optimizing the aerobic environment through an increase in oxygen supply during intermittent cardioplegia.

Adequate distribution of warm cardioplegic solution

Seventy-five patients undergoing coronary artery bypass grafting were randomized to receive warm antegrade (N = 25), warm retrograde (N = 25), or a combination of warm antegrade and retrograde (N = 25) delivery of blood cardioplegic solution. Myocardial oxygen utilization, lactate and acid metabolism, and adenine nucleotides and their degradation products were measured during the operation and cardiac function was assessed postoperatively. Warm retrograde delivery of cardioplegic solution increased lactate and acid release during cardioplegia and reperfusion, decreased left ventricular adenosine triphosphate concentrations, and reduced the washout of adenine nucleotide degradation products from both left and right ventricles. Warm antegrade delivery of cardioplegic solution resulted in less lactate and acid release during cardioplegia but more lactate accumulated in the territory of the left anterior descending artery during the crossclamp period. Intermittent antegrade delivery of the cardioplegic solution during combination cardioplegia washed out lactate and acid, which suggested inhomogeneous delivery of the cardioplegic solution during continuous retrograde cardioplegia. Combination cardioplegia best preserved adenosine triphosphate in the left ventricle and resulted in the best postoperative left and right ventricular function. A combination of intermittent antegrade and continuous retrograde delivery of cardioplegic solution provided better myocardial protection than either antegrade or retrograde delivery of cardioplegic solution alone.

Effects of intraoperative administration of atrial natriuretic peptide

BACKGROUND Biological activity of endogenous atrial natriuretic peptide (ANP) may decrease during cardiopulmonary bypass. To evaluate the effects of intraoperative administration of exogenous ANP in patients undergoing cardiopulmonary bypass, we conducted a prospective randomized study. METHODS Eighteen patients undergoing mitral valve surgery were randomized to receive either ANP treatment (ANP group; n = 9) or no ANP treatment (control group; n = 9). Atrial natriuretic peptide was given immediately after initiation of cardiopulmonary bypass for 6 hours (0.05 microg x kg(-1) x min(-1)). Plasma ANP, brain natriuretic peptide and cyclic guanosine monophosphate (cGMP) levels, hemodynamic variables and renal function were assessed perioperatively. RESULTS Administration of ANP increased plasma cyclic guanosine monophosphate levels, urine output and fractional sodium excretion, and decreased preload, afterload and plasma brain natriuretic peptide levels significantly (p < 0.05). Plasma cyclic guanosine monophosphate levels correlated with plasma ANP levels (r = 0.95, p = 0.0001), correlated with fractional sodium excretion (r = 0.53, p = 0.02), and correlated inversely with systemic vascular resistance (r = -0.54, p = 0.02). CONCLUSIONS Intraoperative administration of ANP had potent effects on natriuresis and systemic vasodilation by elevating cyclic guanosine monophosphate levels. The results suggest that the technique is useful for the management of hemodynamics and water-sodium retention after cardiopulmonary bypass.

Antegrade and retrograde cardioplegia: Alternate or simultaneous?

UNLABELLED Neither antegrade nor retrograde cardioplegic protection provides homogeneous distribution, and a combination may be required to avoid anaerobic metabolism and depressed postoperative ventricular function. Tepid cardioplegia (29 degrees C) avoids the delayed recovery of cardiac function and metabolism associated with cold cardioplegia (15 degrees C) and reduces the anaerobic metabolism seen with warm (37 degrees C) cardioplegia. We compared two techniques that combine antegrade and retrograde tepid cardioplegia: alternate and simultaneous. METHODS Sixty patients undergoing elective isolated coronary artery bypass grafting were randomized to receive near continuous tepid retrograde and either intermittent antegrade cardioplegia (the alternate technique) or antegrade cardioplegia with the solution delivered concurrently through each completed vein graft (the simultaneous technique). RESULTS Myocardial lactate extraction was greater after crossclamp release following simultaneous than alternate cardioplegia. Postoperative ventricular function was better after alternate than simultaneous cardioplegia. CONCLUSION Both techniques permitted rapid postoperative recovery of myocardial metabolism and ventricular function. However, simultaneous cardioplegia was simpler and did not require deairing the aortic root between antegrade infusions.