Coronary artery response to cold-pressor test is impaired early after operation in heart transplant recipients.

OBJECTIVES: The aim of the present study was to evaluate the coronary vasomotor response to the cold-pressor test within 3 months after heart transplantation. BACKGROUND: Normal epicardial coronary arteries dilate in response to sympathetic stimulation evoked by the cold-pressor test. In transplant recipients, abnormal coronary vasomotion has been described shortly after operation. METHODS: Fourteen heart transplant recipients were compared 52 +/- 15 days (mean +/- SD) after operation with 10 control subjects. All had angiographically normal epicardial coronary arteries. Coronary blood flow velocity was measured with a Doppler catheter placed in the proximal left anterior descending coronary artery. Four segments in each patient were analyzed by quantitative coronary angiography to assess the diameter changes during the cold-pressor test and after intracoronary injection of isosorbide dinitrate. RESULTS: Coronary flow velocity increased similarly during the cold-pressor test in control subjects and in transplant recipients, from 7.5 +/- 2.3 to 11.0 +/- 3.9 cm/s and from 10.3 +/- 3.2 to 13.7 +/- 4.8 cm/s (both p < 0.01). In control subjects, 39 of 40 segments analyzed dilated during the cold-pressor test. In transplant recipients, 48 of 56 segments analyzed did not change or constricted. The mean epicardial coronary diameter increased significantly during the cold-pressor test in control subjects (+13 +/- 6%, p < 0.001), whereas it did not change significantly in transplant recipients (-2 +/- 9%, p = NS). In transplant recipients, isosorbide dinitrate elicited coronary vasodilation similar to that in control subjects. CONCLUSIONS: These data indicate that in human transplanted denervated hearts, coronary vasodilation in response to sympathetic stimulation by cold exposure is impaired shortly after operation.

Effects of cryopreservation on the proliferation and anticoagulant activity of human saphenous vein endothelial cells.

Human saphenous veins were cryopreserved in 4% human albumin and 10% dimethyl sulfoxide. The effect of cryopreservation on endothelial cells was studied in terms of the anticoagulant activity of thrombomodulin and in terms of cell proliferation. After storage for 2 weeks at -150 degrees C, 0.45 +/- 0.07 x 10(5) endothelial cells/cm2 were detected in cryopreserved veins and 1.03 +/- 0.04 x 10(5) endothelial cells/cm2 in fresh veins (p < 0.01). The thrombin-catalyzed activation of protein C decreased after cryopreservation, indicating altered thrombomodulin activity in the endothelial cells. On a cell number basis, the release of soluble thrombomodulin was three times higher from the cryopreserved endothelium than from the fresh endothelium (p < 0.05). The amount of spontaneous release of von Willebrand factor from the endothelial surface was not significantly different between fresh and cryopreserved veins. Endothelial cells were cultured from fresh veins and from their cryopreserved counterparts. On plating of endothelial cells in primary culture, the number of adhered cells was 0.9 +/- 0.09 x 10(3) cells/cm2 from fresh veins and 0.25 +/- 0.03 x 10(3) cells/cm2 from cryopreserved veins (p < 0.01). The positive immunohistochemical stain for von Willebrand factor indicated that the endothelial cell character was maintained after cryopreservation. The endothelial desquamation with loss of anticoagulant function and the slow proliferation of surviving cells in vitro suggest an impaired endothelial healing in vivo. The loss of anticoagulant activity complicates the problems of the exposure of thrombogenic subendothelial matrix to blood in implanted cryopreserved veins.

Orthotopic cardiac transplantation with direct caval anastomosis: is it the optimal procedure?

Total excision of the right atrium with a minimal cuff of left atrium remaining around the four pulmonary veins, followed by direct anastomoses on venae cavae, has been proposed as an alternative to the standard procedure described by Shumway and Lower for orthotopic cardiac transplantation. To investigate whether this "anatomic" transplantation should be proposed as the optimal procedure, we prospectively randomized 78 patients having 81 procedures since 1991 into two groups: group I, standard transplantation (n = 40), and group II, "anatomic" transplantation (n = 41). The two groups were statistically similar in recipient age, sex, weight, disease, and status at the time of transplantation. Also similar were donor age, sex, weight, and drug dependency at the time of harvesting. All patients could be weaned from cardiopulmonary bypass with comparable graft ischemic times (group I, 136 +/- 46 minutes; group II, 138 +/- 51 minutes). Immediate recovery of sinus rhythm occurred in 20 cases of group I and 36 cases of group II. Delayed recovery of sinus rhythm in the first postoperative week occurred in 15 cases of group I and 5 cases of group II. Persistence of atrial arrhythmia occurred in 5 cases of group I and never in group II. These differences were highly significant (p < 0.001). Postoperative hemodynamics showed a higher cardiac index at day 1 in group II (4.12 +/- 0.85 L/min per square meter) than in group I (3.77 +/- 0.65 L/min per square meter) (p = 0.04). There were 13 early deaths in group I and 8 early deaths in group II. One death in group I was related to an acute atrioventricular block at 3 weeks with no evidence of cardiac rejection at histologic examination. Two patients in group I (5%) required definitive pacemaker implantation for prolonged sinus node dysfunction. Echocardiographic and Doppler studies of survivors have been performed 2 to 3 months after transplantation. Right atrial area was significantly reduced (p < 0.01) in group II (18 +/- 4.7 cm2) versus group I (24 +/- 7 cm2), as was left atrial area (group I, 24 +/- 4.5 cm2; group II, 20 +/- 5 cm2) (p = 0.01). Mild tricuspid regurgitation was observed in 82% of group I patients versus 57% of group II patients (p < 0.05), inasmuch as mitral regurgitation was comparable (71% in group I, 67% in group II).(ABSTRACT TRUNCATED AT 400 WORDS)

Minimodule dialyser for quantitative ex vivo evaluation of membrane haemocompatibility in humans: comparison of acrylonitrile copolymer, cuprophan and polysulphone hollow fibres.

Minimodule hollow fibre dialysers, representing clinical dialysis modules on a scale of 1/25, enable quantitative evaluation of the haemocompatibility of hollow fibre membranes in an ex vivo flow system in humans. On line heparinization, adjusted for donor sensitivity, is maintained at a minimal level (approximately 0.14 units/ml). Blood samples collected at the minimodule exit over 30 min are analysed for heparin (anti-Xa activity), activated partial thromboplastin time, fibrinopeptide A, platelet count and beta-thromboglobulin, complement fragment C3a, leucocyte count and polymorphonuclear neutrophil elastase. Initial experiments were performed using well-characterized reference materials: acrylonitrile copolymer (AN 69 HF), polysulphone and cuprophan (CUP). Activation of coagulation and platelets was low for AN 69 HF, intermediate for CUP and greatest for polysulphone, while complement activation was negligible in the presence of AN 69 HF, moderate for polysulphone and most important for CUP. Future applications will be directed towards haemocompatibility screening of prototype membranes with the aim of developing clinical dialysers with improved biocompatibility.

Myocardial high-energy phosphate depletion in allograft rejection after orthotopic human heart transplantation.

The present study was designed to assess whether acute rejection affects myocardial energy content of the human orthotopically transplanted heart. Adenosine triphosphate content was measured in one tissue sample obtained during 46 routine right ventricular endomyocardial biopsies 6 to 455 days (98 +/- 110) after transplantation in 19 cyclosporine-treated transplant recipients. Tissue samples were immediately frozen in liquid nitrogen within 10 seconds after excision. Adenosine triphosphate analysis was performed with high performance liquid chromatography. Three groups of biopsy specimens were classified according to the standardized cardiac biopsy grading system. Group 1: Eight biopsy specimens without rejection; group 2: 24 biopsy specimens with mild rejection; group 3: 14 biopsy specimens with moderate or severe rejection. Graft systolic function evaluated by echocardiographic fractional shortening was in the normal range the day of biopsy. All patients had normal coronary angiograms within 1 month of the study. In the presence of mild rejection (grade 1A or 1B), adenosine triphosphate content was not significantly different from that of nonrejecting hearts (26.15 +/- 7.1 and 28.57 +/- 8.23 nmol/mg protein, respectively). By contrast, a significant decrease in adenosine triphosphate content was observed when moderate or severe rejection with focal or diffuse aggressive infiltrates were present (10.46 +/- 4.11 nmol/mg protein; p < 0.01 versus two other groups). In seven cases, sequential analysis showed a significant increase in adenosine triphosphate content after rejection therapy concomittant with histologic improvement: 10.19 +/- 2.9 before and 30.13 +/- 7.0 nmol/mg protein after treatment (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Durability of the Mitroflow pericardial valve at ten years.

From 1983 to 1992, 366 patients received 407 Mitroflow pericardial valves. Mean age was 62 +/- 14 years. Average follow-up was 72 +/- 28 months. Total follow-up was 1,791 patient-years. Overall survival in all patients was 77.2% +/- 2.2% at 5 years and 56.2% +/- 6.4% at 10 years. Freedom from structural valve deterioration was 95% +/- 1.2% and 36.7% +/- 8.1% at 5 and 10 years for all valves, 96.9% +/- 1.3% and 39.2% +/- 9.8% for aortic valve replacement, and 91.7% +/- 3.2% and 36.4% +/- 10% for mitral valve replacement (p = not significant). The freedom from structural valve deterioration in patients older than 70 years of age was 100% and 93.9% +/- 5.8% at 5 and 10 years, respectively. At 10 years, linearized rate of thromboembolism was 0.73% +/- 0.2% per patient-year and freedom from valve-related mortality for all valves was 88.8% +/- 2.8%. The best indication for the implantation of a Mitroflow valve is mitral or aortic disease in patients more than 70 years of age.

Clinical implantation of the wearable Baxter Novacor ventricular assist system.

Implantation of the wearable Novacor electrically powered left ventricular assist system was performed on March 16, 1993, in a 44-year-old man hospitalized for an acute episode of myocardial decompensation after a 6-year history of dilated cardiomyopathy. He was rehabilitated fully and became ambulatory, awaiting a suitable cardiac graft for 59 days. He is now back to work, enjoying a normal life. This case illustrates the progress made by miniaturization of the external components of the system. General acceptance of the system and psychological adaptation to the new way of life were remarkable.

Mitroflow pericardial valve: long-term durability.

Isolated aortic (n = 107), mitral (n = 63), and tricuspid (n = 1) valve replacement and 28 double-valve replacements were performed with a second generation of pericardial valves, the Mitroflow valve, in 199 patients from March 1983 to December 1986. Follow-up (total, 1,058 patient-years) was extended to 106 months and 91.5% complete. Mean age was 58 +/- 13 years. The operative mortality included 22 deaths, non-cardiac-related in 7. The actuarial probability of survival for all patients was 66% +/- 4% at 8.5 years. There were no significant differences between patients with aortic valve replacement, mitral valve replacement, or double-valve replacement. The rate of thromboembolic events, antithromboembolic therapy-related hemorrhage, periprosthetic leak, and endocarditis is extremely minimal. Structural valve dysfunction occurred at a rate of 3.2% +/- 0.5%/patient-year. Actuarial freedom from the event was 94.6% +/- 1.7% at 5 years and 63.7% +/- 6.5% at 8.5 years for all valves. There were no difference in structural valve dysfunction rate between patients having aortic, mitral, or double-valve replacement. Thirty-five patients were reoperated on (3.4 +/- 0.6%/patient-year for all). The rate of all valve-related morbidity and mortality was 5.6% +/- 0.7%/patient-year for all patients, actuarial freedom from the event being 44% +/- 7% at 8.5 years. These data suggest that the excellent hemodynamic characteristics of the valve are balanced by a risk of valve failure that is slightly increased when compared with porcine valves.

Intraoperative transesophageal echocardiography for pulmonary embolectomy without cardiopulmonary bypass.

This case report describes a patient with massive pulmonary embolism and acute circulatory failure in whom transesophageal echocardiography permitted the diagnosis of thrombi in the main pulmonary truncus and in the right branch and guided intraoperatively the surgical embolectomy performed under simple venous inflow occlusion because of a contraindication to heparin administration. Transesophageal echocardiography seems to be a very helpful technique to diagnose promptly massive pulmonary embolism and a very useful tool at the time of operation to guide the embolectomy.

Pharmacological bridge to cardiac transplantation: current limitations.

Addition of intravenous enoximone to sympathomimetic agents permits a rapid and drastic improvement in the clinical and hemodynamical condition of patients in cardiogenic shock referred for a mechanical bridge to transplantation. The present experience, based on the management of 52 patients, permits us to point out the current limitations of this pharmacological bridge: the rate of sudden death, the incompleteness of the physical rehabilitation of the patients, and the vanishing effect of intravenous enoximone.