Cell- and gene therapy for ischemic heart disease.

Despite advances in pharmacological therapies, cardiovascular surgery, use of mechanical assist devices, and organ transplantation, more than half of the patients with clinically evident heart failure die within 5 years of the initial diagnosis. The use of cellular cardiomyoplasty and gene therapy offer a promising approach for both the prevention and treatment of heart failure. This review will discuss the current state of these emerging fields and the prospects of introducing the methods into clinical practice. Since functional restoration of the damaged heart presents a formidable challenge, developing strategies for the prevention of post-infarct heart failure remains of utmost priority. New strategies to optimize cell delivery, homing and survival on the one side and safe and efficient application of gene therapy to the failing myocardium on the other side are indispensable in order to achieve myocardial recovery after acute infarction or chronic ischemic damage.

Pulmonary and aortic blood flow measurements in normal subjects and patients after single lung transplantation at 0.5 T using velocity encoded cine MRI.

PURPOSE: It is the purpose of this study to compare pulmonary and aortic blood flow measurements obtained in patients after single lung transplantation (SLTX) with those in volunteers. METHODS/MATERIAL: In nine patients after SLTX (three male, six female) and nine volunteers (seven male, two female), double oblique phase contrast cine-MRI sequences perpendicular to the direction of blood flow were obtained in the ascending aorta, main, right, and left pulmonary artery on a 0.5-T unit (Philips Gyroscan; Best, the Netherlands) (repetition time, 600 to 800 ms; echo time, 8 ms; alpha=30; field of view=280 mm matrix, 128x256, ECG gating, temporal resolution 16 time frames/RR interval). An initial in vitro study using the same sequence on a nonpulsatile flow phantom showed excellent correlation (r=0.99) between MRI measurements of flow velocity and flow volume and true velocity and flow volume. Measurements of blood flow volume (mL/min), peak mean systolic velocity, resistive index, and distensibility index were obtained in each vessel. RESULTS: We found excellent correlations between left and right cardiac output as measured by velocity encoded cine-MRI (VEC-MRI) in the ascending aorta and main pulmonary artery both in normal volunteers (r=0.95) and in patients (r=0.91). Differential pulmonary blood flow measurements in volunteers showed that 55% of the right cardiac output was directed to the right and 45% to the left lung. Differential pulmonary blood flow in patients showed that most of the blood flow (81%) reaches the transplanted lung and only 19% reaches the patient's own lung (SLTX: 4.5+/-1.8 L/min, patient's own lung: 1.2+/-0.8 L/min). There were significant differences (p<0.05) in peak mean systolic velocity and resistive index obtained in the pulmonary arteries, both between normal volunteers and patients and between measurements obtained in the patient's own lung and the transplanted lung. CONCLUSION: VEC-MRI blood flow measurements are a promising noninvasive tool to monitor the hemodynamic changes of pulmonary blood flow after SLTX.

Combined heart and kidney transplantation using a single donor: a single center's experience with nine cases.

BACKGROUND: Simultaneous double-organ transplants comprising various organ combinations have become frequent. The purpose of this article is to report on a single center's experience of simultaneous heart and kidney transplantation (HNTX) with particular emphasis on selection criteria and patient outcome. METHODS: From September 1990 to January 1997, nine patients underwent HNTX, receiving both grafts from a single donor selected on ABO blood group compatibility and a negative lymphocytotoxic crossmatch, but without regard to HLA-antigen matching. RESULTS: One patient died of acute humoral rejection of the cardiac graft shortly after surgery. Eight patients are alive and well and have normal cardiac and renal function at a mean follow-up of 44+/-28 months. CONCLUSION: HNTX offers a compelling therapeutic solution in the treatment of advanced cardiac and renal failure in carefully selected patients. Because the heart and kidney rejection episodes were independent of each other, rejection surveillance should be carried out separately for each transplanted organ.

The effect of lung transplantation on the neural drive to the diaphragm in patients with severe COPD.

Little is known about the effects of lung transplantation (LT) on the neural drive to the diaphragm and on the endurance of respiratory muscles in patients with severe chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate these effects of single-lung (SLT) and double-lung transplantation (DLT). The neural drive to the diaphragm was assessed during fatiguing inspiratory threshold loading manoeuvres in six SLT recipients, six DLT recipients and seven patients with severe COPD, by using diaphragmatic surface electromyograms. During threshold loading, the patients had to generate 80% of their maximal transdiaphragmatic pressure with each breath. The endurance of inspiratory muscles was defined as the time from the beginning of a resistive breathing trial until exhaustion (t lim). In DLT recipients and even in SLT recipients (on both sides), neural activation of the diaphragm was significantly lower than in COPD patients (p < 0.05). However, no statistically significant difference in t lim was seen between LT recipients and COPD patients. The data suggest that single-lung and double-lung transplantations cause a significant decrease of the neural drive to the diaphragm, while the endurance of inspiratory muscles is well-preserved in patients with advanced chronic obstructive pulmonary disease. This may contribute to reduced sensation of inspiratory effort during ventilatory stress, thus improving the quality of life.

Anemia and erythropoietin levels in lung transplant recipients.

An evaluation of 26 surviving outpatient lung transplant recipients at one center showed that 65% (17/26) had significant anemia (hemoglobin < 11 g/L for women, < 14 g/dl for men) at a median follow-up of 13.5 months after transplantation (range, 1-41 months). There were 14 men and 12 women with a mean age of 45.1 years (range, 23.1-66.7 years). Fifteen had a double allograft and 11 had a single allograft. Anemia was normochromic and normocytic/macrocytic with a tendency to anisocytosis, with normal reticulocyte counts. Iron deficiency (transferrin saturation < 20%) was found in 35% (6/17) of anemic patients, and two of them also had ferritin levels < 15 micrograms/L. In addition, vitamin B12 was decreased in 1 patient. Folate levels were all normal. Erythropoietin levels were significantly decreased in anemic lung transplant recipients as compared with nontransplanted iron-deficient anemic patients (median, 1 mU/ml, range 1-41 mU/ml, vs. 53 mU/ml, 15-88 mU/ml; P < 0.05). In nonanemic lung transplant recipients, erythropoietin levels were decreased too, as compared with normal controls (median, 2 mU/ml, range 1-21 mU/ml, vs. 5 mU/ml, 3-32 mU/ml; P < 0.05). Investigation of peripheral stem cells in 9 patients showed normal stimulation of erythroids (burst-forming unit, erythroid; median, 573 cells/ml; range, 128-1898 cells/ml) independent of erythropoietin concentrations. Analysis of putative prognostic factors, such as age, surgical procedure (double vs. single lung allograft), indication for transplantation, time after transplantation, infection status, presence of bronchiolitis obliterans, immunosuppression (+/- azathioprine), serum creatinine, creatinine clearance, hypertension, and arterial partial pressure of oxygen, did not demonstrate any difference in erythropoietin concentrations. Only the sex variable revealed a trend to higher levels in women than in men (median, 4 mU/ml, range 1-41 mU/ml, vs. 1 mU/ml, 1-16 mU/ml; P > 0.05). The causes for low erythropoietin levels are not quite understood yet; however, they offer a rationale for the treatment of chronic anemia with recombinant human erythropoietin.

In vitro studies on normal and pathological preimplantation development. I. Events of normal mouse preimplantation development as revealed by microcinematography.

After briefly presenting the main historical data of in vitro culture of preimplantation mouse embryos and their filming, the first own observations on normal preimplantation development made by using microcinematography are presented: development from two-cell to eight-cell embryos; compaction and cavitation. The timing and the duration of various developmental events were recorded. Own observations were compared with previous cinematographic data reported by other authors. Some processes needing further investigations are evidenced: rotation within the zona pellucida, penetration of cytoplasmic emissions through the zona, contraction and reexpansion.

A microcinematographic study of the in vitro development of postimplantation rat embryos.

A method for time-lapse cinematography of in vitro cultured rat embryos is presented. Technical details (especially with respect to the possibility of manipulation during filming) and the first results obtained are presented and discussed.