Systolic and Diastolic Properties and Myocardial Blood Flow in the Heterotopically Transplanted Rat Heart during Acute Cardiac Rejection

Abstract

The aim of the study was to characterize the course of systolic and diastolic function, myocardial blood flow, and histologic changes during acute rejection in a model of heterotopic transplantation in rats. For this purpose isogenic Lewis-to-Lewis and allogenic DA (Dark Agouti)-to-Lewis rat cardiac transplants were studied 1 hour and 1, 3, and 5 days, respectively, after heterotopic intraabdominal transplantation. Myocardial tissue blood flow (MBF) was assessed by the hydrogen-clearance method. An implanted balloon was used to measure pressure-volume relations in the transplanted heart. Myocardial water content was determined at the end of the experiments, and histologic examinations were performed. The MBF recovered during the first day postoperatively in both groups and decreased again in the allogenic group after 3 and 5 days (p < 0.05); it remained stable in the isogenic group. Myocardial relaxation was already prolonged in the allogenic group after 3 days and deteriorated further. Left ventricular end-diastolic pressure progressively increased in the allogenic group, whereas it remained unchanged in the isogenic group up to 5 days. After recovery from ischemia, the left ventricular peak systolic pressure was stable in the isogenic group for the entire further observation period, but it significantly decreased in the allogenic group after 5 days (p < 0.05). Myocardial water content showed a significant increase in the allogenic group compared to that in the isogenic group after 5 days. In the allogenic group histologic examination confirmed mild to moderate rejection after 3 days and severe acute rejection after 5 days. Thus, after recovery from ischemia, mild to moderate cardiac rejection was associated with reduced MBF and impaired relaxation. In a typical sequence, generation of edema and impaired diastolic compliance were terminally followed by systolic dysfunction during severe rejection.

Immunomodulatory Effects of Poly(ADP-ribose) Polymerase Inhibition Contribute to Improved Cardiac Function and Survival During Acute Cardiac Rejection

“…In agreement with our previous studies 2, 9 we observed a typical sequence of cardiac dysfunction during the development of acute cardiac rejection: preserved baseline systolic and diastolic function with reduced contractile reserve at the stages of mild to moderate rejection, followed by progressive systolic and diastolic dysfunction during severe rejection. Reduced responsiveness to ␤-adrenergic stimulation at preserved baseline contractility has been also described at early stages of cardiac rejection in ventricular myocytes, 14 isolated papillary muscles, 15 ex vivo Langendorff preparation 16 and rejecting canine orthografts.…”

“…Isogeneic and allogeneic (Lewis to Lewis and DA to Lewis, respectively) heterotopic abdominal cardiac transplantations were performed by one surgeon using the technique of Ono and Lindsay, as previously described. 9,10 In the first series of experiments, animals with allogeneic grafts were treated with either: vehicle; water-soluble PARP inhibitor INO-1001 1 mg/kg/day intraperitoneally (Inotek Pharmaceuticals, Beverly, MA); cyclosporine 2.5 mg/kg/day orally; cyclosporine 5 mg/ kg/day orally; or the combination of INO-1001 and low-dose cyclosporine (n ϭ 6 transplanted animals/ group). This cohort of animals was used to determine the duration of allograft survival by evaluating the heart beat daily by palpation.…”

Leukocyte-Targeted Myocardial Contrast Echocardiography Can Assess the Degree of Acute Allograft Rejection in a Rat Cardiac Transplantation Model

“…8 A study in rats demonstrated that myocardial blood flow assessed by the hydrogen-clearance method recovered during the first day after transplantation in both allografts and isografts but decreased again in allografts 3 days after transplantation, which was followed by systolic dysfunction at day 5. 27 In the present study, MCE based on destructionreplenishment dynamics 25 revealed a significant reduction of myocardial perfusion in the untreated allografts but not in the allografts treated with high-or low-dose CsA. Thus, perfusion imaging was insensitive to any abnormalities in allografts treated with CsA at posttransplantation day 3.…”

First report on fertility after allogeneic uterus transplantation

“…Thus, the left uterine horn was removed after placements of two titanium clips; one just caudal to the Fallopian tube and the second one just cranial to the uterine bifurcation from the common uterine cavity. The median and range of the total surgery time for the Sham-operated animals were 21 minutes [17][18][19][20][21][22][23][24][25].…”

“…Although this Dark Agouti-to-Lewis allogeneic rat model has been used in research on other types of organ transplantations, with proven prominent rejection under non-immunosuppressed conditions (18,19), we tested three animals with uterine grafts and no immunosuppression. After 10 days all showed rejected graft with massive necrosis.…”