THE EFFECT OF LOAD ON ATROPHY, MYOSIN ISOFORM SHIFTS AND CONTRACTILE FUNCTION - STUDIES IN A NOVEL RAT-HEART TRANSPLANT PREPARATION

A novel heterotopic rat heart transplant preparation was used with the objective of investigating the effect of load on cardiac contractile function, mass, myosin and high energy phosphates over a 7-day period. Donor hearts were excised, arrested with a hypothermic (4 degrees C) cardioplegic solution and transplanted (90-min operation time) into the abdomens of recipient rats. The transplanted hearts were reperfused in situ for 7 days. Two groups of hearts (n=14/group) were studied. Group 1: a conventional unloaded transplanted preparation in which the aorta and pulmonary artery were anastomosed to the abdominal aorta and inferior vena cava, respectively. Group 2: a novel loaded preparation in which, additionally, the left atrium was anastomosed to the inferior vena cava which was then ligated proximally so as to divert distal venous flow to the left ventricle of the transplanted heart. Non-transplanted, fresh hearts served as controls. Seven days after transplantation the hearts were excised and perfused aerobically for 20 min. Systolic and diastolic functions had deteriorated severely in Group 1: left ventricular developed pressure (LVDP) had fallen to 96+/-11 v 162+/-6 mmHg in fresh controls (at 12 mmHg of end-diastolic pressure) and left ventricular volume to 80+/-12 v 268+/-20 mu l (P<0.05 in both instances), In Group 2, LVDP (134+/-6 mmHg) and left ventricular volume (144+/-6 mu l) were significantly higher than in Group 1 but were still significantly lower than in fresh controls. Coronary now in absolute terms was similar in all groups; however, when expressed as ml/min/g wet wt, coronary now tended to be greater in unloaded hearts (19.8+/-0.6) than in fresh hearts (15.0+/-0.8; P<0.05) and loaded hearts (17.6+/-1.3; N.S.). Unloaded hearts exhibited a significant loss of left ventricular weight (0.40+/-0.02 g) when compared with fresh aerobic controls (0.57+/-0.02 g; P<0.05). However, there was no significant weight loss in the loaded hearts (0.53+/-0.03 g), The content of V-1 isoform of myosin in left ventricular muscle was 77.8+/-5.0% in fresh hearts; this was reduced to 60.0+/-3.6% in the unloaded hearts (P<0.05). The value in the loaded hearts (73.2+/-3.4%) did not differ significantly from that in fresh controls. The adenine nucleotide pool was similar in all groups. In conclusion, imposing a load on the heterotopically transplanted heart prevents the loss of cardiac mass and the shift of myosin isoforms, however, it does not totally prevent the development of systolic and diastolic dysfunction. The contractile abnormalities do not appear to be related to high energy phosphate content but might well arise as a consequence of the denervation associated with transplantation or the transplantation procedure itself.