Metabolic, functional, and histologic characterization of the heterotopically transplanted rat heart when used as a model for the study of long-term recovery from global ischemia.
The objective of this study was to assess the utility of the heterotopically transplanted rat heart as a model in which to assess long-term (0 to 7 days) postischemic recovery. This was achieved by characterizing the metabolic, functional, and histologic changes that occur during the first week after implantation. In the first series of studies (n = 6/group), hearts were subjected to 1 hour of global ischemia at room temperature (21 degrees +/- 1 degree C), during which time they were transplanted into the abdomens of the recipients. A permanently implanted intraventricular balloon was used to measure pressure-volume relationships in the implanted heart 1, 4, 8, 12, and 18 hours and 1, 2, 3, 4, 5, 6, and 7 days after transplantation. Left ventricular developed pressure (70 microliters loading volume) was 125 +/- 14 mm Hg (mean +/- SEM) after 1 hour of reperfusion, declining to 79 +/- 15 mm Hg after 4 hours before increasing to a maximum (158 +/- 14 mm Hg) at 24 hours. The pressure subsequently declined to 108 +/- 16 mm Hg by 3 days, and then remained essentially unchanged for the following 4 days. Heart rate declined to 197 +/- 26 beats/min after 1 hour of reperfusion, recovered to 380 +/- 21 beats/min after 24 hours, and remained above 300 beats/min for the remainder of the experiment. Left ventricular end-diastolic pressure increased progressively to very high levels through the 7-day period (176 +/- 23 mm Hg at 7 days). Analysis of creatine phosphate (CP) and of adenosine triphosphate (ATP) and its breakdown products indicated a loss of high-energy phosphates after 1 hour of ischemia (CP = 4.8 +/- 0.3 mumol/gm dry wt), a recovery to preischemic values after 24 hours (CP = 24.4 +/- 2.5 vs 23.8 +/- 1.3 mumol/gm dry weight in fresh control hearts), and a subsequent decline over the ensuing 6 days (CP = 8.1 +/- 1.5 mumol/gm dry wt at 7 days). In additional studies to assess the functional capacity of the unloaded transplanted heart, hearts were excised 1 hour and 1 day after transplantation and perfused as isolated working preparations: their function was then compared with that of fresh nontransplanted hearts. A time-dependent deterioration of all indices of cardiac function was observed. Morphologic studies of transplanted hearts with and without an inserted and inflated intraventricular balloon revealed a rapid reduction of left ventricular cavity volume during the first 24 hours in hearts without a balloon, and progressive severe fibrosis, endomyocardial necrosis, and inflammation over the 7-day period in hearts in which the balloon was intermittently inflated for functional assessment.(ABSTRACT TRUNCATED AT 400 WORDS)
Galiñanes
M
M
Cardiovascular Research, Rayne Institute, St. Thomas' Hospital, London, U.K.
Hearse
D J
DJ
D000005:Abdomen; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002314:Cardioplegic Solutions; D016027:Heart Transplantation / Q000502:physiology*; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D016042:Transplantation, Heterotopic / Q000502:physiology*; D016277:Ventricular Function, Left / Q000502:physiology
D002314:Cardioplegic Solutions; D010725:Phosphocreatine; D000255:Adenosine Triphosphate