Age-related response of rabbit heart to normothermic ischemia: a 31P-MRS study

Abstract

The age-related response of the myocardium to 30 min of 37 degrees C global ischemia and 120 min of 37 degrees C reperfusion, measured by phosphorus-31 magnetic resonance spectroscopy and the recovery of isovolumic function, was evaluated by using perfused neonatal (3-8 days old, n = 10), immature (24-30 days old, n = 10), and adult (2-4 mo old, n = 5) rabbit hearts. Basal intracellular pH (pHi) was highest in neonatal hearts and decreased with age. The basal phosphocreatine (PCr)-to-ATP ratio differed in each group, increasing with age. Rapid depletion of PCr occurred in all groups during ischemia; ATP retention was greater in adults than in neonates. Reperfusion resulted in no measurable recovery of ATP in any group. Postischemic pHi stabilized above preischemic values in neonatal and immature hearts and below preischemic values in adult hearts. Recovery of PCr and cytosolic Pi (Pcyi) content, heart rate, and coronary flow during reperfusion was greater in neonatal and immature than in adult hearts. During the final 20 min of ischemia, pHi was lower in immature than in neonatal or adult hearts. Postischemic recovery of left ventricular maximum rate of pressure rise (+dP/dtmax) was depressed in immature compared with neonatal and adult hearts. These results demonstrate increased tolerance of the neonatal heart and increased susceptibility of the immature heart to unprotected normothermic ischemic injury relative to the adult heart and suggest that maturational changes in myocardial pHi regulation may be responsible for the observed age-related response.

Are Age-Related Differences in Response to Myocardial Ischemia and Cardioplegia pH Dependent?

“…Although CCC decreased intracellular acidosis during isch emia in both age groups, during the last 20 min of ischemia the relationship between the age groups was reversed so pHj was greater in adult than in neonatal hearts. These results are similar to those of our previous study of ischemia alone which suggested that recovery of function during reperfusion is inversely related to the magnitude of the fall in pH| dur ing ischemia [3]. In the present study, preser vation of ATP during ischemia after CCC was followed by improved functional recovery in adult hearts.…”

“…These studies provide further evidence that PCr in neonatal rabbit hearts is less than that reported for older rabbit hearts [3,16,22,23,26,30,31]. Although the spectra used to generate our data were acquired from partial ly saturated Pi and PCr, our estimate of T1 for PCr of 2.2 sand the algorithm used by Carr et al [3] and Gadian et al [32] can be used to calculate control PCr/|3-ATP = 0.55, signifi cantly less than the value considered to be a minimum for control adult heart spectra [33].…”

“…Partly for this reason, no consen sus has been reached on how medical treat ment should be designed to adjust for the agerelated differences [10,11], In particular, the effects of cold crystalloid cardioplegia (CCC) on immature myocardium remain controver sial [12,13]. The results of previous studies are consistent with the hypothesis that agerelated differences in myocardial recovery af ter ischemia are the result of an inverse rela tionship between functional recovery and the age-related magnitude of the fall in intracellu lar p H (pHi) that occurs during ischemia [3]. This study was undertaken in order to deter mine whether age-related differences in re sponse to myocardial ischemia after cardio plegia are also consistent with this hypothe sis.…”

“…The experimental protocol and perfusion system were modified from those described previously [3,[21][22][23]. After thoracotomy, the heart was excised and placed in ice-cold perfusate.…”

“…Age-related differences be tween the neonatal and the adult myocardium have been described, but the mechanisms causing the differences have not been eluci dated [3][4][5][6][7][8][9]. Partly for this reason, no consen sus has been reached on how medical treat ment should be designed to adjust for the agerelated differences [10,11], In particular, the effects of cold crystalloid cardioplegia (CCC) on immature myocardium remain controver sial [12,13].…”