Myocardial high-energy phosphate metabolism in heart transplant patients is temporarily altered irrespective of rejection.

A reliable, sensitive, non-invasive alternative for transvenous endomyocardial biopsy in detecting cardiac allograft rejection is desirable for optimal management of heart transplant patients. To establish whether (31)P magnetic resonance spectroscopy can become a non-invasive tool for detecting cardiac allograft rejection, the cardiac high-energy phosphate metabolism of human heart transplants was serially examined in 13 patients by means of (31)P MRS from post-operative day 13 to day 294, and compared with histologic evaluation of endomyocardial biopsies. Biopsy scores of 2 or higher, according to the Working Formulation criteria of Billingham et al., were considered to indicate rejection. Logistic regression, which was corrected for differences between the individual patients and the time after transplantation, showed no significant correlation between the occurrence of histologically detected rejection and the PCr:ATP ratio. However, using an analysis of variance, the PCr:ATP ratios of non-rejecting cases obtained within 50 days after transplantation (mean: 27 +/- 11 days) appeared to be significantly different from those obtained after post-operative day 50 [0.95 +/- 0.17 (n = 25) vs 1.17 +/- 0.17 (n = 32), mean +/- SD; p < 0.01]. No significant difference was observed between the PCr:ATP ratios obtained 100 days after transplantation (mean: 162 +/- 52 days) and the PCr:ATP ratios in the hearts of healthy volunteers [1.18 +/- 0. 18 (n = 19) and 1.23 +/- 0.17 (n = 6), mean +/- SD, respectively; p = 0.55]. The PCr:ATP ratio in transplanted human hearts is not a sensitive indicator for the detection of early acute human cardiac allograft rejection. This may be due to a temporarily altered high-energy phosphate metabolism early after transplantation irrespective of rejection.

Functional recovery after human heart transplantation is related to the metabolic condition of the hypothermic donor heart.

BACKGROUND: Although strict selection criteria are being used for the acceptance of human donor hearts for transplantation, problems with respect to functional recovery on reperfusion sometimes still occur. Therefore, evaluation of the viability of a human donor heart before implantation during heart transplantation may be of great value. METHODS AND RESULTS: In the present study, the energy metabolism of 25 excised human donor hearts arrested with St Thomas' Hospital No. 2 cardioplegic solution was evaluated noninvasively by use of 31P magnetic resonance spectroscopy (MRS) before implantation and was correlated with myocardial function measured with thermodilution in heart transplant patients. No significant correlation was observed between the cardiac index of heart transplant patients during the first hours after transplantation and the phosphocreatine/ATP (r = .13, P = .54), inorganic phosphate/ATP (r = .26, P = .21), phosphomonoesters/ATP (r = .02, P = .92), or phosphocreatine/inorganic phosphate (r = .16, P = .44) ratio or the intracellular pH (r = .06, P = .78) at the time of reperfusion. However, 1 week after transplantation, a significant correlation was observed between the cardiac index and the phosphocreatine/ATP (r = .49, P = .01), phosphomonoesters/ATP (r = .45, P = .02), and phosphocreatine/inorganic phosphate (r = .40, P = .05) ratios at the time of reperfusion. In contrast, the inorganic phosphate/ATP (r = .10, P = .63) ratio and pH (r = .31, P = .13) at the time of reperfusion showed a poor correlation with the cardiac index 1 week after transplantation. CONCLUSIONS: Functional recovery after human heart transplantation is related to the metabolic condition of the hypothermic donor heart.

Heterotopic heart transplantation alters high-energy phosphate metabolism irrespective of cardiac allograft rejection.

This study was undertaken to validate the potential of 31P magnetic resonance spectroscopy (MRS) as a noninvasive alternative for transvenous endomyocardial biopsy in detecting cardiac allograft rejection. Donor hearts from either Lewis rats (L) or Brown-Norway rats (BN) were transplanted into the neck of L rats resulting in a non-rejecting group L-L and a rejecting group L-BN. L-L and L-BN rats were serially studied by means of 31P MRS from postoperatine day 1-8. In addition, rejection was confirmed by histology. A similar, marked decrease in phosphocreative/beta- adenosinetriphosphate (PCr/ATP) ratio from day 1-3 was observed in both L-L and L-BN hearts. This ratio levelled off on postoperative day 3 and remained depressed on subsequent postoperative days in both groups, although histology showed an increase in the severity of rejection in L-BN. However, the PCr signal/noise ratio in L-BN started to decrease after day 4, coinciding with the histologic evidence of severe rejection (score IV), whereas in L-L hearts (score 0) this ratio remained unaltered until day 8. Since high-energy phosphate metabolism is affected by the unloaded status of the heterotopically transplanted heart, irrespective of rejection, the PCr/ATP ratio appears not to be a specific marker for the detection of acute rejection in this model. In contrast, the PCr S/N ratio appears to be a specific and sensitive marker of acute rejection, but only in a late, severe stage.

Saturation correction in human cardiac 31P MR spectroscopy at 1.5 T.

This study was conducted to verify the validity of using saturation factors obtained from unlocalized 31P spectra containing both chest wall and heart muscle signals for correcting human heart muscle phosphocreatine/beta-adenosine triphosphate (PCr/beta-ATP) ratios. Saturation factors and T1 relaxation times were determined from 31P magnetic resonance spectra of human chest wall and heart muscle simultaneously in healthy volunteers using one-dimensional spectroscopic imaging in combination with a two-dimensional ISIS sequence by using adiabatic 180 degrees inversion and adiabatic 90 degrees excitation pulses at 1.5 T. Blood corrected saturation factors for PCr/beta-ATP at a TR of 2.4 s were significantly different in heart muscle and chest wall muscle, 1.30 +/- 0.25 and 1.73 +/- 0.31, respectively (p < 0.05). T1 values for PCr and beta-ATP in heart muscle were 4.28 +/- 0.72 and 2.99 +/- 0.52 and in chest wall muscle 6.82 +/- 1.07 and 3.39 +/- 0.48, respectively. The T1(PCr)/T1(beta-ATP) ratios in chest wall and heart muscle were not identical. The mean PCr/beta-ATP ratios in heart and chest wall muscle of six healthy volunteers were 1.23 +/- 0.17 and 3.71 +/- 0.53, respectively.

Experimental design of 31P MRS assessment of human forearm muscle function: restrictions imposed by functional anatomy.

The restrictions imposed by the functional anatomy of the finger flexor muscles on the experimental design of 31P MRS assessment of human forearm muscle function employing surface coil localization and voluntary exercise were investigated. It was found that 31P MRS metabolic data of finger flexor muscle should be correlated with mechanical data of combined flexion of only the ring and little fingers, rather than all four fingers as has been commonly the case in previously reported studies.