An individualized protocol is more accurate than a standard protocol for assessing exercise capacity after heart transplantation.

BACKGROUND: Subjective improvement and normalization of exercise tolerance are reported by most of patients after heart transplantation. However, objective measurements often do not confirm the subjective improvement. This disparate observation may be related to the methods used to test exercise tolerance. We postulated that an individualized, more gradual exercise protocol might allow a more accurate assessment of exercise tolerance than standard protocols for patients with transplanted, denervated hearts. METHODS: Eleven stable heart recipients exercised on a treadmill using two different protocols. Protocol A was a standard Naughton's protocol, and protocol B was an individualized Naughton's protocol, in which the slope of the treadmill was increased only after a steady state in heart rate and oxygen consumption had been achieved and maintained for 30 seconds. RESULTS: Patients exercised longer and reached a higher workload with protocol B than with protocol A. Time to anaerobic threshold was significantly prolonged by protocol B. Minute ventilation and oxygen consumption at anaerobic threshold were significantly higher with protocol B than with protocol A. At peak exercise, heart rate, oxygen consumption, oxygen pulse, and minute ventilation were similar with the two protocols and exceeded 75% of the predicted corresponding maximal values for a normal matched population. CONCLUSIONS: The use of an individualized, gradual exercise protocol for heart transplant recipients detected a significantly better submaximal exercise capacity than a standard protocol, which is more consistent with the subjective improvement in functional capacity in this population.

Triple-drug immunosuppression with steroid discontinuation by six months after heart transplantation.

BACKGROUND: Triple-drug immunosuppression with cyclosporine, azathioprine, and prednisone is associated with complications which might be reduced by steroid withdrawal. METHODS: In two groups of heart transplant recipients maintained on an identical regimen of cyclosporine and azathioprine, prednisone was withdrawn in group I patients (n = 35) by 6 months after transplantation, whereas in group II patients (n = 49) prednisone was never discontinued. RESULTS: Survival was similar in the two groups. The incidence of acute graft rejection was significantly higher in group I (54%) than in group II (12%), whereas infective complications were significantly lower in group I than in group II (0.63 versus 1.02 episode/patient). The degree of posttransplantation weight gain, lipid abnormalities, and incidence of hypertension were not modified by the fast tapering of prednisone, whereas the incidence of cataract and compression fracture and the degree of bone loss were significantly reduced in group I. Graft function and incidence of coronary artery disease were similar in the two groups. CONCLUSIONS: The present data suggest that prednisone can be safely withdrawn in heart transplant recipients without jeopardizing survival and graft function. Longer follow-up is needed to assess the full impact of early withdrawal of steroids from triple-drug immunosuppression, especially on long-term graft function and incidence of coronary artery disease. Benefits of early steroid withdrawal included a reduction in bone loss, which might ultimately have a major positive impact on the extent of long-term rehabilitation and exercise tolerance after heart transplantation.

Active intestinal chloride secretion in human carriers of cystic fibrosis mutations: an evaluation of the hypothesis that heterozygotes have subnormal active intestinal chloride secretion.

To explain the very high frequency of cystic fibrosis (CF) mutations in most populations of European descent, it has been proposed that CF heterozygotes have a survival advantage when infected with Vibrio cholerae or Escherichia coli, the toxins of which induce diarrhea by stimulation of active intestinal chloride secretion. Two assumptions underlie this hypothesis: (1) chloride conductance by the CF transmembrane conductance regulator (CFTR) is the rate-limiting step for active intestinal chloride secretion at all levels of expression, from approximately zero in patients with CF to normal levels in people who are not carriers of a mutation; and (2) heterozygotes have smaller amounts of functional intestinal CFTR than do people who are not carriers, and heterozygotes therefore secrete less chloride when exposed to secretagogues. The authors used an intestinal perfusion technique to measure in vivo basal and prostaglandin-stimulated jejunal chloride secretion in normal subjects, CF heterozygotes, and patients with CF. Patients with CF had essentially no active chloride secretion in the basal state, and secretion was not stimulated by a prostaglandin analogue. However, CF heterozygotes secreted chloride at the same rate as did people without a CF mutation. If heterozygotes are assumed to have less-than-normal intestinal CFTR function, these results mean that CFTR expression is not rate limiting for active chloride secretion in heterozygotes. The results do not support the theory that the very high frequency of CF mutations is due to a survival advantage that is conferred on heterozygotes who contract diarrheal illnesses mediated by intestinal hypersecretion of chloride.