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Exercise Limitation Following Transplantation

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Abstract

Organ transplantation is one of the medical miracles or the 20th century. It has the capacity to substantially improve exercise performance and quality of life in patients who are severely limited with chronic organ failure. We focus on the most commonly performed solid‐organ transplants and describe peak exercise performance following recovery from transplantation. Across all of the common transplants, evaluated significant reduction in o2peak is seen (typically renal and liver 65%‐80% with heart and/or lung 50%‐60% of predicted). Those with the lowest o2peak pretransplant have the lowest o2peak posttransplant. Overall very few patients have a o2peak in the normal range. Investigation of the cause of the reduction of o2peak has identified many factors pre‐ and posttransplant that may contribute. These include organ‐specific factors in the otherwise well‐functioning allograft (e.g., chronotropic incompetence in heart transplantation) as well as allograft dysfunction itself (e.g., chronic lung allograft dysfunction). However, looking across all transplants, a pattern emerges. A low muscle mass with qualitative change in large exercising skeletal muscle groups is seen pretransplant. Many factor posttransplant aggravate these changes or prevent them recovering, especially calcineurin antagonist drugs which are key immunosuppressing agents. This results in the reduction of o2peak despite restoration of near normal function of the initially failing organ system. As such organ transplantation has provided an experiment of nature that has focused our attention on an important confounder of chronic organ failure‐skeletal muscle dysfunction. © 2012 American Physiological Society. Compr Physiol 2:1937‐1979, 2012.

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Figure 1. Figure 1.

This shows the relationship between o2peak and knee‐extensor muscle strength in liver transplant recipients (1a) and in renal‐transplant recipients (1b). Panel 1c(i) shows relationship between o2peak and knee‐extension strength in cystic fibrosis lung‐transplant recipients versus normal controls. Panel 1c(ii) shows the relationship between o2peak and quadriceps cross‐sectional area in cystic fibrosis lung‐transplant recipients and controls. (Adapted, with permission, from references .)

Figure 2. Figure 2.

The improvements in pre‐ to posttransplant o2peak and pretransplant peak lactate in liver‐transplant recipients is shown. Improvement in o2peak post‐liver Tx is inversely related to pretransplant peak exercise blood lactate concentration (r2 = 0.44). Adapted, with permission, from reference .

Figure 3. Figure 3.

Chronotropic incompetence is seen in the heart and heart‐lung transplant recipients. The heart‐rate response on exercise and postexercise are contrasted with the normal response.

Figure 4. Figure 4.

Relationship between the maximal rates of SR Ca2+ release (A), Ca2+ uptake (B), and Ca2+ATPase activity (C) measured in resting muscle and relative to the proportion of type II muscle fibers. SR units are μmol.min−1.gmuscle wet wt−1. Control subject (diamonds) (n = 7). Lung‐transplant recipients (triangles) (n = 7). The dashed lines show 95% confidence intervals for laboratory normal subjects. Adapted, with permission, from McKenna MJ et al. J Appl Physiol 2003;95:1606‐1616.

Figure 5. Figure 5.

Arterial plasma lactate expressed in relation to peak work rate in seven lung‐transplant recipients (circles) and seven normal controls (squares). This shows early exercise termination with a rapid rise of plasma lactate in lung‐transplant recipients. Adapted, with permission, from source .

Figure 6. Figure 6.

o2peak expressed as %predicted measured pre and the last measurement 3 to 12 months posttransplant. The single largest reported case series (shown in Tables , , , and ) with pre‐ and posttransplant o2peak measured are given for renal transplant (RTx), liver transplant (LTx), heart transplant (HTx), heart lung transplant (HLTx), single lung transplant (SLTx), and bilateral lung transplant (BLTx). Note, in RTx, %predicted are imputed but not reported specifically in the paper.



Figure 1.

This shows the relationship between o2peak and knee‐extensor muscle strength in liver transplant recipients (1a) and in renal‐transplant recipients (1b). Panel 1c(i) shows relationship between o2peak and knee‐extension strength in cystic fibrosis lung‐transplant recipients versus normal controls. Panel 1c(ii) shows the relationship between o2peak and quadriceps cross‐sectional area in cystic fibrosis lung‐transplant recipients and controls. (Adapted, with permission, from references .)



Figure 2.

The improvements in pre‐ to posttransplant o2peak and pretransplant peak lactate in liver‐transplant recipients is shown. Improvement in o2peak post‐liver Tx is inversely related to pretransplant peak exercise blood lactate concentration (r2 = 0.44). Adapted, with permission, from reference .



Figure 3.

Chronotropic incompetence is seen in the heart and heart‐lung transplant recipients. The heart‐rate response on exercise and postexercise are contrasted with the normal response.



Figure 4.

Relationship between the maximal rates of SR Ca2+ release (A), Ca2+ uptake (B), and Ca2+ATPase activity (C) measured in resting muscle and relative to the proportion of type II muscle fibers. SR units are μmol.min−1.gmuscle wet wt−1. Control subject (diamonds) (n = 7). Lung‐transplant recipients (triangles) (n = 7). The dashed lines show 95% confidence intervals for laboratory normal subjects. Adapted, with permission, from McKenna MJ et al. J Appl Physiol 2003;95:1606‐1616.



Figure 5.

Arterial plasma lactate expressed in relation to peak work rate in seven lung‐transplant recipients (circles) and seven normal controls (squares). This shows early exercise termination with a rapid rise of plasma lactate in lung‐transplant recipients. Adapted, with permission, from source .



Figure 6.

o2peak expressed as %predicted measured pre and the last measurement 3 to 12 months posttransplant. The single largest reported case series (shown in Tables , , , and ) with pre‐ and posttransplant o2peak measured are given for renal transplant (RTx), liver transplant (LTx), heart transplant (HTx), heart lung transplant (HLTx), single lung transplant (SLTx), and bilateral lung transplant (BLTx). Note, in RTx, %predicted are imputed but not reported specifically in the paper.

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Trevor J. Williams, Michael J. McKenna. Exercise Limitation Following Transplantation. Compr Physiol 2012, 2: 1937-1979. doi: 10.1002/cphy.c110021