The purpose of this prospective study is to investigate denervation (ie. surgical cutting of autonomic nerves) and re-innervation (ie. growth of autonomic nerves) in heart transplant recipients. More specifically, we focus on:

1. The physiological consequences of denervation, in particular its consequences for clinical symptoms, orthostatic tolerance (ie. the ability to stand upright) and exercise capacity. We hypothesize that denervation has negative consequences for all these factors.
2. The pathological consequences of denervation and reinnervation, in particular its association to acute rejection and coronary artery disease (cardiac allograft vasculopathy, CAV). We hypothesize that reinnervation protects against acute rejection and development of CAV
3. Donor and recipient factors associated with the reinnervation process. We hypothesize that characteristics of the surgical procedure (such as aorta cross-clamp time) as well as the rehabilitation process of the recipient (such as physical activity) impacts on the reinnervation process.

Heart transplantation is annually offered to more than 3500 patients worldwide. In Norway, the number is approximately 30/year, and all transplants are carried out at one single hospital (Oslo University Hospital, Rikshospitalet).

Normally, the heart function is intimately controlled by the autonomic nervous system (ANS), but all nervous connections are lost during the surgical transplantation procedure, and the transplanted heart thus becomes denervated. In time, regrowth of nerves may cause partial reinnervation of the new heart.

Some evidence suggests that reinnervation improves exercise capacity and reduces episodes of acute rejections and the development of cardiac allograft vasculopathy. The purpose of this study is further to investigate the changes over time with respect to all parts of the autonomic nervous system (the sympathetic, parasympathetic and sensoric part), and the associated physiological and pathological consequences.

The study may provide knowledge which ultimately could help us improve health and quality of live for heart transplant recipients.

Inclusion Criteria HTRs:

• Completed heart transplantation during the last 7-12 weeks
• Age > 16 years and < 70 years

Exclusion criteria HTRs:

• Peri- or postoperative complications causing permanent dysfunction of the allograft (such as hyperacute rejection episodes, severe myocardial ischemia, etc.)
• Diabetes with HbA1C > 6,5 % and/or manifest diabetic complications
• Renal failure with plasma creatinine > 200 µmol/L
• ECG abnormalities (scattered ectopic beats ad minor conduction problems are allowed)
• Permanently bed-ridden

Inclusion criteria healthy controls:

- Age and gender matching the HTRs

Exclusion criteria healthy controls:

• Another chronic disease (such as diabetes mellitus)
• Permanent use of pharmaceuticals (including hormone drugs)
• Pregnancy

This study is to enroll 50 Heart Transplant Recipients (HTRs) and 50 healthy control subjects.

HTRs are consecutively invited to participate. Baseline investigations are carried out 7-12 weeks after transplantation surgery. Follow-up investigations are scheduled to 6 months and 1, 2 and 3 years after transplantation

Healthy control subjects will be recruited to matcht the distribution of age and gender among HTRs. The will be examined at one time point only; thus, the healthy controls are not subjected to prospective follow-up.