Cellular abnormalities in chronically denervated myocardium. Implications for the transplanted heart

Area of Science:

• Cardiology
• Physiology
• Transplantation Science

Background:

• Heart transplantation results in chronic denervation, rejection, and immunosuppression.
• The chronically denervated dog heart serves as a model to study denervation effects independently.
• Intrinsic neurons with vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY) have been identified in these hearts.

Purpose of the Study:

• To investigate the metabolic consequences of chronic denervation in the heart.
• To assess myocardial oxygen consumption, enzyme activities, and substrate oxidation in denervated hearts.
• To predict potential metabolic inefficiencies in patients with transplanted hearts.

Main Methods:

• Analysis of myocardial tissue neurotransmitter concentrations (noradrenaline, dopamine).
• Assessment of atrial natriuretic peptide (ANP) release and natriuretic response.
• Measurement of in vitro oxygen consumption and Na-K, ATPase activity.
• Evaluation of in vivo glucose oxidation and key glycolytic enzyme activities (e.g., phosphofructokinase).
• Determination of maximal in vitro activities for various cardiac enzymes.

Main Results:

• Noradrenaline levels significantly decreased, while dopamine remained near normal in denervated hearts.
• The natriuretic response to atrial distension was blunted, indicating reliance on reflex mechanisms.
• In vitro studies showed increased myocardial oxygen consumption and Na-K, ATPase activity.
• In vivo glucose oxidation was inhibited, with evidence suggesting phosphofructokinase activity impairment.
• Despite functional changes, key enzyme protein concentrations and maximal activities were largely normal.

Conclusions:

• Chronic cardiac denervation leads to significant alterations in myocardial metabolism.
• Patients with transplanted hearts may experience myocardial metabolic inefficiency due to denervation.
• Further research is warranted to explore therapeutic strategies to mitigate metabolic dysfunction post-transplantation.