Myocardial flow regulation in people with mitochondrial myopathy, encephalopathy, lactic acidosis, stroke-like episodes/myoclonic epilepsy and ragged red fibers and other mitochondrial syndromes

Coron Artery Dis. 2003 May;14(3):197-205. doi: 10.1097/01.mca.0000065743.52558.51.

Abstract

Objective: This study tests the hypothesis that elevated levels of rest myocardial blood flow (MBF), indicative of inefficient aerobic metabolism, will be present in some patients with mitochondrial disorders but structurally normal hearts.

Background: Regulation of MBF is a complex process closely linked to myocardial energy production. Aerobic metabolism in turn depends on normal mitochondrial function and so investigation of patients with mitochondrial disorders may provide important information regarding heritable mechanisms involved in regulation of myocardial flow.

Methods: Rest and adenosine-stimulated MBF was measured by the positron emission tomography (PET) 13NH(3) technique in nine patients with mitochondrial disorders and compared with 15 age-matched control participants.

Results: Basal heart rate (beats/min) and rate pressure product (mm Hg/min) were elevated in patients (76+/-13 and 9302+/-1910, mean+/-SD, respectively) compared with control participants (63+/-9 and 7411+/-1531, P<0.01 and P<0.05, respectively). However, rest and adenosine-stimulated MBF (ml/min per g) did not differ significantly between groups (patients, 1.13+/-0.52 and 4.17+/-0.84, respectively; control participants, 0.85+/-0.30 and 3.56+/-0.63, respectively). Normalization of rest MBF to rate pressure product, however, demonstrated three patients whose values exceeded that of all control participants (chi2=5.71, P<0.05, Fisher's exact test).

Conclusions: Elevated basal MBF, in some patients with mitochondrial disorders but structurally normal hearts, suggests the level of basal flow is responsive to efficiency of aerobic metabolism, which closely reflects mitochondrial function. Mitochondrial heteroplasmy with relative sparing of myocardial mitochondria may account for normal basal flow in others with these disorders.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / metabolism
  • Acidosis, Lactic / physiopathology*
  • Adult
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Blood Pressure / physiology
  • Boston
  • Brain Ischemia / metabolism
  • Brain Ischemia / physiopathology*
  • Catecholamines / blood
  • Coronary Circulation / physiology*
  • Electrocardiography
  • Epilepsies, Myoclonic / metabolism
  • Epilepsies, Myoclonic / physiopathology*
  • Female
  • Follow-Up Studies
  • Heart Rate / physiology
  • Humans
  • MERRF Syndrome / physiopathology*
  • Male
  • Middle Aged
  • Mitochondria, Heart / diagnostic imaging
  • Mitochondria, Heart / metabolism
  • Mitochondrial Myopathies / metabolism
  • Mitochondrial Myopathies / physiopathology*
  • Myocardial Reperfusion
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Rest / physiology
  • Statistics as Topic
  • Stroke / metabolism
  • Stroke / physiopathology*
  • Syndrome
  • Thyrotropin / blood
  • Tomography, Emission-Computed

Substances

  • Biomarkers
  • Blood Glucose
  • Catecholamines
  • Thyrotropin