Relative importance of enhanced glucose uptake versus attenuation of long-chain acyl carnitines in protecting ischemic myocardium.

Abstract

BACKGROUND:

A number of experimental studies have shown that increasing glucose use or decreasing accumulation of long-chain acyl carnitines (LCAC) protect ischemic hearts.

METHODS:

To evaluate the relative importance of these two strategies in protecting ischemic myocardium, isolated rat hearts (n = 6 in each group) were paced at 300 bpm and subjected to 50 min of low-flow ischemia followed by 60 min of reperfusion. Buffer contained 0.4 m mol/l albumin, 0.4 m mol/l palmitate, and 70 mU/l insulin, and either normal glucose (5 m mol/l) (CON), high glucose (10 m mol/l total) (HG, known to increase glucose use), 5 m mol/l glucose and niacin (10 micromol/l) (NIA, known to increase glucose use and decrease LCAC) or carnitine (10 m mol/l) (CAR, known to increase glucose use and decrease LCAC). Separate groups of hearts were perfused in the presence of 10 micromol/l cytochalasin-B (CB), an inhibitor of insulin-sensitive glucose transporters.

RESULTS:

Ischemic injury, as assessed by creatine kinase (CK) release was diminished by an average of 50% in HG, NIA, and CAR hearts, and the percentage recovery of left ventricular (LV) function with reperfusion was enhanced by approximately 20% compared with CON hearts (P < 0.05 for each comparison). Cytochalasin-B abolished all of the salutary effects. Long-chain acyl carnitines levels were higher in HG hearts compared with NIA- and CAR-treated hearts ( P < 0.05), but ischemic protection and functional recovery was greater in HG hearts.

CONCLUSIONS:

The data support the adjunctive use of agents that promote glucose uptake during ischemia and suggest that increasing glucose use is more important than decreasing LCAC in the protection against ischemic injury or in the recovery of contractile function.

• Authors: Yuying C Hwang, Soliman Bakr, Ravichandran Ramasamy, Steven R Bergmann
• Journal: Coronary artery disease (Coron Artery Dis) Vol. 13 Issue 6 Pg. 313-8 (Sep 2002) ISSN: 0954-6928 [Print] England
• PMID: 12436025 (Publication Type: Comparative Study, Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Vasodilator Agents
• acylcarnitine
• Niacin
• Cytochalasin B
• Creatine Kinase
• Glucose
• Carnitine

Topics

• Animals
• Carnitine (analogs & derivatives, metabolism, pharmacology)
• Creatine Kinase (drug effects, metabolism)
• Cytochalasin B (antagonists & inhibitors)
• Disease Models, Animal
• Glucose (metabolism)
• Models, Cardiovascular
• Myocardial Contraction (drug effects, physiology)
• Myocardial Ischemia (metabolism, physiopathology, prevention & control)
• Myocardial Reperfusion Injury (metabolism, physiopathology, prevention & control)
• Niacin (pharmacology)
• Oxygen Consumption (drug effects, physiology)
• Rats
• Recovery of Function (drug effects, physiology)
• Stroke Volume (drug effects, physiology)
• Vasodilator Agents (pharmacology)
• Ventricular Pressure (drug effects, physiology)