Metabolic support as an adjunct to inotropic support in the hypoperfused heart.
In situations such as severe low-flow ischemia, where myocardial work output is low and dependence on anaerobic glycolysis is high, increasing the myocardial supply of glucose and insulin is cardioprotective. Our goal was to determine whether this strategy of "metabolic support" would also be cardioprotective in the moderately hypoperfused heart receiving inotropic stimulation, i.e. when myocardial work was near normal, and reliance on anaerobic glycolysis was minimal. Isovolumic left ventricular performance and cardiac energetics (31P-NMR spectroscopy) were measured in 20 isolated rat hearts perfused with red blood cell containing perfusate (hematocrit 40%) with either normal (5 m M, 15 microU/ml) or increased (19.5 m M, 250 microU/ml) glucose and insulin in addition to normal levels of lactate and free fatty acids. Lowering global coronary flow to 30% of normal decreased left ventricle developed pressure by 50%. Administering dobutamine for 40 min restored developed pressure to 95+/-13% of baseline but caused diastolic pressure to increase by 23+/-6 mmHg and [ATP] to decrease by 44+/-6%. Glucose and insulin prevented the increase in end-diastolic pressure, and [ATP] fell by only 14+/-3%. Despite these improvements in cardiac energetics and diastolic function, left ventricle developed pressure was not improved by increased glucose and insulin during, or after the hypoperfusion. We conclude that inotropic support of the hypoperfused heart can cause new diastolic dysfunction, but that this diastolic dysfunction can be eliminated by preserving myocardial high-energy phosphates with increased glucose and insulin.
Saupe
K W
KW
Cardiac Muscle Research Laboratory, Boston University School of Medicine, 650 Albany St, X720, Boston, MA 02118, USA. ksaupe@aol.com
Eberli
F R
FR
Ingwall
J S
JS
Apstein
C S
CS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004280:Dobutamine / Q000494:pharmacology; D004594:Electrophysiology; D005227:Fatty Acids / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000494:pharmacology; D019344:Lactic Acid / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D017202:Myocardial Ischemia; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013816:Thermodynamics; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
D005227:Fatty Acids; D007328:Insulin; D019344:Lactic Acid; D004280:Dobutamine; D000255:Adenosine Triphosphate; D005947:Glucose