Insulin improves heart function and metabolism during non-ischemic cardiogenic shock in awake canines.
OBJECTIVE
This study was undertaken to examine in-situ heart function and metabolism during insulin treatment of verapamil-induced cardiogenic shock in awake canines.


METHODS
Twenty mongrel canines were instrumented to monitor myocardial substrate uptakes (glucose, lactate, free fatty acids, oxygen [MVO2]), as well as ventricular (LV) end-systolic elastance (Emax), LV efficiency (LV minute work/MVO2), and Tau. Shock was induced by graded intraportal verapamil infusion followed by randomized assignment to one of 4 treatment groups: saline control (3.0 ml/kg/min, n = 5), epinephrine (5 micrograms/kg/min, n = 5), glucagon (10 micrograms/kg/min, n = 5) or insulin (1000 mU/min, n = 5) with dextrose to clamp arterial [glucose] +/- 10% of basal concentrations.


RESULTS
Insulin treatment significantly increased Emax (34 +/- 3 vs. 17 +/- 3 mmHg/mm, saline control), and shortened Tau (9 +/- 3 ms) compared to saline control (42 +/- 5 ms), epinephrine (20 +/- 4 ms) and glucagon (35 +/- 8 ms). With insulin treatment, mechanical efficiency increased to 20,097 +/- 2070 vs. 12,424 +/- 1615 mmHg.mm/ml/O2/100 g in controls. Simultaneously, insulin increased myocardial lactate uptake (35 +/- 2 vs. 17 +/- 4 mumol/min/100 g. saline control), but did not increase glucose uptake. Epinephrine and glucagon decreased mechanical efficiency compared to saline controls, coincident with increased myocardial fatty acid consumption, but without increasing lactate uptake. One dog died early with glucagon treatment before the first death in the saline-treated group.


CONCLUSIONS
Insulin improves systolic and diastolic heart function during aerobic shock and accelerates in-vivo myocardial lactate oxidation.
Kline
J A
JA
Department of Emergency Medicine, Carolinas Medical Center, Charlotte, NC 28232, USA.
Raymond
R M
RM
Leonova
E D
ED
Williams
T C
TC
Watts
J A
JA
D000818:Animals; D002121:Calcium Channel Blockers; D004285:Dogs; D004837:Epinephrine / Q000627:therapeutic use; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005934:Glucagon / Q000627:therapeutic use; D005947:Glucose / Q000378:metabolism / Q000627:therapeutic use; D005990:Glycerol / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000627:therapeutic use*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011897:Random Allocation; D012770:Shock, Cardiogenic / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D014280:Triglycerides / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000187:drug effects*; D014700:Verapamil
D002121:Calcium Channel Blockers; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014280:Triglycerides; D014662:Vasoconstrictor Agents; D019344:Lactic Acid; D005934:Glucagon; D014700:Verapamil; D005947:Glucose; D005990:Glycerol; D004837:Epinephrine