Effect of enkephalins on cardiac output and regional blood flow in conscious dogs.
To investigate the effects of enkephalins on cardiac output and regional blood flow, we administered D-Ala-D-Leu-enkephalin (DADLE) intracisternally (ic) to 14 chronically instrumented unanesthetized dogs. Measurements were made at base line, 20, 45, and 75 min after DADLE (25 or 125 micrograms/kg) and 15 min after naloxone (5 micrograms/kg ic). After 125 micrograms/kg DADLE, all animals developed hypoventilation, bradycardia, and decreased O2 consumption without hypotension. Cardiac output decreased (-34%), but brain blood flow increased (+110%). Blood flow decreased to the diaphragm (-38%), heart (-21%), skeletal muscle (-40%), skin (-67%), pancreas (-79%), and gastrointestinal tract (-26%). After 25 micrograms/kg DADLE, there were no consistent changes in cardiac output or regional blood flow. Four additional animals (without DADLE) were exposed to altered inspired gases to reproduce the blood gas changes after DADLE. These animals developed hyperventilation without bradycardia and increased brain (+114%) and diaphragm (+649%) blood flow. We conclude that centrally administered enkephalins produce 1) a parallel decrease in ventilation, heart rate, O2 consumption, and cardiac output and 2) a major blood flow redistribution, primarily dictated by the effects of opioids on ventilation, heart rate, and metabolism.
Rosen
C L
CL
Department of Pediatrics, Columbia University, College of Physicians and Surgeons, New York, New York 11791.
Cote
A
A
Haddad
G G
GG
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D002302:Cardiac Output / Q000187:drug effects*; D004285:Dogs; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D006339:Heart Rate / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009928:Organ Specificity; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects*; D012119:Respiration / Q000187:drug effects
D002245:Carbon Dioxide; D009270:Naloxone; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D010100:Oxygen