title: Studies on prolonged acute regional ischemia. V. Metabolic support of remote myocardium during left ventricular power failure.
abstract: This study tests the hypothesis that metabolic support of remote "nonischemic" myocardium during acute infarction will reverse the trend toward cardiogenic shock. Thirty-seven dogs underwent ligation of the left anterior descending coronary artery and 50% stenosis of the circumflex coronary artery. Irreversible ventricular fibrillation developed in 11 of them. The 26 survivors were observed for up to 6 hours; global and regional left ventricular function (cardiac index, stroke work index, ultrasonic crystals) and regional blood flow (radioactive microspheres) were measured. After 2 hours, eight dogs received an intravenous infusion of glutamate/aspartate, glucose-insulin-potassium, coenzyme Q10, and 2-mercapto-propionyl-glycine for 4 hours. Five dogs received the mannitol infusion to raise serum osmolarity 30 mOsm. Four additional dogs received the intravenous substrate infusions over 4 hours without undergoing ischemia. The substrate infusion for 4 hours caused no change in regional or global cardiac function in the four control dogs. Three of nine untreated dogs died of cardiogenic shock, and progressive left ventricular power failure occurred in the six others (40% decrease in cardiac index, 50% decrease in stroke work index, p less than 0.05) because of persistent dyskinesia in the left anterior descending region (-40% of systolic shortening, p less than 0.05) and hypocontractility in the circumflex region (48% of control systolic shortening, p less than 0.05), despite normal transmural blood flow in the posterior left ventricular wall (76 ml/100 gm/min). In contrast, in treated dogs, hypercontractility recovered in the circumflex segment (138% of systolic shortening) and stroke work index rose to control levels (91%) without a change in regional blood flow. Mannitol infusion did not improve hemodynamics or avoid the development of progressive left ventricular power failure. We conclude that cardiogenic shock after myocardial infarction is due, in large part, to impaired ability of "nonischemic" myocardium to maintain hypercontractility. This limitation can be prevented by metabolic support of viable muscle, and the data imply that intravenous substrate infusions may be helpful before definitive treatment (i.e., coronary artery bypass grafting) is undertaken.
authors.affiliation: Division of Cardiothoracic Surgery, University of California, Los Angeles Medical Center 90024-1741.
authors.forename: F
authors.initials: F
authors.lastname: Beyersdorf
authors.forename: C
authors.initials: C
authors.lastname: Acar
authors.forename: G D
authors.initials: GD
authors.lastname: Buckberg
authors.forename: M T
authors.initials: MT
authors.lastname: Partington
authors.forename: F
authors.initials: F
authors.lastname: Okamoto
authors.forename: B S
authors.initials: BS
authors.lastname: Allen
authors.forename: H H
authors.initials: HH
authors.lastname: Young
authors.forename: H I
authors.initials: HI
authors.lastname: Bugyi
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000008:administration & dosage; D003326:Coronary Circulation; D004285:Dogs; D005947:Glucose / Q000008:administration & dosage; D005971:Glutamates / Q000008:administration & dosage; D006439:Hemodynamics; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage; D008353:Mannitol / Q000008:administration & dosage; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism*; D011188:Potassium / Q000008:administration & dosage; D012770:Shock, Cardiogenic / Q000503:physiopathology / Q000517:prevention & control; D008625:Tiopronin / Q000008:administration & dosage; D014451:Ubiquinone / Q000008:administration & dosage; D014693:Ventricular Fibrillation / Q000209:etiology
chemical_list: D005971:Glutamates; D007328:Insulin; D014451:Ubiquinone; D001224:Aspartic Acid; D008353:Mannitol; D008625:Tiopronin; D005947:Glucose; D011188:Potassium