phosphocreatine and Shock--Cardiogenic

The effects of 2-[(5-chloro-2-methoxyphenyl)azo]-1H-imidazole (M6434) were investigated in experimental models of lethal shock produced by hemorrhage, injection of endotoxin, or coronary ligation. M6434 improved the survival rate of rabbits in hemorrhagic shock. M6434, at the dose of 3 or 10 micrograms/kg/min, completely reversed the decreases in the blood pressure and the urine output of shocked rabbits, but did not affect the decreased regional blood flow through the kidneys in the animals. Survival rates of cardiogenic-shock rats improved, and the content of ATP and creatine phosphate in myocardium of these animals were restored by the treatment with 1 or 3 micrograms/kg/min of M6434. Intravenous infusion of M6434, at a dose of 3 or 10 micrograms/kg/min for 3 hr, increased the survival rate of the endotoxin-shocked rabbits. These results indicate that M6434 may be evaluated as a possible therapeutic agent for shock.

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Diuresis; Dobutamine; Dopamine; Heart Rate; Imidazoles; Male; Myocardium; Phosphocreatine; Rabbits; Rats; Rats, Inbred Strains; Renal Circulation; Shock, Cardiogenic; Shock, Hemorrhagic; Shock, Septic; Sympathomimetics

Cardiogenic shock after acute myocardial infarction and open heart surgery having cardiopulmonary bypass may present a difficult clinical problem with high mortality. The present study was carried out to evaluate a newly developed laminar flow centrifugal pump as a left-ventricular-assist device to support the circulation and prevent myocardial damage in such situations. Experimentally induced acute myocardial infarction in dogs was used as the model. Cardiogenic shock was effected by ligating enough branches of the left coronary artery. In addition to recording the haemodynamic parameters, samples of myocardium were taken with a biopsy needle from the infarcted area, transitional zone and intact myocardium for determination of adenosine triphosphate, creatine phosphate and lactate. In the first phase of the work the effects of acute myocardial infarction on haemodynamics and high-energy compounds were defined, to form a basis for the evaluation of the pump as left-ventricular-assist device. Ligation of the branches of the left coronary artery produced a rapid fall in aortic pressure, cardiac output and cardiac performance, elevation of ST-segment in the ECG and fall in high-energy compounds. However, there was a marked spontaneous recovery in the transitional zone within 120 min, despite the haemodynamic deterioration. The laminar flow pump produced a significant improvement in the haemodynamic and metabolic parameters which exceeded the spontaneous changes noted previously.

Topics: Adenosine Triphosphate; Animals; Assisted Circulation; Dogs; Hemodynamics; Intra-Aortic Balloon Pumping; Lactates; Myocardial Infarction; Myocardium; Phosphocreatine; Shock, Cardiogenic

The precise mechanism responsible for early contractile failure after the onset of myocardial anoxia or ischemia has attracted speculation and controversy. The simple and attractive hypothesis that adenosine triphosphate (ATP) deficiency is responsible for this failure has often been dismissed on the basis of claims that there is only a small reduction in cell ATP content at a time when contractile activity is severely reduced. The premise of this article is that the changes in cell ATP content and distribution that theoretically should occur after oxygen depletion may not have been adequately considered and that previous measurements of cell ATP content may not have been carried out at the correct time. Using an isolated rat heart preparation and high speed freeze-clamping techniques it has been possible to demonstrate that a substantial decrease in myocardial ATP and creatine phosphate content occurs after the onset of anoxia but before the onset of contractile failure. Thus, during the first 5 seconds of anoxia contractile activity remains constant whereas ATP decreases by 25 percent and creatine phosphate by 50 percent. Thereafter, contractile failure occurs and the rate of utilization of high energy phosphates declines with the cell content at a plateau or possibly increasing. These results are assessed in the light of the dynamic changes in energy metabolism occurring in early anoxia and suggest that ATP depletion in a specific cell compartment may be the primary trigger for early contractile failure.

Topics: Adenosine Triphosphate; Animals; Coronary Disease; Energy Metabolism; Hypoxia; Male; Myocardial Contraction; Myocardium; Phosphocreatine; Rats; Shock, Cardiogenic

Skeletal muscle metabolite concentrations were determined in 19 patients in either cardiogenic shock or severe left ventricular failure by obtaining a needle biopsy specimen of lateral thigh muscle. Evidence of anaerobic skeletal muscle metabolism was found in both patient groups with the greatest lactate accumulation and most severe high-energy phosphate depletion present in the patients in cardiogenic shock. The skeletal muscle lactate accumulation was most pronounced in the patients that died. Blood lactate values did not absolutely predict skeletal muscle lactate concentrations in those patients in whom skeletal muscle lactate concentrations were the highest. The patients in cardiogenic shock and severe left ventricular failure who survived demonstrated a reduction in skeletal muscle lactate levels and a restoration of high-energy phosphates over several days which correlated with clinical and hemodynamic improvement.

Topics: Adenosine Triphosphate; Adult; Aged; Biopsy, Needle; Carbon Dioxide; Female; Glucose; Glucosephosphates; Glycogen; Heart Failure; Humans; Hydrogen-Ion Concentration; Lactates; Male; Middle Aged; Muscles; Oxygen; Partial Pressure; Phosphocreatine; Shock, Cardiogenic