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Biomedical subjects

H K Hellems

Publications and source records attributed to H K Hellems.

At least 19 recordsLinked to original sources

Increasing survival of dogs subjected to hemorrhagic shock by administration of fructose 1-6 diphosphate.

Previous reports from this laboratory described animal experiments in which intravenous administration of fructose 1-6 diphosphate (FDP) at the onset of hypovolemia, toxemia, and trauma effected improvement in hemodynamic and metabolic parameters, attenuation of tissue damage, and a significant increase in survival. The obvious question remained: Would this agent be as effective if administered after the onset of the shock syndrome? Thus 72 anesthetized dogs were subjected to normotensive hemorrhagic shock and were subsequently treated with FDP at 30 minutes, 1 hour, 90 minutes, and 2 hours after exsanguination. Analysis of the results (as compared with vehicle-treated controls) revealed evidence of improved cardiac output and arterial pressure (p less than 0.02), conservation of effective circulatory volume, better oxygen utilization, and a significant increase in survival (p less than 0.0001). These results, in conjunction with earlier experimental and recent clinical data, indicate that the therapeutic effect of FDP in ischemic and hypoperfusion states is in part metabolically mediated by the augmentation of carbohydrate utilization. Prevention of tissue injury is in part due to the inhibition of generation of oxygen-derived free radicals by neutrophils.

Animals↗

Stimulating effect of fructose 1-6 diphosphate on the phagocytic function of rat RES and on human leukocyte carbohydrate metabolism.

The phagocytic behavior of the reticuloendothelial system in the rat was assessed by a quantitative technique following fructose-1,6-diphosphate (FDP) administration. In addition, the effect of FDP on the carbohydrate metabolism of human leukocytes was investigated. The rate of colloidal carbon clearance from the blood was increased significantly in the FDP-treated rats as compared to dextrose and saline controls (p less than 0.001). FDP also attenuated the hepatic decrease of ATP (p less than 0.005) and creatine phosphate (p less than 0.005) that has been observed after intravenous administration of colloidal carbon. Carbohydrate metabolism in human leukocytes was enhanced by FDP, with a concomitant increase in ATP content (p less than 0.001). Experimental evidence suggests that FDP intervenes in the Embden-Meyerhof pathway both as a metabolic regulator and as a high energy substrate. These properties of FDP in stimulating the carbohydrate metabolism have recently been described in man.

Adenosine Triphosphate↗

Irreversible hemorrhagic shock: treatment and cardiac pathophysiology.

Anesthetized dogs were subjected to hypotension at 35 mm Hg mean arterial pressure for 3 hours according to Wiggers' modified technique. One group of dogs received IV fructose-1,6-diphosphate (FDP) while the other group received equimolar glucose throughout the oligemic period. At 3 hours of hypotension, five glucose-treated and six dogs that received FDP were sacrificed for determination of myocardial ATP, creatine phosphate, and lactic acid tissue content. The remaining 14 dogs (six glucose-treated and eight FDP-treated) were retransfused with the shed blood and allowed to recover. The mean arterial pressure measured at 1 1/2 hours posttransfusion in the FDP-treated group returned to control values while the glucose controls remained 34 mm Hg below control. All controls had EKG ischemic changes, whereas no such changes were observed in the FDP-treated group. Endocardial ATP and creatine phosphate content in the controls were depleted to the same degree as found in acute myocardial ischemia, whereas in the FDP-treated dogs they were nearly normal range. All six retransfused dogs treated with glucose died, whereas all eight dogs that received FDP survived and had normal bowel and renal function and no apparent neurological deficit. These data indicate that FDP appears to be a potential therapeutic agent in the treatment of irreversible hemorrhagic shock by intervening in the Embden-Meyerhof pathway both as a metabolic regulator and high energy substrate.

Adenosine Triphosphate↗

Hemodynamic, electrocardiographic, and metabolic effects of fructose diphosphate on acute myocardial ischemia.

The hemodynamic, electrocardiographic, and metabolic responses of dogs with acute myocardial ischemia to intravenous administration of fructose-1,6-diphosphate (FDP) were assessed. Analysis of the results (compared to dextrose control) revealed evidence of major improvement of LVEDP and cardiac output, significant decrease of the ST segment, and large increases of ATP and CP in the ischemic district and to a lesser degree in the normally perfused myocardium. These results indicate that FDP intervenes in the Embden-Meyerhof pathway not only as a high energy substrate but also as a metabolic regulator influencing the activity of phosphofructokinase and that of pyruvate kinase. FDP also stimulates glycolysis in dog erythrocytes and increases their ATP and 2-3 DPG content by a factor of 2. The most significant finding in these studies is that this biochemical intervention appears to restore the depressed activity of glycolysis in ischemic myocardium.

Adenosine Triphosphate↗

Reversal of acute myocardial ischemia in closed chest animals by retrograde perfusion of the coronary sinus with arterial blood.

The fundamental objective of this study was to develop a technique for salvaging aco the ischemic muscle segment is the coronary venous system. We have been able to ration) in closed chest dogs by placing a double lumen balloon catheter in the coronary sinus, and perfusing it with blood derived from a peripheral artery. We have been able to partially reverse these same manifestations in similar dogs with an ischemic period of 30-60 minutes.

Animals↗

Atraumatic evaluation of myocardial revascularization procedures with 43K1.

Least-squares regression analysis was computerized to provide functional color images of myocardial perfusion patterns. In 8 of the 9 patients studied, changes in pattern indicated that the revascularization procedure speeded the appearance time and/or net rate of 43K uptake. The functional images correlated well with coronary arteriograms made before and after surgery. This noninvasive isotope technique may prove to be clinically useful in (a) evaluating coronary artery disease, (b) defining the remaining viable myocardium when an aneurysm is present, and (c) determining the effectiveness of the revascularization procedure.

Adult↗

Aortometric estimation of stroke volume in the presence of aortic insufficiency.

A formula has been derived for estimating the left ventricular stroke volume (SV) from measurements of the difference between maximum and minimum cross-sectional area of the ascending aorta (am), ascending aorta pulse wave velocity (c) and systolic period (TS): SV=0.54 Ts c am. In open chest dogs, this 'aortometric' formula for estimating SV compared favorably with measurements by the electromagnetic flowmeter method both with and without aortic regurgitation. This suggests that in the presence of aortic regurgitation, the aortic backflow may be estimated from the difference between the aortometric SV measurement and the systemic blood flow estimated by an independent technique.

Animals↗