William R. Drucker

Pathogenesis of post-traumatic sympathetic dystrophy

Abstract 1. 1. Sixty-one cases of sympathetic dystrophy are reviewed with reference to the wide disparity in clinical description and concepts of pathogenesis found in the literature. The only symptom found consistently is pain in the injured extremity. 2. 2. Sympathetic dystrophy is considered to be fundamentally the same entity as causalgia. The only significant difference between them is that causalgia is initiated by an injury to a mixed peripheral nerve whereas in sympathetic dystrophy there may have been no such demonstrable injury. The term, Sudecks atrophy, should be reserved to describe the osteoporosis occasionally found in causalgic states. 3. 3. The pathogenesis of causalgia and causalgic states is represented as a vicious circle of reflexes under the modifying influence of hypothalamic and environmental factors. Pathogenesis is discussed with reference to pertinent neurophysiological experiments. 4. 4. Causalgic pain which is unresponsive to a short trial of conservative measures should be treated by sympathetic denervation of the involved extremity. Failure to institute prompt therapy may result in intractable pain and irreversible structural changes.

The role of blood glucose in defense of plasma volume during hemorrhage.

The purpose of this study was to assess the importance of the hyperglycemic response in defense of plasma volume during hemorrhagic shock. Normal well-fed white rats were divided into four groups of 10 each. Two shock models were used each containing rats fasted for 24 hr and control rats maintained on a standard diet. All rats had free access to water. Hemorrhage was produced either by bleeding to a constant mean arterial blood pressure of 40 mm Hg or by removing a fixed per cent of blood volume at 30-min intervals. All control animals withstood a larger volume of blood loss and survived longer than fasted animals, regardless of which shock model was used. They also manifested a significantly greater mean maximum per cent rise in blood glucose and decline in hematocrit during hypovolemia. A change in blood glucose was correlated with change in hematocrit, and to the extent that the latter is a reflection of plasma refill, fed animals demonstrated a greater ability to refill lost plasma volume. The strong correlation between glucose levels and hematocrit during all phases of hypovolemic shock indicates that blood glucose may be an important determinant of plasma refill. The mechanisms whereby glucose exerts these effects may involve its role as an osmotic agent and as a substrate for energy metabolism.

Glucose infusion arrests the decompensatory phase of hemorrhagic shock

Waning of hyperglycemia has been shown to be closely associated with the deterioration of mechanisms supporting homeostasis during hemorrhagic shock. However, the mechanisms which link plasma glucose levels to maintenance of homeostasis during hemorrhagic shock are not clear. The goal of the present study was to evaluate the importance of glucose to maintenance of compensatory mechanisms. This was undertaken by maintaining plasma glucose levels through infusion of hypertonic glucose (2-3 M) starting at the onset of decompensation during persisting hypovolemia. Administration of glucose at a rate of between 60 and 80 mumoles/min X kg arrested the fall in glucose concentration and significantly slowed or arrested the decompensatory phase. All of the saline infused control animals (n = 6) died within 3 hours after reaching their maximum shed blood volume, averaging 145 +/- 25 minutes, while two of the eight animals in the glucose infusion group died less than 4 hours after reaching the maximum shed blood volume. The remaining six animals were sacrificed between 270 and 397 minutes (average, 340 +/- 22 minutes) after reaching the maximum shed blood volume since decompensation was arrested. Compared to the saline-infused control group, animals receiving glucose infusion exhibited a more moderate acidosis, and the hemoconcentration which normally accompanies decompensation was also prevented. Since the increase in plasma osmolality and the fraction of the total osmolality change accounted for by glucose was less in the glucose-infused animals, these results suggest that the effect is not mediated through a glucose-related maintenance of a transcapillary osmotic gradient.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies of the effect of intravenous tolbutamide on pyruvic and lactic acid concentrations in peripheral venous blood in normal and diabetic subjects, and on splanchnic metabolism of fructose and glucose.

It has been known for some time that a blood sugar depression following the administration of insulin may be accompanied by concomitant elevations in blood pyruvate and blood lactate 1evels.l. 2 , Moorhouse and Kark4 have reported that the blood sugar depression following tolbutamide administration in a diabetic is not accompanied by these changes in pyruvate and lactate; and Hennes et aL6 have reported that in normal subjects the initial pyruvate change associated with hypoglycemia is an elevation following insulin, but a depression following tolbutamide. From this disparity the latter authors concluded that the hypoglycemic actions of the two agents are distinct and that a release of endogenous insulin is not the mechanism of action of tolbutamide. It was our objective to produce with insulin and tolbutamide (Orinase!) blood sugar depressions similar in magnitude and rate of fall and, under these conditions, to compare the pyruvate and lactate changes in both normal and diabetic subjects.

Metabolism of Fructose by the Liver of Diabetic and Non-Diabetic Subjects.∗

Summary and Conclusions The metabolism of fructose in the liver was investigated by hepatic vein catheterization studies in 3 diabetic patients deprived of insulin and in 3 non-diabetic subjects. (1) There was a large hepatic uptake of fructose during the period of intravenous administration in both diabetic and non-diabetic subjects. (2) In all but one case there was a large hepatic output of pyruvic and lactic acid during the fructose infusion. The liver of one diabetic patient in ketosis continued to remove pyruvic and lactic acid from the blood; hepatic glycogen depletion may have accounted for this divergent result. (3) In half the cases (2 diabetic patients and 1 non-diabetic subject) the output of glucose by the liver was increased during fructose administration. (4) In the absence of ketosis, the liver of the diabetic subject without insulin, therefore, metabolized fructose in a manner similar to that of the liver of the non-diabetic individual. The presence of ketosis, however, was accompanied by a decreased output of pyruvic and lactic acid, despite a normal uptake of fructose.

The influence of diet on response to hemorrhagic shock.

Prior nutrition is known to influence tolerance to hypovolemic shock. This study was undertaken to determine the influence of dietary composition on the response of animals subjected to hypovolemic shock. Particular attention was directed to the role of high and low protein diet content with a proportionate change in carbohydrate content to yield isocaloric diets. Rats were placed on one of three diets and were subsequently subjected to shock either by 1) hemorrhage to a pre-determined mean arterial blood pressure, or by 2) hemorrhage of a pre-determined volume of blood based on per cent of body weight. Serial measurements were made of blood pressure, blood volume removed, survival time,hematocrit, blood glucose, pH and blood gases. The results indicate that a high protein diet does not prolong tolerance to recurrent blood loss but there is a greatly reduced tolerance to hemorrhage shock in rats whose body weight was maintained on a low protein/high carbohydrate diet. The latter animals also exhibited impaired refill of plasma volume and a paradoxical, continuing hyperglycemic response during hypovolemia. This study suggests that although an abundant supply of blood glucose is available as an energy source, glucose uptake in the peripheral tissues is inhibited during hypovolemia by unknown mechanisms and thus homeostasis is curtailed. The protein content of the diet may be a critical factor in carbohydrate use during shock.

Influences of fasting and water intake on plasma refill during hemorrhagic shock.

The hyperglycemic response to hypovolemia has been regarded as an essential osmotic force for promoting the early phase of the internal restoration of plasma volume. Our previous studies of rats fasted 24 hours revealed that they did not develop the hyperglycemic response to hemorrhage observed in fed animals but they had a similar hyperosmotic response. The solutes responsible for the hyperosmolality in the fasted animals were primarily products of anaerobic glycolysis, rather than glucose which accounted for most of the hyperosmolality in fed animals. Plasma refill as reflected by a fall in the hematocrit (Hct) and survival time was significantly reduced in the fasted animals. This study was undertaken to test the hypothesis that the failure of fasted rats to exhibit a normal restoration of plasma volume after hemorrhage may reflect the detrimental effects of fasting on the state of hydration and on the plasma oncotic pressure of the fasted animals rather than the absence of a hyperglycemic response. Four groups of anesthetized rats (280-380 gm) were bled acutely and maintained at an arterial pressure of 40 mm Hg. Before hemorrhage animals in Group A were well fed, those in Groups B, C, and D were fasted for 24 hours. Rats in Group B were induced to drink by addition of sodium chloride in their water, rats in Group C spontaneously had a normal fluid intake, and rats in Group D had a significant reduction in their 24-hour fluid intake. The results demonstrated that 24 hours of fasting led to a loss of body weight of 7 to 10% and a fall in the concentration of plasma total protein of 12 to 17% in all rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Liver adenosine triphosphate (ATP) in hypoxia and hemorrhagic shock.

Reduction of liver ATP in proportion to the severity of shock and hypoxia is well known. We have studied the interrelationships among arterial oxygenation, arterial pH, and liver ATP in experimental hypoxia and in hemorrhagic shock in rats. No significant correlation was found between liver ATP and arterial pH in both hemorrhagic shock and hypoxia and between liver ATP and arterial PO2 in hypoxia. Induction of experimental observations suggest that in this form of hemorrhagic shock, arterial pH may be a sensitive indicator of decreased hepatic perfusion and impaired liver ATP production.

Histochemical Investigation of Hepatic Adenosine Triphosphatase and Glucose-6-phosphatase Activity in Hemorrhagic Shock∗

Summary Twelve rats were subjected to hemorrhagic shock. Histochemical study of the liver revealed increased adenosine triphosphatase and glucose-6-phosphatase activity when compared to controls. The reason for these alterations may be either an actual increase in enzymes in the parenchymal cells or altered histochemical reactivity due to cell necrosis, changes in membrane permeability, or deranged intra and extracellular ionic concentrations as a result of hypovolemia. The increased enzyme activities relate logically to altered carbohydrate metabolism and fluid dynamics in shock.

Diminished Adrenal Corticoid Response to Burn and ACTH in the Nephrectomized Dog.

Summary Nephrectomized dogs respond to third degree burns with much less increase in 17 OHCS secretion than do normal dogs. ACTH injection also produces much less increase in 17 OHCS secretion in nephrectomized than in normal dogs. These diminished responses appear to result from decreased adrenal sensitivity to ACTH. It is suggested that the kidney plays an important role in the control of 17 OHCS secretion.