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R M Raymond

Publications and source records attributed to R M Raymond.

At least 55 records · Page 3Linked to original sources
PubMed1986

Myocardial depression during acute pancreatitis: fact or fiction?

Clinical and experimental evidence suggests that myocardial depression occurs during severe pancreatitis, but this evidence is derived from techniques that are not optimal for assessing myocardial contractility (e.g., rate of rise in ventricular pressure [dP/dt]). The slope of the left ventricular (LV) and systolic pressure dimension relationship (Ees), a better indicator of myocardial function, has not been measured in pancreatitis. Ten mongrel dogs underwent surgical instrumentation to monitor systemic arterial and LV pressure, cardiac output, LV dP/dt, and anterior LV wall thickness. End of systole was defined by the peak negative dP/dt. The end-systolic points used to calculate Ees were obtained by aortic and vena caval occlusion. After surgical recovery, pancreatitis was induced via cannulation of the pancreatic duct and injection of autologous bile (1 ml/kg) at 200 mm Hg perfusion pressure. All measurements were taken during a control period and daily after pancreatitis was induced. Pancreatitis was confirmed by a significant increase in serum amylase throughout the study and by autopsy finding of hemorrhagic necrosis. Ees was increased throughout the experimental protocol (1 to 7 days) (p less than 0.05). Myocardial performance as assessed by Ees was significantly increased and myocardial depression did not occur in untreated, conscious dogs with severe pancreatitis. Peak positive LV dP/dt was a poor index of contractility during pancreatitis since it decreased while myocardial contractility was increased. Cardiac depression in pancreatitis noted in other reports was likely due to decreased preload and not to intrinsic cardiac dysfunction.

Acute Disease↗
PubMed1985

Skeletal muscle insulin unresponsiveness during chronic hyperdynamic sepsis in the dog.

Recent reports from our laboratory and others have documented changes in insulin unresponsiveness and electrolyte and hormonal changes characteristic of hypodynamic shock states in anesthetized animals. Since most acute shock protocols do not adequately mimic the clinical profile of sepsis, the present study was undertaken to document the hemodynamic and metabolic changes associated with chronic hyperdynamic peritonitis in dogs. Mongrel dogs of either sex weighing 20 +/- 2 kg were surgically instrumented with an electromagnetic aortic flow probe for monitoring cardiac output determinations, and aortic and central venous catheters for withdrawing blood for blood pressure and chemical analyses. Following a recovery period (7-10 days) control hemodynamic and metabolic measurements were made. Sepsis was induced (peritoneal abscess) by implanting a 4" X 4" gauze sponge, previously inoculated with human fecal bacteria, amid the intestines. Experimental (N = 18) and pair-fed control (N = 6) animals were monitored daily for 21 days or until death. During the septic protocol, cardiac index increased from a control value of 3.4 L/min/m2 to 5.5 L/min/m2 by the end of the experimental period. Mean arterial blood pressure, total peripheral resistance index, body weight, and plasma Ca++ fell below control values during the experimental period. Body temperature, plasma glucose, insulin, glucagon, and Mg++ were all elevated with sepsis. At the end of the chronic experimental period, skeletal muscle insulin responsiveness was assessed in the isolated, innervated, constantly perfused gracilis muscle preparation. Pair-fed control animals responded to various concentrations of local insulin infusion by increasing glucose uptake by the gracilis muscle. However, septic animals had a blunted response to local insulin infusion resulting in a decrease in the maximum dose response effect. These data demonstrate that: chronic, hyperdynamic peritonitis in the dog more closely mimics the human clinical profile of sepsis; and hyperdynamic sepsis is associated with a state of skeletal muscle insulin unresponsiveness which results from a post-receptor defect.

Abscess↗
PubMed1985

Increased myocardial contractility during endotoxin shock in dogs.

The slope of the left ventricular (LV) end-systolic pressure-diameter relationship (Ees) was analyzed in open-chest, pentobarbital-anesthetized dogs before and after endotoxin administration. A lead II electrocardiogram, systemic arterial pressure, LV pressure, LV dP/dt, and LV minor axis diameter were measured. After control measurements were taken, dogs were given either 1 mg/kg Salmonella enteritidis endotoxin (n = 5) or an equivalent volume of saline (n = 4). Control dogs were followed for 240 min. Endotoxic dogs were monitored until death (246 +/- 44 min). There were no significant changes in Ees in control dogs (17 +/- 3 mmHg/mm), which were hemodynamically stable for 4 h. Ees was significantly increased in endotoxic dogs even into the late stages of shock (41 +/- 11 mmHg/mm, P less than 0.01). Only during the terminal phase did Ees fall significantly below control (11 +/- 2 mmHg/mm, P less than 0.05). End-diastolic diameter decreased following endotoxin administration (P less than 0.05) but returned toward control by the terminal stage. Peak + LV dP/dt was depressed following endotoxin injection. Myocardial contractility was not depressed except as a terminal event. Early depression of cardiovascular performance in endotoxic dogs was therefore due to decreased preload and not cardiac dysfunction.

Animals↗
PubMed1984

Skeletal muscle metabolism and insulin resistance during endotoxin shock in the dog.

The effect of locally infused endotoxin on gracilis muscle glucose uptake was determined in anesthetized mongrel dogs. The effects of infusion of small amounts of Escherichia coli endotoxin into the arteries of isolated, innervated, constant flow perfused gracilis muscles on glucose uptake and other metabolic variables were determined. Locally infused endotoxin consistently caused a significant and substantial increase in skeletal muscle glucose uptake with no alterations in muscle arteriovenous difference of insulin, oxygen, carbon dioxode, or pH, or in venous blood hematocrit or temperature. These data demonstrate that endotoxin can act locally to increase glucose uptake by skeletal muscle, independent of the action of insulin or other metabolic factors. During natural (free flow) conditions, glucose uptake by the muscle increased markedly during six hours of shock. Increased glucose uptake occurred concomitantly with muscle ischemia and hypoxia. However, when muscle blood flow was held constant, thereby preventing local muscle ischemia and hypoxia, glucose uptake by the gracilis muscle did not change during shock. These results implicate local muscle ischemia and/or hypoxia as the mediator(s) of the increased muscle glucose uptake during shock. Further studies demonstrated that local muscle hypoxia was the stimulus for increased glucose uptake by skeletal muscle during endotoxin shock, and muscle ischemia per se did not alter muscle glucose uptake. Since approximately 50% of body mass is composed of skeletal muscle, the contribution of this organ system to the hypoglycemia of endotoxin shock in the dog may be substantial. The ability of insulin to promote glucose diffusion into skeletal muscle before and during gram-negative endotoxin shock was studied in mongrel dogs anesthetized with sodium pentobarbital. The in vivo, isolated, innervated, constant flow perfused gracilis muscle preparation was used. Prior to shock induction, close intra-arterial insulin infusion resulted in a 320% increase in muscle glucose uptake. However, at one, two, and three hours of endotoxin shock, gracilis muscle glucose uptake was unaltered by insulin infusion. This loss of responsiveness to insulin occurred with no alteration in gracilis muscle oxygen uptake, muscle venous P02, or muscle blood flow. During control experiments, however, the muscle response to intra-arterial infusion of insulin (increased glucose uptake) was unaltered during the three-hour control period. These data demonstrate that skeletal muscle insulin resistance develops early and is maintained during three hours of endotoxin shock in the dog.

Animals↗
PubMed1982

Forelimb skeletal muscle and skin glucose uptake during Escherichia coli endotoxin shock in the dog.

We previously demonstrated an increase in gracilis muscle glucose uptake during endotoxin shock in the dog. The present study was completed to investigate this phenomenon in forelimb skeletal muscle and skin. The isolated forelimb preparation was used. Mongrel dogs were anesthetized with nembutal and heparinized. Shock was induced by i.v. infusion of E. coli endotoxin. When isolated forelimb temperature was maintained at contralateral intact forelimb temperature (which was always the same as core temperature), forelimb skeletal muscle and skin glucose uptake increased by 30 minutes of shock, and remained above control for the 4 hour shock period. Total forelimb blood flow decreased and the limb became severely hypoxic (mean venous PO2 = 24 mmHg). However, when the isolated forelimb temperature was not artificially maintained at contralateral intact forelimb temperature (same as core temperature), the isolated forelimb temperature fell approximately 3 degrees C and the elevation of glucose uptake was not observed. Although forelimb blood flow decreased to the same level as in the temperature controlled group, the forelimbs were only moderately hypoxic. This study emphasizes the important influence of temperature on tissue metabolism and the recognition of its importance in experimental data interpretation, especially when metabolic variables are involved. It also demonstrates that changes in glucose uptake during shock are similar in dog forelimb skeletal muscle, provided that changes in muscle temperature are similar.

Animals↗
PubMed1982

Mechanism of forelimb skin and skeletal muscle glucose uptake during Escherichia coli endotoxin shock in the dog.

This study was undertaken to investigate mechanisms of increased glucose uptake by forelimb skin and skeletal muscle during endotoxin shock. Anesthetized mongrel dogs were used. Forelimbs were perfused at either natural or constant blood flow. Temperature of the isolated forelimb was maintained at core temperature. Shock was induced by an IV injection of 2 mg/kg Escherichia coli endotoxin. Forelimb skin and skeletal muscle glucose uptake increased by 30 minutes of shock and remained elevated in the natural flow study. In the constant flow study, glucose uptake by both skin and skeletal muscle was increased at 30 minutes of shock but thereafter returned to control. The natural flow forelimbs were ischemic and hypoxic during shock, whereas the constant flow forelimbs were neither ischemic not hypoxic. Progressive hypoglycemia developed in both endotoxin shock groups. These data support the hypothesis that the mechanism of increases in forelimb skin and skeletal muscle glucose uptake during endotoxin shock is related to local tissue hypoxia.

Animals↗
PubMed1982

Direct effects of insulin and endotoxin on glucose uptake by skeletal muscle during high cardiac index sepsis in the dog.

Experiments were completed upon unanesthetized and anesthetized dogs in the control and septic groups. Dogs that were made septic by the intraperitoneal administration of live Escherichia coli bacteria showed an elevation in cardiac index and core temperature and a decrease in total peripheral resistance index and mean arterial blood pressure. Following the seventh day of sepsis, the dogs were anesthetized and the constantly perfused gracilis muscle preparation was used for metabolic and hemodynamic determinations. Insulin stimulated muscle glucose uptake in non-septic dogs was markedly increased, whereas increases in muscle glucose uptake in the septic group of dogs was absent when challenged with local insulin infusion. Resting muscle glucose uptake of the septic group was observed to be greater than that of dogs in the nonseptic group. These data demonstrate a hyperdynamic model of sepsis in the dog which was associated with decreased muscle responsiveness or sensitivity to local insulin infusion, or both. The insulin-like activity of the endotoxin molecule in promoting muscle glucose uptake was maintained in both the septic and control group of dogs. This activity of the endotoxin molecule could explain, in part, the increased resting muscle glucose uptake observed in the septic group of dogs.

Animals↗
PubMed1981

Direct effects of gram-negative endotoxin on skeletal muscle glucose uptake.

The effect of locally infused endotoxin on gracilis muscle glucose uptake was determined in anesthetized mongrel dogs. Locally infused endotoxin consistently caused an increase in skeletal muscle glucose uptake with no alterations in any other metabolic variable. These data demonstrate that endotoxin can act locally to increase glucose uptake by skeletal muscle, independent of the action of insulin or other metabolic factors. On the other hand, when endotoxin was given systemically to induce shock, gracilis muscle glucose uptake did not increase. These differences may reflect the reduction in plasma endotoxin concentration mediated by the reticuloendothelial system (RES). However, live Escherichia coli shock was associated with an increase in glucose uptake in the constant flow perfused gracilis muscle after 4.5 h of shock. We believe this increase in muscle glucose uptake resulted from the direct effects of endotoxin, the plasma concentration of which presumably increased as the RES was overwhelmed and became less effective. The contribution of this phenomenon to the hypoglycemia of gram-negative endotoxin or septic shock cannot be evaluated from this study.

Animals↗
PubMed1981

Involvement of adenosine in cerebral hypoxic hyperemia in the dog.

Theophylline, a competitive adenosine antagonist, was used to evaluate the role of adenosine in cerebral hypoxic hyperemia. Cerebral venous outflow was measured by the Rapela-Green technique in mongrel dogs anesthetized with pentobarbital sodium and ventilated artificially. Theophylline was infused locally into the cerebral arterial system during moderate [cerebral venous O2 tension (PO2) 27-29 mmHg] or severe (cerebral venous PO2 = 10-15 mmHg) hypoxia; theophylline had no direct vascular effects at the concentration used. Cerebral hyperemia was completely reversed during moderate hypoxia, but only partially reversed during severe hypoxia when theophylline was infused during maintained hypoxia. Theophylline had no effect on cerebral; perfusion pressure, blood flow, or vascular resistance during normoxia. In another group, theophylline had no effect on the cerebral hyperemia induced by hypercapnia. In separate experiments, local cerebral arterial infusion of adenosine or AMP during normoxia had no effect on cerebral hemodynamics at any infusion rate tested (up to 100 micrograms/min). This study supports the hypothesis that adenosine is involved in the hyperemia associated with cerebral hypoxia. However, the degree of involvement may be dependent on the degree of hypoxia.

Adenosine↗
PubMed1981

Interactions among inflammatory mediators on edema formation in the canine forelimb.

Prostaglandin E1, 4 microgram/min, infused locally intra-arterially (ia) for 60 minutes into forelimbs perfused at constant pump controlled inflow produced decreases in perfusion pressure, increases in lymph total protein concentration (approximately equal to g/100 ml), and small increases in weight (23 g) owing to edema formation. Histamine, 16 microgram base/min, or bradykinin, 10 microgram base/min, infused locally ia for 60 minutes produced large increases in lymph flow, lymph total protein concentration, total protein transport, and weight (70 g and 130 g, respectively). However, the local ia infusion of prostaglandin E1, 4 microgram/min, together with histamine, 16 microgram base/min, or bradykinin, 10 microgram base/min, produced weight increases of 180 g and 236 g, respectively, and the rate of weight gain during the combination infusions greatly exceeded that produced by infusions of histamine or bradykinin alone. Moreover, the increases in lymph flow and in total protein transport far exceeded those produced by infusions of prostaglandin E1 and histamine or bradykinin alone or additively. The edema produced by the local ia infusion of prostaglandin E1, 4 microgram/min, together with bradykinin, 10 microgram base/min, was even more more marked in naturally perfused forelimbs. Similarly, the local ia infusion of histamine, 4 microgram base/min, or bradykinin, 0.8 microgram base/min, for 60 minutes into forelimbs perfused at constant inflow produced increases in lymph flow, lymph total protein concentration, total protein transport, and weight (38 g and 14 g, respectively). In contrast, histamine, 4 microgram base/min, and bradykinin, 0.8 microgram base/min, infused together locally ia for 60 minutes produced increases in weight of 118 g. The increase in lymph flow and total protein transport was considerably more marked during the combined infusions than during the infusions of histamine or bradykinin alone or additively.

Animals↗
PubMed1981

Insulin-like action of E. coli endotoxin in promoting skeletal muscle glucose uptake in the dog.

The effect of locally infused endotoxin on gracilis muscle glucose uptake was determined in anesthetized mongrel dogs. The effects of infusion of small amounts of E. coli endotoxin into the artery of isolated, innervated, constant-flow-perfused gracilis muscles on glucose uptake and other metabolic variables were determined. Locally infused endotoxin consistently caused a significant and substantial increase in skeletal muscle glucose uptake with no alterations in muscle arterio-venous difference of insulin, oxygen, carbon dioxide, or pH, or in venous blood hematocrit or temperature. These data demonstrate that endotoxin can act locally to increase glucose uptake by skeletal muscle, independent of the action of insulin or other metabolic factors. On the other hand, when endotoxin was given systemically to induce shock, gracilis muscle glucose uptake was maintained for the duration of the 6-hr experiment. These differences we feel reflect the reduction in plasma endotoxin concentration mediated by the reticuloendothelial system (RES). On the other hand, live E. coli septic shock was associated with an increase in glucose uptake in the constant-flow-perfused gracilis muscle after 4.5 hr of shock. We believe this increase in muscle glucose uptake resulted from the direct effects of endotoxin, whose plasma concentration presumably increases substantially as the RES is overwhelmed and becomes less effective. The contribution of this phenomenon to the progressive hypoglycemia characteristic of gram-negative endotoxin or septic shock cannot be evaluated from this study, although it is probably substantial.

Animals↗
PubMed1981

Effects of naloxone therapy on hemodynamics and metabolism following a superlethal dosage of Escherichia coli endotoxin in dogs.

Experiments were done upon anesthetized and unanesthetized dogs given endotoxin only, endotoxin plus naloxone or naloxone only. Dogs given endotoxin and treated with naloxone showed marked hemodynamic and metabolic improvements compared with the dogs given endotoxin only. Beneficial effects of naloxone treatment following the administration of endotoxin are attentuated hypotension, hemoconcentration and acidosis and prevention of hypoglycemia. Results of mortality studies in unanesthetized dogs given endotoxin suggest that naloxone treatment increases the survival time.

Animals↗
PubMed1981

Mechanism of increased glucose uptake by skeletal muscle during E coli endotoxin shock in the dog.

Carbohydrate metabolism of skeletal muscle was studied during 2 mg/kg E coli endotoxin shock in dogs. During natural (free-flow) conditions, glucose uptake by the muscle increased markedly during 6 hours of shock. Increased glucose uptake occurred concomitant with muscle ischemia and hypoxia. However, when muscle blood flow was held constant, thereby preventing local muscle ischemia and hypoxia, glucose uptake by the gracilis muscle did not change during shock. These results implicate local muscle ischemia and/or hypoxia as the mediator(s) of the increased muscle glucose uptake during shock. Further studies demonstrated that local muscle hypoxia was the stimulus for increased glucose uptake by skeletal muscle during endotoxin shock, and muscle ischemia per se did not alter muscle glucose uptake. Since approximately 50% of body mass is composed of skeletal muscle, the contribution of this organ system in the hypoglycemia of endotoxin shock in the dog may be substantial.

Animals↗
PubMed1981

In vivo skeletal muscle insulin resistance during E coli endotoxin shock in the dog.

The ability of insulin to promote glucose diffusion into skeletal muscle before and during gram-negative endotoxin shock was studied in mongrel dogs anesthetized with sodium pentobarbital. The in vivo, isolated, innervated, constant-flow-perfused gracilis muscle preparation was used. Prior to shock induction, close intraarterial insulin infusion resulted in a 320% increase in muscle glucose uptake. However, at one, two, and three hours of endotoxin shock, gracilis muscle glucose uptake was unaltered by insulin infusion. This loss of responsiveness to insulin occurred with no alteration in gracilis muscle oxygen uptake, muscle venous PO2, or muscle blood flow. During control experiments, however, the muscle response to intraarterial infusion of insulin (increased glucose uptake) was unaltered during the three-hour control period. These data demonstrate that skeletal muscle insulin resistance develops early and is maintained during three hours of endotoxin shock in the dog.

Animals↗
PubMed1981

Skeletal muscle insulin resistance during Escherichia coli bacteremic shock in the dog.

Skeletal muscle glucose uptake during close, intra-arterial insulin infusion was studied before and during live Escherichia coli bacteremic shock in the dog. An in vivo, constant-flow perfused gracilis muscle preparation was used. Insulin infusion before shock resulted in a 395% increase in muscle glucose uptake, which was independent of changes in muscle lactate production or oxygen uptake. At 1, 2, and 3 hours of shock, insulin infusion had no effect on gracilis muscle glucose uptake. This loss of responsiveness to insulin occurred with no change in muscle oxygen uptake, muscle venous PO2, or muscle blood flow (held constant). On the other hand, during nonshock control experiments, muscle glucose uptake in response to insulin infusion was maintained during the 3-hour protocol. These data demonstrate that skeletal muscle insulin resistance develops early during bacteremic shock.

Animals↗