Hemorrhagic Shock In Dogs Research Articles

Letters to the Editor

LETTERS TO THE EDITOR Dear Sir: Although most scientists, at least in pubUc and official responses, do indeed try to be fair about rival formulations, the real pragmaticjudgment is reflected in the paths of research they actually pursue [I]. On this basis Lmg and associates righdy feel ignored, for in proportion to the total workers in die field diey are probably far fewer dian were Priesdey and feUow phlogistonists at the end ofdie eighteenth century. Thus, although Ling did publish a paper in thefournal of Physiobgy in 1978 [2], the Science Citation Index through February 1982 lists only 13 citations of this paper, and of these, six have Ling as the first author and two Negendank. Of the remaining five, two citations are from journals not in our library, one favors the association-induction hypothesis [3], one presents evidence against the hypothesis [4], and die last uses die reference to support the statement that die "large gradient in potassium . . . appears to be related to die presence of oxygen-dependent energy supply" [5]. By comparison, a paper on the reaction mechanism ofdie sodium pump published that year [6] has received 68 citations in the same period. The resolution of conflicts among rival hypotheses may not be based on congruity with ultimate trutii (still waiting to be revealed) or even in terms of the weight of available evidence (often against new formulations) [7]. More important , I think, is the perceived fruitfulness ofone formulation as a better guide to further studies and understanding. Each day every scientist must decide what next to do, and an essential role of any formulation is in selecting die next experiment from die universe of possibilities. Few would doubt diat binding is involved in cation disposition, and popular formulations of cellular calcium homeostasis include bodi pumps and binding, with the latter concept supported, and the formulation in turn strengthened, by the identification of calciumbinding proteins, leading to still further studies. Where die association-induction hypodiesis currendy fails may be considered (depending on one's vision of die future) as not necessarily due to the actual absence ofthe proposed high-capacity potassium-binding sites but as the inability to guide an effective search for diem if they do exist. REFERENCES 1. Robinson, J. D. The sodium pump and its rivals: an example of conflict resolution in science. Perspect. Biol. Med. 25:486-495, 1982. Permission to reprint a letter printed in diis section may be obtained only from die audior. Perspectives in Biology andMedicine, 26, 3 · Spring 1983 | 509 2.Ling, G. N. Maintenance of low Na+/high K+ levels in resting muscle cells./. Physiol. 280:105-123, 1978. 3.Edelmann, L. Potassium binding sites in muscle. Histochemistry 67:233-242, 1980. 4.Brown, A. D., and Sturtevant,J. M. State ofwater in extremely halophilic bacteria./. Membr. Biol. 54:21-30, 1980. 5.McKinley, B. ?.; Houtchens, B. ?.; and Janata, J. Continuous monitoring of interstitial fluid potassium during hemorrhagic shock in dogs. Crit. Care Med. 9:845-851, 1981. 6.Karlish, S. j. D.; Yates, D. W.; and Glynn, I. M. Conformational transitions between Na+-bound and K+-bound forms of (Na+ + K+)-ATPase studied widi formycin nucleotides . Biochim. Biophys. Acta 525:252-264, 1978. 7.Feyerabend, P. Against Method. London: Verso, 1978. Joseph D. Robinson Department ofPharmacology State University of New York Syracuse, New York 13210 Dear Sir: I read widi great interest Robinson's [1] essay "The Sodium Pump and Its Rivals: An Example ofConflict Resolution in Science." Having done so, I was led to read notonly the letters by Ling and Negendank [2] and Catchpole [3] but also die original article [4] diat sparked off die exchanges. Robinson has made out a good case for comparing the conflict between the sodium pump and the association-induction hypothesis of die present century with the oxygen/ phlogiston controversy of die late eighteenth. He has argued diat die position of Ling is analogous to diat ofJoseph Priesdey who, by die turn ofdiat century, was almost alone in upholding die phlogiston theory. Ling, on die other hand, has been able to attract collaborators and is dius not alone. This, I believe, has sòme interesting implications. Ling and Negendank [2] as...

Continuous monitoring of interstitial fluid potassium during hemorrhagic shock in dogs.

It appears that ISFET probes can reliably and continuously monitor IF K+ in vivo for intervals of at least several hours. The consistently observed increase in IF K+ in response to hemorrhage, a phenomenon invisible systemically, suggests that such probes may provide clinically valuable information regarding perfusion related events at the cellular level during onset of and resuscitation from hypoperfusion states. Precise correlation of ISFET signal to specific cellular dysfunction awaits investigation in which muscle cell membrane potential, muscle surface pH, and postexperiment cellular histology are studied concurrently.

Effects of verapamil on heart and circulation in hemorrhagic shock in dogs

Myocardial blood flow and left ventricular oxygen utilization were studied in verapamil-treated and untreated pentobarbital-anesthetized dogs subjected to hemorrhagic shock. Blood loss was similar in both groups. The dogs treated with verapamil (n = 15) during shock had a slower heart rate and lower left ventricular oxygen utilization than the untreated dogs (n = 14). Nevertheless, the treated dogs had a significantly higher myocardial blood flow and were able to maintain a higher cardiac index. Thus, verapamil has beneficial hemodynamic and metabolic effects that preserve myocardial function. These effects may explain the improved survival and protection of the heart against anatomic lesions, which have been demonstrated previously in dogs treated with verapamil during hemorrhagic shock.

The effects of catecholamines on hemorrhagic shock in dogs.

The effects of catecholamines on hemorrhagic shock in dogs.

Influence of Fibrinogen Levels in Dogs on Mortality from Hemorrhagic and Traumatic Shock

1) Fibrinogen levels appear related to the outcome of hemorrhagic shock in dogs. 2) Fibrinogen levels can vary with different animals based on location, disease, stress, nutrition, or other factors. 3) Any experiments in hemorrhagic shock (or anything else) should utilize simultaneous and paired controls of animals from the same source or they may be subject to major error.

The influence of disseminated intravascular coagulation on renal function after experimental hemorrhagic shock.

Abstract Experiments were performed to investigate the influence of disseminated intravascular coagulation (DIC) during shock upon renal function after shock. Hemorrhagic hypotension of 2 h duration at 50 mmHg was induced in anesthetized non-heparinized dogs, followed by reinfusion of shed blood (shock group 1). In shock group 2, acute splenectomy was performed prior to hemorrhage and epsilon-amino caproic acid was infused during hemorrhagic hypotension. In shock group 1, during hemorrhagic hypotension the whole blood clotting time and thrombin time shortened (hypercoagulability), the arterial platelet count increased and intrarenal platelet retention was observed. The results of renal function measurements reproduced the well known pattern of renal dysfunction after hemorrhagic shock in dogs: reduction of CPAH to about 55% and of CI to about 70% of pre-shock levels, significant increases of VU, ENa, E F Na (diuresis and natriuresis), decreases of U P Osm and TH2Oc and increase of V U C I and C Osm C I (disturbance of concentrating mechanism). Dogs in shock group 2 developed prolongation of whole blood and plasma clotting times (hypocoagulability), decrease in platelet count and factors V and VIII activity (factor depletion), and increases in titers of FDP (staphylococcal clumping test assay) and fibrin monomers (protamine sulfate test assay). Clotting changes were consistent with the diagnosis of DIC. After reinfusion, a different renal dysfunction pattern was observed: CPAH and CI were both reduced to about 35% of their pre-shock levels and CI as well as EI and EPAH were significantly lower than in shock group 1 and the increase of urine output did not occur. The depression of renal function and urine excretion following shock with DIC could be explained by pronounced cortical ischemia and reproduced the characteristic features of the acute renal failure in man (depression of EPAH, low CI, reduction of C I TRPF , decrease of U P Osm and TH2Oc). It is concluded, that coagulation derangements in addition to vasoconstriction during shock determine the course of renal function after shock and play an important role in the pathogenesis of shock kidney.

His electrocardiographic characterization of terminal arrhythmias of hemorrhagic shock in dogs

Pulseless idioventricular rhythm is the agonal arrhythmia identified in three models of hemorrhagic shock used in this study. This arrhythmia is preceded by atrial and then junctional arrest demonstrated by His electrocardiography in all nine dogs studied. Two additional dogs were used as controls. Acid-base and electrolyte changes were not sufficient to cause the progressive failure of conduction system function seen so consistently. Patients receiving cardiopulmonary resuscitation who have profound bradycardia without pulses may have been in shock prior to cardiopulmonary arrest.

INCREASED PANCREATIC LECITHINASE-A ACTIVITY AND ITS CORRELATION TO ALVEOLAR STABILITY DURING SHOCK

The objective of the present study was to investigate the role of pancreatic lecithinase-A released into systemic circulation during shock involving the deterioration of alveolar surface activity. Mongrel dogs were led to hemorrhagic shock maintaining mean arterial blood pressure 40 mmHg until 40% of shed blood was spontaneously taken up. Then remaining blood was retransfused and the experiment was terminated when arterial pressure declined to 50 mmHg. The changes of lecithinase-A and lysosomal hydrolases in the pancreas and plasma were observed every hour through the experement. Pulmonary surface activity was determined on excised lobes at the terminal stage after retransfusion. Next, the effect of lecithinase-A infused intraveously on arterial blood oxgenation and pulmonary stability was assessed on anesthetized dogs.The arterial blood oxygen tention decreased at the terminal stage following retransfusion in shocked animals. Plasma concentration of lecithinase-A increased markedly 120 minutes after the initiation of oligemic hypotention, being preceded by a rise in lecithin splitting enzyme of the pancreas. Pressure-volume curves of the excised lobes of dogs in hemorrhagic shock and lecithinase infusion showed significant shifts to the right, demonstrating the reduction in pulmonary surface activity. These results suggest that pancreatic lecithinase-A released into plasma may inactivates pulmonary surface active substances.

The effects of cortisone on liver blood flow in experimental hemorrhagic shock: using a new simplified radioisotope clearance method to measure liver blood flow.

Liver blood flow was measured in the dog under control and hemorrhagic shock conditions by the 133Xe clearance method. 133Xe was administered first into the portal vein and its clearance from the liver recorded, and then directly into the liver tissue and another clearance curve was obtained. The resuts were compared. We have also investigated the effects of corticosteroids, given in pharmacologic doses, on liver blood flow in hemorrhagic shock. We have shown that the difference between the results of tissue injection and those of portal injection of 133Xe was not significant (p greater than 1.10). Hemodynamic studies indicated that the liver blood flow is decreased, the liver venous resistance and portal venous pressures are increased in dogs in hemorrhagic shock, and that hydrocortisone, with the blood pressure and the bleedout volume held constant in the experimental model, lowers the liver venous resistance and raises the liver blood flow significantly (p less than 0.05) at various stages of hemorrhagic shock.

Pulmonary vascular effects of acetylsalicylic acid, chloroquine, dextran and methylprednisolone given after haemorrhagic shock in dogs.

We have described increases in lung water and pulmonary vascular resistance and reduced myocardial performance in both pigs and dogs after two hours of haemorrhagic shock followed by re-infusion of blood. In this experiment haemorrhagic shock was induced by removing blood to ACD blood packs in five groups of dogs. After two hours of shock, blood was re-infused and NaHCO3 was given to correct the metabolic acidosis of shock. One group of dogs remained as control and received no drugs. Experiments were carried out on three other groups of dogs with one of aspirin, dextran and methylprednisolone given intravenously at the end of the shock period and before blood was re-infused. To allow absorption, chloroquine was given intramuscularly before the period of shock in the fifth group of dogs. In the group with no drugs pulmonary vascular resistance (PVR) increased 95 per cent (significant) from the control period to the end of the experiment. PVR in the control period was not significantly different from PVR at the end of the experiment in any drug group. However, chloroquin was associated with the greatest increase in PVR between these times (77 per cent N.S.). PVR actually fell from control levels to the end of the experiment in both the aspirin (-3.4 per cent N.S.) and dextran (-2.9 per cent N.S.) groups. PVR rose (14 per cent N.S.) from the control period to the end of the experiment in the methylprednisolone group. The aspirin, dextran and methylprednisolone PVR results are all significantly different from the “no drug” group. In both the aspirin and dextran groups platelet aggregation was inhibited. Only the methylprednisolone group had a significant increase in lung water (21 per cent) and the smallest increase in lung water occurred in the aspirin group (9.8 per cent N.S.). We could not relate lung water changes to PVR changes. The lung water changes were compatible with interstitial pulmonary oedema and did not lead to serious gas exchange problems. Myocardial performance appeared improved with dextran and methylprednisolone after shock. We conclude that while dextran and methylprednisolone confer some benefit in preventing increases in PVR and lung water after haemorrhage shock, aspirin is the best drug of those studied in preventing these changes.

Effect of the inhibitor of angiotensin i converting enzyme on endocrine function and renal perfusion in haemorrhagic shock

The present study was undertaken to investigate the effect of inhibition of angiotensin I converting enzyme on endocrine responses and renal perfusion in haemorrhagic shock. Plasma levels of vasopressin (VP), aldosterone, and plasma renin activity (PRA), and renal cortical tissue blood flow were measured both in control dogs and in those treated with an inhibitor of angiotensin I converting enzyme (SQ20881). The drug was administered with an intention of preventing vasoconstriction induced by angiotensin II and to improve tissue perfusion. No significant differences were found in plasma levels of vasopressin, aldosterone and plasma renin activity between control and SQ20881-treated groups. Secondary elevation of blood pressure following haemorrhage was significantly delayed and reduced by the administration of the inhibitor. Decrease in renal cortical tissue blood flow was observed in the SQ20881-treated group. It is suggested that angiotension II appears to play a role in spontaneous recovery of arterial blood pressure following haemorrhage. Furthermore, angiotensin II does not seem to play an important role in the stimulation of secretion of vasopressin in response to haemorrhage. Our data failed to demonstrate any favourable effects of inhibition of angiotension I converting enzyme on renal perfusion during haemorrhagic shock in dogs.

Beneficial effect of arachidonic acid during hemorrhagic shock in the dog.

Arachidonic acid (AA), precursor of the bisenoic prostaglandins was infused at a rate of 120 mug/kg per min into the vena cava of dogs subjected to hemorrhagic shock to assess the effects of stimulation of the prostaglandin (PG) synthetase system on the shock state. Hemorrhagic shock was induced by bleeding to a mean arterial blood pressure (MABP) of 40 mm Hg for 150 minutes followed by reinfusion of all remaining shed blood. In sham shock dogs receiving AA vehicle (0.1 M Na2C03), there were no significant changes in MABP, superior mesenteric artery flow (SMAF), renal artery flow (RAF), PGF2 or PGF2alpha concentrations, or in cathepsin D or myocardial depressant factor (MDF) activities during a 260-minute experimental period. During oligemia, untreated hemorrhagic shock dogs exhibited dramatic reductions in MABP, SMAF, and RAF which were transiently restored following reinfusion, but markedly decreased 100 minutes after reinfusion. Cathepsin D, MDF, PGE2, and PGF2alpha values increased significantly in these dogs. AA given during oligemia did not prevent changes in SMAF or RAF, but maintained MABP at near-normal values after reinfusion. AA also significantly protected against the plasma accumulation of both cathepsin D an MDF is hemorrhagic shock dogs. Circulating PGF2alpha and PGE2 values increased rapidly in AA-treated dogs and plateaued at 3.6 and 4.8 times control values, respectively, during oligemia. Hemorrhagic shock dogs receiving AA plus Na meclofenamate, a PG synthetase inhibitor, were not significantly different from shock dogs receiving vehicle except that the circulating PG concentrations did not increase. Thus, products of the PG synthetase system appear to prevent the plasma accumulation of lysosomal hydrolases nand of MDF, and may significantly preserve MABP after hemorrhagic shock in the dog.

Isolation of myocardial depressant factor from plasma of dogs in hemorrhagic shock

Starting with 31 of plasma from dogs in hemorrhagic shock, we have purified the myocardial depressant factor and found that the activity is separate from salts and free amino acids. Moreover, the myocardial depressant factor is present in shock plasma in concentrations of about 1 nmol/ml of plasma. The depressant factor exists as multiple chromatographic forms. The best characterized forms are the anionic forms. A preliminary amino acid composition of the anionic forms has been obtained. These findings should allow more rapid processing of plasma containing high myocardial depressant factor activity to separate the factor and to completely identify this small peptide of great physiologic interest.

Subcellular reactions to injury. I. Ultrastructural and biochemical investigations on the hepatic cellular damage produced by haemorrhagic shock in dogs.

The ultrastructural changes produced by haemorrhagic shock in hepatocytes have been studied in dogs. The associated biochemical and biophysical system alterations allow us to propose a unitary pathogenetic mechanism of the cellular injury based on oxygen deprivation and its effect on the function and structure of the cellular compartments.

Hemorrhagic shock in dogs

The Journal of Trauma: Injury, Infection, and Critical Care: June 1976 - Volume 16 - Issue 6 - p 512

Hemorrhagic shock in dogs: Comparison of treatment with shed blood alone versus shed blood plus Ringer's lactate: Intravascular pressures, cardiac output, oxygen consumption, arteriovenous oxygen differences, extracellular fluid PO 2, electrolyte changes, and survival rates

The purpose of our study of hemorrhagic shock in dogs was to examine the efficacy of adding Ringer's lactate to shed blood replacement in increasing animal survival rates. The standard Wiggers' hemorrhagic shock technic was used in two groups of ten animals each. Intravascular pressures, cardiac output, oxygen consumption, arteriovenous oxygen differences, extracellular fluid PO 2 and pH, electrolyte changes, and survival rates were determined. There was a positive correlation between changes in cardiac output, central venous oxygen content, and PO 2 and extracellular fluid PO 2 as measured using subcutaneously implanted Silastic tubing and perforated plastic balls. Four of the dogs that received shed blood alone survived, whereas five of the dogs that received shed blood plus Ringer's lactate survived. This difference was not statistically significant.

Interest of Isoproterenol in the Treatment of Hemorrhagic Shock in Dogs

Four groups of experiments were focused on two problems: first, the replacement of the substracted amount of blood, and second, the correction of the peripheral reactions to substantial blood loss, namely vasoconstriction and acidosis. We stuck to a simple plan in our experiments: lost blood was entirely collected and retransfused. In 26 cases out of 37, we used isoproterenol hydrochloride (Isuprel - WINTHROP) to open the peripheral vascular bed. In six different groups, we followed the response to variations of retranfusion and administration of isoproterenol. Several parameters were studied: arterial blood pressure, central venous pressure, rectal temperature and pH. The association of blood transfusion with injection of isoproterenol, in adequate amounts to correct hypovolemia and to prevent vasoconstriction, is undoubtedly the best treatment of hemorrhagic shock.

Effects of an inotropic agent, RO 2-2985 (X-537A), on regional blood flow and myocardial function in chronically instrumented conscious dogs and anesthetized dogs.

RO 2-2985 produced a marked positive inotropic effect in unanesthetized, chronically instrumented dogs, measured as an increase in left ventricular dP/ dt and an increase in maximum velocity of myocardial fiber shortening. Similar changes produced in dogs in hemorrhagic shock lasted for 2-3 hours. RO 2-2985 increased peripheral blood flow and caused marked increases in both coronary and renal blood flows. The drug altered the response of the renal vascular bed to subsequent norepinephrine administration. After administration of a single dose of RO 2-2985, norepinephrine produced sustained increases in renal blood flow, and this altered responsiveness to norepinephrine persisted for periods ranging from 1 to 3 weeks.

Blood affinity for oxygen in experimental hemorrhagic shock with metabolic acidosis.

This study was designed to evaluate, in vivo, the effect of a severe non-respiratory acidosis on hemoglobin oxygen transport. Oxygen affinity of hemoglobin, Bohr effect, Hill's number and red cell 2,3-DPG were evaluated during experimental hemorrhagic shock in dogs. Three periods were considered: control, hypotension (mean arterial pressure 60 mm Hg for 2 hr 30 min) and blood replacement. There was no significant change in erythrocyte 2,3-DPG following hemorrhagic hypotension but ATP increased significantly. n, the Hill number (2.6), was not changed by in vivo acidosis (pH 7.1). Respiratory Bohr coefficient (BCO2) corresponding to pHe variations was drastically reduced (control BCO2 = 0.55, acidosis BCO2 = 0.31, blood replacement BCO2 = 0.35). P50(7.4) was not modified significantly by hemorrhagic acidosis. It is unlikely that variations of blood affinity for oxygen play a major role in oxygen delivery during early experimental hemorrhagic shock.

Hemorrhagic shock in dogs without major pulmonary changes.

Dogs were submitted to one of three hemorrhagic shock procedures: normovolemic shock, oligemic hypotension or posthemorrhagic hypotension. 13 animals fulfilled well-filled criteria of irreversible hemorrhagic shock, based on mortality, take-up volume and metabolic changes. Lung function was measured at regular intervals. Lungs were fixed by infusion fixation. The macroscopial aspect of the lungs was not different from that of six control dogs which were anesthetized for the same period. Minor microscopical changes were found, but the only histological parameter which was significantly different from the controls was accumulation of granulocytes. Gas exchange remained normal, ventilation was increased with an enlarged dead space and veno-arterial shunting was reduced. Pulmonary vascular resistance was not different from the control group.