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H Haljamäe

Publications and source records attributed to H Haljamäe.

At least 73 records · Page 4Linked to original sources

Pathophysiology of shock-induced disturbances in tissue homeostasis.

A survey is given on disturbances in tissue homeostasis induced by hypovolemic shock conditions. Fluid shifts taking place between the extra- and intravascular fluid compartments are important early compensatory responses following hypovolemia. Usually the supply-to-demand ratio of oxygen in most tissues can however, not be kept up if the hypovolemic insult is severe due to deterioration of the microcirculation. Cellular hypoxia will ensue and may with time affect the integrity of the cells. Cellular functional disturbances occur earlier and are more pronounced in peripheral non-vital tissues such as e.g. skeletal muscle than in central organs, the blood flow of which is more favoured during shock. Anaerobically produced cellular metabolites as well as intracellular components released from hypoxically injured cells in peripheral tissues may be of importance for the initiation of decompensatory reactions. Cellular components reaching the central circulation may induce direct effects on organs or systemic effects due to activation of the cascade systems. Thereby reactions leading to severe complications such as adult respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC) and multiple organ failure may be started. The aim of shock treatment should be to reverse as rapidly and as efficiently as possible the pathophysiological disturbances induced by a shock state. If the cellular hypoxic insult can be limited then the incidence of systemic complications in the post-shock period will also be reduced.

Blood Coagulation↗

Rationale for the use of colloids in the treatment of shock and hypovolemia.

The question, "Are colloids or crystalloids to be preferred for resuscitation in hypovolemic shock conditions?" is detailed in this review. The effects of these two types of fluid regimes on restitution of circulating blood volume, interstitial rehydration, microvascular blood flow, cellular metabolic recovery and on the incidence of systemic complications such as adult respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC) and multiple organ failure are considered. Colloid containing solutions seem superior to crystalloids due to efficient reexpansion of circulating blood volume and enhancement of capillary blood flow. Resuscitation times and thereby the cellular hypoxic insult are considerable reduced while at the same time the formation of excessive tissue oedema is prevented. Colloids do not seem to adversely affect pulmonary function. Dextran has considerable advantages over other types of colloids for the initial shock treatment due to its antithrombotic properties whereby cell aggregability is prevented and the incidence of systemic complications (microembolism syndromes) is convincingly reduced.

Blood Volume↗

Influence of tissue lactic acid and ATP levels on postischemic recovery in rabbit skeletal muscle.

The effect of energy substrate depletion and of high lactic acid (LA) load on the development of irreversible cell injury was evaluated in the lateral gastrocnemius muscle of rabbits subjected to 4 hr of tourniquet hindlimb ischemia. Three groups of animals were studied. Group I, high ATP-ischemia, these animals were subjected to 4 hr of ischemia; group II, low ATP--low LA ischemia, in this group the gastrocnemius muscle was electrically stimulated for 5 min during ischemic conditions to reduce the glycogen store, a short reperfusion period was allowed after the stimulation in order to wash out the built up LA, and the muscle was then subjected to 4 hr of ischemia; group III, low ATP--high LA ischemia, in this group glycogen was depleted as in group II, but no reperfusion period was allowed before the 4 hr period of ischemia. In group I, ATP levels were well preserved during the ischemic period, whereas in the substrate-deprived groups (II and III) a rapid depletion of ATP and phosphocreatine (CP) occurred. The LA was twice as high in the "high LA" group (III) as in the "low LA" group (II) during the ischemic period. The extent of injury was evaluated after 24 hr of reperfusion by measuring ATP and CP content, and contractile force and by light microscopy. No or minor cell damage was found in group I. In group III--high LA--no recovery was obtained in any of the variables used for evaluation. In group II--Low LA--there was a certain recovery. ATP and CP increased to about 35% and contractile force to 25% of control. Morphologically about 20% of the muscle cells appeared to be unaffected by the ischemic insult. It is concluded that reduction of the glycogen available for ATP resynthesis during the ischemic period drastically reduces the ability of skeletal muscle to withstand prolonged ischemia. A high LA load seems to amplify the deleterious effects of a low initial substrate level.

Adenosine Triphosphate↗

Metabolic effects of high dose corticosteroids.

The improved survival following high-dose corticosteroid (HDC) treatment of septic shock conditions has been suggested to be partly due to the metabolic effects of HDC. Endotoxins are known to deplete glycogen stores, hexose phosphates and phosphoenol-pyruvate. Elevated levels of fructose diphosphate and phosphoglycerates are seen and there is an accumulation of lactate. Endotoxemia also seems to inhibit the utilization of non-carbohydrate precursors for glucose production and hypoglycemia is characteristically seen with time in septic states. In severe shock mitochondrial oxidative metabolism and ion transport capacity are defective and tissue energy store will be depleted. The underlying metabolic pathology in shock states is still not known in detail but endotoxins seem to have direct antiglucocorticoid effects. HDC counteracts the acceleration of glycolysis by the Embden- Meyerhof pathway seen in septic states and prevents the endotoxin-mediated stimulation of enzymes in the hexose monophosphate shunt. The levels of Krebs cycle intermediates and pyruvate in the liver are raised after treatment indicating enhanced gluconeogenesis. The conversion of lactate to glucose is increased and the lactate/pyruvate ratio decreased. Protein catabolism is stimulated by HDC elevating the plasma levels of amino acids and thereby further enhancing the potential for gluconeogenesis. The endotoxin-induced mitochondrial dysfunction is reversed and cellular energy production is improved. The beneficial metabolic effects of HDC may to some extent be indirect. A depressed febrile response will decrease tissue oxygen needs. The vasodilatory effects will improve tissue oxygen availability and thereby reduce tissue hypoxia. Stabilization of cellular membranes may also prevent systemic metabolic effects caused by lysosomal enzymes released from damaged cells.

Adrenal Cortex Hormones↗

Microcirculation and hemorrhagic shock.

Blood loss is followed by compensatory cardiovascular readjustments that favor the maintenance of blood flow to central vital organs rather than to peripheral tissues. The microcirculatory changes that occur in skeletal muscle in shock states are of major importance, since skeletal muscle is not only the largest cell mass of the body but also one of the major target organs for neurohumorally mediated compensatory vascular readjustments. Intravital microscopic studies show that the microvascular blood flow in skeletal muscle is intermittent in the early posthemorrhagic period. This probably reflects an interplay between alpha-adrenergic vasoconstrictor and beta-adrenergic vasodilator activities, which serves to enhance a compensatory mobilization of interstitial fluid into the vascular compartment. A period of complete microcirculatory arrest is then seen, followed by reperfusion engaging only 30% to 50% of the capillaries that were seen perfused in resting skeletal muscle. The microvascular blood flow in shock is further characterized by a pronounced heterogeneity in distribution. Many capillaries remain constantly unperfused, while in others a slow, intermittent blood flow is seen. Obstruction of many capillaries by white blood cells and their slow passage through other capillaries seem to be the main reasons for the maldistribution of capillary blood flow in shock. Red blood cell aggregates obstructing capillary blood flow are not seen. The heterogeneous tissue perfusion is accompanied by local variations in cellular hypoxic injury, as is evidenced by multifocal measurements of tissue oxygen tension and by cellular transmembrane potential registrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Emergencies↗

The response of the awake spontaneously hypertensive rat (SHR) to acute blood loss.

In order to evaluate experimentally if the presence of hypertensive disease is an additional risk factor in connection with emergency situations including blood loss, awake spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were subjected to standardized acute haemorrhage (35% of blood volume) via an aortic catheter. Mean arterial blood pressure (MAP), blood gases, acid-base balance, blood glucose and haematocrit values were followed and the 5-h survival rate was determined. In the early posthaemorrhagic phase similar plasma refill, as evidenced from haematocrit readings, was seen in SHR and WKY. Hyperglycaemia occurred in both groups but the hyperglycaemic response was only moderate and transient in SHR. The inability of SHR to maintain hyperglycaemia was intimately correlated to early appearance of metabolic acidosis and short posthaemorrhagic survival times. Determination of liver glycogen content of unbled SHR and WKY indicated that the deficient hyperglycaemic response in SHR was not due to inadequate glycogen stores but rather to poor liver perfusion resulting in liver hypoxia. Since spontaneous hypertension in rats in many ways is considered to be similar to essential hypertension in man, these findings suggest that human hypertensive disease constitutes a considerable risk factor in connection with acute haemorrhage.

Acid-Base Equilibrium↗

Effects of penicillin G on local metabolic changes in skeletal muscle following high velocity missile injury.

The effect of systemic penicillin G treatment on the local tissue damage 12 h after a high velocity missile injury in skeletal muscle has been studied in pigs (n = 13). Blood pressure, rectal temperature, hemoglobin concentrations, hematocrits, blood gases and acid base balances were followed and the tissue levels of ATP, creatine phosphate, glucose-6-phosphate, glucose and lactate were determined in control skeletal muscle as well as in muscle samples taken from the wound area. After 12 h all devitalized tissue was debrided and weighed. Penicillin G treatment slightly diminished the local tissue metabolic deterioration and significantly reduced the amount of debrided tissue as compared to untreated animals. It may be concluded that early treatment with penicillin G will considerably diminish the local tissue damage during the first 12-hour period following a high velocity missile injury.

Animals↗

Effects of hypovolemia on local metabolic changes in skeletal muscle following high velocity missile injury.

The effect of blood loss and reinfusion after 6 h on the tissue damage around a high-velocity missile tract in skeletal muscle has been studied in pigs (n = 13). Hemodynamic variables and blood chemistry were monitored and the levels of ATP, creatine phosphate (CP), glucose, glucose-6-phosphate ( G6 -P), and lactate were repeatedly analyzed in muscle samples from the wound area and from control tissue. In vitro amino acid incorporation into proteins by isolated ribosomes was also studied. The missile injury induced pronounced local metabolic disturbances in the muscle tissue surrounding the missile tract. After 6 h these disturbances were more pronounced and extended further out from the wound channel in bled than in unbled animals. One hour after reinfusion of the shed blood, no remaining difference in the size of the metabolically disturbed tissue area between the two groups of animals could be demonstrated. It is thus concluded that a moderate hypovolemia markedly increases the metabolic deterioration around a high-velocity missile tract in skeletal muscle but that volume restitution, even if given as late as 6 h after the missile injury and the blood loss, will almost completely within 1 h reverse the effects caused by the hypovolemia.

Amino Acids↗

Effects of haemorrhagic hypotension on brain and liver metabolism in normotensive (WKY) and spontaneously hypertensive rats (SHR).

Hypertensive disease is known to increase the risks in connection with acute changes in blood pressure due to the presence of pronounced structural as well as functional changes in the cardiovascular system. In the present study the metabolic consequences of fixed haemorrhagic hypotension [mean arterial pressure (MAP) 70 and 45 mmHg] were studied in spontaneously hypertensive (SHR) and in normotensive rats (WKY). Blood gases and acid-base balance, blood glucose, liver (ATP, glucose, lactate) and brain (ATP, ADP, AMP, CP, glucose, lactate) metabolites were determined in unbled animals and after 35 min hypotension in bled animals. In the liver haemorrhage to MAP 70 mmHg resulted in a 70% reduction of the ATP content in SHR while that in WKY remained unchanged. At MAP 45 mmHg reduced liver ATP levels (35% reduction) were observed in WKY as well. In the brain metabolic changes indicative of tissue ischaemia (reduced CP, increased AMP and lactate, decreased energy charge potential) were present only in SHR at MAP 45 mmHg. The more pronounced metabolic disturbances in SHR than in WKY indicate that blood loss is more deleterious for the hypertensive individual.

Animals↗

A new design of double-barrelled microelectrodes for intracellular pH-measurement in vivo.

Intracellular pH (pHi) is one important regulator of cellular function. Most determinations of pHi in vivo have been performed by using indirect methods, e.g. CO2/HCO3 or DMO techniques, since no suitable direct method for reliable in vivo measurements have been available. In the present study a new type of double-barrelled microelectrode for simultaneous in vivo measurements of pHi and membrane potential (Em) is presented. The electrode was constructed on the basis of a combined recessed- and pencil-tip design. The tip diameter of the double-barrelled microelectrode was about 1.5 microns. The response of the pH channel was 55-60 mV/pH unit and the response time was between 30 s and 1 min. In vivo measurements of pHi and Em of rabbit skeletal muscle fibers are presented. A mean pHi of 7.00 (in 8 animals) at a membrane potential of -90.3 mV (arterial pH: 7.30, arterial PCO2: 6.39 kPa) was obtained. The new design of pH microelectrode offers some advantages over previously described microelectrodes and is well suited for in vivo measurements.

Animals↗

Liver and skeletal muscle metabolism, extracellular K+ concentrations, and survival in spontaneously hypertensive rats following acute blood loss.

The metabolic responses of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) to acute blood loss (30% of the calculated blood volume) have been studied. The initial mean arterial pressure (MAP) was 179 mmHg in SHR and 105 mmHg in WKY. After bleeding, MAP decreased to about 50 mmHg in both groups. SHR failed to increase MAP in the posthemorrhagic period, while in WKY a level of 65-70 mmHg was reached. Metabolic changes in liver and skeletal muscle, indicative of tissue hypoxia, occurred earlier and were more pronounced in SHR than in WKY. In SHR, the ATP content of the liver was almost depleted within 1 h, while during the same time period only a moderate reduction was seen in WKY. Extracellular K+ concentration in sketetal muscle increased more rapidly in SHR than in WKY, but a similar relationship between lactate content and extracellular K+ concentration was found in both groups. The mean posthemorrhagic survival time was only 47 min for SHR, as compared to 193 min for WKY. The present results indicate that a blood loss is more detrimental for hypertensive than normotensive rats.

Acute Disease↗

Extracellular potassium concentration and membrane potential in rabbit gastrocnemius muscle during tourniquet ischemia.

The relationship between the extracellular potassium concentration (K+ e.c.) and the resting membrane potential (MP) of the gastrocnemius muscle was studied in the anesthetized rabbit during a 3-h period of hindleg ischemia and a subsequent 1.5-h period of resumed flow. The K+ e.c. was measured on the skeletal muscle surface, using a potassium selective electrode. The MP was recorded with conventional microelectrodes. Small biopsies were taken and analysed for content of ATP and lactate. The lactate content increased fourfold during the ischemic period, but returned to normal values after reflow. No significant changes occurred in the ATP content during the period of the experiment. K+ e.c. increased from 3.6 +/- 0.2 to 16.1 +/- 0.7 mmol/l, and the MP decreased from -90.2 +/- 0.6 to -58.5 +/- 1.9 mV during the 3-h period of ischemia. After release of the tourniquet there was an initial rapid decrease in K+ e.c. to 7.8 +/- 0.9 mmol/l during the first 15 min of resumed flow, followed by a slower decrease. The MP increased linearly during the first hour of resumed flow and both variables returned to near normal values 1.5 h after releasing the tourniquet.

Adenosine Triphosphate↗

Local metabolic changes in skeletal muscle following high-energy missile injury.

The extent of cellular deterioration around a high-velocity missile injury was studied in canine skeletal muscle biopsies. The tissue levels of high-energy phosphates and glycolytic metabolites were analyzed in four zones surrounding the bullet tract and in an uninjured extremity. Incorporation of leucine into skeletal muscle proteins in vitro in the different zones was determined. In the tissue adjacent to the bullet tract ATP and phosphocreatine (CP) decreased significantly and remained low. No significant changes of ATP and/or CP occurred in the other zones or in the control muscle. Lactate and glucose levels increased in all zones but G6-P levels decreased in the three zones close to the wound indicating anaerobiosis and disturbed utilization of glucose. Incorporation of leucine decreased in the innermost zone and no restoration took place, but more peripherally a certain reversible decrease was seen. The present results indicate that irreversible cell damage will occur in the tissue adjacent to a high-velocity bullet tract. Reversible cellular dysfunction may occur in tissues without gross changes.

Adenosine Triphosphate↗

Hemodynamic and metabolic effects of ketamine anesthesia in the geriatric patient.

The cardiovascular and metabolic effects of ketamine as the sole anesthetic agent for surgical correction of fractured neck of femur were studied in eight spontaneously breathing geriatric patients (mean age 83 years) before premedication, at the end of operation, and 15 min and 2 h after the end of anesthesia. Arterial blood pressure, cardiac index, left ventricular stroke work index and oxygen consumption increased during anesthesia but had returned to preoperative levels 15 min after the end of anesthesia. Vascular resistance, heart rate and stroke volume index were not significantly changed. During anesthesia, arterial carbon dioxide tension increased whereas arterial pH and arterial BE decreased. The levels of glucose and lactate increased in both blood and skeletal muscle during anesthesia and remained elevated throughout the period studied but the lactate:pyruvate ratio was unchanged. High energy phosphagen levels in skeletal muscle did not change. Ketamine anesthesia in the spontaneously breathing geriatric patient induces cardiovascular stimulation and metabolic changes indicative of an increased sympathetic stimulation, whereas respiration is slightly depressed. The magnitude of these changes is, however, small and it thus seems that ketamine can be safely used as the sole anesthetic agent for hip fracture surgery in the average geriatric patient.

Aged↗