Posthemorrhagic Period Research Articles

ENDOCANNABINOID SYSTEM IN THE PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS MODULATES AUTONOMIC AND CARDIOVASCULAR CHANGES BUT NOT VASOPRESSIN RESPONSE IN A RAT HEMORRHAGIC SHOCK MODEL.

We evaluated the participation of the endocannabinoid system in the paraventricular nucleus of the hypothalamus (PVN) on the cardiovascular, autonomic, and plasma vasopressin (AVP) responses evoked by hemorrhagic shock in rats. For this, the PVN was bilaterally treated with either vehicle, the selective cannabinoid receptor type 1 antagonist AM251, the selective fatty acid amide hydrolase amide enzyme inhibitor URB597, the selective monoacylglycerol-lipase enzyme inhibitor JZL184, or the selective transient receptor potential vanilloid type 1 antagonist capsazepine. We evaluated changes on arterial pressure, heart rate, tail skin temperature (ST), and plasma AVP responses induced by bleeding, which started 10 min after PVN treatment. We observed that bilateral microinjection of AM251 into the PVN reduced the hypotension during the hemorrhage and prevented the return of blood pressure to baseline values in the posthemorrhagic period. Inhibition of local 2-arachidonoylglycerol metabolism by PVN treatment with JZL184 induced similar effects in relation to those observed in AM251-treated animals. Inhibition of local anandamide metabolism via PVN treatment with URB597 decreased the depressor effect and ST drop induced by the hemorrhagic stimulus. Bilateral microinjection of capsazepine mitigated the fall in blood pressure and ST. None of the PVN treatments altered the increased plasma concentration of AVP and tachycardia induced by hemorrhage. Taken together, present results suggest that endocannabinoid neurotransmission within the PVN plays a prominent role in cardiovascular and autonomic, but not neuroendocrine, responses evoked by hemorrhage.

Features of the course of traumatic shock when using respiratory mixtures with a high content of inert gases

This study evaluated the efficiency of using gas mixtures with increased concentrations of inert gases on a hemorrhagic shock model in experimental animals. Massive blood loss is considered a trigger mechanism of severe pathophysiological reactions (impaired peripheral perfusion, acidosis, hemostasis system dysfunction, and multiple organ failure). Inert gases (helium, argon, and xenon) attract attention as potentially useful in various pathological conditions. The study was conducted on 15 same-sex pigs of the same breed, weighing 40–50 kg, randomized into three groups with five each: control group, inhalation of 100% oxygen; “agohhep” group, inhalation of the “Aroxxen” gas mixture: 35% argon, 58% oxygen, 0.2% xenon, and nitrogen as the rest of the volume; and “agohhep-krypto” group, inhalation of the gas mixture “Aroxxen-krypto”: 35% argon, 40% oxygen, 10% krypton, and nitrogen as the rest of the volume. Dynamic monitoring of vital signs and sampling of materials were conducted before blood loss, with blood loss of 20% and 45% of the volume of the circulating blood 60, 120, and 180 min after blood loss. The survival rate of animals and respiratory and circulatory states were evaluated by clinical and laboratory indicators. With blood loss of 45% of the circulating blood volume, no statistically significant differences in mortality were found between the groups. All animals survived for 180 min in the post-hemorrhagic period. In the aggohep-krypto group, average blood pressure values after blood loss and throughout the follow-up period were significantly higher than those in the control and aggohep groups (p 0.05). During shock simulation as a result of blood loss, base deficiency gradually worsened in all groups. However, starting from the second hour of observation, base deficiency began to be compensated in the control and aggohep-krypto groups and the aggohep group, it continued to increase significantly (p 0.01). During the follow-up after blood loss, the level of lactatemia significantly increased in the aggohep group (by 10 times at the end of the follow-up), which is significant different from those in the control and aggohep-krypto groups (p 0.01). Thus, compared with the use of Arroxen gas, the use of Arroxen-krypto gas of the proposed composition in acute massive blood loss makes it possible to achieve a less pronounced attrition of the acid–base balance in experimental animals.

N-Methyl-D-aspartate Glutamate Receptor Modulates Cardiovascular and Neuroendocrine Responses Evoked by Hemorrhagic Shock in Rats.

Here, we report the participation of N-methyl-D-aspartate (NMDA) glutamate receptor in the mediation of cardiovascular and circulating vasopressin responses evoked by a hemorrhagic stimulus. In addition, once NMDA receptor activation is a prominent mechanism involved in nitric oxide (NO) synthesis in the brain, we investigated whether control of hemorrhagic shock by NMDA glutamate receptor was followed by changes in NO synthesis in brain supramedullary structures involved in cardiovascular and neuroendocrine control. Thus, we observed that intraperitoneal administration of the selective NMDA glutamate receptor antagonist dizocilpine maleate (MK801, 0.3 mg/kg) delayed and reduced the magnitude of hemorrhage-induced hypotension. Besides, hemorrhage induced a tachycardia response in the posthemorrhage period (i.e., recovery period) in control animals, and systemic treatment with MK801 caused a bradycardia response during hemorrhagic shock. Hemorrhagic stimulus increased plasma vasopressin levels during the recovery period and NMDA receptor antagonism increased concentration of this hormone during both the hemorrhage and postbleeding periods in relation to control animals. Moreover, hemorrhagic shock caused a decrease in NOx levels in the paraventricular nucleus of the hypothalamus (PVN), amygdala, bed nucleus of the stria terminalis (BNST), and ventral periaqueductal gray matter (vPAG). Nevertheless, treatment with MK801 did not affect these effects. Taken together, these results indicate that the NMDA glutamate receptor is involved in the hemorrhagic shock by inhibiting circulating vasopressin release. Our data also suggest a role of the NMDA receptor in tachycardia, but not in the decreased NO synthesis in the brain evoked by hemorrhage.

Elfunat in complex treatment of patients with portal hypertension in the early post-hemorrhagic period

The paper deals with the results of the study of the effect of 2-ethyl-6-methyl-3-hydroxypyridine succinate (Elfunat) on erythroid lineage in patients with alcoholic liver cirrhosis and a history of gastroesophageal variceal bleeding. The study compared the impact on the central nervous system and blood values. The results of this study are important for the management of anemia and encephalopathy in this category of patients.

Dilemma of seizure prophylaxis in sub-arachnoid haemorrhage

There is around 10% risk of developing seizures in post subarachnoid hemorrhage (SAH) period. This is considered to be linked to decreased oxygenation of brain due to increase in intra-cranial pressure obviating use of anti-epileptic drugs (AED) as a prophylactic measure. This review was done to study the effect and changes of blood brain barrier permeability in subarachnoid hemorrhage with regard to the present knowledge available and how it could be utilized to open arenas for future research for the rationalization of therapy for such patients. There is no consensus till date on the etiopathogenesis due to which no established guidelines are present for the management of such patients. It is safer to approach the patient on a case by case basis and assess whether to give prophylaxis or not based on the risk of development of seizures and adverse event profile of drugs. Also, there is a need to conduct prospective studies in this arena so as to get some meaningful interpretations which could be of some use to the future therapeutic guidelines.

CHANGE OF FUNCTIONAL AND LABORATORY PARAMETERS AFTER COMPENSATION OF ACUTE BLOOD LOSS WITH COOLED HYPERTONIC SOLUTION IN EXPERIMENT

Relevance.High efficiency of hypertonic (hyperosmolar) solutions in acute blood loss is known. However, data on changes in the body, developing as a result of infusion of such drugs (including cooled) in the providing of care after acute blood loss is limited or absent. This fact complicates the development of tactics in their use, especially in emergency situations at low temperatures.Intention.To reveal features of functional and laboratory indicators In experiments on animals as a result of infusion of warm (+22 °С) or the cooled (–3 °С) hypertonic solution based on hydroxyethyl starch and sodium chloride (HyperHAES, further – HHES) at the acute blood loss of 50 % of blood volume (BV).Methodology.Animals (20 male sheep) with modeled blood loss were distributed into 2 experimental and 2 control groups of 5 animals each. Sheep in the 1st experimental group were placed in the heat chamber with temperature –7 °С for 15 min. Then they underwent the intravenous infusion of a cooled HHES at a dose of 4 ml/kg of weight through the jugular vein with a disposable syringe (volume 20 ml) evenly with a speed of 60 ml per minute. After that they were left in the heat chamber until the time of 1 hour in total. Individuals in the 2nd experimental group were injected with an equivalent volume of warm solution during the corresponding periods of the experiment at an external temperature of +22 °C. 1 hour after beginning of the infusion all animals were intravenously injected with colloidal solution based on hydroxyethyl starch (“Voluven”) at an external temperature of +22 °C. During 1 day the dynamics of rectal temperature, arterial pressure, heart rate and respiratory movements, osmolarity of blood plasma and content of osmotically active components, quantitative indicators of red blood were evaluated.Results.Animals at a temperature of +22 °C or at a temperature of –7 °C died in (82 ± 3) min and (70 ± 5) min (p < 0.05) respectively after the start of exfusion. Intravenous fluids (warm or cooled HHES) ensured the survival in 100 % of cases. As a result of blood loss, subsequent infusion of cooled HHES and following presence in the heat chamber, rectal temperature in sheep decreased by 4.9 °C (14.2%, p < 0.05) relative to the initial values. Two and 4 min after infusion of cooled or warm HHES systolic blood pressure increased by 24.9 % (p < 0.05) and 14.9 % (p < 0.05), respectively, and were restored to the normal level during the following 40 min. Infusion of “Voluven” contributed to the stabilization of blood pressure within 1 day after infusion of HHES. Blood loss led to increased heart rate by 2.1 times (p < 0.05), infusion of HHES slightly reduced the severity of tachycardia. Within 10 minutes after the introduction of cooled HHES, dynamics of heart rate was less stable. Infusion of warm or cooled HHES increased osmolarity of blood plasma by 9.5–9.9 % (p < 0.05), which was associated with an increase of sodium and glucose concentrations in blood. Infusion of “Voluven” reduced osmolarity of blood plasma, which became similar to initial values at the end of Day 1 after infusion of HHES. Blood loss, infusion of HHES and “Voluven” decreased quantitative indicators of red blood via removal of red blood cells from the bloodstream, as well as compensatory and post-transfusion hemodilution.Conclusion.The infusion of warm or cold hypertonic saline (HyperHAES) ensures the survival of experimental animals in post-hemorrhagic period. The positive effect of the drug is associated with compensatory haemodilution (including increased osmolarity of blood plasma), as well as with better functioning of the cardiovascular system. Specific cooled HHES effects include an earlier and pronounced rise in blood pressure. Considering changes in functional and laboratory parameters after infusion of warm or cooled HHES, a reliable system should be developed to remove casualties from emergency areas and to take earlier and complete diagnostic and treatment measures.

Comparison of Stent-Assisted Coil Placement and Coiling-Only for the Treatment of Ruptured Intracranial Aneurysms.

BackgroundThe use of a stent during the acute post-hemorrhage period is controversial. We conducted a retrospective analysis on the clinical and angiographic outcomes of the ruptured aneurysms that were embolized with stent-assisted coiling or coiling-only.Material/MethodsWe reviewed data of 279 patients with 279 ruptured intracranial aneurysms who underwent coil embolization between July 2004 and June 2015. The baseline data on age, sex, medical history, aneurysm size, location, and Hunt and Hess grade were recorded.ResultsOne hundred and thirteen aneurysms were treated with stent-assisted coiling. Adverse events occurred in similar proportions of patients in the two groups (11.5% in the stenting group and 9.0% in the coiling alone group). The incidence of permanent disabling neurologic deficit was also similar in the two groups (7.1% and 5.4% in the stenting group and coiling alone group respectively). Clinical follow-up data were available in 207 patients with a median period of 28 months. Angiographic follow-up was available in 106 aneurysms with a median period of 7.5 months. Clinical outcomes were correlated with adverse events (p=0.043, odds ratio=4.59), large aneurysms (p=0.013, odds ratio=10.24), and Hunt and Hess grade (p=0.001, odds ratio=13.51). Stent-assisted coiling for ruptured aneurysm, as compared with coiling-only, was not associated with an increased incidence of poor clinical outcome at follow-up. Aneurysm-occlusion status at follow-up were correlated with stent placement (p<0.001, odds ratio=5.85) and initial aneurysm-occlusion status (p=0.027, odds ratio=3.78).ConclusionsCompared with coiling-only, stent-assisted coil placement may have better durability, with comparable safety for ruptured intracranial aneurysm.

Comparative Aspects of the Regulation of Cutaneous and Cerebral Microcirculation During Acute Blood Loss

Objective . Using laser Doppler flowmetry (LDF) and wavelet-analysis of microvascular blood flow oscillations to determine the features of regulation of cutaneous and cerebral microhemocirculation at early stages of acute fixed volume blood loss. Materials and methods. Experiments were carried out on 31 male outbred rats weighing 300 g to 400 g. The animals were anesthetized by intraperitoneal injection of pentobarbital (45 mg/kg). The tail artery was catheterized for invasive measurement of mean blood pressure (BP) and blood withdrawal. The LDF method (ЛАКК-02 device, LAZMA, Russia) was used to record microvascular blood flow simultaneously in the right ear and the pial vessels of the left parietal region. An acute fixed-volume hemorrhage model was used. The target blood loss volume was 30% of the total blood volume (TBV). Within 10 minutes after the end of hemorrhage (posthemorrhagic period), the blood pressure and the LDF-gram were recorded. The following LDF-gram parameters were analyzed: the mean value of IP; the maximum amplitude of blood flow oscillations (Amax) and the corresponding frequency (Fmax) in the frequency band 0.01—0.4 Hz. Statistical processing of the data was performed using Statistica 7.0. Results. At baseline, the values of IP, Аmax and Fmax in the brain were higher than in the skin. At posthemorrhagic period, BP decreased, on average, from 105 to 41 mm Hg. Against this background, IP in the skin decreased by 65%, while in the brain it reduced only by 17%, as compared with the baseline values (P0,0001). In the same time these organs were characterized by a unidirectional dynamics of patterns of fluxmotion. In both investigated organs, Amax increased sharply, and Fmax decreased. In posthemorrhagic period, fluxmotion not only «slowed down», but was also synchronized in a relatively narrow frequency band: for the skin Fmax was about 0.04 Hz (at the border of the endothelial and neurogenic band), for the brain about 0.09 Hz (neurogenic range). Conclusion . Acute blood loss at a volume of 30% of TBV is accompanied by the unidirectional dynamics of changes in the amplitude and frequency characteristics of cutaneous and cerebral blood flow oscillations: an increase in the amplitude, slowing down and synchronization of the fluxmotion in a narrow frequency band. The results of present study and literature data allow assuming that during hypotension, the mechanisms for reducing the dominant fluxmotion pattern frequency are associated with a decrease in pressure on the vessel walls, while an increase in amplitude is associated with the activation of the sympathoadrenal system.

Glutamate Metabolism in Brain Structures in Experimental Hemorrhagic Shock

Purpose. To study glutamate metabolism characteristics in phylogenetically different parts of the mammalian brain in experimentally induced hemorrhagic shock (HS) in cats. Material and methods. Experiments were performed on 76 cats. HS was induced by intermittent bloodletting from femoral artery at a rate of 10ml/kg•10 minutes, with the average volume of 24±0.8 ml/kg. The bloodletting was discontinued after arterial pressure (BP) drop to 60.0±1.5 mmHg. We studied ammonia, glutamate (Gt), and α-ketoglutarate (α-KG) levels and glutaminase (GS) and glutamate dehydrogenase (GDG) activity in specimens harvested from phylogenetically different parts of the brain (cortex, limbic system, diencephalon, and medulla oblongata). Results. In intact animals, the peak GDG activity was found in the medulla oblongata (phylogenetically the oldest part of the brain) and the peak GS activity was registered in the sensorimotor cortex (phylogenetically the youngest part of the brain); the glutaminase activity did not depend on the phylogenetic age of brain structures. In the case of HS, Gt metabolism changes began in the sensorimotor cortex manifested by decreased GS activity, which progresses by the 70th minute of the post%hemorrhagic period (PHP) accompanied by delayed increase in the GDG and glutaminase activity, as well as Gt accumulation. In the limbic system and diencephalon the Gt metabolism was changing (impaired glutamine synthesis, stimuled Gt synthesis with glutamine desamidization and α%KG amination) when developed by the 70th minute of the PHP. Similarly to sensorimotor cortex, changes were associated with Gt accumulation. During the agony, α%KG deficiency developed in all parts of the brain as a result of its increased contribution to Gt synthesis. At the same period of time, in the sensorimotor cortex, limbic system and diencephalon the Gt synthesis from glutamine was stimulated, however, the Gt contribution tothe formation of glutamine was decreased. The accumulation of ammonia regardless of the HS stage was detected only in the sensorimotor cortex, limbic system and diencephalon; in the medulla oblongata ammonium increase was found only during the agony. Сonclusion. HS creates conditions for glutamate accumulation in nerve cells by impairing the metabolism of glutamate in the brain structures. The nature and scope of these disorders depend both on the intensity of glutamate metabolism in phylogenetically different brain structures in acute blood loss and HS.

The Stress and Vascular Catastrophes in Newborn Rats: Mechanisms Preceding and Accompanying the Brain Hemorrhages.

In this study, we analyzed the time-depended scenario of stress response cascade preceding and accompanying brain hemorrhages in newborn rats using an interdisciplinary approach based on: a morphological analysis of brain tissues, coherent-domain optical technologies for visualization of the cerebral blood flow, monitoring of the cerebral oxygenation and the deformability of red blood cells (RBCs). Using a model of stress-induced brain hemorrhages (sound stress, 120 dB, 370 Hz), we studied changes in neonatal brain 2, 4, 6, 8 h after stress (the pre-hemorrhage, latent period) and 24 h after stress (the post-hemorrhage period). We found that latent period of brain hemorrhages is accompanied by gradual pathological changes in systemic, metabolic, and cellular levels of stress. The incidence of brain hemorrhages is characterized by a progression of these changes and the irreversible cell death in the brain areas involved in higher mental functions. These processes are realized via a time-depended reduction of cerebral venous blood flow and oxygenation that was accompanied by an increase in RBCs deformability. The significant depletion of the molecular layer of the prefrontal cortex and the pyramidal neurons, which are crucial for associative learning and attention, is developed as a consequence of homeostasis imbalance. Thus, stress-induced processes preceding and accompanying brain hemorrhages in neonatal period contribute to serious injuries of the brain blood circulation, cerebral metabolic activity and structural elements of cognitive function. These results are an informative platform for further studies of mechanisms underlying stress-induced brain hemorrhages during the first days of life that will improve the future generation's health.

NMDA and non-NMDA glutamate receptors in the paraventricular nucleus of the hypothalamus modulate different stages of hemorrhage-evoked cardiovascular responses in rats

Here we report the involvement of N-Methyl-d-Aspartate (NMDA) and non-NMDA glutamate receptors from the paraventricular nucleus of the hypothalamus (PVN) in the mediation of cardiovascular changes observed during hemorrhage and post-bleeding periods. In addition, the present study provides further evidence of the involvement of circulating vasopressin and cardiac sympathetic activity in cardiovascular responses to hemorrhage. Systemic treatment with the V1-vasopressin receptor antagonist dTyr(CH2)5(Me)AVP (50μg/kg, i.v.) increased the latency to the onset of hypotension during hemorrhage and slowed post-bleeding recovery of blood pressure. Systemic treatment with the β1-adrenergic receptor antagonist atenolol (1mg/kg, i.v.) also increased the latency to the onset of hypotension during hemorrhage. Moreover, atenolol reversed the hemorrhage-induced tachycardia into bradycardia. Bilateral microinjection of the selective NMDA glutamate receptor antagonist LY235959 (2nmol/100nL) into the PVN blocked the hypotensive response to hemorrhage and reduced the tachycardia during the post-hemorrhage period. Systemic treatment with dTyr(CH2)5(Me)AVP inhibited the effect of LY235959 on hemorrhage-induced hypotension, without affecting the post-bleeding tachycardia. PVN treatment with the selective non-NMDA receptor antagonist NBQX (2nmol/100nL) reduced the recovery of blood pressure to normal levels in the post-bleeding phase and reduced hemorrhage-induced tachycardia. Combined blockade of both NMDA and non-NMDA glutamate receptors in the PVN completely abolished the hypotensive response in the hemorrhage period and reduced the tachycardiac response in the post-hemorrhage period. These results indicate that local PVN glutamate neurotransmission is involved in the neural pathway mediating cardiovascular responses to hemorrhage, via an integrated control involving autonomic nervous system activity and vasopressin release into the circulation.

Management of Arterial Vasospasm Following Aneurysmal Subarachnoid Hemorrhage

Despite recent advances, cerebral vasospasm and delayed cerebral ischemia (DCI) still represent a major cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (aSAH). Although a significant portion of the morbidity and mortality associated with aSAH is related to the initial hemorrhagic ictus, cerebral vasospasm and DCI are still the leading cause of poor outcomes and death in the acute posthemorrhage period, causing long-term disability or death in more than one in five of all patients who have suffered aSAH and initially survived.Management of patients following aSAH includes four major considerations: (1) prediction of patients at highest risk for development of DCI, (2) prophylactic measures to reduce its occurrence, (3) monitoring to detect early signs of cerebral ischemia, and (4) treatments to correct vasospasm and cerebral ischemia once it occurs. The authors review the pertinent literature related to each, including both the current management guidelines supported by the literature as well as novel management strategies that are currently being investigated.

Long-Term Outcome Call into Question the Benefit of Positive Fluid Balance and Colloid Treatment After Aneurysmal Subarachnoid Hemorrhage

Aneurysmal subarachnoid hemorrhage (SAH) has a high mortality and morbidity, and long-term outcome is determined by the functional capacity of the patient. Preventing delayed cerebral ischemia that will result in delayed ischemic neurological deficits (DINDs) is a paramount treatment goal during the post-hemorrhage period. There is still controversy regarding the best strategies. While therapeutic induction of hypertension, hypervolemia, and hemodilution (‘‘Triple-H therapy’’) is the most commonly accepted treatment, uncertainty remains, among others, whether colloids versus crystalloids should be utilized, and whether maintaining a positive fluid balance in patients with evidence for vasospasm improves long-term functional outcome. Ibrahim and Macdonald [1] approached the problem by conducting a post-hoc analysis of an existing large database (n = 413; CONSCIOUS-1 trial [2]). First, they used propensity-score matching to determine whether the administration of colloids between days 3 and 14 (period of the highest risk for cerebral vasospasm/DIND after SAH) influences the incidence of DIND and of delayed infarction, and whether it influences the functional outcome 6–12 weeks after SAH (Glasgow outcome scale, modified Rankin scale [mRs], and NIH stroke scale [NIHSS]). Next, using a multivariate logistic regression model, they evaluated any association that an overall fluid balance during the DIND risk period (3–14 days) has on the same outcome parameters. They found that treatment with colloids during the DIND risk period does not reduce the risk for DIND or delayed cerebral infarcts, but that it rather was associated with worse functional outcomes (NIHSS). Equally important, they found that a positive fluid balance during the DIND risk period was associated with prolonged length of stay in the ICU and worse functional outcome (mRS) at 12 months after SAH. However, they also found that patients with angiographic evidence of severe vasospasm had more delayed cerebral infarcts when their fluid balance remained negative during the DIND risk period. The authors conclude that the volume status of patients after SAH should be managed carefully and colloids should be restricted to selected patients and administered only under careful monitoring. Their findings are clinically important despite the limitations of post-hoc analysis. The study has relevance for several reasons: First, over the last several years in the medical literature, studies have surfaced regarding the negative effects of IV fluid over-resuscitation. This includes both positive fluid balance per day over an extended period of time during the hospitalization, as well as high ‘‘throughput’’ of IV fluids in the setting of an even fluid balance. It is now well documented that both management strategies are harmful in patients with sepsis, ARDS, after trauma or during the perioperative period [3–9]. However, the exact mechanism remains unclear. The new results presented by Ibrahim and Macdonald [1] suggest that equally, the injured brain may not be immune to the negative effects of fluid overadministration. Their results are particularly important, as it has been considered a gold standard of therapy to induce and maintain positive IV fluid balance in patients after SAH during the window of vasospasm, in order to prevent DIND. Interestingly enough the data suggest that even in This article is an editorial to 10.1007/S12028-013-9860-Z.

Efficacy of Employment of Isotonic Sterofundin after Experimental Hemorrhagic Shock

Objective: to perform an experimental study of the effect of isotonic sterofundin on the morphology of the myocardium, kidney, lung, pancreas, liver, and brain in the late period after hemorrhagic shock. Material and methods. Hemorrhagic shock was induced in 36 male Wistar rats weighing 230—250 g by acute massive blood loss (AMBL) of 2.5 ml/100 g at a rate of 2 ml/min. An hour after AMBL, hypovolemia was replenished to 200% volume for 60 min with Ringer solution and isotonic sterofundin in control and experimental groups, respectively. Then the blood was reinfused at 70% volume of its loss. The magnitude of morphological changes was estimated 3 days following AMBL. Specimens harvested from organs of euthanized animals were examined histologically and images were recorded using a ^Vizo-103 microvisor. Results. The experimental studies demonstrate significant structural damage of tissues within target organs following traditional infusion therapy with polyionic crystalloid solutions that may cause development of multiple organ dysfunction. Malate-containing solution of sterofundin reduces the degree of organ structural damages that may prevent multiple organ dysfunction in the posthemorrhagic period. Key words: acute massive blood loss, hemorrhagic shock, malate, sterofundin isotonic, multiple organ dysfunction.

Report of two cases of a rare cause of subarachnoid hemorrhage including unusual presentation and an emerging and effective treatment option

PurposeTo report two cases of a rare cause of subarachnoid hemorrhage (SAH), including unusual presentation and an emerging and effective treatment option.Case reportsRuptured basilar perforator artery aneurysm is a rare...

Sympathetic innervation of the splanchnic region mediates the beneficial hemodynamic effects of 8-OH-DPAT in hemorrhagic shock

Administration of the 5-HT(1A) receptor agonist, 8-OH-DPAT, improves cardiovascular hemodynamics and tissue oxygenation in conscious rats subjected to hypovolemic shock. This effect is mediated by sympathetic-dependent increases in venous tone. To determine the role of splanchnic nerves in this response, effects of 8-OH-DPAT (30 nmol/kg iv) were measured following fixed-arterial blood pressure hemorrhagic shock (i.e., maintenance of 50 mmHg arterial pressure for 25 min) in rats subjected to bilateral splanchnic nerve denervation (SD). Splanchnic denervation decreased baseline venous tone as measured by mean circulatory filling pressure (MCFP) and accelerated the onset of hypotension during blood loss. Splanchnic denervation did not affect the immediate pressor effect of 8-OH-DPAT but did reverse the drug's lasting pressor effect, as well as its ability to increase MCFP and improve metabolic acidosis. Like SD, adrenal demedullation (ADMX) lowered baseline MCFP and accelerated the hypotensive response to blood withdrawal but also reduced the volume of blood withdrawal required to maintain arterial blood pressure at 50 mmHg. 8-OH-DPAT raised MCFP early after administration in ADMX rats, but the response did not persist throughout the posthemorrhage period. In a fixed-volume hemorrhage model, 8-OH-DPAT continued to raise blood pressure in ADMX rats. However, it produced only a transient and variable rise in MCFP compared with sham-operated animals. The data indicate that 8-OH-DPAT increases venoconstriction and improves acid-base balance in hypovolemic rats through activation of splanchnic nerves. This effect is due, in part, to activation of the adrenal medulla.

QTc Interval and Neurological Outcomes in Aneurysmal Subarachnoid Hemorrhage

Prolonged heart rate-corrected QT (QTc) interval is frequently observed in subarachnoid hemorrhage (SAH). This study was conducted to determine the relationship between QTc interval and neurological outcome during the acute posthemorrhagic period after aneurysmal SAH. We studied 71 patients undergoing surgery who were admitted within 24 h after the onset of aneurysmal SAH. Standard 12-lead electrocardiography was performed on admission (T1) and at 1 and 7 days after operation (T2 and T3). QT intervals were corrected by heart rate according to the Fridericia formula. The Glasgow Coma Scale (GCS) score was calculated over the period T1-T3. Neurological outcome was assessed using the Glasgow Outcome Scale at hospital discharge. Among the 71 patients, 31 had an unfavorable neurological outcome. Although QTc interval prolongation improved in patients with a good outcome, QTc interval prolongation continued in patients with an unfavorable outcome. The areas under the receiver-operator characteristic curves showed that the QTc and GCS score at T3, and the Hunt and Hess grade were significant predictors of an unfavorable neurological outcome. The threshold value, sensitivity, and specificity for the QTc at T3 were 448 ms, 73% [95% confidence interval (CI), 68-78], and 93% (95% CI, 90-96), respectively. This study confirms that QTc interval prolongation continues in the SAH patients with an unfavorable outcome but that QTc interval prolongation improves in patients with a good outcome, suggesting that a QTc interval of more than 448 ms at 7 days after operation is a predictor of neurological outcome after SAH.

PRIOR EXERCISE ALTERS RESPONSES TO HEMORRHAGE

Traumatic injuries often occur to individuals while exercising. The author sought to determine whether exercise before injury resulting in hemorrhage would alter cardiovascular, metabolic, and neuroendocrine responses. Fifteen chronically instrumented splenectomized immature female swine were trained to run on a treadmill at 70% of maximum heart rate for 60 min. In six swine, responses to exercise were evaluated and found to return to baseline after 60 min of recovery. Swine were then randomly assigned to exercise (n = 7) or rest (n = 8) followed by hemorrhage of 25 mL/kg for 60 min then observed for an additional 60 min. The decrease in mean arterial pressure (MAP) was less after exercise, 26 +/- 9 mmHg compared with 49 +/- 2 mmHg with rest, with the difference sustained during the posthemorrhage period. Cardiac output decreased similarly in both groups. Posthemorrhage lactate and glucose concentrations were lower in exercise. The increase in plasma epinephrine was reduced in exercise, with significantly lower levels in epinephrine and norepinephrine noted posthemorrhage. Vasopressin levels and plasma renin activity were not different. In response to hemorrhage after exercise, blood pressure is better maintained although catecholamine levels were reduced, suggesting increased adrenoreceptor sensitivity. In addition, indices of increased glucose utilization and correction of lactate acidosis support a metabolic shift after exercise. Prior exercise alters responses to hemorrhage that mask the extent of hypovolemia and should be considered in the initial evaluation of a patient with hemorrhage caused by traumatic injuries.

Choice of an Infusion Agent for the Prevention of Multiple Organ Dysfunction in Acute Massive Blood Loss (Experimental Study)

Objective: to perform an experimental study of the effect of sterofundin isotonic on the biochemical parameters characterizing the degree of organ injury after acute massive blood loss (AMBL). Material and methods. Experiments were carried out on 36 male Wistar rats weighing 230—250 g. Hemorrhagic stroke was simulated via AMBL in a volume of 2.5 ml/100 g at a rate of 2 ml/min. An hour after AMBL, there was hypovolemia compensation within 60 minutes in a volume of 200% of the blood loss: by Ringer&#8217;s solution in a control group and by sterofundin isotonic in an experimental group. Then blood reinfu-sion was made in a volume of 70% of blood loss. The biochemical parameters of multiple organ dysfunction (glucose, lactate, urea, creatinine, bilirubin, total protein, albumin), enzymemia (aspartate aminotransferase, alanine aminotransferase, creatine phosphokinase, lactate dehydrogenase, amylase), endotoxemia (low- and medium-molecular-weight substances in the plasma and erythrocytes), acid-base condition, electrolytes of venous blood, and animal survival were determined on days 1 and 3 following AMBL. Results. There was a reduction in the time and degree of posthemorrhagic metabolic, biochemical, and electrolyte disorders, enzymemia, and endotoxemia in the experimental animals. Conclusion. The experimental studies suggest that Ringer&#8217;s solution is inadequately effective in preventing multiple organ dysfunction due to AMBL. The malate-containing blood substitute sterofundin isotonic that is used during early therapy for AMBL exerts a marked preventive effect on the development of visceral organ injuries when multiple organ dysfunction occurs in the early and late posthemorrhagic period. The experimental findings make it possible to recommend that sterofundin isotonic should be used in intensive care of hypovolemic shock arising from AMBL. Key words: acute massive blood loss, malate, sterofun dinisotonic, lactate, endotoxemia, multiple organ dysfunction.

The Relationship between Intraocular Pressure Reduction and Rates of Progressive Visual Field Loss in Eyes with Optic Disc Hemorrhage

To evaluate rates of visual field progression in eyes with optic disc hemorrhages and the effect of intraocular pressure (IOP) reduction on these rates. Observational cohort study. The study included 510 eyes of 348 patients with glaucoma who were recruited from the Diagnostic Innovations in Glaucoma Study (DIGS) and followed for an average of 8.2 years. Eyes were followed annually with clinical examination, standard automated perimetry visual fields, and optic disc stereophotographs. The presence of optic disc hemorrhages was determined on the basis of masked evaluation of optic disc stereophotographs. Evaluation of rates of visual field change during follow-up was performed using the visual field index (VFI). The evaluation of the effect of optic disc hemorrhages on rates of visual field progression was performed using random coefficient models. Estimates of rates of change for individual eyes were obtained by best linear unbiased prediction (BLUP). During follow-up, 97 (19%) of the eyes had at least 1 episode of disc hemorrhage. The overall rate of VFI change in eyes with hemorrhages was significantly faster than in eyes without hemorrhages (-0.88%/year vs. -0.38%/year, respectively, P<0.001). The difference in rates of visual field loss pre- and post-hemorrhage was significantly related to the reduction of IOP in the post-hemorrhage period compared with the pre-hemorrhage period (r = -0.61; P<0.001). Each 1 mmHg of IOP reduction was associated with a difference of 0.31%/year in the rate of VFI change. There was a beneficial effect of treatment in slowing rates of progressive visual field loss in eyes with optic disc hemorrhage. Further research should elucidate the reasons why some patients with hemorrhages respond well to IOP reduction and others seem to continue to progress despite a significant reduction in IOP levels. Proprietary or commercial disclosure may be found after the references.