Search

Physiological compensatory mechanisms can mask the extent of hemorrhage in conscious mammals, which can be further complicated by individual tolerance and variations in hemorrhage onset and duration. We assessed the effect of hemorrhage rate on tolerance and early physiologic responses to hemorrhage in conscious sheep. Eight Merino ewes (37.4 ± 1.1 kg) were subjected to fast (1.25 mL/kg/min) and slow (0.25 mL/kg/min) hemorrhages separated by at least 3 days. Blood was withdrawn until a drop in mean arterial pressure (MAP) of >30 mmHg and returned at the end of the experiment. Continuous monitoring includedMAP, central venous pressure, pulmonary artery pressure, pulse oximetry, and tissue oximetry. Cardiac output by thermodilution and arterial blood samples were also measured. The effects of fast versus slow hemorrhage rates were compared for total volume of blood removed and stoppage time (whenMAP < 30 mmHg of baseline) and physiological responses during and after the hemorrhage. Estimated blood volume removed whenMAPdropped 30 mmHg was 27.0 ± 4.2% (mean ± standard error) in the slow and 27.3 ± 3.2% in the fast hemorrhage (P = 0.47, pairedttest between rates). Pressure and tissue oximetry responses were similar between hemorrhage rates. Heart rate increased at earlier levels of blood loss during the fast hemorrhage, but hemorrhage rate was not a significant factor for individual hemorrhage tolerance or hemodynamic responses. In 5/16 hemorrhages MAP stopping criteria was reached with <25% of blood volume removed. This study presents the physiological responses leading up to a significant drop in blood pressure in a large conscious animal model and how they are altered by the rate of hemorrhage., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Uncontrolled elevation in plasma potassium within minutes of rapid blood volume loss is associated with mortality and distinguishes nonsurvivors of severe hemorrhage from survivors. In a pig model of severe hemorrhage, we discovered that along with a sharp increase in plasma potassium coincident with a shut down of urine flow, nonsurvivors also had an insufficient vasopressin response to hemorrhage. In contrast, survivors did have elevated vasopressin levels in response to hemorrhage and maintained plasma potassium within normal limits. While it has been demonstrated for some time that vasopressin can influence secretion of potassium in the distal nephron, the magnitude of this effect and conditions under which this contributes to physiological modulation of potassium excretion has yet to be defined. In this review, we assess the evidence that would suggest that vasopressin plays a key role in modulating potassium excretion and is important in the regulation of potassium homeostasis during hemorrhage.

1. The aims of the present study were to determine the cardiovascular effects of arachidonic acid (AA) and to investigate the peripheral mechanisms mediating these effects in haemorrhage-induced hypotensive rats. 2. Acute haemorrhage was induced by withdrawing a total volume of 2.2 mL blood/100 g bodyweight over a period of 10 min. Rats were then injected with 75-300 microg, i.c.v., AA and cardiovascular changes were monitored over the next 60 min. Plasma catecholamine and vasopressin levels, as well as plasma renin activity (PRA), were measured 10 min after injection of 150 microg AA in haemorrhage-induced hypotensive awake rats. In addition, rats were pretreated with saline (1 mL/kg, i.v.), the vasopressin V(1) receptor antagonist [beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1),O-Me-Tyr(2),Arg(8)]-vasopressin (10 microg/kg, i.v.), the alpha(1)-adrenoceptor antagonist prazosin (500 microg/kg, i.v.), the non-specific angiotensin II receptor antagonist saralasin (250 microg/kg, i.v.) or a combination of these three antagonists 5 min before injection of AA (150 microg, i.c.v.). The effects of these antagonists on responses to AA were determined. 3. Arachidonic acid caused dose- and time-dependent increases in mean arterial pressure and heart rate and reversed hypotension in haemorrhaged rats. Haemorrhage itself produced an increase in plasma catecholamine and vasopressin levels, as well as PRA; injection of AA produced further increases in these parameters, ranging from 39-123%, under hypotensive conditions. Under hypotensive conditions, pretreatment of rats with all three receptor antagonists produced similar partial blockade of the pressor response to AA, but not the increase in heart rate. Moreover, combined administration of all three receptor antagonists prior to the i.c.v. injection of 150 microg AA completely abolished the pressor response to AA in haemorrhage-induced hypotensive rats. 4. These results indicate that centrally administered AA reverses hypotension by increasing blood pressure and heart rate in the hypotensive setting. The observed increases in plasma catecholamine and vasopressin levels, as well as PRA, mediate the pressor response to AA in haemorrhage-induced hypotensive rats.

The increase of plasma and blood viscosity is usually associated with pathological conditions; however, elevation of both parameters often results in increased perfusion and the lowering of peripheral vascular resistance. In extreme haemodilution, blood viscosity is too low and insufficient to maintain functional capillary density, a problem that in experimental studies is shown to be corrected by increasing plasma viscosity up to 2.2 cP. This effect is mediated by mechanotransduction-induced nitric oxide (NO) production via shear stress in the endothelium as shown by microelectrode perivascular measurements of NO concentration. Moderate elevations of blood viscosity by increasing haematocrit ( approximately 10%) result in comparable reductions of blood pressure and peripheral vascular resistance, an effect also NO-mediated as it is absent after Nomega-nitro-L-arginine methyl ester treatment and in endothelial nitric oxide synthase-deficient mice. These findings show that the rheological properties of plasma affect vessel diameter in the microcirculation leading to counterintuitive responses to the changes in blood and plasma viscosity. Application of these findings to haemorrhagic shock resuscitation leads to the concept of hyperosmotic-hyperviscous resuscitation as a modality for maintaining the recovery of microvascular function.

1. In the present study, we aimed to determine the involvement of brain thromboxane A2 (TXA2) in blood pressure decreases evoked by acute and/or graded haemorrhage in rats. 2. Sprague-Dawley rats were used throughout the study. Acute haemorrhage was achieved by withdrawing a total volume of 2.1 and 2.5 mL blood/100 g bodyweight over a period of 10 min. A microdialysis study was performed in a hypothalamic area to measure extracellular TXA2 levels. Graded haemorrhage was conducted successively by withdrawing carotid arterial blood (0.55 mL/100 g bodyweight) over a 10 s period four times (S1-S4) at 5 min intervals. Furegrelate (125, 250 and 500 microg), a TXA2 synthase inhibitor, was injected intracerebroventricularly (i.c.v.) 60 min before acute or graded haemorrhage was initiated. U-46619 (0.5, 1 and 2 microg, i.c.v.), a synthetic TXA2 analogue, was administered 5 min before acute haemorrhage (2.1 mL/100 g bodyweight). 3. Acute haemorrhage produced a severe and long-lasting decrease in blood pressure and had a tendency to increase heart rate. Both haemorrhage protocols (2.1 or 2.5 mL/100 g) generated similar approximate twofold increases in extracellular hypothalamic TXA2 levels. Intracerebroventricular furegrelate (250 microg) pretreatment completely blocked the TXA2 increases induced by acute haemorrhage. Furegrelate administration (100, 250 and 500 microg, i.c.v.) attenuated the fall in arterial pressure evoked by acute haemorrhage and caused significant increases in heart rate at all doses injected. 4. Graded haemorrhage progressively lowered arterial pressure and increased plasma vasopressin and adrenaline levels in the last period. Furegrelate-injected rats were greatly resistant to the hypotensive effect of haemorrhage for all degrees of blood removed. Plasma adrenaline and vasopressin levels were significantly elevated in furegrelate-pretreated rats compared with the saline-treated group during S2-S3 and S4, respectively. U-46619 administration caused small but statistically significant decreases in arterial pressure induced by haemorrhage. 4. The results show that acute hypotensive haemorrhage increases extracellular hypothalamic TXA2 levels. The increase in brain endogenous TXA2 levels involves a decrease in blood pressure evoked by haemorrhage because the blockade of TXA2 synthesis by furegrelate pretreatment attenuated the haemorrhagic hypotension. Increases in plasma adrenaline and vasopressin levels may mediate this effect.

Adrenomedullin (ADM) is a novel peptide with actions which include reduction of arterial pressure and interaction with a number of hormone systems. In order to assess possible interactions with the renin-angiotensin system (RAS) and the hypothalamo-pituitary-adrenal (HPA) axis, we have examined neurohumoral responses to hypotensive haemorrhage (15 ml/kg over 15 min) with or without co-infusions of ADM (5.5 pmol/kg per min) in six non-pregnant and eight pregnant conscious sheep. Haemorrhage induced a greater decrease in arterial pressure, but a blunted increase in heart rate in pregnant sheep. There was no significant effect of ADM on haemodynamic responses to haemorrhage in either group. In non-pregnant sheep, haemorrhage-induced activation of both RAS and HPA was significantly augmented by ADM, as indicated by greater increases in plasma renin activity (P<0.01), angiotensin II (P<0.05) and arginine vasopressin (P<0.01). In contrast, ADM did not augment these responses to haemorrhage in pregnant sheep. Rather, plasma concentrations of aldosterone (P=0.039) and adrenocorticotrophic hormone (P=0.012) were decreased by ADM. In conclusion, ADM-induced augmentation of the RAS and HPA responses to hypotensive haemorrhage is abolished in the pregnant state.

In a rat model of volume-controlled irreversible haemorrhagic shock, which results in a severe metabolic acidosis and the death of all control animals within 30 min., intracerebroventricular injection of histamine (100 nmol) produces a prompt and long-lasting increase in mean arterial pressure and heart rate, with a 100% survival of 2 h after treatment. Histamine action is accompanied by a decrease in haematocrit value, haemoglobin concentration, erythrocyte and platelet count, and an increase in residual blood volume at the end of the experiment (2 h). Cardiovascular effects are also associated with a long-lasting rise in respiratory rate and biphasic blood acid-base changes - initial increase of metabolic acidosis with the decrease in arterial and venous pH, bicarbonate concentration and base excess, followed by almost a complete recovery of blood gas and acid-base parameters to the pre-bleeding values, with normalisation of arterial and venous pH, Pco2 bicarbonate concentration and base excess at the end of experiment. It can be concluded that in the late phase of central histamine-induced reversal of haemorrhagic hypotension there is almost a complete restoration of blood gas and acid-base status due to circulatory and respiratory compensations, while accompanying haematological changes are the result of the haemodilution and the increase in residual blood volume.

The goal of this study was to determine the role of the pontine lateral parabrachial nucleus (LPBN) in the compensatory responses to blood loss. Conscious unrestrained rats with complete, partial, or sham bilateral ibotenic acid lesions of the LPBN were subjected to a hypotensive 16-ml/kg blood withdrawal via arterial catheter. Complete lesions (LPBNx) encompassed the entire LPBN and extended into the ventrolateral parabrachial region to encroach on the Kolliker-Fuse nucleus. Partial lesions were restricted to the body of the LPBN and spared the outer rim of the external lateral subnucleus of the LPBN. In all three groups, serum corticosterone concentration and plasma renin activity increased four- to fivefold after hemorrhage (P < 0.01), and immunocytochemistry demonstrated numerous Fos-positive neurons in the hypothalamic supraoptic nucleus. However, the cardiovascular responses to hypotensive blood loss differed for complete and partial lesions. Blood pressure failed to recover in LPBNx rats and was significantly lower in LPBNx (66 +/- 4 mmHg) than in rats with partial or sham lesions (98 +/- 4 and 85 +/- 5 mmHg, respectively) at 40 min posthemorrhage. In contrast, rats with partial lesions had a significant attenuation of the posthemorrhage bradycardia. This implies that a population of neurons within the body of the LPBN is essential for full expression of the bradycardia that accompanies hemorrhagic hypotension, whereas the ventrolateral parabrachial region is essential for normal restoration of arterial pressure after hypotensive hemorrhage.

In a model of uncontrolled hemorrhagic hypotension (UCHH) in rats, we examined whether blood loss or blood chemistry were affected by (1) deliberate, controlled hypotension induced with labetalol (L) or sodium nitroprusside (SNP) and (2) intravenous (iv) fluid therapy. Two hours of UCHH was induced by resecting the distal 25% of the tail. L or SNP was infused with the aim of decreasing MAP to 50 mmHg. In the groups receiving iv fluid, 3 ml of 0.9% saline was given for each 1 ml of blood loss. L decreased blood loss (2.8+/-2.0 and 3.0+/-1.9 ml, respectively, in the groups not receiving and receiving iv fluid) compared to the groups not given hypotensive drugs (6.3+/-4.1 and 13.5+/-6.6 ml). SNP did not decrease blood loss (5.7+/-4.7 and 11.0+/-6.2 ml), increased serum potassium (5.0+/-0.6 and 5.8+/-0.4 mEq l(-1)), and with accompanying iv fluid administration decreased hematocrit, worsened acidosis, and increased mortality. In this model of 2 h of UCHH in rats, hypotension to MAP of 50 mmHg with L but not with SNP decreased blood loss.

This in vivo study confirmed impaired hemostasis during hypothermia in a swine model. Group I (normothermic, n = 8) and group II (hypothermic, n = 8) animals were anesthetized and instrumented for continuous peritoneal irrigation and monitoring of heart rate and blood pressure. The effects of hypothermia, hypotension, and inotrope on bleeding time and bleeding from two types of arterial injuries were evaluated. Our findings were that (1) bleeding time was significantly prolonged in hypothermic animals; (2) the differences in blood loss from partially torn artery (PTA) and completely cut artery (CCA) at both normothermic and hypothermic temperatures did not reach statistical significance; and (3) blood loss from PTA was greater than CCA when norepinephrine (Levophed) was infused to elevate blood pressure in hypotensive animals at normal core temperature.

The effects of iso- and hypo-osmotic reduction of the CSF [Na+] on the tolerance to blood loss and concomitant cardiovascular and humoral responses were studied in conscious sheep. Animals only subjected to haemorrhage served as controls. The changes in CSF composition were induced by intracerebroventricular infusions of 0.3 M mannitol, respectively, 0.04 M NaCl. In the former instance the CSF [Na+] was reduced by 18 mM whereas a lowering by 13 mM concomitant with decreased CSF osmolality (mean change 25 mOsm kg-1) was seen in response to the NaCl solution. Apart from a slight lowering of the cardiac output during the infusion of 0.3 M mannitol preceding haemorrhage, the changes in CSF composition did not have any significant haemodynamic effects in the normovolaemic animal, or altered the cardiovascular responses to a subsequent hypotensive haemorrhage. The amount of blood needed to be withdrawn to obtain the predefined degree of hypotension did not differ significantly between treatment groups. The plasma vasopressin and angiotensin II concentrations were consistently increased by the hypotensive haemorrhage, but the magnitude of the vasopressin response was significantly reduced when the CSF [Na+] was lowered. We conclude that lowered CSF [Na+] and/or osmolality, in contrast to increased CSF [Na+], does not influence the tolerance to blood loss or the accompanying haemodynamic changes in sheep, in spite of an attenuated vasopressin response.

Haemodynamic and humoral responses to two subsequent hypotensive haemorrhages, separated by 3 hours and each followed by retransfusion, were studied in unanaesthetized sheep. Haemorrhage was induced by removal of blood from a jugular vein at a rate of 0.7 ml kg-1 min-1 until the mean systemic arterial pressure suddenly decreased by 35 mmHg or more. In addition to the mean systemic arterial pressure, the cardiac output, the mean pulmonary arterial pressure, the central venous pressure and the pulmonary capillary wedge pressure decreased in response to each haemorrhage. The recovery of the systemic and pulmonary arterial pressure was slower and/or less efficient after the second haemorrhage, due to a less pronounced increase of the vascular resistance. Relative bradycardia, in association with the abrupt fall of the mean systemic arterial pressure, was more apparent during the first haemorrhage. The plasma levels of vasopressin, renin activity and angiotensin II were increased by each blood removal, but the vasopressin response to the second haemorrhage was significantly reduced. The plasma noradrenaline concentration was slightly and transiently elevated only in response to the second haemorrhage. The concentration of neuropeptide Y-like immunoreactivity in plasma was unaffected by both haemorrhages. It is suggested that the reduced and delayed increase in the systemic vascular resistance, accompanied by impaired recovery of the arterial pressure, and the relative absence of 'bleeding bradycardia', during the second haemorrhage, were due to the diminished vasopressin response.

The acute effects of oxymetazoline, an alpha 2-adrenoceptor agonist, and idazoxan, an alpha 2-adrenoceptor antagonist, on the release of neuropeptide Y were evaluated during haemorrhage in pentobarbital-anaesthetized dogs. Plasma concentrations of neuropeptide Y and catecholamines (adrenaline, noradrenaline, and dopamine) were determined in samples simultaneously collected from aorta, portal vein, and adrenal veins. In control dogs, adrenal catecholamine output, aortic concentrations neuropeptide Y and catecholamines markedly increased during the hypotension period. However, adrenal neuropeptide Y output decreased significantly during this period. Portal venous noradrenaline and neuropeptide Y concentrations increased significantly. In dogs treated with idazoxan, catecholamine output from the adrenals increased to an extent similar to that observed in control dogs. However, the increase in noradrenaline and neuropeptide Y in aortic or portal venous blood during haemorrhage was significantly potentiated in the presence of idazoxan. Administration of oxymetazoline abolished this increase, but did not alter adrenal catecholamine or neuropeptide Y output. The present study demonstrates that neuropeptide Y is co-released with noradrenaline from sympathetic nerve fibers during haemorrhage. Since the release of neuropeptide Y appeared to follow a similar time course to that of noradrenaline release, the present observations suggest that haemorrhagic hypotension enhances both neuropeptide Y and noradrenaline release presumably through a common releasing mechanism. These results also indicate that, in peripheral sympathetic nerves but not in the adrenal gland, neuropeptide Y release is also modulated presynaptically by the inhibitory alpha 2-adrenoceptors in conjunction with the noradrenaline release.

Sixteen anesthetized foxhounds were instrumented for hemodynamic measurements. The adrenolumbar vein was cannulated, and hemorrhagic hypotension (MAP = 40 mmHg for 3h) was induced by bleeding. The plasma levels of beta-endorphin (beta-END), methionine-enkephalin (M-ENK), and leucine-enkephalin (L-ENK) were determined in systemic and adrenal venous blood by specific RIA. Five dogs received an i.v. bolus of naloxone (2 mg/kg) and a subsequent naloxone infusion of 2 mg/kg per hour 1 h after onset of hypovolemia. Eleven dogs served as controls and received equivalent volumes (1 ml/kg per hour) of saline. Hemorrhage resulted in a sharp increase in plasma concentrations of all measured opioid peptides, particularly of M-ENK (26-fold) and L-ENK (24-fold) in the adrenal effluent. Systemic beta-END levels remained 3-fold increased, whereas the ENK release decreased spontaneously. Naloxone treatment inhibited the spontaneous fall of adrenal ENK release during the hypotensive phase; the ENK values remained elevated 20- to 35-fold. Reinfusion of the autologous blood resulted in a normalization of the concentrations of all peptides in both groups. These data demonstrate that hemorrhagic hypotension will cause stimulation of release of endogenous opioid peptides. The high levels of ENK in the adrenal effluent indicate that the adrenal gland is the main source of these peptides in the circulation. In addition to beta-END, the ENK have therefore to be considered as possible factors perpetuating circulatory shock.

Effects of acute, short-lasting haemorrhage have been studied in six goats. The experiments were made 55 +/- 3 days (mid-pregnancy = MP), and 24 +/- 2 days (late pregnancy = LP) before parturition, in lactation weeks 3-8, and in the non-pregnant, non-lactating (= control) period. The room temperature was kept at 20 +/- 1 degrees C, except during one experimental series in lactating goats, which was performed at +30 degrees C. Approximately the same volume of blood had been removed in all periods, when the mean arterial blood pressure (MAP) fell. At this moment bleeding was stopped. The volume loss, calculated as per cent of total blood volume, was significantly smaller during pregnancy and lactation than in the control period. The fastest heart rate, both at rest and during haemorrhage, was observed in LP goats. The respiratory frequency of the LP goats increased markedly in response to haemorrhage, but the most rapid respiratory rate was observed in lactating goats bled at the room temperature +30 degrees C. The increase in plasma vasopressin (AVP) concentration coincided with the fall in MAP. The AVP rise seen during late pregnancy was significantly higher than in all the other periods. The plasma noradrenaline (NA) concentration increased by about five times in LP goats, but did not change significantly in the other periods. Plasma renin activity did not rise, with the exception of a small increase in lactating goats bled at +30 degrees C. The plasma aldosterone concentration rose, but there was no difference between periods.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of angiotensin converting enzyme inhibitor (CEI) upon blood pressure and plasma aldosterone (PA) were studied in rabbits with a simultaneous infusion of angiotensin I (ANG I) or with hemorrhagic hypotension. Pretreatment with CEI (SQ 20881), 1.0 mg/Kg, inhibited the effects of infused ANG I, 30 ng/Kg/min, upon PA and blood pressure at 30 min of the infusion, but the inhibition on PA was not significant at 60 min of the infusion. The same dose of CEI was ineffective in blocking the effect of 100 ng/Kg/min of ANG I on PA and blood pressure even at 30 min of the infusion. In rabbits with hemorrhagic hypotension, injection of CEI resulted in the decrement in blood pressure, whereas no decrement in blood pressure was observed in normal control rabbits. This study suggests that CEI exerts it's effect in part by inhibiting conversion of ANG I to angiotensin II (ANG II), but this can't exclude other mechanisms.

Changes of the arterial plasma osmolality and of the glucose concentration were followed during a 30 min period of graded hemorrhagic hypotension (80, 50, and 30 mmHg) in the cat. Bleeding evoked a significant plasma hyperosmolality at all three hypotension levles and the responses were quantitatively related to the degree of hypotension. An approximate steady state increase in the arterial plasma osmolality was reached about 20 min after the start of the bleeding and it then averaged 8. 20, and 25 mOsm/kg H2O at 80, 50, and 30 mmHg, respectively. Bleeding also evoked an increase in the plasma glucose concentration, which almost entirely accounted for the observed hyperosmolality, especially at 80 and 50 mmHg. In late stages of hypotension at 30 mmHg, elevated plasma lactate and potassium concentrations contributed to the overall hyperosmolality. --Previous hemorrhagic hypotension experiments at 50 mmHg (Järhult 1975 b) have shown that hyperosmolality serves as an important regulator of the plasma and extracellular fluid volumes during bleeding. The present results indicate that such an osmolar compensatory mechanism is operating over wide ranges of hemorrhagic hypotension.

In eleven dogs made hypotensive by means of rapid exsanguination over a period of forty to seventy minutes, mean glucagon rose to a peak of 516 plus or minus (S.E.) 150 pg/ml. and mean glucose to a peak of 341 plus or minus 27 mg. per 100 ml. The hyperglucagonemia induced by exsanguination was substantially reduced, although not abolished, by propranolol infusion, but was not diminished by phentolamine, suggesting that it was largely a beta-adrenergic effect. Its possible contribution to survival during shock is considered.

Tyrosine is the precursor for catecholamine neurotransmitters. When catecholamine-containing neurons are physiologically active (as sympathoadrenal cells are in hypotension), tyrosine administration increases catecholamine synthesis and release. Since hypotension can alter plasma amino acid composition, we examined the effects of an acute hypotensive insult on tyrosine concentrations in plasma and spinal cord. Rats were cannulated and bled until the systolic blood pressure was 50 mmHg, or were kept normotensive for 1 h. Tyrosine and other large neutral amino acids (LNAA) known to compete with tyrosine for brain uptake were assayed in plasma and spinal cord. The rate at which intra-arterial [3H]tyrosine disappeared from the plasma was also estimated in hemorrhaged and control rats. In plasma of hemorrhaged animals, both the tyrosine concentration and the tyrosine/LNAA ratio was elevated; moreover, the disappearance of [3H]tyrosine was slowed. Tyrosine concentrations also increased in spinal cords of hemorrhaged-hypotensive rats when compared to normotensive controls. Changes in plasma amino acid patterns may thus influence spinal cord concentrations of amino acid precursors for neurotransmitters during the stress of hemorrhagic shock.

The goal of the present study was to investigate the relationships among CBF, CMRO2, MTT and tissue/superior sagittal sinus hemoglobin saturations over a wide range of CPP using a canine model of hypotension. Microsphere-determined CBF was autoregulated in all tested cerebral regions over the 40-130 mmHg CPP range, but it decreased 50% around 30 mmHg. MTT, calculated by an indicator-dilution technique, progressively and proportionately increased over the 40-130 mmHg CPP range. The HbO2 content, measured in the same area by an optical method, parallely decreased. Around 30 mmHg CPP, MTT disproportionately lengthened (700% of control). CMRO2 maintenance was accompanied by a progressive decrease of tissue HbO2 and sagittal sinus hemoglobin saturation. In this framework, MTT measurement and tissue HbO2 monitoring by NIRS might give a sensitive evaluation of the hemodynamic reserve than CBF measurement in anesthesia and intensive care.

Heart rate and arterial blood pressure were monitored in 20 consecutive patients during resuscitation from haemorrhagic shock. The mean blood loss (2.3 (SEM 0.3) 1) corresponded to 36(4)% of their estimated mean blood volume. During shock the mean blood pressure was 81/55 (3/2) mm Hg and heart rate 73 (3) beats/min. Administration of blood and crystalloids resulted in immediate increases to 111/72 (2/2) mm Hg and 102 (3) beats/min followed by steady state values of 131/79 (6/3) mm Hg and 82 (2) beats/min. In three otherwise healthy patients plasma concentrations of the vagally regulated hormone pancreatic polypeptide rose from resting values of 64-77 pmol/l (272-327 pg/ml) to 198-280 pmol/l (842-1190 pg/ml). These findings suggest that reversible hypotensive hypovolaemic shock is characterised by a decrease in heart rate conceivably reflecting an increase in vagal tone.

A study was made of the dynamics of the lysozyme activity of the serum in dogs which sustained clinical death on the background of a 2-hour hypovolemic hypotension due to blood loss. There was revealed a progressive increase in the lysozyme activity of the serum during the hypotension and during the first 30 minutes of the postreanimation period. Lysozyme activity of the serum was increased in the course of 4 days after the revival. The significance of the lysozyme activity of the serum as an index of hypoxic injury of the internal organs in terminal conditions is discussed.

The role which beta-endorphin plays in the pathogenesis of hemorrhagic hypotension is controversial. In the present experiment, 20 ml/kg of blood was bled from ten healthy male baboons (Papio anubis) over 60 min and then retransfused over the next 30 min. We found that the mean plasma beta-endorphin level increased 109% above baseline (p less than .05) within 15 min after starting hemorrhage, and rapidly returned to a baseline concentration with retransfusion. We conclude that in a primate species, circulating endogenous opioid peptide concentrations increase rapidly in response to sublethal hemorrhagic hypotension and normalize with restoration of the baseline intravascular volume. These findings support the concept that endogenous opioid peptides may mediate the hypotension of shock states.

Renal renin and the juxtaglomerular cells evolved in primitive bony fishes, whereas the macula densa emerged later in vertebrate phylogeny. We attempted to determine whether a renal arteriolar baroreceptor exists in the toadfish Opsanus tau, which possess renin and granulated cells in the kidneys, but lack glomeruli and macula densa. Cumulative hemorrhage of 1.5, 3, 6, 12, and 18 ml/kg, or a single massive bleeding from unanesthetized toadfish, kept in 50% seawater, caused an immediate and significant decrease in mean aortic pressure and stepwise increases (5-20 times) of plasma renin activity (PRA). Papaverine (10 mg/kg) caused hypotension and increased PRA. Minoxidil (6-12 mg/kg) neither decreased blood pressure nor increased PRA. The results suggest that toadfish respond to hemorrhage and acute hypotension with renin release despite the absence of a macula densa. It remains to be determined whether decreased renal perfusion pressure due to decreased dorsal aortic pressure stimulated the receptor in the granulated cells or whether the renal nerves may be involved.

The relative contribution of the splanchnic sympathetic innervation and the adrenal medulla for metabolism and hormone secretion during two different levels of hemorrhagic hypotension was investigated in 3 groups of anesthetized cats, viz, intact, adrenalectomized and splanchnicotomized (adrenalectomy + cutting of splanchnic nerves). In intact cats, hemorrhage caused very marked elevations of arterial plasma glucose, adrenaline, noradrenaline, dopamine, lactate, cAMP, glycerol and glucagon concentrations whereas plasma insulin fell to only 20% of control values. Adrenalectomy attenuated the glucose, adrenaline, noradrenaline and cAMP responses whereas the normal insulin inhibition was abolished. Splanchnicotomy further reduced the hemorrhagic glucose and glycerol responses and, possibly, also that of glucagon. It is concluded that the adrenergic system as a whole is important for the adjustments of the release of glucose, cAMP, glycerol, insulin and glucagon that occur during hemorrhage in cats. The adrenal medulla seems to be of particular importance for the regulation of cAMP release.