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Biomedical subjects

B Driessen

Publications and source records attributed to B Driessen.

At least 19 recordsLinked to original sources
PubMed2006

Pharmacodynamic effects and pharmacokinetic profile of a long-term continuous rate infusion of racemic ketamine in healthy conscious horses.

Ketamine (KET) possesses analgesic and anti-inflammatory activity at sub-anesthetic doses, suggesting a benefit of long-term KET treatment in horses suffering from pain, inflammatory tissue injury and/or endotoxemia. However, data describing the pharmacodynamic effects and safety of constant rate infusion (CRI) of KET and its pharmacokinetic profile in nonpremedicated horses are missing. Therefore, we administered to six healthy horses a CRI of 1.5 mg/kg/h KET over 320 min following initial drug loading. Cardiopulmonary parameters, arterial blood gases, glucose, lactate, cortisol, insulin, nonesterified fatty acids, and muscle enzyme levels were measured, as were plasma concentrations of KET and its metabolites using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Levels of sedation and muscle tension were scored. Respiration and heart rate significantly increased during the early infusion phase. Glucose and cortisol significantly varied both during and after infusion. During CRI all horses scored 0 on sedation. All but one horse scored 0 on muscle tension, with one mare scoring 1. All other parameters remained within or close to physiological limits without significant changes from pre-CRI values. The mean plasma concentration of KET during the 1.5 mg/kg/h KET CRI was 235 ng/mL. The decline of its plasma concentration-time curve of both KET and norketamine (NKET) following the CRI was described by a two-compartmental model. The metabolic cascade of KET was NKET, hydroxynorketamine (HNK), and 5,6-dehydronorketamine (DHNK). The KET median elimination half-lives (t1/2alpha and t1/2beta) were 2.3 and 67.4 min, respectively. The area under the KET plasma concentration-time curve (AUC), elimination was 76.0 microg.min/mL. Volumes of C1 and C2 were 0.24 and 0.79 L/kg, respectively. It was concluded that a KET CRI of 1.5 mg/kg/h can safely be administered to healthy conscious horses for at least 6 h, although a slight modification of the initial infusion rate regimen may be indicated. Furthermore, in the horse KET undergoes very rapid biotransformation to NKET and HNK and DHNK were the major terminal metabolites.

Analgesics↗
PubMed2006

Effects of isovolemic resuscitation with hemoglobin-based oxygen carrier Hemoglobin glutamer-200 (bovine) on systemic and mesenteric perfusion and oxygenation in a canine model of hemorrhagic shock: a comparison with 6% hetastarch solution and shed blood.

OBJECTIVE: To study Hemoglobin glutamer-200 bovine (Hb-200), 6% hetastarch (HES) and shed whole blood (WB) resuscitation in canine hemorrhagic shock. STUDY DESIGN: Prospective laboratory investigation. Animals Twelve adult dogs [29 +/- 1 kg (mean +/- SD)]. METHODS: Anesthetized dogs were instrumented for recording systemic and mesenteric hemodynamic parameters and withdrawal of arterial, mixed and mesenteric venous blood, in which hematological, oxygenation, blood gas and acid-bases variables were determined. Recordings were made before [baseline (BL)], after 1 hour of hypovolemia and immediately and 3 hours post-resuscitation with 30 mL kg(-1) of either Hb-200, HES, or WB. RESULTS: Blood withdrawal (average 34 +/- 2 mL kg(-1)) caused significant hemodynamic changes, metabolic acidosis and hyperlactatemia characteristic for hemorrhagic shock. Only WB transfusion restored all variables. Hemoglobin glutamer-200 bovine infusion returned most hemodynamic parameters including cardiac output and mesenteric arterial blood flow to BL but increased mean arterial pressure above BL (p < 0.05). However, Hb-200 failed to restore total Hb and arterial oxygen content (CaO2), leaving systemic (DO2I) and mesenteric O2 delivery (DO2Im) below BL (p < 0.05). Nevertheless, acid-base variables recovered completely after Hb-200 resuscitation, and met-hemoglobin (Met-Hb) levels increased (p < 0.05). Hetastarch resuscitation returned hemodynamic variables to or above BL but further decreased total Hb and CaO2, preventing recovery of sDO2I and mDO2I (p < 0.05). Thus, systemic and mesenteric O2 extraction stayed above BL (p < 0.05) while acid-base variables recovered to BL, although slower than in Hb-200 and WB groups (p < 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: Resuscitation with Hb-200 seemed to resolve metabolic acidosis and lactatemia more rapidly than HES, but not WB; yet it is not superior to HES in improving DO2I and DO2Im. The hyperoncotic property of solutions like Hb-200 that results in rapid volume expansion with more homogenous microvascular perfusion and the ability to facilitate diffusive O2 transfer accelerating metabolic recovery may be the key mechanisms underlying their beneficial effects as resuscitants.

Animals↗
PubMed2006

Influence of supplemental magnesium, tryptophan, vitamin C, vitamin E, and herbs on stress responses and pork quality.

This study investigated the effects of supplemental Mg, Trp, vitamin C, vitamin E, and herbs on stress responses, skin lesions, and meat quality of slaughter pigs (106.0 +/- 8.6 kg of BW). These 5 supplements were tested in 4 similar experiments. In Exp. 1, 2 treatments were tested: 1) control treatment without supplementation, and 2) supplementation of an herbal product (2.5 g/L of drinking water for 2 d). Eighty-eight pigs per treatment were involved, of which 40 were selected for meat quality measurements (over 4 replicates). The experimental design of Exp. 2 and 3 was the same as Exp. 1, except that in Exp. 2 Mg (3 g/L of drinking water for 2 d) was supplemented and in Exp. 3 Trp (6 g/kg of feed, as-fed basis) was supplemented. In Exp. 4, 3 treatments were tested: 1) control treatment without supplementation, 2) supplementation of vitamin C (300 mg/kg of feed for 21 d, as-fed basis), and 3) supplementation of vitamin E (150 mg/kg of feed for 21 d, as-fed basis). In Exp. 4, 66 pigs per treatment were used, of which 42 were evaluated for meat quality (over 6 replicates). Pigs supplemented with vitamin E ate less than control (P = 0.03) or vitamin C-supplemented pigs (P = 0.03). Pigs were transported to a commercial slaughterhouse and were slaughtered after a lairage period. Blood sampling at slaughter revealed no differences between the control and supplemented pigs in plasma cortisol, glucose, lactate, or creatine kinase concentrations. Pigs provided with Mg (P = 0.002) or Trp (P = 0.04) had lower plasma NEFA concentrations than control pigs, and pigs supplemented with vitamin C had greater concentrations than the control (P = 0.03) or vitamin E-supplemented pigs (P = 0.01). Supplementation of the herbal product increased the frequency of pigs with shoulder (P = 0.05) and loin lesions (P = 0.03), whereas Mg lowered the incidence of loin lesions (P = 0.01). Measurements of pH and temperature in the LM and biceps femoris 45 min postmortem revealed no differences among treatments, and no influence of treatments on LM pH, electrical conductivity, and water holding capacity was observed 48 h postmortem. Compared with the control loins, loins of pigs supplemented with vitamin C (Japanese color scale, L*, and a* value; P < 0.05) or vitamin E (Japanese color scale and a* value; P < 0.03) were redder and less pale, and the loin of vitamin E-supplemented pigs was more yellow (b* value; P = 0.04). Generally, Mg could lower loin damage, whereas vitamin C and vitamin E supplementation resulted in a color improvement of the loin.

Animal Feed↗
PubMed2006

Growth factor and receptor mRNA expression in the intestine of horses with large colon volvulus: a pilot study.

REASONS FOR PERFORMING STUDY: Growth factors (GF) are important for maintenance and repair of intestinal mucosal structure and function, but there have been no studies investigating growth factor (GF) or growth factor receptor (GF-R) mRNA expression in the intestine of horses with large colon volvulus (LCV). OBJECTIVES: (1) To determine mRNA expression for epidermal growth factor (EGF), EGF receptor (EGF-R), insulin-like growth factor-I (IGF), IGF receptor (IGF-R), vascular endothelial growth factor (VEGF) and VEGF receptor (VEGF-R) in the intestine of horses with an LCV compared to normal intestine. (2) To measure the correlation between histological intestinal injury and mRNA expression. METHODS: In 5 horses, samples were collected from the mid-jejunum (small intestine, SI), pelvic flexure (PF) and right dorsal colon (RDC) prior to creation of the LCV (NORM), 1 h following creation of the LCV (ISCH) and 1 h following correction of the LCV (REPER). In 2 clinical cases of LCV, samples were collected from the PF and RDC. Samples were assessed histologically for the amount of intestinal injury. The mRNA expressions of growth factors and receptors were determined using qRT-PCR. RESULTS: VEGF and VEGF-R mRNA expression was greater in horses with an LCV compared to NORM. Expression of IGF-R mRNA increased in the SI during ISCH and REPER. CONCLUSION AND POTENTIAL RELEVANCE: The increase compared to NORM in VEGF and VEGF-R mRNA expression in horses with LCV may be important in early intestinal healing and may also explain, in part, the increase in vascular permeability in horses with a LCV. Expression of IGF and IGF-R in the SI warrants further investigation and may be important for understanding post operative complications in horses with SI lesions.

Animals↗
PubMed2005

Variability in the eruption of the permanent incisor teeth in sheep.

The incisor teeth of 176 sheep of six breeds were inspected every two to three months for a year to record the shedding of the deciduous teeth and the eruption of the permanent teeth. In all the breeds the permanent central incisors erupted at between 12 and 18 months of age. In 96 per cent of the sheep the permanent middle incisors erupted at between 18 and 26 months; and in 92 per cent the permanent lateral incisors erupted at between 24 and 36 months of age. The permanent corner teeth erupted at between 32 and 44 months in 96 per cent of the sheep. The gingival redness and swelling accompanying the eruption of a permanent tooth disappeared within two months. In 14 cases two pairs of incisors erupted during the year, in 18 cases the incisors erupted asymmetrically, and in 22 cases no incisors erupted. Rotation of one incisor was observed in five sheep and was combined with dental deviation in one.

Animals↗
PubMed2004

Effect of supplemental tryptophan, vitamin E, and a herbal product on responses by pigs to vibration.

Economic losses related to increased stress during the transport of pigs are well documented. The effects of supplementing of tryptophan (Trp), vitamin E, or a herbal product via feed or drinking water were investigated in terms of effects on stress response in pigs during transport simulation. The study consisted of three analogous experiments. For the testing in each experiment, the pigs (23.5+/-3.2 kg) were allocated to one of two treatments, with and without supplementation of a product. The applied doses were Trp (5 g/L drinking water for 3 d), vitamin E (additional amount of 300 mg/kg feed for 21 d, as-fed basis), and Sedafit (2.5 g/L drinking water for 2 d). Sedafit is a commercial herbal product containing Valeriana officinalis L. and Passiflora incarnata L. as active components. In each experiment of the study, at least 47 pigs were involved, which were treated in groups of 3. The day before transport simulation, a Holter device was attached to the pigs to produce an electrocardiogram during the night (rest values), as well as during vibration in the transport simulator (1.2 Hz, 1 m/s2), where the behavior of the pigs (standing-sitting-lying) was also observed. Samples of saliva (taken before, during, and after [3x] vibration) and blood (taken before and after vibration) were analyzed for cortisol and intermediate metabolites (glucose, lactate, creatine kinase, and nonesterified fatty acids), respectively. Pigs supplemented with Trp tended to spend more time lying down during the second hour of vibration (P < 0.05). Vitamin E decreased the peak heart rate (P < 0.05), ventricular ectopic beats (P < 0.01), and ST elevation (P < 0.10). The supplementation of Sedafit resulted in smaller increases of the investigated heart variables (minimum heart rate, P < 0.05; ventricular ectopic beats, P < 0.05; ST elevation, P < 0.01) during and after stress evocation compared with the control group. None of the tested products influenced the intermediate metabolites; one possible explanation for this finding may be that peak values were reached before the time of bleeding. In conclusion, Trp had a positive behavioral effect in this experiment, and vitamin E and Sedafit mediated an increase in some heart variables, suggesting sedative and antianxiety effects.

Animals↗
PubMed2002

Serum fluoride concentrations, biochemical and histopathological changes associated with prolonged sevoflurane anaesthesia in horses.

The volatile anaesthetic sevoflurane is degraded to fluoride (F-) and a vinyl ether (Compound A), which have the potential to harm kidney and liver. Whether renal and hepatic injuries can occur in horses is unknown. Cardiopulmonary, biochemical and histopathological changes were studied in six healthy thoroughbred horses undergoing 18 h of low-flow sevoflurane anaesthesia. Serum F- concentrations were measured and clinical laboratory tests performed to assess hepatic and renal function before and during anaesthesia. Necropsy specimens of kidney and liver were harvested for microscopic examination and compared to pre-experimental needle biopsies. Cardiopulmonary parameters were maintained at clinically acceptable levels throughout anaesthesia. Immediately after initiation of sevoflurane inhalation, serum F- levels began to rise, reaching an ongoing 38-45 micromol 1(-1) plateau at 8 h of anaesthesia. Serum biochemical analysis revealed only mild increases in glucose and creatinine kinase and a decrease in total calcium. Beyond 10 h of anaesthesia mild, time-related changes in urine included increased volume, glucosuria and enzymuria. Histological examination revealed mild microscopic changes in the kidney involving mainly the distal tubule, but no remarkable alterations in liver tissue. These results indicate that horses can be maintained in a systemically healthy state during unusually prolonged sevoflurane anaesthesia with minimal risk of hepatocellular damage from this anaesthetic. Furthermore, changes in renal function and morphology observed after sevoflurane inhalation are judged minimal and appear to be clinically irrelevant; they may be the result of anaesthetic duration, physiological stressors, sevoflurane (or its degradation products) or other unkown factors associated with these animals and study conditions.

Anesthetics, Inhalation↗
PubMed2001

Validation of in vivo MR measurement of oxygen saturation after resuscitation with a hemoglobin-based oxygen carrier in a rabbit model.

RATIONALE AND OBJECTIVES: The authors tested whether noninvasive magnetic resonance (MR) oximetry is accurate in the in vivo measurement of oxygen saturation in a stroma-free, hemoglobin-based oxygen carrier (HBOC). MATERIALS AND METHODS: A central venous catheter was placed in the inferior vena cava (IVC) of 10 New Zealand white rabbits (weight range, 2.5-3.2 kg). Each rabbit underwent removal of 20% of blood volume followed by resuscitation with 10 mL/kg of bovine HBOC-200. Oxygen saturation of the blood mixture was measured in vivo at the IVC with MR oximetry, with separate in vitro calibration for each animal. Blood drawn from the IVC was measured with ex vivo oximetry, which was used as the standard of reference. The in vivo and ex vivo measurements were compared. RESULTS: There was no significant difference (P > .1) between measurements obtained with MR oximetry and ex vivo oximetry. The results with in vivo MR oximetry demonstrated excellent correlation with those from ex vivo oximetry (r = 0.99) over a wide range of physiologic oxygen saturation values (16.7%-74.9%) in venous blood. CONCLUSION: Noninvasive in vivo MR measurement of oxygen saturation is valid for whole blood mixed with stroma-free hemoglobin. Therefore, MR oximetry may be clinically useful for assessing the oxygenation status in patients resuscitated with a HBOC.

Animals↗
PubMed2001

Inadequacy of low-volume resuscitation with hemoglobin-based oxygen carrier hemoglobin glutamer-200 (bovine) in canine hypovolemia.

Stroma-free hemoglobin-based oxygen carriers (HBOC) have been developed to overcome problems associated with transfusion of allogeneic blood. We have studied the efficacy of the first licensed veterinary blood substitute, hemoglobin glutamer-200 bovine (Oxyglobin; Biopure, Cambridge, MA, USA, Hb-200), in a canine model of acute hypovolemia and examined whether clinically commonly used criteria are adequate to guide fluid resuscitation with this product. Twelve anesthetized dogs were instrumented for measurements of physiological variables including hemodynamic, oxygenation, and blood gas and acid-base parameters. Dogs were bled to a mean arterial pressure (MAP) of 50 mmHg for 1 h followed by resuscitation with either shed blood (controls) or Hb-200 until heart rate (HR), MAP and central venous pressure (CVP) returned to baseline. Recordings were repeated immediately and 3 h after termination of fluid resuscitation. Hemorrhage (average 32 mL/kg) caused significant decreases in total hemoglobin (Hb), mean pulmonary arterial pressure (PAP), cardiac output (CO) and oxygen delivery (DO2I), increases in HR and systemic vascular resistance (SVRI), and lactic acidosis. In controls, only re-transfusion of all shed blood returned HR, MAP and CVP to prehemorrhage values, whereas in other dogs this endpoint was reached with infusion of 10 mL/kg Hb-200. Unlike blood transfusion, Hb-200 infusion failed to return CI and DO2I to baseline and to increase arterial oxygen content (CaO2) and total Hb; SVRI further increased. Thus, commonly used criteria (HR, MAP, CVP) to guide transfusion therapy in patients posthemorrhage prove insufficient when HBOCs with pronounced vasoconstrictive action are used and lead to inadequate volume repletion.

Animals↗
PubMed2001

Effects of haemoglobin-based oxygen carrier hemoglobin glutamer-200 (bovine) on intestinal perfusion and oxygenation in a canine hypovolaemia model.

The objective of this investigation was to study the effects of the first marketed haemoglobin-based oxygen carrier, Hemoglobin glutamer-200 (bovine) (Hb-200) (Oxyglobin) on splanchnic perfusion and oxygenation in a canine model of acute hypovolaemia. Twelve anaesthetized dogs [mean weight 30.8 (S.D. 1.4) kg] were instrumented for recordings of heart rate (HR), mean arterial pressure (MAP), central venous pressure (CVP), cardiac output and cranial mesenteric arterial (CMA) and venous blood flows (CMV). Total and plasma haemoglobin (Hb), oxygen content and saturation, lactate concentration, pH and blood gases were analysed in arterial, mixed venous and mesenteric venous blood samples. Measurements were made before (baseline) and after 1 h of haemorrhage, after which animals were resuscitated with either shed blood (controls) or Hb-200 until HR, MAP and CVP returned to prehaemorrhage levels. Recordings were repeated immediately and 3 h after termination of fluid resuscitation, after which organ specimens were obtained for microscopic examination. Haemorrhage (average 32 ml kg(-1)) reduced MAP to 50 mm Hg, increased HR and systemic vascular resistance (SVR), and was accompanied in both the systemic and the splanchnic circulation by significant decreases in blood flow, Hb content and oxygen delivery (DO2), and lactic acidosis. In controls, all variables recovered to baseline after isovolaemic resuscitation with shed blood. In dogs resuscitated with a small volume of Hb-200 (10 ml kg(-1)), HR, MAP, CVP and CMA and CMV blood flows returned to baseline. However, cardiac output, total Hb, oxygen content and systemic and mesenteric DO2 remained depressed while SVR increased further. Mesenteric and systemic acid-base status recovered in both groups, and there was no difference in microscopic tissue damage between groups. Thus, Hb-200 reconstituted splanchnic perfusion and oxidative metabolism in spite of pronounced systemic vasoconstriction and insufficient restoration of CO and DO2; it may improve diffusive oxygen transport in the microvasculature by virtue of haemodilution and its high efficiency in the uptake and release of oxygen.

Acid-Base Equilibrium↗
PubMed2001

A novel approach to measuring circulating blood volume: the use of a hemoglobin-based oxygen carrier in a rabbit model.

UNLABELLED: Hemoglobin-based oxygen carriers (HBOC) may be ideal for monitoring circulating plasma volume (CV-P) and circulating blood volume (CV-B). We used an HBOC (Hemoglobin glutamer-200 [bovine], Oxyglobin; Biopure, Cambridge, MA) as an indicator for relative CV-B in the rabbit model. Accuracy of the technique was determined by comparison with the Evans blue dye (EBD) dilution technique in 19 anesthetized female New Zealand rabbits weighing 2.0 to 10.6 kg. The measurements were performed at baseline, after hemorrhage (1/3 of CV-B), normovolemic hemodilution (replacement of 1/3 CV-B by Hextend; Abbot Laboratories, North Chicago, IL), and hypervolemic hemodilution (additional infusion of Hextend(R) in a volume equal to 1/3 of CV-B). Hemoglobin concentration was measured by using a HemoCue photometer (HemoCue AB, Angelholm, Sweden). EBD concentration was analyzed by using linear regression to estimate Time 0 concentration; Time 0 was defined as EBD injection time. The difference between CV-P values determined by EBD and HBOC dilution was independent from the magnitude of the CV-P value. The relative bias was 1.29 mL, and the precision (one SD) was 2.82 mL. The difference did not reach statistical significance. IMPLICATIONS: Circulating plasma and blood volumes can be accurately estimated by plasma hemoglobin concentration measurements by using hemoglobin-based oxygen carrier infusion.

Animals↗
PubMed2001

The effects of hemoglobin glutamer-200 (bovine) on the microcirculation in a canine hypovolemia model: a noninvasive computer-assisted intravital microscopy study.

UNLABELLED: We sought to correlate in vivo microvascular, systemic function, hemodynamic, and oxygenation changes in autologous shed blood (n = 4) and hemoglobin glutamer-200 (Hb-200) (n = 4) resuscitations in hypovolemic dogs. Hemorrhage (approximately 40% blood loss) reduced mean arterial pressure to approximately 50 mm Hg and caused significant (P < 0.01) decreases in hematocrit, total hemoglobin, mean pulmonary arterial pressure, cardiac output, and oxygen delivery and significant (P < 0.01) increases in heart rate, systemic vascular resistance, and lactic acidosis. Significant (P < 0.01) changes in conjunctival microvascular variables also occurred, including a 19% decrease in venular diameter and 79% increase in average blood flow velocity. Shed blood resuscitation returned microvascular, systemic function, hemodynamic, and oxygenation variables to prehemorrhagic baseline values. In contrast, Hb-200 failed to restore hematocrit, total hemoglobin, cardiac output, oxygen delivery index, and systemic venous resistance to baseline, but it restored other systemic functions and all hemodynamic and microvascular changes. In addition, Hb-200 resuscitation in hypovolemic dogs (approximately 40% blood loss) did not cause extreme hemodilution or fatal outcome. This study confirms that real-time (in vivo) microvascular studies, which were conducted only in small rodent models in the past, can be performed simultaneously with systemic function, hemodynamic, and oxygenation studies in a large animal model for relevant data correlation. IMPLICATIONS: This is the first time that changes in the blood circulation have been studied, quantified, and correlated with systemic function, hemodynamic, and oxygenation changes in shock and during shock treatment in a large animal model. This study was performed by a new technology developed in-house to noninvasively and quantitatively study blood vessels in real time.

Animals↗
PubMed2000

Validation of oxygen saturation measurements in a canine model of hemoglobin based oxygen carrier (HBOC) infusion.

OBJECTIVE: The study was designed to validate oxygen saturation measurements from the NOVA CO-Oximeter, the i-STAT System, and the Corning 170 blood gas analyzer under conditions similar to the clinical application of a hemoglobin-based oxygen carrier. DESIGN: A canine model was used for both in-vitro and in-vivo experiments. SETTING: Canine laboratory for in-vivo, and tonometry laboratory for in-vitro sets. PARTICIPANTS: 6 mixed-breed canines, 30 kg; canine remainder sample blood. INTERVENTIONS: In the first set of experiments, the target blood pO2 levels were reached by tonometry. In the second set of experiments, quantitative measurements of total oxygen content with the LEXO2Con-K, were performed immediately followed by measurements with the NOVA CO-Oximeter and the i-STAT system. HBOC was added in concentrations of 16.2, 32.5, 65.0, and 97.5 g/L. To analyze the clinical significance of the differences in the results obtained with the different investigated instruments; blood samples from dogs treated with HBOC after acute hemorrhagic shock were used. RESULTS: There was a strong correlation between the oxygen saturation values measured with the investigated instruments in samples after tonometry and known oxygen partial pressure. The total calculated O2 content varied by 5% based on results generated by calculations based on the investigated instruments. The results did not change with different oxygenation of the sample. The differences among methods were not significant when HBOC concentration was 16.2 g/L. Higher concentrations of HBOC increased the difference between calculated and measured oxygen content; i-STAT system demonstrated a greater deviation from the results of the other two instruments. Systemic oxygen uptake based on investigated instruments showed high correlation with values based on LEXO2CON-K measurements (r=0.97 for CO-Oximeter, 0.96 for gas analyzer, and 0.79 for i-STAT). Systemic oxygen uptake values based on CO-Oximeter and blood gas analyzer data showed a 75% accuracy; i-STAT accuracy was 63% for control samples and 50% for samples after HBOC infusions. CONCLUSION: The NOVA CO-OXimeter is an accurate analyzer for measurement of oxygen saturation after HBOC infusion in the canine model. Use of the i-STAT system should be limited to arterial samples or for samples with a low HBOC concentration.

Animals↗
PubMed1999

Haemodynamic effects of ATP in dogs during hypoxia-induced pulmonary hypertension.

Pulmonary hypertension may result from an increase in vascular resistance caused by persistent hypoxia. We have investigated the effects of adenosine triphosphate (ATP), administered into the pulmonary artery, on haemodynamic changes occurring in anaesthetized adult dogs subjected to acute hypoxic pulmonary vasoconstriction. Hypoxia alone (ventilation with 10% O2/90% N2) caused significant increases in mean pulmonary arterial blood pressure (PAP), central venous pressure (CVP), and cardiac index (CI) by 71, 102 and 38%, respectively. ATP (0.03-3.0 micromol/kg/min approximately 0.02-1.65 mg/kg/min), when infused under hypoxic conditions, significantly reduced both mean PAP and systemic arterial blood pressure (ABP) in a dose-dependent manner. The maximum decrease in mean PAP amounted to 20%; mean ABP, on the other hand, was decreased by up to 52% (P<0.01). Heart rate, CI, CVP and pulmonary occlusion pressure were not dose-dependently affected by ATP. Our data indicate that while pulmonary arterial administration of ATP in mature dogs during hypoxic pulmonary hypertension causes dilation in the pulmonary vascular bed, it is even more effective in dilating the systemic vasculature. This result suggests a need for further evaluation and warrants cautious use of ATP in the treatment of hypoxic pulmonary hypertension in adult dogs.

Adenosine Triphosphate↗
PubMed1998

Depression of C fiber-evoked activity by intrathecally administered reactive red 2 in rat thalamic neurons.

To investigate the possible role of spinal purinoceptors in nociception, the potent P2-purinoceptor antagonist reactive red 2 was studied in rats under urethane anesthesia in which nociceptive activity was elicited by electrical stimulation of afferent C fibers in the sural nerve and recorded from single neurons in the ventrobasal complex of the thalamus. Intrathecal (i.t.) application of reactive red 2 (6-200 micrograms) caused a dose-dependent reduction of the evoked activity in thalamic neurons. The estimated ED50 was 30 micrograms, and the maximum depression of nociceptive activity amounted to about 70% of the control activity at a dose of 100 micrograms. Morphine, administered i.t. at a maximally effective dose (80 micrograms), inhibited the evoked nociceptive activity by only up to 55% of the control activity. An i.t. co-injection of reactive red 2 (100 micrograms) and morphine (80 micrograms) caused a maximum reduction of the evoked thalamic activity by up to 85% of the control activity, thus, exceeding significantly the effect elicited by either drug alone. Similarly, i.t. co-injection of almost equipotent dosages of reactive red 2 (30 micrograms) and morphine (30 micrograms) caused a maximum reduction of the evoked activity by up to 72% of the control activity, which again exceeded significantly the effect of either drug alone. The results suggest that in rats reactive red 2 exerts antinociception by blockade of P2-purinoceptors in the spinal cord and, hence, support the idea that ATP may play an important role in spinal transmission of nociceptive signals. An activation of the spinal opioid system does not seem to contribute to the effect of reactive red 2 but might act additive or even synergistically with its antinociceptive action.

Animals↗
PubMed1996

Inhibition of neural ATP release by atrial natriuretic peptide in guinea-pig vas deferens.

Effects of atrial natriuretic peptide (ANP) and 8-bromoguanosine 3':5'-cyclic monophosphate (8-BrcGMP) on contraction, overflow of tritium (after [3H]noradrenaline labelling) and overflow of ATP elicited by electrical field stimulation (210 pulses/7 Hz) were studied in guinea-pig vas deferens. ANP (1-100 nM) slightly increased contractions, did not alter the overflow of tritium but decreased the overflow of ATP by up to 50%. 8-BrcGMP (3-300 mu M) markedly reduced contractions and ATP overflow with no effect on tritium overflow. Contractions were suppressed in the presence of prazosin plus suramin, and evoked overflow of ATP declined to 11%. ANP now gradually increased tritium overflow but again decreased the overflow of ATP. 8-BrcGMP did not change tritium overflow, as before, but increased ATP overflow. The results indicate that ANP inhibits neural release of ATP by a mechanism independent of guanylyl cyclase activation with no major effect on noradrenaline release.

Adenosine Triphosphate↗
PubMed1996

ATP release and its prejunctional modulation.

We studied some properties of the release of noradrenaline and ATP in isolated sympathetically innervated tissues. Release was elicited by electric stimulation and assessed as overflow of tritiated compounds (after labelling with [3H]noradrenaline) and enzymically measured ATP, respectively. Evans blue, which inhibits ectonucleotidases, greatly increased the evoked overflow of ATP, indicating that a major part of the ATP was metabolized after release. Much of the ATP was postjunctional in origin. The neural fraction was isolated when postjunctional release was suppressed by prazosin (alpha 1-adrenoceptor antagonist) and suramin (P2 purinoceptor antagonist). Comparison of neural ATP and [3H]-noradrenaline release showed that prostaglandin E2 reduced the release of both co-transmitters to a similar extent. Activation of prejunctional alpha 2-adrenoceptors, however, preferentially reduced the release of [3H]noradrenaline, and activation of prejunctional A1 purinoceptors reduced preferentially the release of ATP. Nucleotides such as ATP depressed the release of [3H]noradrenaline through two receptors: the well-known prejunctional A1 receptors and a separate group of prejunctional P2 purinoceptors. P2 antagonists increased the release of [3H]-noradrenaline. Overall, the results indicate differential storage, release and modulation of release of the two sympathetic co-transmitters. They also indicate that postganglionic sympathetic axons possess receptors for both co-transmitters: alpha 2 and P2 autoreceptors.

Adenosine Triphosphate↗