Oxytocin receptor antagonist reverses the blunting effect of pair bonding on fear learning in monogamous prairie voles.

Social relationships among spouses, family members, and friends are known to affect physical and mental health. In particular, long-lasting bonds between socio-sexual partners have profound effects on cognitive, social, emotional, and physical well-being. We have previously reported that pair bonding in monogamous prairie voles (Microtus ochrogaster) is prevented by a single prolonged stress (SPS) paradigm, which causes behavioral and endocrine symptoms resembling post-traumatic stress disorder (PTSD) patients in rats (Arai et al., 2016). Since fear memory function is crucial for anxiety-related disorders such as PTSD, we investigated the effects of pair bonding on fear learning in prairie voles. We applied an SPS paradigm to male prairie voles after the cohabitation with a male (cage-mate group) or female (pair-bonded group). The cage-mate group, but not the pair-bonded group, showed enhanced fear response in a contextual fear conditioning test following the SPS treatment. Immunohistochemical analyses revealed that cFos-positive cells in the central amygdala were increased in the pair-bonded group after the contextual fear conditioning test and that oxytocin immunoreactivity in the paraventricular nucleus of the hypothalamus was significantly higher in the pair-bonded group than the cage-mate group. This pair-bonding dependent blunting of fear memory response was confirmed by a passive avoidance test, another fear-based learning test. Interestingly, intracerebroventricular injection of an oxytocin receptor antagonist 30 min before the passive avoidance test blocked the blunting effect of pair bonding on fear learning. Thus, pair bonding between socio-sexual partners results in social buffering in the absence of the partner, blunting fear learning, which may be mediated by oxytocin signaling.

Involvement of the oxytocin system in the bed nucleus of the stria terminalis in the sex-specific regulation of social recognition.

Sex differences in the oxytocin (OT) system in the brain may explain why OT often regulates social behaviors in sex-specific ways. However, a link between sex differences in the OT system and sex-specific regulation of social behavior has not been tested. Here, we determined whether sex differences in the OT receptor (OTR) or in OT release in the posterior bed nucleus of the stria terminalis (pBNST) mediates sex-specific regulation of social recognition in rats. We recently showed that, compared to female rats, male rats have a three-fold higher OTR binding density in the pBNST, a sexually dimorphic area implicated in the regulation of social behaviors. We now demonstrate that OTR antagonist (5 ng/0.5 µl/side) administration into the pBNST impairs social recognition in both sexes, while OT (100 pg/0.5 µl/side) administration into the pBNST prolongs the duration of social recognition in males only. These effects seem specific to social recognition, as neither treatment altered total social investigation time in either sex. Moreover, baseline OT release in the pBNST, as measured with in vivo microdialysis, did not differ between the sexes. However, males showed higher OT release in the pBNST during social recognition compared to females. These findings suggest a sex-specific role of the OT system in the pBNST in the regulation of social recognition.

Effect of vaginal infiltration with ornipressin or saline on intraoperative blood loss during vaginal prolapse surgery: a randomised controlled trial.

INTRODUCTION AND HYPOTHESIS: Hydrodissection incorporating different types of vasoconstrictors is commonly used in vaginal prolapse surgery. There is little evidence as to whether it adds clinical value or whether it exposes the patient to unnecessary risk. The aim of this study was to compare the effect of a vasoconstrictor compared with saline alone on operative blood loss and cardiovascular parameters in a randomised clinical trial setting. METHODS: Patients undergoing vaginal prolapse surgery were randomised to an ornipressin (Por-8, Ferring) solution or saline alone for hydrodissection. The surgeon and patient were blinded to the solution used. Operative blood loss was accurately quantified and blood pressure and pulse readings recorded Pre, intra- and postoperatively. RESULTS: Eighty women were randomised. There was a statistically significant difference in the median blood loss: 35 ml (1-209 ml) in the ornipressin group compared with 81 ml (2-328 ml) in the saline group, p = 0.03. There was no statistically significant difference in the median pre and postoperative blood pressure or pulse rate between groups. CONCLUSIONS: The use of a vasoconstrictor (ornipressin) resulted in a statistically significant decrease in operative blood loss during vaginal prolapse surgery. This occurred without any significant changes in measured cardiovascular parameters.

Oxytocin mediates rodent social memory within the lateral septum and the medial amygdala depending on the relevance of the social stimulus: male juvenile versus female adult conspecifics.

Brain oxytocin (OXT) plays an important role in short-term social memory in laboratory rodents. Here we monitored local release of OXT and its functional involvement in the maintenance and retrieval of social memory during the social discrimination test. We further assessed, if the local effects of OXT within the medial amygdala (MeA) and lateral septum (LS) on social discrimination abilities were dependent on the biological relevance of the social stimulus, thus comparing male juvenile versus adult female conspecifics. OXT release was increased in the LS of male rats during the retrieval, but not during the acquisition or maintenance, of social memory for male juvenile stimuli. Blockade of OXT activity by intracerebroventricular (ICV) administration of a specific OXT receptor antagonist (OXTR-A, rats: 0.75 µg/5 µl, mice: 2 µg/2 µl) immediately after acquisition of social memory impaired the maintenance of social memory, and consequently discrimination abilities during retrieval of social memory. In contrast, ICV OXTR-A was without effect when administered 20 min prior to retrieval of social memory in both species. Non-social memory measured in the object discrimination test was not affected by ICV OXTR-A in male mice, indicating that brain OXT is mainly required for memory formation in a social context. The biological relevance of the social stimulus seems to importantly determine social memory abilities, as male rats recognized a previously encountered female adult stimulus for at least 2h (versus 60 min for male juveniles), with a region-dependent contribution of endogenous OXT; while bilateral administration of OXTR-A into the MeA (0.1 µg/1 µl) impaired social memory for adult females only, administration of OXTR-A into the LS via retrodialysis (10 µg/ml, 1.0 µl/min) impaired social memory for both male juveniles and female adults. Overall, these results indicate that brain OXT is a critical mediator of social memory in male rodents and that, depending on the biological relevance of the social stimulus, distinct brain regions are recruited to mediate its effects.

Role of spinal V1a receptors in regulation of arterial pressure during acute and chronic osmotic stress.

Vasopressinergic neurons in the paraventricular nucleus project to areas in the spinal cord from which sympathetic nerves originate. This pathway is hypothesized to be involved in the regulation of mean arterial pressure (MAP), particularly under various conditions of osmotic stress. Several studies measuring sympathetic nerve activity support this hypothesis. However, the evidence that spinal vasopressin influences MAP under physiological or pathophysiological conditions in conscious animals is limited. The purpose of this study was to investigate, in conscious rats, if the increases in MAP during acute or chronic osmotic stimuli are due to activation of spinal vasopressin (V1a) receptors. Three conditions of osmotic stress were examined: acute intravenous hypertonic saline, 24- and 48-h water deprivation, and 4 wk of DOCA-salt treatment. Rats were chronically instrumented with an indwelling catheter for intrathecal injections and a radiotelemeter to measure MAP. In normotensive rats, intrathecal vasopressin and V1a agonist increased MAP, heart rate, and motor activity; these responses were blocked by pretreatment with an intrathecal V1a receptor antagonist. However, when the intrathecal V1a antagonist was given during the three conditions of osmotic stress to investigate the role of "endogenous" vasopressin, the antagonist had no effect on MAP, heart rate, or motor activity. Contrary to the hypothesis suggested by previous studies, these findings indicate that spinal V1a receptors are not required for elevations of MAP under conditions of acute or chronic osmotic stress in conscious rats.

Mesotocin and nonapeptide receptors promote estrildid flocking behavior.

Proximate neural mechanisms that influence preferences for groups of a given size are almost wholly unknown. In the highly gregarious zebra finch (Estrildidae: Taeniopygia guttata), blockade of nonapeptide receptors by an oxytocin (OT) antagonist significantly reduced time spent with large groups and familiar social partners independent of time spent in social contact. Opposing effects were produced by central infusions of mesotocin (MT, avian homolog of OT). Most drug effects appeared to be female-specific. Across five estrildid finch species, species-typical group size correlates with nonapeptide receptor distributions in the lateral septum, and sociality in female zebra finches was reduced by OT antagonist infusions into the septum but not a control area. We propose that titration of sociality by MT represents a phylogenetically deep framework for the evolution of OT's female-specific roles in pair bonding and maternal functions.

Antagonism of oxytocin prevents suckling- and estradiol-induced, but not progesterone-induced, secretion of prolactin.

In female rats, estradiol (E(2)) and suckling induce prolactin (PRL) secretion. This involves inhibition of hypothalamic dopaminergic tone and stimulation by a PRL-releasing hormone, possibly oxytocin (OT). Infusing an OT antagonist (OTA) i.v., we evaluated the role of OT on suckling- and E(2)-induced PRL secretion. Three days after parturition at 0900 h, lactating dams were fitted with 24-h osmotic minipumps filled with saline or OTA. On d 5 of lactation, pups were separated from their dams for 6 h. Immediately or 20 min after the resumption of suckling, dam trunk blood was collected. Also, ovariectomized (OVX) rats were treated with E(2) (OVE) and OTA at 1000 h on d 1. Blood samples were obtained from 1300 to 2100 h on d 2 for PRL measurements. Additionally, OVX rats were evaluated on d 2 after receiving progesterone (P(4)). OTA blocked suckling and E(2)-induced release of PRL but not that induced by E(2)+P(4). Pups from treated dams failed to gain weight when allowed to nurse for 20 min on d 5 but gained more than 7 g when nursed on d 7 of lactation, indicating that the OTA was active 48 h later. Western blot analysis showed that E(2) treatment increased OT receptors in the anterior pituitary when compared with OVX animals. No further increase was observed in response to the P(4), suggesting that the enhancing effect of P(4) on E(2)-induced PRL release may act through mechanisms independent of OT. These data demonstrate the role of OT in the control of suckling and steroid-induced PRL secretion.

Synergistic interaction of endogenous platelet-activating factor and vasopressin in generating angina in rats.

We examined the involvement of endogenous vasopressin and platelet-activating factor (PAF) in the pathogenesis of two types of experimental angina in urethane-anaesthetised male Wistar rats. In the first model, epinephrine (10 microg kg(-1)) was injected into the tail vein, followed at the development of the maximum blood pressure response, i.e., 30 s later, by phentolamine (15 mg kg(-1)). In the second model, the vasopressin V1 receptor agonist ornithine-vasopressin (ornipressin; 0.5 IU kg(-1), i.v.) was administered. The heart rate, mean arterial blood pressure and surface electrocardiogram (ECG, standard lead II) were registered simultaneously. As a measure of myocardial ischaemia, at 1 min after phentolamine or ornipressin administration, we found significant ST-segment depression, lasting for more than 10 or 5 min, respectively. Pretreatment (15 min, s.c.) with the vasopressin V1 receptor antagonist Mca1,Tyr(Me)2AVP (the Manning peptide; 0.02-0.2 microg kg(-1)) or the platelet-activating factor receptor antagonist ginkgolide B (BN 52021; 0.25-2.5 mg kg(-1)) alone caused a dose-dependent reduction of the ST-segment depression. Concurrent administration of the two antagonists in their threshold doses (0.02 microg kg(-1) and 0.25 mg kg(-1)) also attenuated the ST-segment depression in both models. Neither antagonist affected the blood pressure or heart rate changes throughout the studies. Our results suggest that endogenous vasopressin and platelet-activating factor interact synergistically in provoking myocardial ischaemia in vivo in experimental angina in the rat.

Hemodynamic effects of endobronchial application of ornipressin versus terlipressin.

BACKGROUND: Ornipressin and terlipressin, two ADH-derivates, are instilled endobronchially for bronchoscopy- related bleeding without sufficient evidence of efficacy, nor safety. OBJECTIVES: To compare the immediate hemodynamic effects of ornipressin and terlipressin used for procedure-related bleeding during flexible bronchoscopy. METHODS: This retrospective study included patients referred for flexible bronchoscopy who needed administration of ornipressin (15 patients) or terlipressin (15 patients) for procedure-related bleeding. Endobronchial ornipressin (5 IU) or terlipressin (0.5 mg) was administered through the bronchoscope when bleeding persisted for 2 min of continuous suction, or when bleeding was considered increasing in time or major. Hemodynamic data were collected before, during and after administration of either drug. RESULTS: Biopsy-associated hemoptysis requiring medical treatment occurred in 110 (4.2%) of 2,592 bronchoscopies. After administration of ornipressin, no significant change in heart rate or blood pressure was observed. Following terlipressin instillation, heart rate increased from 93 +/- 17 to 101 +/- 22 b.p.m. (p = 0.03), and blood pressure decreased from 107 +/- 14 to 101 +/- 17 mm Hg (p = 0.04). Oxygen saturation under supplemental nasal oxygen was not different in both groups. None of the 110 patients died from bronchoscopy-related hemoptysis or needed further intervention to stop bleeding or prolonged monitoring because of hemodynamic instability. CONCLUSIONS: In contrast to ornipressin, administration of terlipressin is associated with significant changes in heart rate and blood pressure. However, these changes are of minor clinical importance, and terlipressin can be safely given for bronchoscopy-associated bleeding.

Dilute ornitin vasopressin and a myoma drill for laparoscopic myomectomy.

To improve enucleation of uterine myomas, we designed a reusable 5-mm laparoscopic drill with a distal forked pin and locking system. Because the device is jointed, it can apply traction not only along its own axis, but also along planes, depending on its bending radius. We compared enucleation time for myomas 5 to 8 cm in size before and after introduction of the drill. The last 23 procedures performed with this instrument were easier, with a reduction in operating time of about 28.5% for the enucleation part of the procedure (p <0.001). (J Am Assoc Gynecol Laparosc 6(2):189-193, 1999)

Effects of the vasopressin V1 agonist [Phe2,Ile3,Orn8]] vasopressin on regional kidney perfusion and renal excretory function in anesthetized rabbits.

To test whether renal V1-receptors selectively influence blood flow in the renal medulla, we compared the effects of infusion of [Phe2,Ile3,Orn8]vasopressin (3-30 ng/kg/min) by the intravenous, renal arterial, and renal medullary interstitial routes in anesthetized rabbits. Intravenous [Phe2,Ile3,Orn8]vasopressin (30 ng/kg/min) reduced renal medullary perfusion (MBF) by 36 +/- 5% but did not significantly affect cortical perfusion (CBF). MBF was also reduced with the renal arterial (35 +/- 5%) and renal medullary interstitial (40 +/- 7%) routes but, in contrast to the intravenous infusion, CBF was also reduced, by 21 +/- 3% and 15 +/- 3%, respectively. Urine flow and sodium excretion were increased by [Phe2,Ile3,Orn8]vasopressin, and with direct intrarenal administration, this effect was similar for both the infused (left) and noninfused (right) kidneys. After a 20-min renal medullary interstitial infusion of [3H]norepinephrine, radiolabel concentration was approximately fivefold greater in the left medulla than in the left cortex. We conclude that [Phe2,Ile3,Orn8]vasopressin acts on V1-receptors to alter regional kidney blood flow and tubular salt and water handling. The V1-receptors involved are almost certainly within the kidney itself, but given the contrasting effects of the different infusion routes on MBF and CBF, we cannot exclude the possibility that some of the observed effects of [Phe2,Ile3,Orn8]vasopressin are mediated by activation of extra-renal V1-receptors.

Effects of renal medullary infusion of a vasopressin V1 agonist on renal antihypertensive mechanisms in rabbits.

The factors responsible for the development of hypertension during chronic activation of intrarenal V1 receptors are unknown. We therefore tested whether medullary interstitial infusion of the selective V1-receptor agonist [Phe2,Ile3,Orn8]vasopressin (V1 agonist) influences renal antihypertensive mechanisms initiated by increased renal perfusion pressure (RPP). In intact anesthetized rabbits, the V1 agonist (10 ng . kg-1 . min-1) reduced medullary perfusion by 36 +/- 7%, whereas cortical perfusion was reduced by only 14 +/- 2%. An extracorporeal circuit was used to increase RPP in a stepwise manner from 65 to 85, 110, 130, and 160 mmHg for consecutive 20-min periods. Increased RPP reduced mean arterial pressure by 35 +/- 8% in vehicle-treated rabbits, but by only 10 +/- 3% in V1 agonist-treated rabbits. Simultaneously, pressure-diuresis-natriuresis was induced; urine flow and sodium excretion increased similarly in the two groups of rabbits, but hematocrit did not change. We suggest that the depressor response to increased RPP is mainly due to release of a putative renal medullary depressor hormone (RMDH). Suppression of the release and/or actions of RMDH may therefore contribute to the hypertensive effect of chronic V1 receptor activation.

Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion.

Hepatorenal syndrome is caused by a marked vasoconstriction of the renal circulation. It is suggested that the renal vasoconstriction is related to an overactivity of vasoconstrictor systems secondary to a vasodilation of the arterial circulation that causes a reduction in effective arterial blood volume. To test this hypothesis, 16 cirrhotic patients with hepatorenal syndrome were treated with a combination of ornipressin, a potent vasoconstrictor agent, and plasma volume expansion with albumin to improve effective arterial blood volume. The combined treatment was administered either for 3 or 15 days (8 patients each), and the effects on renal function, vasoactive systems, and systemic hemodynamics were assessed. The 3-day treatment with ornipressin and albumin was associated with a normalization of the overactivity of renin-angiotensin and sympathetic nervous systems, a marked increase in atrial-natriuretic peptide levels, and only a slight improvement in renal function. However, when ornipressin and albumin were administered for 15 days, a remarkable improvement in renal function was observed, with normalization of serum-creatinine concentration, a marked increase in renal plasma flow and glomerular filtration rate, and a persistent suppression in the activity of vasoconstrictor systems. However, 3 of 8 patients on 15-day therapy treatment had to be discontinued because of ischemic complications. In conclusion, the decrease in effective arterial blood volume and the activation of vasoconstrictor systems play a crucial role in the pathogenesis of hepatorenal syndrome. Although the prolonged administration of ornipressin combined with plasma volume expansion reverses hepatorenal syndrome, this treatment should be used with great caution in clinical practice because of the risk of ischemic complications.

Experimental studies of injection agents for peptic ulcer bleeding endoscopic control.

AIM: To evaluate haemostatic effectiveness and tissue effects of injected therapy agents used for peptic ulcer bleeding endoscopic control. METHODS: Bleeding gastric mucosa lesions were produced during operation in 11 heparinised dogs. Bleeding lesions were treated with injections of 1 ml of epinephrine (1:10000), ornipressin (0.2 IU/m]), 98% ethanol, 1% polidocanol, thrombin (1000 U/ml), or fibrin sealant. In another 18 dogs, gastric submucosal injections of tested agents were performed during operations. Dogs were killed 48 h after injections and tissue effects were studied. RESULTS: The agents tested had similar effectiveness in achieving initial control of experimental bleeding (chi2 = 1.43). Vasoconstrictors caused no tissue injury or thrombosis in vessels after 48 h. Ethanol produced mucosa and submucosa necrosis and thrombosis in vessels. Polidocanol caused mucosa necrosis, submucosa oedema and thrombosis in vessels. Thrombin tissue effects were mucosa oedema, submucosa thrombosis in vessels. Fibrin sealant caused agent insertion between mucosa and submucosa, but no tissue injury or thrombosis in vessels. CONCLUSIONS: Experiments did not show significant differences between investigated agents in achieving initial bleeding control. The investigated agents, according to the stomach tissue injury they caused in our experiment, would produce series: epinephrine = ornipressin < fibrin sealant < thrombin < polidocanol < ethanol, and according to their effect on vascular thrombosis: epinephrine = ornipressin = fibrin sealant < polidocanol < ethanol < thrombin.

[Successful conservative therapy of hepatorenal syndrome with vasopressin-1-receptor antagonist ornipressin]. / Erfolgreiche konservative Therapie des hepatorenalen Syndroms mit dem Vasopressin-l-Rezeptoragonisten Ornipressin.

A 47-year-old male patient with alcoholic cirrhosis Child-Pugh grade C was admitted to our center for evaluation of liver transplantation. Serum creatinine had increased from 1.6 to 4.3 mg/100 ml within the previous two weeks, creatinine clearance was 12 ml/min, and urinary sodium 12 mmol/24 h. The diagnosis of HRS type I was established. Diuretic treatment was discontinued. Following albumin infusion, central venous pressure was increased to above 10 cm H2O and dopamine (2 micrograms/kg/min) infusion was started. However, renal function did not improve. An i.v. infusion of ornipressin (POR8, Sandoz; 6 IU/h) was started and dopamine infusion continued. During a four-hour interval, urinary volume and sodium excretion doubled. Therefore treatment was continued for three weeks. After 22 days, renal function had normalized (creatinine 1.2 mg/100 ml, creatinine clearance 65 ml/min, urinary sodium 62 mmol/24 h) and diuretic therapy was resumed. No adverse effects were observed. Ornipressin/dopamine infusion was discontinued and renal function remained normal. Three weeks later, the patient underwent liver transplantation with normal renal function. Ornipressin infusion had no effect on circulating endothelin, but decreased the activation of the renin-aldosterone system and of the sympathetic activity. So far, no noninvasive therapy of hepatorenal syndrome has been established. This is the first report of successful medical treatment of HRS type I with a three-week infusion of the vasopressin-l-receptor agonist ornipressin.

Renal and neurohormonal changes following simultaneous administration of systemic vasoconstrictors and dopamine or prostacyclin in cirrhotic patients with hepatorenal syndrome.

BACKGROUND/AIMS: Intravenous ornipressin in cirrhotic patients with hepatorenal syndrome causes marked improvement of systemic hemodynamics and suppression of plasma renin and norepinephrine but only moderate improvement of renal function. This study was designed to investigate whether these beneficial effects could be enhanced by the simultaneous administration of dopamine. The renal effects of the i.v. infusion of norepinephrine plus prostacyclin in patients with hepatorenal syndrome were also assessed. METHODS: Renal plasma flow, glomerular filtration rate, free water clearance, sodium excretion and the plasma levels of renin and norepinephrine were measured in baseline conditions and during the administration of ornipressin (6 i.u./h) and ornipressin (6 i.u./h) plus dopamine (2 micrograms/kg.min) in nine patients with hepatorenal syndrome. Five additional patients with hepatorenal syndrome were studied prior to and following the administration of norepinephrine (0.45 +/- 0.1 microgram/kg.min) and norepinephrine (0.85 +/- 0.2 microgram/kg.min) plus prostacyclin (5 ng/kg.min). RESULTS: Despite a significant increase in arterial pressure and marked suppression of plasma renin activity during ornipressin and ornipressin plus dopamine administration, no significant improvement in renal function was observed. Norepinephrine and norepinephrine plus prostacyclin also failed to increase renal perfusion and glomerular filtration rate. CONCLUSIONS: The combined administration of systemic vasoconstrictors (ornipressin or norepinephrine) and vasodilators (dopamine or prostacyclin), at the doses used in the current study and for a short period of time, does not improve renal function in cirrhotic patients with hepatorenal syndrome. The current study does not confirm a potential role for ornipressin in the treatment of hepatorenal syndrome.

[The effect of nitroglycerin on ornipressin (POR 8)-induced systemic and cardiovascular circulatory changes. An animal experimental study]. / Untersuchungen zur Wirkung von Nitroglyzerin (TNG) auf die Ornipressin (POR 8)-induzierten systemischen und kardiovaskulären Kreislaufveränderungen. Eine tierexperimentelle Studie.

OBJECTIVE: Local infiltration of ornipressin (OR) is widely used to reduce intraoperative bleeding. However, OR can cause severe side effects including hypertension, deterioration of cardiac performance and coronary vasoconstriction. Suggestions for therapy of haemodynamic side effects of OR include the use of nitroglycerin (TNG). This experimental study was designed to investigate the influence of TNG on changes of systemic haemodynamics and coronary perfusion produced by i.v. administration of OR. METHODS: 16 anesthetized closed-chest mongrel dogs were studied. Anaesthesia was administered using N2O/O2 (FiO2: 0.33) and enflurane (1Vol%ET). Saline-filled catheters were used to measure intravascular pressures. Left ventricular pressure change (dP/dt) was monitored with a cathetertip manometer. Cardiac output (CO) was determined using thermodilution, myocardial blood flow (MBF) using a Pitot catheter. Baseline values were taken (control) followed by a bolus injection of 0.03 U/kg OR i.v. The dogs were randomly assigned to two groups. Group I (Gr.I) (n = 9) received OR only and group II (Gr.II) (n = 7) was treated by infusion of 4 mg/kg.min TNG 7 to 30 min after injection of OR. Haemodynamic and cardiovascular changes were measured for 60 min at fixed time intervals. RESULTS: In both groups (Gr.I; Gr.II) OR produced significant changes in systolic (APS) (+29%; +32%) and diastolic (APD) (+47%; +37%) aortic pressure, cardiac index (CI) (-33%; -33%), peripheral vascular resistance (TPR) (+116%); +104%), stroke volume index (SVI) (-23%; -34%), ejection fraction (EF) (-29%; -29% endsystolic volume (ESV) (+39%; +45%) and left ventricular enddiastolic pressure (LVEDP) (+50%; +66%). Myocardial blood flow (MBF) was reduced by 30% and 29% respectively and coronary vascular resistance (CVR) was increased (+97%; +84%). Coronary venous O2 saturation (SO2cor) decreased to 19% and 20% resulting in high AVDO2cor. As compared to Gr.I the administration of TNG resulted in significant decreases of APS, APD, TPR, ESV and LVEDP close to control values. However, administration of TNG did not effect MBF, CVR, SO2cor and AVDO2cor. CONCLUSION: Systemic haemodynamic effects of OR include hypertension due to peripheral vasoconstriction and impaired cardiac performance resulting in reduced cardiac output with low EF, high ESV and LVEDP. Concomitantly, OR produces coronary constriction with a distinct fall in MBF. Thus, myocardial oxygen balance is impaired. With TNG peripheral vascular effects of OR can be abolished but there is no effect of TNG on OR-induced reduction of coronary blood flow. Therefore, use of TNG for treatment of cardiovascular complications following the administration of OR must be considered with extreme caution.