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Biomedical subjects

H M Snow

Publications and source records attributed to H M Snow.

At least 19 recordsLinked to original sources
PubMed2006

Vagal postganglionic origin of vasoactive intestinal polypeptide (VIP) mediating the vagal tachycardia.

Our aim was to confirm the role of postganglionic vagal fibres and vasoactive intestinal polypeptide (VIP) in mediating the vagal tachycardia in anaesthetised dogs. Vagal postganglionic stimulation after atenolol (1 mg/kg) and hexamethonium (10 mg/kg) caused a bradycardia (40 beats/min, n = 2), after atropine (0.5 mg/kg i.v.) the resulting tachycardia (37 beats/min) was attenuated by VIP receptor antagonism with VIP (6-28) (100 mug i.c.) by approximately 50%. VIP release from vagal postganglionic fibres mediates the vagal tachycardia.

Adrenergic beta-Antagonists↗
PubMed2006

Differential inhibition by hyperglycaemia of shear stress- but not acetylcholine-mediated dilatation in the iliac artery of the anaesthetized pig.

Clinical hyperglycaemia affects vascular endothelial function, but the effect on shear stress-induced arterial dilatation has not yet been established. We hypothesized that hyperglycaemia would inhibit this response via impaired glycocalyx mechanotransduction. Experiments were carried out in the anaesthetized pig in which pressure, blood flow and diameter of the left iliac artery were measured at two sites: proximal (d1) and distal (d2). Infusion of glucose, sufficient to raise blood glucose to 16-30 mm along the whole length of the artery, attenuated the shear stress-dependent dilatation in both sections of the artery with preservation of the responses to acetylcholine. The distal site was then isolated using snares and the lumen exposed to blood containing 25-35 mm glucose for 20 min. In the control situation, after exposure of both sections to normoglycaemia (5.7 mm glucose), both sections of artery showed increases in diameter in response to shear stress and acetylcholine. Hyperglycaemia attenuated the shear stress-dependent dilatation in the distal section only (P < 0.25), but not the response to acetylcholine. It is concluded from these results that the hyperglycaemia-impaired dilatation is consistent with loss of mechanotransducing properties of the endothelial glycocalyx by hyperglycaemia. These findings offer a possible explanation for the increased incidence of vascular disease in diabetic patients.

Acetylcholine↗
PubMed2006

An investigation into the physiological relevance of the vagal tachycardia in the anaesthetized dog.

AIM: Our aim was primarily to assess whether or not a vagal tachycardia can be elicited in vivo without administration of atropine, and secondly to evaluate whether the dose of atropine, a muscarinic antagonist, determines the magnitude of the tachycardia. METHODS: Experiments were carried out in the presence of atenolol (2 mg kg(-1)). The vagal tachycardia requires high vagal activity which was induced by noradrenaline infusion (20 microg min(-1)). Two techniques were then used to elicit a tachycardia, vagal section and atropine administration. RESULTS: The increase in blood pressure caused heart rate to fall to 60 +/- 7 beats min(-1) (mean +/- SEM). When the vagi were sectioned (n = 5) heart rate increased by 9 +/- 2 beats min(-1) above the intrinsic rate which was 108 beats min(-1), this increase was not significant. In contrast atropine given (9-20 microg kg(-1)) (n = 5) during high vagal activity increased heart rate by 81 +/- 22 beats min(-1) above the intrinsic rate (P < 0.05). To assess if the dose of atropine affects the magnitude of the vagal tachycardia, the right vagus was stimulated electrically at increasing frequencies (2, 4, 8, 16, 32 Hz) before and after increasing doses of atropine (0.02, 0.05, 1 mg kg(-1)). This reduced the magnitude of the bradycardia; however, the magnitude of the vagal tachycardia was unaffected. CONCLUSION: The vagal tachycardia cannot be elicited without atropine suggesting that it does not play a significant physiological role.

Animals↗
PubMed2003

Effects of fenoldopam on renal blood flow and its function in a canine model of rhabdomyolysis.

BACKGROUND AND OBJECTIVE: Our hypothesis was that fenoldopam, a selective DA1 agonist, would protect against rhabdomyolysis-induced renal injury. METHODS: We studied the effects of intravenous fenoldopam (0.1-1.0 microg kg(-1) min(-1)) or saline on renal blood flow and function in 10 anaesthetized Labrador dogs in whom rhabdomyolysis and myoglobinuric acute renal failure had been induced by administration of glycerol 50% (10mL kg(-1)) intramuscularly. Haemodynamic measurements including renal blood flow and derived parameters of renal function including creatinine clearance were recorded before and for the 30 min following glycerol injection, and during the 3 h following commencement of each infusion. Serum malondialdehyde concentrations were measured before and 15 min after glycerol intramuscularly, and 30 and 150 min after commencement of the infusion. RESULTS: In the fenoldopam group, creatinine clearance was less than placebo at 1 and 2 h after commencing the infusion (12.7 +/- 11.5 versus 31.3 +/- 9.9 mL min(-1), P = 0.04; 8.5 +/- 5.3 versus 20.1 +/- 7.4 mL min(-1), P = 0.03). A 140-fold increase in serum malondialdehyde concentration occurred in one dog (fenoldopam group). CONCLUSION: Fenoldopam increased the severity of the renal injury in this canine model of myoglobinuric acute renal failure.

Animals↗
PubMed2003

The efficacy of nicorandil, calcium chloride and nitroglycerin in treatment of ropivacaine-induced cardiotoxicity.

BACKGROUND AND OBJECTIVE: The amide-linked local anaesthetics, bupivacaine and ropivacaine, can cause depression of cardiac contractility and dysrhythmias. In a previous study, we observed decreased contractility and ST segment depression following ropivacaine administration in anaesthetized dogs. The efficacy of intravenous (i.v.) and intracoronary nicorandil (30 and 100 microg kg(-1)), i.v. nitroglycerin (glyceryl trinitrate) (5 microg kg(-1)) and calcium chloride (1, 2 and 4 mmol) in reversing the cardiotoxic effects of intracoronary ropivacaine were studied following the administration of intracoronary ropivacaine. METHODS: Six dogs were studied. The dogs were anaesthetized with i.v. pentobarbital (30 mg kg(-1)). A left-sided thoracotomy was performed and the left circumflex coronary was cannulated. For each dog, the dose of ropivacaine was identified, which produced measurable cardiotoxicity. In each case, ropivacaine was followed by one of the three resuscitation drugs. The effects of each resuscitation drug on ST segments and left ventricular contractility (dP/dt) produced by ropivacaine alone were compared with those produced by ropivacaine followed by each of the three resuscitation drugs using Fisher's exact test. RESULTS: The doses of ropivacaine required to produce depression of left ventricular dP/dt and ST segments ranged from 1 to 8 mg. Ropivacaine-induced depression of left ventricular contractility (dP/dt) was more rapidly and completely reversed by calcium chloride than by either nitroglycerin or nicorandil (P = 0.008). CONCLUSIONS: Calcium chloride may be effective in the treatment of inadvertent intravascular administration of amide local anaesthetic agents.

Amides↗
PubMed2002

The effect of tezosentan, a non-selective endothelin receptor antagonist, on shear stress-induced changes in arterial diameter of the anaesthetized dog.

The effects of changes in the mean (S(m)) and pulsatile (S(p)) components of arterial wall shear stress on arterial dilatation of the iliac artery of the anaesthetized dog were examined in the absence and presence of the endothelin receptor antagonist tezosentan (10 mg kg(-1) I.V.; Ro 61-0612; [5-isopropyl-pyridine-2-sulphonic acid 6-(2-hydroxy-ethoxy)-5-(2-methoxy-phenoxy)-2-(2-1H-tetrazol-5-yl-pyridin-4-yl)-pyrimidin-4-ylamide]). Changes in shear stress were brought about by varying local peripheral resistance and stroke volume using a distal infusion of acetylcholine and stimulation of the left ansa subclavia. An increase in S(m) from 1.81 +/- 0.3 to 7.29 +/- 0.7 N m(-2) (means +/- S.E.M.) before tezosentan caused an endothelium-dependent arterial dilatation which was unaffected by administration of tezosentan for a similar increase in S(m) from 1.34 +/- 0.6 to 5.76 +/- 1.4 N m(-2) (means +/- S.E.M.). In contrast, increasing the S(p) from 7.1 +/- 0.8 to a maximum of 11.5 +/- 1.1 N m(-2) (means +/- S.E.M.) before tezosentan reduced arterial diameter significantly. Importantly, after administration of tezosentan subsequent increases in S(p) caused arterial dilatation for the same increase in S(p) achieved prior to tezosentan, increasing from a baseline of 4.23 +/- 0.4 to a maximum of 9.03 +/- 0.9 N m(-2) (means +/- S.E.M.; P < 0.001). In conclusion, the results of this study provide the first in vivo evidence that pulsatile shear stress is a stimulus for the release of endothelin from the vascular endothelium.

Animals↗
PubMed2002

Reverse arterial wall shear stress causes nitric oxide-dependent vasodilatation in the anaesthetised dog.

The effects of a maintained increase in mean arterial wall shear stress (SS(m)) caused by blood flow in the normal and reverse direction on dilatation of the iliac artery were examined in the anaesthetised dog. Blood flow in the left iliac artery was varied in both the forwards and reverse directions by a perfusion pump connecting the right and left femoral arteries. An increase in blood flow, and therefore SS(m) in either direction, caused an increase in arterial diameter. However, an increase in forwards SS(m) (control 4.1+/-0.11 mm) caused a significantly greater change in arterial diameter than an equivalent increase in the reverse direction (control 4.3+/-0.08), 0.198+/-0.02 mm vs. 0.132+/-0.02 mm (mean+/-SEM) respectively, for the same increase in SS(m) (3.23 N/m(2)). The increase in arterial diameter in response to an increase in forwards or reverse SS(m) was attenuated by L-NAME (80 mg/kg i.v.), indicating that the arterial dilatation was mediated by nitric oxide (NO). These findings confirm that endothelial NO release is dependent on the steady-state SS(m) and that the response occurs irrespective of the direction in which this force is applied, but is attenuated in the reverse direction.

Animals↗
PubMed2002

Nitric oxide facilitates vagal control of heart rate via actions in the cardiac parasympathetic ganglia of the anaesthetised dog.

The effects of neuronal inhibition of nitric oxide (NO) production on the bradycardia resulting from stimulation of preganglionic and postganglionic parasympathetic fibres were investigated in an anaesthetised dog preparation following transection of the cervical vagi and in the presence of a beta-adrenoreceptor antagonist. Injection of 1-(2-trifluoromethylphenyl) imidazole (TRIM), an inhibitor of neuronally released NO, into the sinus node artery reduced the bradycardia evoked by right cervical vagal stimulation. In contrast, when the response to preganglionic stimulation had been abolished by hexamethonium (10 mg kg(-1)), the bradycardia following stimulation of postganglionic parasympathetic fibres on the atrial epicardium was unaffected by TRIM. First, these results confirm the facilitatory actions of neuronally released NO on vagal heart responses in the dog. Second, they indicate that this modulatory and facilitatory role of NO is likely to be exerted at vagal preganglionic-postganglionic synaptic mechanisms in the cardiac parasympathetic ganglia and not at the postganglionic-sinoatrial node synapse.

Anesthesia↗
PubMed2002

An evaluation of the efficacy of vasoactive intestinal polypeptide antagonists in vivo in the anaesthetized dog.

The effectiveness of competitive peptide vasoactive intestinal polypeptide (VIP) receptor antagonists was evaluated on heart rate in the anaesthetized dog. Two specific antagonists, VIP (6-28) and [D-p-Cl-Phe(6), Leu(17)]-VIP, and a nonspecific antagonist, pituitary adenylate cyclase activating peptide fragment (6-27) (PACAP), were studied. VIP (6-28) and [D-p-Cl-Phe(6), Leu(17)]-VIP (100 microg i.c.) increased the heart rate, whereas PACAP (100 microg i.c.) reduced the baseline heart rate. All three shifted the VIP dose-response curve to the right by two- to threefold for 30 min. In conclusion, PACAP, VIP (6-28), and [D-p-Cl-Phe(6), Leu(17)]-VIP have a direct effect on the heart rate, are equally effective, and the effects last approximately 30 min in vivo.

Animals↗
PubMed2001

Characteristics of arterial wall shear stress which cause endothelium-dependent vasodilatation in the anaesthetized dog.

1. The effects of changes in the mean and amplitude of arterial wall shear stress on endothelium-dependent arterial dilatation of the iliac artery of the anaesthetized dog were examined. 2. Changes in the mean and amplitude of blood flow and wall shear stress were brought about by varying local peripheral resistance and stroke volume using a distal infusion of acetylcholine and the stimulation of the left ansa subclavia. Changes in the diameter of a segment of the iliac artery with the endothelium intact, relative to a segment with no endothelium, were used as an index of the release of nitric oxide. 3. The increase in mean blood flow was from 84 +/- 12 to 527 +/- 53 ml min-1 and in amplitude was from 365 +/- 18 to 695 +/- 38 ml min-1 (means +/- S.E.M.). The increase in mean wall shear stress was from 1.78 +/- 0.30 to 7.66 +/- 1.01 N m-2 and in amplitude was from 7.37 +/- 0.46 to 13.9 +/- 2.00 N m-2 (means +/- S.E.M.). 4. Increases in mean shear stress caused an increase in the diameter only of the section of artery with endothelium; the slope of the relationship was 0.064 +/- 0.006 mm N-1 m2 (mean +/- S.E.M., P < 0.001); changes in the amplitude of shear stress did not cause an increase in diameter. Changes in both the mean and amplitude of shear stress had no significant effect on the diameter of the section of artery with no endothelium. 5. These findings coupled with the known anti-atheroma effects of nitric oxide and the effect of shear stress on cell adhesion and platelet aggregation offer a possible explanation for the disposition of atheroma in those parts of the arterial system which have low mean and high amplitude of wall shear stress.

Acetylcholine↗
PubMed2001

Effects of prophylactic fenoldopam infusion on renal blood flow and renal tubular function during acute hypovolemia in anesthetized dogs.

OBJECTIVE: It was hypothesized that fenoldopam mesylate, a selective dopamine agonist, may preserve renal perfusion and decrease tubular oxygen consumption during states of hypoperfusion, such as hypovolemic shock. The objective of this study was to quantify the effects of fenoldopam (0.1 microg x kg(-1) x min(-1)) on renal blood flow, urine output, creatinine clearance, and sodium clearance in pentobarbital anesthetized dogs that had undergone partial exsanguination to acutely decrease cardiac output. DESIGN: Prospective, randomized, controlled experiment. SETTING: University-based animal laboratory and research unit. SUBJECTS: Eight female beagle dogs. INTERVENTIONS: Arterial blood pressure, heart rate, cardiac output, renal blood flow, urine output, creatinine clearance, and fractional excretion of sodium were measured and calculated at four times: a) before infusion of fenoldopam or normal saline; b) during infusion of fenoldopam or normal saline (1 hr); c) during a 90-min period of hypovolemia (induced by acute partial exsanguination), with concurrent infusion of fenoldopam or normal saline; and d) during a 1-hr period after retransfusing the dogs. MEASUREMENTS AND MAIN RESULTS: Administration of fenoldopam (0.1 microg x kg(-1) x min(-1)) was not associated with hemodynamic instability. Renal blood flow and urine output decreased significantly from baseline (p <.01) during the hypovolemic period in the placebo group (72 +/- 20 to 47 +/- 6 mL/min and 0.26 +/- 0.15 to 0.08 +/- 0.05 mL/min, respectively) but not in the fenoldopam group (75 +/- 14 to 73 +/- 17 mL/min and 0.3 +/- 0.19 to 0.14 +/- 0.05 mL/min, respectively). Creatinine clearance and fractional excretion of sodium decreased significantly from baseline (p <.01) in the placebo group during the hypovolemic period (3.0 +/- 0.4 to 1.8 +/- 0.8 mL x kg(-1) x min(-1) and 1.7% +/- 0.9% to 0.4% +/- 0.2%, respectively) but not in the dogs that received fenoldopam (3.0 +/- 1.0 to 2.9 +/- 0.5 mL x kg(-1) x min(-1) and 1.9% +/- 1.1% to 1.7% +/- 2.7%, respectively). CONCLUSIONS: Fenoldopam ablated the tubular prerenal response to profound hypovolemia and maintained renal blood flow, glomerular filtration rate, and natriuresis without causing hypotension. This suggests that fenoldopam may have a renoprotective effect in acute ischemic injury.

Acute Kidney Injury↗
PubMed2001

Inhibition of neuronal nitric oxide reduces heart rate variability in the anaesthetised dog.

In the vagally intact anaesthetised dog, we have investigated the role of nitric oxide (NO) on a normal sinus arrhythmia using an inhibitor of neuronally released NO, 1-(2-trifluoromethylphenyl) imidazole (TRIM). The mean and S.D. of the R-R interval was used to describe mean heart rate and heart rate variability, respectively. TRIM (0.8 mg I.C.) injected into the sinus node artery increased the mean heart rate slightly but reduced heart rate variability 3-fold from a control of 790 +/- 124 ms (mean +/- S.D.; n = 5) to 666 +/- 36 ms (P < 0.01 Student's paired t test, n = 5). These results suggest that neuronally released NO may have a vagal facilitatory role in the maintenance of sinus arrhythmia in the normal heart.

Acetylcholine↗
PubMed2000

The effects of fenoldopam on renal blood flow and tubular function during aortic cross-clamping in anaesthetized dogs.

Postoperative renal impairment is a recognized complication of infrarenal aortic cross-clamping. Fenoldopam, a selective dopamine agonist, may increase renal blood flow and decrease tubular oxygen consumption. The objective of this study was to quantify the effects of fenoldopam (0.1 microg kg-1 min-1) on renal blood flow and renal tubular function in anaesthetized dogs that have undergone aortic cross clamping. Eight labrador dogs were selected to receive either saline or fenoldopam (0.1 microg kg-1 min-1) intravenously. Arterial pressure, heart rate, renal blood flow, urinary output, fractional excretion of sodium, creatinine clearance and lithium clearance were measured (a) prior to infusions of saline or fenoldopam (b) 1 h after commencing the infusion (c) during a 90-min period of infrarenal aortic cross-clamping with concurrent infusion of fenoldopam or saline and (d) for 1 h after simultaneous aortic declamping and discontinuation of the infusions. There was no haemodynamic instability upon commencing the infusion of fenoldopam (0.1 microg kg-1 min-1). Creatinine clearance (2.03 +/- 0.5-2.45 +/- 0.3 mL min-1 kg-1 (mean +/- SD)), urine output (0.23 +/- 0.16-0.35 +/- 0.23 mL min-1 (mean +/- SD)), and fractional excretion of sodium (0.7 +/- 0.52-1.3 +/- 0.73% (mean +/- SD)) increased (P < 0.05), following commencement of the fenoldopam infusion. Fractional excretion of sodium (1.2 +/- 0.7% (mean +/- SD)) and urine output (0. 36 +/- 0.21 mL min-1 (mean +/- SD)) were maintained during the aortic cross-clamp period (P < 0.05). Renal blood flow increased when the fenoldopam infusion was commenced (145 +/- 43.3-161 +/- 39. 2 mL min-1 (mean +/- SD)) and remained greater than baseline during the aortic cross-clamping period (152 +/- 44 mL min-1 (mean +/- SD)), although these increases did not reach statistical significance. The most striking abnormalities observed by electron microscopy were marked disruption of the microvillus brush border in proximal tubules, vacuolation and separation of epithelial cells on basolateral infolds. The changes were similar in the two groups. In conclusion fenoldopam (0.1 microg kg-1 min-1) may have renoprotective effects which persist during infrarenal aortic cross clamping.

Anesthesia, General↗
PubMed2000

Effects of respiratory and metabolic pH changes and hypoxia on ropivacaine-induced cardiotoxicity in dogs.

We have studied the effects of acute changes in acid-base status and hypoxia on the cardiotoxic effects of intracoronary injection of ropivacaine in anaesthetized dogs. The effects of intracoronary ropivacaine were compared when ropivacaine was administered during eucapnia and during each of another nine states in random order: hypocapnia, hypercapnia, hypoxia, metabolic alkalosis, metabolic acidosis, combined metabolic acidosis and hypocapnia, combined metabolic alkalosis and hypercapnia, combined hypoxia and hypercapnia, and combined metabolic acidosis and hypoxia. Hypocapnic alkalosis consistently reduced the cardiotoxic effects of intracoronary ropivacaine (P < 0.01). Our findings indicate that induction of hypocapnic alkalosis may provide a useful adjunct to standard resuscitative measure after inadvertent administration of amide local anaesthetic agents.

Acid-Base Imbalance↗
PubMed1994

The relationship between blood flow and diameter in the iliac artery of the anaesthetized dog: the role of endothelium-derived relaxing factor and shear stress.

The quantitative relationship between, increase in blood flow and arterial diameter was determined in an anaesthetized dog preparation (pentobarbitone, induction 30 mg kg-1 i.v., maintenance 3 mg kg-1 i.v. every 30 min). Changes in external iliac artery diameter were measured using piezoelectric ultrasound transducers capable of measuring diameters within the range of 2-20 mm with a resolution of +/- 0.005 mm. The diameter of the artery was measured at two sites, at one of which the endothelium was damaged using a balloon angioplasty catheter. Increases in blood flow were brought about by a combination of vasodilatation and cardiac stimulation (intra-arterial administration of acetylcholine, downstream to the sites of diameter measurement, and electrical stimulation of the left ansa subclavia), thereby preventing large changes in blood pressure. The effects of both transient and maintained increases in blood flow on mean arterial diameter in the section of artery with intact endothelium were measured. Transient increases in mean flow from 147 +/- 0.21 to 611 +/- 80.0 ml min-1 caused increases in diameter of 0.12 +/- 0.02 mm from a control of 5.42 +/- 0.19 mm. The mean delay between maximum flow and maximum diameter was 24.51 +/- 1.1 s and the half-time for the return to control diameter was 82.0 +/- 9.6 s, compared with 12.1 +/- 1.5 s for the return to control flow. Maintained (3-4 min) increases in mean blood flow (from 104.7 +/- 15.1 to 694.7 +/- 135.1 ml min-1) produced larger increases in diameter of 0.48 +/- 0.30 mm from a control diameter of 4.89 +/- 0.12 mm. These changes in diameter were abolished by N omega-nitro-L-arginine methyl ester (L-NAME. 10-100 mg kg-1 i.v.). In the section of artery with damaged endothelium, changes in diameter were relatively small and associated with small changes in blood pressure. This effect of a nearly 7-fold increase in flow on arterial diameter is dependent upon the integrity of the endothelium and the release of endothelium-derived relaxing factor and causes a 29% reduction in calculated boundary wall shear stress.

Acetylcholine↗
PubMed1993

Redirection of arachidonic acid metabolism by ICI D1542: effects on thrombus formation in the coronary artery of the anaesthetized dog.

1. The effects of simultaneous redirection of arachidonic acid metabolism, by inhibition of thromboxane A2 (TXA2) synthase and blockade of the platelet thromboxane A2 receptor (TP-receptor), was examined on the rate of thrombus formation in a stenosed coronary artery with damaged endothelium in an anaesthetized dog. 2. Redirection of arachidonic acid metabolism was achieved by intravenous doses of ICI D1542, a selective and potent inhibitor of TXA2 synthase and the TP-receptor. 3. Redirection of arachidonic acid metabolism was demonstrated in whole blood, stimulated ex vivo by collagen. The ED50 for inhibition of TXB2 production was 7.1 micrograms kg-1, i.v.; there were corresponding increases in the production of the eicosanoids prostaglandin D2 (PGD2), PGE2 and PGF2 alpha. 4. Thrombus formation was inhibited by D1542 (ED50 0.55 micrograms kg-1, i.v.), but could be restarted by an intravenous infusion of adrenaline (0.2-38 micrograms kg-1 min-1, i.v.). In the presence of the maximum effective dose of D1542 (1 mg kg-1, i.v.) a 190 fold increase in the infusion rate of adrenaline was required to restore thrombus formation. 5. In the presence of D1542, removal of endoperoxide metabolites by inhibition of cyclo-oxygenase with aspirin (5 mg kg-1, i.v.) caused thrombus formation to restart, indicating the ability of the endoperoxide metabolites to inhibit thrombus formation in vivo. 6. These results indicate that, in the stenosed and damaged coronary artery of the dog, redirection of arachidonic acid metabolism by D1542 is more effective at preventing thrombus formation than inhibition of cyclo-oxygenase by aspirin.

Anesthesia↗
PubMed1993

Interaction between the effects of 5-hydroxytryptamine and adrenaline on the growth of platelet thrombi in the coronary artery of the anaesthetized dog.

1. The interaction between adrenaline and 5-hydroxytryptamine (5-HT) has been quantitated on the rate of thrombus formation, in the stenosed coronary artery with damaged endothelium of the anaesthetized dog. 2. Changes in the plasma concentration of adrenaline were produced by varying the rate of an intravenous infusion of adrenaline and in the effects of 5-HT, by intravenous injections of the selective 5-HT2 receptor antagonist, ICI 170809. 3. Increases in the plasma concentration of adrenaline, which did not cause significant changes in blood pressure and heart rate, increased the rate of thrombus formation. 4. Antagonism of the 5-HT2 receptor by ICI 170809, in the absence of an infusion of adrenaline, abolished thrombus formation (mean ED50 0.41 microgram kg-1, i.v.). 5. The effects of adrenaline were non-competitively antagonized by ICI 170809; maximum effects were obtained in the dose-range 50-200 micrograms kg-1, i.v., when the mean dose-ratio increase in adrenaline required to restore equivalent rates of thrombus formation was 39 fold. 6. These results are consistent with a synergism between adrenaline and 5-HT and emphasize the importance of both on thrombus formation.

Anesthesia↗