Wavelet-based estimation of the hemodynamic responses in diffuse optical imaging

Diffuse optical imaging uses light to provide a surrogate measure of neuronal activation through the hemodynamic responses. The relative low absorption of near-infrared light enables measurements of hemoglobin changes at depths reaching the first centimeter of the cortex. The rapid rate of acquisition and the access to both oxy and deoxy-hemoglobin leads to new challenges when trying to uncouple physiology from the signal of interest. In particular, recent work provided evidence of the presence of a 1/f noise structure in optical signals and showed that a general linear model based on wavelets can be used to decorrelate the structured noise and provide a superior estimator of response amplitude when compared with conventional techniques. In this work the wavelet techniques are extended to recover the full temporal shape of the hemodynamic responses. A comparison with other models is provided as well as a case study on finger-tapping data.     

Development of BOLD signal hemodynamic responses in the human brain

In the rodent brain the hemodynamic response to a brief external stimulus changes significantly during development. Analogous changes in human infants would complicate the determination and use of the hemodynamic response function (HRF) for functional magnetic resonance imaging (fMRI) in developing populations. We aimed to characterize HRF in human infants before and after the normal time of birth using rapid sampling of the Blood Oxygen Level Dependent (BOLD) signal. A somatosensory stimulus and an event related experimental design were used to collect data from 10 healthy adults, 15 sedated infants at term corrected post menstrual age (PMA) (median 41+1weeks), and 10 preterm infants (median PMA 34+4weeks). A positive amplitude HRF waveform was identified across all subject groups, with a systematic maturational trend in terms of decreasing time-to-peak and increasing positive peak amplitude associated with increasing age. Application of the age-appropriate HRF models to fMRI data significantly improved the precision of the fMRI analysis. These findings support the notion of a structured development in the brain's response to stimuli across the last trimester of gestation and beyond.     

Plasma catecholamine and hemodynamic responses during isoproterenol infusions in humans

We infused isoproterenol (ISO) intravenously into 23 subjects (3.5, 7, 14, and 35 ng/kg/min for 20 minutes at each dose) and measured venous plasma concentrations of ISO and the circulatory and plasma norepinephrine (NE) and epinephrine (E) responses. At the lowest dose, venous plasma ISO averaged 48 pg/ml and was associated with increased heart rate (9%; P less than 0.001), cardiac index (20%; P less than 0.001), and stroke volume (9%; P less than 0.02) and decreased total peripheral resistance index (-21%; P less than 0.001). Linear concentration-response relationships were observed between plasma ISO and cardiac index and between plasma ISO and heart rate. Plasma NE increased as a function of plasma ISO (mean increase 81% at 35 ng/kg/min), whereas plasma E was unchanged or decreased. The results indicate that circulatory effects of ISO are detectable in humans at plasma concentrations in the range of physiologic levels of E. Since ISO increases plasma NE, ISO may act presynaptically to enhance NE release from sympathetic nerve terminals and thereby stimulate alpha-adrenoceptors indirectly. ISO does not appear to stimulate secretion from the adrenal medulla or corelease of E with NE from sympathetic nerve endings.     

Endogenous angiotensin II facilitates sympathetically mediated hemodynamic responses in pithed rats

The influence of endogenous angiotensin II on the hemodynamic responses to electrical stimulation of the sympathetic outflow was assessed in pithed male normotensive Wistar rats fitted with aortic flow probes for continuous measurement of cardiac output (CO). The frequency-related increments (0.25-4.0 Hz) in blood pressure (BP) and total peripheral resistance (TPR) were significantly attenuated by treating animals with the angiotensin converting enzyme inhibitor captopril (5 mg/kg i.v.) or the angiotensin II receptor antagonist saralasin (10 micrograms/kg/min i.v.). However, the increments in CO and heart rate during neural stimulation were unaffected by blockade of the renin-angiotensin system. After captopril treatment, infusion of angiotensin II (40 ng/kg/min i.v.) to replace the loss of endogenous angiotensin II restored stimulation-induced TPR and BP responses toward precaptopril levels; CO and heart rate responses to stimulation were not altered. The hemodynamic responses to exogenous norepinephrine were affected by inhibition of the renin-angiotensin system with captopril and saralasin in a manner analogous to the neurally mediated responses. The results obtained with nerve stimulation and norepinephrine indicate that endogenous angiotensin II selectively interacted with sympathetic neural control of vascular resistance, whereas cardiac responsiveness to noradrenergic neurons was not altered. Moreover, in the absence of nerve stimulation, the antagonism of the renin-angiotensin system lowered base-line BP by reducing CO without measurably affecting TPR. Infusion of angiotensin II reversed these effects and restored BP toward precaptopril levels by increasing CO without measurably affecting TPR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of aerobic fitness on hemodynamic responses to upright tilting

The purpose of this study was to examine the influence of aerobic fitness on heart rate, systolic and diastolic blood pressure, mean arterial pressure, and pulse pressure responses to upright tilting in 10 below-average (BA Group) and 10 above-average (AA Group) aerobically fit adults. Aerobic fitness levels were predicted using the Astrand and Ryhming submaximal exercise test. Mean predicted maximal aerobic capacities were significantly higher (p less than .05) for the AA Group (46.0 +/- 6.0 mL.kg-1.min-1) compared with the BA Group (31.0 +/- 4.8 mL.kg-1.min-1) subjects. Heart rate and blood pressure responses were obtained at rest (supine position for 30 minutes) and during 5 minutes of upright tilting to 70 degrees (electric tilt table). A two-factor analysis of variance indicated that the increase in heart rate to upright tilting was significant (p less than .05) (significant treatment effect). More importantly, the study revealed a significant treatment x group interaction (p less than .05), indicating that the heart rate response for the BA Group was significantly greater than for the AA Group. Similar results occurred for blood pressure responses. A separate analysis of variance demonstrated significant changes in hemodynamic responses to upright tilting and significant treatment x group interactions. These results demonstrated significantly smaller (p less than .05) changes in blood pressure and heart rate to upright tilting for the AA Group compared with the BA Group. The results, therefore, indicate that reflex responses to central hypovolemia are different between above-average and below-average aerobically fit adults.     

Effects of propofol on hemodynamic and inflammatory responses to endotoxemia in rats

OBJECTIVE: To document the effects of propofol on the hemodynamic and inflammatory responses to endotoxemia in an animal model. DESIGN: Randomized, prospective laboratory study. SETTING: University experimental laboratory. SUBJECTS: Thirty-two male rats. INTERVENTIONS: The animals were randomly assigned to one of four groups: a) endotoxemia group (n = 8), which received intravenous Escherichia coli endotoxin (15 mg/kg over 2 mins); b) control group (n = 8), which was treated identically to the endotoxemia group except for the substitution of 0.9% saline for endotoxin; c) propofol group (n = 8), which was treated identically to the control group but also received propofol (10 mg/kg bolus, followed by infusion at 10 mg/kg/hr) immediately after the injection of 0.9% saline; and d) propofol-endotoxemia group (n = 8), which was treated identically to the endotoxemia group with the additional administration of propofol (10 mg/kg bolus, followed by infusion at 10 mg/kg/hr) immediately after endotoxin injection. MEASUREMENTS AND MAIN RESULTS: Hemodynamics, arterial blood gases, and acid-base status were recorded and the blood propofol concentrations and plasma cytokine concentrations were measured during the 5-hr observation. Microscopic findings of lung tissue for each group were obtained at necropsy. The systolic arterial pressure and heart rate of the propofol-endotoxemia group were similar to those of the endotoxemia group. The increases in the plasma cytokine (tumor necrosis factor, interleukin-6, and interleukin-10) concentrations, in the base deficit, and in the infiltration of neutrophils in the air space or vessel walls of the lungs were attenuated in the propofol-endotoxemia group compared with the endotoxemia group. CONCLUSIONS: Propofol attenuated cytokine responses, base deficit, and activation of neutrophils to endotoxemia. These findings suggest that propofol may inhibit inflammatory response and prevent the development of metabolic acidosis during endotoxemia.     

Monitoring in language perception: electrophysiological and hemodynamic responses to spelling violations

The monitoring theory of language perception proposes that competing representations that are caused by strong expectancy violations can trigger a conflict which elicits reprocessing of the input to check for possible processing errors. This monitoring process is thought to be reflected by the P600 component in the EEG. The present study further investigated this monitoring process by comparing syntactic and spelling violations in an EEG and an fMRI experiment. To assess the effect of conflict strength, misspellings were embedded in sentences that were weakly or strongly predictive of a critical word. In support of the monitoring theory, syntactic and spelling violations elicited similarly distributed P600 effects. Furthermore, the P600 effect was larger to misspellings in the strongly compared to the weakly predictive sentences. The fMRI results showed that both syntactic and spelling violations increased activation in the left inferior frontal gyrus (lIFG), while only the misspellings activated additional areas. Conflict strength did not affect the hemodynamic response to spelling violations. These results extend the idea that the lIFG is involved in implementing cognitive control in the presence of representational conflicts in general to the processing of errors in language perception.     

Nurses’ responses to people with schizophrenia

General nurses, psychiatric nurses and lay people were investigated to identify differences between their personal standards concerning how they should respond, and beliefs about how they actually would respond, towards the target group, ‘people with schizophrenia’, in each of three response domains (thinking, feeling and behaving). Significant differences were identified between the response types and between the different response domains. Significant interaction effects were also identified based on participants professional status in nursing. It is argued that the results support 8 ) theory concerning the automatic activation of stereotypes and their controlled inhibition in favour of different personal beliefs. It is also argued that professional specialization in psychiatric nursing facilitates this process in relation to the target group.     

Heterogeneity and prediction of hemodynamic responses to dobutamine in patients with septic shock

OBJECTIVE: To establish the heterogeneity of hemodynamic responses to dobutamine in patients with septic shock and to identify the predictive factors of these hemodynamic responses. DESIGN: Prospective study. SETTING AND PATIENTS: A total of 12 patients with septic shock in a tertiary medical intensive care unit. INTERVENTIONS: A 20-min dobutamine infusion at 5 microg.kg(-1).min(-1) with subsequent increments to 8, 12.6, and 20 microg.kg(-1).min(-1), on two consecutive days. Responses were dichotomized into changes in heart rate (HR) or stroke volume index (SVI) of >10% and < or =10% at the maximal dobutamine infusion. MEASUREMENTS AND MAIN RESULTS: No differences were found in survival, Acute Physiology and Chronic Health Evaluation II score, maximal dobutamine doses, or pharmacokinetics of dobutamine between HR and SVI groups. In DeltaHR > 10% vs. DeltaHR < or = 10%, baseline HR was lower, and baseline mixed venous oxygen tension and saturation were higher. During dobutamine infusion, mean arterial pressure decreased in DeltaHR > 10%. Cardiac index and the systemic oxygen delivery index increased and the systemic vascular resistance index decreased at unchanged SVI. Pressure work index increased and the ratio of the diastolic to systolic aortic pressure time indices decreased but not to <0.6. In DeltaHR < or = 10%, systemic vascular resistance index and the ratio of the diastolic to systolic aortic pressure time indices decreased (but remained >0.6) without changes in SVI or cardiac index. Baseline hemodynamic and metabolic variables did not differ between SVI groups. In DeltaSVI > 10%, cardiac index increased with dobutamine, but Pao2 and the systemic oxygen delivery index decreased. In DeltaSVI < or = 10%, HR and the systemic oxygen delivery index increased; mean arterial pressure, left ventricular stroke work index, systemic vascular resistance index, and the ratio of the diastolic to systolic aortic pressure time indices decreased. CONCLUSIONS: Patients with a positive chronotropic response to dobutamine had lower baseline HR values, and a chronotropic rather than inotropic response predicted an increase in cardiac index and systemic oxygen delivery index. Incremental dosages of dobutamine did not compromise indirectly measured myocardial oxygen balance.     

不同剂量瑞芬太尼对全麻诱导期气管插管血流动力学的影响

目的 观察复合异丙酚下不同剂量瑞芬太尼对全麻诱导期气管插管时血流动力学的影响,探索瑞芬太尼全麻诱导期气管插管的较佳剂量.方法 将60例患者随机分为4组,对照组诱导给予芬太尼,其它3组诱导给予不同剂量的瑞芬太尼,其余诱导药物一致,待患者意识消失后,行气管内插管.观察从入室到插管后5分钟之内的HR、SBP、DBP、MAP.结果 瑞1组SBP、MAP值在插管后1 min、2 min时均有较大的升高,与其余3组组间相比差异有统计学意义（P〈0.05）;R2和R3组从插管插入即刻起,血压开始回升,而R2组血压回升平稳,T3、T4、T5、T6比较差异无统计学意义.结论 瑞芬太尼1 μg/kg单次静脉注射诱导不能很好的抑制插管后心血管应激反应.与瑞芬太尼2 μg/kg对比,1.5 μg/kg剂量诱导可以很好的抑制插管后心血管应激反应.     

Effects of prostaglandin synthesis inhibition on sympathetic-and parasympathetic-mediated coronary hemodynamic responses

In chloralose-anesthetized dogs with the left circumflex coronary artery perfused at constant flow, the effects of indomethacin or naproxen on coronary and systemic responses to sympathetic and parasympathetic stimulation were evaluated. Sympathetic stimulation was evoked either by 1-min carotid artery occlusion or by epinephrine (5 micrograms) or norepinephrine (5 micrograms) intracoronary administration. Reflex or direct parasympathetic stimulation was produced by ouabain (40 micrograms) or acetylcholine (2.5 micrograms) injection, respectively, in the perfused coronary artery. The administration of indomethacin or naproxen reduced the integrated areas of coronary vasodilatation induced by epinephrine and norepinephrine. The extent of this reduction was dose-dependent with both indomethacin (epinephrine: r = 0.774, n = 35, P less than .001; norepinephrine: r = 0.766, n = 35, P less than .001; norepinephrine: r = 0.799, n = 35, P less than .001) up to 1.5 and 7 mg/kg, respectively. Further increase in dosage of both prostaglandin synthesis inhibitors failed to induce further reduction of integrated areas of coronary vasodilatation. In contrast, the maximum fall in coronary perfusion pressure, induced by both catecholamines, remained unmodified after inhibition of prostaglandin synthesis, whereas a faster return of the perfusion pressure to base line was observed. The extent of cyclooxygenase activity inhibition induced by indomethacin or naproxen, assessed through the radioimmunoassay of thromboxane B2, showed a consistent dose-dependent increase until complete inhibition was attained with 1.5 mg/kg of indomethacin and 7 mg/kg of naproxen. No significant change in the coronary and systemic hemodynamic response induced by carotid occlusion and by ouabain or acetylcholine intracoronary administration was observed. Furthermore, complete cyclooxygenase inhibition, induced by either indomethacin or naproxen, was able to reduce the coronary vasodilatation induced by isoproterenol (5 micrograms) intracoronary injection but failed to modify the coronary vasoconstriction elicited by both epinephrine and norepinephrine in propranolol-treated dogs. These data indicate that the prostaglandin system is involved in the coronary vasodilatation induced by humoral sympathetic stimulation, whereas coronary hemodynamic responses to both neural sympathetic or parasympathetic stimulation are not influenced by the administration of prostaglandin synthesis inhibitors.     

肥胖对男青年血流动力学运动反应影响的实验研究

目的：探究肥胖对血流动力学运动反应的影响，为肥胖相关心血管疾病的运动监控提供理论支持。方法：体重正常和肥胖男青年各10名，连续采集运动前后系统血流动力学指标（BP、HR、DP、SI、CI）和指端血流动力学参数（K′、VDF、VCF、PCII、VCTI）进行分析。结果：肥胖青年男性运动前的SBP、rHR和rPCII明显高于体重正常者；运动后eSI和eCI明显低于体重正常者；运动后eK′和ePCII明显高于体重正常者。相关分析表明，Fat%与rSBP、rHR、eSI、eCI、eK′和ePCII密切相关；系统血流动力学指标和指端血流动力学指标间的偏相关分析表明，rPCII与rHR、eK′和eCI、ePCII和eCI密切相关。结论：肥胖会引发青年男性运动前后指端血流动力学改变。运动前后系统血流动力学和指端血流动力学指标间具有相关性，提示指端容积血流脉搏波参数有望成为运动心血管机能监测的新指标。     

Hemodynamic responses in visual, motor, and somatosensory cortices in schizophrenia

Recent advances in functional neuroimaging allow comparisons between individuals with schizophrenia and control groups. Previous studies of schizophrenia have used blocked task paradigms and, more recently, "rapid event-related" designs in which stimuli of different types are presented close together in an intermixed fashion. The validity of between-group comparisons in both of these types of paradigms depends on excluding the possibility that observed functional response differences are attributable to altered hemodynamic responses in individuals with schizophrenia. The goal of the current study was to begin a systematic examination of the hemodynamic response in schizophrenia. We administered a flashing checkerboard paradigm with a motor response to 17 individuals with schizophrenia and 24 healthy controls. Both groups showed robust activation of visual, motor, somatosensory, and supplementary motor regions. For the most part, the individuals with schizophrenia demonstrated intact peak amplitude, variance, latency, and linear summation properties in regions activated by this task. We did find some evidence for increased variability in the amplitude and latency of the hemodynamic responses in the visual and somatosensory cortices, although the magnitudes of these group differences were relatively small. These results begin to validate the interpretation of functional neuroimaging studies of schizophrenia in terms of neuronal as opposed to vascular mechanisms.     

Hemorrhage alters neuroendocrine, hemodynamic, and compartment-specific TNF responses to LPS

The aim of the present study was to determine the effects of fixed pressure (40 mmHg) hemorrhage (HEM) followed by fluid resuscitation with Ringer's lactate on the subsequent hemodynamic, neurohormonal, and TNF response elicited by systemic lipopolysaccharide (LPS) administration. Chronically catheterized, conscious, unrestrained male Sprague-Dawley rats were randomized to either HEM (n = 12) or sham (n = 12) groups. HEM and sham animals were randomized to receive either LPS (100 mg/100 g body weight) or an equal volume of intravenous saline 1.5 h after completion of the resuscitation period. LPS administration produced an immediate 20% decrease in mean arterial pressure in sham animals, which was accentuated in HEM animals (40%, P < 0.05 versus sham). Moreover, HEM blunted (75%, P < 0.05) the LPS-induced increase in plasma TNF concentrations. TNF was not detected in bronchoalveolar lavage fluid (BALF) obtained from sham LPS-treated animals. In contrast, TNF levels were significantly elevated (35 +/- 17 pg/mL) in HEM LPS-treated animals. A 400% increase in lung TNF content following LPS treatment was not affected by prior HEM. LPS administration produced a marked increase in plasma epinephrine, norepinephrine, and corticosterone levels in sham animals. HEM blunted the LPS-induced rise in circulating levels of epinephrine and corticosterone without altering that of norepinephrine. Our second set of studies showed that the increase in BALF TNF was associated with a 30% increase in wet-to-dry lung weight ratios, suggesting that this is most likely the result of leaky endothelium following hemorrhage and LPS. Furthermore, alterations in LPS-induced alveolar macrophage TNF production following HEM were not detected. These results indicate that HEM altered the hemodynamic, neurohormonal, and circulating TNF responses to systemic LPS administration. In addition, our results suggest that HEM impaired the compartmentalization of the inflammatory response to LPS, without affecting alveolar macrophage responses to LPS. The role of altered neuroendocrine responses to a second challenge in modulating proinflammatory responses remains to be elucidated.     

Opiate modulation of hemodynamic, hormonal, and cytokine responses to hemorrhage

The aim of the present study was to examine the role of opiate receptor activation in modulating the hemodynamic, neuroendocrine, and tissue (lung and spleen) cytokine responses to fixed pressure (40 mm Hg) hemorrhage. Chronically catheterized, conscious unrestrained non-heparinized male Sprague-Dawley rats were pretreated with either naltrexone (15 mg/kg intraperitoneally in 0.5 mL of saline) or saline (0.5 mL) 15 min prior to hemorrhage followed by fluid resuscitation with Ringer's lactate. Animals were sacrificed at completion of the 60-min resuscitation period. Blood loss required to achieve mean arterial blood pressure (MABP) of 40 mm Hg was higher in naltrexone-treated animals than in time-matched saline controls (4.4+/-0.2 versus 3.7+/-0.2 mL/100 g BW, P< 0.05). Hemorrhage increased plasma levels of corticosterone (30%) and ACTH (3-fold) within 15 min. Naltrexone prevented the hemorrhage-induced rise in corticosterone without affecting the rise in ACTH. Hemorrhage increased beta-endorphin levels (4-fold) and produced an immediate (5 min) and progressive increase in circulating epinephrine and norepinephrine levels reaching values that were 50- and 20-fold, respectively, higher than basal. Pre-treatment with naltrexone did not alter the time course or magnitude of the hemorrhage-induced increases in plasma beta-endorphin or catecholamines. Hemorrhage increased lung and spleen content of TNF (60%), IL-1alpha (300%), IL-6 (40%-60%), and IL-10 (80%) above values of time-matched sham control animals. Pre-treatment with naltrexone blunted the magnitude of the increases in tissue cytokine content in response to a given blood loss. These results indicate that endogenous opiates modulate the hemodynamic instability, neuroendocrine, and cytokine responses to hemorrhagic shock.     

Role of the central nervous system in hemodynamic and sympathoadrenal responses to cocaine in rats

These studies were undertaken to examine the contribution of central nervous system mechanisms to the cardiovascular and sympathoadrenal effects of cocaine. Changes in systolic and diastolic blood pressure, heart rate and plasma catecholamine concentrations were determined in response to cocaine injected i.a. or i.c.v. in conscious unrestrained rats. Systemically administered cocaine produced brisk, transient dose-related increases in systolic and diastolic pressure at doses of 0.05 to 5 mg/kg i.a. Plasma catecholamine concentrations increased in a dose-related manner, reaching peak levels at 5 to 10 min after i.a. cocaine injection. Only the higher doses of cocaine induced reflex vagal bradycardia that was blocked by atropine (0.4 mg/kg i.a.). Propranolol (1 mg/kg i.a.) prolonged the duration of cocaine-induced hypertension and bradycardia. Ganglionic blockade with chlorisondamine (7.5 mg/kg i.a.) antagonized completely the cardiovascular and sympathoadrenal effects of cocaine, indicating that intact ganglionic transmission is required for full expression of the autonomic responses. Antagonist drugs selective for the D-1 or D-2 dopamine receptors attenuated effects of cocaine on plasma catecholamine concentrations but not on cardiovascular parameters. Intracerebroventricular injection of cocaine (50-250 micrograms) increased systolic pressure and plasma catecholamine concentrations, providing direct evidence for an action of cocaine in the central nervous system. These results demonstrate that cocaine acts centrally to increase sympathetic outflow leading to hypertension and reflex bradycardia in conscious rats.     

Renal hemodynamic and excretory responses to renin inhibition induced by A-64662

Experiments were conducted in sodium-depleted anesthetized monkeys to determine the effects of the primate-selective renin inhibitor A-64662 on renal function. Five groups of monkeys were examined with each group receiving an i.v. infusion of vehicle or A-64662 at doses (bolus plus continuous infusion) of 0.1 + 0.01, 1.0 + 0.1, 10 + 1.0 or 100 micrograms/kg + 10 micrograms/kg/min (n = 6/dose). Plasma renin activity was inhibited (P less than .05) at all infusion doses ranging from 33 +/- 8% at the lowest dose to 95 +/- 3% at the highest dose. Inhibition of plasma renin activity was accompanied by renal vasodilation as renal blood flow (RBF) increased (P less than .05) in a dose-dependent manner beginning at the dose of 1.0 microgram/kg + 0.1 micrograms/kg/min. RBF increased 36 +/- 7% at the highest dose of A-64662 examined. Associated with the increments in RBF, renal vascular resistance progressively decreased (P less than .05) by 12 +/- 3, 31 +/- 3 and 40 +/- 6%, respectively, with increasing doses of A-64662. Glomerular filtration rate was unchanged at all doses of A-64662. As a result, a significant (P less than .05) fall in the filtration fraction was observed as the dose of A-64662 increased. Mean arterial pressure was unaffected by the two lowest doses of A-64662, but decreased (P less than 0.05) by 13 +/- 1 and 18 +/- 4 mm Hg, respectively, at the two highest doses of A-64662 infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Coagulation defects and altered hemodynamic responses in mice lacking receptors for thromboxane A2.

Thromboxane A2 (TXA2) is a labile metabolite of arachidonic acid that has potent biological effects. Its actions are mediated by G protein-coupled thromboxane-prostanoid (TP) receptors. TP receptors have been implicated in the pathogenesis of cardiovascular diseases. To investigate the physiological functions of TP receptors, we generated TP receptor-deficient mice by gene targeting. Tp-/- animals reproduce and survive in expected numbers, and their major organ systems are normal. Thromboxane agonist binding cannot be detected in tissues from Tp-/- mice. Bleeding times are prolonged in Tp-/- mice and their platelets do not aggregate after exposure to TXA2 agonists. Aggregation responses after collagen stimulation are also delayed, although ADP-stimulated aggregation is normal. Infusion of the TP receptor agonist U-46619 causes transient increases in blood pressure followed by cardiovascular collapse in wild-type mice, but U-46619 caused no hemodynamic effect in Tp-/- mice. Tp-/- mice are also resistant to arachidonic acid-induced shock, although arachidonic acid signifi-cantly reduced blood pressure in Tp-/- mice. In summary, Tp-/- mice have a mild bleeding disorder and altered vascular responses to TXA2 and arachidonic acid. Our studies suggest that most of the recognized functions of TXA2 are mediated by the single known Tp gene locus.