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Nicardipine inhibits the endothelin-1-induced constriction of systemic capacitance and resistance vessels.

We estimated the effects of intravenous injection of endothelin-1 (ET-1; 400 pmol/kg) on the systemic capacitance and resistance vessels in anesthetized mongrel dogs by measuring changes in the mean circulatory pressure (MCP) and total peripheral resistance (TPR), respectively. In addition, the present study investigated the inhibiting action of nicardipine (NIC; 10 micrograms/kg bolus injection followed by 1.0-2.0 micrograms/kg/min continuous infusion) against the vasoconstrictor action of ET-1. We examined the effects of ET-1 (30 to 1,000 pmol/0.1 ml) on the femoral arterial system by measuring the percent changes in the perfusion pressure (% delta PP) of the femoral artery perfused with a constant flow, and investigated the effect of NIC on the vasoconstrictor action of ET-1 in this preparation. We obtained the following results: (a) Intravenous injection of ET-1 raised both TPR and MCP. However, in the presence of NIC, ET-1 raised TPR without influencing MCP. (b) Intra-arterial injection of ET-1 caused a dose-dependent increase in % delta PP. NIC shifted the dose-response curve of ET-1 for % delta PP to the right in a parallel fashion.

Animals↗

Effects of intravenous endothelin on hemodynamics and cardiac contractility in conscious Milan normotensive rats.

The effects of endothelin-1 (ET-1) on hemodynamics and cardiac contractility were compared with the responses to angiotensin I (AI) and phenylephrine (PE) in Milan normotensive rats. Intravenous (i.v.) injection of ET-1 (0.8 nmol/kg) initially decreased mean blood pressure (MBP), total peripheral resistance (TPR), and dP/dt (-28 +/- 2, -34.8 +/- 3.7, and -9.4 +/- 1.3%, p less than 0.01, respectively), and increased heart rate (HR), cardiac output (CO), and the velocity of myocardial anterior wall shortening (dL/dt) (11.8 +/- 2.1, 10.4 +/- 2.9, and 28.3 +/- 8.3% p less than 0.05, respectively). These effects were followed by a sustained increase in MBP and TPR and a decrease in CO. As compared with AI (0.25 nmol/kg) and PE (35 nmol/kg), which produced a similar degree of increase in TPR, the reduction in CO induced by ET-1 was more prominent (-25 +/- 2 by ET-1 vs. -14 +/- 2 by AI and -14 +/- 3% by PE, p less than 0.05, respectively). Moreover, ET-1 induced a significant decrease in dP/dt, shortening fraction (SF), and dL/dt (-6.1 +/- 1.6, -35.0 +/- 3.8, and -38.6 +/- 5.5%, p less than 0.01, respectively), whereas these indexes of left ventricle performance were not affected by either AI or PE. Furthermore, the reduction in SF induced by ET-1 was mainly due to the decrease in myocardial diastolic segment length, suggesting reduction in diastolic filling volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗

Factors associated with hyperdynamic or hypodynamic circulation and role of platelet-activating factor in hemodynamic alterations in bacterial peritonitis in conscious rats.

Male Wistar rats injected intraperitoneally (i.p.) with 10(9) U Escherichia coli ATCC 25922 developed acute bacterial peritonitis. Hemodynamic studies, with microspheres labeled with 103Ru 57Co, and 113Sn, were performed before, 30 min after bacterial injection, and 30 min after administration of either the platelet-activating factor (PAF) antagonist BN-52021 (5 mg/kg body weight) or isotonic saline. A blood sample of 0.3 ml was obtained for bacterial culture and endotoxemia measurements. Plasma PAF levels were measured in a different group of 10 control rats and 20 animals with experimental peritonitis. One group of rats injected with E. coli (n = 13) displayed hyperdynamic circulation, with an increase in cardiac output (CO) from 15.1 +/- 1.2 to 19.4 +/- 1.1 ml/min/100 g body weight and a decrease in total peripheral resistance (TPR) from 19.5 +/- 2.4 to 14.9 +/- 1.1 dynes.s.cm-5 10(-4). Furthermore, these rats showed high endotoxin blood concentrations and low hemoculture levels. The remaining 7 peritonitic rats showed a significant decrease in CO from 16.3 +/- 1.6 to 12.7 +/- 1.2 ml/min/100 g body weight and an increase in TPR from 17.3 +/- 1.8 to 22.6 +/- 2.8 dynes.s.cm-5 10(-4). In addition, these rats showed low endotoxin blood concentrations and high hemoculture levels. Endotoxin blood concentrations were positively correlated with the change in CO (r = 0.87, p < 0.05), and cell hemocultures were positively correlated with CO (r = 0.89, p < 0.05). Rats with high endotoxin blood levels showed higher PAF plasma levels than control rats or peritonitic rats with low endotoxin blood levels. When peritonitic rats were injected with the specific PAF-receptor blocker BN-52021 (5 mg/kg body weight) as a bolus, CO and TPR returned to baseline values in both groups of animals. These data suggest that the hemodynamic changes induced by bacterial peritonitis depend on endotoxemia and bacteremia in opposite ways. In addition, PAF appears to be involved in both the hyperdynamic and hypodynamic hemodynamic changes shown by peritonitic rats.

Animals↗

Effects of endothelin-induced nitric oxide on venous circulation and renal water-electrolyte handling.

To assess the interaction of endothelin (ET) with nitric oxide (NO) and the effects on venous circulation and handling of renal water and electrolytes, ET (1.0 ng/kg/min) or saline was administered with or without three doses (0.27, 2.7 and 27 ng/kg/min for 40 min) of N omega-nitro-L-arginine methyl ester (L-NAME), and NO synthase inhibitor, in anesthetized dogs. ET increased total peripheral resistance (TPR), pulmonary capillary wedge pressure (PCWP), urine flow (UF), and urinary K excretion (UKV), and decreased cardiac output (CO), urinary osmolality (Uosm), renal plasma flow (RPF), and glomerular filtration rate (GFR). L-NAME increased blood pressure (BP), TPR, PCWP, right atrial pressure (RAP), and mean circulatory filling pressure (MCFP), and decreased CO, RPF, and GFR, ET plus L-NAME markedly increased TPR, resistance to venous return, and plasma atrial natriuretic peptide (ANP), but not BP and MCFP, and curtailed the ET-induced responses in UF, UKV, and Uosm. Plasma aldosterone (ALD) was decreased in all groups, but plasma vasopressin (AVP) and renin activity (PRA) were not altered in any group. These results indicate that ET-induced NO formation might mitigate increases in venous as well as arterial vascular resistance and changes in renal handling of water and electrolytes, and might also play an inhibitory role in ANP release but not in PRA or AVP and ALD release.

Animals↗

Acute cardiovascular effects of experimental spinal cord injury.

The effects of acute head injury or subarachnoid hemorrhage on the cardiovascular system (CVS) are well known, but data are lacking on the effects of acute spinal cord injury (SCI) on the CVS. The clip compression SCI rat model was used to measure changes in the mean systemic arterial pressure (mSAP), cardiac output (CO), heart rate (HR), total peripheral resistance (TPR), and central venous pressure (CVP) after SCI. Three groups of five animals each were anesthetized with chloralose-urethane: one group underwent only the surgical procedures including laminectomy, and the other two received either a 2.3- or 53.0-gm injury at the T1 spinal cord segment for 1 minute. The CO was measured using the thermodilution technique. CVS parameters were measured before injury, and then at designated times for 135 minutes after SCI. Analysis of variance and paired t-test with significance at p = 0.05 were used for analysis. There were no CVS changes as a result of anesthesia, operative time, or laminectomy alone. Cardiovascular system (CVS) changes occurred after the 2.3- and 53.0-gm. injuries but were significantly different only in the 53.0-gm injured animals. In this group mSAP increased from a preinjury value of 105 +/- 8 mm Hg to 178 +/- 11 mm Hg as a result of SCI, followed by a prolonged period of hypotension (46 +/- 15 mm Hg) lasting until 135 min post SCI. The CO after SCI also decreased from 394 +/- 22 to 218 +/- 29 ml/min/kg with the TPR reaching a minimal level at 45 min post SCI (265 +/- 23 to 213 +/- 29 mm Hg/ml/min gm wt), after which it returned to preinjury values. There were no significant changes in the CVP in either group. In the 53.0-gm group significant bradycardia (492 +/- 7 to 356 +/- 44 beats/min) was observed by 45 min and continued to decrease until 135 min after SCI. Thus the CVS showed two major alterations after severe SCI: post-traumatic hypotension, and a parallel decline in CO. There were no major changes in TPR, HR, or CVP, although HR ultimately declined. These findings suggest that the decline in CO was not entirely due to decreased sympathetic tone, but may also have resulted from direct myocardial injury, similar to that demonstrated after head injury or subarachnoid hemorrhage.

Animals↗

Cardiovascular response of trained and untrained old men to mental challenge.

PURPOSE: The cardiovascular response to mental challenge of trained and untrained older men was examined. METHODS: Blood pressure, heart rate, stroke volume, cardiac output, total peripheral resistance (TPR), rate pressure product, and cardiac contractility of 10 aerobically trained (trained) and 10 untrained (untrained) older men during and recovering from the Stroop task were compared. Fitness was assessed by online, open-circuit spirometry using a bicycle ergometer. RESULTS: Trained compared with untrained men showed significantly lower absolute heart rate during and recovering from the Stroop and greater left ventricular ejection time recovering from Stroop. Delta TPR scores were greater for Trained during and recovering from the Stroop, whereas delta systolic blood pressure was greater recovering from Stroop. CONCLUSION: These results indicate that although aerobically trained men possessed lower absolute heart rate their change in TPR and systolic blood pressure during mental challenge was significantly greater than that of untrained older men. The greater vascular response of the trained to mental challenge may reflect greater sensitivity to alpha-adrenergic stimulation.

Aged↗

Hemodynamic responses to stress among black women: fitness and parental hypertension.

PURPOSE: We compared hemodynamic aspects of the relationship between cardiorespiratory fitness and blood pressure changes during and after laboratory stress in young black women with or without parental history of hypertension. METHODS: Participants were 30 normotensive, black American women having low to moderate fitness levels (i.e., VO2peak) assessed by cycle ergometry who performed standard active and passive coping laboratory stressors. Blood pressure, heart rate, stroke volume, cardiac output, total peripheral resistance (TPR), calf blood flow (CBF), and calf vascular resistance (CVR) were assessed during exposure to forehead and hand cold pressors, and mental arithmetic, as well as during recovery after the tasks. RESULTS: Fitness was positively related to increases in either TPR or CVR during each stressor. In contrast, fitness was positively related to blunted blood pressure during or after passive stress (i.e., hand or forehead cold) and enhanced recovery of blood pressure and TPR after the active stressor (i.e., mental arithmetic); effects of fitness on the vascular responses during and after mental arithmetic were stronger among women having a negative history of parental hypertension. CONCLUSION: The findings confirm our previous report that fitness blunts systolic blood pressure response during the hand cold pressor in young women. They also suggest that future studies of fitness and blood pressure reactivity during stress should focus on the regulation of vascular responses and their recovery after stress. Weaker effects of VO2peak after mental arithmetic in the positive history group indicate that the level of fitness required to modify recovery from mental stress among black American women may differ according to parental history of hypertension.

Adolescent↗

Cardiovascular function during cognitive stress in men before and after coronary artery bypass grafts.

Cardiovascular function during cognitive stress using the Stroop Color Test (SCWT) was documented in 25 men with ischemic heart disease (IHD) before and after coronary artery bypass grafting (CABG). Impedance cardiography was used to measure changes from resting baseline in heart rate (HR), stroke volume (SV), cardiac output (CO), myocardial contractility, and total peripheral resistance (TPR). Cognitive stress was associated with significant increases in HR, blood pressure, SV, CO, and myocardial contractility. TPR did not change from resting baseline during cognitive stress before CABG. However, TPR decreased significantly from resting baseline during cognitive stress after CABG. These findings support the theory that cognitive stress is associated with a significant increase in myocardial oxygen demand.

Adult↗

An architectural map of the anaphase-promoting complex.

The anaphase-promoting complex or cyclosome (APC) is an unusually complicated ubiquitin ligase, composed of 13 core subunits and either of two loosely associated regulatory subunits, Cdc20 and Cdh1. We analyzed the architecture of the APC using a recently constructed budding yeast strain that is viable in the absence of normally essential APC subunits. We found that the largest subunit, Apc1, serves as a scaffold that associates independently with two separable subcomplexes, one that contains Apc2 (Cullin), Apc11 (RING), and Doc1/Apc10, and another that contains the three TPR subunits (Cdc27, Cdc16, and Cdc23). We found that the three TPR subunits display a sequential binding dependency, with Cdc27 the most peripheral, Cdc23 the most internal, and Cdc16 between. Apc4, Apc5, Cdc23, and Apc1 associate interdependently, such that loss of any one subunit greatly reduces binding between the remaining three. Intriguingly, the cullin and TPR subunits both contribute to the binding of Cdh1 to the APC. Enzymatic assays performed with APC purified from strains lacking each of the essential subunits revealed that only cdc27Delta complexes retain detectable activity in the presence of Cdh1. This residual activity depends on the C-box domain of Cdh1, but not on the C-terminal IR domain, suggesting that the C-box mediates a productive interaction with an APC subunit other than Cdc27. We have also found that the IR domain of Cdc20 is dispensable for viability, suggesting that Cdc20 can activate the APC through another domain. We have provided an updated model for the subunit architecture of the APC.

Anaphase-Promoting Complex-Cyclosome↗

The crooked neck gene of Drosophila contains a motif found in a family of yeast cell cycle genes.

The crooked neck (crn) gene of Drosophila encodes a protein of 702 amino acids and contains 16 tandemly arranged copies of a 34-amino-acid repeat that is similar to the tetratrico peptide repeat (TPR). Multiple copies of the TPR motif have also been found in a family of yeast genes, including several members that are necessary for cell division. TPR-containing proteins encoded by the yeast genes CDC16, CDC23, and nuc2+ are required for progression through the G2/M transition of the cell cycle. Loss of zygotic expression of crn causes defects in the proliferation of brain neuroblasts and results in the absence of identified neuronal lineages in the central and peripheral nervous systems. The sequence similarity and mutant phenotypes are consistent with a cell cycle requirement for the crn gene product.

Amino Acid Sequence↗

Fischer-Tropsch synthesis: study of the promotion of Pt on the reduction property of Co/Al2O3 catalysts by in situ EXAFS of Co K and Pt LIII edges and XPS.

The addition of platinum metal to cobalt/alumina-based Fischer-Tropsch synthesis (FTS) catalysts increases both the reduction rate and, consequently, the density of active cobalt sites. Platinum also lowers the temperature of the two-step conversion of cobalt oxide to cobalt metal observed in temperature programmed reduction (TPR) as Co3O4 to CoO and CoO to Co0. The interaction of the alumina support with cobalt oxide ultimately determines the active site density of the catalyst surface. This interaction can be controlled by varying the cobalt loading and dispersion, selecting supports with differing surface areas or pore sizes, or changing the noble metal promoter. However, the active site density is observed to depend primarily on the cluster size and extent of reduction, and there is a direct relationship between site density and FTS rate. In this work, in situ extended X-ray absorption fine structure (EXAFS) at the LIII edge of Pt was used to show that isolated Pt atoms interact with supported cobalt clusters without forming observable Pt--Pt bonds. K-edge EXAFS was also used to verify that the cobalt cluster size increases slightly for those systems with Pt promotion. X-ray absorption near-edge spectroscopy (XANES) was used to examine the remaining cobalt clusters after the first stage of TPR, and it revealed that the species were almost entirely cobalt (II) oxide. After the second stage of TPR to form cobalt metal, a residual oxide persists in the sample, and this oxide has been identified as cobalt (II) aluminate using X-ray photoelectron spectroscopy (XPS). Sequential in situ reduction of promoted and unpromoted systems was also monitored through XPS, and Pt was seen to increase the extent of cobalt reduction by a factor of two.

Journal Article↗

On the adaptive detection of blood vessels in retinal images.

This paper proposes an automated blood vessel detection scheme based on adaptive contrast enhancement, feature extraction, and tracing. Feature extraction of small blood vessels is performed by using the standard deviation of Gabor filter responses. Tracing of vessels is done via forward detection, bifurcation identification, and backward verification. Tests over twenty images show that for normal images, the true positive rate (TPR) ranges from 80% to 91%, and their corresponding false positive rates (FPR) range from 2.8% to 5.5%. For abnormal images, the TPR ranges from 73.8% to 86.5% and the FPR ranges from 2.1% to 5.3%, respectively. In comparison with two published solution schemes that were also based on the STARE database, our scheme has lower FPR for the reported TPR measure.

Algorithms↗

Use of truncated pyramid representation methodology in three-dimensional reconstruction: an example.

This paper describes a new methodology for three-dimensional (3D) representation of biological structures contained in a series of sections, using an illustrative example. Spatial reconstruction of a specific area of an astrocytoma biopsy was carried out with alignment of the serial sections at an accuracy of 0.01% (or 1 micro m cm(-1)), using the truncated pyramid representation (TPR) methodology. TPR includes: (a) serial tissue sectioning in a ribbon form; (b) alignment of the serial sections based on the properties of a 'truncated pyramid'; (c) identification and localization of structures in every section using a field frame, and representation of the contours of the structures in every section as topographic contours (charting); (d) artificial reconstruction of the missing space between serial sections, by drawing intermediate contours based on the prototype contours of successive sections in order to provide smoother and more elegant representation of the volumes (complementation); and (e) 3D reconstruction. Application of TPR in a selected area of the astrocytoma enabled us to observe the morphology and spatial distribution of neoplastic astrocytic nuclei, which encircled an adjacent blood vessel.

Astrocytoma↗

Possible significance of the pharmacological differentiation of beta-blockers for therapy of hypertension.

1 Cardioselective and non-selective beta-blockers affect to a different degree several aspects of the circulatory homeostasis. The evidence available in this regard has been evaluated and the possible clinical importance of these differences has been discussed. 2 Venous return in partly regulated by beta-receptors (possibly of the beta 2 type) in the venous resistance vessels. Differences in blockade of venous return by the two classes of beta-blockers may, therefore, influence the degree of increase in left ventricular size, left ventricular end diastolic BPs and stroke volume during beta-blockade. 3 At the first part of the dose-reponse curve, non-selective beta-blockers seem to block more effectively renin release than cardioselective beta-blockers. 4 The direction and the extent to which beta-blockers 'directly' affect total peripheral resistance (TPR), is determined by the resultant of the degree of decrease in TPR by blockade of renin release and the extent of the increase in TPR by blockade of the beta 2-receptors in the arteriolar wall. 5 The clinical relevance of these differences could be that--especially in the low doses range--non-selective beta-blockers may be more 'safe' in patients with compromised cardiac function and may be more appropriate for the therapy of high renin hypertension than cardioselective blockers, whereas the latter may be more appropriate for the majority of hypertensive patients who have low to normal renin hypertension.

Adrenergic beta-Antagonists↗

Role of vagal activity in the cardiovascular responses to phenylephrine in man.

The effects of phenylephrine on blood pressure (BP), left ventricular function and total peripheral resistance (TPR) were evaluated in six normotensive male volunteers before and after vagal blockade with atropine. Before atropine, phenylephrine dose-related increased TPR, systolic and diastolic BP and decreased cardiac output by decreases in both stroke volume and heart rate. Post-atropine, the BP (but not TPR) responses to phenylephrine were markedly potentiated, related to an increase in stroke volume despite the higher afterload. Thus vagal tone may regulate cardiac output via effects on both heart rate and venous return.

Adult↗

Central haemodynamics during halothane and enflurane anaesthesia in vascular surgery.

Central haemodynamics were studied before and during reconstructive vascular surgery in 18 patients receiving halothane or enflurane anaesthesia (nine patients in each group). In both groups cardiac output (CO), stroke volume (SV), oxygen uptake (VO2) and arterial blood pressure fell significantly after induction of anaesthesia, whereas the arterio-venous oxygen difference (AVD) and the total peripheral resistance (TPR) remained unchanged. In spite of an average intraoperative blood loss of 600 ml, which had not been substituted for, surgery brought about an increase in CO, SV and VO2, while the AVD and TPR remained unchanged. Following transfusion of 900 ml of blood, CO and SV showed a further significant increase in both groups, whereas VO2 was unchanged and the AVD and TPR fell significantly. The pulmonary capillary venous pressure (PPCV) was stable during induction of anaesthesia and surgery but increased after blood transfusion. The changes in SV and PPCV were analyzed in relation to the concept of ventricular function curves. It is concluded that there were no fundamental differences in central haemodynamics between halothane and enflurane anaesthesia either before or during surgery. In both groups the changes in CO and SV were due mainly to a reduced demand of oxygen transport and expected changes in sympatho-adrenergic tone rather than to myocardial depression.

Aged↗

Maternal haemodynamic changes during caesarean section: a comparison of epidural and general anaesthesia.

Haemodynamic measurements were performed on 20 healthy women before and during elective caesarean section under epidural (10 women) or general anaesthesia (10 women). The influence of the two anaesthetic techniques on the haemodynamic changes associated with operative delivery was compared. The following haemodynamic variables were studied: cardiac output (CO), stroke volume (SV) determined non-invasively with impedance cardiography, heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP), pulse pressure, mean arterial pressure (MAP) and total peripheral vascular resistance (TPR). During epidural anaesthesia, SV was largely unchanged before delivery but increased (P less than 0.05) following delivery. However, CO increased (P less than 0.05) prior to delivery due to an increase (P less than 0.01) in HR. A further increase (P less than 0.05) in CO was recorded following delivery. SBP, DBP, MAP and TPR decreased (P less than 0.01) during epidural anaesthesia. In the patients undergoing general anaesthesia, SV decreased (P less than 0.05) prior to delivery. However, CO remained largely unchanged due to an increase (P less than 0.01) in HR. Following delivery, CO (P less than 0.05) and SV (P less than 0.01) increased whereas HR decreased (P less than 0.01). SBP, DBP and MAP increased (P less than 0.01) prior to delivery, returning to the same level as prior to induction of anaesthesia following delivery. TPR was largely unchanged prior to delivery but decreased (P less than 0.01) following delivery.

Anesthesia, Epidural↗

Circulatory changes associated with heat stroke: observations in an experimental animal model.

1. Although heat stroke is a frequent cause of death in both humans and animals as a result of climatic or exercise-imposed stress, underlying mechanisms are understood poorly. In order to develop more effective strategies for prevention and treatment of this cause of death and suffering, controlled experiments were conducted on a small number of sheep to examine cardiovascular involvement in the thermoregulatory failure of heat stroke. 2. Sheep were studied in a hot environment at rest and then during exercise until collapse. 3. With exercise, mean arterial pressure (MAP) increased slightly, cardiac output (CO) increased markedly and total peripheral resistance (TPR) decreased slightly. As collapse was imminent, MAP increased but CO and TPR did not change significantly. On collapse, MAP and TPR increased markedly and CO decreased markedly. 4. Radioactive microsphere measurements demonstrated during exercise a redistribution of blood flow (BF) away from abdominal viscera and torso skin, to muscles involved in exercise, respiratory muscles, myocardium, fat, limb skin and nasobuccal tissues. With progressively increasing heat stress and exercise, BF increased in exercise muscles and decreased in limb skin and fat. As collapse was imminent, there were sharp increases in BF in exercise muscles, brain and spinal cord. On collapse, BF decreased markedly in exercise and respiratory muscles and fat. 5. It is concluded that collapse and ultimately heat stroke are not due primarily to cardiovascular 'failure' but, rather, to consequences of high body temperatures resulting from thermoregulatory failure attributable to demands for blood pressure regulation dominating requirements for body temperature regulation.

Animals↗