Biomedical subjects

B Biber

Publications and source records attributed to B Biber.

At least 19 recordsLinked to original sources

PubMed2005

Positive inotropic and negative lusitropic effects of endothelin receptor agonism in vivo.

The endothelin (ET) system is involved in the regulation of myocardial function in health as well as in several diseases, such as congestive heart failure, myocardial infarction, and septic myocardial depression. Conflicting results have been reported regarding the acute contractile properties of ET-1. We therefore investigated the effects of intracoronary infusions of ET-1 and of the selective ET(B) receptor-selective agonist sarafotoxin 6c with increasing doses in anesthetized pigs. Myocardial effects were measured through analysis of the left ventricular pressure-volume relationship. ET-1 elicited increases in the myocardial contractile status (end-systolic elastance value of 0.94 +/- 0.11 to 1.48 +/- 0.23 and preload recruitable stroke work value of 68.7 +/- 4.7 to 83.4 +/- 7.2) that appear to be mediated through ET(A) receptors, whereas impairment in left ventricular isovolumic relaxation (tau = 41.5 +/- 1.4 to 58.1 +/- 5.0 and t(1/2) = 23.0 +/- 0.7 to 30.9 +/- 2.6, where tau is the time constant for pressure decay and t(1/2) is the half-time for pressure decay) was ET(B) receptor dependent. In addition, intravenous administration of ET-1 impaired ventricular relaxation but had no effect on contractility. Intracoronary sarafotoxin 6c administration caused impairments in left ventricular relaxation (tau from 43.3 +/- 1.8 to 54.4 +/- 3.4) as well as coronary vasoconstriction. In conclusion, ET-1 elicits positive inotropic and negative lusitropic myocardial effects in a pig model, possibly resulting from ET(A) and ET(B) receptor activation, respectively.

Anesthesia↗

PubMed2005

Dopamine or norepinephrine infusion during thoracic epidural anesthesia? Differences in hemodynamic effects and plasma catecholamine levels.

BACKGROUND: During thoracic epidural anesthesia, an intravenous dopamine infusion augments the systemic pressure response and modifies plasma catecholamine levels. If such an altered response occurs when norepinephrine is infused is not clear. Therefore, dopamine and norepinephrine induced circulatory and catecholamine responses were studied before and during thoracic epidural anesthesia. METHODS: Nine chloralose-anesthetized dogs were equipped with thoracic epidural catheters. Dopamine (5, 10, and 20 microg kg(-1) min(-1)), and norepinephrine (0.1, 0.25, and 0.5 microg kg(-1) min(-1)) were infused before and during epidural anesthesia, while cardiovascular performance and plasma catecholamine changes were studied. RESULTS: Thoracic epidural anesthesia decreased arterial pressure, and cardiac contractility. The systemic pressure response induced by dopamine was augmented during epidural anesthesia. Norepinephrine did not increase arterial pressure and myocardial contractility as markedly as dopamine, and cardiac output was not altered. Thoracic epidural anesthesia attenuated the plasma norepinephrine level. Plasma dopamine levels were augmented by the dopamine infusion during epidural anesthesia, while plasma norepinephrine levels were attenuated. In contrast, norepinephrine augmented the plasma norepinephrine levels during epidural anesthesia. In general, plasma norepinephrine levels were three to six times higher during a norepinephrine infusion compared to a dopamine infusion. CONCLUSION: The cardiovascular response to a graded dopamine infusion is augmented during thoracic epidural anesthesia, while norepinephrine-induced effects are unaltered. The modified plasma catecholamine levels may contribute to the hemodynamic differences between dopamine and norepinephrine infusions during thoracic epidural anesthesia.

Anesthesia, Epidural↗

PubMed2004

Assessment of graded intestinal hypoperfusion and reperfusion using continuous saline tonometry in a porcine model.

OBJECTIVE: To evaluate effects of graded intestinal hypoperfusion and reperfusion on intestinal metabolic parameters as assessed by a modified continuous saline tonometry technique. MATERIALS: Twelve barbiturate-anaesthetized female pigs. METHODS: Measurements were performed prior to and during three predefined levels of superior mesenteric mean arterial blood pressure (P(SMA) 70, 50 and 30 mmHg, respectively, each 80 min long), obtained by an adjustable clamp around the origin of the superior mesenteric artery, and during reperfusion. We continuously measured jejunal mucosal perfusion (laser Doppler flowmetry), jejunal tissue oxygen tension (PO(2TISSUE); microoximetry) and intramucosal PCO(2) (continuous saline tonometry) and calculated net intestinal lactate production, mesenteric oxygenation, PCO(2) gap (jejunal mucosal PCO(2)-arterial PCO(2)) and pHi. RESULTS: At P(SMA) 70 and 50 mmHg mesenteric oxygen uptake and net lactate production remained unaltered, in spite of decreased oxygen delivery. At these P(SMA) levels PCO(2) gap increased, while pHi and PO(2TISSUE) decreased. At P(SMA) 30 mmHg pronounced increases in PCO(2) gap and mesenteric net lactate production as well as marked decreases in PO(2TISSUE) and pHi were demonstrated. Data indicate absence of anaerobic conditions at an intestinal perfusion pressure (IPP)> or =41 mmHg, a pHi> or =7.22 or PCO(2) gap< or =15.8 mmHg. CONCLUSIONS: Continuous saline tonometry detected intestinal ischemia as induced by graded reductions in IPP. A threshold could be defined above which intestinal ischemia does not occur.

Animals↗

PubMed2004

Pressure-independent cardiac effects of angiotensin II in pigs.

BACKGROUND: Angiotensin II (Ang II) is a potent vasoconstrictor with an important role in the development of cardiovascular disease. Earlier results have shown a positive acute inotropic effect of Ang II in anaesthetized pigs together with significant vasoconstriction. This investigation was designed to study cardiac effects of Ang II, when blood pressure was maintained constant by experimental means. METHODS: Ang II (200 microg h(-1)) was infused in anaesthetized pigs (n = 10) at two different arterial blood pressures, the first determined by the effects of Ang II alone, and the second maintained at baseline blood pressure with nitroprusside. Cardiac systolic and diastolic function was evaluated by analysis of left ventricular pressure-volume relationships. RESULTS: Heart rate, end-systolic elastance (Ees) and pre-load adjusted maximal power (PWRmax EDV(-2)) increased at both blood pressure levels, although less when blood pressure was kept constant with nitroprusside. The time constant for isovolumetric relaxation (tau(1/2)) was prolonged with Ang II alone and shortened with Ang II infused together with nitroprusside. CONCLUSION: Ang II infusion in the pig has inotropic and chronotropic properties independent of arterial blood pressure levels, although the effects seem to be blunted by pharmacological actions of the nitric oxide donor nitroprusside.

Angiotensin II↗

PubMed2003

Preload changes by positive pressure ventilation can be used for assessment of left ventricular systolic function.

BACKGROUND: Assessment of preload independent left ventricular function with conductance volumetry is traditionally accomplished by inflating a balloon in the inferior caval vein. Our aim was to investigate if a similar change in preload could be achieved by positive pressure ventilation with large tidal volume. METHODS: Conductance volumetry generating left ventricular pressure-volume loops was used in seven pentobarbital-anesthetized pigs. Changes in preload recruitable stroke work were studied, comparing the effects of inferior vena cava occlusion (IVCO) or large tidal volume (LTV). Cardiodepression was induced by halothane anesthesia and halothane + phenylephrine, and stimulation by epinephrine infusion. RESULTS: Although the decreasis in left ventricular end diastolic volume was slightly less with LTV (16.5 +/- 1.7 ml, mean +/- SEM) than with IVCO (22.4 +/- 1.7 ml) (P < 0.0001) the PRSW-slopes showed a high degree of correlation (r=0.80, P < 0.0001). Although peak tracheal pressures increased significantly to 27.8 +/- 0.9 mmHg during LTV, esophageal pressures (used as an indicator of pericardial pressure) were unchanged. CONCLUSIONS: Positive pressure ventilation with LTV is similar to IVCO in creating transient changes in preload, necessary for assessment of left ventricular systolic function. This observation was valid also during drug-induced cardiac depression and stimulation. The preload recruitable stroke work used for this validation was shown to be a reliable and stable method.

Anesthetics, Inhalation↗

PubMed2002

Splanchnic vasoconstriction by angiotensin II is arterial pressure dependent.

BACKGROUND: Our hypothesis was that splanchnic vasoconstriction by exogenous angiotensin II (Ang II) is significantly potentiated by local mechanisms increasing vasomotor tone and that splanchnic tissue oxygenation during administration of Ang II is perfusion pressure dependent. The aim was to study local splanchnic circulatory effects and tissue oxygenation during intravenous infusion of Ang II at different levels of regional arterial driving pressure in a whole-body large animal model. METHODS: Ang II was infused in incremental doses (0-200 microg x h-1) in anaesthetised instrumented pigs (n=8). Mean superior mesenteric arterial pressure (PSMA) was adjusted by a local variable perivascular occluder. Perivascular ultrasound and laser-Doppler flowmetry were used for measurements of mesenteric venous blood flow and superficial intestinal blood flow, respectively. Intestinal oxygenation was evaluated by oxygen tissue tension (PtiO2) and lactate fluxes. RESULTS: Ang II produced prominent and dose-dependent increases in mesenteric vascular resistance (RSMA) when the intestine was exposed to systemic arterial pressure, but Ang II increased RSMA only minimally when PSMA was artificially kept constant at a lower level (50 mmHg) by the occluder. Although Ang II decreased PtiO2 at a PSMA of 50 mmHg, splanchnic lactate production was not observed. CONCLUSION: We demonstrate that splanchnic vasoconstriction by exogenous Ang II is dependent on arterial driving pressure, suggesting significant potentiation through autoregulatory increases in vasomotor tone. Intestinal hypoxaemia does not seem to occur during short-term infusion of Ang II in doses that significantly increases systemic arterial pressure.

Angiotensin II↗

PubMed2002

Does dopexamine influence regional vascular tone and oxygenation during intestinal hypotension?

BACKGROUND: Local effects of dopexamine on intestinal vascular tone and oxygenation were investigated during intestinal hypotension. To this end, we employed an experimental model, in which the superior mesenteric arterial pressure (PSMA) was controlled by an adjustable perivascular clamp. This approach enabled us to keep the intestinal perfusion pressure (IPP) constant in the face of any systemic circulatory alterations. METHODS: In 11 barbiturate-anesthetized pigs, we instrumented the superior mesenteric circulation for assessments of vascular resistance (RMES), IPP, jejunal mucosal perfusion (Laser Doppler) and intestinal tissue oxygenation (microoximetry). Measurements were carried out before and during dopexamine infusions (0.5 and 1.0 micro g.kg-1.min-1) at a freely variable PSMA (i.e. the perivascular clamp fully open) and at a PSMA of 50 mmHg and 30 mmHg. RESULTS: At a constant PSMA of 50 mmHg, dopexamine had no significant intestinal vascular effects. However, at a constant PSMA of 30 mmHg, both doses of dopexamine were associated with decreases in RMES. Effects of dopexamine on intestinal oxygen delivery and extraction were minimal during these procedures, while a minor decrease in intestinal tissue oxygen tension was observed during dopexamine administration at the lowest IPP level. CONCLUSION: At very low intestinal perfusion pressures (approximately 30 mmHg) dopexamine produces intestinal vasodilation in excess of what is produced by intrinsic autoregulation. This suggests that there is a vasodilatory reserve in the intestine under such conditions and that a pharmacological vasodilator like dopexamine may improve intestinal circulation during regional severe hypotension.

Animals↗

PubMed2002

Myocardial ischemia induces coronary t-PA release in the pig.

BACKGROUND: Tissue-type plasminogen activator (t-PA) is the key factor in initiating endogenous fibrinolysis in the vascular compartment. Regulated release of t-PA from endothelial stores is rapidly induced by several humoral factors as well as coagulation activation products. The aim of the present study was to test the hypothesis that regional myocardial ischemia induces regulated release of t-PA in the coronary vasculature in vivo. METHODS: Healthy anesthetized (pentobarbital) pigs (n=8) were studied before and after a 10-min left anterior descending region coronary artery occlusion (LAD). Coronary fluxes of lactate, total t-PA antigen (ELISA, detecting both complex bound and free fraction) and active t-PA (functional assay detecting biological free fraction) were determined at 1, 3, 5 and 10 min of reflow. RESULTS: Coronary occlusion induced myocardial lactate production in all animals. Net coronary release of total t-PA, which was 21 ng/min during control, increased rapidly during reflow with a peak after only 1 min (136 ng/min), and returned to baseline within 3 min. Net release of active t-PA mirrored the overall net release response, but fell short of statistical significance. CONCLUSION: Data indicate a local myocardial profibrinolytic response following regional ischemia, which may serve as a prompt defence against coronary thromboembolic events.

Animals↗

PubMed2002

Streptozotocin induced diabetes in minipig: a case report of a possible model for type 1 diabetes?

Studies on the pathogenic process in type 1 diabetes are often performed in animal models. Low-dose administration of streptozotocin has been used to induce diabetes with pathological alterations similar to human type 1 diabetes in the animals. Rodent models are frequently used but there is a need of developing new models including larger animals. In this study we wanted to investigate to what extent a minipig was sensitive to low-dose streptozotocin for induction of diabetes with features of human Type I diabetes. A female Göttingen minipig received two low-doses (40 mg/kg) of streptozotocin with an 11-day interval. Serum was analysed for the presence of the enzyme glutamic acid decarboxylase, isoform 65, (GAD65) and autoantibodies against glutamic acid decarboxylase, isoform 65 (GAD65A), isoform 67 (GAD67A), insulinoma antigen 2 (IA-2) and insulin (IAA). Pancreas tissue was fixated in formaldehyde and was sent for pathoanatomical examination. The minipig became hyperglycaemic after the second injection of streptozotocin. The pathoanatomical examination showed atrophy of the beta-cell population, depletion of insulin with preserved glucagon content. There was no sign of insulitis. Both GAD65 and GAD65A were detected while GAD67A and IAA were absent. It is concluded that chronic diabetes developed after low-dose streptozotocin injection in a female minipig with the characteristics of the end stage of type 1 diabetes. This pilot study suggests that minipigs show promise as a model to induce diabetes by injections of low-dose streptozotocin.

Animals↗

PubMed2002

The cardiac effects of intracoronary angiotensin II infusion.

UNLABELLED: Angiotensin II (Ang II) is a potent vasoconstrictor, which recently has been shown to also have significant inotropic effects. Previous results regarding the mechanisms of the acute inotropic effects of Ang II are not conclusive. We designed this study to investigate the local cardiac effects of intracoronary Ang II infusion in doses not affecting systemic circulation. Ang II (2.5-40 microg/h) was infused in the left coronary artery of Yorkshire pigs (n = 9) reaching calculated intracoronary Ang II concentrations of 842 +/- 310, 3342 +/- 1238, and 12448 +/- 4393 pg/mL, respectively. Cardiac systolic and diastolic function was evaluated by analysis of the left ventricular pressure-volume relationship. Coronary flow was measured by using a coronary sinus catheter and the retrograde thermodilution technique. No significant changes were seen in the systolic and diastolic function variables of heart rate, end-systolic elastance, preload recruitable stroke work, the time constant for isovolumetric relaxation, or in coronary vascular resistance and flow. The positive inotropic and chronotropic effects of Ang II seen in previous studies seem thus to be mediated via extracardiac actions of Ang II. Coronary vascular tone is not affected by local Ang II infusion in anesthetized pigs. IMPLICATIONS: The positive inotropic and chronotropic effects of angiotension II (Ang II) seen in previous studies seem to be mediated via extracardiac actions of Ang II. Coronary vascular tone is not affected by local Ang II infusion in anesthetized pigs.

Angiotensin II↗

PubMed2001

Heart-lung interactions during positive pressure ventilation: left ventricular pressure-volume momentary response to airway pressure elevation.

BACKGROUND: Left ventricular (LV) pressure and volume changes are known to occur in response to positive airway pressure (PAP). We aimed to further describe the immediate LV response to increased PAP as demonstrated in successive heart cycles with LV pressure and volume alterations. We postulated that these acute systematic LV events during institution of PAP can follow a distinct pattern that would allow calculation of parameters of systolic function, including end-systolic elastance (Ees) and preload recruitable stroke work (PRSW). We also aimed to examine the relationship of PAP-derived Ees and PRSW to the same parameters derived from vascular occlusion. METHODS: Eight anesthetized adult pigs were studied with invasive circulatory measurements including LV pressure and volume (conductance). The PAP intervention was an airway pressure plateau of 15 cm H2O for 6 s (APP). Venous occlusion was performed by transient balloon inflation in the inferior vena cava (IVCO). Ees and PRSW were derived for each APP and IVCO intervention. RESULTS: Central circulatory variables during APP and IVCO are reported. LV systolic function parameters could be derived from each of the heart-lung interactions during APP sequences. Ees and PRSW derived from APP showed a significant positive bias in relation to those derived from the IVCO sequence. CONCLUSIONS: We conclude that the heart-lung interactions during APP of the magnitude and duration shown here can allow derivation of Ees and PRSW. These parameters are not interchangeable with Ees and PRSW derived from IVCO.

Air Pressure↗

PubMed2001

Analysis of left ventricular systolic function during elevated external cardiac pressures: an examination of measured transmural left ventricular pressure during pressure-volume analysis.

BACKGROUND: Variations or disturbances in intrathoracic and extracardiac pressures (ECP) occur in critically ill and anaesthetised patients. There are uncertainties concerning the analysis of left ventricular pressure-volume relationship (LVPVR) and the calculation of systolic function parameters when conducted without reference to transmural left ventricular pressure (LVPtm) in the setting of elevated ECP. METHODS: In 7 anaesthetised adult pigs, we measured LVPVR using conductance volumetry and tip manometry along with measurement of pericardial and other intrathoracic pressures. Experimental pericardial infusion and pleural insufflation were performed. Transient controlled preload reductions were accomplished using balloon occlusion of the inferior vena cava. Preload recruitable stroke work (PRSW) was calculated using both intracavitary left ventricular pressure (LVPic) and LVPtm, and differences were tested for using a paired t-test. RESULTS: The pericardial and pleural interventions produced significant elevations in ECP. No difference in PRSW calculated using LVPic and LVPtm was detected. CONCLUSION: These results suggest that LVPtm need not be measured and included in LVPVR analysis of systolic function when there is significant external cardiac pressure. To be able to employ LVPVR analysis of systolic function without reference to LVPtm is important for simplified application in the clinical setting, particularly when elevated extracardiac pressures are suspected, or have been therapeutically induced, as with continuous positive pressure ventilation.

Anesthesia↗

PubMed2001

Effects of positive end-expiratory pressure on intestinal circulation during graded mesenteric artery occlusion.

BACKGROUND: Reduced gut perfusion is associated with multiple organ failure. Positive end-expiratory pressure (PEEP) reduces cardiac output (CO) and portal blood flow, and might be detrimental in a situation of already compromised intestinal circulation. The aim of this study was to investigate regional circulatory and metabolic effects of PEEP during graded regional hypoperfusion. METHODS: In 12 barbiturate-anesthetized pigs, we measured systemic and regional blood flows (superior mesenteric arterial, QSMA and portal venous, QPORT), jejunal mucosal perfusion (LDF), tissue oxygenation (PO2TISSUE) and metabolic parameters at PEEP (0, 4, 8 and 12 cm H2O) in a randomized order. Measurements were performed at unrestricted intestinal perfusion pressures (IPP) and at IPP levels of 50 and 30 mmHg. RESULTS: During unrestricted IPP, PEEP decreased MAP, CO, QSMA and QPORT, while systemic, and preportal (RPORT) vascular resistances and jejunal mucosal perfusion were not significantly changed. Preportal tissue oxygen delivery and PO2TISSUE decreased, while preportal tissue oxygen uptake was unaltered. During restricted IPP, PEEP produced the same pattern of hemodynamic alterations as when IPP was not restricted. QPORT and QSMA were lowered by the reductions in IPP, and QPORT was further reduced during PEEP. At an IPP of 30 mmHg, this reduction in QPORT decreased preportal tissue oxygen uptake. Consequently, intestinal ischemia, as indicated by increased net lactate production, occurred. Simultaneously, jejunal mucosal perfusion and PO2TISSUE declined. CONCLUSION: At IPP levels below 50 mmHg, even moderate levels of PEEP impaired local blood flow enough to cause intestinal ischemia. Our data underscore the importance of considering regional circulatory adaptations during PEEP ventilation.

Anesthesia↗

PubMed2001

Acute effects of angiotensin II on myocardial performance.

BACKGROUND: Specific angiotensin II (Ang II) receptors exist in many organs including peripheral blood vessels, cardiac myocytes and the central nervous system. This suggests multiple sites of actions for Ang II throughout the cardiovascular system. Cardiac effects of Ang II are not completely understood, though its prominent vasoconstrictor actions are well described. This study was designed to assess left ventricular function during administration of Ang II using relatively load-independent methods in a whole-animal model. METHODS: Ang II was infused in incremental doses (0-200 microg x h(-1)) in anaesthetised instrumented pigs (n=10). Cardiac systolic and diastolic function were evaluated by analysis of the left ventricular pressure-volume relationship. RESULTS: Heart rate (HR), mean arterial pressure (MAP) and systemic vascular resistance (SVR) increased dose-dependently with Ang II, while cardiac output (CO) remained unchanged. Systolic function indices, end-systolic elastance (Ees) and preload recruitable stroke work (PRSW), demonstrated dose-dependent increases. The diastolic function parameter tau (tau) did not change with increasing Ang II dose. CONCLUSION: Ang II infusion caused increases in contractility indices in anaesthetised pigs in the doses used in this study. The mechanisms for these systolic function effects may be a direct myocardial effect or modulated through changes in autonomic nervous system activity.

Angiotensin II↗

PubMed2000

Cutaneous sympathetic vasoconstrictor reflexes for the evaluation of interscalene brachial plexus block.

BACKGROUND: Although signs of sympathetic blockade following interscalene brachial plexus block include Horner's syndrome, increased skin temperature and vasodilatation, the degree of sympathetic blockade is not easily determined. The aim of this study was, therefore, to use activation of cutaneous finger pad vasoconstrictor reflexes for description and quantification of the degree of sympathetic blockade following unilateral interscalene brachial plexus block. METHODS: Eight patients scheduled for acromioplasty under general anesthesia were studied. An interscalene plexus catheter was inserted preoperatively on the side to be operated upon and used postoperatively for administration of bupivacaine, given as a bolus (1.25 mg kg(-1)) followed by a continuous infusion (0.25 mg kg(-1) h(-1)). Skin blood flow (SBF) in the pad of the index finger was assessed by the laser Doppler technique, and regional skin vascular resistance (RVR) was calculated. The inspiratory gasp test (apnea at end-inspiration) or a local heat provocation were used as provocations of the cutaneous microcirculation. RESULTS: Interscalene brachial plexus block increased SBF and decreased RVR at rest, and produced satisfactory sensory and motor block. The inspiratory gasp test decreased SBF and increased RVR in the unblocked arm, while the opposite, increased SBF and decreased RVR, were observed during local heat provocation. In the blocked arm, these gasp-induced cutaneous vasoconstrictor and heat-induced vasodilator responses were attenuated. CONCLUSIONS: Interscalene brachial plexus block reduces regional sympathetic nervous activity, illustrated by increases in skin blood flow, skin temperature and attenuated vasoconstrictor responses to an inspiratory gasp. The inspiratory gasp vasoconstrictive response is a powerful and sensitive indicator for monitoring the sympathetic blockade following interscalene brachial plexus block.

Adult↗

PubMed2000

Surgical stress induces acute coronary release of tissue-type plasminogen activator in the pig.

BACKGROUND: Tissue-type plasminogen activator (t-PA) is an endothelium derived key enzyme in the initiation of endogenous fibrinolysis. Acute regulated release of active t-PA occurs within minutes in response to threatening thrombotic vessel occlusion. The aim of this study was to investigate the impact of surgical stimulation on the kinetics of t-PA release in the coronary vascular bed in the pig. METHODS: In anaesthetised pigs (n=16), arterio-venous concentration gradients of t-PA, and plasma flows (retrograde thermodilution) were obtained across the coronary vascular bed before (control) and at 1, 3, 5 and 10 min after sternotomy. RESULTS: At control, no significant coronary net flux (release or uptake) of t-PA was observed, while sternotomy induced a rapid net release of total t-PA (132.6 ng x min(-1)), with an associated increase in active t-PA (93.6 ng x min(-1)). This response, evident already after 1 min, showed a peak at 5 min and returned towards baseline levels within 10 min. No concurrent alterations in aortic levels of active t-PA were found and haemodynamic variables were unaltered. CONCLUSION: The rapidly increasing and transient net coronary release of t-PA after sternotomy suggests that the endothelium actively promotes local endogenous fibrinolysis during surgery. Such events could reflect a dynamic responsiveness to protect the coronary circulation during stress.

Animals↗

PubMed2000

Angiotensin II mesenteric and renal vasoregulation: dissimilar modulatory effects with nitroprusside.

BACKGROUND: The role of systemic arterial pressure for the vascular effects of angiotensin II (Ang II) and the interactions between Ang II and perfusion pressure-dependent local vascular control mechanisms are not well understood. This study addresses these aspects of exogenous Ang II in the mesenteric and renal regional circulations. METHODS: Ang II was infused in incremental doses (0-200 microg/h) in anesthetized instrumented pigs (n=10). Renal and portal blood flows were measured by perivascular ultrasound. In the second part of the study, sodium nitroprusside (SNP) was infused at doses titrated to keep mean arterial pressure constant, in spite of concurrent Ang II administration. RESULTS: Powerful dose-dependent vasoconstrictions by Ang II were found in renal and mesenteric vascular beds (at highest Ang II doses vascular resistances increased by 109% and 88% respectively). Ang II-induced vasoconstriction was fully inhibited in the mesenteric, but not in the renal circulation, during conditions of constant mean arterial pressures achieved by SNP infusion. CONCLUSIONS: Mesenteric, but not renal, vasoconstriction by Ang II was inhibited by pharmacological maintenance of perfusion pressure. This could reflect differences between these vascular beds as regards the importance of co-acting myogenic pressure-dependent vasoconstriction. Alternatively, as the drug chosen for pressure control, sodium nitroprusside, serves as a nitric oxide donor, the relative balance between nitric oxide-mediated vasodilation and Ang II-induced vasoconstriction could have regional differences.

Angiotensin II↗

PubMed2000

Specific angiotensin II receptor blockage improves intestinal perfusion during graded hypovolemia in pigs.

OBJECTIVE: To investigate the potential of specific angiotensin II subtype 1 (AT1) receptor blockade to modify the mesenteric hemodynamic response to acute hypovolemia and retransfusion. DESIGN: Prospective, randomized, controlled experimental study. SETTING: University-affiliated animal research laboratory. SUBJECTS: Fasted, anesthetized, ventilated, juvenile domestic pigs of both sexes. INTERVENTIONS: Acute, graded hypovolemia by 20% and 40% of the total estimated blood volume followed by retransfusion in control animals (CTRL; n = 10) and animals pretreated with the AT1 receptor blocker candesartan (CAND; n = 10). MEASUREMENTS AND MAIN RESULTS: Invasive monitoring of arterial and central venous blood pressures, cardiac output, portal venous blood flow, and jejunal mucosal blood flow. Blood gases were repeatedly analyzed to calculate oxygen delivery and consumption. Thirty minutes after each level of hypovolemia at 20% and 40%, cardiac output was decreased in CTRL animals from a baseline of 2.9 +/- 0.1 to 1.8 +/- 0.2 and 1.1 +/- 0.2 L/min, with no differences compared with CAND animals. Cardiac output was restored to 3.0 +/- 0.3 L/min 30 mins after retransfusion in CTRL animals, with no significant intergroup differences. Baseline portal venous blood flow (Q(MES)) and jejunal mucosal perfusion (PU(JEJ)) were greater in CAND animals compared with CTRL animals. During graded hypovolemia, CAND animals maintained Q(MES) and PU(JEJ) at significantly higher levels compared with CTRL animals, particularly after 40% hemorrhage (+221% and + 244%, respectively, relative to the mean values in CTRL animals). The same pattern was observed after retransfusion. Moreover, the calculated mesenteric critical oxygen delivery was significantly greater in CTRL animals (74 mL/min) compared with CAND animals (34 mL/min). No animals died in the CAND group, whereas four animals died during 40% hypovolemia or retransfusion in the CTRL group. CONCLUSIONS: Specific AT1 blockade before acute hypovolemia significantly ameliorated mesenteric and, in particular, jejunal mucosal hypoperfusion. In addition, cardiovascular stability was improved, and mortality in conjunction with acute hypovolemia and retransfusion could be completely avoided. These findings support a fundamental role of the renin-angiotensin system in the mesenteric response to acute hypovolemia and indicate a substantial interventional potential for candesartan in conjunction with circulatory stress.

Acid-Base Equilibrium↗