Drop In Mean Pressure Research Articles

Nonlinear generation of sound and mean pressure drop in shock–shear interaction

Interactions of shear fluctuations with shock waves are ubiquitous in high-speed flow applications from scramjet propulsion to cosmic events like supernova explosions. They also serve as fundamental building blocks for the study of shock–turbulence interaction. In this work, we study the nonlinear effects in pressure arising due to the interaction of a normal shock with a two-dimensional shear wave. It employs the weakly nonlinear framework (WNLF) developed recently for vorticity amplification by Thakare et al. [“A weakly nonlinear framework to study shock–vorticity interaction,” J. Fluid Mech. 933, A48 (2022)]. The analysis includes the effect of intermodal interactions that is neglected in the widely used linear interaction analysis (LIA) of shock–turbulence interaction. It is found that the deformation of the shock wave and the fluctuation mass flux normal to the shock contribute to the dominant physical mechanisms responsible for the observed nonlinearities. Interestingly, the WNLF predicts a drop in mean pressure behind the shock due to a second-order intermodal interaction, which is consistent with the well-established results by Lele [“Shock-jump relations in a turbulent flow,” Phys. Fluids A 4, 2900–2905 (1992)] at low Mach numbers and brings out additional effects of shock deformation that are important at higher Mach numbers. We extend the WNLF to three-dimensional interaction of homogeneous isotropic turbulence with a normal shock. Comparison with existing direct numerical simulation data shows good agreement for low turbulent Mach numbers, which is a significant improvement over the prediction capability of LIA. We also compute the dilatation fields from WNLF and use them to distinguish between the acoustic and non-acoustic components of the second-order pressure fluctuations generated by the shock wave.

Vasodilator use in precapillary pulmonary hypertension with end stage kidney disease: A single center experience

Background and objectivesPulmonary hypertension is commonly seen in end stage kidney disease and is most commonly due to elevated left heart pressures. There is limited data about vasodilator use during the management of Group 1 pulmonary arterial hypertension in the context of those who also have or later developed end stage kidney disease. The objective of this study was to determine safety and efficacy of vasodilator therapy in precapillary pulmonary hypertension requiring renal replacement therapy. DesignThis was a single-center retrospective case series. Patients were identified from our Pulmonary Hypertension Clinic using a historical roster from 2012 to 2020. Patients were included if they >18 years of age, had Group 1 or Group 4 (precapillary) pulmonary hypertension on right heart catheterization, and also had end stage kidney disease requiring either intermittent hemodialysis or peritoneal dialysis. Results18 patients were identified with invasively confirmed Group 1 or Group 4 pulmonary hypertension and end stage kidney disease on renal replacement therapy. Scleroderma was the most common etiology for renal failure. 17 patients were treated with vasodilator therapy. Fifteen patients had paired right heart catheterizations that showed a significant decrease in mean pulmonary artery pressure and pulmonary vascular resistance. Therapy was relatively well tolerated but hypotension was common and midodrine was often helpful. Two patients had successful renal transplantation after starting vasodilator therapy. ConclusionWe found vasodilator therapy was reasonably well tolerated and associated with a drop in mean pressure and pulmonary vascular resistance in patients with end stage kidney disease on dialysis.

Comparison of Tramadol and Pethidine for Control of Shivering Following Central Neuraxial Blockade

Background: Central neuraxial blockade is associated with shivering in 40-60% of the patients. A popularly used drug to control shivering is pethidine. The present study was conducted to evaluate the effect of tramadol on shivering and compare it with the efficacy of pethidine. The study was also intended to compare the haemodynamics, complications and recurrence of shivering with the use of pethidine and tramadol. Subjects and Methods: This prospective comparative study was conducted in Department of Anaesthesiology, Akash Institute of Medical Sciences and Research Centre, Devanahalli, Bengaluru. In this study, 80 consenting patients of either gender, aged between 20-60 years, in American Society of Anesthesiologists (ASA) Grades 1, 2 and 3 according to ASA who experienced shivering during or immediately after elective surgeries under central neuraxial blockade (spinal, epidural and combined spinal and epidural) were randomized to receive either pethidine 1mg/kg or tramadol 1 mg/kg for control of shivering. The time interval for the onset of shivering after regional anaesthesia, onset of disappearance of shivering after drug administration, complete disappearance of shivering, hemodynamics, recurrence of shivering and complications were recorded. Results: There was no statistical difference in the onset of disappearance between the 2 groups (p=0.615). Time taken for complete disappearance of shivering after 5 minutes interval period was statistically more in Group T (17.5% vs 5% in Group P) with p= 0.154. Recurrence of shivering occurred more in the tramadol group as compared to pethidine group which was strongly significant statistically (27.5% vs 5.0%) with p=0.006. However the incidence of complications was higher with pethidine with a greater drop in mean blood pressure, increased indicators of respiratory depression, more sedation, greater nausea, vomiting and itching. Conclusion: The present study results may conclude that tramadol is an effective drug in the control of shivering with more stable hemodynamic and fewer side effects such as sedation, respiratory depression, nausea, vomiting and itching. However one must be prepared for a slight delay in the onset of its action and expect a recurrence of shivering which may require further therapy. Pethidine, with its equal efficacy may be advocated in patients allergic to tramadol and where sedation is desirable.

Mean flow and turbulence statistics through a sluice gate in a navigation lock system: A numerical study

The flow through partially-open control valves in navigation locks, particularly at the early portion of an operation cycle, is characterized by high velocities, flow recirculation, significant pressure drops, and pressure fluctuations within the culverts. Optimizing the flow control system is a key point in hydraulic projects of high-drop locks. In order to analyze the hydraulic parameters of the mean flow and turbulence statistics through a navigation lock control valve, experimental and numerical work was undertaken. This paper focuses on the numerical aspects of the research. A physical model with a rectangular culvert (25 cm x 25 cm) test section with a segment gate (Tainter) installed in its inverted position was used in the experimental research. Physical tests were carried out under steady conditions for six gate openings and nine discharges. During these tests, mean and instantaneous pressures were recorded along the base and the ceiling of the culvert. The numerical investigation was carried out using the Computational Fluid Dynamics (CFD) software FLOW- 3D®. In FLOW- 3D®, the Reynolds-Averaged Navier–Stokes (RANS) equations were solved by the methods of finite volumes/finite differences in two dimensions. To solve the problem of closing RANS equations, the turbulence model k−ε was adopted. Based on the results, it was possible to verify that the numerical model very nicely reproduced the behavior of experimental data of mean hydraulic head and mean flow velocities. Although along the culvert ceiling, particularly close to the gate, the drop in mean pressure was slightly underestimated by the numerical model at the flow recirculating zone, it is possible to state with confidence that the overall results underscore the accuracy of this CFD approach in the study of the mean flow downstream from the control valves in navigation lock filling–emptying systems.

Percutaneous balloon mitral valvuloplasty in pregnant patients with rheumatic mitral stenosis: A ten-year single-center experience

Rheumatic mitral Stenosis is a common issue in Tunisia causing significant morbidity and mortality. Women with severe mitral stenosis often do not tolerate cardiovascular demands of pregnancy despite medical therapy, with an urgent need to enhance mitral valve area by percutaneous balloon mitral valvuloplasty (BMV). To determine immediate and long-term maternal and fœtal outcomes after BMV during pregnancy. This was retrospective single center experience, analysing data from BMV registry from January 2008 to December 2018. During the study period, 40 pregnant women among a total of 461 patients (9%) underwent BMV for severe mitral stenosis. The mean age was 35 ± 5 years. The mean gestational age was 26 ± 8 weeks. The BMV was successful in 38 out of 40 patients (95%), achieving mitral area > 1.5 cm 2 with a drop in left atrial mean pressure from 30 ± 9 mmHg to 16 ± 5 mmHg. In all successful procedures, patients improved their NYHA status by at least one stage. There was no maternal mortality in our series. One procedure had to be abandoned because of failed septal puncture. One patient developed severe mitral regurgitation secondary to chordae rupture, and had as a consequence emergent valve replacement. Thirty-three patients had a normal delivery while seven patients underwent a caesarean section. We reported a single neonatal death 48 hours after delivery caused by preterm respiratory distress. The BMV permitted a clinical and hemodynamic improvement and allowed the pursuit of pregnancy until end of term in most of cases. On 57-month mean follow-up, there were 3 cases of mitral restenosis, all babies maintained normal growth and development. Percutaneous balloon mitral valvuloplasty was associated with low maternal and fœtal risk and should be considered as the treatment of choice in pregnant women with severe mitral stenosis.

A Simplified Waveform Energetics Approach to Interpreting Arterial and Venous Pressure

Abstract This paper develops a novel methodology for extracting simple, beat-to-beat, lumped metrics of systemic circulation performance by comparing the catheter pressure waveforms from the femoral artery and vena cava. Their diagnostic potential is compared to the similar, clinically used metric ΔMP, the drop in mean blood pressure between the aorta and vena cava, across an experimental cohort encompassing the progression of sepsis and several clinical interventions known to alter circulatory state. Both Ofe→vc, the model derived pressure attenuation between the femoral artery and vena cava, and the clinical metric, ΔMP, performed well. However, Ofe→vc reduced the optimal average time to sepsis detection from endotoxin infusion from 46.2 minutes for ΔMP to 11.6 minutes, for a slight increase in false positive rate from 1.8% to 6.2%. Thus, the potential diagnostic benefits of this novel approach are demonstrated, and a case is made for further investigation.

Intrapulmonary artery balloon pulsation improves circulatory function after acute myocardial infarction in pigs.

To examine whether pulmonary artery balloon pulsation (PABP) could improve circulatory function in acute myocardial infarction (AMI) in pigs. Ten downsize pigs were sedated and ventilated. AMI was induced by inserting a plug into the left anterior descending artery. A pulsation balloon was placed in the pulmonary artery in all animals. In the treatment group (TG), pulsations began when life-threatening arrhythmia or > 30% drop in mean blood pressure (MBP) or > 40% decrease in cardiac output compared to baseline occurred. Pulsation rate was 120/min, independent of the heartbeat, maintained for 10 min. The control group (CG) received no pulsation. In the TG (n = 5), mean BP after the AMI improved by 7 ± 12 mmHg after 150 min while in the CG, MBP decreased by 17 ± 25 mmHg, P < 0.05; coronary perfusion pressure improved by 8 ± 7 mmHg in the TG but decreased by 15 ± 12 in the CG (P < 0.05). In the CG, cardiac output did not change but in the TG it improved from 3.5 ± 0.9 after the AMI to 4.2 ± 1.1 l/min 150 min after AMI (P < 0.05). The TG required 1.8 ± 0.4 electric shocks for ventricular fibrillation versus 0.8 ± 0.4 in the pulsation group (P < 0.05). PABP could be useful in the management of AMI due to improved mean arterial BP, coronary perfusion pressure, cardiac output and electrical stability. The mechanism of this effect remains to be determined.

Toxic Effects of Palladium Compounds on the Isolated Rat Heart

Taken into consideration limited data about effects of palladium on cardiovascular system, the aim of our study was to compare toxicity of inorganic and organic palladium compounds on the isolated rat heart. The hearts (total number n=30, 6 for each experimental group) excised from Wistar albino rats, male sex, age 8 weeks, and body mass 180-200 g, were retrogradely perfused according to the Langendorff technique at constant perfusion pressure (70 cm H2O). After the insertion of sensor in the left ventricle, the parameters of heart function: maximum rate of left ventricular pressure development (dP/dt max), systolic left ventricular pressure (SLVP), diastolic left ventricular pressure (DLVP), mean blood pressure (MBP) and heart rate (HR)), were continuously registered. The experiments were performed during control conditions, and in the presence of perfusion with incresing concentration of the following: (triethanolamine (TEA), triethanolamine acetate (TEAA), palladium(II)chloride (PdCl2), and trans-dichlorobis(triethanolamine-N)palladium(II) complex (trans-[PdCl2(TEA)2])) started every 30 minutes (30, 60, 90, 120 minute). dP/dt max was not affected significantly by either TEAA, TEA, PdCl2 or Pd complex. SLVP was, also, not affected significantly by either TEAA, TEA, PdCl2, or Pd complex. DLVP was significantly decreased by both TEAA and PdCl2, while TEA and Pd complex did not show significant effect. MBP was significantly decreased only by PdCl2, while TEAA, TEA and Pd complex did not show significant effect. HR was significantly decreased by all compounds- PdCl2, TEAA, TEA and Pd complex. In our study, inorganic palladium compound (PdCl2) induced clear depression of the isolated rat heart contractility, manifested as drop in diastolic and mean blood pressure , and as decrease of the heart rate. On the other hand, it seems that palladium, when bound in an organic compound (linked to TEA in Pd complex), does not contribute significantly to cardio-toxicity in our experimental conditions.

Maintenance of Minute Circulation Volume during Orthotopic Liver Transplantation

Objective: to optimize procedures to maintain minute circulation volume at different stages of orthotopic liver transplantation. Subjects and methods. In the period 2005—2010, Sverdlovsk Regional Clinical Hospital One performed 32 orthotopic liver transplantations, including one retransplantation. The patients’ ASA class was (4—5). The operations were carried out under general anesthesia. The mean duration of surgery was 8.1 (range 5.8—10.5) hours. The investigators applied anesthesia based on iso-fluorane 0.6—0.9 MAC (by monitoring the anesthesia depth index with cerebral state index (CSI-40-60)), as well as extended central hemodynamic monitoring (prepulmonary hemodilution). All the operations were made via portofemoroaxillary bypass, by using a centrifugal Biopump. Eight surgical stages were identified: 1) run-in (after tracheal intubation); 2) liver mobilization; 3) partial bypass; 4) complete bypass (hepatectomy, a liver-free period); 5) reperfusion; 6) a postreperfusion period (bypass end); 7) biliary repair; 8) the end of an operation. The concentrations of blood parameters, electrolytes, acid-base balance, and the levels of lactate and glucose were examined. The data were processed statistically. Central hemodynamics was monitored by prepulmonary thermodilution, by calculating cardiac index (CI), stroke index, and total peripheral vascular resistance index (TPVRI) at the stages: liver mobilization, postreperfusion period (bypass end), and the end of surgery. Results. Even during partial bypass, there was a significant drop in mean blood pressure (MBP) as compared to the baseline levels (p<0.05). Reperfusion was also accompanied by a significant decrease in MBP and an increase in heart rate. At the end of reperfusion and in the postreperfusion period, TPVRI was halved (689.2±68.0) as compared to the baseline levels. In the postreperfusion period, central venous and pulmonary artery pressures were significantly increased by 32 and 21%, respectively. That period was marked by a significant rise in CI. Serum lactate and glucose elevations starting from the complete bypass stage were associated with the liver being excluded from the circulation and cannot be a marker of inadequate tissue perfusion. Conclusion. The decrease in MBP during portofemoroaxillary bypass is associated with hypovolemia and mainly with vasoplegia during reperfusion. Approaches to maintaining the adequate minute circulation volume depend on the surgical stage: sufficient preload is needed during complete bypass and it is expedient to combine an infused load with vasopressors for the correction of the reperfusion syndrome with low TPVR. Key words: liver transplantation, minute circulation volume, general anesthesia, central hemodynamics.

Acute amiodarone toxicity due to an administration error: could excipient be responsible?

Acute amiodarone toxicity due to an administration error: could excipient be responsible?

High-frequency oscillatory ventilation: Mechanisms of gas exchange and lung mechanics

Overview of the mechanisms governing gas transport, mechanical factors influencing the transmission of pressure and flow to the lung, and the measurement of lung mechanics during high-frequency oscillatory ventilation (HFOV) in acute respiratory distress syndrome. Studies indexed in PubMed illustrating key concepts relevant to the manuscript objectives. Pressure transmission during HFOV in the adult lung was simulated using a published theoretical model. Gas transport during HFOV is complex and involves a range of different mechanisms, including bulk convection, turbulence, asymmetric velocity profiles, pendelluft, cardiogenic mixing, laminar flow with Taylor dispersion, collateral ventilation, and molecular diffusion. Except for molecular diffusion, each mechanism involves generation of convective fluid motion, and is influenced by the mechanical characteristics of the intubated respiratory system and the ventilatory settings. These factors have important consequences for the damping of the oscillatory pressure waveform and the drop in mean pressure from the airway opening to the lung. New techniques enabling partitioning of airway and tissue properties are being developed for measurement of lung mechanics during HFOV. Awareness of the different mechanisms governing gas transport and the prevailing lung mechanics during HFOV represents essential background for the physician planning to use this mode of ventilation in the adult patient. Monitoring of lung volume, respiratory mechanics, and ventilation homogeneity may facilitate individual optimization of HFOV ventilatory settings in the future.

NO and KATP channels underlie endotoxin-induced smooth muscle hyperpolarization in rat mesenteric resistance arteries.

1 Smooth muscle membrane potential and tension measurements were made in isolated mesenteric resistance arteries from rats exposed to bacterial endotoxin (lipopolysaccharide, LPS; 10 mg kg(-1), i.p.) for 3 h to mimic septic shock syndrome. 2 Over this period, rats developed an endotoxaemic response, assessed in vivo as a 41+/-4 mmHg drop in mean blood pressure, vascular hyporeactivity to noradrenaline (1 microg kg(-1), i.v.) and a significant increase in core body temperature. 3 In mesenteric small resistance arteries from these rats (o.d. 180 - 240 microm), phenylephrine (0.01-3 microm)-evoked contraction was not altered when compared with arteries from sham-operated animals, but the concentration-relaxation curve to acetylcholine (ACh; 0.01 - 3 microm) displayed a small, but significant, shift to the right. 4 The smooth muscle resting membrane potential (-70.3+/-1.6 mV) in arteries from LPS-treated rats was significantly greater than in control arteries (-55.4+/-1.2 mV), but in both cases the smooth muscle was depolarized to a similar potential by the application of N(omega)-nitro-L-arginine methyl ester (L-NAME; 0.3 mm; -54.1+/-2.3 vs -52.4+/-2.5 mV) or glibenclamide (10 microm; -55.0+/-2.1 vs -50.4+/-2.0 mV). 5 ACh (1 microm) elicited a maximal hyperpolarization, which ranged from -14.7+/-3.2 mV (in arteries from LPS-treated rats) to -20.6+/-2.4 mV (in arteries from sham-operated rats), and was not altered by the presence of L-NAME. Levcromakalim (1 microm) increased the smooth muscle membrane potential by around -24 mV in arteries from both sets of experimental animals. 6 These results indicate that at the level of the resistance vasculature, endotoxaemia is associated with pronounced smooth muscle hyperpolarization reflecting the action of NO on KATP channels. These changes were not associated with vascular hyporeactivity or depressed endothelial cell function in vitro, suggesting that mesenteric resistance arteries may not contribute to equivalent changes in vivo.

Hemodynamic effects of a new percutaneous circulatory support device in a left ventricular failure model.

We have tested a new percutaneous circulatory support device in seven anesthetized calves with induced left ventricular failure. The device is based on a flexible catheter with a foldable propeller and cage at the distal end. The rotation of the propeller (1,000-15,000 rpm) is transmitted from a drive unit at the proximal end to the propeller by way of a rotating wire inside the catheter. This also contains an umbrella-like mechanism to open the pump head from the folded (diameter 4.6 mm) to the active position. The rotation of the propeller creates a pressure drop in front of the propeller and a pressure rise behind. Heart failure was induced with metoprolol and verapamil in combination with a VVI pacemaker to create a left atrial pressure greater than 20 mm Hg. A centrifugal pump was used to bypass the right ventricle and to ensure a sufficient filling of the left ventricle. After baseline recordings, the pump was run at 14,000 rpm, and the hemodynamic response was compared with the baseline. A 24 +/- 10 mm Hg pressure gradient was generated across the pump, resulting in a drop in the right carotid artery mean pressure from 80 +/- 11 to 71 +/- 13 mm Hg (p = 0.008) and a drop in the left ventricular systolic pressure from 109 +/- 17 to 100 +/- 19 mm Hg (p = 0.004). The pressure in the left atrium decreased from 25 +/- 3 to 20 +/- 5 mm Hg (p = 0.008). The mean femoral pressure increased from 78 +/- 10 to 95 +/- 20 mm Hg (p = 0.005). A moderate reduction in the right carotid flow was observed (15%, p = 0.029), whereas no significant changes were found in the coronary flow, the flow in the right femoral artery, or in the left kidney. The device showed a significant unloading of the left ventricle and an increased perfusion pressure for the lower part of the body. The moderate changes in flow were probably caused by still active autoregulation, and this needs to be tested with more pronounced circulatory failure.

Single lead dual-chamber pacing

The patient was a 62-year-old man routinely ventilated and paced at 90 beats per minute following an uncomplicated triple coronary artery bypass graft. The temporary pacemaker was set in atrial pacing AAI mode in order to provide atrial transport and a narrow QRS complex. The atrioventricular (spike-to-QRS) interval was 0.20 s. The paced P waves were isoelectric in this lead; their presence was inferred by atrial pacing at different rates (not shown). The staff reported that at times the atrial lead was pacing the ventricle (Fig 1, upper strip). The ventricular pacing was associated with a drop in mean blood pressure of 10 to 12 mm Hg. While the pacemaker output was being decreased to determine the pacing threshold, atrial pacing was resumed (Fig 1, bottom strip), with improved blood pressure recorded on the readout. No movements or changes in the ventilator or patient status were observed apart from the deliberate reduction in the pacemaker output. This had to be accounted for. Whereas transvenous temporary pacing wires can “flip” between the right ventricle and the right atrium, this was not (and still is not) known to happen to epicardial leads inserted by the surgeon during the operation. The pacemaker was next set into a sequential (DDD) mode, proving that the lead pacing the ventricle was the original atrial lead (Fig 2, upper strip). The ventricular spike, as programmed, followed the atrial spike by 0.12 s and fell in the middle of the broad (paced) QRS complex. This was harmless, but looked vaguely alarming; the pulse generator was reset to the AAI mode. Next, repeated manipulation of the output showed that, at higher outputs, the lead behaved as a ventricular pacer and at lower outputs, as atrial From Canberra Hospital, ACT, Australia.

Effect of Ticlopidine Hydrochloride on Erythropoietin-Induced Rise in Blood Pressure in Patients on Maintenance Hemodialysis

Background/Aims: A recent observation that antiplatelet-aggregation drugs, including ticlopidine hydrochloride, may prevent erythropoietin (EPO)-induced rise in blood pressure in hemodialysis (HD) patients remains a subject of particular interest. The aim of the present study was to determine the effect of ticlopidine hydrochloride on EPO-induced rise in blood pressure of HD patients with special reference to blood levels of vasoactive substances. Methods: HD patients who showed hypertension or aggravation of preceding hypertension with EPO treatment were selected for this study. Ticlopidine hydrochloride was administered at a dose of 200 mg daily for 4 weeks. Blood pressure and serum levels of nitric oxide (NO), atrial natriuretic peptide (ANP) and endothelin (ET) were determined before and after drug administration. Patients were divided into two groups, one of which showed a drop in mean blood pressure (MBP) of >10 mm Hg (group I) and one which did not (group II), and a comparison was made between them with respect to the blood parameters. Results: Five of 15 patients showed a drop of MBP of >10 mm Hg (group I), and 10 patients did not show any change in MBP (group II). In group I, there was a significant increase in blood NO levels compared to the concentrations before ticlopidine administration, while there was no change in group II. With respect to ANP and ET, there was no significant change in either of the groups. Conclusion: The findings suggest that the preventive effect of ticlopidine hydrochloride on EPO-induced rise in blood pressure may partly be related to the enhancement of NO production in patients on maintenance HD.

Complementary effects of adenosine and angiotensin II in hypoxemia-induced renal dysfunction in the rabbit

The acute renal effects of hypoxemia and the ability of the co-administration of an angiotensin converting enzyme inhibitor (perindoprilat) and an adenosine receptor antagonist (theophylline) to prevent these effects were assessed in anesthetized and mechanically-ventilated rabbits. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by the clearances of para-aminohippuric acid and inulin, respectively. Each animal acted as its own control. In 8 untreated rabbits, hypoxemia induced a significant drop in mean blood pressure (−12 ± 2%), GFR (−16 ± 3%) and RBF (−12 ± 3%) with a concomitant increase in renal vascular resistance (RVR) (+ 18 ± 5%), without changes in filtration fraction (FF) (−4 ± 2%). These results suggest the occurrence of both pre- and postglomerular vasoconstriction during the hypoxemic stress. In 7 rabbits pretreated with intravenous perindoprilat (20 μg/kg), the hypoxemia-induced changes in RBF and RVR were prevented. FF decreased significantly (−18 ± 2%), while the drop in GFR was partially blunted. These results could be explained by the inhibition of the angiotensin-mediated efferent vasoconstriction by perindoprilat. In 7 additional rabbits, co-administration of perindoprilat and theophylline (1 mg/kg) completely prevented the hypoxemia-induced changes in RBF (+ 11 ± 3%) and GFR (+ 2 ± 3%), while RVR decreased significantly (−14 ± 3%). Since adenosine and angiotensin II were both shown to participate, at least in part, in the renal changes induced by hypoxemia, the beneficial effects of perindoprilat and theophylline in this model could be mediated by complementary actions of angiotensin II and adenosine on the renal vasculature.

Potentiation of sildenafil-induced hypotension is minimal with nitrates generating a radical intermediate.

Recently the new specific phosphodiesterase-5 inhibitor sildenafil was introduced into therapy for erectile dysfunction. Because of the phosphodiesterase-5 inhibitor-induced increases of cyclic GMP in the vasculature, vasodilation in various vascular beds is induced, which in combination with various nitrovasodilators (e.g., when used simultaneously for the treatment of coronary artery disease), may lead to excessive hypotension. Thus nitrovasodilators are contraindicated when sildenafil may be used and reports of a number of accidents have recently been published. We therefore studied the acute interactions of glyceryl trinitrate (GTN), pentaerythritol tetranitrate (PETN), and isosorbide dinitrate (ISDN) with sildenafil in six chronically instrumented conscious dogs for each nitrate to assess the magnitude of blood pressure drops (and compensatory increases in heart rate) during a 24-h nitrate administration (infusion into the pulmonary artery). Sildenafil (3 mg/kg) was given orally (after a 24-h fast) 30 min after start of nitrate infusion. GTN, PETN, or ISDN (which follow different steps of metabolic conversion to nitric oxide) were applied at submaximal dosages leading to 90% of maximal coronary artery dilation at 1.5 microg/kg per min, 0.75 microg/kg per min, or 6 microg/kg per min, respectively. During GTN infusion sildenafil caused a maximum drop in mean blood pressure of 21 +/- 3 mm Hg (rise in heart rate from 117.0 +/- 7.2 to 126.0 +/- 6 .0/min) and during ISDN infusion of 18 +/- 3 mm Hg (rise in heart rate from 115.0 +/- 7.0 to 125 +/- 6/min), which was significantly less (p < 0.01) during PETN (only 6 +/- 1 mm Hg with a rise in heart rate from 107.0 +/- 5.0 to 122.0 +/- 7.0/min). When sildenafil is used during exposure to nitrates (e.g., in coronary artery disease), the PETN-induced drop in blood pressure at equi-effective dosages (with regard to coronary dilation) is substantially smaller compared with that of GTN or ISDN, which is probably because of lesser potentiation of phosphodiesterase-5 inhibitor-induced effects in the arteriolar bed, thus minimizing critical drops in blood pressure.

Instability Of Cerebral Blood Flow In Diabetic Patients With Cardiovascular Autonomic Neuropathy And Orthostatic Hypotension

Cardiovascular autonomic neuropathy (CAN) is a risk factor for stroke in people with diabetes mellitus, and orthostatic hypotension (OH) is a feature of CAN. Therefore, the purpose of this study was to evaluate the mean cerebral blood flow velocity (MFV) in response to standing up in patients with diabetes and OH. We studied 27 patients with diabetes mellitus, among whom 8 had CAN and OH (OH+, age: 46.4 ± 13.5 years, diabetes duration: 25.0 ± 11.0 years; mean ± SD), 7 had CAN but without orthostatic hypotension (OH‐, age: 47.3 ± 12.7, diabetes duration: 26.4 ± 12.1 years), 12 had no evidence of CAN (CAN‐, age: 44.1 ± 13.8, diabetes duration: 17.1 ± 10.2 years), and 14 control subjects (age: 42.6 ± 9.1 years). The MFV in the right middle cerebral artery was recorded using transcranial Doppler sonography in the supine position after 15 minutes of rest and immediately after standing up. The change from the supine position to standing resulted in a pronounced drop in mean blood pressure in the OH+ group (−14.0 ± 20.9 mmHg), while there were no significant changes in blood pressure in the other groups. MFV in the supine position was not different between the diabetic (either with or without CAN or OH) and control groups. However, the relative percentage changes in MFV immediately after standing up were −23.3 ± 17.2% in OH+, +0.6 ± 14.6% in OH‐, −2.3 ± 15.1% in CAN‐, and −10.5 ± 11.1% in the control group (p &lt; 0.05 for OH+ vs. the other groups). Patients with diabetes mellitus complicated by CAN and OH may show instability in cerebral blood flow regulation on standing. Whether this finding is associated with a higher susceptibility to stroke in these patients remains to be established in prospective studies.

Comparison of the abilities of human parathyroid hormone(1-31)NH2 and human parathyroid hormone-related protein(1-31)NH2 to stimulate femoral trabecular bone growth in ovariectomized rats.

N-terminal fragments of PTH and PTHrP, such as hPTH-(1-34) and hPTHrP-(1-34), are sufficiently similar with respect to amino acid sequence, location of functional domains, and higher order configuration to activate the same PTH/PTHrP receptor and the same two signal enzymes, adenylyl cyclase and phospholipase-Cbeta. Therefore, it was expected that hPTHrP-(1-31)NH2 would stimulate bone growth in ovariectomized rats as strongly as hPTH-(1-31)NH2. Like hPTH-(1-31)NH2, hPTHrP-(1-31)NH2 stimulated adenyly cyclase in ROS 17/2 osteosarcoma cells as strongly as the standard hPTH-(1-34) and like hPTH-(1-31)NH2, triggered a large drop in mean blood pressure when injected intravenously. Unlike hPTH-(1-31)NH2, however, hPTHrP-(1-31)NH2 could not stimulate trabecular growth in the distal femurs of young, sexually mature, ovariectomized rats.

Prevention of hypoxemia-induced renal dysfunction by perindoprilat in the rabbit

The role of angiotensin II, a potent postglomerular vasoconstrictor, in the hypoxemiainduced renal changes is still controversial. The ability of perindoprilat, an angiotensin converting-enzyme inhibitor, to prevent the acute renal effects of hypoxemia was assessed in 22 anesthetized-ventilated rabbits. In 8 untreated rabbits, hypoxemia induced a significant drop in mean blood pressure (MBP) (−12 ± 2%), glomerular filtration rate (GFR) (−16 ± 3%) and renal blood flow (RBF) (−12 ± 3%) with a concomittant increase in renal vascular resistance (RVR) (+18 ± 5%) and urine flow rate (+33 ± 14%), and without any changes in filtration fraction (FF) (−4 ± 2%). This suggests the occurrence of glomerular vasoconstriction during the hypoxemic stress. In 7 normoxemic rabbits, intravenous perindoprilat (20 μg kg ) induced an increase in urine flow rate (+17 ± 4%) and RBF (+17 ± 4%), and a decrease in MBP (−6 ± 1%), RVR (−14 ± 3%) and FF (−11 ± 2%) without a significant change in GFR. The drop in FF and the increase in RBF suggests preferential postglomerular vasodilatation. In 7 rabbits, perindoprilat prevented the occurence of the hypoxemia-induced changes in RBF and RVR without improving MBP. FF decreased significantly (−18 ± 2%), while the drop in GFR (−7 ± 2%) was partially blunted and the increase in urine flow rate (+25 ± 9%) was confirmed. These results could be explained by the inhibition of the angiotensin-mediated efferent vasoconstriction and by the inhibition of bradykinin degradation by perindoprilat. These data confirm the ability of converting-enzyme inhibitors to prevent the renal hypoperfusion induced by acute hypoxemia.