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Early detection of endothelial injury and dysfunction in conjunction with correction of hemodynamic maladjustment can effectively restore renal function in type 2 diabetic nephropathy.

This paper was aimed to investigate (1) the early marker of endothelial injury in type 2 diabetes, (2) the intrarenal hemodynamics and renal function, and (3) the therapeutic strategy aiming to restore renal function. Fifty patients (35 normoalbuminuric and 15 albuminuric type 2 diabetes) were examined. Blood was collected for determination of circulating vascular endothelial cells (CEC) and the serum was prepared for determination of transforming growth factor beta (TGFbeta), ratio of CEC/TGFbeta, and soluble vascular cell adhesion molecule. Intrarenal hemodynamics and renal function were also assessed. The results showed that increased number of circulating EC, elevated TGFbeta and depleted ratio of CEC/TGFbeta were significantly observed. Intrarenal hemodynamic study revealed a hemodynamic maladjustment characterized by preferential constriction of the efferent arteriole, intraglomerular hypertension and reduction in peritubular capillary flow. It was concluded that early marker of endothelial injury is reflected by increasing number of CEC. Such markers correlate with the glomerular endothelial dysfunction associated with hemodynamic maladjustment. Early detection of endothelial injury and appropriate correction of hemodynamic maladjustment by multidrug vasodilators can effectively restore renal function in type 2 diabetic nephropathy.

Adult↗

Venous obstruction: an analysis of one hundred thirty-seven cases with hemodynamic, venographic, and clinical correlations.

One hundred thirty-seven limbs with venous obstruction were analyzed. The arm/foot venous pressure differential and reactive hyperemia tests were found to be useful techniques to diagnose and grade venous obstruction. Traditional techniques including venography and ambulatory venous pressure are inferior in this regard. The newer techniques have provided newer insights in venous obstruction which are detailed herein. The hand-held Doppler was surprisingly very sensitive in grade I as well as in more severe forms of obstruction. Neither anatomic locale of obstruction nor its extent determined hemodynamic severity. Extensive proximal lesions could be hemodynamically mild, and conversely distal crural obstructions and single segment lesions could be hemodynamically severe. Phlebographic appearance was a poor index of collateralization. The paradoxical venous pressure response to the reactive hyperemia test in grade IV obstruction was found to be due to suppression or delay of the reactive hyperemia response itself in the presence of severe venous obstruction. The pain of venous claudication may be related to this phenomenon. Skin ulceration in the presence of venous obstruction was related to the associated reflux rather than the hemodynamic severity of the obstruction itself. The Linton procedure was found to be useful in treating such skin ulcerations. After perforator disruption, obstruction did not become hemodynamically worse, but reflux as measured by the Valsalva test improved with ulcer healing. The improvement in reflux related to Valsalva offers for the first time a hemodynamic rationale for the Linton procedure.

Arm↗

Specific retinal diacylglycerol and protein kinase C beta isoform modulation mimics abnormal retinal hemodynamics in diabetic rats.

PURPOSE: Elevation of diacylglycerol (DAG) and protein kinase C (PKC) levels in diabetic vascular tissue is associated with abnormalities of retinal and renal hemodynamics. The object of this study was to determine whether direct elevation of retinal DAG levels, in the absence of diabetes or hyperglycemia, can mimic the hemodynamic abnormalities normally observed in diabetic rats. Retinal DAG levels were elevated using an inhibitor of DAG kinase that converts DAG to phosphatidic acid. The effectiveness of a specific PKC-beta isoform inhibitor introduced directly into the retinas of diabetic rats in reversing diabetes-related abnormal retinal hemodynamics was also investigated. METHODS: For retinal blood flow studies, diacylglycerol kinase (DGK) inhibitor R59949, at various concentrations, was injected into the vitreous of nondiabetic Sprague-Dawley rats (n = 33), and a PKC-beta isoform-selective inhibitor LY333531 was injected into the vitreous of rats with streptozotocin (STZ)-induced diabetes of 2 weeks' duration (n = 21). Retinal hemodynamic changes were quantitated using video-based fluorescein angiography. Total DAG levels were assayed from five nondiabetic rat retinas after DGK inhibition and retinal PKC activities were assayed from six diabetic rat retinas after PKC-beta inhibition. RESULTS: DGK inhibitor R59949 injected into the vitreous dose dependently increased the mean circulation time (MCT) and decreased retinal blood flow (EC50 = 10(-8) M). After 30 minutes, 10(-5) M R59949 induced a 1.7-fold increase in total retinal DAG levels, compared with the levels in vehicle-injected eyes, an increase in MCT from 0.87 +/- 0.05 seconds to 1.44 +/- 0.12 seconds (P < 0.01) and a decrease in retinal blood flow from 105.3 +/- 6.5 pixel2/second to 64.1 +/- 5 pixel2/second (P < 0.01). The effect of R59949 was sustained for 60 minutes after injection. These retinal hemodynamic parameters after DGK inhibition were comparable to those measured at baseline in rats with STZ-induced diabetes of 2 weeks' duration (MCT = 1.38 +/- 0.20 seconds; retinal blood flow = 68 +/- 11.2 pixel2/second). Intravitreal injection of the PKC-beta inhibitor (LY333531) at 10(-5) M in diabetic rats decreased by a factor of 1.6 the diabetes-related increased PKC activation, decreased the prolonged MCT (0.98 +/- 0.13 seconds; P < 0.01) and increased retinal blood flow (93.4 +/- 14.2 pixel2/second; P < 0.01). The measured retinal circulatory parameters after PKC inhibition in the retina were comparable to those measured at baseline in the nondiabetic rats. CONCLUSIONS: These results provide direct evidence that DAG elevation and subsequent PKC-beta isoform activation are the primary biochemical sequelae responsible for the development of the abnormal retinal hemodynamics observed in diabetic rats.

Animals↗

Impact of Chewing Behavior Change on Cognition and Cerebral Hemodynamics.

BACKGROUND: Impaired chewing ability is a recognized risk factor for cognitive decline in older adults, potentially due to reduced neural stimulation in cognition-related brain regions. While short-term studies have demonstrated transient increases in neural activity from chewing, the sustained cognitive and neurophysiological effects of encouraging thorough chewing habits in daily life remain unclear. OBJECTIVE: This randomized controlled trial investigated whether promoting thorough chewing during meals could improve cognitive function and cerebral hemodynamics in older adults. METHODS: Fifty participants aged 65 y or older were randomly assigned to either a 1-mo intervention group, which used a wearable device to monitor and increase chewing strokes during meals, or a control group that maintained usual chewing habits. Chewing behavior, cognitive performance (including memory and executive function via the color Stroop test), and cerebral hemodynamics in the dorsolateral prefrontal cortex (DLPFC) were measured at baseline and after 1 mo. Statistical analyses included t tests, chi-square tests, 2-way analysis of variance with post hoc tests, Pearson correlations, and generalized linear models to evaluate group differences and associations between chewing and cognitive outcomes. RESULTS: Significant time-by-group interactions were observed for memory, F(1, 48) = 6.24, P = 0.043, and hemodynamic responses in the left DLPFC, F(1, 48) = 6.19, P = 0.013. The intervention group showed increased chewing frequency (P = 0.017), improved memory performance, and reduced left DLPFC responses compared with controls. Chewing frequency was positively correlated with Stroop test scores (r = 0.53, P = 0.010) and negatively with hemodynamic changes in the left DLPFC (r = -0.30, P = 0.040). Although improvements in other cognitive outcomes and hemodynamic measures favored the intervention group, these differences did not reach statistical significance. CONCLUSIONS: Promoting intentional chewing habits for 1 mo may enhance memory-related cognitive performance and neural efficiency in the DLPFC during working memory tasks in older adults. This nonpharmacologic, low-burden strategy warrants further research with longer interventions to support cognitive health and dementia prevention. TRIAL REGISTRATION ID: UMIN000044280Knowledge Transfer Statement:This study demonstrates that promoting thorough chewing habits in older adults can improve memory and enhance neural efficiency in the brain. Encouraging intentional mastication is a simple, nonpharmacologic approach that may help maintain cognitive health and prevent dementia, providing a practical strategy for clinicians and policymakers to support healthy aging.

Humans↗

Does a visible retinal embolus increase the likelihood of hemodynamically significant carotid artery stenosis in patients with acute retinal arterial occlusion?

OBJECTIVE: To determine the value of visible retinal emboli as a diagnostic "test" for the detection of hemodynamically significant carotid artery stenosis in the setting of acute retinal artery occlusion. METHODS: A cross-sectional diagnostic accuracy study was performed in a tertiary North American center, with the results of the dichotomous diagnostic test (the presence or absence of visible retinal emboli) being placed against the dichotomous outcome of the presence or absence of hemodynamically significant carotid artery stenosis (defined as > or = 60%, or < 60%, carotid artery stenosis on either side). RESULTS: Forty-eight (18.7%) of our 256 patients had hemodynamically significant carotid artery stenosis. The sensitivity and specificity of retinal emboli for the detection of hemodynamically significant carotid artery stenosis were 39% and 68%, respectively. The presence of a visible retinal embolus generated a likelihood ratio of 1.24 (95% confidence interval, 0.84-1.86). This value corresponds to a patient with a pretest probability of 50% having a posttest probability of 55.3%. The absence of a visible retinal embolus generated a likelihood ratio of 0.88 (95% confidence interval, 0.68-1.15). CONCLUSIONS: The presence of a visible retinal embolus is a poor diagnostic test for the detection of hemodynamically significant carotid artery stenosis in the setting of acute retinal artery occlusion. Accordingly, the presence of an embolus should not influence the decision to perform carotid Doppler ultrasonography in patients with acute retinal arterial occlusion.

Adult↗

Reversal of adverse hemodynamic effects of pneumoperitoneum by pressure equilibration.

HYPOTHESIS: The creation of positive-pressure pneumoperitoneum during laparoscopic operations can lead to adverse hemodynamic changes, mainly decreased cardiac output. We hypothesized that pneumatic compression sleeves worn on the legs during pneumoperitoneum could abolish the pressure gradient between the abdominal cavity and the legs and so eliminate these adverse hemodynamic changes. DESIGN: Prospective, randomized, controlled clinical trial with an additional calibration group. SETTING: A regional referral center. PATIENTS: Forty-five consecutive patients undergoing laparoscopic cholecystectomy who developed hemodynamic changes on induction of positive-pressure pneumoperitoneum were randomized to 3 groups. INTERVENTIONS: Low-pressure, nonsequential pneumatic compression sleeves, wrapped around the legs, were used to equilibrate the pressure gradient in the study group and to gradually exceed it in the calibration group. In the control group, no sleeves were used. MAIN OUTCOME MEASURES: Transesophageal Doppler cardiac output, stroke volume, and systemic vascular resistance were monitored noninvasively. RESULTS: The creation of positive-pressure pneumoperitoneum caused a significant decrease of cardiac output and stroke volume and increased systemic vascular resistance. In the experimental groups of patients, pressurizing the sleeves to the pneumoperitoneal pressure caused a significant increase of cardiac output (from 4.82 to 6.74 L/min), increased stroke volume, and decreased systemic vascular resistance (P<.001). This was not seen in the control group. Additional gradual pressure increase in the sleeves of the calibration group produced no further improvement. Releasing the pressure abolished the hemodynamic advantages. CONCLUSIONS: Applying pressure on the legs equivalent to the positive-pressure pneumoperitoneum improves hemodynamic performance during pneumoperitoneum by nullifying the pressure gradient that is responsible for the adverse consequences. This might be of major practical value, especially for cardiac patients undergoing prolonged laparoscopic operations.

Abdominal Cavity↗

Sustained beneficial hemodynamic effects of low transdermal nitroglycerin doses compared with placebo in patients with congestive heart failure.

In an attempt to resolve some of the controversies concerning the dose requirements and duration of effects of transdermal nitroglycerin (NTG) in patients with heart failure (CHF), the short-term hemodynamic responses to transdermal NTG, in a 20 cm2 self-adhesive patch (10 mg/24 h), were evaluated in 10 patients with severe chronic CHF using a randomized, within-patient, double-blind, placebo-controlled cross-over trial. Serial hemodynamic measurements over 24 h revealed sustained effects that began 1 h after the application of nitroglycerin patch and fully persisted throughout the study. The peak effect occurred at 4 h with the pulmonary capillary wedge pressure decreasing from 33.7 +/- 8.4 to 21.4 +/- 9 mmHg (mean +/- SD) (p less than 0.05) and the cardiac index increasing from 2.5 +/- 0.6 to 3 +/- 0.6 l/min/m2 (p less than 0.01). Transdermal nitroglycerin also significantly reduced pulmonary arterial and right atrial pressures (from 43.5 +/- 9.5 to 31 +/- 11.4 and from 7.4 +/- 6.6 to 3.8 +/- 4.7 at peak effect, respectively) as well as pulmonary and systemic vascular resistances (from 10.7 +/- 6.6 to 6.5 +/- 3.2 and from 26.2 +/- 5.1 to 22.5 +/- 5.7, respectively). There was no change in heart rate or systemic arterial pressure. These beneficial hemodynamic responses persisted for 24 h. No rebound deterioration occurred upon withdrawal of the nitroglycerin. No significant hemodynamic changes occurred during placebo treatment period. Thus, low doses (10 mg/24 h) of transdermal nitroglycerin induce significant hemodynamic benefit that is sustained for 24 h in patients with heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

Hemodynamic and neuroendocrine response to acute administration of the phosphodiesterase inhibitor BM14.478 in patients with congestive heart failure.

The benzimidazol analogue BM14.478 is a phosphodiesterase inhibitor with both vasodilator and positive inotropic properties. Hemodynamic parameters and plasma hormone levels of 8 patients (1 female, 7 male) with chronic congestive heart failure NYHA Classes II-IV (1 patient with coronary artery disease, 7 patients with primary dilated cardiomyopathy) were assessed before and until 6 h after the intravenous application of 1.0 mg BM14.478. There was a significant decrease of mean pulmonary artery pressure (28 +/- 11 vs. 23 +/- 11 mmHg; p less than 0.05), mean right atrial pressure (8.6 +/- 5.2 vs. 5.0 +/- 4.7 mmHg; p less than 0.02), and systemic vascular resistance (1651 +/- 484 vs. 1206 +/- 252 dynes.s.cm-5; p less than 0.05) as early as 10 min after injection of BM14.478. Pulmonary vascular resistance also was reduced (128 +/- 86 vs. 61 +/- 39 dynes.s.cm-5, 30 min after injection; p less than 0.02). Simultaneously there was a significant increase of cardiac index (2.3 +/- 0.7 vs. 3.1 +/- 0.8 l.min-1.m-2, 10 min after injection; p less than 0.02), and stroke volume index (28.8 +/- 11.7 vs. 33.9 +/- 8.5 ml.min-1.m-2; 30 min after injection; p less than 0.05). Although mean heart rate did not change significantly, some patients reacted with a transient increase. There was also a slight but insignificant increase of the double product. No serious side effects were observed. The hemodynamic improvement was followed by a delayed reduction of plasma levels of epinephrine (51 +/- 20 vs. 41 +/- 21 pg/ml; p less than 0.02; 30 min after injection) and atrial natriuretic peptide (229 +/- 283 vs. 121 +/- 168 pg/ml; p less than 0.05; 1 h after injection). Mean levels of plasma norepinephrine, however, did not change significantly and individual responses showed large variations, which could not be predicted by the behavior of the hemodynamic parameters. Three of eight patients (2 of these with elevated baseline filling pressures) even showed a marked increase of plasma norepinephrine levels after BM14.478. Response of plasma renin activity and plasma vasopressin levels to BM14.478 also was heterogeneous. According to the results of this study, acute administration of the phosphodiesterase inhibitor BM14.478 has an immediate beneficial hemodynamic effect in patients with severe congestive heart failure by reducing both preload and afterload, and by increasing cardiac index and stroke volume. However, this improvement of hemodynamic parameters is not necessarily accompanied by a favorable short-term response of plasma hormones, and therefore does not allow any conclusions on survival of these patients.

Adult↗

Direct measurement of hepatic blood flow in native and transplanted organs, with accompanying systemic hemodynamics.

The purpose of this study was to investigate intraoperatively a population of patients with end-stage liver disease before and after liver transplantation with respect to (a) the range of hepatic and systemic hemodynamics and their changes associated with transplantation and (b) the ability to identify native hemodynamic correlates with specific diagnostic groups. Hepatic artery and portal vein blood flows were determined with square-wave electromagnetic flowmetry. Significant differences related to the type of preservation solution used--Euro-Collins or University of Wisconsin--were identified in some hepatic and systemic hemodynamic measurements from the graft livers. Specifically, cardiac output, total liver blood flow and liver weight were significantly increased in the Euro-Collins group compared with the native and University of Wisconsin groups. Hepatic artery flow was significantly greater and portal vein pressure was significantly lower in the University of Wisconsin group than in the native or Euro-Collins group. In general, comparing the graft and native livers, hepatic artery and portal vein blood flow increased significantly after transplantation, as did hepatic oxygen consumption. Portal vein pressures were dramatically reduced, but systemic arterial pressure remained remarkably constant. The percentage of cardiac output going to the liver increased, as did the portal vein percentage of the total liver blood flow. Diagnostic groups could not clearly be associated with characteristic native liver or systemic hemodynamics. Hemodynamics may be associated more with the stage of the disease process than the disease itself.

Adult↗

Hemodynamic effects of esmolol, an ultrashort-acting beta blocker.

The hemodynamic effects of esmolol were evaluated in 12 male patients at rest (mean age, 51 +/- 10 years) undergoing routine cardiac catheterization. Hemodynamic measurements were obtained during baseline (prior to esmolol), at steady state (during an intravenous infusion of esmolol 300 micrograms/kg/min), and at 30 minutes after stopping esmolol (postinfusion). Esmolol produced hemodynamic effects similar to the effects of other beta blockers. Significant reductions in rate-pressure product (mean decrease, 15%), cardiac index (mean decrease, 17%), stroke volume index (mean decrease, 13%), left ventricular stroke work index (mean decrease, 20%), and left ventricular ejection fraction (mean decrease, 18%) were observed. In contrast to other beta blockers, all hemodynamic effects of esmolol had returned to baseline values within 30 minutes after the infusion stopped. One patient exhibited hypotension during the esmolol infusion; this episode resolved without sequelae after discontinuation of esmolol. In summary, the effects of esmolol at rest on hemodynamic parameters and left ventricular function are similar to other beta-adrenergic blocking agents. Due to its ultrashort half-life, esmolol can be administered safely in critically ill patients whose disease status makes treatment with currently available beta blockers risky.

Adrenergic beta-Antagonists↗

Hemodynamic effects of flestolol, a titratable short-acting intravenous beta-adrenergic receptor blocker.

The hemodynamic effects of flestolol were evaluated in 30 patients undergoing routine cardiac catheterization. Hemodynamic measurements were obtained during baseline (prior to flestolol), at steady state during IV flestolol infusion (1, 5, and 10 micrograms/kg/min) and at 20 to 30 minutes after discontinuation (postinfusion). Flestolol-induced hemodynamic changes were similar to those induced by other beta blockers without intrinsic sympathomimetic activity. Significant dose-dependent reduction in heart rate, rate pressure product, and increase in peripheral vascular resistance were seen. Flestolol produced clinically insignificant decrease in myocardial contractility as shown by slight decrease in LVdp/dt, CI, and LVEF. Hemodynamic data from patients with paced heart rate, further confirms a direct mild cardiac depressant effect of flestolol, a finding common to other beta blockers. Consistent with the short elimination half-life of flestolol (t1/2 = 6.5 minutes), most of the hemodynamic changes rapidly returned to preinfusion level within 20 to 30 minutes following its discontinuation. Thus flestolol, with its unique pharmacokinetic profile and titrability, may be beneficial in the treatment of critically ill patients.

Adrenergic beta-Antagonists↗

The hemodynamic effects of ibopamine, a dopamine congener, in patients with congestive heart failure.

Ten patients with congestive heart failure underwent noninvasive and invasive hemodynamic testing before and sequentially after the administration of ibopamine to determine the cardiovascular effects of this oral dopamine congener. Single doses of 200, 400 and 600 mg were administered to all patients and 5 repeated doses of 200 or 400 mg were studied in 8. Hemodynamic effects occurred as early as 30 minutes and lasted up to 4 hours after dosing. In general, ibopamine elicited statistically significant dose-related increases in cardiac output and reductions in the derived resistance of the systemic and pulmonary circulations. A biphasic response in central and peripheral pressures was observed; up to 1 hour after administration, ibopamine elevated mean right and left atrial pressures and pulmonary and systemic arterial pressures with a significant reduction of these measurements beyond 1 hour. It did not alter heart rate. Repeated doses qualitatively affected hemodynamics similar to the initial dose and did not appear to be accompanied by short-term tolerance. While oral ibopamine elicits some favorable hemodynamic effects in humans with cardiac failure, the biphasic hemodynamic response is generally undesirable in the majority of these patients.

Adult↗

Hemodynamic study of serial double-filtration plasmapheresis.

Although hypotension is a potential complication for all procedures involving extracorporeal circulation, including plasmapheresis, the effects of serial double-filtration plasmapheresis (DFP) on hemodynamic status have rarely been reported. Blood pressure (BP) and pulse rate (PR) were prospectively monitored at 30-minute intervals (baseline, M30, M60, M90, and Ml20) during procedures for 20 myasthenia gravis patients who underwent one course of five consecutive DFP treatments on alternate days, with hemodynamic parameters recorded and analyzed for all sessions. To evaluate the hemodynamic influence of protein loss resulting from serial DFP treatment, additional analysis of serum protein levels including albumin and globulin was conducted before and after the entire course of treatment. Longitudinal analysis on the systolic BP (SBP) changes over five sessions revealed that the SBP at baseline and at M30 dropped significantly during the third and fourth sessions, in comparison to the first (P < 0.05). By contrast, SBP at M120 rose significantly (P < 0.05) after the second session of treatment. A similar trend was revealed for the diastolic BP (DBP) with a significant fall recorded at baseline and at M30 for the fourth session. The PR did not differ significantly during consecutive DFP treatments. Globulin removal rates were correlated significantly with falls in SBP (r(2) = 0.250, P = 0.048) and DBP (r(2) = 0.405, P = 0.008). However, analogous albumin removal rate was not correlated with these hemodynamic parameters. In conclusion, our results confirm that hypoproteinemia is an important factor for contributing to unstable hemodynamics during serial DFP.

Adult↗

Does N-acetylcysteine improve hemodynamics and graft function in liver transplantation?

The release of toxic oxidative free radicals induced by ischemia and reperfusion may jeopardize liver graft function. N-acetylcysteine (NAC) has shown protective effects on hypothermic and warm ischemia reperfusion liver injury in animals. NAC improves hemodynamics and survival rates in patients with fulminant hepatic failure. The aim of this study was to investigate whether intraoperative treatment with NAC would improve hemodynamics and postoperative graft function in liver transplantation. Sixty patients with chronic end-stage liver disease were included in a prospective randomized placebo-controlled study. NAC or the same volume of 5% glucose was started during the anhepatic phase. Hemodynamic data and calculated tissue oxygenation parameters were compared throughout the procedure. Postoperative graft function was assessed by measurements of aminotransferases, prothrombin time, and monoethylglycinexylidide test over the 3 first postoperative days. Patient demographics were similar before the infusion of NAC or glucose. Hemodynamic parameters, oxygen consumption, oxygen delivery, oxygen extraction ratio, and lactates were not different throughout the procedure. One hour after the revascularization of the hepatic artery, the oxygen extraction ratio by the liver was similar (17% +/- 7.6% v 17% +/- 6.2%) in both groups. Postoperative graft function was comparable within the 3 first postoperative days. This study failed to show any beneficial effect of the intraoperative administration of NAC on hemodynamics and graft function in liver transplantation in patients with chronic liver disease.

Acetylcysteine↗

The effect of soluble tumor necrosis factor receptor-II on endotoxin-mediated hemodynamic instability.

Tumor necrosis factor-alpha (TNF-alpha), a central mediator in the hemodynamic response to injury and infection, is a primary mediator of endotoxin-induced hemodynamic instability. Two types of naturally occurring soluble TNF receptors circulate in human experimental endotoxemia and the recombinant proteins of both have been hypothesized as potential therapeutic agents antagonizing TNF-mediated effects of endotoxemia. The administration of recombinant sTNFr-I has been previously shown to attenuate the hemodynamic collapse of lethal bacteremia. In the current study, we investigated the role of recombinant sTNFR-II at low (0.5 mg/kg) and high (2.5 mg/kg) doses as a potential therapeutic agent for the inhibition of endotoxin lipopolysaccharide (LPS)-mediated hemodynamic instability. Eighteen male Sprague-Dawley rats were anesthetized and cannulated for continuous blood pressure monitoring and cardiac output measurement by thermodilution. Groups of animals received saline, LPS (1 mg/kg), or sTNFr-II (at 0.5 or 2.5 mg/kg) 15 min prior to LPS (1 mg/kg). Hemodynamic variables (blood pressure, cardiac output, heart rate) were monitored every 15 min for 2 hr. LPS caused a 30% decrease in mean arterial pressure by 60 min, which began to recover by 120 min. sTNFr-II was unable to prevent LPS-induced hypotension at low or high dose. Serum levels of immunoreactive TNF-alpha, undetectable in control animals, were significantly increased by sTNFr-II compared to LPS alone. Serum from animals treated with high-dose sTNFr-II showed significantly less TNF cytotoxicity than those treated with low-dose sTNFr-II, indicating that high doses of sTNFr-II are required for the inhibition of the bioactivity of TNF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Comparison of the hemodynamic effects of gasless abdominal distention and CO2 pneumoperitoneum during incremental positive end-expiratory pressure.

Laparoscopy is used increasingly in managing critically ill patients. Carbon dioxide (CO2) pneumoperitoneum is used during these procedures. The increased intra-abdominal pressure of CO2 pneumoperitoneum, however, can affect cardiopulmonary performance adversely. Recently, gasless abdominal wall distention has been introduced as an alternative to CO2 pneumoperitoneum. The purpose of this study was to compare the hemodynamic effects of gasless abdominal distention (GAD) with those of CO2 pneumoperitoneum during mechanical ventilation with positive end-expiratory pressure (PEEP). Six anesthetized, paralyzed, mechanically ventilated adult swine were monitored with pulmonary artery and arterial catheters at incremental values of PEEP (0-20 cm H2O, by 5, Control) and then allowed to return to baseline hemodynamic status at 0 cm H2O PEEP. The animals were then randomly assigned to receive either CO2 pneumoperitoneum at 15 mm Hg intra-abdominal pressure (PNEUMO) or GAD (equal to anterior abdominal wall displacement of CO2) and PEEP was reapplied. The animals were allowed to return to hemodynamic baseline and PEEP was reapplied with the alternate method of abdominal wall distention. A complete hemodynamic profile and arterial/mixed venous blood gas measurements were monitored at each value of PEEP. With GAD, central venous pressure (CVP), pulmonary artery pressure (PAP), pulmonary capillary wedge pressure (PCWP), and PaCO2 were significantly reduced, compared to PNEUMO, and PaO2 was increased. Cardiac index was higher in GAD versus PNEUMO at baseline, but was lower for GAD at PEEP levels above 10 cm H2O. These results indicate that in its net effect, GAD does not exacerbate the adverse hemodynamic effects of PEEP.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdomen↗

Effector of hemodynamics during laparoscopy: CO2 absorption or intra-abdominal pressure?

Controversy has been raised about the effects of systemic carbon dioxide accumulation versus the intra-abdominal pressure on hemodynamics during laparoscopy. We compared the acid-base and hemodynamic changes during pneumoperitoneum in a randomized cross-over study between CO2 and nitrogen gases to test the hypothesis that the CO2 absorbed during laparoscopy, rather than the 15 mmHg intra-abdominal pressure created, accounted for these changes. Eight adult pigs were anesthetized and ventilated with a fixed minute ventilation. Metabolic function was measured from analysis of expired flow by a metabolic measurement cart. After baseline periods, animals were randomized into two groups, for 2 hr of either CO2 or nitrogen pneumoperitoneum at 15 mmHg intra-abdominal pressure, followed by 1 hr of recovery. After at least a 48-hr recovery period, the experiment was repeated with the other gas. Metabolic data revealed that there was a significant absorption of CO2 gas across the peritoneal epithelium during CO2 pneumoperitoneum. Animals insufflated with CO2 gas experienced a 75% increase in pulmonary CO2 excretion, with significant acidemia and hypercapnia, whereas there were no acid-base disturbances in those with nitrogen insufflation. Oxygen consumption remained essentially unchanged in both groups, even during pneumoperitoneum. CO2 pneumoperitoneum was also associated with systemic and pulmonary arterial hypertension and a reduction in stroke volume of up to 15%. Pneumoperitoneum alone did not compromise hemodynamics. Pneumoperitoneum using CO2 gas during laparoscopy resulted in systemic CO2 absorption across the peritoneum. This led to acidemia, hypercapnea, and depressed hemodynamics. The intra-abdominal pressure routinely used during laparoscopic surgery did not affect metabolic function, acid-base balance, or hemodynamics in the experimental model.

Acid-Base Equilibrium↗

Hemodynamic and inotropic effects of nitric oxide in pulmonary hypertension.

Right ventricular failure following cardiac transplantation is most commonly related to pre-existent recipient pulmonary hypertension secondary to chronic congestive heart failure. Although nitric oxide has had some role clinically in improving pulmonary hemodynamics and right ventricular function in this setting, an appropriate large-animal model of stable pulmonary hypertension has not been available for basic investigation of this problem. This study was designed to examine the hemodynamic and inotropic effects of inhaled nitric oxide using a canine model of monocrotaline pyrrole-induced chronic pulmonary hypertension. Eight mongrel dogs (22-25 kg) were used. All animals underwent percutaneous pulmonary artery catheterization to measure right heart hemodynamics prior to and 8 weeks after a right atrial injection of monocrotaline pyrrole. Eight weeks post-injection, all hearts were instrumented with a pulmonary artery flow probe, sonomicrometric dimension transducers, and micromanometers. Data were collected at baseline and following nitric oxide administration. Eight weeks post-monocrotaline pyrrole injection, significant increases were observed in the pulmonary hemodynamics compared to pre-injection. Nitric oxide led to significant decreases in pulmonary vascular impedance. Significant improvements in pulmonary blood flow, transpulmonary efficiency, and right ventricular contractility were also observed. This investigation demonstrates the well-known clinical effects of nitric oxide in improving pulmonary hemodynamics which were also associated with an increase in pulmonary blood flow, transpulmonary efficiency, and right ventricular contractility in the setting of monocrotaline pyrrole-induced pulmonary hypertension.

Animals↗