Hyperdynamic Circulatory State Research Articles

Abstract 3152: Hyperdynamic Circulatory State And Volume Overload Without Left Ventricular Intrinsic Myocardial Dysfunction Is Detected In Normotensive Non Diabetic Patients With Morbid Obesity

Background: increasing reports suggest that morbid obesity (BMI ≥ 40 kg/m2) is associated with an early impairment of intrinsic myocardial function, possibly contributing to an increased susceptibility to heart failure. However, the relative role of obesity and associated comorbidities such as HBP and diabetes in LV dysfunction is still unclear. Aim of the study: to investigate subclinical cardiovascular involvement in patients with isolated morbid obesity as compared to age-matched lean subjects. Methods: 38 lean healthy volunteers (BMI ≤ 25 kg/m2, 21 females, mean age 39 ± 11, BP 118 ± 9/69 ± 8 mmHg) and 29 non diabetic normotensive patients with morbid obesity (24 females, mean age 34 ± 10, BP 123 ± 10/78 ± 9 mmHg) were studied. LV geometry, pump function, midwall circumferential shortening, diastolic filling, myocardial longitudinal systolic and diastolic velocities, were evaluated by 2-D and M-mode echo, transmitral Doppler and Tissue Doppler Imaging of mitral annulus and interventricular septum and lateral wall (Aloka SSD-5500). Indices of aortic stiffness and arterial wave reflection were obtained by carotid-femoral pulse wave velocity (PWV) and carotid augmentation index (AIx). Ratio of stroke volume to pulse pressure (SV/PP) was used as an index of total arterial compliance Results: Compared to lean subjects, obese patients had significantly (p < at least 0.05) higher HR (75 ± 10 vs 62 ± 9 bpm), LV diastolic diameter (5.5 ± 0.7 vs 5.0 ± 0.5 cm), LV mean wall thickness (0.85 ± 0.11 vs 0.73 ± 0.13), LVMI (51 ± 15 vs 34 ± 9 g/m2.7), cardiac output (6.9 ± 2.5 vs 4.9 ± 1.1 L), LV stroke work (160 ± 50 vs 135 ± 34 g-ml/beat), mitral A velocity (0.63 ± 0.14 vs 0.52 ± 0.12 m/s), E/Ea ratio (a Doppler index related to capillary pulmonary pressure: 6.6 ± 4.4 vs 4.5 ± 1.1) and SV/PP (2.0 ± 0.6 vs 1.6 ± 0.4 ml/mmHg). Total peripheral resistance was significantly lower (1199 ± 419 vs 1452 ± 360 dyn*s/cm5). No differences between groups were found for LV midwall systolic shortening, longitudinal myocardial velocities, PWV and AIx. Conclusion: young to middle age patients with morbid obesity still free of comorbidities show an hyperdynamic circulatory state associated to volume overload, without detectable subclinical abnormalities of intrinsic myocardial function and arterial function.

Renal blood flow and function during recovery from experimental septic acute kidney injury

To measure renal blood flow (RBF) and renal function during recovery from experimental septic acute kidney injury (AKI). Controlled experimental study. Nine merino ewes. University physiology laboratory. We recorded systemic and renal hemodynamics during a 96-h observation period (control) via implanted transit-time flow probes. We then compared this period with 96[Symbol: see text]h of septic AKI (48 h of Escherichia coli infusion) and subsequent recovery (48 h of observation after stopping E. coli). Compared with the control period, E. coli infusion induced hyperdynamic sepsis (increased cardiac output and decreased blood pressure) and septic AKI (serum creatinine 65.4 +/- 8.7 vs. 139.9 +/- 33.0 micromol/l; creatinine clearance 73.8 +/- 12.2 vs. 40.2 +/- 17.2 ml/min; p < 0.05) with a mortality of 22%. RBF increased (278.8 +/- 33.9 vs. 547.9 +/- 124.8 ml/min; p < 0.05) as did renal vascular conductance (RVC). During recovery, we observed a decrease in RVC and RBF with all values returning to control levels. Indices of tubular function [fractional excretion of sodium (FENa) and urea (FEUn) and urinary sodium concentration (UNa)], which had been affected by sepsis, returned to control values after 18 h of recovery, as did serum creatinine. Infusion of E. coli induced a hyperdynamic circulatory state with hyperemic AKI. Recovery was associated with relative renal vasoconstriction and reduction in RBF and RVC back to control levels. Indices of tubular function normalized more rapidly than changes in RBF.

Pre- and postoperative systemic hemodynamic evaluation in patients subjected to esophagogastric devascularization plus splenectomy and distal splenorenal shunt: A comparative study in schistomomal portal hypertension

To investigate the systemic hemodynamic effects of two surgical procedures largely employed for treatment of schistosomal portal hypertension. Thirty-six patients undergoing elective surgical treatment of portal hypertension due to hepatosplenic mansonic schistosomiasis were prospectively evaluated. All patients were subjected to preoperative pulmonary artery catheterization; 17 were submitted to esophagogastric devascularization and splenectomy (EGDS) and 19 to distal splenorenal shunt (DSRS). The systemic hemodynamic assessment was repeated 4 d after the surgical procedure. Preoperative evaluation revealed (mean +/- SD) an increased cardiac index (4.78 +/- 1.13 L/min per m(2)), associated with a reduction in systemic vascular resistance index (1457 +/- 380.7 dynes.s/cm(5).m(2)). The mean pulmonary artery pressure (18 +/- 5.1 mmHg) as well as the right atrial pressure (7.9 +/- 2.5 mmHg) were increased, while the pulmonary vascular resistance index (133 +/- 62 dynes x s/cm(5) x m(2)) was decreased. Four days after EGDS, a significant reduction in cardiac index (3.80 +/- 0.4 L/min per m(2), P < 0.001) and increase in systemic vascular resistance index (1901.4 +/- 330.2 dynes x s/cm(5) x m(2), P < 0.001) toward normal levels were observed. There was also a significant reduction in pulmonary artery pressure (12.65 +/- 4.7 mmHg, P < 0.001) and no significant changes in the pulmonary vascular resistance index (141.6 +/- 102.9 dynes x s/cm(5) x m(2)). Four days after DSRS, a non-significant increase in cardiac index (5.2 +/- 0.76 L/min per m(2)) and systemic vascular resistance index (1389 +/- 311 dynes x s/cm(5) x m(2)) was observed. There was also a non-significant increase in pulmonary artery pressure (19.84 +/- 5.2 mmHg), right cardiac work index (1.38 +/- 0.4 kg x m/m(2)) and right ventricular systolic work index (16.3 +/- 6.3 g x m/m(2)), without significant changes in the pulmonary vascular resistance index (139.7 +/- 67.8 dynes xs/cm(5) x m(2)). The hyperdynamic circulatory state observed in mansonic schistosomiasis was corrected by EGDS, but was maintained in patients who underwent DSRS. Similarly, the elevated mean pulmonary artery pressure was corrected after EGDS and maintained after DSRS. EGDS seems to be the most physiologic surgery for patients with schistosomal portal hypertension.

Shear stress induces hepatocytePAI-1gene expression through cooperative Sp1/Ets-1 activation of transcription

Partial hepatectomy causes hemodynamic changes that increase portal blood flow in the remaining lobe, where the expression of immediate-early genes, including plasminogen activator inhibitor-1 (PAI-1), is induced. We hypothesized that a hyperdynamic circulatory state occurring in the remaining lobe induces immediate-early gene expression. In this study, we investigated whether the mechanical force generated by flowing blood, shear stress, induces PAI-1 expression in hepatocytes. When cultured rat hepatocytes were exposed to flow, PAI-1 mRNA levels began to increase within 3 h, peaked at levels significantly higher than the static control levels, and then gradually decreased. The flow-induced PAI-1 expression was shear stress dependent rather than shear rate dependent and accompanied by increased hepatocyte production of PAI-1 protein. Shear stress increased PAI-1 transcription but did not affect PAI-1 mRNA stability. Functional analysis of the 2.1-kb PAI-1 5'-promoter indicated that a 278-bp segment containing transcription factor Sp1 and Ets-1 consensus sequences was critical to the shear stress-dependent increase of PAI-1 transcription. Mutations of both the Sp1 and Ets-1 consensus sequences, but not of either one alone, markedly prevented basal PAI-1 transcription and abolished the response of the PAI-1 promoter to shear stress. EMSA and chromatin immunoprecipitation assays showed binding of Sp1 and Ets-1 to each consensus sequence under static conditions, which increased in response to shear stress. In conclusion, hepatocyte PAI-1 expression is flow sensitive and transcriptionally regulated by shear stress via cooperative interactions between Sp1 and Ets-1.

Heart dysfunction evaluated by troponin, stroke work analysis and QT dispersion can predict outcome in patients with septic shock

Sepsis is the leading cause of mortality in ICUs. The mortality rate approaches 29%. As far as the heart is concerned, adequately volume-resuscitated patients in septic shock present a hyperdynamic circulatory state with high cardiac output and reduced systemic vascular resistance, and this profile seems to persist throughout the septic event regardless of the outcome. Myocardial depression in patients with septic shock is characterized by biventricular dilatation and decreased systolic contractile function, all in the presence of an overall hyperdynamic circulation. In addition, sepsis and septic shock is characterized by an impaired sympathetic modulation of the heart, suggesting that a central autonomic regulatory impairment contributes to the circulatory failure that is seen. The purpose of this study was to analyze echocardiographic, ultrasonographic, hemodynamic and serum cardiac markers in patients with septic shock and to evaluate their relationship to the outcome.

Changes in Hemodynamics and Acid-Base Balance during Cross-Clamping of the Descending Thoracic Aorta

Aim of the Study: In the clinical situation there is discrepancy between various investigations regarding the cardiac response of thoracic aortic cross-clamping. The aim was therefore to investigate the hemodynamic response and blood gases during proximal aortic cross-clamping (XC) in patients operated for descending thoracic and thoracoabdominal aortic aneurysm without circulatory support. Patients and Methods: Altogether 51 patients operated on for thoracoabdominal (n = 31) or descending thoracic aortic aneurysm (n = 20) were included in the investigation. All patients were operated with aortic XC, but no circulatory support was applied. Hemodynamic variables and blood gases were recorded before and during XC. Results: A significant increase in cardiac output during XC from 4.7 to 6.0 liters/min was observed (p < 0.01). There was a similar percentual increase in heart rate and also the proximal systolic blood pressure increased. A metabolic acidosis occurred during XC. Conclusion: Cardiac output was significantly increased during XC in patients operated on for thoracoabdominal or descending thoracic aneurysm using direct aortic XC without circulatory support. Simultaneously, the heart rate was increased and there was a hyperdynamic circulatory state proximal to the aortic clamp. Redistribution of the blood volume in addition to catecholamine release may be responsible for the observed changes. These observations may influence the selection of operative strategy for some of these patients.

Mechanisms of Pulmonary Vascular Complications of Liver Disease

To assess the incidence of oral complementary and alternative medicine (CAM) usage by gastroenterology patients at a single university center and compare against controls. The public awareness and usage of CAM have increased. The use of CAM has been described in patients with functional bowel disorders; however, their role in patients with gastrointestinal disease is less clear. Patients attending luminal gastroenterology clinics and customers at local supermarkets completed a 30-point, structured questionnaire assessing their use of CAM. A total of 1,409 subjects were recruited. The incidence of CAM use was 49.5% for inflammatory bowel disease, 50.9% for irritable bowel syndrome, 20% for general gastrointestinal diseases, and 27% for controls. Pearson's chi(2) tests showed that patients with inflammatory bowel disease (IBD) or irritable bowel syndrome were more likely to use CAM than controls (P < 0.001). Binary logistic regression analysis showed that females were more likely to take CAM than men (P < 0.05). The percentage of CAM users among patients with IBD is similar to those with a functional diagnosis. Increasing numbers of IBD patients are using CAM in addition to conventional therapy. Awareness of this may prevent adverse CAM and conventional drug interactions.

Bacterial translocation and its consequences in patients with cirrhosis

Bacterial translocation is the passage of viable bacteria from the intestinal lumen to mesenteric lymph nodes and other extraintestinal sites. Spontaneous bacterial peritonitis is the main clinical consequence of bacterial translocation in cirrhosis. Translocation of bacterial products of viable or non-viable bacteria, such as endotoxin and/or bacterial DNA, through the intestinal wall could stimulate the immune system and the hyperdynamic circulatory state in cirrhosis with clinical consequences that are under evaluation. Bacterial translocation is currently considered the passage of viable gut flora across the intestinal barrier to extraluminal sites. Aerobic Gram-negative bacilli are the most common translocating bacteria. Intestinal bacterial overgrowth, impairment in permeability of the intestinal mucosal barrier, and deficiencies in local host immune defences are the major mechanisms postulated to favour bacterial translocation in cirrhosis. Bacterial translocation is a key step in the pathogenesis of spontaneous bacteraemia and spontaneous bacterial peritonitis in cirrhosis. Translocation of intestinal bacterial products from viable or non-viable bacteria, such as endotoxin and bacterial DNA, has recently been associated with pathophysiological events, such as activation of the immune system and derangement of the hyperdynamic circulatory status in cirrhosis. Clinical consequences of these effects of bacterial products are presently under investigation.

Role of PGI2in the formation and maintenance of hyperdynamic circulatory state of portal hypertensive rats

To investigate the role of prostacyclin (PGI(2)) and nitric oxide (NO) in the development and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats. Ninety male Sprague-Dawley rats were divided into three groups: intrahepatic portal hypertension (IHPH) group by injection of CCl(4), prehepatic portal hypertension (PHPH) group by partial stenosis of the portal vein and sham-operation control (SO) group. One week after the models were made, animals in each group were subdivided into 4 groups: saline controlled group (n = 23), Nomega-nitro-L-arginine (L-NNA) group (n = 21) group, indomethacin (INDO) group (n = 22) and high-dose heparin group (n = 24). The rats were administrated 1 mL of saline, L-NNA (3.3 mg/kg.d) and INDO (5 mg/kg.d) respectively through gastric tubes for one week, then heparin (200 IU/Kg/min) was given to rats by intravenous injection for an hour. Splanchnic and systemic hemodynamics were measured using radioactive microsphere techniques. The serum nitrate/nitrite (NO(2)(-)/NO(3)(-)) levels as a marker of production of NO were assessed by a colorimetric method, and concentration of 6-keto-PGF1alpha, a stable hydrolytic product of PGI(2), was determined by radioimmunoassay. The concentrations of plasma 6-keto-PGF1alpha (pg/mL) and serum NO(2)(-)/NO(3)(-) (micromol/L) in IHPH rats (1123.85+/-153.64, 73.34+/-4.31) and PHPH rats (891.88+/-83.11, 75.21+/-6.89) were significantly higher than those in SO rats (725.53+/-105.54, 58.79+/-8.47) (P<0.05). Compared with SO rats, total peripheral vascular resistance (TPR) and spanchnic vascular resistance (SVR) decreased but cardiac index (CI) and portal venous inflow (PVI) increased obviously in IHPH and PHPH rats (P<0.05). L-NNA and indomethacin could decrease the concentrations of plasma 6-keto-PGF1alpha and serum NO(2)(-)/NO(3)(-) in IHPH and PHPH rats (P<0.05). Meanwhile, CI, FPP and PVI lowered but MAP, TPR and SVR increased (P<0.05). After deduction of the action of NO, there was no significant correlation between plasma PGI(2) level and hemodynamic parameters such as CI, TPR, PVI and SVR. However, after deduction of the action of PGI(2), NO still correlated highly with the hemodynamic parameters, indicating that there was a close correlation between NO and the hemodynamic parameters. After administration of high-dose heparin, plasma 6-keto-PGF(1alpha) concentrations in IHPH, PHPH and SO rats were significantly higher than those in rats administrated vehicle (P<0.05). On the contrary, levels of serum NO(2)(-)/NO(3)(-) in IHPH, PHPH and SO rats were significantly lower than those in rats administrated Vehicle (P<0.05). Compared with those rats administrated vehicle, the hemodynamic parameters of portal hypertensive rats, such as CI and PVI, declined significantly after administration of high-dose heparin (P<0.05), while TPR and SVR increased significantly (P<0.05). It is NO rather than PGI(2) that is a mediator in the formation and maintenance of hyperdynamic circulatory state of chronic portal hypertensive rats.

Portopulmonary hypertension and the issue of survival

Can orthotopic liver transplantation (OLT) result in complete resolution of portopulmonary hypertension (POPH)? More specifically, under what conditions will the normal posttransplant normal hepatic/portal physiology cause a resolution of pulmonary artery hypertension and improve long-term survival? OLT, orthotopic liver transplantation; POPH, portopulmonary hypertension; MELD, model for end-stage liver disease. This survival issue is put into some perspective by the article in this month's Liver Transplantation, wherein Kawut and colleagues describe a 38% 3-year survival when POPH complicates liver disease.1 Their series is small (n = 13), retrospective, and burdened by the uncontrolled management interventions that must address consequences of 2 disorders: pulmonary artery hypertension and portal hypertension. Liver transplantation did not appear to be one of the endpoints in Kawut's analysis. These limited data in the era of OLT mirror the discouraging experience from referrals to other major liver centers. Robalino and Moodie2 via a literature review and Cleveland Clinic experience described a 21% 30-month survival in 49 patients with coexistent pulmonary and portal hypertension in the pre-OLT era. Herve et al. from France3 reported a 50% 5-year survival (n = 39; no data on OLT effects), and Swanson et al. documented a Mayo Clinic experience showing a 28% 5-year survival without OLT (n = 66) and 56% 5-year survival with OLT (n = 28).4 These studies and the Kawut contribution beg 2 broad questions that larger series must address. First, why do such patients with POPH have such poor survival? Second, is it hopeless to consider OLT (with long-term survival) when moderate to severe POPH exists? These questions must be considered in the current context of an evolving treatment armamentarium of vasomodulating (not just vasodilating) drugs such as prostacyclins, endothelin receptor antagonists, and phosphodiesterase inhibitors designed to reverse events that obstruct the pulmonary arterial flow (proliferation of endothelium, platelet aggregation with in situ thrombosis, and vasoconstriction due a proliferation of smooth muscle. For the most part, these drugs appear to be safe and effective in POPH.5-13 Regarding the reasons for poor survival, details are crucial.14 What are the specific cardiovascular endpoints described within the Kawut paper? Has death occurred because of an initiating acute gastrointestinal event (bleeding, sepsis, encephalopathy leading to aspiration with hypoxemia) in the setting of stable or even improving pulmonary hemodynamics? Was death directly a consequence of progressive right heart failure unresponsive to aggressive pulmonary vasomodulating drugs? Did sudden cardiovascular collapse occur (hemodynamically intolerable tachydysrhythmia)? Is survival related to current hepatic disease severity measures such as model for end-stage liver disease (MELD) and Child-Turcotte-Pugh classification, as well as severity of POPH? The statistical overview provided by the Kawut paper does not answer these specific queries. Regarding outcome expectations of OLT in the setting of POPH, is pre-OLT or post-OLT POPH survival related to the changing MELD score? Would we dare assign more MELD points to those with moderate POPH who respond “significantly” to pulmonary vasomodulating drugs or their combinations? The most recent multicenter data suggest that pre-OLT mean pulmonary artery pressure greater than 35 mm Hg (n = 30 with increased pulmonary vascular resistance carries a worrisome OLT prognosis (12 deaths or 40% mortality within 18 days of transplant surgery.15 Only one patient had received pre-OLT prostacyclin.15 One could hypothesize a better outcome facilitated by using current drug therapies. Indeed, the major message of the Kawut study relates to the worse prognosis for POPH compared to idiopathic pulmonary artery hypertension (the new term for primary pulmonary hypertension). To me this is not surprising, since we are trying to cope with and treat effects of disease in 2 vascular beds (pulmonary and portal). But we do need to reconsider the effects of modifying cardiac output and pulmonary vascular resistance in the context of a hyperdynamic circulatory state that accompanies portal hypertension. There probably exists a pathologic point of “no return” in the damaged pulmonary arterial bed, whereby pulmonary hemodynamics are no longer responsive to vasomodulating therapy, despite our best efforts. And the stressed right heart can tolerate only so much adverse change in afterload, preload, and downstream effect of “bad humors” arriving from the portal circulation. Following an accurate diagnosis of POPH, our efforts should (as a minimum) focus upon reducing mean pulmonary artery pressure to less than 35 mm Hg prior to the accomplishment of OLT. Additionally, improvement in other parameters such as pulmonary vascular resistance and indices of right heart function may prove to be prognostic. Hopefully, treatment with a protocolized, combined approach of pulmonary arterial vasomodulation and OLT (cadaveric or living donor) will clarify and improve the POPH long-term survival issue.

Prevention of hepatopulmonary syndrome and hyperdynamic state by pentoxifylline in cirrhotic rats.

Inhibition of tumour necrosis factor-alpha (TNF-alpha), levels of which are increased in the blood of cirrhotic rats, prevents hyperdynamic circulatory state, mainly by decreasing the vascular overproduction of nitric oxide. Hepatopulmonary syndrome, which is characterised by intrapulmonary vascular dilatation and increased alveolar to arterial oxygen tension difference (PA-a,O2), is mainly related to pulmonary over-production of NO by macrophages accumulated in lung vessels. Since TNF-alpha is a potent activator of macrophagic inducible nitric oxide synthase (NOS), the aim of this study was to investigate whether TNF-alpha inhibition prevented hepatopulmonary syndrome and hyperdynamic circulatory state in rats with cirrhosis. TNF-alpha was inhibited by 5 weeks of pentoxifylline (10 mg x kg body weigh(-1) x day(-1)) in rats with cirrhosis induced by common bile duct ligation. Cardiac output, pulmonary and systemic vascular resistance, PA-a,O2 and cerebral uptake of intravenous technetium-99m-labelled albumin macroaggregates (which reflects intrapulmonary vascular dilatation) were similar in sham- and pentoxifylline-treated cirrhotic rats. Blood TNF-alpha concentrations and pulmonary intravascular macrophage sequestration, as assessed by morphometric analysis and radioactive colloid uptake, were decreased with pentoxifylline. Pentoxifylline also prevented increases in aorta and lung NOS activities and inducible NOS expression. Thus pentoxifylline prevents development of hyperdynamic circulatory state and hepatopulmonary syndrome, probably by inhibiting the effects of tumour necrosis factor-alpha on vascular nitric oxide synthase and intravascular macrophages. These results support an important role for tumour necrosis factor-alpha in the genesis of hepatopulmonary syndrome.

Stimulated acoustic emission to image a liver-specific phase of Levovist® in normal volunteers and patients with liver disease

Objective: Quantitative studies were performed to investigate liver-specific uptake of the microbubble Levovist®, using stimulated acoustic emission (SAE), which can detect microbubbles even when stationary or slow moving. It is well known that in the progressing state of liver disease, such as liver cirrhosis, there are arterialization of the liver; formation of intrahepatic shunts between the branches of the hepatic artery, the portal vein, and the hepatic veins; pulmonary arteriovenous shunts; and a hyperdynamic circulatory state with increased cardiac output and reduced systemic vascular resistance. The aim of this investigation using an ultrasound contrast agent was to assess whether those changes in circumstance of liver parenchymal flow were able to be determined or not.

Current pharmacotherapy in the management of cirrhosis: focus on the hyperdynamic circulation

Many major complications of hepatic cirrhosis relate to the development of a characteristic hyperdynamic circulatory state in these patients, irrespective of the underlying disease aetiology. Vasodilatation of the systemic and splanchnic circulations leads to a reduced total systemic vascular resistance, increased cardiac output and intense activation of neurohumoral vasoconstrictor systems including the sympathetic nervous system, renin-angiotensin system and vasopressin. Vasoconstriction of the renal and hepatic circulations contributes to the development of renal failure and portal hypertension, respectively. Current treatments that focus on amelioration of these circulatory derangements offer much promise, however, they are often limited by side effects in these patients.

Mice with targeted deletion of eNOS develop hyperdynamic circulation associated with portal hypertension.

Systemic vasodilation is the initiating event of the hyperdynamic circulatory state, being most likely triggered by increased levels of vasodilators, primarily nitric oxide (NO). Endothelial NO synthase (eNOS) is responsible for this event. We tested the hypothesis that gene deletion of eNOS and inducible NOS (iNOS) may inhibit the development of the hyperdynamic circulatory state in portal hypertensive animals. To test this hypothesis, we used mice lacking eNOS (eNOS-/-) or eNOS/iNOS (eNOS/iNOS-/-) genes. A partial portal vein ligation (PVL) was used to induce portal hypertension. Sham-operated animals were used as a control. Hemodynamic characteristics were tested 2 wk after surgery. As opposed to our hypothesis, PVL also caused significant reduction in peripheral resistance in eNOS-/- compared with sham animals (0.33 +/- 0.02 vs. 0.41 +/- 0.03 mmHg. min x kg body wt x ml(-1); P = 0.04) and in eNOS/iNOS-/- animals with PVL compared with that of the sham-operated group (0.44 +/- 0.02 vs. 0.54 +/- 0.04; P = 0.03). This demonstrates that, despite gene deletion of eNOS, the knockout mice developed hyperdynamic circulation. Compensatory vasodilator molecule(s) are upregulated in place of NO in the systemic and splanchnic circulation in portal hypertensive animals.

Myocardial dysfunction in the patient with sepsis.

The nature of myocardial dysfunction during sepsis and septic shock has been investigated for more than half a century. This review traces the evolution of scientific thought regarding this phenomenon during this period with particular emphasis on the current understanding of both the clinical manifestations and the molecular/cellular basis of septic myocardial dysfunction in critically ill patients. Current data suggest, contrary to older literature, that patients with septic shock develop a hyperdynamic circulatory state after fluid resuscitation and maintain this hyperdynamic circulatory state until death or recovery. Overt myocardial depression, as manifested by decreased cardiac output, is decidedly uncommon, even in the preterminal phase. Nonetheless, myocardial depression, as evidenced by biventricular dilation and depression of the ejection fraction, can be demonstrated in most patients with septic shock by using either radionuclide cineangiography or echocardiography. Depression is reversible over the course of 7 to 10 days in survivors. Available evidence suggests that myocardial hypoperfusion is not responsible for septic myocardial depression, because examination of humans with septic shock demonstrates increased myocardial perfusion, and animal models of septic shock appear to maintain myocardial high-energy phosphates. A circulating factor or factors, including the cytokines tumor necrosis factor alpha and interleukin-1beta, appear to have a significant role in the phenomenon. In addition, septic myocardial depression appears to be mediated in part through combinations of nitric oxide-dependent and -independent alterations of basal and catecholamine-stimulated cardiac myocyte contractility.

CHANGE IN RHEOLOGY AS PROBABLE CAUSE OF INTESTINAL ISCHEMIA FOLLOWING CORRECTION OF AN AXI-ASYMMETRIC ABDOMINAL AORTIC ANEURSYM

Non-traumatic intestinal ischemia is a frequent post-surgical complication of abdominal aortic aneurysm (AAA) repair, the exact cause of which, remains unknown. We report a case, and propose that changes in segmental aortic rheology may have a probable role in the pathogenesis. A 67 year old male with a 7.5 cm axi-asymmetric fusiform AAA extending from below the infra-renal artery had in endoluminal stent placement. He developed clinical features of intestinal ischemia (6th post-operative day) and subsequently died (16th post-operative day) of complications. At autopsy, the endoluminal stent was anatomically intact. The superior mesenteric artery (SMA) ostia, located 2.2 cm proximal to the aneurysm showed a 98% atherosclerotic narrowing. The narrowing was focal, 0.2–1 cm from the ostia. Other arterial ostia proximal and distal to the aneurysm were relatively unaffected by atherosclerosis. Axi-asymmetric AAA causes turbulent flow proximal to the aneurysm, and atherosclerosis develops at arterial branch points due to hemodynamic injury. We propose that turbulent flow proximal to the aneurysm is responsible for localized atherosclerosis in the SMA, and this flow results in a local hyperdynamic circulatory state, with an increased pulsatile feed pressure to the SMA ostia. Endoluminal correction results in a change from turbulent flow to laminar flow with drop in feed pressure to SMA ostia, leading to intestinal ischemia.

Hemodynamic Response to a Rapid Fluid Challenge in End-Stage Liver Disease

Background: Patients with end-stage liver disease have a hyperdynamic circulatory state complicated by a high right ventricular end-diastolic volume index (RVEDVI) and a low ventricular performance. These changes often make if difficult to evaluate volume status and preload. In this study, we analyzed hemodynamic profiles after a rapid fluid challenge in the recipients of a liver transplant. Methods: Hemodynamic responses were evaluated before and after 200 ml of a 5% albumin challenge in forty patients, recipients of a liver transplant with a Swan-Ganz right-heart ejection fraction oximetry thermodilution cathether. Patients were divided into two groups, group A (responders, n = 12, 10% increase in stroke volume index (SVI) after fluid challenge) and group B (non-responders, n = 28, decrease or 5.9% vs 42.8 5.7%), a higher RVEDVI (120.8 19.4 ml/ vs 143.6 26.3 ml/), and a higher right ventricular end-systolic volume index (RVESVI) (60.8 14.0 ml/ vs 82.8 20.5 ml/) than group A. In group B, the cardic index (CI) and right ventricular stroke work index (RVSWI) were not increased after the fluid challenge. There was a mild decrease in the mean arterial pressure (MAP) in group B after the fluid challenge. There was a moderate negative correlation between the fluid-induced change in SVI and the baseline RVEDVI in all patients (r = -0.40, P

Relationship of asymmetric dimethylarginine to dialysis treatment and atherosclerotic disease

The pathogenesis of renal sodium and water retention in cirrhosis involves extrarenal mechanisms because when kidneys from cirrhotic patients are transplanted into persons with normal livers, renal sodium and water retention no longer occurs. Cirrhosis is accompanied by portal hypertension, which leads to a hyperdynamic circulatory state. The Peripheral Arterial Vasodilation Hypothesis incriminates a relative underfilling of the arterial vascular compartment, which leads to the same neurohumoral responses that occurs in low cardiac output. Activation of the renain-angiotensin-aldosterone axis and the sympathetic system as well as non-osmotic release of vasopressin are well documented in cirrhosis. This sequence of events results in renal water and sodium retention, failure to escape from the sodium-retaining effect of aldosterone, and renal resistance to atrial natriuretic peptide. Dilutional hyponatremia is the strongest predictor of the occurrence of hepatorenal syndrome. The pathogenesis of the peripheral arterial vasodilation is not completely elucidated, but there is evidence for a major role of nitric oxide (NO). Increased vascular NO production has been demonstrated in cirrhosis. In the rat model of cirrhosis, normalization of vascular NO production with a NOS inhibitor corrects the hyperdynamic circulation, improves sodium and water excretion, and decreases neurohumoral activation. This insight into the mechanism(s) of the peripheral arterial vasodilation in cirrhosis should provide new tools in the treatment of edema and ascites, a major cause of morbidity and mortality in cirrhosis.

Effects of nitric oxide synthesis inhibitor in long-term treatment on hyperdynamic circulatory state in cirrhotic rats

Effects of nitric oxide synthesis inhibitor in long-term treatment on hyperdynamic circulatory state in cirrhotic rats

Hemodynamic and Cardiac Function Parameters During Heated Intraoperative Intraperitoneal Chemotherapy Using the Open ?Coliseum Technique?

Heated intraoperative intraperitoneal chemotherapy achieves high peritoneal concentrations with limited systemic absorption and has become an important tool in the management of patients with peritoneal carcinomatosis from low-grade malignancies such as pseudomyxoma peritonei and in selected cases of high-grade tumors such as colon adenocarcinoma. When the closed abdomen technique is used, its perioperative toxicity seems to be related to the hemodynamic and cardiac function changes associated with increased body temperature and increased intra-abdominal pressure. Hemodynamic and cardiac function variables during heated intraoperative intraperitoneal chemotherapy, using an open abdomen "coliseum technique," were measured in 15 patients with the use of a noninvasive esophageal Doppler monitor. The hemodynamic and cardiac function changes were characterized by an increased heart rate, increased cardiac output and decreased systemic vascular resistance associated with an increased body temperature, and decreased effective circulating volume with the urinary output tending to decrease as the therapy progressed. Heated intraoperative intraperitoneal chemotherapy with the open abdomen coliseum technique induces a hyperdynamic circulatory state with an increased intravenous fluid requirement and avoids changes because of increased intra-abdominal pressure. Hemodynamic and cardiac stability, as documented by normal blood pressure and adequate urinary output, can be achieved by liberal intravenous fluids, titrated to frequent urinary output determination.