Small Increase In Mean Arterial Pressure Research Articles

Polymerized Hemoglobin With Increased Molecular Size Reduces Toxicity in Healthy Guinea Pigs

Hemoglobin (Hb)-based oxygen (O2) carriers (HBOCs) have been developed as an alternative to red blood cells (RBCs) for use in transfusion medicine. HBOCs have many benefits over RBCs; however, previous generations of HBOCs failed in clinical trials due to unanticipated cardiotoxicity. These problems likely originated from vasoconstriction, hypertension, oxidative stress, and the presence of low-molecular-weight (MW) Hb species in the HBOC formulation. Therefore, the objective of this study is to compare the toxicity of small-MW Polymerized bovine Hb (SPolyHb) to large-MW Polymerized bovine Hb (LPolyHb) in guinea pigs, since they lack the ability to synthesize vitamin C and are more sensitive to oxidative stress than other preclinical animal models. The two PolyHbs used in this study have similar molecular diameters (72 and 69 nm, respectively), but the SPolyHb included approximately 15% Hb polymers with MW below 256 kDa, which were significantly removed from LPolyHb. Solutions were injected as a hypervolemic (topload) infusion of 10% of the blood volume into animals. SPolyHb caused a 50% elevation in mean arterial pressure (MAP) from the baseline, while LPolyHb caused only a small increase in MAP. Both PolyHbs also increased markers of organ damage and tissue and systemic inflammation compared to controls. SPolyHb caused significant changes in tissue function and vital organ toxicity markers compared to LPolyHb, specifically markers related to kidney, liver, and lung injury and systemic inflammation and iron transport by the reticuloendothelial system. LPolyHb had a longer half-life than SPolyHb, which correlates with observations made in the reticuloendothelial and iron transport systems. These studies indicate that the molecular size of PolyHb determines vasoactivity, circulation time, mechanism of elimination, toxicity, and inflammation induced by its infusion.

Non-invasive continuous haemodynamic monitoring and response to intervention in haemodynamically unstable patients during rapid response team review

IntroductionDuring rapid response team (RRT) management of haemodynamic instability (HI), continuous non-invasive haemodynamic monitoring may provide supplemental physiological information. ObjectivesTo continuously and non-invasively obtain the cardiac index (CI) and mean arterial pressure (MAP) in patients with HI at baseline and during RRT management using the ClearSight™ device. MethodsWe performed a prospective observational study in adult patients managed by the RRT for tachycardia or hypotension or both. We assessed changes from baseline in heart rate (HR), MAP, CI, stroke volume index (SVI) and systemic vascular resistance index (SVRI) (i) at 5-minutely intervals up to 20 min, and (ii) over the entire 20-min period. We analysed patients by RRT trigger (tachycardia/hypotension) and intervention (fluid bolus therapy [FBT]/ no FBT). ResultsWe successfully recorded the CI in 47 of 50 (94%) patients. RRT reviews triggered by hypotension rather than tachycardia had a lower baseline HR (−45.4 bpm, p = <0.0001), MAP (−16.1 mmHg, p = 0.0007) and CI (1.0 L/min/m2, p = 0.0025). Compared to baseline, in the tachycardia group, there was a small increase in MAP overall and at the 15–20 min time-block from 83.2 mmHg to 87.1 mmHg (+3.9 mmHg, p = 0.0066) and 85.5 mmHg (+2.3 mmHg, p = 0.0061), respectively. In those who received FBT, there was a statistically significant increase in MAP overall and at the 15–20 min time-block compared to baseline, from 70.1 mmHg to 73.5 mmHg (+3.4 mmHg, p = 0.0036) and 74.3 mmHg (+4.2 mmHg, p = 0.0037), respectively. However, there were no statistically significant changes in mean HR, CI, SVI, or SVRI when comparing baseline to the entire 20-min period or 5-min time-blocks within any group. ConclusionsContinuous non-invasive measurement of haemodynamics during RRT management for HI was possible for 20 min. Patients with hypotension rather than tachycardia had lower baseline HR, MAP and CI values. There was a statistically significant but small increase in MAP at the 15–20 min time-block and overall, for both the tachycardia and FBT groups.

Hypophysectomy attenuates leptin‐induced tachycardia without affecting leptin's action on appetite and body weight.

Leptin, a hormone produced by adipocytes, regulates energy homeostasis and cardiovascular function by activating its receptors in the central nervous system. Since leptin also modulates pituitary function we examined the role of pituitary hormones in contributing to the effects of leptin on energy homeostasis and cardiovascular function. Male 12‐week‐old hypophysectomized Sprague‐Dawley rats (Hypo, n=5) were instrumented with telemetry probes for determination of mean arterial pressure (MAP) and heart rate (HR) 24‐hrs/day and an intracerebroventricular (ICV) cannula was placed in the brain lateral ventricle for continuous infusion of leptin (15 μg/day). Compared to control rats (Ctrl, n=5), Hypo rats were lighter (215±4 vs 415±6 g), had lower MAP and HR (83±4 and 317±2 vs 105±4 mmHg and 339±4 bpm), with similar caloric intake per gram of body weight (174±19 vs 195±10 kcal/kg) and plasma glucose levels (84±4 vs 80±4 mg/dl). Chronic ICV leptin infusion for 7 days reduced caloric intake (−60%) and body weight (−10%) in both groups. Leptin treatment markedly increased HR in Ctrl rats (~25 bpm) while causing only a modest 8 bpm increase in Hypo rats. Leptin also induced a small increase in MAP in both groups (3 mmHg). These results suggest that hypophysectomy attenuates leptin's effect on HR regulation without altering leptin's ability to suppress appetite and to promote weight loss. (NHLBI‐PO1HL51971/ AHA SDG5680016)

Blood Pressure Lowering and Vasomodulator Effects of Piperine

This study was aimed to explore underlying mechanism(s) of cardiovascular effects of piperine. Intravenous administration of piperine caused a dose-dependent (1 to 10 mg/kg) decrease in mean arterial pressure (MAP) in normotensive anesthetized rats; the next higher dose (30 mg/kg) did not cause any further change in MAP. The fall in blood pressure (BP) was followed by small increase in MAP after each dose. In Langendorrf's rabbit heart preparation, piperine caused partial inhibition and verapamil caused complete inhibition of force and rate of ventricular contractions and coronary flow. In rabbit aortic rings, piperine inhibited high K+ (80 mM) precontractions and partially inhibited phenylephrine (PE), suggesting Ca2+ channel blockade (CCB), which was further confirmed when pretreatment of tissues with piperine caused rightward shift in Ca2+ concentration-response curves, similar to verapamil. In Ca2+-free medium, piperine (1 to 30 microM) exhibited vasoconstrictor effect. In rat aorta, piperine demonstrated endothelium-independent vasodilator effect and was more potent against high K+ precontractions than PE. In bovine coronary artery preparations, piperine inhibited high K+ precontractions completely. These data indicate that piperine possesses a blood pressure-lowering effect mediated possibly through CCB, while consistent decrease in BP was restricted by associated vasoconstrictor effect. Additionally, species selectivity exists in the CCB effect of piperine.

Influence of retrograde flushing via the caval vein on the post‐reperfusion syndrome in liver transplantation

The reperfusion phase during orthotopic liver transplantation (LTX) is a critical event with sometimes profound hemodynamic and cardiac changes. We present the influence of retrograde reperfusion in LTX on the post-reperfusion syndrome (PRS). Fifty-six LTXs in 53 patients were performed with the piggy-back technique with retrograde reperfusion via the caval vein and antegrade reperfusion via the portal vein. The incidence of PRS was evaluated. We observed a PRS in two patients (3.6%), four patients (7.1%) had a decrease in mean arterial pressure (MAP) of 20-29%, 18 patients (32.2%) of 10-19%, 27 patients (48.2%) of 1-9% and five patients (8.9%) had a small increase in MAP. Our retrospective study showed that retrograde reperfusion seems to maintain stability during the reperfusion phase. Hemodynamic disturbances during LTX were uncommon, leading us to suppose that the incidence of PRS could be diminished with retrograde reperfusion.

Role of hypothalamic melanocortin 3/4-receptors in mediating chronic cardiovascular, renal, and metabolic actions of leptin.

The present study examined whether blockade of melanocortin receptors subtypes 3 and 4 (MC3/4-R) inhibits chronic cardiovascular and dietary responses to leptin infusion. A cannula was placed in the lateral ventricle of male Sprague-Dawley rats for chronic intracerebroventricular (ICV) infusion via osmotic minipump, and arterial and venous catheters were implanted for measurement of mean arterial pressure (MAP) and heart rate (HR) 24 h/d and IV infusions. After a 5-day control period, rats received (1) 0.9% saline vehicle ICV for 12 days plus leptin (1 microg/kg per minute IV, n=5) during the final 7 days; (2) MC3/4-R antagonist SHU-9119 (1 nmol/h ICV) for 12 days plus leptin (1 microg/kg per minute IV, n=6) during the final 7 days; and (3) SHU-9119 (1 nmol/h ICV, n=8) for 12 days. Leptin infusion in vehicle-treated rats caused a small increase in MAP (5+/-1 mm Hg) despite reduced food intake (23+/-1 to 10+/-1 g/d) and decreased body weight (-6%+/-1%). SHU-9119 infusion completely prevented the cardiovascular and dietary actions of leptin, leading to increased food intake (23+/-1 to 49+/-4 g/d) and body weight (+30%+/-2%), markedly decreased HR (-77+/-9 bpm), and caused a decrease in MAP (-6+/-1 mm Hg). Similar results were observed when SHU-9119 was infused alone in vehicle-treated rats. Leptin decreased plasma insulin to 30% of control values, an effect that was also abolished by SHU-9119 treatment, which caused a 5-fold increase in plasma insulin concentration. Thus, MC3/4-R antagonism completely blocked the chronic cardiovascular, satiety, and metabolic effects of leptin, suggesting that the hypothalamic melanocortin system plays an important role in mediating these actions of leptin.

Adrenalectomy abolishes antagonism of α‐adrenoceptor‐mediated hypotension by a β‐blocker in conscious rats

1. The effects of a single bolus injection of propranolol, atenolol or ICI 118,551, non-selective beta-, selective beta 1- and selective beta 2-adrenoceptor antagonists, respectively, on mean arterial pressure (MAP) and plasma catecholamine concentrations were examined in seven groups of conscious and unrestrained adrenalectomized rats receiving a continuous infusion of the alpha-adrenoceptor antagonist phentolamine. In all rats adrenaline was undetectable in the plasma four days after adrenalectomy. 2. In the first three groups, phentolamine significantly decreased MAP and increased the plasma concentrations of noradrenaline. The injection of propranolol, atenolol or ICI 118,551 in Groups I, II and III, respectively, caused a small increase in MAP and a small, but not significant, decrease in plasma noradrenaline concentrations. 3. Groups IV, V and VI were given a continuous infusion of adrenaline for 1 h prior to the infusion of phentolamine, followed by a bolus injection of propranolol, atenolol or ICI 118,551, respectively. Group VII was treated similarly to IV, but was also given daily cortisone replacement after adrenalectomy. Adrenaline slightly, but not significantly, decreased MAP while phentolamine significantly decreased MAP and increased plasma noradrenaline concentrations in all groups. A subsequent injection of a beta-blocker caused a significant increase in MAP in each group and a slight decrease in the plasma level of noradrenaline which reached statistical significance in group VII. The pressor effect of propranolol was significantly greater in the cortisone-treated rats (Group VII) than in Group IV. 5. The results suggest that adrenaline and adrenocortical steroids are both involved in the antagonism of alpha-adrenoceptor-induced hypotension by a beta-blocker.