Changes In Systemic Vascular Resistance Research Articles

New Insights into Mechanisms of Action of Carvedilol Treatment in Chronic Heart Failure Patients—A Matter of Time for Contractility

BackgroundIt is unclear whether improvement in left ventricular (LV) ejection fraction (LVEF) following treatment with a combined α1,β1,β2-blockade can be attributed to improvement in LV contractility, to a reduction in afterload, and/or to improvements in LV remodeling and chamber size. We aimed to examine whether the observed improvement in LVEF following carvedilol treatment is due to changes in intrinsic myocardial contractility beyond changes in LV chamber size or loading conditions. Methods and ResultsIn 49 consecutive patients with chronic heart failure (HF), LVEF ≤35%, NYHA functional class II–IV, on angiotensin-converting enzyme inhibitors but not on ß-blockers, LV contractile performance and remodeling were assessed by comprehensive echocardiography at baseline and after 3 and 6 months of treatment with carvedilol. Carvedilol treatment resulted in significant improvements in LVEF, shortening fraction, and velocity of circumferential shortening (VCFc). There were no significant changes in the mean arterial blood pressure or systemic vascular resistance index; but LV end-systolic wall stress (LVESS), effective arterial elastance, ventriculoarterial coupling, and LV end-diastolic and end-systolic dimensions and volumes were significantly reduced. Estimated end-systolic elastance, VCFc-to-LVESS ratio, and pulsatile arterial compliance significantly improved after 6 months of treatment with carvedilol. The slope of the VCFc relationship to LVESS worsened from 0 to 3 months, but significantly improved from 3 to 6 months. ConclusionsDespite an initial transient negative inotropic effect from 0 to 3 months, carvedilol treatment was associated with a positive inotropic effect with significant improvement in load-independent indexes of myocardial contractility beyond what can be attributed to changes in LV chamber size and load after 3 months. There were no changes in systemic vascular resistance with carvedilol treatment; however, improvement in pulsatile arterial compliance and ventriculoarterial coupling suggested enhanced cardiac mechanoenergetic performance along with improved systemic arterial compliance.

An Adult Patient with Fontan Physiology: A TEE Perspective

Fontan and Baudet described in 1971 the separation of the pulmonary and systemic circulations resulting in univentricular physiology. The evolution of the Fontan procedure, most notably the substitution of right atrial-to-pulmonary artery anastomosis with cavopulmonary connections, resulted in significantly improved late outcomes. Many patients survive well into adulthood and are able to lead productive lives. While ideally under medical care at specialized centers for adult congenital cardiac pathology, these patients may present to the outside hospitals for emergency surgery, electrophysiologic interventions, and pregnancy. This presentation presents a “train of thought,” linking the TEE images to the perioperative physiologic considerations faced by an anesthesiologist caring for a patient with Fontan circulation in the perioperative settings. Relevant effects of mechanical ventilation on pulmonary vascular resistance, pulmonary blood flow and cardiac preload, presence of coagulopathy and thromboembolic potential, danger of abrupt changes of systemic vascular resistance and systemic venous return are discussed.

Cerebral Vascular Response in Airmen Exposed to Hypobaric Hypoxia

Cerebral vascular response via local and reflex adjustments is part of the integrated response to hypoxia and is coupled with changes in systemic vascular resistances that allow a redistribution of blood flow toward the brain. The cerebral vascular response in airmen exposed to simulated high altitude is not clear, thus we sought to investigate this aspect. Four healthy military airmen were exposed to simulated high altitude in a hypobaric chamber according to a standard training protocol. Blood saturation (SpO2) and blood flow velocity with transcranial Doppler from the left middle cerebral artery (Vm) were continuously recorded. Pulsatility Index (PI), resistance index (RI), and systolic/diastolic ratio (S/D ratio) were computed. Alternate hypoxia-hyperoxia trials for 2 and 1 min, respectively, were used to assess the cerebrovascular response. Acute hypoxia induced an increase in Vm that promptly recovered when the oxygen supply was restored (mean increase of 5.5% at 18,000 ft and 17.2% at 25,000 ft). Alternate hypoxia-hyperoxia at 25,000 and 18,000 ft elicited changes in both SpO2 and Vm. In hypoxia, PI significantly decreased (mean decrease o" 25.6% at 18,000 ft and 39.5% at 25,000 ft), as did RI (mean decrease of 18.7% at 18,000 ft and 34.4% at 25,000 ft), while S/D ratio increased. The standard altitude training protocol induced a transient cerebrovascular response. The response was as expected, with hypoxia-induced vasodilation and opposite changes when breathing pure oxygen.

Salt Sensitivity in Blacks

In healthy, mostly normotensive blacks, 19 salt-sensitive (SS) and 18 salt-resistant (SR), we tested the hypothesis that, in SS subjects, dietary NaCl loading induces its initial pressor effect by inducing a normal increase of cardiac output, while failing to induce a normal pressor-offsetting vasodilatation, consequent to its inhibition by asymmetrical dimethylarginine that is abnormally increased by NaCl. In SS and SR subjects, dietary NaCl loading, 250 from 30 mmol/d, over a 7-day period, induced similar, immediate increases in external Na(+) balance (by day 2, ≈360 mmol), plasma volume (+11%), and cardiac output (+8%). In SR subjects, from day 1, transient decreases occurred in both systemic vascular resistance (nadir: -13%, day 2) and mean arterial pressure (nadir: -5%, day 2). In SS subjects, systemic vascular resistance did not change over days 1 to 3, whereas mean arterial pressure increased progressively after day 1, ultimately by 10 mm Hg. Failure of systemic vascular resistance to normally decrease, while cardiac output normally increased, accounted for salt's initial pressor effect in the SS subjects. In SS subjects, baseline plasma levels of asymmetrical dimethylarginine (0.76 μmol/L) and symmetrical dimethylarginine (0.60 μmol/L), which does not affect vasodilatation, approximated those in SR subjects. In SS but not SR subjects, NaCl loading induced increases in asymmetrical dimethylarginine on both days 2 (+38%, median) and 7 (+14%, median). Symmetrical dimethylarginine changed in neither group. For all of the subjects combined, changes in asymmetrical dimethylarginine on day 2 predicted changes in systemic vascular resistance (R=0.751; P<0.001) and mean arterial pressure (R=0.527; P=0.006) on day 2 and similarly on day 7. These observations support the hypothesis tested.

The Efficacy and Safety of Sildenafil in Patients With Pulmonary Arterial Hypertension Associated With the Different Types of Congenital Heart Disease

The difference in underlying pathophysiology in different congenital heart disease (CHD) may have an influence on clinical outcome. It remains unclear whether the effect of sildenafil on pulmonary arterial hypertension (PAH) varies in different types of CHD. The potential effect of sildenafil on pulmonary arterial hypertension related to CHD may be associated with shunt location. In this 12-week, prospective, open label, multicenter trial, 55 patients with CHD were divided into the 3 groups: atrial septal defects group (ASD, n = 15), ventricular septal defects group (VSD, n = 24), and patent ductus arteriosus group (PDA, n = 16). Exercise capacity, hemodynamic parameters, and arterial oxygen saturation were assessed at baseline and after sildenafil therapy (25 mg, 3 times daily). Six-minute walk distance significantly increased from 377.2 ± 68.7 m to 436.0 ± 70.4 m in patients with ASD, from 371.2 ± 66.0 m to 413.7 ± 83.1 m in VSD, and from 384.3 ± 90.2 m to 440.9 ± 71.8 m in PDA (P<0.01, respectively). Moreover, sildenafil also improved the pulmonary vascular resistance and pulmonary blood flow index in the 3 groups, whereas no significant changes in systemic vascular resistance and systemic arterial pressure were observed. However, arterial oxygen saturation was significantly improved in the ASD group only. The incidence of adverse events was similar among the 3 groups. Sildenafil therapy seems to be effective and safe for PAH secondary to ASD, VSD, and PDA, although some clinical and hemodynamic parameters were changed in a different manner among the 3 groups.

Dobutamine-norepinephrine, but not vasopressin, restores the ventriculoarterial matching in experimental cardiogenic shock

We assessed the hemodynamic effects of guideline therapy in experimental cardiogenic shock and compared this treatment with a combination containing an alternative vasopressor (arginine vasopressin, AVP). Our hypothesis was that combined dobutamine-norepinephrine still is the superior inopressor therapy assessed by ventriculoarterial matching in both systole and diastole. Cardiogenic shock (CS) was induced by coronary microembolization in 16 pigs. Dobutamine (Dobu, 2ug/kg/min) alone and combined with either norepinephrine (NE, 100 ng/kg/min) or the pure vasopressor AVP (0.001 u/kg/min) were infused. In CS, Dobu increased cardiac output (CO) and central venous oxygen saturation (SVO₂) from 74 ± 3 mL/kg and 37 ± 2% to 103 ± 8 mL/kg and 49 ± 3%. Adding NE resulted in a further improvement of CO (125 ± 9 mL/kg) and SVO₂ (59 ± 4%) because of an increased heart rate and contractility with minimal change in systemic vascular resistance. Also, energy transfer from the ventricle to the arterial system was restored partly by Dobu and was normalized by supplementing NE. In contrast, supplemental AVP further worsened the shock state by decreasing CO (70 ± 6 mL/kg) and SVO₂ (45 ± 5%) compared with Dobu alone. Combined Dobu-NE has an efficient hemodynamic profile in CS. A pure afterload increasing substance used in acute ischemic CS aggravates the shock state by causing a ventriculoarterial mismatch despite its use in combination with an inotropic compound.

The cardiovascular effects of normobaric hyperoxia in patients with heart rate fixed by permanent pacemaker

To investigate whether the established reductions in heart rate and cardiac output with hyperoxia in humans are primary effects or secondary to increases in systemic vascular resistance, we paced the hearts of nine patients with permanent pacemakers at a fixed rate when breathing either medical air (inspired O(2) fraction 0.21) or oxygen (inspired O(2) fraction 0.80) in a randomised, double-blind fashion. A thoracic bio-impedance machine was used to measure heart rate, stroke volume and blood pressure and calculate cardiac index and systemic vascular resistance index. Oxygen caused no change in cardiac index (p = 0.18), stroke index (p = 0.44) or blood pressure (p = 0.52) but caused a small (5.5%) increase in systemic vascular resistance index (p = 0.03). This suggests that hyperoxia has no direct myocardial depressant effects, but that the changes in cardiac output reported in previous studies are secondary to changes in systemic vascular resistance.

Low-dose versus a Higher-dose Bupivacaine Spinal Anesthesia for Cesarean Delivery

Low-dose <i>versus</i> a Higher-dose Bupivacaine Spinal Anesthesia for Cesarean Delivery

Treating pulmonary hypertension post cardiopulmonary bypass in pigs: milrinone vs. sildenafil analog

Procedures using cardiopulmonary bypass (CPB) and aortic cross-clamping are associated with a variable degree of ischemia/reperfusion of the lungs, leading to acute pulmonary hypertension (PHT). The purpose of this study was to compare the effects of the sildenafil analog (UK343-664), a phosphodiesterase type V(PDEV) inhibitor, with milrinone, a PDE type III inhibitor, in a porcine model of acute PHT following CPB. After the pigs were anesthetized, pressure-tipped catheters were placed in the right ventricle and carotid and pulmonary arteries. Cardiac output was measured with an ultrasound probe on the ascending aorta. After heparinization and placement of aortic and right atrial cannulae, non-pulsatile CPB was instituted and cardioplegia administered following aortic cross-clamping. After 30 minutes, the clamp was removed and the animals re-warmed and separated from CPB in sinus rhythm. The animals were randomized to 3 groups, and 16 animals were studied to completion: milrinone (n=5) 50 microg/kg; sildenafil-analog (n=5) 500 microg/kg; and normal saline (NS) (n=6). Hemodynamic data were collected at baseline pre-CPB and, following termination of CPB, at baseline, 5, 10 and 30 minutes after administration of the drug. Pulmonary hypertension was present in all groups following CPB. After administration of the drugs, mean pulmonary artery pressure decreased in all 3 groups; however, only in the sildenafil-analog group did pulmonary vascular resistance(PVR) decrease by 35%, from 820 to 433 dynes . cm . sec(-5) at 5 minutes (p<0.05), and continued to be decreased at 10 minutes by 26% (P<0.05). Pulmonary selectivity was demonstrated with sildenafil-analog, because there were no similar changes in systemic vascular resistance(SVR) and no significant changes in systemic hemodynamics. Sildenafil-analog, a PDEV inhibitor, shows a promising role for managing the PVR increases that occur following CPB.

Effects of changes in vascular tone on the agreement between pulse contour and transpulmonary thermodilution cardiac output measurements within an up to 6-hour calibration-free period*

To examine whether the agreement between pulse contour and transpulmonary thermodilution cardiac index (CI) measurements is altered by changes in vascular tone within an up to 6-hr calibration-free period. Observational study. Medical intensive care unit of a university hospital. Fifty-nine critically ill patients. None. Data from 59 critically ill patients equipped with a PiCCO device were retrospectively analyzed. The database contained the transpulmonary thermodilution CI (CI(T)) value obtained at each time point the device was calibrated and the pulse contour CI (CI(PC)) value recorded immediately before this time point. Seven subsets of CI pairs were defined according to intervals of time elapsed from the previous calibration (within the first 30 mins, between 30 mins and 1 hr, and every hour up to 6 hrs). In the whole set of 400 CI pairs, CI(PC) correlated with CI(T) (r2 = .68, p < .001). The bias +/- SD was 0.12 +/- 0.61 L/min/m2, and the percentage error was 35%. Among the seven time-interval subsets, the percentage error was <30% only in the two first ones (27% and 26%, respectively). When changes in systemic vascular resistance by >15% occurred (129 times), CI(PC) correlated with CI(T) (r2 = .64), the bias +/- SD was 0.12 +/- 0.62 L/min/m2, and the percentage error was 36%. In the subset of CI pairs recorded within the 1-hr calibration-free period while vascular resistance changed by >15% (n = 32), the bias +/- SD was 0.04 +/- 0.47 L/min/m and the percentage error was 29%. Our study in critically ill patients suggests that the agreement between pulse contour cardiac output and transpulmonary thermodilution cardiac output was not significantly influenced by changes in vascular tone. However, after a 1-hr calibration-free period, recalibration may be encouraged. Such a procedure provides helpful information drawn from other thermodilution-derived variables.

The Effect of Body Mass Index on Patients Admitted with Acute Decompensated Heart Failure

Introduction: Elevated body mass index (BMI) is associated with ventricular remodeling by augmenting hemodynamic load and increasing neurohumoral activation in patients with heart failure. Carvedilol is unique among beta blockers because of its alpha blocking properties giving it increased non-nitric oxide dependent vasodilatory properties. We sought to evaluate the effect of BMI on changes in systemic vascular resistance (ΔSVR) in patients with acute decompensated heart failure treated with B1 selective beta-blockers compared with carvedilol.

What Initiates the Pressor Effect of Salt in Salt-Sensitive Humans?

We tested the traditional hypothesis that an abnormally enhanced renal reclamation of dietary NaCl alone initiates its pressor effect (“salt sensitivity”). Under metabolically controlled conditions, we grouped 23 normotensive blacks as either salt-sensitive (SS) or salt-resistant (SR), depending on whether or not dietary NaCl loading did or did not increase mean arterial blood pressure (MAP) by ≥5 mm Hg. We determined whether dietary NaCl loading induces greater increases in external Na + balance, plasma volume, and cardiac output in SS, compared with any in SR subjects, and differential changes in systemic vascular resistance (SVR) that could account for the pressor differences between SS and SR subjects. Using impedance cardiography, we measured cardiac output and SVR daily at 4-hour intervals throughout the last 3 days of a 7-day period of low NaCl intake (30 mmol per day) and throughout a subsequent 7-day period of NaCl loading (250 mmol per day). In the 11 SS subjects, compared with the 12 SR subjects, NaCl loading induced no greater increases in Na + balance, body weight, plasma volume, and cardiac output. Yet, from days 2 to 7 of NaCl loading, changes of MAP in SS diverged progressively from those in SR. From days 2 to 4, progressive increases of MAP in SS subjects reflected importantly impaired decreases of SVR, as judged from “normal” decreases of SVR in SR subjects. In SS and SR subjects combined, changes in both MAP and SVR on day 2 strongly predicted changes in MAP on day 7. In many normotensive blacks, vascular dysfunction is critical to the initiation of a pressor response to dietary NaCl.

Phosphodiesterase-5 Inhibitor in Eisenmenger Syndrome

Phosphodiesterase-5 inhibitors produce a significant decrease in pulmonary vascular resistance in patients with idiopathic pulmonary arterial hypertension. We studied the effects of tadalafil, a phosphodiesterase-5 inhibitor, on short-term hemodynamics, tolerability, and efficacy over a 12-week period in patients of Eisenmenger syndrome having a pulmonary vascular pathology similar to idiopathic pulmonary arterial hypertension. Sixteen symptomatic Eisenmenger syndrome patients (mean age, 25+/-8.9 years) were assessed hemodynamically at baseline and 90 minutes after a single dose of tadalafil (1 mg/kg body weight up to a maximum of 40 mg). The same dose was then continued daily for 12 weeks, and the patients were restudied. There was a significant decrease in mean pulmonary vascular resistance immediately (24.75+/-8.49 to 19.22+/-8.23 Woods units; P<0.005) and at 12 weeks (19.22+/-8.23 to 17.02+/-6.19 Woods units; P=0.03 versus 90 minutes). Thirteen of 16 patients (81.25%) showed a > or = 20% decrease in pulmonary vascular resistance and were defined as responders. The mean systemic oxygen saturation improved significantly both immediately (84.34+/-5.47% to 87.39+/-4.34%; P<0.005) and at 12 weeks (87.39+/-4.34% to 89.16+/-3.8%; P<0.02 versus 90 minutes) without a significant change in systemic vascular resistance. None of the patients had a fall in systemic arterial pressure, worsening of systemic oxygen saturation, or any adverse reactions to the drug. The mean World Health Organization functional class improved from 2.31+/-0.47 to 1.25+/-0.44 (P<0.0001), and the 6-minute walk distance improved from 344.56+/-119.06 to 387.56+/-117.18 m (P<0.001). Preliminary evaluation of tadalafil has shown efficacy and safety in selected patients with Eisenmenger syndrome, warranting further investigation in this subgroup of patients.

Hemodynamic Changes After Low-Dosage Hydrocortisone Administration in Vasopressor-Treated Preterm and Term Neonates

We sought to investigate whether the increase in blood pressure and decrease in vasopressor support after hydrocortisone administration are associated with changes in systemic hemodynamics in neonates who receive high-dosage dopamine to maintain blood pressure at the lowest acceptable levels. In this prospective, observational study, preterm and term neonates who required dopamine > or = 15 microg/kg per minute to maintain minimum acceptable blood pressure received intravenous hydrocortisone 2 mg/kg followed by up to 4 doses of 1 mg/kg every 12 hours. Fifteen preterm and 5 term neonates without a patent ductus arteriosus composed the study population. Echocardiograms and vascular Doppler studies were performed immediately before the first dose of hydrocortisone and at 1, 2, 6 to 12, 24, and 48 hours thereafter. In the 15 preterm infants, during the first 12 hours of hydrocortisone treatment, the 28% increase in blood pressure paralleled that in the systemic vascular resistance without changes in stroke volume or cardiac output, whereas dopamine dosage decreased. By 24 hours, the dosage of dopamine continued to decrease, whereas stroke volume increased without additional changes in systemic vascular resistance. By 48 hours, dopamine dosage decreased by 72%; blood pressure and stroke volume increased by 31% and 33%, respectively; and systemic vascular resistance and cardiac output tended to be higher (14% and 21%, respectively) compared with baseline. Contractility, global myocardial function, and Doppler indices of blood flow in the middle cerebral and renal artery remained normal and unchanged. The findings in the 5 term infants showed a similar pattern for changes in cardiac function, systemic hemodynamics, and organ blood flow after hydrocortisone administration. In preterm and term neonates who require high-dosage dopamine to maintain blood pressure at the lowest acceptable levels, hydrocortisone improves blood pressure without compromising cardiac function, systemic perfusion, or cerebral and renal blood flow.

Extrapulmonary Effects of Inhaled Nitric Oxide: Role of Reversible S-Nitrosylation of Erythrocytic Hemoglobin

Early applications of inhaled nitric oxide (iNO), typically in the treatment of diseases marked by acute pulmonary hypertension, were met by great enthusiasm regarding the purported specificity of iNO: vasodilation by iNO was specific to the lung (without a change in systemic vascular resistance), and within the lung, NO activity was said to be confined spatially and temporally by Hb within the vascular lumen. Underlying these claims were classical views of NO as a short-lived paracrine hormone that acts largely through the heme groups of soluble guanylate cyclase, and whose potential activity is terminated on encountering the hemes of red blood cell (RBC) Hb. These classical views are yielding to a broader paradigm, in which NO-related signaling is achieved through redox-related NO adducts that endow NO synthase products with the ability to act at a distance in space and time from NO synthase itself. Evidence supporting the biological importance of such stable NO adducts is probably strongest for S-nitrosothiols (SNOs), in which NO binds to critical cysteine residues in proteins or peptides. The circulating RBC is a major SNO reservoir, and RBC Hb releases SNO-related bioactivity peripherally on O2 desaturation. These new paradigms describing NO transport also provide a plausible mechanistic understanding of the increasingly recognized peripheral effects of inhaled NO. An explanation for the peripheral actions of inhaled NO is discussed here, and the rationale and results of attempts to exploit the "NO delivery" function of the RBC are reviewed.

Sildenafil Improves Dynamic Vascular Function in the Brain: Studies in Patients with Pulmonary Hypertension

Background: Prostaglandins and nitric oxide play a pivotal role in the regulation of macro- and microcirculatory blood flow distribution. Interference with both mediator systems have been implicated in cerebrovascular dysfunction. Inhaled iloprost (long-acting prostacyclin analogue) and the phosphodiesterase-5 inhibitor sildenafil have recently shown efficacy in the treatment of chronic pulmonary hypertension. We investigated the impact of these agents on cerebral microcirculatory regulation in patients suffering from this disease. Methods: In 11 patients suffering from severe pulmonary hypertension, a functional transcranial Doppler test utilizing a visual stimulation paradigm was undertaken to measure the evoked flow velocity in the posterior cerebral artery. Measurements were performed in parallel to right heart catheterization and pharmacological testing of the pulmonary vasoreactivity. After assessment of baseline measurements, inhaled iloprost and oral sildenafil were given consecutively for testing of cerebral and pulmonary vascular function. The data gained from the Doppler measurements were compared to data from 22 healthy volunteers. Results: Both substances provoked a significant reduction of pulmonary arterial pressure and vascular resistance, accompanied by minor changes in systemic vascular resistance. In contrast to these superimposable hemodynamic profiles opposite effects were observed regarding cerebral vascular tone: cerebral microvascular reactivity, as assessed by attenuation and time rate parameters, was significantly improved by sildenafil, but slightly worsened by iloprost. Conclusions: Sildenafil has beneficial effects on cerebral vascular reactivity indicative of an improvement in neurovascular coupling in patients with pulmonary hypertension. These results warrant further investigations of the influence of sildenafil on dynamic vascular function in the brain independent of the underlying disease.

Assessment of fluid responsiveness in mechanically ventilated cardiac surgical patients

Accurate assessment of preload responsiveness is an important goal of the clinician to avoid deleterious volume replacement associated with increased morbidity and mortality in mechanically ventilated patients. This study was designed to evaluate the accuracy of simultaneously assessed stroke volume variation and pulse pressure variation using an improved algorithm for pulse contour analysis (PiCCO plus, V 5.2.2), compared to the respiratory changes in transoesophageal echo-derived aortic blood velocity (deltaVpeak), intrathoracic blood volume index, central venous pressure and pulmonary capillary wedge pressure to predict the response of stroke volume index to volume replacement in normoventilated cardiac surgical patients. We studied 20 patients undergoing elective coronary artery bypass grafting. After induction of anaesthesia, haemodynamic measurements were performed before and after volume replacement by infusion of 6% hydroxyethyl starch 200/0.5 (7 mL kg(-1) ) with a rate of 1 mL kg(-1) min(-1). Baseline stroke volume variation correlated significantly with changes in stroke volume index (deltaSVI) (r2 = 0.66; P < 0.05) as did baseline pulse pressure variation (r2 = 0.65; P < 0.05), whereas baseline values of deltaVpeak, intrathoracic blood volume index, central venous pressure and pulmonary artery wedge pressure showed no correlation to deltaSVI. Pulse contour analysis underestimated the volume-induced increase in cardiac index measured by transpulmonary thermodilution (P < 0.05). The results of our study suggest that stroke volume variation and its surrogate pulse pressure variation derived from pulse contour analysis using an improved algorithm can serve as indicators of fluid responsiveness in normoventilated cardiac surgical patients. Whenever changes in systemic vascular resistance are expected, the PiCCO plus system should be recalibrated.

Validation of Mean Arterial Pressure as an Indicator of Acute Changes in Cardiac Output

Changes in mean arterial pressure (MAP) are often assumed to reflect changes in cardiac output (CO). A linear relationship is postulated to exist between these two quantities based upon the circuit model for systemic circulation. Previous studies have correlated changes in CO and MAP. However, to our knowledge, no studies have tested the relationship between CO and MAP in vivo without changes in systemic vascular resistance. Research on baroreceptor stimulation and vasomotor response has shown that vasomotor tone changes 15 to 60 seconds after an acute change in CO. Maximal activation of vasomotor response occurs after approximately 30 seconds. Thus MAP should correlate directly with CO during acute changes (< 15 seconds). To test this, we examined the relationship between CO and MAP during 10 second occlusions of the inferior vena cava in anesthetized pigs. A linear relationship existed between CO and MAP in seven pigs (%MAP = 0.60[%CO] - 0.41, p = 0.0001). This study validates the use of MAP as an indicator of acute changes in CO. Fluctuations in MAP correlate well with acute changes in CO in the absence of changes in vascular tone.

Hypovolaemia-induced vasodilatation during angiotensin AT 1 receptor blockade: role of the AT 2 receptor

AT 1 receptor antagonists may interfere with the haemodynamic determinants of arterial pressure either directly or indirectly through the stimulation of AT 2 receptor provided Ang II is available to interact with them. In order to evaluate the counteracting haemodynamic effect of AT 2 receptor, a prospective, randomized, controlled experimental study was carried out in anaesthetised juvenile pigs. Pigs were randomly assigned to receive placebo ( n = 6), valsartan, an AT 1 receptor antagonist (a-AT 1 group; n = 6), or valsartan and PD 123319, an AT 2 receptor antagonist (a-AT 1–2 group; n = 6) after anaesthesia and before hypovolaemia by 20% of the total estimated blood volume. Thirty minutes after bleeding, the mean arterial pressure decreased significantly and similarly in the three groups (25–30%). The placebo group had a significant decrease in cardiac output (CO) without significant change in systemic vascular resistance (SVR). Conversely, in the a-AT 1 group, SVR decreased significantly with a moderate change in CO and addition of the AT 2 antagonist to the AT 1 antagonist (a-AT 1–2 group) did not abolish the lowering in SVR. The results suggest that AT 2 receptor has only a small if any contribution in the vasodilatation observed in the AT 1-blockade group.

Phasic negative intrathoracic pressures enhance the vascular responses to stimulation of pulmonary arterial baroreceptors in closed-chest anaesthetized dogs.

We investigated whether the reflex responses to stimulation of pulmonary arterial baroreceptors were altered by intrathoracic pressure changes similar to those encountered during normal breathing. Dogs were anaesthetized with alpha-chloralose, a cardiopulmonary bypass was established, and the pulmonary trunk and its main branches as far as the first lobar arteries were vascularly isolated and perfused with venous blood. The chest was closed following connection to the perfusion circuit and pressures distending the aortic arch, carotid sinus and coronary artery baroreceptors were controlled. Changes in the descending aortic (systemic) perfusion pressure (SPP; flow constant) were used to assess changes in systemic vascular resistance. Values of SPP were plotted against mean pulmonary arterial pressure (PAP) and sigmoid functions applied. From these curves we derived the threshold pressures (corresponding to 5% of the overall response of SPP), the maximum slopes (equivalent to peak gain) and the corresponding PAP (equivalent to 'set point'). Stimulus-response curves were compared between data obtained with intrathoracic pressure at atmospheric and with a phasic intrathoracic pressure ranging from atmospheric to around -10 mmHg (18 cycles min(-1)). Results were obtained from seven dogs and are given as means +/-S.E.M. Compared to the values obtained when intrathoracic pressure was at atmospheric, the phasic intrathoracic pressure decreased the pulmonary arterial threshold pressure in five dogs; average change from 28.4 +/- 5.9 to 19.3 +/- 5.9 mmHg (P > 0.05). The inflexion pressure was significantly reduced from 37.8 +/- 4.8 to 27.4 +/- 4.0 mmHg (P < 0.03), but the slopes of the curves were not consistently changed. These results have shown that a phasic intrathoracic pressure, which simulates respiratory oscillations, displaces the stimulus-response curve of the pulmonary arterial baroreceptors to lower pressures so that it lies within a physiological range of pressures.