Initial Stroke Volume Research Articles

Mean arterial pressure targeted fluid resuscitation may lead to fluid overload: A bleeding-resuscitation animal experiment.

IntroductionFluid resuscitation is the cornerstone of treatment in hemorrhagic shock. Despite increasing doubts, several guidelines recommend to maintain mean arterial pressure (MAP) >65 mmHg as the most frequent indication of fluid therapy. Our aim was to investigate the effects of a MAP-guided management in a bleeding-resuscitation animal experiment.Materials and methodsAfter anesthesia and instrumentation (tbsl) animals were bled till the initial stroke volume index dropped by 50% (t0). Fluid replacement was performed in 4 equivalent steps (t1-4) with balanced crystalloid solution to reach the baseline values of MAP. Invasive hemodynamic measurements and blood gas analyses were performed after each step.ResultsMean arterial pressure dropped from tbsl to t0 (114±11 vs 76.9±16.9 mmHg, p<0.001) and returned to baseline by t4 (101.4±14.4 mmHg). From tbsl-t0 stroke volume index (SVI), cardiac index (CI) decreased (SVI: 40±8.6 vs 19.3±3.6 ml/m2, p<0.001; CI: 3.4±0.3 vs 1.9±0.3 l/min/m2, p<0.001), pulse pressure variation (PPV) increased (13.2±4.3 vs 22.1±4.3%, p<0.001). There was a decrease in oxygen delivery (464±45 vs 246±26.9 ml/min, p<0.001), central venous oxygen saturation (82.8±5.4 vs 53.6±12.1%, p<0.001) and increase in lactate levels (1.6±0.4 vs 3.5±1.6 mmol/l, p<0.005). SVI, CI and PPV returned to their initial values by t2. To normalize MAP fluid therapy had to be continued till t4, with the total infused volume of 4.5±0.8 l.ConclusionIn the current experiment bleeding led to hemorrhagic shock, while MAP remained higher than 65 mmHg. Furthermore, MAP was unable to indicate the normalization of SVI, CI and PPV that resulted in unnecessary fluid administration. Our data give further evidence that MAP may be an inappropriate parameter to follow during fluid resuscitation.

Low cardiac index and stroke volume on admission are associated with poor outcome in critically ill burn patients: a retrospective cohort study.

BackgroundImpact of early systemic hemodynamic alterations and fluid resuscitation on outcome in the modern burn care remains controversial. We investigate the association between acute-phase systemic hemodynamics, timing of fluid resuscitation and outcome in critically ill burn patients.MethodsRetrospective, single-center cohort study was conducted in a university hospital. Forty critically ill burn patients with total body surface area (TBSA) burn-injured >20 % with invasive blood pressure and cardiac output monitoring (transpulmonary thermodilution technique) within 8 h from trauma were included. We retrospectively examined hemodynamic variables during the first 24 h following admission, and their association with 90-day mortality.ResultsThe median (interquartile range 25th–75th percentile) TBSA, Simplified Acute Physiology Score II (SAPS II) and Abbreviated Burn Severity Index of the study population were 41 (29–56), 31 (23–50) and 9 (7–11) %, respectively. 90-Day mortality was 42 %. There was no statistical difference between the median pre-hospital and 24-h administered fluid volume in survivors and non-survivors. On admission, stroke volume (SV), cardiac index (CI), oxygen delivery index and mean arterial pressure (MAP) were significantly lower in patients who died despite similar fluid resuscitation volume. ROC curves comparing the ability of initial SV, CI, MAP and lactate to discriminate 90-day mortality gave areas under curves of, respectively, 0.89 (CI 0.77–1), 0.77 (CI 0.58–0.95), 0.73 (CI 0.53–0.93) and 0.78 (CI 0.63–0.92); (p value <0.05 for all). In multivariate analysis, SAPS II and initial SV were independently associated with 90-day mortality (best cutoff value for SV was 27 mL, sensitivity 92 %, specificity 69 %). During 24 h, no interaction was found between time and outcome regarding macrocirculatory parameters changes. Hemodynamic parameters improved during the first 24-h resuscitation in all patients but patients who died had lower SV and CI on admission, which remained through the first 24 h.ConclusionLow initial SV and CI were associated with poor outcome in critically ill burn patients. Very early hemodynamic monitoring may in help detecting under-resuscitated patients. Future prospective interventional studies should explore the impact of early goal-directed therapy in these specific patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-016-0192-y) contains supplementary material, which is available to authorized users.

Excitotoxicity and Metabolic Changes in Association With Infarct Progression

We investigated to what extent excitotoxicity and metabolic changes in the peri-infarct region of patients with malignant hemispheric stroke are associated with delayed infarct progression. In 18 patients with malignant hemispheric stroke, 2 microdialysis probes were implanted within the peri-infarct tissue at a distance of 5 and 15 mm to the infarct. Precise probe placement was achieved by intraoperative laser speckle imaging. Glutamate, glucose, pyruvate, and lactate levels were monitored for 5 days after surgery. Delayed infarct progression was determined from serial MRI on the day after surgery and after the monitoring period. Initial stroke volume ranged from 122 to 479 cm3 with a median of 295 cm3. Nine of 18 patients (50%) had delayed infarct progression (median, 44 cm3; range, 19-93 cm3). In these patients, glucose and individual pyruvate levels were significantly lower when compared with patients without infarct progression, whereas glutamate and the lactate-pyruvate ratio were significantly elevated in patients with infarct progression early after surgery (12-36 hours) at the 15-mm microdialysis probe location. Lactate was elevated but without difference between groups. Excitotoxic or metabolic impairment was associated with delayed infarct progression and could serve as a treatment target.

Comparison of infarct volume and behavioral deficit in Wistar Kyoto and spontaneously hypertensive rat after transient occlusion of the middle cerebral artery

Rodent models of focal cerebral ischemia are important tools in experimental stroke research. Such models have proven instrumental for the understanding of injury mechanisms in cerebral stroke and helped to identify potential new therapeutic options. A plethora of neuroprotective substances have been shown to be effective in preclinical stroke research but failed to prove effectiveness in subsequent clinical trials. Interestingly, preclinical studies have shown that neuroprotective agents are selectively effective in different rat strains. The underlying mechanisms for this discrepancy are so far unknown, but differences in initial stroke volume with concomitant neuroinflammatory processes in the expanding stroke area might be relevant.In the current project, we compared the stroke volume and behavioral outcome between Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR), subjected to transient middle cerebral artery occlusion (tMCAO) for 1 h, followed by 23 h reperfusion. We further analyzed the expression of well-known pro-inflammatory mediators in the cortical peri-infarct area region using a TTC-based isolation approach.Initial reduction of local cerebral blood flow was comparable between both strains. Mean infarct volume and the extent of tMCAO-provoked functional deficits did not differ between WKY and SHR rats. Furthermore, the induction of pro-inflammatory mediators, among CCL3 and CCL5, in the isolated ischemic peri-infarct area region was equal in both rat strains.We were able to demonstrate that stroke outcome is comparable 23 h after transient MCAO in WKY and SHR rats. Future studies have to show whether this observation confirms in the long-term, and which factors contribute to differences observed with respect to therapeutic responsiveness.

Initial stroke volume is an independent outcome predictor

A new study suggests that lesion volume assessed within 72 h of stroke onset is an important independent predictor of 90-day functional outcome and neurological recovery. If used in stroke trials, outcome models including stroke volume, age and NIH Stroke Scale scores could increase power for detecting treatment effect.

Does nicotinic acid (niacin) lower blood pressure?

Nicotinic acid (niacin) is a well-established treatment for dyslipidaemia – an important cardiovascular disease (CVD) risk factor. However, niacin may also reduce blood pressure (BP), which is another important CVD risk factor. This review examines the limited publicly available data on niacin’s BP effects. Acute administration of immediate-release niacin may lower BP because of niacin’s acute vasodilatory effects. Although not always supported by clinical trial data, the package insert of a prescription, extended-release niacin describes niacin-induced acute hypotension. From a chronic standpoint, larger studies, such as the Coronary Drug Project, suggest that niacin may lower BP when administered over a longer period of time. Post hoc analyses of some of the more recent niacin clinical trials also support a more chronic, dose-dependent, BP-lowering effect of niacin. Because laropiprant [a prostaglandin D2 (PGD2) type 1 (DP1) receptor antagonist] does not attenuate niacin’s BP-lowering effects, it is unlikely that any chronic lowering of BP by niacin is due to dilation of dermal vessels through activation of the DP1 receptor by PGD2. Further research is warranted to evaluate the extent and mechanisms of niacin’s effects on BP.

Serial magnetic resonance imaging in a rat pup filament stroke model

Neonatal stroke is increasingly recognized in preterm and term infants but the ability to study this condition has been limited by the technical challenges in developing suitable animal models. In the current study we report the use of transient filament middle cerebral artery occlusion for 1.5 h in 10-day-old rat pups in which we were able to perform serial magnetic resonance imaging (MRI) studies. Serial MRI was performed immediately after the onset of stroke until 28 days after injury in an 11.7 T scanner using diffusion weighted and T2-weighted images. At 28 days the rat pups were sacrificed and standard histological stains were performed to validate stroke area. Serial behavioral assessments were also performed on the day of each imaging study. The anatomical distribution of stroke was similar to that expected from occlusion of the middle cerebral artery in adult models and represents a specific model of neonatal stroke in contrast to the commonly used model of carotid artery occlusion with 8% hypoxia. The initial stroke volume from MR measurements was 39% of the ipsilateral hemisphere at 0 h post-occlusion, reached a maximum at 24 h (44%) and then decreased in size (17%) with subsequent cavitation by 28 days. Infarction was more visible early with diffusion weighted imaging whereas T2-mapping provided more accurate infarct volumes at later time points. Despite the relatively large infarct volume, we saw little evidence of behavioral neurological deficit suggesting that this may also serve as a model of developmental plasticity and recovery.

Apelin has in vivo inotropic effects on normal and failing hearts.

Apelin has been shown ex vivo to be a potent cardiac inotrope. This study was undertaken to evaluate the in vivo effects of apelin on cardiac function in native and ischemic cardiomyopathic rat hearts using a novel combination of a perivascular flow probe and a conductance catheter. Native rats (n =32) and rats in heart failure 6 weeks after left anterior descending coronary artery ligation (n =22) underwent median sternotomy with placement of a perivascular flow probe around the ascending aorta and a pressure volume conductance catheter into the left ventricle. Compared with sham-operated rats, the ligated rats had significantly decreased baseline Pmax and max dP/dt. Continuous infusion of apelin at a rate of 0.01 microg/min for 20 minutes significantly increased Pmax and max dP/dt compared with infusion of vehicle alone in both native and failing hearts. Apelin infusion increased cardiac contractility, indicated by a significant increase in stroke volume (SV) without a change in left ventricular end diastolic volume (102+/-16% change from initial SV versus 26+/-20% for native animals, and 110+/-30% versus 26+/-11% for ligated animals), as well as an increase in preload recruitable stroke work (180+/-24 mm Hg versus 107+/-9 mm Hg for native animals). The present study is the first to show that apelin has positive inotropic effects in vivo in both normal rat hearts and rat hearts in failure after myocardial infarction. Apelin may have use as an acute inotropic agent in patients with ischemic heart failure.

Estimation of stroke volume in the dog by a pulse contour method.

A method for estimating the stroke volume (SV) from the systolic area of a single-channel record of the central aortic pressure has been tested in 12 anesthetized open-chest dogs. The formula used was SV = K·Psa·(1 + Ts/Td), where Psa is the area under the systolic part of the curve above end-diastolic pressure, Ts and Td are the durations of systole and diastole, respectively, and K is an arbitrary constant derived from measurement of an initial SV by electromagnetic flowmeter in each dog and used thereafter without change, in that dog. In the 12 dogs, 541 simultaneous determinations of SV by the pressure contour and electromagnetic flowmeter methods were compared under normal and altered circulatory conditions employing 12 different interventions. The total range of SV was 2.4 to 28.1 ml, of heart rate 35 to 207/min, and of mean arterial pressure 24 to 166 mm Hg. The overall correlation coefficient (r) was 0.928 with a regression line y = 1.04x + 0.21 ml (SE) of estimate, ±17.4%. Except for three sympathomimetic drugs, the r values for all other interventions ranged from 0.93 to 0.99. These observations compare favorably with those of previously reported pulse contour methods. The windkessel origin of the formula is noted, and a new derivation from a modification of the "water-hammer" equation is given.