The athlete's heart: allometric considerations on published papers and relation to cardiovascular variables.

To evaluate the morphology of the "athlete's heart", left ventricular (LV) wall thickness (WT) and end-diastolic internal diameter (LVIDd) at rest were addressed in publications on skiers, rowers, swimmers, cyclists, runners, weightlifters (n = 927), and untrained controls (n = 173) and related to the acute and maximal cardiovascular response to their respective disciplines. Dimensions of the heart at rest and functional variables established during the various sport disciplines were scaled to body weight for comparison among athletes independent of body mass. The two measures of LV were related (r = 0.8; P = 0.04) across athletic disciplines. With allometric scaling to body weight, LVIDd was similar between weightlifters and controls but 7%-15% larger in the other athletic groups, while WT was 9%-24% enlarged in all athletes. The LVIDd was related to stroke volume, oxygen pulse, maximal oxygen uptake, cardiac output, and blood volume (r = ~ 0.9, P < 0.05), while there was no relationship between WT and these variables (P > 0.05). In conclusion, while cardiac enlargement is, in part, essential for the generation of the cardiac output and thus stroke volume needed for competitive endurance exercise, an enlarged WT seems important for the development of the wall tension required for establishing normal arterial pressure in the enlarged LVIDd.

Attenuated pulsatile transition to the cerebral vasculature during high-intensity interval exercise in young healthy men.

NEW FINDINGS: What is the central question of this study? High-intensity interval exercise (HIIE) is recommended for its favourable haemodynamic stimulation, but excessive haemodynamic fluctuations may stress the brain: is the cerebral vasculature protected against exaggerated systemic blood flow fluctuation during HIIE? What is the main finding and its importance? Time- and frequency-domain indices of aortic-cerebral pulsatile transition were lowered during HIIE. The findings suggest that the arterial system to the cerebral vasculature may attenuate pulsatile transition during HIIE as a defence mechanism against pulsatile fluctuation for the cerebral vasculature. ABSTRACT: High-intensity interval exercise (HIIE) is recommended because it provides favourable haemodynamic stimulation, but excessive haemodynamic fluctuations may be an adverse impact on the brain. We tested whether the cerebral vasculature is protected against systemic blood flow fluctuation during HIIE. Fourteen healthy men (age 24 ± 2 years) underwent four 4-min exercises at 80-90% of maximal workload (Wmax ) interspaced by 3-min active rest at 50-60% Wmax . Transcranial Doppler measured middle cerebral artery blood velocity (CBV). Systemic haemodynamics (Modelflow) and aortic pressure (AoP, general transfer function) were estimated from an invasively recorded brachial arterial pressure waveform. Using transfer function analysis, gain and phase between AoP and CBV (0.39-10.0 Hz) were calculated. Stroke volume, aortic pulse pressure and pulsatile CBV increased during exercise (time effect: P < 0.0001 for all), but a time-domain index of aortic-cerebral pulsatile transition (pulsatile CBV/pulsatile AoP) decreased throughout the exercise bouts (time effect: P < 0.0001). Furthermore, transfer function gain reduced, and phase increased throughout the exercise bouts (time effect: P < 0.0001 for both), suggesting the attenuation and delay of pulsatile transition. The cerebral vascular conductance index (mean CBV/mean arterial pressure; time effect: P = 0.296), an inverse index of cerebral vascular tone, did not change even though systemic vascular conductance increased during exercise (time effect: P < 0.0001). The arterial system to the cerebral vasculature may attenuate pulsatile transition during HIIE as a defence mechanism against pulsatile fluctuation for the cerebral vasculature.

Endothelial Cell Phenotypes Demonstrate Different Metabolic Patterns and Predict Mortality in Trauma Patients.

In trauma patients, shock-induced endotheliopathy (SHINE) is associated with a poor prognosis. We have previously identified four metabolic phenotypes in a small cohort of trauma patients (N = 20) and displayed the intracellular metabolic profile of the endothelial cell by integrating quantified plasma metabolomic profiles into a genome-scale metabolic model (iEC-GEM). A retrospective observational study of 99 trauma patients admitted to a Level 1 Trauma Center. Mass spectrometry was conducted on admission samples of plasma metabolites. Quantified metabolites were analyzed by computational network analysis of the iEC-GEM. Four plasma metabolic phenotypes (A-D) were identified, of which phenotype D was associated with an increased injury severity score (p < 0.001); 90% (91.6%) of the patients who died within 72 h possessed this phenotype. The inferred EC metabolic patterns were found to be different between phenotype A and D. Phenotype D was unable to maintain adequate redox homeostasis. We confirm that trauma patients presented four metabolic phenotypes at admission. Phenotype D was associated with increased mortality. Different EC metabolic patterns were identified between phenotypes A and D, and the inability to maintain adequate redox balance may be linked to the high mortality.

Effect of adrenaline on serum mid-regional pro-atrial natriuretic peptide and central blood volume.

NEW FINDINGS: What is the central question in this study? Atrial natriuretic peptide (ANP) is secreted in response to atrial wall distension and thus allows for evaluation, albeit indirect, of the central blood volume. Adrenaline has chronotropic and inotropic effects. We evaluated whether the chronotropic and inotropic effects of adrenaline were reflected in mid-regional proANP. What is the main finding and its importance? Central blood volume remained stable with infusion of adrenaline and yet mid-regional proANP increased. Thus, the chronotropic and inotropic state of the heart or adrenaline directly induces release of ANP variants from the myocytes. ABSTRACT: Atrial natriuretic peptide (ANP) has vasodilatory, natriuretic and diuretic properties. It is secreted in response to atrial wall distension and thereby provides an indirect evaluation of central blood volume (CBV). Adrenaline has chronotropic and inotropic effects that increase cardiac output. In the present study, we evaluated whether these effects were influenced by an increase in CBV and reflected in mid-regional proANP (MR-proANP) concentrations in the circulation, a stable proxy marker of bioactive ANP. Changes in CBV were evaluated by thoracic electrical admittance and haemodynamic variables monitored by pulse-contour analysis during two intervals with graded infusion of adrenaline. Adrenaline infusion increased heart rate (by 33 ± 18%) and stroke volume (by 6 ± 13%), hence cardiac output (by 42 ± 23%; all P < 0.05). The increase in cardiac output did not result from an increase in CBV, because thoracic electrical admittance remained stable (-3 ± 17%; P = 0.230). Serum MR-proANP concentrations were increased (by 26 ± 25%; P < 0.001) by adrenaline infusion and remained elevated 60 min postinfusion. We conclude that MR-proANP in the circulation is affected not only by CBV, but also by increased chronotropy/inotropy of the heart, or that adrenaline directly induces release of ANP variants from the myocytes.

The role of lactate in sepsis and COVID-19: Perspective from contracting skeletal muscle metabolism.

NEW FINDINGS: What is the topic of this review? Lactate is considered an important substrate for mitochondria in the muscles, heart and brain during exercise and is the main gluconeogenetic precursor in the liver and kidneys. In this light, we review the (patho)physiology of lactate metabolism in sepsis and coronavirus disease 2019 (COVID-19). What advances does it highlight? Elevated blood lactate is strongly associated with mortality in septic patients. Lactate seems unrelated to tissue hypoxia but is likely to reflect mitochondrial dysfunction and high adrenergic stimulation. Patients with severe COVID-19 exhibit near-normal blood lactate, indicating preserved mitochondrial function, despite a systemic hyperinflammatory state similar to sepsis. ABSTRACT: In critically ill patients, elevated plasma lactate is often interpreted as a sign of organ hypoperfusion and/or tissue hypoxia. This view on lactate is likely to have been influenced by the pioneering exercise physiologists around 1920. August Krogh identified an oxygen deficit at the onset of exercise that was later related to an oxygen 'debt' and lactate accumulation by A. V. Hill. Lactate is considered to be the main gluconeogenetic precursor in the liver and kidneys during submaximal exercise, but hepatic elimination is attenuated by splanchnic vasoconstriction during high-intensity exercise, causing an exponential increase in blood lactate. With the development of stable isotope tracers, lactate has become established as an important energy source for muscle, brain and heart tissue, where it is used for mitochondrial respiration. Plasma lactate > 4 mM is strongly associated with mortality in septic shock, with no direct link between lactate release and tissue hypoxia. Herein, we provide evidence for mitochondrial dysfunction and adrenergic stimulation as explanations for the sepsis-induced hyperlactataemia. Despite profound hypoxaemia and intense work of breathing, patients with severe coronavirus disease 2019 (COVID-19) rarely exhibit hyperlactataemia (> 2.5 mM), while presenting a systemic hyperinflammatory state much like sepsis. However, lactate dehydrogenase, which controls the formation of lactate, is markedly elevated in plasma and strongly associated with mortality in severe COVID-19. We briefly review the potential mechanisms of the lactate dehydrogenase elevation in COVID-19 and its relationship to lactate metabolism based on mechanisms established in contracting skeletal muscle and the acute respiratory distress syndrome.

Fluid-responsiveness, blood volume and perfusion in preoperative haemodynamic optimisation of hip fracture patients; a prospective observational study.

BACKGROUND: Preoperative resuscitation strategies in patients with hip fracture (HF) are lacking. We aimed to investigate fluid-responsiveness, peripheral perfusion index (PPI) and blood volume (BV)-status in patients with HF undergoing resuscitation in the preoperative phase. METHODS: In a prospective observational study, we evaluated preoperative fluid-responsiveness, indices of perfusion and BV before and after lumbar epidural analgesia in 50 patients with HF shortly after admittance. RESULTS: Initially, 18 (36%) patients were fluid-responsive (≥10% increased SV in response to 250 ml fluid bolus) and 13 (26%) presented hypovolaemia (deviation of measured BV from estimated BV ≤ 0.9). According to fluid-responsiveness, no difference in absolute values of cardiac index (CI) (2.7 L [2.1-3.3] vs. 2.8 L [2.3-3.4], p = .5) was seen, but cardiac output (CO) rose significantly in the hypovolaemic patients: 9% [5-18] vs. 1% [-3-7], p = .004. After epidural analgesia, 26 (52%) patients were again fluid-responsive and 15 (30%) were hypovolaemic. CI was now significantly lower in fluid-responsive patients (2.2 L [1.7-2.7] vs. 2.9 L [2.3-3.5], p = .001). Prior to epidural analgesia, no significant trend towards hypovolaemic patients having lower indices of perfusion was seen. After epidural analgesia, more patients with hypovolaemia presented with PPI≤1.5 (8 (53%) vs. 3 (9%), p = .001) and absolute values of PPI were also significantly lower if IBV was low (1.4 [0.9-3.2] vs. 3.2 [2.4-4.8], p = .01). PPI correlated with hypovolaemia after epidural analgesia (rho 0.4 [0.1-0.7], p = .007). CONCLUSIONS: Preoperative fluid-responsivity in HF patients might be attributable to elements of hypovolaemia and sympathetic compensatory ability conjointly, confounding the use of SV-guided resuscitation. PPI could be associated with BV, which may support clinicians during perioperative haemodynamic optimisation.

The effect of vasoconstriction on intestinal perfusion is determined by preload dependency: A prospective observational study.

BACKGROUND: The effects of vasoconstriction on cardiac stroke volume (SV) and indices of peripheral and intestinal perfusion are insufficiently described. METHODS: In a non-randomized clinical study, 30 patients undergoing elective rectal surgery were exposed to modulation of preload. The primary endpoint was intestinal perfusion (flux), measured by single-point laser Doppler flowmetry. Secondary endpoints were central cardiovascular variables obtained by the LiDCO rapid monitor, the peripheral perfusion index (PPI) derived from the pulse oximetry signal and muscle (StO2 ) and cerebral oxygenation (ScO2 ) determined by near-infrared spectroscopy. RESULTS: For the whole cohort (n = 30), administration of Phenylephrine during HUT induced a median [IQR] increase in SV by 22% [14-41], p = .003 and in mean arterial pressure (MAP) by 54% [31-62], p < .001, with no change in PPI, StO2 and ScO2 or flux. In patients who were preload dependent during HUT (stroke volume variation; SSV >10%; n = 23), administration of phenylephrine increased SV by 29% [12-43], p = .01 and MAP by 54% [33-63], p < .001, followed by an increase in intestinal perfusion flux by 60% [15-289], p = .05, while PPI, StO2 and ScO2  remained unchanged. For non-preload dependent patients (SSV <10%; n = 7), no changes in hemodynamic indices were seen besides an increase in MAP by 54% [33-58], p = .002. CONCLUSION: The reflection of vasoconstrictive modulation of preload in systemic cardiovascular variables and indices of perfusion was dependent on preload responsiveness. Administration of phenylephrine to increase preload did not appear to compromise organ perfusion.

Mid-regional plasma pro-atrial natriuretic peptide and stroke volume responsiveness for detecting deviations in central blood volume following major abdominal surgery.

BACKGROUND: A reduced central blood volume is reflected by a decrease in mid-regional plasma pro-atrial natriuretic peptide (MR-proANP), a stable precursor of ANP, and a volume deficit may also be assessed by the stroke volume (SV) response to head-down tilt (HDT). We determined plasma MR-proANP during major abdominal procedures and evaluated whether the patients were volume responsive by the end of the surgery, taking the fluid balance and the crystalloid/colloid ratio into account. METHODS: Patients undergoing pancreatic (n = 25), liver (n = 25), or gastroesophageal (n = 38) surgery were included prospectively. Plasma MR-proANP was determined before and after surgery, and the fluid response was assessed by the SV response to 10° HDT after the procedure. The fluid strategy was based mainly on lactated Ringer's solution for gastroesophageal procedures, while for pancreas and liver surgery, more human albumin 5% was administered. RESULTS: Plasma MR-proANP decreased for patients undergoing gastroesophageal surgery (-9% [95% CI -3.2 to -15.3], p = .004) and 10 patients were fluid responsive by the end of surgery (∆SV > 10% during HDT) with an administered crystalloid/colloid ratio of 3.3 (fluid balance +1389 ± 452 ml). Furthermore, plasma MR-proANP and fluid balance were correlated (r = .352 [95% CI 0.031-0.674], p < .001). In contrast, plasma MR-proANP did not change significantly during pancreatic and liver surgery during which the crystalloid/colloid ratio was 1.0 (fluid balance +385 ± 478 ml) and 1.9 (fluid balance +513 ± 381 ml), respectively. For these patients, there was no correlation between plasma MR-proANP and fluid balance, and no patient was fluid responsive. CONCLUSION: Plasma MR-proANP was reduced in fluid responsive patients by the end of surgery for the patients for whom the fluid strategy was based on more lactated Ringer's solution than human albumin 5%.

Results for World Rowing Federation and Olympic events 1893-2019.

Results in rowing have improved and here we estimate results for Olympic and World rowing championships based on the winning results from 1893 to 2019 obtained in the current seven Olympic events for men (n = 556) and women (n = 239). Data were collected from the official World Rowing Federation online records and from published results and the development analysed by linear regression analysis for the year of competition. Results improved by about 0.7 s per year (15 ± 9.4%) (mean ± SD). Depending on the event, 2020 predicted mean time for the winning boat for men is 363 s (range 326-397) vs. 404 s (362-439) for women (10.3 ± 1.1% slower). The ten-year coefficient of variance for the original boats in Olympic and World Rowing Federation regatta remaining within the Olympic programme, single scull and eight, decreased from 9 ± 2% (1893-1903) to 2 ± 0.4% (2009-2019). Reduced variability in winning times illustrates the standardization of the rowing course and boats, and the improvement in performance point to that body size becomes ever more important for success in competitive rowing.

Influence of blood pressure on internal carotid artery blood flow during combined propofol-remifentanil and thoracic epidural anesthesia.

Background and Aims: Anesthesia often reduces mean arterial pressure (MAP) to a level that may compromise cerebral blood flow. We evaluated whether phenylephrine treatment of anesthesia-induced hypotension affects internal carotid artery (ICA) blood flow and whether anesthesia affects ICA flow and CO2 reactivity. Material and Methods: The study included twenty-seven patients (65 ± 11 years; mean ± SD) undergoing esophageal resection (n = 14), stomach resection (n = 12), or a gastroentero anastomosis (n = 1) during combined propofol-remifentanil and thoracic epidural anesthesia. Duplex ultrasound evaluated ICA blood flow. Evaluations were before and after induction of anesthesia, before and after the administration of phenylephrine as part of standard care to treat anesthesia-induced hypotension at a MAP below 60 mmHg, and the hypocapnic reactivity of ICA flow was determined before and during anesthesia. Results: Induction of anesthesia reduced MAP from 108 ± 12 to 66 ± 16 mmHg (P < 0.0001) and ICA flow from 340 ± 92 to 196 ± 52 mL/min (P < 0.0001). Phenylephrine was administered to 24 patients (0.1-0.2 mg) and elevated MAP from 53 ± 8 to 73 ± 8 mmHg (P = 0.0001) and ICA flow from 191 ± 43 to 218 ± 50 mL/min (P = 0.0276). Furthermore, anesthesia reduced the hypocapnic reactivity of ICA flow from 23 (18-33) to 14%/kPa (10-22; P = 0.0068). Conclusion: Combined propofol-remifentanil and thoracic epidural anesthesia affect ICA flow and CO2 reactivity. Phenylephrine partly restored ICA flow indicating that anesthesia-induced hypotension contributes to the reduction in ICA flow.

Reactive oxygen species play a modulatory role in the hyperventilatory response to poikilocapnic hyperoxia in humans.

KEY POINTS: The proposed mechanism for the increased ventilation in response to hyperoxia includes a reduced brain CO2 -[H+ ] washout-induced central chemoreceptor stimulation that results from a decrease in cerebral perfusion and the weakening of the CO2 affinity for haemoglobin. Nonetheless, hyperoxia also results in excessive brain reactive oxygen species (ROS) formation/accumulation, which hypothetically increases central respiratory drive and causes hyperventilation. We then quantified ventilation, cerebral perfusion/metabolism, arterial/internal jugular vein blood gases and oxidant/antioxidant biomarkers in response to hyperoxia during intravenous infusion of saline or ascorbic acid to determine whether excessive ROS production/accumulation contributes to the hyperoxia-induced hyperventilation in humans. Ascorbic acid infusion augmented the antioxidant defence levels, blunted ROS production/accumulation and minimized both the reduction in cerebral perfusion and the increase in ventilation observed during saline infusion. Hyperoxic hyperventilation seems to be mediated by central chemoreceptor stimulation provoked by the interaction between an excessive ROS production/accumulation and reduced brain CO2 -[H+ ] washout. ABSTRACT: The hypothetical mechanism for the increase in ventilation ( V̇E ) in response to hyperoxia (HX) includes central chemoreceptor stimulation via reduced CO2 -[H+ ] washout. Nonetheless, hyperoxia disturbs redox homeostasis and raises the hypothesis that excessive brain reactive oxygen species (ROS) production/accumulation may increase the sensitivity to CO2 or even solely activate the central chemoreceptors, resulting in hyperventilation. To determine the mechanism behind the HX-evoked increase in V̇E , 10 healthy men (24 ± 4 years) underwent 10 min trials of HX under saline and ascorbic acid infusion. V̇E , arterial and right internal right jugular vein (ijv) partial pressure for oxygen (PO2 ) and CO2 (PCO2 ), pH, oxidant (8-isoprostane) and antioxidant (ascorbic acid) markers, as well as cerebral blood flow (CBF) (Duplex ultrasonography), were quantified at each hyperoxic trial. HX evoked an increase in arterial partial pressure for oxygen, followed by a hyperventilatory response, a reduction in CBF, an increase in arterial 8-isoprostane, and unchanged PijvCO2 and ijv pH. Intravenous ascorbic acid infusion augmented the arterial antioxidant marker, blunted the increase in arterial 8-isoprostane and attenuated both the reduction in CBF and the HX-induced hyperventilation. Although ascorbic acid infusion resulted in a slight increase in PijvCO2 and a substantial decrease in ijv pH, when compared with the saline bout, HX evoked a similar reduction and a paired increase in the trans-cerebral exchanges for PCO2 and pH, respectively. These findings indicate that the poikilocapnic hyperoxic hyperventilation is likely mediated via the interaction of the acidic brain interstitial fluid and an increase in central chemoreceptor sensitivity to CO2 , which, in turn, seems to be evoked by the excessive ROS production/accumulation.

Association of the intraoperative peripheral perfusion index with postoperative morbidity and mortality in acute surgical patients: a retrospective observational multicentre cohort study.

BACKGROUND: We hypothesised that in acute high-risk surgical patients, a lower intraoperative peripheral perfusion index (PPI) would indicate a higher risk of postoperative complications and mortality. METHODS: This retrospective observational study included 1338 acute high-risk surgical patients from November 2017 until October 2018 at two University Hospitals in Denmark. Intraoperative PPI was the primary exposure variable and the primary outcome was severe postoperative complications defined as a Clavien-Dindo Class ≥III or death, within 30 days. RESULTS: intraoperative PPI was associated with severe postoperative complications or death: odds ratio (OR) 1.12 (95% confidence interval [CI] 1.05-1.19; P<0.001), with an association of intraoperative mean PPI ≤0.5 and PPI ≤1.5 with the primary outcome: OR 1.79 (95% CI 1.09-2.91; P=0.02) and OR 1.65 (95% CI 1.20-2.27; P=0.002), respectively. Each 15-min increase in intraoperative time spend with low PPI was associated with the primary outcome (per 15 min with PPI ≤0.5: OR 1.11 (95% CI 1.05-1.17; P<0.001) and with PPI ≤1.5: OR 1.06 (95% CI 1.02-1.09; P=0.002)). Thirty-day mortality in patients with PPI ≤0.5 was 19% vs 10% for PPI >0.5, P=0.003. If PPI was ≤1.5, 30-day mortality was 16% vs 8% in patients with a PPI >1.5 (P<0.001). In contrast, intraoperative mean MAP ≤65 mm Hg was not significantly associated with severe postoperative complications or death (OR 1.21 [95% CI 0.92-1.58; P=0.2]). CONCLUSIONS: Low intraoperative PPI was associated with severe postoperative complications or death in acute high-risk surgical patients. To guide intraoperative haemodynamic management, the PPI should be further investigated.

Effect of low vs high haemoglobin transfusion trigger on cardiac output in patients undergoing elective vascular surgery: Post-hoc analysis of a randomized trial.

BACKGROUND: During vascular surgery, restricted red-cell transfusion reduces frontal lobe oxygen (ScO2 ) saturation as determined by near-infrared spectroscopy. We evaluated whether inadequate increase in cardiac output (CO) following haemodilution explains reduction in ScO2 . METHODS: This is a post-hoc analysis of data from the Transfusion in Vascular surgery (TV) Trial where patients were randomized on haemoglobin drop below 9.7 g/dL to red-cell transfusion at haemoglobin below 8.0 (low-trigger) vs 9.7 g/dL (high-trigger). Fluid administration was guided by optimizing stroke volume. We compared mean intraoperative levels of CO, haemoglobin, oxygen delivery, and CO at nadir ScO2 with linear regression adjusted for age, operation type and baseline. Data for 46 patients randomized before end of surgery were included for analysis. RESULTS: The low-trigger resulted in a 7.1% lower mean intraoperative haemoglobin level (mean difference, -0.74 g/dL; P < .001) and reduced volume of red-cell transfused (median [inter-quartile range], 0 [0-300] vs 450 mL [300-675]; P < .001) compared with the high-trigger group. Mean CO during surgery was numerically 7.3% higher in the low-trigger compared with the high-trigger group (mean difference, 0.36 L/min; 95% confidence interval (CI.95), -0.05 to 0.78; P = .092; n = 42). At the nadir ScO2 -level, CO was 11.9% higher in the low-trigger group (mean difference, 0.58 L/min; CI.95, 0.10-1.07; P = .024). No difference in oxygen delivery was detected between trial groups (MD, 1.39 dLO2 /min; CI.95, -6.16 to 8.93; P = .721). CONCLUSION: Vascular surgical patients exposed to restrictive RBC transfusion elicit the expected increase in CO making it unlikely that their potentially limited cardiac capacity explains the associated ScO2 decrease.

Fluctuations in cardiac stroke volume during rowing.

Preload to the heart may be limited during rowing because both blood pressure and central venous pressure increase when force is applied to the oar. Considering that only the recovery phase of the rowing stroke allows for unhindered venous return, rowing may induce large fluctuations in stroke volume (SV). Thus, the purpose of this study was to evaluate SV continuously during the rowing stroke. Eight nationally competitive oarsmen (mean ± standard deviation: age 21 ± 2 years, height 190 ± 9 cm, and weight 90 ± 10 kg) rowed on an ergometer at a targeted heart rate of 130 and 160 beats per minute. SV was derived from arterial pressure waveform by pulse contour analysis, while ventilation and force on the handle were measured. Mean arterial pressure was elevated during the stroke at both work rates (to 133 ± 10 [P < .001] and 145 ± 11 mm Hg [P = .024], respectively). Also, SV fluctuated markedly during the stroke with deviations being largest at the higher work rate. Thus, SV decreased by 27 ± 10% (31 ± 11 mL) at the beginning of the stroke and increased by 25 ± 9% (28 ± 10 mL) in the recovery (P = .013), while breathing was entrained with one breath during the drive of the stroke and one prior to the next stroke. These observations indicate that during rowing cardiac output depends critically on SV surges during the recovery phase of the stroke.

Influence of breathing on variation in cardiac stroke volume at the onset of cycling.

PURPOSE: During cycling, the variation in cardiac stroke volume (SVV) is similar to that at rest. However, SVV may be influenced by ventilation at the start of cycling, e.g., by a Valsalva-like maneuver used to stabilize the body. This study evaluated the influence of ventilation on SV during initiation of cycling. METHODS: Ten healthy recreationally physical active males (mean ± SD: age 26 ± 3 years, height 184 ± 9 cm, weight 85 ± 9 kg) cycled on an ergometer for four 30 s intervals at submaximal workloads while synchronizing ventilatory and cardiovascular variables derived from gas exchange and arterial pulse contour analysis, respectively. RESULTS: At exercise onset, cardiac output increased by an instantaneous rise in heart rate and SV (P < 0.05). In contrast, blood pressure increased only after 15 s (P < 0.05), reflected in a decline in total peripheral resistance from exercise onset (P < 0.05). SVV was similar at rest (20 ± 6%) and during exercise (21 ± 5%) except for the first 5 s of exercise when a ~ 2.5-fold elevation (47 ± 6%; P < 0.05) was correlated to variation in respiratory frequency (= 0.71, P = 0.02) and tidal volume (R = 0.66, P = 0.04) but not to variation in heart rate or blood pressure. Stepwise multiple regression analysis indicated a respiratory frequency influence on SVV at the onset of ergometer cycling. CONCLUSION: The data provide evidence for a ventilatory influence on SVV at the onset of cycling exercise.

Laser speckle contrast imaging of forehead cutaneous blood flow during carotid endarterectomy as a potential non-invasive method for surrogate monitoring of cerebral perfusion.

Monitoring cerebral perfusion is important for goal-directed anesthesia. Taking advantage of the supply of the supraorbital region and Glabella from the internal carotid artery (ICA), we evaluated changes in cutaneous blood flow using laser speckle contrast imagining (LSCI) as a potential method for indirect real-time monitoring of cerebral perfusion. Nine patients (8 men, mean age 70 years) underwent eversion carotid endarterectomy under local anesthesia. Cutaneous blood flow of the forehead was monitored using LSCI. During clamping of the common carotid artery (CCA), ipsilateral supraorbital region and Glabellas cutaneous blood flow dropped from 334 ± 135 to 221 ± 109 AU (p = 0.023) (AU: arbitrary flux units) and from 384 ± 151 to 276 ± 107 AU (p = 0.023), respectively, whilst the contralateral supraorbital region cutaneous blood flow remained unchanged. The supraorbital cutaneous blood flow did not change significantly following reperfusion of the external carotid artery (ECA) (221 ± 109 to 281 ± 154 AU; p = 0.175) and ICA (281 ± 154 to 310 ± 184 AU; p = 01). A comparable trend for Glabella followed ECA (276 ± 107 to 342 ± 170 AU; p = 0.404) and ICA (342 ± 170 to 352 ± 191 AU; p = 01) reperfusion. In patients undergoing carotid endarterectomy under local anesthesia, LSCI of the supraorbital and Glabella regions reflected clamping of the CCA but did not distinguish reperfusion of the ICA from that of the ECA.

KATP channels modulate cerebral blood flow and oxygen delivery during isocapnic hypoxia in humans.

KEY POINTS: ATP-sensitive K+ (KATP ) channels mediate hypoxia-induced cerebral vasodilatation and hyperperfusion in animals. We tested whether KATP channels blockade affects the increase in human cerebral blood flow (CBF) and the maintenance of oxygen delivery (CDO2 ) during hypoxia. Hypoxia-induced increases in the anterior circulation and total cerebral perfusion were attenuated under KATP channels blockade affecting the relative changes of brain oxygen delivery. Therefore, in humans, KATP channels activation modulates the vascular tone in the anterior circulation of the brain, contributing to CBF and CDO2 responses to hypoxia. ABSTRACT: ATP-sensitive K+ (KATP ) channels mediate hypoxia-induced cerebral vasodilatation and hyperperfusion in animals. We tested whether KATP channels blockade affects the increase in cerebral blood flow (CBF) and the maintenance of oxygen delivery (CDO2 ) during hypoxia in humans. Nine healthy men were exposed to 5-min trials of normoxia and isocapnic hypoxia (IHX, 10% O2 ) before (BGB) and 3 h after glibenclamide ingestion (AGB). Mean arterial pressure (MAP), arterial saturation ( SaO2 ), partial pressure of oxygen ( PaO2 ) and carbon dioxide ( PaCO2 ), internal carotid artery blood flow (ICABF), vertebral artery blood flow (VABF), total (t)CBF (Doppler ultrasound) and CDO2 were quantified during the trials. IHX provoked similar reductions in SaO2 and PaO2 , while MAP was not affected by oxygen desaturation or KATP blockade. A smaller increase in ICABF (ΔBGB: 36 ± 23 vs. ΔAGB 11 ± 18%, p = 0.019) but not in VABF (∆BGB 26 ± 21 vs. ∆AGB 27 ± 27%, p = 0.893) was observed during the hypoxic trial under KATP channels blockade. Thus, IHX-induced increases in tCBF (∆BGB 32 ± 19 vs. ∆AGB 14 ± 13%, p = 0.012) and CDO2 relative changes (∆BGB 7 ± 13 vs. ∆AGB -6 ± 14%, p = 0.048) were attenuated during the AGB hypoxic trial. In a separate protocol, 6 healthy men (5 from protocol 1) underwent a 5-min exposure to normoxia and IHX before and 3 h after placebo (5 mg of cornstarch) ingestion. IHX reduced SaO2 and PaO2 , but placebo did not affect the ICABF, VABF, tCBF, or CDO2 responses. Therefore, in humans, KATP channels activation modulates vascular tone in the anterior rather than the posterior circulation of the brain, contributing to tCBF and CDO2 responses to hypoxia.

Differential vasomotor responses to isocapnic hyperoxia: cerebral versus peripheral circulation.

Isocapnic hyperoxia (IH) evokes cerebral and peripheral hypoperfusion via both disturbance of redox homeostasis and reduction in nitric oxide (NO) bioavailability. However, it is not clear whether the magnitude of the vasomotor responses depends on the vessel network exposed to IH. To test the hypothesis that the magnitude of IH-induced reduction in peripheral blood flow (BF) may differ from the hypoperfusion response observed in the cerebral vascular network under oxygen-enriched conditions, nine healthy men (25 ± 3 yr, mean ± SD) underwent 10 min of IH during either saline or vitamin C (3 g) infusion, separately. Femoral artery (FA), internal carotid artery (ICA), and vertebral artery (VA) BF (Doppler ultrasound), as well as arterial oxidant (8-isoprostane), antioxidant [ascorbic acid (AA)], and NO bioavailability (nitrite) markers were simultaneously measured. IH increased 8-isoprostane levels and reduced nitrite levels; these responses were followed by a reduction in both FA BF and ICA BF, whereas VA BF did not change. Absolute and relative reductions in FA BF were greater than IH-induced changes in ICA and VA perfusion. Vitamin C infusion increased arterial AA levels and abolished the IH-induced increase in 8-isoprostane levels and reduction in nitrite levels. Whereas ICA and VA BF did not change during the vitamin C-IH trial, FA perfusion increased and reached similar levels to those observed during normoxia with saline infusion. Therefore, the magnitude of IH-induced reduction in femoral blood flow is greater than that observed in the vessel network of the brain, which might involve the determinant contribution that NO has in the regulation of peripheral vascular perfusion.

The central blood volume as measured by thoracic electrical impedance and plasma proANP is not compromised by donation of 900 mL of blood in men.

OBJECTIVES: To evaluate whether the donation of 900 mL of blood reduces the central blood volume (CBV) assessed by thoracic electrical impedance (TI) and plasma pro-atrial natriuretic peptide (proANP). BACKGROUND: Donation of 450 mL of blood carries a 1% risk of a vasovagal reaction. Withdrawal of 900 mL of blood decreases cardiac output; however, the effect on CBV remains unknown. METHODS/MATERIALS: A randomised, single-blinded, placebo-controlled, crossover design was used, where 21 healthy semi-recumbent men donated 2 × 450 mL blood or were sham-phlebotomised. Changes in CBV were estimated by proANP and TI at 1.5 (TI1.5 ) and 100 (TI100 ) kHz, reflecting extracellular volume and (regional) total body water, respectively, and the index value (IDX; 1/T1.5 -1/TI100 ) was used to estimate changes in intracellular (red cell) volume. Systolic, diastolic and mean arterial blood pressure; heart rate; stroke volume; cardiac output; and systemic vascular resistance were monitored. After completion of the study, 1000 mL of isotonic saline was infused. RESULTS: Changes (mean% ± SD) in TI1.5 , TI100 and IDX were similar after 450 mL (-0.2 ± 1.6%, 0.0 ± 1.1%, -0.4 ± 10.1%) and 900 mL (0.1 ± 1.6%, 0.2 ± 1.5% and -2.0 ± 15.8%) of blood donation compared to after a sham donation of 450 mL (-0.9 ± 1.2%, -0.5 ± 1.5% and -0.1 ± 6.1%) and 900 mL (-1.2 ± 1.5%, -0.6 ± 1.3% and 0.5 ± 9.9%). In addition, changes in plasma proANP were similar after 450 and 900 mL of blood donation (-0.8 ± 6.7% and -7.6 ± 7.9%) as after sham donations (1.3 ± 7.3% and -4.5 ± 5.6%). Monitoring haemodynamic variables revealed that stroke volume decreased after the donation of 900 mL of blood (-12 ± 12 mL) compared to sham donations. CONCLUSION: During a 900-mL blood loss in semi-recumbent men, CBV measured by TI and plasma proANP is not affected.

CO2 supplementation dissociates cerebral oxygenation and middle cerebral artery blood velocity during maximal cycling.

This study evaluated whether the reduction of prefrontal cortex oxygenation (ScO2 ) during maximal exercise depends on the hyperventilation-induced hypocapnic attenuation of middle cerebral artery blood velocity (MCA Vmean ). Twelve endurance-trained males (age: 25 ± 3 years, height: 183 ± 8 cm, weight: 75 ± 9 kg; mean ± SD) performed in three separate laboratory visits, a maximal oxygen uptake (VO2 max) test, an isocapnic (end-tidal CO2 tension (PetCO2 ) clamped at 40 ± 1 mmHg), and an ambient air controlled-pace constant load high-intensity ergometer cycling to exhaustion, while MCA Vmean (transcranial Doppler ultrasound) and ScO2 (near-infrared spectroscopy) were determined. Duration of exercise (12 min 25 s ± 1 min 18 s) was matched by performing the isocapnic trial first. Pulmonary VO2 was 90 ± 6% versus 93 ± 5% of the maximal value (P = .012) and PetCO2 40 ± 1 versus 34 ± 4 mmHg (P < .05) during the isocapnic and control trials, respectively. During the isocapnic trial MCA Vmean increased by 16 ± 13% until clamping was applied and continued to increase (by 14 ± 28%; P = .017) until the end of exercise, while there was no significant change during the control trial (P = .071). In contrast, ScO2 decreased similarly in both trials (-3.2 ± 5.1% and -4.1 ± 9.6%; P < .001, isocapnic and control, respectively) at exhaustion. The reduction in prefrontal cortex oxygenation during maximal exercise does not depend solely on lowered cerebral blood flow as indicated by middle cerebral blood velocity.