Monge Garcia et al. Critical Care (2018) 22:325 https://doi.org/10.1186/s13054-018-2260-1 RESEARCH Open Access Performance comparison of ventricular and arterial dP/dtmax for assessing left ventricular systolic function during different experimental loading and contractile conditions Manuel Ignacio Monge Garcia1*, Zhongping Jian2, Jos J. Settels2, Charles Hunley3, Maurizio Cecconi4, Feras Hatib2 and Michael R. Pinsky5 Abstract Background: Maximal left ventricular (LV) pressure rise (LV dP/dtmax), a classical marker of LV systolic function, requires LV catheterization, thus surrogate arterial pressure waveform measures have been proposed. We compared LV and arterial (femoral and radial) dP/dtmax to the slope of the LV end-systolic pressure-volume relationship (Ees), a load-independent measure of LV contractility, to determine the interactions between dP/dtmax and Ees as loading and LV contractility varied. Methods: We measured LV pressure-volume data using a conductance catheter and femoral and radial arterial pressures using a fluid-filled catheter in 10 anesthetized pigs. Ees was calculated as the slope of the end-systolic pressure-volume relationship during a transient inferior vena cava occlusion. Afterload was assessed by the effective arterial elastance. The experimental protocol consisted of sequentially changing afterload (phenylephrine/nitroprusside), preload (bleeding/fluid bolus), and contractility (esmolol/dobutamine). A linear-mixed analysis was used to assess the contribution of cardiac (Ees, end-diastolic volume, effective arterial elastance, heart rate, preload-dependency) and arterial factors (total vascular resistance and arterial compliance) to LV and arterial dP/dtmax. Results: Both LV and arterial dP/dtmax allowed the tracking of Ees changes, especially during afterload and contractility − 1 changes, although arterial dP/dtmax was lower compared to LV dP/dtmax (bias 732 ± 539 mmHg⋅s for femoral dP/dtmax, − 1 and 625 ± 501 mmHg⋅s for radial dP/dtmax). Changes in cardiac contractility (Ees) were the main determinant of LV and arterial dP/dtmax changes. Conclusion: Although arterial dP/dtmax is a complex function of central and peripheral arterial factors, radial and particularly femoral dP/dtmax allowed reasonably good tracking of LV contractility changes as loading and inotropic conditions varied. Keywords: dP/dtmax, Contractility, Arterial pressure, Left ventricular function * Correspondence: [email protected] 1Unidad de Cuidados Intensivos, Hospital Universitario SAS de Jerez, C/ Circunvalación, s/n, 11407 Jerez de la Frontera, Spain Full list of author information is available at the end of the article © The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Monge Garcia et al. Critical Care (2018) 22:325 Page 2 of 12 Background Animal Research: Reporting of In Vivo Experiments Left ventricular (LV) contractility is one of the main de- (ARRIVE) guidelines were used for the elaboration of terminants of cardiac function and an important element this manuscript [12]. of the hemodynamic evaluation of the critically ill [1]. Ten females adult Yorkshire cross breed pigs weighing Impaired LV contractility is frequently seen in patients 81 ± 6 kg were studied. They were maintained in with acute coronary syndrome and sepsis [2]. Although temperature-controlled and humidity-controlled rooms LV end-systolic elastance (Ees) is the reference method with a typical light–dark cycle and given standard chow for assessing LV contractility [3], its bedside use is lim- and tap water ad libitum. Prior to anesthesia induction, ited by its invasiveness and the technical difficulties as- a general physical examination was performed including sociated with its estimation [4]. LV ejection fraction weight, temperature, heart rate, respiratory rate, mucus (EFLV), estimated by echocardiography as the fractional membrane, capillary refill time, general condition, and area of contraction, is currently the most used clinical heart and lung auscultation. If found to be stable, the index for estimating LV systolic function. However, EFLV animal then was premedicated with an intramuscular − has known limitations as an index of cardiac inotropy, combination of telazol (4.4 mg⋅kg 1), ketamine (2.2 − − such as the high dependency on the cardiac loading con- mg⋅kg 1) and xylazine (1.1 mg⋅kg 1). Once the animal ditions [5, 6]. Although new echocardiographic indexes, was on the preparation table, an endotracheal tube was such as speckle-tracking-derived LV global longitudinal placed in the trachea, and was anesthetized by gas with strain or strain rate, have been recently introduced [7], a mixture of 3–4% isoflurane and 100% oxygen. An their need of sophisticated software and trained opera- intravenous catheter was placed in the auricular artery tors precludes their use for continuous hemodynamic and vein and the neck and inguinal areas were shaved monitoring of the LV systolic function. and cleaned, and the electrocardiogram (EKG) elec- The maximum rate of LV pressure during isovolumetric trodes applied. Once on the operating table the pig was contraction (LV dP/dtmax) has been classically considered mechanically ventilated in a volume-controlled mode − as a marker of LV inotropic state [8]. However, as LV dP/ with respiratory rate set at 13–15 cycles⋅min 1, tidal vol- − 1 dtmax requires a direct measure of LV pressure, other sur- ume at 10 ml⋅kg (plus 100 ml compensation for dead rogates have been proposed using the arterial pressure space), and anesthesia was maintained with isoflurane waveform. Peripheral dP/dtmax, as measured from cathe- 1.5–2.5% and a mixture of oxygen, air and/or nitrous ters inserted into the femoral or radial arteries have been oxide and fraction of inspired oxygen (FiO2)of60–80%. suggested as feasible surrogates for LV dP/dtmax [9, 10]. Fluid was maintained by an intravenous infusion of − − However, as the arterial pressure results from the com- Ringer’s lactate solution (2–4ml⋅kg 1⋅h 1). Rectal bined interaction of the LV ejection and the arterial sys- temperature was monitored and kept between 36 and tem properties, other potential factors could also 37 °C using a heating pad. Animal anesthesia were moni- contribute to the peripheral dP/dtmax, degrading its accur- tored and recorded approximately every 15 min for the acy as a measure of LV contractile state [10, 11]. duration of the experimentation. Anesthesia depth and To address this issue, we compared LV and peripheral pain were assessed throughout the study by performing dP/dtmax during different preloading and afterloading jaw tone and toe pinch. Positive jaw tone and negative and contractility conditions against the LV end-systolic toe pinch meant that the animal was under a elastance, a load-independent measure of cardiac con- non-painful depth of anesthesia. No paralytic agents tractility, and the other cardiac and arterial factors that were used for this study. were influencing these parameters in our established Instantaneous LV pressure-volume (PV) measure- porcine model. ments were obtained from a 7Fr-lumen dual-field cath- eter with 12-equidistant electrodes and a high-fidelity Methods pressure sensor (CA71083PL, CD Leycom, Zoetermeer, The study was approved by the Institutional Animal the Netherlands) connected to a PV signal processor Care and Use Committee (IACUC) at the Edwards Re- (Inca®, CD Leycom, Zoetermeer, the Netherlands). The search Center, and all experimentation was performed in catheter tip was positioned in the LV apex and the cor- accordance with the USDA Animal Welfare Act regula- rect placement was confirmed by fluoroscopy and the tions (AWArs), and the Guide for the Care and Use of examination of the segmental LV PV loops. Laboratory Animals (ILAR, NAP, Washington, DC, 2010, 8th edition). The Test Facility is accredited by the Data collection and analysis Association for the Assessment and Accreditation of La- Volume signal calibration was performed via right-side boratory Animal Care, International (AAALACi) and heart catheterization with a Swan-Ganz catheter in the registered with the United States Department of Agricul- pulmonary artery (Vigilance, Edwards Lifesciences, Irvine, ture to conduct research with laboratory animals. The CA, USA). Volume signal calibration comprised 3–5 Monge Garcia et al. Critical Care (2018) 22:325 Page 3 of 12 thermodilution boluses for the determination of cardiac parameter of LV afterload calculated as Ea = Pes/SV [15]), output (CO). Correction for parallel conductance (the arterial (radial and femoral) and LV dP/dtmax were calcu- conductance of the surrounding tissues, which was sub- lated from 3 to 5 beats in steady-state conditions during tracted from the raw catheter volume) was performed the respiratory pause just before the IVC occlusion. Ees with the injection of 10-ml boluses of 5% hypertonic saline was determined as the slope of the end-systolic through the distal port of the pulmonary artery catheter. pressure-volume relationship during