Search

Background: Levosimendan improves ventricular function, induces vasodilation and induces myocardial preconditioning. We determined the external efficiency and assessed the effects on arrhythmias., Methods: In isolated, blood-perfused rabbit hearts, levosimendan (0.75 micromol) or placebo was administered, while hemodynamics were recorded. After no-flow ischemia and reperfusion, data were recorded again., Results: Placebo in normoxic hearts did not affect measurements, while levosimendan increased heart rate (+ 18 %) and improved coronary output (+ 52 %), stroke volume (+ 28 %), maximal left ventricular pressure (+ 30 %), maximal rate of pressure increase (+ 36 %), work (+ 68 %), minimal rate of pressure increase (+ 53 %), coronary blood flow (+ 41 %), coronary resistance (- 19 %) and external efficiency (33 %; P < 0.05). During reperfusion, hemodynamics in the levosimendan group were significantly better preserved compared with the placebo group. Early reperfusion arrhythmias were decreased (levosimendan group: 7 +/- 3 % vs. placebo group: 25 +/- 17 %; P < 0.05)., Conclusions: Levosimendan does not impair diastole, dilates coronary vessels, induces pharmacological preconditioning, improves external efficiency and exerts antiarrhythmic properties during reperfusion. As this drug protects the heart from reperfusion injury, it seems well suited for treating dysfunctional hearts after cardiac surgery.

Background: The isolated heart as an experimental model has been firmly established for more than 100 years., Material and Methods: In this study, five modifications are compared: 1. modified Langendorff apparatus (LA) with modified Krebs-Henseleit (KH) solution a) not containing bovine serum albumin (BSA; n = 13) and b) containing BSA (n = 16), 2. LA with KH solution containing BSH and bovine erythrocytes (n = 14), 3. LA with support rabbit (n = 6), and 4. "working heart" preparation with KH solution, BSA and bovine erythrocytes (n = 16). In the latter modification, no balloon was inserted into the left ventricular cavity, i. e., systemic and coronary circuits were not separated from each other. After completion of the preparation and 20-min stabilization, hemodynamic and metabolic data were assessed while the hearts were contracting in the ejecting mode. Thereafter, protocols for different studies were performed that are not presented here. However, the stability of the modifications within their individual protocols is reported., Results: The results suggest that hearts perfused with KH solution are well suited for short protocols. In spite of the additional costs and time, blood perfusion is required for long-lasting protocols or if changes in coronary flow are to be investigated., Conclusions: The working heart exhibits both the best function and stability at a relatively low experimental expenditure. Yet, it is not suited for studies where perfusion pressure needs to be changed independent of arterial pressure.

Unlabelled: We conducted this study to determine the interaction of MCI-154, 6-[4-(4'-pyridylamino)phenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride, a calcium sensitizer, and isoflurane on myocardial contractility as well as systemic and coronary hemodynamics in chronically instrumented dogs after pharmacological autonomic nervous system activity blockade. MCI-154 increased heart rate and left ventricular function with no change in rate pressure product, pressure work index, and coronary blood flow, with a decrease in coronary vascular resistance (CVR) in the conscious state. Isoflurane decreased heart rate and left ventricular function, with a decrease in rate pressure product and pressure work index. Isoflurane also decreased CVR, but not coronary blood flow. The cardiovascular actions of MCI-154 during isoflurane anesthesia were qualitatively similar to those observed in the conscious state. In contrast to the finding in the conscious state, MCI-154 reversed the decrease in cardiac output and preload recruitable stroke work caused by isoflurane, but these are not significantly different from the effects of isoflurane alone. These results indicate that MCI-154 increases myocardial contractility and decreases CVR without changing calculated myocardial oxygen consumption during both the conscious state and isoflurane anesthesia., Implications: MCI-154, a calcium sensitizer, restores the myocardial contractility depressed by isoflurane and enhances the coronary vasodilating effect of isoflurane in chronically instrumented dogs.

The mean systemic pressure analog (Pmsa), calculated from running hemodynamic data, estimates mean systemic filling pressure (MSFP). This post hoc study used data from a porcine veno-arterial extracorporeal membrane oxygenation (ECMO) model [n = 9; Sus scrofa domesticus; ES breed (Schweizer Edelschwein)] with eight experimental conditions; Euvolemia [a volume state where ECMO flow produced normal mixed venous saturation (SVO2) without vascular collapse]; three levels of increasing norepinephrine infusion (Vasoconstriction 1-3); status after stopping norepinephrine (Post Vasoconstriction); and three steps of volume expansion (10 mL/kg crystalloid bolus) (Volume Expansion 1-3). In each condition, Pmsa and a "reduced-pumpspeed- Pmsa" (Pmsared) were calculated from baseline and briefly reduced pump speeds, respectively. We calculated agreement for absolute values (per condition) and changes (between consecutive conditions) of Pmsa and Pmsared, against MSFP at zero ECMO flow. Euvolemia venous return driving pressure was 5.1 ± 2.0 mmHg. Bland--Altman analysis for Pmsa vs. MSFP (all conditions; 72 data pairs) showed bias (confidence interval) 0.5 (0.10.9) mmHg; limits of agreement (LoA) -2.7 to 3.8 mmHg. Bias for ΔPmsa vs. ΔMSFP (63 data pairs): 0.2 (-0.2 to 0.6) mmHg, LoA -3.2 to 3.6 mmHg. Bias for Pmsared vs. MSFP (72 data pairs): 0.0 (-0.3 to -0.3) mmHg; LoA -2.3 to 2.4 mmHg. Bias for ΔPmsared vs. ΔMSFP (63 data pairs) was 0.2 (-0.1 to 0.4) mmHg; LoA -1.8 to 2.1 mmHg. In conclusion, during veno-arterial ECMO, under clinically relevant levels of vasoconstriction and volume expansion, Pmsa accurately estimated absolute and changing values of MSFP, with low between-method precision. The within-method precision of Pmsa was excellent, with a least significant change of 0.15 mmHg. [ABSTRACT FROM AUTHOR]

This article describes the modified arterial reservoir in detail. The modified arterial reservoir makes explicit the wave nature of both reservoir (Pres) and excess pressure (Pxs). The mathematical derivation and methods for estimating Pres in the absence of flow velocity data are described. There is also discussion of zero-flow pressure (Pzf), the pressure at which flow through the circulation ceases; its relationship to asymptotic pressure (P∞) estimated by the reservoir model; and the physiological interpretation of Pzf. A systematic review and meta-analysis provides evidence that Pzf differs from mean circulatory filling pressure. [ABSTRACT FROM AUTHOR]

Potentially, mean circulatory filling pressure (Pmcf) could aid hemodynamic management in patients admitted to the intensive care unit (ICU). However, data regarding the normal range for Pmcf do not exist challenging its clinical use. We aimed to define the range for Pmcf for ICU patients and also calculated in what percentage of cases equilibrium between arterial blood pressure (ABP) and central venous pressure (CVP) was reached. In patients in whom no equilibrium was reached, we corrected for arterial-to-venous compliance differences. Finally, we studied the influence of patient characteristics on Pmcf. We hypothesized fluid balance, the use of vasoactive medication, being on mechanical ventilation, and the level of positive end-expiratory pressure would be positively associated with Pmcf. We retrospectively studied a cohort of 311 patients that had cardiac arrest in ICU while having active recording of ABP and CVP 1 min after death. Median Pmcf was 15 mmHg [interquartile range (IQR) 12–18]. ABP and CVP reached an equilibrium state in 52% of the cases. Correction for arterial-to-venous compliances differences resulted in a maximum alteration of 1.3 mmHg in Pmcf. Fluid balance over the last 24 h, the use of vasoactive medication, and being on mechanical ventilation were associated with a higher Pmcf. Median Pmcf was 15 mmHg (IQR 12–18). When ABP remained higher than CVP, correction for arterial-to-venous compliance differences did not result in a clinically relevant alteration of Pmcf. Pmcf was affected by factors known to alter vasomotor tone and effective circulating blood volume. NEW & NOTEWORTHY In a cohort of 311 intensive care unit (ICU) patients, median mean circulatory filling pressure (Pmcf) measured after cardiac arrest was 15 mmHg (interquartile range 12–18). In 48% of cases, arterial blood pressure remained higher than central venous pressure, but correction for arterial-to-venous compliance differences did not result in clinically relevant alterations of Pmcf. Fluid balance, use of vasopressors or inotropes, and being on mechanical ventilation were associated with a higher Pmcf. [ABSTRACT FROM AUTHOR]

Background: Mean systemic filling pressure (Pmsf) is a quantitative measurement of a patient's volume status and represents the tone of the venous reservoir. The aim of this study was to estimate Pmsf after severe hemorrhagic shock and cardiac arrest in swine anesthetized with propofol-based total intravenous anesthesia, as well as to evaluate Pmsf's association with vasopressor-free resuscitation. Methods: Ten healthy Landrace/Large-White piglets aged 10-12 weeks with average weight 20±1 kg were used in this study. The protocol was divided into four distinct phases: stabilization, hemorrhagic, cardiac arrest, and resuscitation phases. We measured Pmsf at 5-7.5 seconds after the onset of cardiac arrest and then every 10 seconds until 1 minute postcardiac arrest. During resuscitation, lactated Ringers was infused at a rate that aimed for a mean right atrial pressure of =4 mm Hg. No vasopressors were used. Results: The mean volume of blood removed was 860±20 ml (blood loss, ~61%) and the bleeding time was 43.2±2 minutes while all animals developed pulseless electrical activity. Mean Pmsf was 4.09±1.22 mm Hg, and no significant differences in Pmsf were found until 1 minute postcardiac arrest (4.20±0.22 mm Hg at 5-7.5 seconds and 3.72±0.23 mm Hg at 55-57.5 seconds; P=0.102). All animals achieved return of spontaneous circulation (ROSC), with mean time to ROSC being 6.1±1.7 minutes and mean administered volume being 394±20 ml. Conclusions: For the first time, Pmsf was estimated after severe hemorrhagic shock. In this study, Pmsf remained stable during the first minute post-arrest. All animals achieved ROSC with goal-directed fluid resuscitation and no vasopressors. [ABSTRACT FROM AUTHOR]

Various methods for indirect assessment of mean systemic filling pressure (MSFP) produce controversial results compared with MSFP at zero blood flow. We recently reported that the difference between MSFP at zero flow measured by right atrial balloon occlusion (MSFPRAO) and MSFP estimated using inspiratory holds depends on the volume status. We now compare three indirect estimates of MSFP with MSFPRAO in euvolemia, bleeding, and hypervolemia in a model of anesthetized pigs (n = 9) with intact circulation. MSFP was estimated using instantaneous beat-to-beat venous return during tidal ventilation (MSFPinst_VR), right atrial pressure-flow data pairs at flow nadir during inspiratory holds (MSFPnadir_hoid), and a dynamic model analog adapted to pigs (MSFPa). MSFPRAO was underestimated by MSFPnadir_hold and MSFPa in all volume states. Volume status modified the difference between MSFPRAO and all indirect methods (method X volume state interaction, P ≤ 0.020). All methods tracked changes in MSFPRAO concordantly, with the lowest bias seen for MSFPa [bias (confidence interval): -0.4 (-0.7 to -0.0) mmHg]. We conclude that indirect estimates of MSFP are unreliable in this experimental setup. NEW & NOTEWORTHY For indirect estimations of MSFP using inspiratory hold maneuvers, instantaneous beat-to-beat venous return, or a dynamic model analog, the accuracy was affected by the underlying volume state. All methods investigated tracked changes in MSFPRAO concordantly. [ABSTRACT FROM AUTHOR]

Key points Wave travel plays an important role in cardiovascular physiology. However, many aspects of pulmonary arterial wave behaviour remain unclear., Wave intensity and reservoir-excess pressure analyses were applied in the pulmonary artery in subjects with and without pulmonary hypertension during spontaneous respiration and dynamic stress tests., Arterial wave energy decreased during expiration and Valsalva manoeuvre due to decreased ventricular preload. Wave energy also decreased during handgrip exercise due to increased heart rate., In pulmonary hypertension patients, the asymptotic pressure at which the microvascular flow ceases, the reservoir pressure related to arterial compliance and the excess pressure caused by waves increased. The reservoir and excess pressures decreased during Valsalva manoeuvre but remained unchanged during handgrip exercise., This study provides insights into the influence of pulmonary vascular disease, spontaneous respiration and dynamic stress tests on pulmonary artery wave propagation and reservoir function., Abstract Detailed haemodynamic analysis may provide novel insights into the pulmonary circulation. Therefore, wave intensity and reservoir-excess pressure analyses were applied in the pulmonary artery to characterize changes in wave propagation and reservoir function during spontaneous respiration and dynamic stress tests. Right heart catheterization was performed using a pressure and Doppler flow sensor tipped guidewire to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery in control subjects and patients with pulmonary arterial hypertension (PAH) at rest. In controls, recordings were also obtained during Valsalva manoeuvre and handgrip exercise. The asymptotic pressure at which the flow through the microcirculation ceases, the reservoir pressure related to arterial compliance and the excess pressure caused by arterial waves increased in PAH patients compared to controls. The systolic and diastolic rate constants also increased, while the diastolic time constant decreased. The forward compression wave energy decreased by ∼8% in controls and ∼6% in PAH patients during expiration compared to inspiration, while the wave speed remained unchanged throughout the respiratory cycle. Wave energy decreased during Valsalva manoeuvre (by ∼45%) and handgrip exercise (by ∼27%) with unaffected wave speed. Moreover, the reservoir and excess pressures decreased during Valsalva manoeuvre but remained unaltered during handgrip exercise. In conclusion, reservoir-excess pressure analysis applied to the pulmonary artery revealed distinctive differences between controls and PAH patients. Variations in the ventricular preload and afterload influence pulmonary arterial wave propagation as demonstrated by changes in wave energy during spontaneous respiration and dynamic stress tests. [ABSTRACT FROM AUTHOR]

Mean systemic filling pressure (Pmsf) is a major determinant of venous return. Its value is unknown in critically ill patients (ICU). Our objectives were to report Pmsf in critically ill patients and to look for its clinical determinants, if any. We performed a prospective study in 202 patients who died in the ICU with a central venous and/or arterial catheter. One minute after the heart stopped beating, intravascular pressures were recorded in the supine position after ventilator disconnection. Parameters at admission, during the ICU stay, and at the time of death were prospectively collected. One-minute Pmsf was 12.8 ± 5.6 mmHg. It did not differ according to gender, severity score, diagnosis at admission, fluid balance, need for and duration of mechanical ventilation, or length of stay. Nor was there any difference according to suspected cause of death, classified as shock (cardiogenic, septic, and hemorrhagic) and nonshock, although a large variability of values was observed. The presence of norepinephrine at the time of death (102 patients) was associated with a higher 1-min Pmsf (14 ± 6 vs. 11.4 ± 4.5 mmHg), whereas the decision to forgo life-sustaining therapy (34 patients) was associated with a lower 1-min Pmsf (10.9 ± 3.8 vs. 13.1 ± 5.3 mmHg). In a multiple-regression analysis, norepinephrine (β = 2.67, P = 0.0004) and age (β = -0.061, P = 0.022) were associated with 1-min Pmsf. One-minute Pmsf appeared highly variable without any difference according to the kind of shock and fluid balance, but was higher with norepinephrine. [ABSTRACT FROM AUTHOR]

Cardiac output has never been assessed during free-diving diving in the sea. Knowledge of human diving response in this setting is therefore scarce. 3 immersions were performed by 7 divers: at depths of 10 m, 20 m and 30 m. Each test consisted of 3 apnea phases: descent, static and ascent. An impedance cardiograph provided data on stroke volume, heart rate and cardiac output. Mean blood pressure, arterial O2 saturation and blood lactate values were also collected. Starting from a resting value of 4.5±1.6 L·min-1, cardiac output at 10 m showed an increase up to 7.1±2.2 L·min-1 (p < 0.01) during the descent, while conditions during the static and ascent phases remained unchanged. At 20 m cardiac output values were 7.3±2.4 L·min-1 and 6.7±1.2L·min-1 during ascent and descent, respectively (p < 0.01), and 4.3±0.9 L·min-1 during static phase. At 30 m cardiac output values were 6.5±1.8 L·min-1 and 7.5±2 L·min-1 during descent and ascent, respectively (p < 0.01), and 4.7±2.1 L·min-1 during static phase. Arterial O2 saturation decreased with increasing dive depth, reaching 91.1±3.4% (p < 0.001 vs. rest) upon emergence from a depth of 30 m. Blood lactate values increased to 4.1±1.2 mmol·L-1 at the end of the 30 m dive (p < 0.001 vs. rest). Results seem to suggest that simultaneous activation of exercise and diving response could lead to an absence of cardiac output reduction aimed at an oxygen-conserving effect. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate an analogue of mean systemic filling pressure ( P) and derived variables to quantitatively assess the effectiveness of volume expansion in increasing cardiac output. Methods: Sixty-one cardiac post-surgical patients were studied and 107 fluid boluses were captured. Cardiac output, mean arterial pressure and right atrial pressure were recorded with P before and after a bolus fluid. An increase in cardiac output greater than 10 % following a fluid bolus defined a patient as a responder. Cardiac power (i.e. the product of arterial pressure and cardiac output) and P to right atrial pressure gradient (i.e. the driving pressure for venous return and hence cardiac output) were evaluated to assess the efficiency of volume expansion to increase cardiac output. Cardiac power relative to P (CP), its dynamic changes and the dynamic changes in P-right atrial pressure gradient relative to the P change ( E) were investigated. Results: CP was lower and E was higher in responders vs. non-responders. Furthermore, in patients receiving a second fluid bolus, E correlated with the degree of increase in cardiac output. Multivariate regression analysis identified both CP and E as independent variables associated with volume responsiveness. Conclusions: Using an algorithm to derive a mean systemic filling pressure analogue, cardiac power and dynamic measures of the venous return pressure gradient relative to the mean systemic filling pressure provided an assessment of the efficiency of volume expansion in post-surgical cardiac patients. [ABSTRACT FROM AUTHOR]

Controversy exists about whether one-dimensional wave theory can explain the "self-canceling" waves that accompany the diastolic pressure decay and discharge of the arterial reservoir. Although it has been proposed that reservoir and wave effects be treated as separate phenomena, thus avoiding the issue of self-canceling waves, we have argued that reservoir effects are a phenomenological and mathematical subset of wave effects. However, a complete wave-based explanation of self-canceling diastolic expansion (pressure-decreasing) waves has not yet been advanced. These waves are present in the forward and backward components of arterial pressure and flow (P± and Q±, respectively), which are calculated by integrating incremental pressure and flow changes (dP± and dQ±, respectively). While the integration constants for this calculation have previously been considered arbitrary, we showed that physiologically meaningful constants can be obtained by identifying "undisturbed pressure" as mean circulatory pressure. Using a series of numeric experiments, absolute P± and Q± values were shown to represent "wave potential," gradients of which produce propagating wavefronts. With the aid of a "one-dimensional windkessel," we showed how wave theory predicts discharge of the arterial reservoir. Simulated data, along with hemodynamic recordings in seven sheep, suggested that self-canceling diastolic waves arise from repeated and diffuse reflection of the late systolic forward expansion wave throughout the arterial system and at the closed aortic valve, along with progressive leakage of wave potential from the conduit arteries. The combination of wave and wave potential concepts leads to a comprehensive one-dimensional (i.e., wave-based) explanation of arterial hemodynamics, including the diastolic pressure decay. [ABSTRACT FROM AUTHOR]

Purpose: Voluntary breath-holding (BH) elicits several hemodynamic changes, but little is known about maximal static immersed-body BH. We hypothesized that the diving reflex would be strengthened with body immersion and would spare more oxygen than maximal dry static BH, resulting in a longer BH duration. Methods: Eleven trained breath-hold divers (BHDs) performed a maximal dry-body BH and a maximal immersed-body BH. Cardiac output (CO), stroke volume (SV), heart rate (HR), left ventricular end-diastolic volume (LVEDV), contractility index (CTI), and ventricular ejection time (VET) were continuously recorded by bio-impedancemetry (PhysioFlow PF-05). Arterial oxygen saturation (SaO) was assessed with a finger probe oximeter. Results: In both conditions, BHDs presented a bi-phasic kinetic for CO and a tri-phasic kinetic for SV and HR. In the first phase of immersed-body BH and dry-body BH, results (mean ± SD) expressed as percentage changes from starting values showed decreased CO (55.9 ± 10.4 vs. 39.3 ± 16.8 %, respectively; p < 0.01 between conditions), due to drops in both SV (24.9 ± 16.2 vs. 9.0 ± 8.5 %, respectively; p < 0.05 between conditions) and HR (39.7 ± 16.7 vs. 33.6 ± 17.0 %, respectively; p < 0.01 between conditions). The second phase was marked by an overall stabilization of hemodynamic variables. In the third one, CO kept stabilizing due to increased SV (17.0 ± 20.2 vs. 10.9 ± 13.8 %, respectively; p < 0.05 between conditions) associated with a second HR drop (14.0 ± 10.0 vs. 12.7 ± 8.9 %, respectively; p < 0.01 between conditions). Conclusion: This study highlights similar time-course patterns for cardiodynamic variables during dry-body and immersed-body BH, although the phenomenon was more pronounced in the latter condition. [ABSTRACT FROM AUTHOR]

Cardiac changes induced by repeated breath-hold diving were investigated after a fish-catching diving competition. Eleven healthy subjects carried out repeated breath-hold dives at a mean maximal depth of 20 ± 2.7 msw (66 ± 9 fsw) during 5 h. One hour after the competition, the body mass loss was −1.7 ± 0.5 kg. Most of the breath-hold divers suffered from cold and although the core temperature remained normal, a decrease in cutaneous temperature was recorded in the extremities. Systolic blood pressure was reduced in both upper and lower limbs. Heart rate was unchanged, but left ventricular (LV) stroke volume was reduced leading to a decrease in cardiac output (−20%). Left atrial and LV diameters were significantly decreased. LV filling was assessed on a trans-mitral profile. An increase in the contribution of the atrial contraction to LV filling was observed. Right cavity diameters were increased. The cardiac autonomic alterations were in favor of sympathetic hyperactivity. After a fish-catching diving competition in cold water, alterations suggesting dehydration, contraction in plasma volume and sympathetic hyperactivity were observed. Furthermore, enlargements of right cavities were in favor of right ventricular strains. Repeated apnea and swimming in cold water may account for these alterations. [ABSTRACT FROM AUTHOR]

Human underwater breath-hold diving is a fascinating example of applied environmental physiology. In combination with swimming, it is one of the most popular forms of summer outdoor physical activities. It is performed by a variety of individuals ranging from elite breath-hold divers, underwater hockey and rugby players, synchronized and sprint swimmers, spear fishermen, sponge harvesters and up to recreational swimmers. Very few data currently exist concerning the influence of regular breath holding on possible health risks such as cerebrovascular, cardiovascular and respiratory diseases. A literature search of the PubMed electronic search engine using keywords 'breath-hold diving' and 'apnoea diving' was performed. This review focuses on recent advances in knowledge regarding possibly harmful physiological changes and/or potential health risks associated with breath-hold diving. Available evidence indicates that deep breath-hold dives can be very dangerous and can cause serious acute health problems such a collapse of the lungs, barotrauma at descent and ascent, pulmonary oedema and alveolar haemorrhage, cardiac arrest, blackouts, nitrogen narcosis, decompression sickness and death. Moreover, even shallow apnoea dives, which are far more frequent, can present a significant health risk. The state of affairs is disturbing as athletes, as well as recreational individuals, practice voluntary apnoea on a regular basis. Long-term health risks of frequent maximal breath holds are at present unknown, but should be addressed in future research. Clearly, further studies are needed to better understand the mechanisms related to the possible development or worsening of different clinical disorders in recreational or competitive breath holding and to determine the potential changes in training/competition regimens in order to prevent these adverse events. [ABSTRACT FROM AUTHOR]

Immersion pulmonary edema (IPE) is a condition with sudden onset in divers and swimmers suspected to be due to pulmonary arterial or venous hypertension induced by exercise in cold water, although it does occur even with adequate thermal protection. We tested the hypothesis that cold head immersion could facilitate IPE via a reflex rise in pulmonary vascular pressure due solely to cooling of the head. Ten volunteers were instrumented with ECG and radial and pulmonary artery catheters and studied at 1 atm absolute (ATA) during dry and immersed rest and exercise in thermoneutral (29-31°C) and cold (18-20°C) water. A head tent varied the temperature of the water surrounding the head independently of the trunk and limbs. Heart rate, Fick cardiac output (CO), mean arterial pressure (MAP), mean pulmonary artery pressure (MPAP), pulmonary artery wedge pressure (PAWP), and central venous pressure (CVP) were measured. MPAP, PAWP, and CO were significantly higher in cold pool water (P ≤ 0.004). Resting MPAP and PAWP values (means ± SD) were 20 ± 2.9/13 ± 3.9 (cold body/cold head), 21 ± 3.1/14 ± 5.2 (cold/warm), 14 ± 1.5/10 ± 2.2 (warm/warm), and 15 ± 1.6/10 ± 2.6 mmHg (warm/cold). Exercise values were higher; cold body immersion augmented the rise in MPAP during exercise. MAP increased during immersion, especially in cold water (P < 0.0001). Except for a transient additive effect on MAP and MPAP during rapid head cooling, cold water on the head had no effect on vascular pressures. The results support a hemodynamic cause for IPE mediated in part by cooling of the trunk and extremities. This does not support the use of increased head insulation to prevent IPE. [ABSTRACT FROM AUTHOR]

Although it has long been recognized that thyroid hormone is an effective positive inotrope, its efficacy in supporting hemodynamics in the acute setting of ischaemia and reperfusion (R) without worsening reperfusion injury remains largely unknown. Thus, we investigated the effects of triiodothyronine (T3) on reperfusion injury in a Langendorff–perfused rat heart model of 30 min zero-flow ischaemia and 60 min of (R) with or without T3 (40 µg/l) at R, T3-R60, n = 11 and CNT-R60, n = 10, respectively. Furthermore, phosphorylated levels of intracellular kinases were measured at 5, 15 and 60 min of R. T3 markedly improved postischaemic recovery of left ventricular developed pressure (LVDP%); 56.0% (SEM, 4.4) in T3-R60 versus 38.8% (3.1) in CNT-R60, P < 0.05. Furthermore, LDH release was significantly lower in T3-R60. Apoptosis detection by fluorescent probe optical imaging showed increased fluorescent signal in CNT-R60 hearts, while the signal was hardly detectable in T3-R60 hearts. Similarly, caspase-3 activity was found to be 78.2 (8.2) in CNT-R60 vs 40.5 (7.1) in T3-R60 hearts, P < 0.05. This response was associated with significantly lower levels of phospho-p38 MAPK at any time point of R. No significant changes in phospho- ERK1/2 and JNK levels were observed between groups. Phospho–Akt levels were significantly lower in T3 treated group at 5 min and no change in phospho–Akt levels were observed at 15 and 60 min between groups. In conclusion, T3 administration at reperfusion can improve postischaemic recovery of function while limiting apoptosis. This may constitute a paradigm of a positive inotropic agent with anti-apoptotic action suitable for supporting hemodynamics in the clinical setting of ischaemia-reperfusion. [ABSTRACT FROM AUTHOR]

BACKGROUND: Levosimendan improves ventricular function, induces vasodilation and induces myocardial preconditioning. We determined the external efficiency and assessed the effects on arrhythmias. METHODS: In isolated, blood-perfused rabbit hearts, levosimendan (0.75??mol) or placebo was administered, while hemodynamics were recorded. After no-flow ischemia and reperfusion, data were recorded again. RESULTS: Placebo in normoxic hearts did not affect measurements, while levosimendan increased heart rate (+?18?%) and improved coronary output (+?52?%), stroke volume (+?28?%), maximal left ventricular pressure (+?30?%), maximal rate of pressure increase (+?36?%), work (+?68?%), minimal rate of pressure increase (+?53?%), coronary blood flow (+?41?%), coronary resistance (??19?%) and external efficiency (33?%; P?

Myocardial blood flow is unevenly distributed, but the cause of this heterogeneity is unknown. Heterogeneous blood flow may reflect heterogeneity of oxygen demand. The aim of the present study was to assess the relation between oxygen consumption and blood flow in small tissue regions in porcine left ventricle. In seven male, anesthetized,open-chest pigs, local oxygen consumption was quantitated by computational model analysis of the incorporation of 13C in glutamate via the tricarboxylic acid cycle during timed infusion of [13C]acetate into the left anterior descending coronary artery. Blood flow was measured with radioactive microspheres before and during acetate infusion. High-resolution nuclear magnetic esonance 13C spectra were obtained from extracts of tissue samples (159 mg mean dry wt) taken at the end of the acetate infusion. Mean regional myocardial blood flow was stable [5. ± 1.6 (SD) and 5.0 ± 1.4 ml·min-1·g dry t-1 before and after 30 min of acetate infusion, respectively]. Mean left ventricular oxygen consumption measured with the NMR method was 18.6 ± 7.7 micro;mol·min-1·g dry wt-1 and correlated well (r = 0.85, P = 0.02, n = 7) with oxygen consumption calculated from blood flow, hemoglobin, and blood gas measurements (mean 22.8 ± 4.7 µmol·min-1·g dry wt-1). Local blood flow and oxygen consumption were significantly correlated (r = 0.63 for pooled normalized data, P < 0.0001, n = 60). We calculate that, in the heart at normal workload, the variance of left ventricular oxygen delivery at submilliliter resolution is explained for 43% by heterogeneity in oxygen demand. [ABSTRACT FROM AUTHOR]

Objective: Myocardial oxygen consumption (MVO2) in the septic myocardium is increased despite reduced left ventricular mechanical work. We investigated the mechanism behind this energetic inefficiency in the septic myocardium. Methods: To clarify whether energy consumption in basal metabolism or excitation–contraction (EC) coupling is elevated in the septic myocardium, we separated MVO2 used for these two processes. We assessed hemodynamics, left ventricular pressure–volume area, left ventricular MVO2, myocardial substrate metabolism and the inflammatory response in eight control pigs and in eight septic pigs receiving E. coli endotoxin. Using cardiopulmonary bypass (CPB), unloaded MVO2 was assessed before and after arrest of electromechanical activity using KCl infusions. Results: Unloaded MVO2 was significantly higher in the septic group compared to the control group (65.7±12.9 vs. 43.3±15.1 J·min-1·100 g LV-1, p<0.005), but basal MVO2 after 5 min KCl arrest was equal in the two groups. No difference in mechanical energy consumption or substrate metabolism was observed between groups. Conclusion: Basal MVO2 in the septic myocardium is not elevated, but an increased MVO2 for EC coupling is responsible for the energetic inefficiency. [Copyright &y& Elsevier]

Background: The role of AT1 receptors in myocardial ischemia/reperfusion injury is unclear. We, therefore, investigated the effects of the AT1 receptor antagonist irbesartan (Irb) in isolated hearts of selective myocardial AT1 overexpressing transgenic [transgenic(αMHC-hAT1)594-17] and Sprague–Dawley rats (SD) subjected to ischemia/reperfusion injury. Methods and results: Hearts of 4-week-old male SD or transgenic rats were isolated and perfused with Krebs–Henseleit buffer with or without 10 μM Irb in Langendorff mode. After 15 min of stabilization, pressure–volume curves were obtained and the hearts subjected to 20 min ischemia followed by 30 min reperfusion. A second set of pressure–volume curves was obtained thereafter. Left ventricular developed pressure (LVDP), end-diastolic pressure (LVEDP), total coronary flow (CF) and oxygen consumption (MVO2) were recorded continuously. Myocardial efficiency was derived from the slope of relations of MVO2 to pressure/volume area. After 20 min ischemia, LVEDP was significantly higher in transgenic than in SD (35.7±1.8 vs. 29.2±1.0 mmHg, P<0.05) or Irb treated transgenic hearts (24.3±1.6 mmHg, P<0.05). Myocardial efficiency was increased by Irb before ischemia. Ischemia increased efficiency in SD but not in transgenic rats, Irb increased efficiency in transgenic hearts post-ischemia. Conclusion: Transgenic hearts developed ischemic contracture more rapidly than SD hearts as indicated by higher LVEDP during ischemia. This response was antagonized by Irb, indicating a role of AT1 receptors in ischemic contracture, AT1-receptors also appear to be involved in the control of myocardial efficiency. [Copyright &y& Elsevier]

The literature is reviewed on methods to assess heterogeneity of blood flow, substrate uptake and oxidative end energy metabolism in the normal heart, and their interrelations. Even though the factors controlling matching on the regional level remain largely obscure, the evidence that heterogeneous blood flow partially correlates to indicators of metabolism in the normal heart is accumulating, particularly in face of a correlation between acetate metabolism indicative of regional O2 consumption to microsphere blood flow. Moreover, the partial matching cannot be explained by vascular anatomical differences from one region to the other, since, although fractal theory can partially describe the branching patterns of the coronaries, vasodilation is similar among regions upon metabolic stimulation of the heart. It is dissimilar among regions, so that blood flow is redistributed, upon maximum vasodilation with adenosine or hypoxia, denoting regionally different maximum vessel diameter and flow reserve. However, regionally differing tissue composition could also contribute somewhat to regional differences in (the need for) blood flow. It is still unknown, because of technical limitations, how the foregoing measures relate to regional work load. [ABSTRACT FROM AUTHOR]

Myocardial blood flow exhibits considerable heterogeneity. Consequently, oxygen supply to the myocardium is also heterogeneous, as is myocardial metabolism. Many lines of evidence show a close correlation between local flow and local metabolism in the normoxic myocardium. So far, myocardial metabolism has pre-dominantly been assessed indirectly by using labeled substrates. We used the 18O isotope, permitting analytical separation of H218O from the 18O isotope, as well as quantification of regional oxidative metabolism by measuring the tissue residue of oxidation water in the rabbit myocardium. Correlation of local flow with oxidative metabolism was significant in the normoxic myocardium. This correlation was lost in the postischemic/reperfused myocardium. Apart from the established mechanisms underlying myocardial stunning, a mismatch between local flow and oxidative metabolism might thus also contribute to the postischemic dysfunction. In the normoxic myocardium, function should correlate with metabolism and blood flow. For technical reasons, function has not been assessed on a very local scale. Nevertheless, some considerations are presented on the heterogeneity of function as well as on the scale on which heterogeneity should be investigated to convey physiologically meaningful information on regulatory cardiac mechanisms. [ABSTRACT FROM AUTHOR]

Myocardial blood flow exhibits the most marked heterogeneity at the microvascular level. Its within-layer spatial distribution can be described from subepi- to subendocardium with resolutions of 0.1 × 0.1 to 1 × 1 mm2 by quantitative digital radiography based on the technique of desmethylimipramine deposition. In the subendocardium, flow heterogeneity is the highest, whereas local flow randomness is the lowest, showing the clustered pattern of high- or low-flow regions. The resolution-dependence of flow heterogeneity is characterized by its fractality, which holds consistently down to the microvascular level through the vascular structural transition from the treelike arteriolar to the non-treelike capillary network. Flow heterogeneity is adjustable in a transmurally different manner to local metabolic changes. The redistribution of flow is considered as a result of adaptive coordination of microperfusion between adjacent microcirculatory units, which are perfused by a single precapillary arteriole. [ABSTRACT FROM AUTHOR]

It is well established that myocardial blood flow is heterogeneous on the local level. During recent years comprehensive studies have been undertaken to assess the relation between myocardial metabolism and spatial blood flow heterogeneity. Based on the type of measurements two major groups of studies have been performed: enzyme activity and tissue metabolite level assessments. Enzyme activity measurements have provided only limited insight into the coupling of local metabolism and flow. This is probably due to the fact that, in addition to estimated Vmax values, local substrate affinity (Km values) and substrate concentrations affect the metabolite fluxes. However, the latter two variables remain normally unknown. In contrast, valuable insight has been obtained concerning flow-metabolism matching from tissue metabolite measurements, especially when connected with mathematical model analyses. The latter permitted the calculation of metabolic flux rates (e.g., production of oxidation water, citric acid cycle flux, glucose uptake, fatty acid uptake) or the translation of the metabolic indexes into physiologically meaningful local metabolite concentrations (e.g., free cytosolic adenosine). The bottom line of the studies reported to date is that the broad range of myocardial flows observed under resting control conditions correlates with local metabolism possibly affected by spatial differences in adrenergic stimulation. Thus, high flow samples exhibit a higher oxidative metabolism than low flow samples. As a result the flow threshold below which local myocardial ischemia ensues is higher in control high flow samples. The importance of these findings with respect to local flow-metabolism matching is underlined by the finding that the probability of developing an infarction following ischemia/reperfusion is related to the functional state of the myocardium under control conditions, i.e., the local level of flow-metabolism matching. [ABSTRACT FROM AUTHOR]

The present article describes the concept of perfusion-contraction matching originally proposed by Ross, goes on to critically discuss the available techniques to measure both regional myocardial blood flow and function in the experimental and clinical setting, and finally analyzes the available evidence for perfusion-contraction match and mismatch during normoperfusion and various scenarios of myocardial ischemia/reperfusion, including acute and subacute ischemia, coronary microembolization, stunning and hibernation. [ABSTRACT FROM AUTHOR]

: Aims In the heart and other tissues, perfusion and metabolic activity are heterogeneous and spatially correlated. The goal of this work is to investigate the causes of this behaviour. Theoretical simulations are used to examine the effects on flow distribution and oxygen levels in terminal vascular beds of inherent irregularity in network structure, considering structural adaptation of vessel diameters to haemodynamic and metabolic stimuli, and adaptation of oxygen demand to local oxygen availability. : Methods and results A mathematical model based on experimentally observed microvascular network structures (rat mesentery and m. sartorius) is used to simulate blood flow, oxygen transport, and adaptation of vessel diameters and tissue oxygen demand. Inherent geometric heterogeneities of vascular networks cause heterogeneity of blood flow and oxygen levels that cannot be eliminated by increasing metabolic sensitivity of diameter adaptation. Adaptation of oxygen demand to differences in oxygen availability causes increased oxygen extraction, implying improved functional capacity, and establishes a correlation between local oxygen demand and flow rate, as observed experimentally. Such a correlation is not predicted if the heterogeneity of oxygen demand is assumed to be an intrinsic tissue property. : Conclusion A central mechanism generating heterogeneous perfusion is the inevitable structural heterogeneity of terminal vascular beds, which cannot be fully compensated by structural adaptation of vessel diameters. Heterogeneity of metabolism may result from adaptation of tissue function to the heterogeneous oxygen availability. These findings are of interest for the understanding of tissue function, including the heart, and of results obtained by corresponding imaging approaches. [ABSTRACT FROM AUTHOR]