The induction of mild hypothermia improves systolic function of the resuscitated porcine heart at no further sympathetic activation

Aim: Mild hypothermia (MH) after cardiac arrest attenuates hypoxic brain injury and improves survival. As MH increases contractility in normal hearts, we hypothesized that MH improves cardiovascular function after cardiac arrest. Methods: In 16 anaesthetized pigs (64 ± 2 kg), ventricular fibrillation was induced electrically for 5 min. At 10 min after resuscitation and return of spontaneous circulation (ROSC), pigs were assigned to normothermia (NT, 38 °C, n = 8) or MH (33 °C, n = 8, intravascular cooling). Results: At ROSC 6 h vs. baseline, heart rate (HR) was unchanged in NT, but decreased in MH. Cardiac output (CO, l min^?1) decreased in MH (3.5 ± 0.2 vs. 5.5 ± 0.4, P < 0.05) more than in NT (4.8 ± 0.4 vs. 5.7 ± 0.4, P = ns). Mixed venous oxygen saturation decreased in NT (56 ± 2 vs. 66 ± 3%, P < 0.05), but remained constant in MH (64 ± 2 vs. 65 ± 2%) due to a 35% decrease of whole body oxygen consumption. Left ventricular (LV) dP/dt_max (mmHg s^?1) decreased in NT (1163 ± 97 vs. 1665 ± 134, P < 0.05), but was preserved in MH (1602 ± 102 vs. 1603 ± 96), whereas LV relaxation was profoundly slowed during MH. Pressure–volume analysis confirmed improved LV systolic function during MH, but also demonstrated decreased LV end‐diastolic distensibility, which was further potentiated by right atrial pacing at baseline HR. MH did not increase plasma catecholamine levels. Spectral analysis of heart rate variability revealed reduced sympathetic activation during MH. Conclusion: The induction of MH after cardiac resuscitation improves systolic myocardial function without further sympathetic activation. A reduced metabolism during MH outweighs a decreased CO and thereby acts favourably on systemic oxygen supply/demand balance.     

Left ventricular pressure–volume relationships during normal growth and development in the adult rat – studies in 8‐ and 50‐week‐old male Wistar rats

Aims: Left ventricular (LV) pressure–volume relations provide relatively load‐independent indexes of systolic and diastolic LV function, but few data are available on pressure–volume relations during growth and development in the normal adult heart. Furthermore, to quantify intrinsic ventricular function the indexes should be normalized for heart weight. However, in many studies the indexes are reported in absolute terms, or body weight‐correction is used as a surrogate for heart weight‐correction. Methods: We determined pressure–volume relations in young (8‐week‐old, n = 13) and middle‐aged (50‐week‐old, n = 19) male Wistar rats in relation to their heart and body weights. The animals were anaesthetized and a 2F pressure‐conductance catheter was introduced into the LV to measure pressure–volume relations. Results: Heart and body weights were significantly higher in the 50‐week‐old rats, whereas the heart‐to‐body weight ratio was significantly lower (2.74 ± 0.32 vs. 4.41 ± 0.37 mg g^?1, P < 0.001). Intrinsic systolic function, quantified by the slopes of the end‐systolic pressure–volume relation (E_ES), the dP/dt_MAX vs. end‐diastolic volume relation (S‐dP), and the preload recruitable stroke work relation (PRSW), normalized for heart weight, was slightly decreased in the 50‐week‐old rats (S‐dP: ?6%, P < 0.004; PRSW: ?3%, P < 0.06). Heart weight‐corrected diastolic indexes were not significant different. The absolute indexes qualitatively showed the same results, but body‐weight corrected pressure–volume indexes showed improved systolic function and significantly depressed diastolic function. Conclusions: Intrinsic systolic function slightly decreases from the juvenile to the middle‐aged period in normal male Wistar rats. Furthermore, correction of pressure–volume indexes for body weight is not an adequate surrogate for heart weight‐correction in these animals.     

The effect of sarcoplasmic reticulum blockade on the force/frequency relationship and systolic contraction patterns in the newborn pig heart

 We investigated the relationship between heart rate and contractility in seven anaesthetized young piglets by measuring contractility at different atrial pacing rates. To study the origin of this relationship we repeated the measurements after blocking the sarcoplasmic reticulum calcium release channel with ryanodine. We assessed contractility using indices derived from instantaneous left ventricular pressure and volume measured by micromanometric and conductance catheters during rapid inferior vena cava occlusion, thus generating the end-systolic pressure-volume relationship, which was characterized by its slope E _es, and the maximum rate of change of ventricular pressure (dP/dt _max)/end-diastolic volume relationship, also charaterized by its slope. All animals showed an increase in contractility with increasing heart rate (intact force/frequency relationship) which was abolished after ryanodine. The most striking effect of ryanodine on baseline haemodynamics was the dramatic decrease of dP/dt _max to about 50% of its original value, while peak developed pressure and E _es did not change. We conclude that the young piglet, despite its immaturity, has a functional sarcoplasmic reticulum, illustrated by an intact force/frequency relationship. In addition, blockade of the sarcoplasmic reticulum in vivo has profoundly different effects during early and late systole, indicating that indices of contractility derived during different parts of the cardiac cycle represent different aspects of systole. Received: 22 August 1996 / Received after revision and accepted: 18 August 1997     

The isolated working mouse heart: methodological considerations

 Our aim was to develop a working isolated murine heart model, as the extensive use of genetically engineered mice in cardiovascular research requires development of new miniaturized technology. Left ventricular (LV) function was assessed in the isolated working mouse heart perfused with recirculated oxygenated Krebs-Henseleit bicarbonate buffer (37 °C pH 7.4) containing 11.1 mM glucose and 0.4 mM palmitate bound to 3% albumin. The hearts worked against an afterload reservoir at a height equivalent to 50 mmHg, and heart rate was controlled by electrical pacing of the right atrium. LV pressure was measured with a micromanometer connected to a small steel cannula inserted through the apex of the heart. The experimental protocol consisted of two interventions. First, following instrumentation and stabilization, the preload reservoir was raised from a pressure equivalent of 7 to 22.5 mmHg, while pacing at 390 beats·min^–1. Thereafter the height of the preload reservoir was set to 10 mmHg, and the pacing rate was varied from 260 to 600 beats·min^–1. Aortic and coronary flows were measured by timed collections of effluent from the afterload line and that dripping from the heart, respectively [aortic+coronary flow=cardiac output (CO)]. Elevation of LV end-diastolic pressure (LVEDP) from approximately 5 to 10 mmHg resulted in a twofold increase in average cardiac power [product of LV developed pressure (LVDevP) and CO], whereas myocardial contractility (first derivative of LV pressure, dP/dt) and LVDevP (LV systolic pressure–LVEDP) increased only minimally (5–10%). Measured LVEDP was lower than the equivalent height of the preload reservoir by an amount that was related to the heart rate. Cardiac power, LVDevP and dP/dt were stable at heart rates up to 400 beats·min^–1, but declined markedly with higher rates, consistent with the decrease in LVEDP. Thus, cardiac power was reduced to 50% of its maximum value when stimulated at approximately 500 beats·min^–1, and at even higher rates there was little ejection. By systematic manipulation of the height of the preload reservoir and heart rate, we conclude that LV afterload and preload can be assessed only by high-fidelity measurement of intraventricular pressures. The heights of the afterload column and the preload reservoir are unreliable and potentially misleading indicators of LV afterload and preload. Received: 28 September 1998 / Accepted: 25 January 1999     

Angiotensin II infusion during β-adrenergic stimulation by isoproterenol. Effects on hepatic,splenic and cardiac blood volumes and on the magnitude and distribution of cardiac output in the dog

The cardiac and peripheral vascular adjustments to angiotensin II (0.1–0.2 μg kg^-1 min^-1 i.v.) during high β-adrenergic activity by a continuous isoproterenol infusion (0.2–0.3 μg kg^-1 min^-1 i.v.) were examined in anaesthetized, atropinized dogs. Hepatic, splenic and left ventricular (LV) volume changes were estimated by an ultrasonic-technique, and the blood flow distribution was measured by injecting radioactive microspheres and by electromagnetic flowmetry on the caval veins, the hepatic artery and the portal vein. During isoproterenol infusion, angiotensin II increased the systolic LV pressure by 45 ± 3 mmHg and the stroke volume by 17 ± 6 %. Concomitantly, the hepatic and splenic blood volumes declined by 29 ± 4 and 14 ± 6 ml, respectively, and the LV end-diastolic segment length increased by 3 ± 1 %. The flow through the inferior caval vein increased by 39 ± 9%, whereas the superior vena caval flow remained unchanged. The hepatic arterial flow more than doubled. Thus, at high inotropy by isoproterenol infusion, angiotensin II relocates blood from the liver and the spleen towards the heart. By activating the Frank-Starling mechanism, cardiac output is increased and conducted through the lower body, especially through the hepatic artery, because of the poor autoregulation of flow through this vessel.,     

Single-beat estimation of the left ventricular end-systolic pressure–volume relationship in patients with heart failure

Aim: The end-systolic pressure–volume relationship (ESPVR) constructed from multiple pressure–volume (PV) loops acquired during load intervention is an established method to asses left ventricular (LV) contractility. We tested the accuracy of simplified single-beat (SB) ESPVR estimation in patients with severe heart failure. Methods: Nineteen heart failure patients (NYHA III-IV) scheduled for surgical ventricular restoration and/or restrictive mitral annuloplasty and 12 patients with normal LV function scheduled for coronary artery bypass grafting were included. PV signals were obtained before and after cardiac surgery by pressure-conductance catheters and gradual pre-load reductions by vena cava occlusion (VCO). The SB method was applied to the first beat of the VCO run. Accuracy was quantified by the root-mean-square-error (RMSE) between ESPVR_SB and gold-standard ESPVR_VCO. In addition, we compared slopes (E_ES) and intercepts (end-systolic volume at multiple pressure levels (70–100 mmHg: ESV₇₀–ESV₁₀₀) of ESPVR_SB vs. ESPVR_VCO by Bland–Altman analyses. Results: RMSE was 1.7 ± 1.0 mmHg and was not significantly different between groups and not dependent on end-diastolic volume, indicating equal, high accuracy over a wide volume range. SB-predicted E_ES had a bias of −0.39 mmHg mL⁻¹ and limits of agreement (LoA) −2.0 to +1.2 mmHg mL⁻¹. SB-predicted ESVs at each pressure level showed small bias (range: −10.8 to +9.4 mL) and narrow LoA. Two-way anova indicated that differences between groups were not dependent on the method. Conclusion: Our findings, obtained in hearts spanning a wide range of sizes and conditions, support the use of the SB method. This method ultimately facilitates less invasive ESPVR estimation, particularly when coupled with emerging noninvasive techniques to measure LV pressures and volumes.     

The pericardial hypothesis: a mechanism of acute shifts of the left ventricular diastolic pressure-volume relation

Changes in LV diastolic P-V relations may be caused by changes in myocardial distensibility and by changes in extraventricular constraint. Experimental studies suggest that the upward shift of the LV diastolic P-V relation associated with pacing tachycardia, in patients with angina pectoris, is due to decreased myocardial distensibility which possibly represents incomplete relaxation. However, shifts in the LV diastolic P-V relation with vasodilator and vasoconstrictor agents seem to be caused by changes in extraventricular constraint. Experimental and clinical data show that such interventions do not significantly change the LV transmural P-V relation. This supports the hypothesis that these shifts are due to changes in pericardial pressure. Our data suggest that such vasoactive agents act by shifting blood between the (splanchnic) venous compartment and the heart, thereby changing heart size and in turn pericardial pressure. These concepts have significantly improved our understanding of the mechanisms of action of vasoactive agents. It seemed a paradox that vasodilators (e.g., nitroglycerine) could substantially lower filling pressure of the failing left ventricle without reducing cardiac output. Because of the downward-shift in the P-V relation with nitroglycerine, preload is virtually unchanged and therefore stroke volume is maintained. Appreciation of these phenomena has considerable impact on how haemodynamic measurements are interpreted. It is obvious that the use of LV end-diastolic pressure as an index of end-diastolic volume may lead to serious misinterpretations of ventricular function. Our demonstration that right atrial pressure might be used to assess pericardial pressure provides a potentially useful way to estimate LV transmural pressure, and therefore an accurate measure of preload.     

Predicted hemodynamic benefits of counterpulsation therapy using a superficial surgical approach

A volume-displacement counterpulsation device (CPD) intended for chronic implantation via a superficial surgical approach is proposed. The CPD is a pneumatically driven sac that fills during native heart systole and empties during diastole through a single, valveless cannula anastomosed to the subclavian artery. Computer simulation was performed to predict and compare the physiological responses of the CPD to the intraaortic balloon pump (IABP) in a clinically relevant model of early stage heart failure. The effect of device stroke volume (0-50 ml) and control modes (timing, duration, morphology) on landmark hemodynamic parameters and the LV pressure-volume relationship were investigated. Simulation results predicted that the CPD would provide hemodynamic benefits comparable to an IABP as evidenced by up to 25% augmentation of peak diastolic aortic pressure, which increases diastolic coronary perfusion by up to 34%. The CPD may also provide up to 34% reduction in LV end-diastolic pressure and 12% reduction in peak systolic aortic pressure, lowering LV workload by up to 26% and increasing cardiac output by up to 10%. This study demonstrated that the superficial CPD technique may be used acutely to achieve similar improvements in hemodynamic function as the IABP in early stage heart failure patients.     

Role of aspirin in modulating myocardial ischemic reperfusion injury

The role of low-dose aspirin (3 mg/kg, i.v.) in attenuating ischemic reperfusion injury was studied in a canine model. Regional ischemia for 40 min was produced by temporary occlusion of the left anterior descending coronary artery and thereafter reperfusion instituted for 3 h. Mean arterial pressure (MAP), heart rate (HR), left ventricular end diastolic pressure (LVEDP), positive (+) LV dP/dt _max and negative (–) LV dP/dt _max were monitored alongwith myocardial adenosine triphosphate (ATP), creatine phosphate (CP), glycogen and lactate. Following reperfusion, there was a significant fall in (i) MAP, (ii) (+) LV dP/dt _max and (iii) (–) LV dP/dt _max. LVEDP was corrected after about 2h of reperfusion. Replenishment of only myocardial CP occurred, without any change in ATP and glycogen, although lactate accumulation was corrected.Aspirin administered 15 min before reperfusion (posttreatment) caused normalisation of LVEDP within 15 min and prevented any deterioration in (–) LV dP/dt _max, although it had no effect on MAP and (+) LV dP/dt _max. After 3h of reperfusion (post-treatment), myocardial ATP, CP, glycogen and lactate contents became normal. The number of premature ventricular complexes was significantly reduced after aspirin treatment. The present study indicates that low-dose aspirin post-treatment can ameliorate at least some of the deleterious consequences of reperfusion injury of the myocardium.     

Mechanical function,glycolysis, and ultrastructure of perfused working mouse hearts following thoracic aortic constriction

BackgroundGlycolytic flux in the mouse heart during the progression of left ventricular hypertrophy (LVH) and mechanical dysfunction has not been described.MethodsThe main objectives of this study were to characterize the effects of thoracic aortic banding, of 3- and 6-week duration, on: (1) left ventricular (LV) systolic and diastolic function of perfused working hearts quantified by analysis of pressure–volume loops; (2) glycolytic flux in working hearts expressed as the rate of conversion of ³H-glucose to ³H₂O, and (3) ultrastructure of LV biopsies assessed by quantitative and qualitative analysis of light and electron micrographs.ResultsResults revealed that (1) indexes of systolic function, including LV end-systolic pressure, cardiac output, and rate of LV pressure development and decline, were depressed to similar degrees at 3 and 6 weeks post-banding; (2) diastolic dysfunction, represented by elevated LV end-diastolic pressure and volume, was more severe at 6 than at 3 weeks, consistent with a transition to failure; (3) a progressive decline in glycolytic flux that was roughly half the control rate by 6 weeks post-banding; and (4) structural derangements, manifested by increases in interstitial collagen content and myocyte Z-band disruption, that were more marked at 3 weeks than at 6 weeks.ConclusionThe results are consistent with the view that myocyte damage, fibrosis, and suppressed glycolytic flux represent maladaptive structural and metabolic remodeling that contribute to the development of failure in high pressure load-induced LVH in the mouse.     

Cardiac end-diastolic dilation during acute blood pressure elevation is inotropy dependent

To examine if the degree of left ventricular (LV) end-diastolic dilation during an acute blood pressure elevation is inotropy dependent, the descending thoracic aorta was occluded before and during a continuous isoproterenol infusion into the left coronary artery in 10 open-chest pigs. The increase in peak LV systolic pressure and in LV tension-time-index induced by aortic occlusion, were equal before and during the isoproterenol infusion. Left and right ventricular (RV) segment lengths were continuously recorded in the free walls of both ventricles, by an ultrasonic technique. A slight fall in LV end-diastolic segment length by the intracoronary isoproterenol infusion was corrected by an i.v. saline infusion. Left ventricular end-diastolic volume was therefore equal at both levels of inotropy when the aorta was occluded, and the heart rate was kept constant by right atrial pacing. At control inotropy, aortic occlusion induced a rise in LV end-diastolic segment length; 6.0 (4.0-8.2)% (median and 95% confidence interval), compared with the smaller (P less than 0.05) increase of 3.8 (2.6-5.5)% during isoproterenol infusion. The end-systolic segment length increased more (P less than 0.01) at control inotropy than during intracoronary isoproterenol infusion: 10.9 (6.9-14.4)% and 4.1 (1.5-7.4)%, respectively. In the RV, both end-diastolic and end-systolic segment length increased slightly during aortic occlusion but only at control inotropy. Thus during an acute blood pressure elevation, the end-diastolic and end-systolic ventricular volumes are better maintained at high than at control inotropy.     

Variations in left ventricular volume alter myocardial oxygen consumption more at low than at high inotropy

Variations in left ventricular (LV) wall tension during changes in LV end-diastolic volume significantly affect myocardial oxygen consumption (MVO2). In the present study we examined if the reduction in MVO2 per beat accompanying a decline in LV end-diastolic volume at constant LV systolic pressure (LVSP) is dependent on the level of myocardial inotropy. In six anaesthetized open-chest pigs, the blood volume was expanded by i.v. infusion of a Ringer solution. At constant heart rate (by atrial pacing) and LVSP (by adjustments of a proximal aortic snare), LV end-diastolic volume was reduced in steps by withdrawals of blood. This procedure was performed at high inotropy (during a continuous intracoronary infusion of isoproterenol, 0.40 +/- 0.08 micrograms min-1), and at low inotropy (after i.v. injection of 3.4 +/- 0.2 mg propranolol). LVSP was about 25 mmHg higher at high than at low inotropy. The fall in LV tension was therefore greater during blood volume reductions at high than at low inotropy because the fall in LV end-diastolic volume was almost identical and was initiated from the same level at both high and low inotropy. Nevertheless, the slope of the MVO2/LV end-diastolic volume relationship was significantly (P less than 0.05) less steep at high (1.26 +/- 0.30 mumol 100 g-1 mm-1) than at low inotropy (2.06 +/- 0.48 mumol 100 g-1 mm-1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of reduced total blood volume on left ventricular volumes and kinetics in type 2 diabetes

Aim: Although impaired left ventricular (LV) diastolic function is commonly observed in patients with type 2 diabetes, it remains unclear whether the impairment is caused by altered LV relaxation or changes in LV preload. The purpose of this study was to examine the influence of LV function and LV loading conditions on stroke volume in men with type 2 diabetes. Methods: Cardiac magnetic resonance imaging scans were performed in eight men with type 2 diabetes and 11 non-diabetic men matched for age, weight and physical activity level. Total blood volume was determined with the Evans blue dye dilution technique. Results: End-diastolic volume (EDV), the ratio of peak early to late mitral inflow velocity (E/A) and stroke volume were lower in men with type 2 diabetes than in non-diabetic individuals. Peak filling rate and peak ejection rate were not different between diabetic and non-diabetic individuals; however, men with type 2 diabetes had proportionally longer systolic duration than non-diabetic individuals. Heart rate was higher and total blood volume was lower in men with type 2 diabetes. The lower total blood volume was correlated with a lower EDV in men with type 2 diabetes. Conclusions: Men with type 2 diabetes have an altered cardiac cycle and lower end-diastolic and stroke volume. A lower total blood volume and higher heart rate in men with type 2 diabetes suggest that changes in LV preload, independent of changes in LV relaxation or contractility, influence LV diastolic filling and stroke volume in this population.     

CardioClasp: a new passive device to reshape cardiac enlargement

In dilated heart failure, geometric distortions place an extra load on the myocardial cells. If this extra burden can be eliminated, the myocardial wall stress would decrease leading to improved systolic ventricular performance. In a dilated heart failure model, we wanted to see whether the CardioClasp (which uses two indenting bars to reshape the left ventricle [LV] as two widely communicating "lobes" of reduced radius) could improve systolic performance by passively reshaping the LV and reducing the wall stress. In mongrel dogs (n = 7; 25-27 kg), rapid ventricular pacing (210 ppm 1st week to 240 ppm 4th week) induced dilated heart failure. After 4 weeks, LV performance was evaluated at baseline and with the CardioClasp by measuring LV end-diastolic and peak LV systolic pressure, LV +dP/dt, LV -dP/ dt, and cardiac output. With the Clasp on, LV wall stress was reduced to 58.6+/-3.5 from 108.3+/-8.2 g/cm2. The fractional area of contraction (FAC) with the Clasp on (28.4+/-4.4) was significantly increased (p < 0.05) from baseline (20.8+/-4.6) and consistent with improved systolic performance. Cardiac output, LV peak systolic and end-diastolic pressures, and regional myocardial blood flow were unaltered. The Clasp was able to acutely reshape the left ventricle, while preserving the contractile mass, and reduced the tension on the myocardial cells and increased the fractional area of contraction without decreasing the systolic blood pressure.     

Experimental acute hypoxia in healthy subjects: evaluation of systolic and diastolic function of the left ventricle at rest and during exercise using echocardiography

To clarify whether or not systolic and diastolic function of the human left ventricle (LV) were decreased during acute hypoxia, at rest and with exercise, 14 healthy male volunteers [age 25.9 (SD 3.0) years, height 182.9 (SD 7.1) cm, body mass 75.9 (SD 6.9)kg] were examined using M-mode and 2D-mode echocardiography to determine the systolic LV function as well as Doppler-echocardiography for the assessment of diastolic LV function on 2 separate test days. In random order, the subjects breathed either air on 1 day (N) or a gas mixture with reduced oxygen content on the other (H; oxygen fraction in inspired gas 0.14). Measurements on either day were made at rest, several times during incremental cycle exercise in a supine position (6-min increments of 50 W, maximal load 150 W) and in 6th min of recovery. Corresponding measurements during N and H were compared statistically. Arterial O₂ tension (P _aO₂) was normal on N-day. All subjects showed a marked acute hypoxia at rest [P _aO₂, 54.5 (SD 4.6) mmHg], during exercise and recovery on H-day. The latter was associated with tachycardia compared to N-day. All echocardiographic measurements at rest were within the limits of normal values on both test days. Ejection time, end-systolic and end-diastolic left ventricular dimensions as well as the thickness of left posterior wall and of interventricular septum showed no statistically significant influence of H either at rest or during exercise. Stroke volume and cardiac output were always higher on H-day, which could be attributed to a slight reduction in end-systolic volume with unaffected end-diastolic volume as well as to increased heart rates. Among the indices of systolic LV function the fractions of thickening in the left ventricular posterior wall and interventricular septum showed no differences between H and N at rest or during exercise. However, fibre shortening, ejection fraction and mean circumferential fibre shortening were increased on H-day on all occasions. The mitral-valve-Doppler ratio, the index of diastolic LV function, was decreased with H at rest, showed a more pronounced reduction during exercise and was still lower in 6th min of recovery compared to N-day. It was concluded that with acute hypoxia of the severity applied in this study left ventricular systolic function in our healthy subjects showed a pronounced improvement and left ventricular diastolic function was reduced, both at rest and with exercise.     

The effect of 18 h of simulated high altitude on left ventricular function

High altitude produces increased pulmonary capillary pressure by hypoxia induced pulmonary vasoconstriction. It is also possible that hypoxia results in mildly elevated left ventricular (LV) filling pressures that may contribute to the elevated capillary pressures. This study investigates the impact of simulated high altitude on global and regional echocardiographic measures of LV performance and filling pressure. Seventeen healthy individuals underwent transthoracic echocardiography, including tissue Doppler of the septal mitral annulus and basal segments before and after an 18-h overnight stay in a high altitude simulation tent with a FiO₂ of 12%, simulating an altitude of approximately 4,000 m above sea level. In simulated high altitude, the ratio of early transmitral flow velocity to early myocardial relaxation velocity increased 22%, P < 0.001, and the Index of Myocardial Performance increased 30%, P < 0.01 due to an 58% increase in the isovolumic relaxation time (IVRT), P < 0.001. Simulated high altitude leads to a reduction in LV performance with an accompanying increase in markers of LV filling pressure. The significant changes in filling pattern and IVRT in the setting of normal and unchanged systolic function, indicates that hypoxia induces mild diastolic dysfunction in young healthy individuals.     

Angiotensin II infusion during beta-adrenergic stimulation by isoproterenol. Effects on hepatic, splenic and cardiac blood volumes and on the magnitude and distribution of cardiac output in the dog

The cardiac and peripheral vascular adjustments to angiotensin II (0.1-0.2 microgram kg-1 min-1 i.v.) during high beta-adrenergic activity by a continuous isoproterenol infusion (0.2-0.3 microgram kg-1 min-1 i.v.) were examined in anaesthetized, atropinized dogs. Hepatic, splenic and left ventricular (LV) volume changes were estimated by an ultrasonic technique, and the blood flow distribution was measured by injecting radioactive microspheres and by electromagnetic flowmetry on the caval veins, the hepatic artery and the portal vein. During isoproterenol infusion, angiotensin II increased the systolic LV pressure by 45 +/- 3 mmHg and the stroke volume by 17 +/- 6%. Concomitantly, the hepatic and splenic blood volumes declined by 29 +/- 4 and 14 +/- 6 ml, respectively, and the LV end-diastolic segment length increased by 3 +/- 1%. The flow through the inferior caval vein increased by 39 +/- 9%, whereas the superior vena caval flow remained unchanged. The hepatic arterial flow more than doubled. Thus, at high inotropy by isoproterenol infusion, angiotensin II relocates blood from the liver and the spleen towards the heart. By activating the Frank-Starling mechanism, cardiac output is increased and conducted through the lower body, especially through the hepatic artery, because of the poor autoregulation of flow through this vessel.     

Influence of body position and pneumoperitoneum on respiratory variation of venous return in anesthetized dogs

Summary Blood flow in the vena cava was measured in anesthetized dogs in supine, lateral, or prone position by a catheter velocity probe at four levels, i. e., above and below the veno-atrial junction and above and below the confluence of the renal veins, with the diameter of the vena cava fixed Teflon rings placed around it. Also the influence of pneumoperitoneum at atmospheric pressure on venous return was examined in supine position. In supine position there was an increase of venous return in the thoracic venae cavae and of calculated hepatic outflow during inspiration, whereas flow in the abdominal vena cava showed less and reversed variations as compared with the thoracic inferior caval venous pattern, i.e., a trough during inspiration and a peak during early expiration. Pneumoperitoneum reduced the inspiratory increase of thoracic inferior vena cava flow and of hepatic outflow. Lateral and prone positions induced a decrease or early leveling off of the inspiratory increase of flow in the thoracic inferior vena cava and of hepatic outflow. Superior caval venous flow remained almost unchanged with postural change. In all positions renal outflow did not show any clear-cut relationship with respiration. These variations of pattern of vena cava flow and hepatic outflow were attributed to an increase in the resistance of the vena cava in the infradiaphragmatic part, induced by the change of body position, as shown by an increase of the preinspiratory caval venous pressure difference between thorax and abdomen to 5.3±0.92 cm H₂O (mean±S.D.,n=14) in lateral position, and to 6.5±0.81 cm H₂O (n=4) in prone position from 2.0±0.85 cm H₂O (n=18) in supine position (p<0.001 for the increase from supine position).     

Validation of left ventricular end-diastolic volume from stroke volume and ejection fraction

The present study examines an innovative approach to measurement of left ventricular (LV) end-diastolic volume (LVEDV). Measurement of LVEDV is fundamental to the assessment of intraoperative systolic and diastolic LV function. We compared steady state LVEDV values obtained from stroke volume (SV) and ejection fraction (EF) with echocardiographic and postmortem LVEDV measurements. Five anesthetized pigs (40-45 kg) underwent median sternotomy and pericardiotomy. A transit time ultrasonic flow probe was placed on the ascending aorta to provide cardiac output. A micromanometer provided LV end-diastolic pressure. LV short axis cross sectional echocardiograms and electrocardiograms were also obtained. LV end-diastolic area (LVEDA) and end-systolic area (LVESA) were measured to obtain EF. LVEDVsv/ef was calculated from cardiac output, heart rate, and EF. LVEDVecho was determined using a three-plane echocardiography model. Postmortem (LVEDVpm/vv) volumes were also measured. LVEDVsv/ef correlated well with volumes obtained by echocardiography (r2 = 0.92) and postmortem (r2 = 0.73) measurements. Values of p < 0.05 indicated significant linearity of LVEDA-LVEDVsv/ef (r2 =0.93), LVEDA-LVEDVecho (r2 = 0.96), and LVEDA-LVEDVpm/vv (r2 = 0.81) relationships. Determination of LVEDV from SV and EF is valid and may facilitate real-time determination of LV mechanics.     

Left ventricular external constraint: Relationship between pericardial,pleural and esophageal pressures during positive end-expiratory pressure and volume loading in dogs

Left ventricular (LV) diastolic filling is limited by the constraining effects exerted by the pericardium (PE) and the lung/chest wall. The aim of the present study was to assess the validity of various estimates of external cardiac constraint, compared to pericardial surface pressure (P_pe) measured lateral to the LV myocardium. In nine anesthetized dogs we measured P_pe, pleural surface pressure (P_pl) (lateral to the pericardium) and esophageal pressure (P_es) under conditions of volume loading and positive end-expiratory pressure (PEEP). We measured P_pe and P_pl with flat, liquidcontaining silastic rubber balloons and P_es with an air-containing cylindrical balloon. After instrumentation, the chest was resealed and continuous suction (−5 mm Hg, 1 mm Hg=0.133 kPa) was maintained. Volume loading with incremental intravenous infusions of saline was used to increase LV end-diastolic pressure to 20–25 mm Hg. PEEP of 0, 10 and 20 mm Hg were applied at baseline and after each increment of volume loading. At low volume, increases in PEEP caused simultaneous increases in LV end-diastolic pressure (P<0.01) and in P_pe (P<0.0001) but a reduction in transmural LV pressure (P<0.0005). P_pl and P_es both increased with PEEP (P<0.001 and P<0.01, respectively). However, P_pe always exceeded P_pl, while P_es remained at only approximately 1/3 P_pl throughout. Volume loading caused a significant increase in P_pe (P<0.0001) and a smaller, but significant increase in P_pl (P<0.05). P_es remained unchanged during volume loading. Thus external cardiac constraint increased markedly during volume loading and PEEP as evidenced by a marked elevation of P_pe. Both P_pl and P_es markedly underestimated this increase. Therefore, calculation of transmural LV pressure by subtracting pleural or esophageal pressure from intracavitary pressure can lead to overestimation of LV preload. The decrease in cardiac output during PEEP occurs secondary to decreased preload, i.e. decreased transmural pressure and end-diastolic dimension. Analysis of performance using cardiac function curves does not suggest a change in contractility with PEEP.