Transient Inferior Vena Cava Occlusion Research Articles

Performance comparison of ventricular and arterial dP/dtmax for assessing left ventricular systolic function during different experimental loading and contractile conditions

BackgroundMaximal 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.MethodsWe 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.ResultsBoth LV and arterial dP/dtmax allowed the tracking of Ees changes, especially during afterload and contractility changes, although arterial dP/dtmax was lower compared to LV dP/dtmax (bias 732 ± 539 mmHg⋅s− 1 for femoral dP/dtmax, and 625 ± 501 mmHg⋅s− 1 for radial dP/dtmax). Changes in cardiac contractility (Ees) were the main determinant of LV and arterial dP/dtmax changes.ConclusionAlthough 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.

Inhibition of Soluble Epoxide Hydrolase Augments Hypoxic Pulmonary Vasoconstriction and Improves Gas Exchange in Mice

Recent studies report that cytochrome P‐450‐derived epoxyeicosatrienoic acids (EETs) increase pulmonary vascular tone. We hypothesized that inhibiting the metabolism of EETs by inhibition of soluble epoxide hydrolase (sEH) would augment hypoxic pulmonary vasoconstriction (HPV) and improve gas exchange.Mice were anesthetized, intubated, and ventilated at FIO2=1. Animals received an i.v. infusion of the sEH inhibitor, IK‐950, or vehicle 30 minutes prior to assessing HPV. After thoracotomy, pulmonary artery pressure (PAP) and left lung blood flow (QLPA) were measured before and during transient inferior vena cava occlusion. Left lung pulmonary vascular resistance (PVRL) was calculated from the slope of the PAP‐QLPA relationship. The pulmonary vasoconstrictor response to unilateral left lung hypoxia was estimated by comparing PVRL before and after left main stem bronchial occlusion (LMBO).Infusion of vehicle or IK‐950 did not change baseline hemodynamic parameters. LMBO increased PVRL, without changing PAP in both vehicle‐and IK‐950‐pretreated mice. Increase in PVRL during LMBO was greater in mice pretreated with IK‐950 than in those pretreated with vehicle (Table). PaO2 after LMBO was greater in mice pretreated with IK‐950 than in those pretreated with vehicle.Taken together, these results indicate that IK‐950 acts as a selective pulmonary vasoconstrictor of hypoxic lung regions, enhancing the perfusion of ventilated lung regions.

Cytochrome P‐450 2J epoxygenase gene function in murine hypoxic pulmonary vasoconstriction (HPV)

Recent studies suggest that cytochrome P‐450 (CYP) epoxygenase‐derived epoxyeicosatrienoic acids (EETs) play an important role in the regulation of the pulmonary vascular tone. To assess the role of the CYP2J‐signaling pathway in HPV, we studied CYP2J+/+ and CYP2J−/− mice, as well as CYP2J−/− mice carrying a transgene specifying human CYP2J (CYP2J−/−‐Tg). Mice were anesthetized, intubated, and ventilated at FIO2=1. After thoracotomy, pulmonary artery pressure (PAP) and left lung blood flow (QLPA) were measured before and during transient inferior vena cava occlusion. Left pulmonary vascular resistance (LPVR) was calculated from the slope of the PAP‐QLPA relationship. The pulmonary vasoconstrictor response to unilateral left lung hypoxia was estimated by comparing LPVR before and after left main stem bronchial occlusion (LMBO). LMBO increased LPVR in CYP2J+/+ and CYP2J−/−‐Tg mice but not in CYP2J−/− mice (see Table). PaO2 during LMBO was greater in CYP2J+/+ and CYP2J−/−‐Tg mice than in CYP2J−/− mice. Administration of MS‐PPOH, a selective inhibitor of CYP‐mediated epoxygenation, blocked the ability of LMBO to increase LPVR in CYP2J+/+ mice. Taken together, these results indicate that CYP2J epoxygenase contributes importantly to HPV in mice. (Supported by MGH, Department of Anesthesia, Critical Care and Pain Medicine).

Ability of pulse contour and esophageal Doppler to estimate rapid changes in stroke volume

Two technologies to acquire beat-to-beat stroke volume values exist, pulse contour analysis and esophageal Doppler monitoring. Pulse contour analysis assumes fixed aortic impedance. Esophageal Doppler assumes a constant proportional descending aortic flow and diameter. These assumptions may not be correct as arterial tone or myocardial contractility vary. We tested these relationships in the setting of rapidly changing stroke volumes and different cardiovascular states over a period of 10-15 cardiac cycles. In a university research facility we compared beat-to-beat changes in stroke volume as measure by aortic root flow probe or conductance catheter to pulse contour analysis and stroke distance as measured by esophageal Doppler. Five purpose-bred research hounds. To obtain a wide range of rapidly changing stroke volumes measurements were made during transient inferior vena cava occlusion. Data were gathered under baseline conditions and during norepinephrine, nitroprusside, and dobutamine infusions. The pulse contour stroke volumes and esophageal Doppler stroke distance paralleled flow probe stroke volumes under all conditions (R(2)=0.89 for all measures). However, the absolute changes and proportional changes and the absolute values for both surrogate measures differed from absolute stroke volumes. Bland-Altman analysis showed no consistent bias or degree of precision across all animals under any given cardiovascular state. Both pulse contour stroke volumes and esophageal Doppler derived stroke distance estimates yield significant correlations with aortic root flow probe. However, the absolute values, absolute changes, or proportional changes may not reflect actual stroke volumes as cardiovascular state varies, making their use in estimating absolute changes in stroke volume potentially inaccurate.

Nitric oxide donor FK409 and 8-bromoguanosine-cyclic monophosphate attenuate cardiac contractility assessed by Emax.

FK409 decomposes and releases nitric oxide (NO) spontaneously when it is dissolved in phosphate buffer solution at 37 degrees C. With the use of this NO donor, the effect of exogenous NO on cardiac contractility was examined by assessing Emax. alpha-chloralose-anaesthetized dogs were instrumented for measurements of left ventricular (LV) pressure and volume and coronary blood flow (CBF) in the left anterior descending artery (LAD). FK409, 8-bromoguanosine-cyclic-monophosphate (8-Br-cGMP) and papaverine were infused into the LAD, and Emax was determined by transient inferior vena cava occlusion when CBF was increased and reached its peak. Neither drug affected heart rate nor LV pressure just before the measurement of Emax. FK409 increased CBF and decreased Emax in a dose-dependent manner. 8-Br-cGMP also increased CBF and decreased Emax in a dose-dependent manner. Pretreating with propranolol did not affect the effects of FK4098-Br-cGMP on CBF and Emax. Papaverine increased mean CBF but did not affect Emax. In conclusion NO attenuates cardiac contractility in vivo, while increasing CBF. This effect seems to be mediated by cyclic-guanosine monophosphate, a second messenger of NO.

Right ventricular function in respiratory distress syndrome and subsequent partial liquid ventilation. Homeometric autoregulation in the right ventricle of the newborn animal.

Infant respiratory distress syndrome (IRDS) and subsequent partial liquid ventilation (PLV) cause increased pulmonary vascular resistance, thus raising afterload. In nine newborn lambs the effects of IRDS and subsequent PLV on right (RV) and left ventricular (LV) contractility and systolic pump function were assessed using indices derived from RV and LV pressure-volume relations, obtained by micromanometric and conductance catheters during transient inferior vena cava occlusion. Pulmonary function deteriorated during IRDS with a significant decrease in the ratio of arterial oxygen pressure to fraction of inspired oxygen (Pa(O(2))/FI(O(2))) whereas pulmonary artery pressure (Ppa) showed a significant increase and pulmonary vascular resistance showed a substantial though not significant increase. Cardiac output (Q), stroke volume (SV), and end-diastolic volume (EDV) did not change. RV contractility showed a significant increase during IRDS: the slope of the end-systolic pressure-volume relation (RV-E (ES)) increased whereas its volume intercept at 5 kPa (RV-V(5)) decreased. The preload-corrected time derivative of ventricular pressure (RV-dP/dt(max)), however, did not change significantly. LV pump function and contractility were unchanged. During PLV pulmonary function showed a recovery but Ppa and pulmonary vascular resistance remained high; indices for RV contractility showed a sustained significant increase compared with baseline conditions whereas indices for LV pump function and contractility remained unchanged. These results show that the right ventricle of the newborn heart, in the face of increased pulmonary vascular resistance, is able to maintain cardiac output through homeometric autoregulation.

Cardiac contractility is not depressed in early canine endotoxic shock.

We investigated effects of acute endotoxemia (Escherichia coli endotoxin, 1 mg/kg, intravenously) on left ventricular (LV) function in the first 4 h after induction of endotoxic shock in anesthetized canine preparations (n = 7 each, endotoxin and control groups). LV pressure and conductance (volume) catheters were used to construct pressure-volume loops. Transient inferior vena cava occlusion was used to rapidly and reversibly alter LV end-diastolic volume. LV contractility was assessed from the slope of the LV end-systolic pressure-volume relationship (Ees) and from preload-recruitable stroke work (PRSW), and from their change (DeltaEes and DeltaPRSW, respectively, measured at 2 and 4 h only), in response to a dobutamine infusion (5 microg/kg/min). Diastolic function and arterial tone were assessed as the maximal negative change in filling pressure versus time (max -dP/dt), filling rate, and arterial elastance (Ea), respectively. Ees, PRSW, Ea, diastolic function, and hemodynamics were measured hourly. Endotoxemia induced an immediate hypotensive, hyperdynamic, tachycardic state with progressive lactic acidosis. By 2.5 h after endotoxin infusion, heart rate returned to preendotoxin and control levels, but the other changes remained. However, no change occurred in LV Ees, DeltaEes, PRSW, DeltaPRSW, diastolic function, or Ea during the 4-h measurement interval. The cardiovascular collapse seen during the first 4 h of endotoxemia is therefore not due even partly to alterations in LV contractility.

Improved efficiency of energy transfer to external work in chronic cardiomyoplasty based on the pressure-volume relationship

Objective: Cardiomyoplasty is a surgical procedure to support the failing heart, in which a burst-stimulated latissimus dorsi muscle flap is transposed and wrapped around the ventricles. The effect of dynamic cardiac compression, implemented as cardiomyoplasty, on left ventricular performance remains controversial; the mechanism by which clinical symptoms are improved remains unclear. To investigate the mechanism for improvement of patients' symptoms, it is important to evaluate the effects of cardiomyoplasty on left ventricular energetics and on left ventricular systolic and diastolic function. We therefore evaluated the efficiency of energy transfer from the native pressure-volume area to external work under conditions of 1:3 skeletal muscle burst pacing in an animal model with chronic heart failure. Methods: In seven Merino-Wether sheep, cardiomyoplasty was performed after stable heart failure was induced by staged coronary embolizations (ejection fraction < 35%). Hemodynamic assessment including the assessment of the pressure-volume relationship was performed 8 weeks after cardiomyoplasty when the latissimus dorsi muscle was fully trained. Instantaneous left ventricular pressure and volume were measured with a catheter-tipped manometer and a conductance catheter during steady-state conditions and after a transient inferior vena cava occlusion. The effect of dynamic cardiac compression on left ventricular systolic function was assessed by comparing pre-assisted and assisted beats and on diastolic function by comparing assisted and post-assisted beats. Result: The slope of the end-systolic pressure-volume relationship decreased by 30.5% ± 27.8% ( p = 0.02) during assisted beats. However, left ventricular pump performance improved by increasing stroke volume and external work by 35.9% ± 36.0% ( p = 0.03) and 9.7% ± 6.8% ( p = 0.03), respectively, resulting in a reduction of the volume intercept. As a result, the end-systolic pressure-volume relationship shifted to the left. The efficiency of energy transfer from the native pressure-volume area to the overall external work improved by 7.6% ± 8.2% ( p = 0.04). Cardiomyoplasty did not affect the time constant of left ventricular isovolumic pressure decline or the maximal rate of pressure decay, which suggested that cardiomyoplasty did not affect left ventricular relaxation. Conclusions: Dynamic cardiac compression in the form of cardiomyoplasty enhanced left ventricular pump performance without interrupting left ventricular filling. The ratio of energy transfer from the native pressure-volume area to the overall external work suggests a myocardial oxygen-sparing effect of cardiomyoplasty. (J Thorac Cardiovasc Surg 1998;115:1358-66)

Chronic Changes of End-Systolic Pressure-Volume Relationship After Regional Myocardial Infarction

The chronic changes of the end-systolic pressure-volume relationship (ESPVR) after regional myocardial infarction were evaluated in a sheep model. Pressure-volume area (PVA) obtained from the pressure-volume diagram and left ventricular oxygen consumption (LVO2) were studied. The regional myocardial infarction was created by ligating distal branches of the left coronary artery. ESPVR was obtained using a conductance catheter during transient inferior vena cava occlusion. Measurements were performed at baseline (n = 13), 1 hour (n = 8), 3 months (n = 9), and 6 months (n = 4) after infarction. Ees, the slope of the ESPVR did not change at 1 hour after infarction and remained the same at 3-month and 6-month measurements (baseline 2.26 +/- 1.24 mmHg/mL, 1 hour 2.71 +/- 1.06, 3 months 3.46 +/- 1.51, 6 months 2.45 +/- 0.64, NS). Because of the ventricular dilatation, which was demonstrated as an increase in changes of end-systolic volume (Ves) correlating with the time course after infarction (y = -3.21 + 0.12x, r = 0.454, p < 0.05), V0, the volume intercept of the ESPVR increased at 1 hour after the infarction, and showed a tendency to increase at 3 months and 6 months after the infarction (baseline -18.0 +/- 22.5 mL; 1 hour -0.9 +/- 11.6; 3 months 5.4 +/- 10.9, 6 months 9.2 +/- 23.1, baseline vs 3 months p < 0.05, baseline vs 6 months p < 0.05). PVA and LVO2 were unchanged over time after infarction (PVA: baseline 2097 +/- 1526 mmHg/mL per 100 g-1; 1 hour 1771 +/- 699; 3 months 2483 +/- 1086; 6 months 1,608 +/- 1,010, NS), (LVO2: baseline 40.6 +/- 13.1 x 10(-3) mL/100 g-1 per beat-1; 1 hour 42.9 +/- 9.7; 3 months 35.0 +/- 8.6; 6 months 31.2 +/- 18.1, NS). Chronic regional infarction in the sheep model did not affect Ees over 6 months, but significantly increased V0 after the increase in the acute phase. PVA and LVO2 were not affected by this regional infarction either acutely or over 6 months.

Inhibition of cardiac phosphodiesterase III activity BYH 2O 2 and related active oxygenspecies

The end-systolic pressure-volume relation has been postulated as a load-independent measure of cardiac contractility, but has been difficult to measure because of technical problems associated with the serial measurement of intracardiac volume over a physiologic range of ventricular loading conditions. Utilizing a multielectrode impedance catheter to assess continuous, on-line left ventricular relative volume during transient inferior vena cava occlusion, a method is described for determining the end-systolic pressure-volume relation and for assessing changes in this relation secondary to inotropic modulation. In particular, using this method, the relative inotropic properties were determined of four drugs: dobutamine, milrinone, epinephrine and an experimental cardiotonic agent (Ro 13-6438, Posicor).Left ventricular micromanometer pressure and impedance catheter volume were measured continuously in 10 open chest, anesthetized dogs and 14 pigs. Arterial pressure was altered over a range of 20 to 60 mm Hg by brief inferior vena cava constriction. A linear end-systolic pressure-volume relation was observed in pressure-volume diagrams constructed from on-line pressure and impedance catheter recordings. Administration of dobutamine, milrinone and epinephrine resulted in a leftward shift and an increase in the slope of the end-systolic pressure-volume relation as compared with baseline; Posicor did not alter the slope over a range of doses, despite an increase in the cardiac output secondary to arterial vasodilation. Volume changes as measured by the impedance method closely paralleled simultaneous changes in the ultrasonic crystal-determined segment length, and the impedance end-systolic pressure-volume relation slope was reproducible with repeated load-altering manuevers.It is concluded that the end-systolic pressure-impedance volume relation can be determined on a beat to beat basis during acute decreases in ventricular preload induced by transient inferior vena cava occlusion. This method of determining relative changes in the end-systolic pressure-volume relation may be useful in the assessment of relative inotropic effects of experimental cardiotonic drugs.

Reduced left ventricular compliance in human mitral stenosis. Role of reversible internal constraint.

The mechanisms of depressed left ventricular (LV) pump performance in human mitral stenosis (MS) remain poorly understood, because reduced filling alone affects many hemodynamic measurements. Therefore, pressure-volume relations were examined in nine subjects with MS and compared with eight age-matched normal controls. Data were obtained by conductance catheter/micromanometer technique with transient inferior vena cava occlusion used to alter load and generate pressure-volume relations. In a subset of patients (n = 5), data were obtained both acutely and at 3 months (n = 4) after balloon valvuloplasty. MS patients had reduced cardiac output (3.3 +/- 0.9 versus 5.6 +/- 1.7 l/min) and end-diastolic volume (68.0 +/- 6.9 versus 115 +/- 31 ml) versus controls (p less than 0.001), with a mean transvalvular gradient of 14 +/- 6 mm Hg and estimated valve area of 0.6 +/- 0.2 cm2. Systolic function as assessed by the end-systolic pressure-volume relation was virtually the same in MS and control subjects. In contrast, end-diastolic pressure-volume relations in MS were consistently shifted leftward and had an increased slope (lower compliance) at matched pressure ranges (6.5 +/- 3.0 versus 2.2 +/- 0.53 ml/mm Hg at a mean diastolic pressure of 8 mm Hg, p less than 0.001). This change was not a result of reduced LV filling or probably of increased right heart loading. Valvuloplasty acutely returned chamber compliance to near normal, a change that was sustained at 3-month follow-up. Systolic function was little altered at this time. These data indicate an impairment of diastolic function in human MS that can be acutely reversed by balloon valvuloplasty. Lowered LV compliance probably results from a functional restriction caused by ventricular attachment to a thickened and immobile valve apparatus.

Effects of left ventricular pressure reductions on right ventricular systolic performance.

Reductions in left ventricular pressure (LVP) have been shown to produce a leftward shift of the interventricular septum and to reduce left ventricular contribution to right ventricular performance. To evaluate the magnitude of this contribution in the intact heart, five anesthetized pigs were implanted with a left prosthetic ventricle to gradually decrease LVP while maintaining arterial systemic pressure. Three descriptors of RV global and regional systolic function were studied in the septum to free wall (RVSFW) and anterior to posterior (RVAP) dimensions and in an outflow tract segment length (RVSL), during both steady state and transient inferior vena cava occlusion. LVP gradual reduction from 102 +/- 4 to 11 +/- 3 mmHg (90% decrease in peak systolic pressure) produced no changes in the RV global stroke work curve or in the RVAP and RVSL pressure-dimension relationships. However, the reduction in LVP resulted in parallel shifts in the RVSFW dimension, with 16.6 +/- 6.7% increase in the intercept D(o) of the end-systolic relationship and 16.5 +/- 2.5% increase in D(o) of the dimensional stroke work relationship, with no significant changes in their respective slopes as calculated by linear regression. Therefore, in the normal intact heart, large reductions in left ventricular pressure affect the geometry of the right ventricle because of septal shifting, but there is a negligible net effect of this anatomic ventricular interaction on overall right ventricular performance.

Assessment of left ventricular end-systolic pressure-volume relations with an impedance catheter and transient inferior vena cava occlusion: Use of this system in the evaluation of the cardiotonic effects of dobutamine, milrinone, posicor and epinephrine

The end-systolic pressure-volume relation has been postulated as a load-independent measure of cardiac contractility, but has been difficult to measure because of technical problems associated with the serial measurement of intracardiac volume over a physiologic range of ventricular loading conditions. Utilizing a multielectrode impedance catheter to assess continuous, on-line left ventricular relative volume during transient inferior vena cava occlusion, a method is described for determining the end-systolic pressure-volume relation and for assessing changes in this relation secondary to inotropic modulation. In particular, using this method, the relative inotropic properties were determined of four drugs: dobutamine, milrinone, epinephrine and an experimental cardiotonic agent (Ro 13-6438, Posicor). Left ventricular micromanometer pressure and impedance catheter volume were measured continuously in 10 open chest, anesthetized dogs and 14 pigs. Arterial pressure was altered over a range of 20 to 60 mm Hg by brief inferior vena cava constriction. A linear end-systolic pressure-volume relation was observed in pressure-volume diagrams constructed from on-line pressure and impedance catheter recordings. Administration of dobutamine, milrinone and epinephrine resulted in a leftward shift and an increase in the slope of the end-systolic pressure-volume relation as compared with baseline; Posicor did not alter the slope over a range of doses, despite an increase in the cardiac output secondary to arterial vasodilation. Volume changes as measured by the impedance method closely paralleled simultaneous changes in the ultrasonic crystal-determined segment length, and the impedance end-systolic pressure-volume relation slope was reproducible with repeated load-altering maneuvers.(ABSTRACT TRUNCATED AT 250 WORDS)