Robert W.M. Frater

Left ventricular filling dynamics: influence of left ventricular relaxation and left atrial pressure

Peak rapid filling rate (PRFR) is often used clinically as an index of left ventricular relaxation, i.e., of early diastolic function. This study tests the hypothesis that early filling rate is a function of the atrioventricular pressure difference and hence is influenced by the left atrial pressure as well as by the rate of left ventricular relaxation. As indexes, we chose the left atrial pressure at the atrioventricular pressure crossover (PCO), and the time constant (T) of an assumed exponential decline in left ventricular pressure. We accurately determined the magnitude and timing of filling parameters in conscious dogs by direct measurement of phasic mitral flow (electromagnetically) and high-fidelity chamber pressures. To obtain a diverse hemodynamic data base, loading conditions were changed by infusions of volume and angiotensin II. The latter was administered to produce a change in left ventricular pressure of less than 35% (A-1) or a change in peak left ventricular pressure of greater than 35% (A-2). PRFR increased with volume loading, was unchanged with A-1, and was decreased with A-2; T and PCO increased in all three groups (p less than .005 for all changes). PRFR correlated strongly with the diastolic atrioventricular pressure difference at the time of PRFR (r = .899, p less than .001) and weakly with both T (r = .369, p less than .01) and PCO (r = .601, p less than .001). The correlation improved significantly when T and PCO were both included in the multivariate regression (r = .797, p less than .0001). PRFR is thus determined by both the left atrial pressure and the left ventricular relaxation rate and should be used with caution as an index of left ventricular diastolic function.

Passive properties of canine left ventricle: diastolic stiffness and restoring forces

Left ventricular (LV) diastolic pressure-volume (P-V) relations arise from a complex interplay of active decay of force (i.e., relaxation), passive elastic myocardial properties, and time-varying inflow across the mitral orifice. This study was designed to quantify the passive properties of the intact ventricle and the effects of elastic recoil by separating filling from relaxation with a method of LV volume clamping with a remote-controlled mitral valve. Eleven open-chest fentanyl-anesthetized dogs were instrumented with aortic and mitral flow probes, LV and left atrium micromanometers, and a remote-controlled mitral valve. We prevented complete (end-systolic volume clamping) or partial filling at different times in diastole. The ventricle thus relaxed completely at different volumes, and we generated P-V coordinates for the passive ventricle that included negative, as well as positive, values of pressure. We then estimated ventricular volumes from ventricular weight in eight dogs, using regression equations based on data in the literature, to determine the equilibrium volume (V0), that is, volume at zero transmural pressure, in the working ventricle. We abandoned the traditional exponential approach and characterized the P-V relation with a logarithmic approach that included maximum LV volume (Vm), minimum volume (Vd), and stiffness parameters (Sp and Sn) for the positive (p) and negative (n) phases: Pp = -Sp In[(Vm - V)/(Vm-V0)] and Pn = Sn In[(V-Vd)/(V0-Vd)]. With this formulation, the chamber compliance, dP/dV, is normalized by the LV operating volume, and Sp and Sn are size-independent chamber stiffness parameters with the units of stress. In eight ventricles with LV weight = 131 ± 20 g, Vm = 116 ± 18 ml, V0 = 37 ± 6 ml, and Vd = 13 ± 2ml, stiffness Sp = 14.6 mm Hg and Sn = 5.1 mm Hg were determined from the slopes of the log-linearized equations. Also, the duration of LV relaxation is increased by the process of ventricular filling (161 ± 31 msec, filling versus 108 ± 36 msec, nonfilling, measured from dP/dtmin, p < 0.0001). We conclude that volume clamping is a useful method of studying restoring forces and that the logarithmic approach is conceptually and quantitatively useful in characterizing the passive properties of the intact ventricle.

Application of transesophageal echocardiography to continuous intraoperative monitoring of left ventricular performance

Transesophageal M mode echocardiography was used for continuous monitoring of left ventricular dimensions in 21 patients (11 with valvular and 10 with coronary heart disease) undergoing open heart surgery. Echocardiograms were recorded in six stages of the procedure and simultaneous measurements of cardiac output (with dye dilution) and atrial pressures were made. Measurements of left ventricular diameters with the transesophageal technique correlated excellently with the corresponding measurements obtained with the standard parasternal method. In patients with volume overload, surgical correction was accompanied by a decrease in diastolic dimension, velocity of circumferential fiber shortening, mid wall stress and end-diastolic stiffness, and an increase in cardiac output. Pericardial and chest wall closures generally caused a significant decrease in cardiac output, and correlated with a decrease in diastolic diameter and an increase in the stiffness constant of the left ventricle. Thus, the decrease in cardiac output may have been due to decreased distensibility of the ventricular cavity secondary to mechanical restriction by the pericardium and chest wall. Pericardial opening caused a significant delay in septal motion that was reversed by closing the pericardium. This study confirms the validity of transesophageal echocardiography and its usefulness in monitoring changes in ventricular function during cardiac surgery.

Dynamic aspects of acute mitral regurgitation: effects of ventricular volume, pressure and contractility on the effective regurgitant orifice area.

The dynamics of acute mitral regurgitation were studied in six open-chest dogs in whom a portion of the anterior leaflet was excised. Phasic mitral and aortic flows were measured electromagnetically and left ventricular filling volume, regurgitant volume (RV) and forward stroke volume (SV) were calculated. The systolic pressure gradient (SPG) between the left ventricle (LV) and left atrium (LA) was obtained from highfidelity pressure transducers. The effective mitral regurgitant orifice area (MRA) was calculated from the hydraulic equation of Gorlin.Volume infusion resulted in significant increases in both left atrial and left ventricular pressures; thus, the SPG was unchanged and the increase in RV was due primarily to the increase in MRA. Angiotensin infused to raise arterial pressure resulted in greater increments in left ventricular than left atrial pressure, so that SPG rose significantly. The increase in RV was due to increases in both MRA and SPG. Norepinephrine infusion increased systolic left ventricular pressure and SPG, while left ventricular end-diastolic pressure and left atrial pressure diminished. Despite a significant increase in SPG, RV did not increase, due to a substantial decrease in MRA. Thus, angiotensin and volume infusion induced a substantial increase in regurgitation due to the increase in MRA, while augmentation of contractility after norepinephrine infusion resulted in a decrease in regurgitation through reduction of MRA. These findings support the clinical view that maintaining a small LV with sustained myocardial contractility will reduce mitral regurgitation. Alternatively, left ventricular dilatation can enhance mitral regurgitation by increasing the effective regurgitant orifice independent of SPG.

Age and valve size effect on the long-term durability of the Carpentier-Edwards aortic pericardial bioprosthesis☆

BACKGROUND Bioprosthesis durability decreases with time and younger age. However, the time-scale and determinants of durability of the aortic Carpentier-Edwards stented bovine pericardial prosthesis are incompletely characterized. METHODS Between September 1981 and January 1984, 267 patients underwent implantation of the pericardial aortic prosthesis at four centers. Mean age at implant was 65 +/- 12 years (range 21 to 86 years). Follow-up averaged 12 +/- 4.5 years. The primary end point was explant for structural valve dysfunction (SVD), which was analyzed multivariably in the context of death as a competing risk. RESULTS Freedom from explant due to SVD was 99%, 94%, and 77% at 5, 10, and 15 years. Risk of SVD increased exponentially with time and younger age (p = 0.0001) at implantation; an increased risk of small valve size was not reliably demonstrated (p = 0.1). Considering the competing risk of death, patients aged 65 years or older had a less than 10% chance of explant for SVD by 15 years. CONCLUSIONS Durability of this stented pericardial aortic bioprosthesis is excellent and justifies its use in patients aged 65 or older.

Mechanism of reduction of mitral regurgitation with vasodilator therapy

Acute mitral regurgitation was produced in six open chest dogs by excising a portion of the anterior valve leaflet. Electromagnetic flow probes were placed in the left atrium around the mitral anulus and in the ascending aorta to determine phasic left ventricular filling volume, regurgitant volume and stroke volume. The systolic pressure gradient was calculated from simultaneously measured high fidelity left atrial and left ventricular pressures. The effective mitral regurgitant orifice area was calculated from Gorlins hydraulic equation. Infusion of nitroprusside resulted in a significant reduction in mitral regurgitation. No significant change occurred in the systolic pressure gradient between the left ventricle and the left atrium because both peak left ventricular pressure and left atrial pressure were reduced. The reduction of mitral regurgitation was largely due to reduction in the size of the mitral regurgitant orifice. Reduction of ventricular volume rather than the traditional concept of reduction of impedance of left ventricular ejection may explain the effects of vasodilators in reducing mitral regurgitation.

Influence of vegetation size on clinical outcome of right-sided infective endocarditis

Endocarditis involving right-sided valvular structures is largely a disease of intravenous drug abusers. The majority of these patients respond to antibiotic therapy with clearing of their bacteremia and preservation of their hemodynamic status. This study evaluated the prognostic value of echocardiographically determined vegetation size in 23 episodes of right-sided valvular endocarditis in 21 patients. Right-sided vegetations were visualized in 19 of 23 episodes (83 percent). Of these, a vegetation of 1.0 cm or greater was found in 11. No patient with an echocardiographically determined vegetation size of less than 1.0 cm required surgery, whereas four of 11 (36 percent) of those episodes in which the vegetation size was 1.0 cm or greater required surgery for persistent pyrexia (p less than 0.05). In all patients requiring surgery, a bioprosthetic tricuspid valve was placed at the time of initial surgery and in no patient did early reinfection occur. This study reconfirms the benign prognosis of right-sided valvular endocarditis. Further, although vegetations of less than 1.0 cm identify those patients who will respond to medical therapy, echocardiographically documented vegetations of 1.0 cm or greater are associated with a significantly lower response rate to appropriate medical therapy. The association of fever that persists for more than three weeks in the absence of another source of infection with an echocardiographically demonstrable right-sided vegetation of 1 cm or more identifies those patients who will require surgical intervention. Finally, tricuspid valve replacement can be performed at the time of initial surgery without undue concern for early reinfection or valve dysfunction.

Immunogenicity of Glutaraldehyde-Tanned Bovine Pericardium

Glutaraldehyde-tanned bovine pericardium was tested for its ability to induce immunologic responses in vivo. Sections of glutaraldehyde-tanned bovine pericardium were implanted between the abdominal muscles of rats and guinea pigs. Control animals received Dacron implants. Lymphocytes and sera from animals were isolated at 2 and 4 weeks after implantation (four animals per group per time). Tritiated thymidine incorporation and an enzyme-linked immunosorbent assay were used to measure T- and B-lymphocyte responses to glutaraldehyde-tanned bovine pericardium antigens. At the same time points, implants and surrounding tissue from all animals were processed for histologic data. Results show that T-lymphocytes from animals with glutaraldehyde-tanned bovine pericardium implants responded significantly (p less than 0.001) to glutaraldehyde-tanned bovine pericardium antigens in vitro but not to Dacron. In contrast, lymphocytes from animals with Dacron implants failed to respond to glutaraldehyde-tanned bovine pericardium or Dacron preparations. Results of enzyme-linked immunosorbent assay show that animals with glutaraldehyde-tanned bovine pericardium implants produced antibody directed against glutaraldehyde-tanned bovine pericardium antigens. Histologic study revealed a dense mononuclear and multinuclear giant cell infiltrate at the interface between glutaraldehyde-tanned bovine pericardium and surrounding host tissues, with focal degradation of implant collagen. Dacron elicited a nonspecific lymphocytic and foreign body-type reaction. These results indicate that glutaraldehyde-tanned bovine pericardium can induce immunologic responses in vivo consistent with a host-versus-graft reaction.

Left-to-right ventricular interaction with a noncontracting right ventricle.

UNLABELLED Left ventricular systole is known to contribute to generation of right ventricular pressure and stroke volume. To study the interactions in a dilated noncontractile right ventricle after cardiopulmonary bypass we created a variable volume, neo-right ventricle by excision and replacement of the right ventricular free wall with a xenograft pericardial patch. We investigated the interactions in eight dogs with neo-right ventricle, instrumented to measure cardiac pressures and cardiac output in control conditions (n = 69) and during partial pulmonary artery occlusion (n = 50). RESULTS The size of the neo-right ventricle was increased from original right ventricular volume V0 to V1 (V1 = V0 + 54 +/- 23 ml), V2 (V2 = V0 + 124 +/- 85 ml), and V3 (V3 = V0 + 223 +/- 162 ml). Cardiac output increased with increasing left ventricular end-diastolic pressure, indicating that the Frank-Starling mechanism was operating in the left ventricle. However, cardiac output decreased with increasing neo-right ventricular size (p < 0.001) and during pulmonary artery occlusion (p < 0.001). Maximal neo-right ventricular pressure was a linear function of the maximal left ventricular pressure at each neo-right ventricular size and decreased with the increase in neo-right ventricular size (p < 0.001), both in control conditions and during pulmonary artery occlusion (p < 0.004). Stroke work of the neo-right ventricle and left ventricle decreased with increasing neo-right ventricular size (p < 0.002). The relationship between neo-right ventricular stroke work and left ventricular stroke work at different neo-right ventricular sizes was linear both in control conditions and during pulmonary artery occlusion: in control Y = 0.24X (r = 0.968, n = 69); in pulmonary artery occlusion Y = 0.35X (r = 0.986, n = 50). In both conditions the intercept of the linear relationship was not significantly different from zero (p < 0.974 in control; p < 0.614 in pulmonary artery occlusion). The slope was significantly increased in pulmonary artery occlusion (p < 0.001). CONCLUSION Left ventricular contraction contributes 24% of left ventricular stroke work to the generation of right ventricular stroke work via the septum in the absence of a contracting right ventricle; this increases to 35% in the face of increased pulmonary afterload. This mechanism can maintain adequate global cardiac function in the case of a noncontracting right ventricle while right ventricular volume is kept small and afterload is not increased. The interventricular interaction of the ventricles must be considered when patients with postbypass right ventricular failure are treated.

Reproducible Replacement of Elongated or Ruptured Mitral Valve Chordae

Anatomical rules that make it possible to accurately replace mitral anterior cusp chordae tendineae with tanned xenograft pericardium are defined. Anterior and posterior cusp chordae were replaced with xenograft and autologous pericardium in 11 patients who had ruptured or elongated chordae. The xenograft occasionally became calcified; however, because it did not become elongated or shortened, competence was maintained for up to 3 years. Insufficiency was corrected, and the correction maintained for up to 4 months. Degenerative disease proved easier to treat than rheumatic disease. Two-dimensional echocardiography was a valuable aid in both preoperative planning and postoperative evaluation.