Accounting for the Gregg effect in tetanised coronary arterial pressure-flow relationships.

OBJECTIVE: Myocardial contraction shifts the diastolic coronary pressure-flow relationship to lower flows at any given pressure, the amount of shift being determined primarily by the contractile level. A portion of this shift may be attributable to the Gregg effect. The purpose of this study was to quantify the influence of the Gregg effect and thereby demonstrate the pure effect of activation at a constant contractile level on the pressure-flow relationships. METHODS: It was first shown in beating canine interventricular septa that transverse stiffness induced by small high frequency indentations transverse to the plane of the tissue was an index of contractility. At constant perfusion pressure and preload, there was an inverse relationship between peak transverse stiffness and contractile level (induced by graded doses of 2,3-butanedione monoxime) for both isotonic and auxotonic contractions. A Gregg effect was next verified by showing a linear dependence between transverse stiffness and perfusion pressure during ryanodine induced tetanizations. Finally, the relationship between changes in flow and transverse stiffness was determined from diastole to tetany at two contractile levels. These relationships suffice to quantify the Gregg effect. RESULTS: Correcting for the Gregg effect from the transverse stiffness measurements obtained concomitantly with previously reported pressure-flow data in six specimens showed the following: using a linear fit to the pressure-flow data, the mean slope of the diastolic pressure-flow relationships decreased from 0.88 to 0.81 and 0.74 ml.min-1 x mmHg-1 during tetanisation at normal and reduced contractile levels, respectively. Correcting for the Gregg effect decreased the tetanised slopes to intermediate values of 0.85 and 0.79 ml.min-1 x mmHg-1, respectively. CONCLUSIONS: A small but clearly discernible portion of the shift in tetanised pressure-flow relationships is attributable to the Gregg effect. Similar conclusions pertained when quadratic regressions were fitted to the pressure-flow data.

Effect of tetanic myocardial contraction on coronary pressure-flow relationships.

Cardiac contraction causes a decrease in coronary flow. Despite many studies, it is still not clear what mechanism or mechanisms are responsible for this flow decrease. The phasic nature of myocardial contraction and the complexities intrinsic to intact heart preparations make it difficult to elucidate the mechanisms. We therefore studied coronary pressure-flow relationships during steady-state (tetanic) contractions in the maximally vasodilated isolated canine interventricular septum to see whether waterfall-type behavior is present. Using ryanodine and electrical stimulation allowed the production of reproducible and reversible tetani. This preparation minimizes the difficulties associated with transmural variations and also the effects of intramyocardial capacitance. Two separate protocols were performed to delineate the pressure-flow relationships in the passive and tetanized states. The first compared diastolic and tetanized pressure-flow relationships. In the second protocol, 2,3-butanedione monoxime was added to obtain an intermediate contractile level, thus allowing the comparison of two contractile states. Both the diastolic and tetanized pressure-flow relationships were curvilinear in the low-pressure range. Linear and nonlinear fits to the data showed that the primary effect of contraction was a shift of the pressure-flow relationships to higher pressures at a given flow. This effect was graded by the level of contractility and was independent of developed stress. Although other mechanisms may also be operative, these results support the presence of waterfall behavior in the coronary vascular bed.

Estimation of myocardial mechanical properties with dynamic transverse stiffness.

There are currently no validated methods for accurately estimating regional ventricular mechanical properties. We recently developed a dynamic indentation system that can determine dynamic transverse stiffness (the slope of the relation between the indentation stress and indentation strain during high frequency indentations) in as little as 10 msec. The apparatus consists of an indentation probe coupled to a linear-motor and a computerized control system. This indentation system was tested on beating, canine ventricular septa that were mounted in a biaxial system that could apply strains in the plane of the septum and measure the resulting in-plane stresses. The probe indented the septa with peak displacements of 0.1-0.5 mm at frequencies of 20 and 50 Hz. The transverse stiffness was shown to be related to the in-plane stress and stiffness in the isolated septa. Dynamic transverse stiffness was then used to study the effects of myocardial perfusion on passive tissue stiffness and on contractility. In addition, the transverse stiffness was studied in intact canine hearts during diastole, where it was related to the chamber stiffness. Thus, dynamic transverse stiffness appears to allow estimation of myocardial mechanical properties.

In-plane myocardial wall stress is not the primary determinant of coronary systolic flow impediment. A study in the isolated, perfused dog septum.

The hypothesis that ventricular in-plane tensile wall stresses are the major determinant of systolic coronary flow was investigated in this study. We measured coronary artery inflow in the maximally vasodilated bed of the isolated beating septum (n = 10) during two modes of contraction characterized by markedly different levels of developed in-plane stress. An increase in contractility was induced by changing from the control steady-state pacing state to a postextrasystolic potentiated state induced by a modified rapid pacing protocol. Over a range of increments of passive stretch, the systolic flow impediment versus the diastolic wall strain was described by an inverse linear relation. Despite the differences in developed in-plane wall stresses between the two modes of contraction (p less than 0.001), the slope and intercept of these relations in both the control and potentiated states were not different for the low versus high developed stress modes. The systolic flow impediment versus diastolic wall strain relation for the potentiated beats, compared with the control beats, was characterized by an increase in the intercept in both the low developed stress beats (p less than 0.05) and the high developed stress beats (p less than 0.05). These data indicate that the impediment to coronary flow during systole is not primarily determined by systolic myocardial in-plane tensile wall stresses but rather by the contractile state of the muscle.

Effect of wall stretch on coronary hemodynamics in isolated canine interventricular septum.

The effects of stretch on coronary pressure-flow relations are not well understood. To examine the role of wall stretch per se on coronary hemodynamics, we studied arterially perfused isolated canine interventricular septa in a noncontracting state with vasodilated vessels. We compared the hemodynamic parameters of zero-flow pressure and resistance during passive stretching in the circumferential and the base-to-apex directions alone as well as during simultaneous biaxial stretching in both directions. Even in the unloaded state the zero-flow pressure was positive. Any type of stretching significantly increased the zero-flow pressure and the resistance from their unloaded values. The pressure-flow responses also showed directional dependence. When stretches with matched strains or stresses in each direction were applied sequentially, the resistance increases corresponded to the direction of higher stress. Conversely, the zero-flow pressure response increase corresponded to the direction of greater strain. However, neither response correlated with a measure of global tissue stiffness. Thus there is a complex and tight mechanical interaction between the vessels and the surrounding tissue. These interactions, but not the tissue stiffness, are important determinants of coronary pressure-flow responses during stretch.

Systemic sclerosis (scleroderma): clinical, genetic, and serologic subsets.

Immunogenetic markers, autoantibodies, and clinical features were studied in 47 patients, 35 Caucasian and 12 black, with systemic sclerosis. Twenty-two had generalized scleroderma, while 25 had limited skin involvement. HLA-DR1 (RR = 2.1, p = 0.08) and DR5 (RR = 2.1, p = 0.08) were increased in Caucasian patients vs controls as was the supertypic specificity HLA-DRw52 (RR = 2.8, p = 0.02, pc = 0.04). HLA-DR6.1 was increased in black patients vs controls (RR = 15.4, p = 0.008, pc = 0.088). There were no significant increases in any of the complement allotypes in either racial group. Anticentromere antibody was noted in 10 patients, all Caucasian; 7 had limited disease. Anti-Scl-70 was noted in 4 patients; all had generalized disease (p = 0.036). HLA-DR2 was present in all anti-Scl-70 positive patients (RR = 22.5, p = 0.006). Our results suggest that clinical subsets of systemic sclerosis can be defined by genetic and serological markers.