Tachycardia, contractility and volume loading alter conventional indexes of coronary flow reserve, but not the instantaneous hyperemic flow versus pressure slope index.

OBJECTIVES AND BACKGROUND: Because measurements of flow reserve are often made in the setting of fluctuating hemodynamic variables that cause alterations in basal or hyperemic coronary blood flow, traditional flow reserve indexes may be difficult to interpret. Prior work in this laboratory has suggested that the instantaneous hyperemic flow versus pressure slope index is a more hemodynamically stable alternative to measures of flow reserve. Although this index has no hemodynamic dependence on changes in aortic pressure, the extent to which it is affected by other factors that alter myocardial work is unknown. Therefore, the purpose of this investigation was to analyze the effects of tachycardia (induced by atrial pacing at 10 beats/min above the basal heart rate), dobutamine infusion (10 micrograms/kg per min) and saline solution volume loading (500 ml) on measurements of traditional coronary flow reserve, the resistance reserve ratio and the instantaneous hyperemic flow versus pressure slope index. METHODS: Twenty-nine open chest anesthetized dogs were studied in four sequential stages: baseline, tachycardia, dobutamine infusion and saline solution volume loading. Traditional coronary flow reserve was defined as the ratio of hyperemic coronary blood flow to basal coronary blood flow, the resistance reserve ratio as the ratio of basal coronary resistance to hyperemic coronary resistance and the instantaneous hyperemic flow versus pressure slope index as the slope of the instantaneous relation between diastolic hyperemic coronary blood flow and diastolic aortic pressure normalized by perfusion bed weight. Hyperemia was induced by intravenous adenosine infusion (1 mg/kg per min). Mean aortic pressure was kept nearly constant during the interventions by manipulation of an aortic clamp or a vena caval snare. RESULTS: The final study group comprised 18 open chest dogs. Coronary flow reserve was significantly decreased by tachycardia (3.7 +/- 1.2 to 3.0 +/- 1.2, p < 0.0001), decreased by saline solution volume loading (3.2 +/- 1.3 vs. 2.7 +/- 0.8, p = 0.06) and significantly increased by dobutamine infusion (3.2 +/- 1.3 to 4.3 +/- 1.5, p < 0.0005). In contrast, the instantaneous hyperemic flow versus pressure slope index was not affected by the three interventions (7.4 +/- 3.1 vs. 7.3 +/- 3.3, 7.4 +/- 3.2 vs. 7.4 +/- 3.4 and 7.5 +/- 3.1 vs. 7.3 +/- 3.4, respectively, all p = NS). The changes observed in the resistance reserve ratio were of similar or greater magnitude and significance to the changes in coronary flow reserve. CONCLUSIONS: The instantaneous hyperemic flow versus pressure slope index offers a hemodynamically stable alternative to measures of vascular reserve because it is independent of moderate changes in heart rate, contractility and volume loading that may occur commonly in clinical situations.

Sensitivity and reproducibility of the instantaneous hyperemic flow versus pressure slope index compared to coronary flow reserve for the assessment of stenosis severity.

The objective of this study was to compare the reproducibility and sensitivity of the instantaneous hyperemic flow versus pressure slope index (i-HFVP) and coronary flow reserve (CFR). The i-HFVP is the slope of the relationship between diastolic hyperemic coronary flow and diastolic aortic pressure, normalized for bed weight. In contrast to CFR (the ratio of hyperemic to basal coronary flow), the i-HFVP has been shown to be independent of changes in aortic pressure, heart rate, contractility, and preload. To compare reproducibility, i-HFVP and CFR were measured three times in eight dogs instrumented with high-fidelity micromanometers and flow probes, allowing for full hemodynamic recovery between phases (15 to 40 minutes). Maximum hyperemia was induced with intravenous adenosine. The sensitivity of i-HFVP and CFR was assessed in 16 instrumented dogs. Measurements were performed for one basal state and for five subcritical incremental stenoses created with a screw occluder during hyperemia. Intraclass variability correlation coefficients were 0.96 for i-HFVP but only 0.56 for CFR. Both i-HFVP and CFR showed significant decrements with each increasing stenosis. However, the percentage reductions at each level were significantly greater for the i-HFVP. The difference in percentage reduction favoring increased sensitivity of the i-HFVP ranged from 11% to 23%. It was concluded that the i-HFVP is more reproducible and more sensitive to the presence of stenoses than CFR.

Instantaneous hyperemic flow-versus-pressure slope index. Microsphere validation of an alternative to measures of coronary reserve.

BACKGROUND: The instantaneous hyperemic flow-versus-pressure (i-HFVP) slope index is a new method of assessing maximal coronary conductance and can be used as an alternative to conventional measures of coronary reserve. The i-HFVP slope index is determined by measuring the slope of the linear diastolic segment of the relation between instantaneous aortic pressure and hyperemic coronary flow. METHODS AND RESULTS: To validate the i-HFVP slope index as a measure of maximal coronary conductance, we compared this method with a microsphere-derived measurement of maximal coronary conductance (m-HFVP slope index) by determining the slope of the least-squares regression line of the data points for coronary flow during maximal hyperemia and four or five steady-state alterations of aortic pressure in 43 dogs (open-chest, anesthetized preparations) with or without coronary stenoses. The i-HFVP slope index demonstrated no dependence on heart rate, left ventricular end-diastolic pressure, or mean aortic pressure and was highly reproducible within the groups studied (intraclass correlation coefficient, 0.86 for normal arteries, 0.87 for stenotic arteries, and 0.93 for combined groups; for all coefficients, p less than 0.001). The i-HFVP slope index was significantly decreased in the presence of a stenosis (10.3 +/- 3.9 for normal arteries versus 3.6 +/- 1.6 for stenotic arteries, p less than 0.001) as was the transmural m-HFVP slope index (8.9 +/- 4.6 for normal arteries versus 5.3 +/- 3.1, p less than 0.01). Of special importance, the i-HFVP slope index measurement for normal arteries was not significantly different from the transmural and subendocardial m-HFVP slope index measurements (10.3 +/- 3.9 versus 8.9 +/- 4.6 and 9.2 +/- 5.7, respectively). For stenotic arteries, the i-HFVP slope index measurement was also not significantly different from the transmural and subendocardial m-HFVP slope index measurements (3.6 +/- 1.6 versus 5.3 +/- 3.1 and 4.1 +/- 2.3, respectively). The i-HFVP slope index correlated best with subendocardial m-HFVP slope index measurements (correlation coefficient, 0.57; p less than 0.001). When the 95% confidence intervals for the transmural (or subendocardial) m-HFVP slope index in normal arteries were compared with the i-HFVP slope index values, the latter demonstrated a systematic trend to overestimate the m-HFVP slope index. In the presence of a stenosis, this effect was minimized, and the slope values were nearly identical. CONCLUSIONS: The i-HFVP slope index correlates most closely with subendocardial coronary conductance; the index is a hemodynamically independent measure of coronary reserve that is reproducible over a broad range of aortic pressures; and the methodology is applicable to an intact circulation in experimental preparations and may with future developments also prove useful in humans.