Yasunori Nakayama

Reflection in the arterial system and the risk of coronary heart disease.

BACKGROUND Although it was reported that the augmentation index and inflection time are closely related to reflection in the arterial system and large artery function, it is not known whether these indices of the ascending aortic pressure waveform increase the risk of coronary heart disease (CHD). The purpose of this study was to evaluate whether the aortic reflection of the ascending aortic pressure waveform is related to an increased risk of CHD. METHODS We enrolled 190 men and women who had chest pain, normal contractions, no local asynergy, and no history of myocardial infarction. We measured the ascending aortic pressure using a fluid-filled system. The inflection time was defined as the time interval from initiation of a systolic pressure waveform to the inflection point. We investigated the association between the inflection time and augmentation index of the ascending aorta and the risk of CHD. RESULTS Both the inflection time and augmentation index were associated with an increased risk of CHD. The crude prevalence rates of CHD were 66.0% for the shortest quartile and 10.6% for the longest quartile of the inflection time, and 17.0% for the lowest quartile and 40.4% for the highest quartile of the augmentation index. The multiple-adjusted odds ratio of CHD was 30.8 (95% confidence interval [CI] 7.43-128.05) for the shortest quartile of the inflection time compared with the longest quartile and was 3.82 (95% CI 1.26-11.59) for the highest quartile of the augmentation index compared with the lowest quartile. CONCLUSIONS The augmentation index and inflection time were associated with an increased risk of CHD.

Characteristics of Pulmonary Artery Pressure Waveform for Differential Diagnosis of Chronic Pulmonary Thromboembolism and Primary Pulmonary Hypertension

OBJECTIVES The accurate diagnosis of chronic pulmonary thromboembolism (CPTE) is a prerequisite for life-saving surgical interventions. To help in the differential diagnosis of CPTE and primary pulmonary hypertension (PPH), we characterized the configuration of the pulmonary artery pressure waveform. BACKGROUND Because CPTE predominantly involves the proximal arteries, whereas PPH involves the peripheral arteries, we hypothesized that patients with CPTE would have stiff or high resistance proximal arteries, whereas those affected by PPH would have high resistance peripheral arteries. These differences in the primary lesions would make arterial pulsatility relative to mean pressure larger in CPTE than in PPH. METHODS In 34 patients with either CPTE (n = 22) or PPH (n = 12) whose pulmonary systolic pressure was > or = 50 mm Hg, we measured pulmonary artery pressure using a fluid-filled system that included a balloon-tipped flow-directed catheter. RESULTS To quantify the magnitude of pulsatility relative to mean pressure, we normalized pulse pressure by mean pressure, hereinafter referred to as fractional pulse pressure (PPf). PPf was markedly higher in CPTE than in PPH (mean [+/-SD] 1.41 +/- 0.20 and 0.80 +/- 0.18, respectively, p < 0.001) and was diagnostic in separating the two groups without overlap. Similarly, the coefficient of variation of pulmonary artery pressure also separated the two groups without overlap (0.45 +/- 0.06 and 0.25 +/- 0.06, respectively, p < 0.001). Fractional time to half the area under the pressure curve separated the two groups reasonably well (0.35 +/- 0.02 and 0.43 +/- 0.03, respectively, p < 0.001). CONCLUSIONS The analysis of pulsatility of pulmonary artery pressure is useful in the differential diagnosis of CPTE and PPH.

Pulsatility of ascending aortic blood pressure waveform is associated with an increased risk of coronary heart disease

BACKGROUND Although it was reported that pulse pressure of the peripheral artery could differentiate patients with coronary heart disease (CHD) from those without CHD, it is not known whether pulsatility of the ascending aortic pressure waveform differentiates patients with CHD from those without CHD. The purpose of this study was to evaluate whether the pulsatility of ascending aortic pressure is associated with an increased risk of CHD. METHODS For this study, we enrolled 293 subjects who had chest pain, normal contractions, no local asynergy, and no history of myocardial infarction. We measured the ascending aortic pressure using a fluid-filled system. To quantify the relative magnitude of the pulsatile to mean artery pressure, we normalized the pulse pressure to the mean pressure and referred to this value as the fractional pulse pressure (PPf). We investigated the association between the PPf and the risk of CHD. RESULTS The PPf of the ascending aorta was associated with an increased risk of CHD. The multiple-adjusted odds ratio of CHD was 2.93 (95% CI, 1.44 to 5.94) for the middle tertile of the PPf level and was 3.93 (95% CI, 1.74 to 8.85) for the highest tertile compared with the lowest tertile. CONCLUSION Ascending aortic pulsatility is related to an increased risk of CHD.

HUMAN NEUTROPHILS EXPRESS MESSENGER RNA OF VITAMIN D RECEPTOR AND RESPOND TO 1α,25-DIHYDROXYVITAMIN D3

ABSTRACT 1α,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been shown to modulate the production of various cytokines or the expression of certain differentiation markers in human T cells or monocytes. Its effects on neutrophils, however, are poorly understood. In this paper, we show several lines of evidence indicating that neutrophils express functional vitamin D receptors (VDR). Sort-purified neutrophils from human peripheral blood expressed VDR mRNA at a level comparable to that of monocytes. As reported to occur in monocytes, protein expression of CD14 on the cell surface of neutrophils was augmented when the cells were incubated with 1,25(OH)2D3. To investigate the physiological roles for VDR in neutrophils, we investigated possible modulating effects of 1,25(OH)2D3 on the expression of several genes in lipopolysaccharide-stimulated neutrophils by using differential display analysis. Of the genes we identified, trappin-2/elafin/SKALP, which was originally reported to be an inhibitor of elastase, was induced in neutrophils by lipopolysaccharide, but was suppressed significantly in the presence of 1,25(OH)2D3. Under the same conditions, interleukin-1β expression was also inhibited. These findings suggest that 1,25(OH)2D3 has a potential to affect the inflammatory process by modulating the expression of neutrophil genes.

Pulmonary artery reflection for differentially diagnosing primary pulmonary hypertension and chronic pulmonary thromboembolism

OBJECTIVES The purpose of this investigation was to differentiate chronic pulmonary thromboembolism (CPTE) from primary pulmonary hypertension (PPH) by means of the indexes of pulmonary arterial reflection. BACKGROUND These differences in the primary lesions would make pulmonary artery reflection occur earlier in CPTE than in PPH. Although the analysis of pulsatility of pulmonary arterial pressure is useful in the differential diagnosis of PPH and CPTE, it is not known whether the analysis of pulmonary artery reflection can differentiate CPTE from PPH. METHODS Since CPTE predominantly involves the proximal arteries, whereas PPH involve the peripheral arteries, we hypothesized that patients with CPTE have a large augmentation index and a short inflection time. For this study, we enrolled 62 patients who had CPTE (31 patients) and PPH (31 patients). We measured pulmonary arterial pressure using a fluid filled system that included a balloon-tipped flow directed catheter. To quantify the pulmonary artery reflection, we used the augmentation index and inflection time. RESULTS The augmentation index was markedly higher in CPTE than it was in PPH (27.4% +/- 15.2% [SD] and -25.1% +/- 26.9%, respectively, p < 0.001) and was diagnostic in separating the two groups. Inflection time separated the two groups reasonably well (97 +/- 20 ms and 210 +/- 49 ms, respectively, p < 0.001). CONCLUSIONS The analysis of pulmonary arterial reflection is useful in the differential diagnosis of CPTE and PPH.

Noninvasive differential diagnosis between chronic pulmonary thromboembolism and primary pulmonary hypertension by means of Doppler ultrasound measurement.

OBJECTIVES The purpose of this investigation was to differentiate chronic pulmonary thromboembolism (CPTE) from primary pulmonary hypertension (PPH) by using noninvasive Doppler ultrasound techniques. BACKGROUND A recent investigation in our laboratory has indicated that the pulmonary artery (PA) pressure waveform conveys significant information that can be used to differentiate CPTE from PPH. Pulse pressure was markedly larger in CPTE than in PPH, indicating that the major occlusive site is central in CPTE and peripheral in PPH. METHODS In 19 patients with CPTE and 16 patients with PPH, we estimated PA systolic pressure and diastolic pressure from the velocities of tricuspid regurgitation and pulmonary regurgitation, respectively. RESULTS Estimated systolic pressure was not significantly different between CPTE and PPH (mean [+/-SD] 81+/-20 and 79+/-21 mm Hg, respectively, p=NS). Pulse pressure normalized by systolic pressure was higher in CPTE than in PPH (0.82+/-0.05 vs. 0.63+/-0.10, respectively, p < 0.01). Pulse pressure normalized by mean pressure was also higher in CPTE than in PPH (1.65+/-0.30 vs. 0.94+/-0.25, respectively, p < 0.01). Receiver operating characteristic analysis indicated that pulse pressure normalized by systolic pressure separated CPTE from PPH, with a sensitivity of 0.95 and a specificity of 1.00. Pulse pressure normalized by mean pressure also separated them, with a sensitivity of 0.95 and a specificity of 1.00. CONCLUSIONS Normalized pulse pressures estimated from Doppler ultrasound measurements enable us to noninvasively differentiate between CPTE and PPH.

Dynamic sympathetic regulation of left ventricular contractility studied in the isolated canine heart

We investigated the dynamic sympathetic regulation of left ventricular end-systolic elastance (Ees) using an isolated canine ventricular preparation with functioning sympathetic nerves intact. We estimated the transfer function from both stellate ganglion stimulation to Ees and ganglion stimulation to heart rate (HR) for both left and right ganglia by means of the white noise approach and transformed those transfer functions into corresponding step responses. The HR response was much larger with right sympathetic stimulation than with left sympathetic stimulation (4.3 +/- 1.4 vs. 0.7 +/- 0.6 beats . min-1 . Hz-1, P < 0.01). In contrast, the Ees responses without pacing were not significantly different between left and right sympathetic stimulation (0.72 +/- 0.34 vs. 0.76 +/- 0. 42 mmHg . ml-1 . Hz-1). Fixed-rate pacing significantly decreased the Ees response to right sympathetic stimulation (0.53 +/- 0.43 mmHg . ml-1 . Hz-1, P < 0.01), but not to left sympathetic stimulation (0.67 +/- 0.32 mmHg . ml-1 . Hz-1, not significant). Although the mechanism by which the sympathetic nervous system regulates cardiac contractility is different depending on whether the left or right sympathetic nerves are activated, this difference does not affect the apparent response of Ees to dynamic sympathetic stimulation.We investigated the dynamic sympathetic regulation of left ventricular end-systolic elastance ( E es) using an isolated canine ventricular preparation with functioning sympathetic nerves intact. We estimated the transfer function from both stellate ganglion stimulation to E es and ganglion stimulation to heart rate (HR) for both left and right ganglia by means of the white noise approach and transformed those transfer functions into corresponding step responses. The HR response was much larger with right sympathetic stimulation than with left sympathetic stimulation (4.3 ± 1.4 vs. 0.7 ± 0.6 beats ⋅ min-1 ⋅ Hz-1, P < 0.01). In contrast, the E es responses without pacing were not significantly different between left and right sympathetic stimulation (0.72 ± 0.34 vs. 0.76 ± 0.42 mmHg ⋅ ml-1 ⋅ Hz-1). Fixed-rate pacing significantly decreased the E es response to right sympathetic stimulation (0.53 ± 0.43 mmHg ⋅ ml-1 ⋅ Hz-1, P < 0.01), but not to left sympathetic stimulation (0.67 ± 0.32 mmHg ⋅ ml-1 ⋅ Hz-1, not significant). Although the mechanism by which the sympathetic nervous system regulates cardiac contractility is different depending on whether the left or right sympathetic nerves are activated, this difference does not affect the apparent response of E es to dynamic sympathetic stimulation.

Mechanoenergetics of the negative inotropism of isoflurane in the canine left ventricle : No O2 wasting effect

Background: The mechanisms underlying the negative inotropic effects of isoflurane are incompletely understood. One suggested mechanism is that isoflurane may decrease Ca2+ sensitivity of contractile proteins. If so, more free calcium would be needed to activate contractile proteins to the same degree, which would impose a greater requirement for myocardial oxygen consumption used in the cycling of calcium. In this study, the authors use the excised, cross‐circulated, canine heart model and the volume servopump technique to measure the effects of isoflurane on Emax (a contractile index) and on the relationship between pressure‐volume area (PVA, a measure of total mechanical energy) and myocardial oxygen consumption per beat (VO2). Methods: Effects of intracoronary isoflurane infused via a precoronary oxygenator on myocardial mechanoenergetics were studied during isovolumic contractions. The authors measured left ventricular (LV) pressure, LV volume, coronary flow, and arteriovenous oxygen content difference and computed Emax, VO2 and PVA at 0, 1.0, 1.5, and 2.0% isoflurane. From these data, the authors obtained oxygen costs of PVA and Emax in control subjects and in those receiving 2.0% isoflurane. Results: Emax, PVA, and VO2 dose‐dependently decreased by similar degrees (P < 0.05). Isoflurane did not change the oxygen costs at 1.5% and 2.0% concentration (P < 0.05). Conclusions: These mechanoenergetic findings suggest that the primary method by which isoflurane decreases contractility is not by decreasing Ca sup 2+ sensitivity of contractile proteins but mainly by decreasing Ca2+ handling in the excitation‐contraction coupling without myocardial oxygen wasting effect.

Inflection Point of Ascending Aortic Waveform Is a Powerful Predictor of Restenosis After Percutaneous Transluminal Coronary Angioplasty

BACKGROUND Although it was reported that the pulsatility of ascending aortic pressure is closely related to restenosis after percutaneous transluminal coronary angioplasty (PTCA), it is not known whether the reflection period of ascending aortic pressure can predict restenosis after PTCA. The purpose of this study was to evaluate whether reflection in the arterial system can be used to predict restenosis after PTCA. METHODS We used the inflection point as the reflection period index and measured the coronary artery diameter, aortic pressure, and inflection time before PTCA. We defined the inflection time as the time interval from the initiation of systolic pressure waveform to the inflection point. We prospectively investigated the effect of inflection time in relation to the subsequent risk of restenosis after PTCA in patients with coronary artery disease. RESULTS Crude cumulative incidence rates of restenosis were 74.1% for the lowest, 33.3% for the middle, and 26.1% for the highest tertile of inflection point levels. After adjustments for age, gender, smoking habits, hypertension, type 2 diabetes, hypercholesterolemia, old myocardial infarction, vessel location, post-minimal lumen diameter, heart rate, and ejection fraction, the odds ratio of restenosis was 6.99 (95% confidence interval, 1.54 to 31.7) for the lowest tertile of the inflection time level compared with the highest tertile level. CONCLUSIONS Inflection time is a powerful predictor of restenosis after PTCA.

Effects of Intracoronary Fentanyl on Left Ventricular Mechanoenergetics in the Excised Cross-circulated Canine Heart

Background: It is still unclear whether fentanyl directly alters left ventricular (LV) contractility and oxygen consumption. This is because of the difficulty in defining and evaluating contractility and energy use independently of ventricular loading conditions and heart rate in beating whole hearts. Methods: This study was conducted to clarify the mechanoenergetic effects of intracoronary fentanyl in six excised cross‐circulated canine hearts. The authors used the framework of the Emax (a contractility index)‐PVA (systolic pressure‐volume area, a measure of total mechanical energy)‐VO2 (myocardial oxygen consumption per beat) relationship practically independent of ventricular loading conditions. The authors measured LV pressure, volume, coronary flow, and arteriovenous oxygen content difference to calculate Emax, PVA, and VO2. They first obtained the VO2 ‐PVA relationship for varied LV volumes at control Emax. The authors then obtained the VO2 ‐PVA relationship at a constant LV volume, whereas coronary blood fentanyl concentration was increased in steps up to 240 ng/ml. Finally, they obtained the VO2 ‐PVA relationship for varied LV volumes at the final dose of fentanyl. Results: Fentanyl at any concentrations did not significantly change Emax, PVA, and VO2 from the control. The linear end‐systolic pressure‐volume relations and their slopes were virtually the same between the control and fentanyl volume loading in each heart. Further, either the slope (oxygen cost of PVA) or the VO2 intercept (unloaded VO2) of the linear VO2 ‐PVA relationship remained unchanged by fentanyl. Conclusions: These results indicate that intracoronary fentanyl produces virtually no effects on LV mechanoenergetics for a wide range of its blood concentration.