Hyperemic vs non-hyperemic indexes discordance: Role of epicardial and microvascular resistance (HyperDisco Study).

BACKGROUND: Literature reports a 20 % discordance between hyperemic (FFR) and non-hyperemic indexes (NHi) of coronary stenosis lesions. This work aims to develop and test clinically, a formula relating FFR and NHi (including iFR, RFR and Pd/Pa) to study their discordance. METHODS: We conducted a prospective, single-center, clinical study enrolling all patients undergoing full coronary physiology assessment with Coroventis CoroFlow Cardiovascular System (Abbott Vascular, St. Paul, Minnesota) to validate the developed formula: [Formula: see text] where IMR(BMR) is the hyperemic (basal) microvascular resistance and HSR(BSR) is the hyperemic (basal) stenosis resistance. RESULTS: A total of 51 patients were enrolled, 72 % male, average age 67.4 ± 8.9. Mean hemodynamic data were: FFR 0.87 ± 0.07, iFR 0.93 ± 0.05, RFR 0.91 ± 0.05, Pd/Pa 0.92 ± 0.05, BMR 76.6 ± 51.6 mmHg*s, IMR 28.4 ± 22.8 mmHg*s, BSR 5.5 ± 4.7 mmHg, HSR 3.8 ± 2.9 mmHg*s, coronary flow reserve (CFR) 2.9 ± 1.6, resistive reserve ratio (RRR) 3.3 ± 2.0. Lin's Concordance and Bland Altman analysis showed an optimal correlation between measured and estimated data. Sensitivity analysis showed that: (1) FFR can underestimate epicardial stenosis severity leading to FFR- vs NHi + discordance in case of elevated IMR, (2) NHi can overestimate epicardial stenosis severity leading to FFR- vs NHi + in the case of low BMR, (3) if BSR > HSR, FFR- vs NHi + discordance can occur, while if BSR < HSR, FFR+ vs NHi- discordance can occur. CONCLUSION: (1) NHi can be more reliable in case of elevated IMR; (2) FFR-CFR combination can be more reliable for low BMR occurring to compensate an epicardial stenosis; (3) NHi-CFR combination can be more reliable when BSR > HSR, while FFR-CFR combination can be more reliable when BSR < HSR. The combination between pressure and flow indexes (FFR-CFR or NHi-CFR) is more reliable when compensatory mechanisms occur.

Sensitivity Analysis of Single Beat Left Ventricular Elastance Estimation by Chen Method.

INTRODUCTION: Left ventricular (LV) end-systolic elastance (Ees) can be estimated using single-beat (Ees(sb)) Chen method, employing systolic and diastolic arm-cuff pressures, stroke volume (SV), ejection fraction and estimated normalized ventricular elastance at arterial end-diastole. This work aims to conduct a sensitivity analysis of Chen formula to verify its reliability and applicability in clinical scenario. METHODS: Starting from a baseline condition, we evaluated the sensitivity of Ees(sb) to the parameters contained in the formula. Moreover, a mathematical model of the cardiovascular system was used to evaluate the sensitivity of Ees(sb) to end-diastolic LV elastance (Eed), Ees, arterial systemic resistance (Ras) and heart rate (HR). RESULTS: In accordance with Ees definition, Ees(sb) increases by increasing aortic pressure and pre-ejection time, reaching the highest value for a pre-ejection time = 40 ms, and then decreases. In contrast with Ees definition, Ees(sb) increases (from 3.21 mmHg/mL to 12.15 mmHg/mL) by increasing the LV end-systolic volume and decreases by increasing the SV. In the majority of the analysis with the mathematical model, Ees was underestimated using the Chen method: by increasing Ees (from 0.5 to 2.5 mmHg/mL), Ees(sb) passes only from 0.56 to 1.54 mmHg/mL. Ees(sb) increases for higher Eed (from 1.03 to 2.33 mmHg/mL). Finally, Ees(sb) decreases (increases) for HR < 50 bpm (< 50 bpm), and for Ras < 1100 mmHg/gcm4 (> 1100 mmHg/gcm4). CONCLUSION: Unexpectedly Ees(sb) increases for higher LV end-systolic volume and decreases for higher SV. These results contrast with Ees definition, which is the ratio between the LV end-systolic pressure and the LV end-systolic volume. Moreover, Ees(sb) is influenced by cardiocirculatory parameters such as LV Eed, HR, Ras, ejection time, and pre-ejection time. Finally, Ees(sb) computed with the model output often underestimates model Ees.

Studies on antihistaminic action. II: In vitro and in vivo effect of chlorpheniramine and its analogs on the uptake and retention of 5-hydroxytryptamine by rabbit blood platelets.

We have previously shown that the antihistaminic drug, chlorpheniramine maleate (CTM) increased blood histamine levels more rapidly than it did the blood 5-hydroxytryptamine (5-HT) levels in the rabbit (Sankar, Li and Santare, 1974). The present studies show that, while the in vitro addition of CTM to isolated rabbit blood platelets inhibited the platelet uptake of labeled 5-HT-14C, its administration to rabbits increased such in vitro uptake by platelets isolated from recipient animals. This is possibly due to the enhancement of release (depletion) of 5-HT from platelets in vivo. Such depleted platelets, will take up larger amounts of 5-HT on in vitro incubation. Our studies also show increased levels of blood 5-HT within minutes after administration of CTM to rabbits, further indicating that CTM deplets the platelets of their 5-HT on in vivo administration. Our present studies show that D-CTM is more active than brompheniramine in this system, while the fluorine derivative is least active. It is postulated that the antecedent release of histamine and 5-HT from tissues by antihistamines, renders further anaphylactic challenge or hypersensitivity episode less severe.

Quantum chemical studies on drug action V: Involvement of structure-activity, quantum chemical, and hydrophobicity factors in thrombocyte uptake of 5-hydroxytryptamine.

Inhibition of the uptake of 5-hydroxytryptamine (serotonin) in the thrombocyte by various tryptamine derivatives was investigated. The activity depended on the nature and position of the substituent. This activity was correlated with the total orbital energy and hydrophobicity factors. Other quantum parameters, such as the highest occupied molecular orbital energy and the lowest empty molecular orbital energy, failed to correlate. The possible involvement of two receptor sites that are sterically and electronically dissimilar is postulated because compounds fell into two distinct groups. The hydrophobicity factor was important in only one group of compounds, while the electronic factor was important in both.