Early Hyperdynamic Sepsis Alters Coronary Blood Flow Regulation in Porcine Fecal Peritonitis

Background: Sepsis is a common condition known to impair blood flow regulation and microcirculation, which can ultimately lead to organ dysfunction but such contribution of the coronary circulation remains to be clarified. We investigated coronary blood flow regulatory mechanisms, including autoregulation, metabolic regulation, and endothelial vasodilatory response, in an experimental porcine model of early hyperdynamic sepsis.Methods: Fourteen pigs were randomized to sham (n = 7) or fecal peritonitis-induced sepsis (n = 7) procedures. At baseline, 6 and 12 h after peritonitis induction, the animals underwent general and coronary hemodynamic evaluation, including determination of autoregulatory breakpoint pressure and adenosine-induced maximal coronary vasodilation for coronary flow reserve and hyperemic microvascular resistance calculation. Endothelial-derived vasodilatory response was assessed both in vivo and ex vivo using bradykinin. Coronary arteries were sampled for pathobiological evaluation.Results: Sepsis resulted in a right shift of the autoregulatory breakpoint pressure, decreased coronary blood flow reserve and increased hyperemic microvascular resistance from the 6th h after peritonitis induction. In vivo and ex vivo endothelial vasomotor function was preserved. Sepsis increased coronary arteries expressions of nitric oxide synthases, prostaglandin I2 receptor, and prostaglandin F2α receptor.Conclusion: Autoregulation and metabolic blood flow regulation were both impaired in the coronary circulation during experimental hyperdynamic sepsis, although endothelial vasodilatory response was preserved.

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Overview of mathematical modeling of myocardial blood flow regulation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00563.2019 ◽

2020 ◽

Vol 318 (4) ◽

pp. H966-H975

Author(s):

Ravi Namani ◽

Yoram Lanir ◽

Lik Chuan Lee ◽

Ghassan S. Kassab

Keyword(s):

Blood Flow ◽

Coronary Blood Flow ◽

Coronary Flow ◽

Oxygen Demand ◽

Flow Regulation ◽

Flow Reserve ◽

Arterial Blood ◽

Blood Flow Regulation ◽

Highly Nonlinear ◽

Coronary Flow Regulation

The oxygen consumption by the heart and its extraction from the coronary arterial blood are the highest among all organs. Any increase in oxygen demand due to a change in heart metabolic activity requires an increase in coronary blood flow. This functional requirement of adjustment of coronary blood flow is mediated by coronary flow regulation to meet the oxygen demand without any discomfort, even under strenuous exercise conditions. The goal of this article is to provide an overview of the theoretical and computational models of coronary flow regulation and to reveal insights into the functioning of a complex physiological system that affects the perfusion requirements of the myocardium. Models for three major control mechanisms of myogenic, flow, and metabolic control are presented. These explain how the flow regulation mechanisms operating over multiple spatial scales from the precapillaries to the large coronary arteries yield the myocardial perfusion characteristics of flow reserve, autoregulation, flow dispersion, and self-similarity. The review not only introduces concepts of coronary blood flow regulation but also presents state-of-the-art advances and their potential to impact the assessment of coronary microvascular dysfunction (CMD), cardiac-coronary coupling in metabolic diseases, and therapies for angina and heart failure. Experimentalists and modelers not trained in these models will have exposure through this review such that the nonintuitive and highly nonlinear behavior of coronary physiology can be understood from a different perspective. This survey highlights knowledge gaps, key challenges, future research directions, and novel paradigms in the modeling of coronary flow regulation.

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Recovery of blood flow regulation in microvascular resistance networks during regeneration of mouse gluteus maximus muscle

The Journal of Physiology ◽

10.1113/jp277247 ◽

2019 ◽

Vol 597 (5) ◽

pp. 1401-1417 ◽

Cited By ~ 1

Author(s):

Charmain A. Fernando ◽

Aaron M. Pangan ◽

DDW Cornelison ◽

Steven S. Segal

Keyword(s):

Blood Flow ◽

Gluteus Maximus ◽

Flow Regulation ◽

Blood Flow Regulation ◽

Gluteus Maximus Muscle ◽

Microvascular Resistance

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Isoflurane and Coronary Blood Flow Regulation

Anesthesia, The Heart and the Vascular System - Developments in Critical Care Medicine and Anesthesiology ◽

10.1007/978-94-009-3295-1_19 ◽

1987 ◽

pp. 173-177

Author(s):

Sebastian Reiz

Keyword(s):

Blood Flow ◽

Coronary Blood Flow ◽

Flow Regulation ◽

Blood Flow Regulation

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A novel method for measuring absolute coronary blood flow and microvascular resistance in patients with ischaemic heart disease

Cardiovascular Research ◽

10.1093/cvr/cvaa220 ◽

2020 ◽

Cited By ~ 2

Author(s):

Paul D Morris ◽

Rebecca Gosling ◽

Iwona Zwierzak ◽

Holli Evans ◽

Louise Aubiniere-Robb ◽

...

Keyword(s):

Blood Flow ◽

Heart Disease ◽

Coronary Flow ◽

Microvascular Disease ◽

Flow Reserve ◽

Catheter Laboratory ◽

Novel Method ◽

Microvascular Resistance

Abstract Aims Ischaemic heart disease is the reduction of myocardial blood flow, caused by epicardial and/or microvascular disease. Both are common and prognostically important conditions, with distinct guideline-indicated management. Fractional flow reserve (FFR) is the current gold-standard assessment of epicardial coronary disease but is only a surrogate of flow and only predicts percentage flow changes. It cannot assess absolute (volumetric) flow or microvascular disease. The aim of this study was to develop and validate a novel method that predicts absolute coronary blood flow and microvascular resistance (MVR) in the catheter laboratory. Methods and results A computational fluid dynamics (CFD) model was used to predict absolute coronary flow (QCFD) and coronary MVR using data from routine invasive angiography and pressure-wire assessment. QCFD was validated in an in vitro flow circuit which incorporated patient-specific, three-dimensional printed coronary arteries; and then in vivo, in patients with coronary disease. In vitro, QCFD agreed closely with the experimental flow over all flow rates [bias +2.08 mL/min; 95% confidence interval (error range) −4.7 to +8.8 mL/min; R2 = 0.999, P < 0.001; variability coefficient <1%]. In vivo, QCFD and MVR were successfully computed in all 40 patients under baseline and hyperaemic conditions, from which coronary flow reserve (CFR) was also calculated. QCFD-derived CFR correlated closely with pressure-derived CFR (R2 = 0.92, P < 0.001). This novel method was significantly more accurate than Doppler-wire-derived flow both in vitro (±6.7 vs. ±34 mL/min) and in vivo (±0.9 vs. ±24.4 mmHg). Conclusions Absolute coronary flow and MVR can be determined alongside FFR, in absolute units, during routine catheter laboratory assessment, without the need for additional catheters, wires or drug infusions. Using this novel method, epicardial and microvascular disease can be discriminated and quantified. This comprehensive coronary physiological assessment may enable a new level of patient stratification and management.

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Quantifying coronary microvascular disease: assessing absolute microvascular resistance reserve (MRR) by continuous coronary thermodilution

European Heart Journal ◽

10.1093/ehjci/ehaa946.1282 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

E Gallinoro ◽

I Colaiori ◽

G Di Gioia ◽

S Fournier ◽

M Kodeboina ◽

...

Keyword(s):

Blood Flow ◽

Coronary Blood Flow ◽

Infusion Rate ◽

Guide Wire ◽

Microvascular Disease ◽

Individual Values ◽

Flow Reserve ◽

Absolute Flow ◽

Significant Difference ◽

Microvascular Resistance

Abstract Background and aim Hyperemic absolute coronary blood flow (in mL/min) can be safely and reproducibly measured with intracoronary continuous thermodilution of saline at room temperature at an infusion rate of 20 mL/min. This study aims at assessing whether continuous thermodilution can also measure resting flow and microvascular resistance. Methods and results In 87 coronary arteries (58 patients) with angiographic non-significant stenoses absolute flow was assessed by continuous thermodilution of saline at infusion rates of 10 mL/min and 20 mL/min using a pressure/temperature sensored guide wire, a dedicated infusion catheter and a dedicated software. In addition, in 26 arteries, average peak velocity (APV) was measured simultaneously using an intracoronary Doppler-wire. There was no significant difference between Pd/Pa at baseline and during saline infusion at 10 mL/min, (0.95±0.053 vs 0.94±0.054, respectively (p=0.53) and there was no significant difference in APV at baseline and during the infusion of saline at 10 mL/min (22.2±8.40 vs 23.2±8.39 cm/s, respectively, p=0.63), thus indicating presence of resting coronary blood flow during the infusion of 10 mL/min of saline. In contrast, at an infusion rate of 20 mL/min, a significant decrease in Pd/Pa was observed compared to baseline: (0.85±0.089 vs 0.95±0.053, respectively, p<0.001) and a significant increase in APV was observed (22.2±8.4 cm/s to 57.8±25.5 cm/s, respectively, p<0.001). The coronary flow reserve (CFR) calculated by thermodilution and by Doppler flow velocity were similar (2.73±0.85 vs 2.72±1.07, respectively) and their individual values correlated closely (r=0.87, 95% CI 0.72–0.94, p<0,001). Microvascular resistance (Rμ), defined as the distal coronary pressure divided by the absolute flow was calculated both at rest (Rμ-rest) and during hyperemia (Rμ-hyper). Microvascular Resistance Reserve (MRR), is calculated as the ratio of Rμ-rest and Rμ-hyper and showed a good correlation with the analogous Doppler-derived parameter (using the APV instead of absolute flow). Mean doppler and thermodilution derived MRR were similar (3.32±1.50 vs 3.23±1.16) and values correlated closely (r=0.91, 95% CI 0.81 - 0.96, p<0.001; Bland-Altman analysis: mean bias = 0.071, limit of agreement −1.195 to 1.338). Conclusion Absolute coronary blood flow (in mL/min) can be measured by continuous thermodilution both at rest and during hyperemia. This allows accurate, reproducible, and operator-independent direct volumetric calculation of CFR and MRR. The latter is a quantitative metric which is specific for microvascular function and independent from myocardial mass. Doppler and Thermodilution derived MRR Funding Acknowledgement Type of funding source: None

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