Coronary Vascular Resistance Research Articles

Myocardial oxygen handling and metabolic function of ex-situ perfused human hearts from circulatory death donors

BackgroundThis study investigated oxygen handling of human hearts donated after circulatory death (DCD) on normothermic ex-situ heart perfusion (ESHP) and evaluated oxygen handling markers as adjuncts to cardiac viability assessment. MethodsThis single-center retrospective study included human DCD heart transplantation procedures using ESHP. Lactate concentrations, blood gas, myocardial oxygen consumption (MVO2), delivery (MDO2) and extraction (MEO2), coronary blood flow (CBF), coronary vascular resistance (CVR), and adenosine infusion were reported over time. Correlation between parameters was assessed, and statistical testing compared patients who did and did not require extracorporeal membrane oxygenation (ECMO) support after transplantation. ResultsLactate concentrations decreased during ESHP in all transplanted hearts (n=25) and increased in 1 rejected heart. Arterial PO2 was 75.2±2.9 kPa, with an arteriovenous ΔPO2 of 44.8±10.4 kPa. Oxygen saturation was 100% in most arterial and venous samples. Average MVO2 was 2.7±0.6 mL·min-1·100·g-1 myocardium, MDO2 98.5±20.4 mL·min-1, and MEO2 8.6±1.8%. Average CVR was 0.025±0.006 mmHg∙min∙mL-1∙100 g-1 and increased over time. ΔPO2 correlated strongly with MVO2 (R=0.797, p<0.001) and lactate trend (R=0.799, p<0.001) in transplanted hearts, without differences compared to the rejected heart with increasing lactate. Adenosine infusion on ESHP was significantly higher in patients requiring ECMO post-transplantation versus non-ECMO cases (11.7 (4.5-21.0) vs. 2.2 (1.5-6.7) mL·h-1, p=0.039). ConclusionsHearts on normothermic ESHP receive excessive MDO2, due to high PO2 and CBF, while the MVO2 is relatively low. Thus, CBF and PO2 can potentially be lowered. Furthermore, ΔPO2 could serve as additional marker of metabolic function under these hyperoxic circumstances. The adenosine infusion rate might predict post-transplantation ECMO requirement.

Role of potassium as a coronary metabolic vasodilator

K+ release from the myocardium is associated with decreased coronary vascular resistance. Accumulation of extracellular K+ has been linked to mechanisms of vasodilation in the coronary circulation including activation of the electrogenic Na+-K+ pump in smooth muscle (Murray and Sparks, Circ. Res. 1977) and endothelial-mediated hyperpolarization via Kir2.1 channels (Zhao et al., PNAS 2020). Our objective was to examine K+ as a coronary metabolic vasodilator in vivo. Further, we addressed two potential shortcomings of previous studies: the short duration of the bolus K+ stimulus employed and the seemingly high concentrations required to produce vasodilation. We hypothesized that continuous, steady-state intracoronary infusions of K+ would produce sustained coronary vasodilation in a concentration-dependent manner. Our methods involved instrumenting anesthetized, open-chest Yorkshire swine (male and female, 60 kg) for measurements of coronary blood flow, as well as arterial and coronary venous blood sampling. The left anterior descending coronary artery was cannulated and perfused under the control of a pressure servo, allowing us to determine flow and infuse K+. Our results show small, but statistically significant (* represents p &lt; 0.05), effects of K+ on coronary hemodynamics. The coronary venous K+ concentration was 4.0 ± 0.1 mM at baseline. Infusing K+ into the coronary artery at increasing rates increased coronary venous K+ to 4.9 ± 0.2*, 6.4 ± 0.2*, and 7.9 ± 0.2* mM. Higher K+ concentrations caused fatal arrhythmias. Coronary blood flow was 0.73 ± 0.14 ml/min/g at baseline. Infusing K+ into the coronary artery at increasing rates increased coronary blood flow to 0.78 ± 0.14*, 0.82 ± 0.15*, and 0.86 ± 0.16* ml/min/g. These small coronary blood flow changes were sustained during continuous K+ infusion. We conclude that K+ is a coronary vasodilator, as has been demonstrated previously. Importantly, however, we emphasize that the effects of K+ are extremely modest and the concentrations required to produce physiologically significant vasodilation are life-threatening. With the assumption that the venous K+ concentration is in equilibrium with that surrounding the smooth muscle and cardiac muscle of the working heart, we urge caution in interpreting isolated artery studies that routinely use 15-20 mM K+ to elicit hyperpolarization and vasodilation. Our data do not support the idea that K+ plays a major role in regulating coronary vascular resistance. This work was supported by National Institutes of Health grant R01 HL158723. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cardiac PET Myocardial Blood Flow Quantification Assessment of Early Cardiac Allograft Vasculopathy

BackgroundPositron emission tomography (PET) has demonstrated utility for diagnostic and prognostic assessment of cardiac allograft vasculopathy (CAV) but has not been evaluated in the first year after transplant. ObjectivesThe authors sought to evaluate CAV at 1 year by PET myocardial blood flow (MBF) quantification. MethodsAdults at 2 institutions enrolled between January 2018 and March 2021 underwent prospective 3-month (baseline) and 12-month (follow-up) post-transplant PET, endomyocardial biopsy, and intravascular ultrasound examination. Epicardial CAV was assessed by intravascular ultrasound percent intimal volume (PIV) and microvascular CAV by endomyocardial biopsy. ResultsA total of 136 PET studies from 74 patients were analyzed. At 12 months, median PIV increased 5.6% (95% CI: 3.6%-7.1%) with no change in microvascular CAV incidence (baseline: 31% vs follow-up: 38%; P = 0.406) and persistent microvascular disease in 13% of patients. Median capillary density increased 30 capillaries/mm2 (95% CI: −6 to 79 capillaries/mm2). PET myocardial flow reserve (2.5 ± 0.7 vs 2.9 ± 0.8; P = 0.001) and stress MBF (2.7 ± 0.6 vs 2.9 ± 0.6; P = 0.008) increased, and coronary vascular resistance (CVR) (49 ± 13 vs 47 ± 11; P = 0.214) was unchanged. At 12 months, PET and PIV had modest correlation (stress MBF: r = −0.35; CVR: r = 0.33), with lower stress MBF and higher CVR across increasing PIV tertiles (all P < 0.05). Receiver-operating characteristic curves for CAV defined by upper-tertile PIV showed areas under the curve of 0.74 for stress MBF and 0.73 for CVR. ConclusionsThe 1-year post-transplant PET MBF is associated with epicardial CAV, supporting potential use for early noninvasive CAV assessment. (Early Post Transplant Cardiac Allograft Vasculopahty [ECAV]; NCT03217786)

Sex Differences in Systemic and Coronary Arterial Hemodynamics in Heart Failure With Preserved Ejection Fraction

Heart failure (HF) with preserved ejection fraction (HFpEF) predominantly affects females. Systemic and coronary arterial abnormalities are present in HFpEF and may contribute to HFpEF in females. We performed a cross-sectional study of 32 participants with HFpEF and 26 controls. Arterial hemodynamics were noninvasively assessed by combining arterial tonometry with echocardiography. Coronary microvascular function was assessed by rubidium-82 positron emission tomography as the myocardial flow reserve. Coronary vascular resistance (CVR) at rest and vasodilator stress were calculated using positron emission tomography. CVR reserve was calculated as stress-rest CVR. Multivariable linear regression assessed the associations of female sex with arterial hemodynamics in participants with and without HF, and the association of HF with arterial hemodynamics within each sex stratum. Demographics and left ventricular systolic and diastolic function were similar between males and females. Among those with HFpEF, females had a higher steady and pulsatile arterial load and more impaired (less negative) CVR reserve than males. Conversely, in controls, females had similar hemodynamics to males. We then divided the sample based on sex. Femaleswith HFpEF had a higher pulsatile arterial load and higher stress CVR than control females. Among males, arterial hemodynamics were similar, regardless of HFpEF status. The measures of early pulsatile arterial load were independently associated with higher E/e' and lower myocardial flow reserve in females only. In conclusion, despite similar left ventricular function between sexes, older females with HFpEF are characterized by additional systemic and coronary arterial hemodynamic abnormalities compared with males with HFpEF and similarly aged females without HFpEF.

Cinnamaldehyde protects donor heart from cold ischemia–reperfusion injury via the PI3K/AKT/mTOR pathway

With the growing shortage of organs, improvements in donor organ protection are needed to meet the increasing demands for transplantation. Here, the aim was to investigate the protective effect of cinnamaldehyde against ischemia–reperfusion injury (IRI) in donor hearts exposed to prolonged cold ischemia. Donor hearts were harvested from rats pretreated with or without cinnamaldehyde, then subjected to 24 h of cold preservation and 1 h of ex vivo perfusion. Hemodynamic changes, myocardial inflammation, oxidative stress, and myocardial apoptosis were evaluated. The PI3K/AKT/mTOR pathway involved in the cardioprotective effects of cinnamaldehyde was explored through RNA sequencing and western blot analysis. Intriguingly, cinnamaldehyde pretreatment remarkably improved cardiac function through increasing coronary flow, left ventricular systolic pressure, +dp/dtmax, and −dp/dtmax, decreasing coronary vascular resistance and left ventricular end-diastolic pressure. Moreover, our findings indicated that cinnamaldehyde pretreatment protected the heart from IRI by alleviating myocardial inflammation, attenuating oxidative stress, and reducing myocardial apoptosis. Further studies showed that the PI3K/AKT/mTOR pathway was activated after cinnamaldehyde treatment during IRI. The protective effects of cinnamaldehyde were abolished by LY294002. In conclusion, cinnamaldehyde pretreatment alleviated IRI in donor hearts suffering from prolonged cold ischemia. Cinnamaldehyde exerted cardioprotective effects through the activation of the PI3K/AKT/mTOR pathway.

Therapeutic and safety outcomes of intracoronary nicardipine in coronary artery disease patients: a systematic review.

Aim: This systematic review aimed to shed light on the efficacy of intracoronary (IC) nicardipine in treating no reflow with CAD undergoing revascularization. Methods: Literature search was performed on databases with following eligibility criteria: adult patients with CAD; clinical trials or observational studies; IC nicardipine as intervention; therapeutic and safety outcome reported. Results: A total of 1249 papers were yielded during the literature search. Of these, 11 studies were finalized for this systematic review. Complete restoration of TIMI 3 flow was observed in 98.6% of the patients receiving IC nicardipine. A significant increase in the CBF after infusion of IC nicardipine (p<0.05) was also observed. Conclusion: IC nicardipine significantly increases CBF and decreases coronary vascular resistance.

The evaluation of constant coronary artery flow versus constant coronary perfusion pressure during normothermic ex situ heart perfusion.

Evidence suggests that hearts that are perfused under ex-situ conditions lose normal coronary vasomotor tone and experience contractile failure over a few hours. We aimed to evaluate the effect of different coronary perfusion strategies during ex situ heart perfusion on cardiac function and coronary vascular tone. Porcine hearts (n=6 each group) were perfused in working mode for 6 hours with either constant aortic diastolic pressure (40 mmHg) or constant coronary flow rate (500 mL/min). Functional and metabolic parameters, cytokine profiles, cardiac and vascular injury, coronary artery function and oxidative stress were compared between groups. Constant coronary flow perfusion demonstrated better functional preservation and less edema formation (Cardiac index: flow control=8.33 vs pressure control=6.46 mL·min-1·g-1, p=0.016; edema formation: 7.92% vs 19.80%, p < 0.0001). Pro-inflammatory cytokines, platelet activation as well as endothelial activation were lower in the flow control group. Similarly, less cardiac and endothelial injury was observed in the constant coronary flow group. Evaluation of coronary artery function showed there was loss of coronary autoregulation in both groups. Oxidative stress was induced in the coronary arteries and was relatively lower in the flow control group. A strategy of controlled coronary flow during ex situ heart perfusion provides superior functional preservation and less edema formation, together with less myocardial damage, leukocyte, platelet, endothelial activation, and oxidative stress. There was loss of coronary autoregulation and decrease of coronary vascular resistance during ESHP irrespective of coronary flow control strategy. Inflammation and oxidative stress state in the coronary vasculature may play a role.

Abstract 11882: Exploring Abnormalities in Coronary Vascular Resistance Reserve as a Distinct Feature of The Hfpef Syndrome in Women

Introduction: Heart failure with preserved ejection fraction (HFpEF) is more common in women than men, but mechanisms underlying this female predominance are incompletely understood. Impaired systemic vasodilatory reserve and coronary microvascular dysfunction have been separately described as key abnormalities of HFpEF. However, the coronary vascular resistance reserve (CVRR), defined as the drop in coronary vascular resistance (CVR) from rest to peak stress, and its sex-specific nuances have not been explored in HFpEF. We sought to: (1) determine whether stress CVR differs between HFpEF and controls, and (2) assess sex differences in CVRR in HFpEF. Methods: We performed a cross-sectional study of 32 HFpEF participants and 26 controls, all without obstructive epicardial coronary artery disease. HFpEF was defined according to ESC Guidelines. Dipyridamole stress 82 Rb positron emission tomography was performed, and rest and stress CVR was calculated by dividing mean arterial pressure by coronary flow at rest and stress. Multivariable linear regression assessed (1) the association of HFpEF with stress CVR; and (2) the association of female sex with CVRR in patients with and without HFpEF. Results: Mean age was 74±7 years, 67% were women and mean LVEF was 62±5%: no difference between HFpEF and controls (P&gt;0.05 for each). Results of the multivariable models are summarized in the Image. HFpEF was independently associated with higher global left ventricular CVR at peak vasodilatory stress. In addition, women had lower global left ventricular CVRR as compared to men, and this was unique to women with HFpEF. Results were the same for coronary-specific CVR and CVRR (analyses not shown). Conclusions: To our knowledge, this is the first study to non-invasively explore CVR and CVRR in HFpEF. Our findings suggest increased stress CVR in HFpEF, with a distinct abnormality in CVRR in women with HFpEF. Abnormal CVRR in women may contribute to the female predominance of HFpEF.

Deodorized Garlic Decreases Oxidative Stress Caused by Lipopolysaccharide in Rat Heart through Hydrogen Sulfide: Preliminary Findings.

Deodorized garlic (DG) may favor the activity of the antioxidant enzymes and promote the synthesis of hydrogen sulfide (H2S). The objective was to test if DG favors an increase in H2S and if it decreases the oxidative stress caused by lipopolysaccharide (LPS) in rat hearts. A total of 24 rats were divided into 4 groups: Group 1 control (C), Group 2 LPS, Group 3 DG, and Group 4 LPS plus DG. The cardiac mechanical performance (CMP), coronary vascular resistance (CVR), and oxidative stress markers, such as total antioxidant capacity (TAC), glutathione (GSH), selenium (Se), lipid peroxidation (LPO), thiols, hydrogen sulfide (H2S), and the activities and expressions of thioredoxin reductase (TrxR), glutathione peroxidase (GPx), and glutathione-S-transferase (GST), cystathionine synthetase (CBS), cystathionine γ-lyase (CTH), iNOS, and eNOS-p, were analyzed in the heart. Infarct zones in the cardiac tissue were present (p = 0.01). The CMP and CVR decreased and increased (p ≤ 0.05), TAC, GSH, H2S, NO, thiols, and GST activity (p ≤ 0.01) decreased, and LPO and iNOS increased (p ≤ 0.05). The activities and expressions of TrxR, GPx, eNOS-p, CTH, and CBS (p ≤ 0.05) decreased with the LPS treatment; however, DG normalized this effect. DG treatment decreases heart damage caused by LPS through the cross-talk between the H2S and NO systems.

Haemodynamic characterisation of different endotypes in coronary artery vasospasm in reaction to acetylcholine.

Vasoreactivity testing with high-dose acetylcholine is considered vasospasm provocation and low-dose as endothelial function testing. To assess the changes in reaction to low- and high-dose acetylcholine in the endotypes of CAS as defined by the Coronary Vasomotor Disorders International Study Group (COVADIS) working group. Changes in coronary epicardial diameter, coronary blood flow (CBF) and vascular resistance were determined at low-dose acetylcholine. A total of 88 ANOCA patients were included in this analysis. In the negative group (n=14) incremental infusion of acetylcholine produced a progressive increase in CBF (p=0.008). In reaction to low-dose acetylcholine, the epicardial vasospasm group (n=30) is characterised by epicardial vasoconstriction that is significantly more severe compared to the microvascular vasospasm group (p=0.004)(n=23). The equivocal group (n=21) is characterised by an increase in CBF and reduction in vascular resistance that are both significantly different compared to the epicardial vasospasm group (p=0.036 and p=0.007, respectively). High-dose acetylcholine decreased epicardial diameter and CBF significantly in the epicardial vasospasm, microvascular vasospasm and in the equivocal group (all p<0.05. Vascular resistance increased significantly in the epicardial vasospasm group (p<0.001) and equivocal group (p=0.009). In reaction to low-dose acetylcholine the negative and equivocal endotype has haemodynamic changes that suggest intact endothelium. In reaction to high-dose acetylcholine the epicardial vasospasm, microvascular vasospasm and equivocal endotype have hemodynamic changes that suggest VSMC-hyperreactivity. These results suggest that the equivocal endotype is a positive test comparable to microvascular vasospasm in the presence of normal endothelial function.

Remote ischemic preconditioning promotes cardioprotection through a central nervous system dependent mechanism

Remote ischemic preconditioning (rIPC) is the phenomenon of brief periods of ischemia and reperfusion applied to a distant organ promote cardioprotection against a subsequent ischemia/reperfusion injury (I/R). Although a neurohumoral hypothesis has been proposed, the cardioprotective mechanisms of rIPC have not been fully elucidated. We investigated whether rIPC could induce cardioprotection in a pithed Wistar rat model hypothesizing that the absence of central nervous system (CNS) structures would prevent its cardioprotective effect. rIPC protocol consisting of 3 cycles of 4 minutes of ischemia and 4 minutes of reperfusion was applied to the left posterior extremity of male Wistar rats. I/R was induced surgically by left coronary descending artery ligation for 30 minutes followed by 2h of reperfusion. Isolated rat hearts were perfused in a Langendorff system to measure coronary vascular resistance (CVR). Finally, the infarct size was evaluated by Evans blue and triphenyltetrazolium staining. rIPC reduced the infarct size of the ischemic hearts; however, this effect was abolished in pithed rats. rIPC also prevented the rise of CVR of ischemic hearts while there was no difference compared to pithed rats. We concluded that rIPC reduces the infarct size of hearts during I/R preserving the coronary artery tone through a CNS‐dependent mechanism.

Control of coronary vascular resistance by eicosanoids via a novel GPCR.

Arachidonic acid metabolites epoxyeicosatrienoates (EETs) and hydroxyeicosatetraenoates (HETEs) are important regulators of myocardial blood flow and coronary vascular resistance (CVR), but their mechanisms of action are not fully understood. We applied a chemoproteomics strategy using a clickable photoaffinity probe to identify G protein-coupled receptor 39 (GPR39) as a microvascular smooth muscle cell (mVSMC) receptor selective for two endogenous eicosanoids, 15-HETE and 14,15-EET, which act on the receptor to oppose each other's activity. The former increases mVSMC intracellular calcium via GPR39 and augments coronary microvascular resistance, and the latter inhibits these actions. Furthermore, we find that the efficacy of both ligands is potentiated by zinc acting as an allosteric modulator. Measurements of coronary perfusion pressure (CPP) in GPR39-null hearts using the Langendorff preparation indicate the receptor senses these eicosanoids to regulate microvascular tone. These results implicate GPR39 as an eicosanoid receptor and key regulator of myocardial tissue perfusion. Our findings will have a major impact on understanding the roles of eicosanoids in cardiovascular physiology and disease and provide an opportunity for the development of novel GPR39-targeting therapies for cardiovascular disease.

Prognostic utility of longitudinal quantification of PET myocardial blood flow early post heart transplantation

BackgroundMyocardial blood flow (MBF) quantification by Rubidium-82 positron emission tomography (PET) has shown promise for cardiac allograft vasculopathy (CAV) surveillance and risk stratification post heart transplantation. The objective was to determine the prognostic value of serial PET performed early post transplantation. Methods and ResultHeart transplant (HT) recipients at the University of Ottawa Heart Institute with 2 PET examinations (PET1 = baseline, PET2 = follow-up) within 6 years of transplant were included in the study. Evaluation of PET flow quantification included stress MBF, coronary vascular resistance (CVR), and myocardial flow reserve (MFR). The primary composite outcome was all-cause death, re-transplant, myocardial infarction, revascularization, allograft dysfunction, cardiac allograft vasculopathy (CAV), or heart failure hospitalization. A total of 121 patients were evaluated (79% male, mean age 56 ± 11 years) with consecutive scans performed at mean 1.4 ± 0.7 and 2.6 ± 1.0 years post HT for PET1 and PET2, respectively. Over a mean follow-up of 3.0 (IQR 1.8, 4.6) years, 26 (22%) patients developed the primary outcome: 1 death, 11 new or progressive angiographic CAV, 2 percutaneous coronary interventions, 12 allograft dysfunction. Unadjusted Cox analysis showed a significant reduction in event-free survival in patients with PET1 stress MBF < 2.1 (HR: 2.43, 95% CI 1.11-5.29 P = 0.047) and persistent abnormal PET1 to PET2 CVR > 76 (HR: 2.19, 95% CI 0.87-5.51 P = 0.045). There was no association between MFR and outcomes. ConclusionLow-stress MBF and persistent increased CVR on serial PET imaging early post HT are associated with adverse cardiovascular outcomes. Early post-transplant and longitudinal assessment by PET may identify at-risk patients for increased surveillance post HT.

PET Scan for CAV Screening in Heart Transplant Patients: A Real World Experience

<h3>Purpose</h3> Cardiac allograft vasculopathy (CAV) is a major cause of late morbidity and mortality after heart transplantation (HT). Positron emission tomography (PET) has emerged as a non-invasive screening modality, associated with invasive hemodynamic flow indices and outcomes in several small-scale studies. Our aim was to assess the real-world performance of 13N-Ammonia PET scan (PET) for the development of CAV. <h3>Methods</h3> Single center retrospective analysis of all HT patients who had an angiogram within one year before and after PET scan for CAV screening. CAV was defined as International Society of Heart and Lung Transplantation CAV_1-3. PET indices indicative of CAV were defined as any of: myocardial flow reserve (MFR) < 2.9, stress blood flow (SBF) < 2.3, or coronary vascular resistance (CVR) > 55. <h3>Results</h3> A total of 112 patients met study criteria, 13 were excluded for having CAV on pre-PET angiogram. Of the remaining 99 patients, Mean age was 52±14, 67 (68%) were males, 28 (28%) had ischemic cardiomyopathy, 35 (35%) had diabetes and 26 (26%) were hypertensive. PET was abnormal in 53 pts (54%). Repeat LHC demonstrated new CAV in 9 of these, all of whom had non-obstructive coronary artery disease (NCAD) on LHC. Overall PET had a 100% sensitivity and 51% specificity for identifying CAV. Two or more abnormal PET parameters showed 78% specificity (67% sensitivity) for the prediction of CAV. <h3>Conclusion</h3> Implementing a strategy of 13N-Ammonia PET scan performed a year after a negative LHC for CAV screening, resulted in excellent sensitivity but low specificity. Epicardial CAV was strongly associated with microvascular dysfunction evident by increased CVR and NCAD. Optimal PET thresholds for CAV screening need further refinement.

Lactic Acid and Metabolic Analysis of Human Donor Hearts Preserved with Organ Care System

<h3>Purpose</h3> Primary graft dysfunction (PGD) is the most common cause of early death in patients of heart transplantation (HTx) and the requirement of ECMO is one of the definitive criteria of PGD. The Organ Care System (OCS) offers ex-vivo donor heart perfusion and currently, the decision to use the OCS preserved donor heart for HTx depends upon the lactate trend and the ventricular contractility. We performed a metabolic analysis of the OCS perfusate samples to predict donor hearts that may develop PGD following HTx. <h3>Methods</h3> Between February 2013 and September 2019, 204 donor hearts procured from the donation after brain death was assessed using OCS. 53 hearts were declined for HTx based on lactate trend and ventricular contractility (No Tx); whereas in the remaining 152 hearts that were transplanted, 42 recipients required ECMO following HTx (Tx with ECMO) while 109 recipients did not require ECMO (Tx without ECMO). <h3>Results</h3> The proportion of unfavourable lactate trend and high ‘end lactate' was significantly higher in the hearts declined for the HTx (no Tx group); however, there was no difference between ‘Tx with ECMO' and ‘Tx without ECMO' groups. The rate of fall of lactate was higher in the ‘Tx without ECMO' compared to the ‘Tx with ECMO'; however, did not reach statistical significance. Coronary blood flow was significantly low in the ‘No Tx' group compared to the other two groups. O2 content, O2 delivery and O2 return were significantly low in the No Tx group and these markers were higher in ‘Tx without ECMO' compared to ‘Tx with ECMO', although not statistically significant. The diastolic pressure and the coronary vascular resistance fell after 30 minutes of OCS perfusion in the donor hearts that did not suffer PGD whereas it remained high in the donor hearts that suffered PGD. <h3>Conclusion</h3> The rate of fall of arterial lactate offered more valuable information compared to the overall lactate trend and end lactate in the prediction of PGD after HTx. Hearts declined for the HTx based on the unfavourable lactate trend, high-end lactate and suboptimal ventricular contractility are justified by the metabolic analysis that showed significantly low CaO2, DO2 and Oxygen return in the declined hearts. Hearts procured from donors after brain death and preserved with OCS that show consistently high coronary vascular resistance may develop PGD requiring ECMO.

Prognostic value of microvascular resistance and its association to fractional flow reserve: a DEFINE-FLOW substudy

ObjectiveThis study aimed to evaluate the prognostic value of hyperemic microvascular resistance (HMR) and its relationship with hyperemic stenosis resistance (HSR) index and fractional flow reserve (FFR) in stable coronary...

Peripheral Coronary Artery Circulatory Dysfunction in Remote Stage Kawasaki Disease Patients Detected by Adenosine Stress 13N-Ammonia Myocardial Perfusion Positron Emission Tomography.

Coronary peripheral circulatory disturbances in the remote stage of Kawasaki disease have been reported. In this study, of the 50 patients in the remote stage of Kawasaki disease who underwent coronary perfusion evaluation using adenosine-loaded 13N-ammonia positron emission tomography, 28 patients who did not have stenosis of ≥75% in the left coronary artery underwent an evaluation for myocardial flow reserve (MFR) of the left anterior descending artery (LAD) and left circumflex artery (LCx). Clinical findings were compared between patients with normal (≥2.0) and abnormal (<2.0) MFRs. In the group with an abnormal MFR in the LAD, the responsiveness of the coronary vascular resistance to adenosine stress decreased even in the LCx (3.50 ± 1.23 vs. 2.39 ± 0.25, p = 0.0100). In the group with an abnormal MFR in the LCx, the responsiveness of the coronary vascular resistance in the LAD also decreased (3.27 ± 1.39 vs. 2.03 ± 0.25, p = 0.0105), and the age of onset of Kawasaki disease tended to be younger in the group with abnormal MFR in the LAD and LCx. We found that the peripheral coronary circulation was extensively impaired in the remote stage of Kawasaki disease, suggesting that an early onset of Kawasaki disease may affect the peripheral coronary circulation in later years.

Validation of multiparametric rubidium-82 PET myocardial blood flow quantification for cardiac allograft vasculopathy surveillance

BackgroundWe previously demonstrated high diagnostic accuracy of Rubidium-82 positron emission tomography (PET) myocardial blood flow (MBF) quantification for CAV. The purpose of this study was to validate multiparametric PET detection of CAV by combined rate-pressure-product-corrected myocardial flow reserve (cMFR), stress MBF, and coronary vascular resistance (CVR) assessment. Methods and ResultsDiagnostic CAV cut-offs of cMFR < 2.9, stress MBF < 2.3, CVR > 55 determined in a previous study (derivation) were assessed in heart transplant recipients referred for coronary angiography and intravascular ultrasound (IVUS) (validation). CAV was defined as International Society of Heart and Lung Transplantation CAV1-3 on angiography; and maximal intimal thickness ≥ 0.5 mm on IVUS. Eighty patients (derivation n = 40, validation n = 40) were included: 80% male, mean age 54±14 years, 4.5±5.6 years post transplant. The prevalence of CAV was 44% on angiography and 78% on IVUS. Combined PET cMFR < 2.9, stress MBF < 2.3, CVR > 55 CAV assessment yielded high 88% (specificity 75%) and 83% (specificity 40%) sensitivity for ≥ 1 abnormal parameter and high 88% (sensitivity 59%) and 90% (sensitivity 43%) specificity for 3 abnormal parameters, in the derivation and validation cohorts, respectively. ConclusionWe validate the diagnostic accuracy of multiparametric PET flow quantification by cMFR, stress MBF, and CVR for CAV.

Mineralocorticoid receptor blockade normalizes coronary resistance in obese swine independent of functional alterations in Kv channels.

Impaired coronary microvascular function (e.g., reduced dilation and coronary flow reserve) predicts cardiac mortality in obesity, yet underlying mechanisms and potential therapeutic strategies remain poorly understood. Mineralocorticoid receptor (MR) antagonism improves coronary microvascular function in obese humans and animals. Whether MR blockade improves in vivo regulation of coronary flow, a process involving voltage-dependent K+ (Kv) channel activation, or reduces coronary structural remodeling in obesity is unclear. Thus, the goals of this investigation were to determine the effects of obesity on coronary responsiveness to reductions in arterial PO2 and potential involvement of Kv channels and whether the benefit of MR blockade involves improved coronary Kv function or altered passive structural properties of the coronary microcirculation. Hypoxemia increased coronary blood flow similarly in lean and obese swine; however, baseline coronary vascular resistance was significantly higher in obese swine. Inhibition of Kv channels reduced coronary blood flow and augmented coronary resistance under baseline conditions in lean but not obese swine and had no impact on hypoxemic coronary vasodilation. Chronic MR inhibition in obese swine normalized baseline coronary resistance, did not influence hypoxemic coronary vasodilation, and did not restore coronary Kv function (assessed in vivo, ex vivo, and via patch clamping). Lastly, MR blockade prevented obesity-associated coronary arteriolar stiffening independent of cardiac capillary density and changes in cardiac function. These data indicate that chronic MR inhibition prevents increased coronary resistance in obesity independent of Kv channel function and is associated with mitigation of obesity-mediated coronary arteriolar stiffening.

Mineralocorticoid Receptor Blockade Normalizes Coronary Resistance in Obese Swine Independent of Functional Alterations in K v Channels

Impaired coronary microvascular function (e.g., reduced dilation to physiological stimuli and decreased coronary flow reserve) predicts cardiac mortality in obesity, yet underlying mechanisms and potential therapeutic strategies remain poorly understood. Mineralocorticoid receptor (MR) antagonism improves coronary microvascular function in obese humans and animals. Whether this results from improved regulation of coronary resistance, a process dependent on voltage-dependent K+ (Kv) channel activation, or reduced coronary structural remodeling is unclear. Indeed, recent evidence suggests MR-dependent regulation of vascular K+ channels and pathologic stiffening. Thus, the goals of this investigation were to determine: 1) the effects of obesity on coronary vasodilation to graded reductions in arterial PO2; 2) the contribution of Kv channels to hypoxemic coronary vasodilation; and 3) whether chronic MR blockade improves hypoxemia-induced coronary vasodilation in obesity and underlying mechanisms. Hypoxemia increased coronary blood flow to a similar degree in lean and obese swine, however coronary vascular resistance was significantly higher in obese swine. Inhibition of Kv channels reduced coronary blood flow and augmented coronary resistance under baseline conditions in lean but not obese swine and had no impact on hypoxemic coronary vasodilation. Chronic MR inhibition in obese swine normalized baseline coronary resistance, did not influence hypoxemic coronary vasodilation, or restore coronary Kv function (assessed in vivo, ex vivo, and via patch clamping). Lastly, MR blockade prevented obesity-associated coronary arteriolar stiffening independent of cardiac capillary density. These data indicate that chronic MR inhibition prevents increased coronary resistance in obesity independent of alterations in Kv channel function.