scholarly journals Myocardial Energy Response to Glyceryl Trinitrate: Physiology Revisited

2021 ◽  
Vol 12 ◽  
Author(s):  
William D. Watson ◽  
Peregrine G. Green ◽  
Ladislav Valkovič ◽  
Neil Herring ◽  
Stefan Neubauer ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Magnetic Resonance ◽  
Glyceryl Trinitrate ◽  
Clinical Medicine ◽  
Left Ventricular ◽  
Forward Rate ◽  
Rate Pressure Product ◽  
Resonance Spectroscopy ◽  
Stroke Work ◽  
Atp Production

Objective: Although intravenous nitrates are commonly used in clinical medicine, they have been shown to increase myocardial oxygen consumption and inhibit complex IV of the electron transport chain. As such we sought to measure whether myocardial energetics were impaired during glyceryl trinitrate (GTN) infusion.Methods: 10 healthy volunteers underwent cardiac magnetic resonance imaging to assess cardiac function and 31phosphorus magnetic resonance spectroscopy to measure Phosphocreatine/ATP (PCr/ATP) ratio and creatine kinase forward rate constant (CK kf) before and during an intravenous infusion of GTN.Results: During GTN infusion, mean arterial pressure (78 ± 7 vs. 65 ± 6 mmHg, p < 0.001), left ventricular (LV) stroke work (7,708 ± 2,782 vs. 6,071 ± 2,660 ml mmHg, p < 0.001), and rate pressure product (7,214 ± 1,051 vs. 6,929 ± 976 mmHg bpm, p = 0.06) all fell. LV ejection fraction increased (61 ± 3 vs. 66 ± 4%, p < 0.001), with cardiac output remaining constant (6.2 ± 1.5 vs. 6.5 ± 1.4 l/min, p = 0.37). Myocardial PCr/ATP fell during GTN infusion (2.17 ± 0.2 vs. 1.99 ± 0.22, p = 0.03) with an increase in both CK kf (0.16 ± 0.07 vs. 0.25 ± 0.1 s−1, p = 0.006) and CK flux (1.8 ± 0.8 vs. 2.6 ± 1.1 μmol/g/s, p = 0.03).Conclusion: During GTN infusion, despite reduced LV stroke work and maintained cardiac output, there was a 44% increase in myocardial ATP delivery through CK. As PCr/ATP fell, this increase in ATP demand coincided with GTN-induced impairment of mitochondrial oxidative phosphorylation. Overall, this suggests that while GTN reduces cardiac work, it does so at the expense of increasing ATP demand beyond the capacity to increase ATP production.

Myocardial creatine kinase kinetics in hearts with postinfarction left ventricular remodeling

1999 ◽  
Vol 276 (3) ◽  
pp. H892-H900 ◽  
Author(s):  
Yo Murakami ◽  
Jianyi Zhang ◽  
Marcel H. J. Eijgelshoven ◽  
Wei Chen ◽  
Wenda C. Carlyle ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Ventricular Remodeling ◽  
Left Ventricular Remodeling ◽  
High Energy ◽  
Left Ventricular ◽  
Forward Rate ◽  
Rate Pressure Product ◽  
Resonance Spectroscopy ◽  
Coronary Artery Ligation ◽  
Artery Ligation

This study examined whether alterations in myocardial creatine kinase (CK) kinetics and high-energy phosphate (HEP) levels occur in postinfarction left ventricular remodeling (LVR). Myocardial HEP and CK kinetics were examined in 19 pigs 6 wk after myocardial infarction was produced by left circumflex coronary artery ligation, and the results were compared with those from 9 normal pigs. Blood flow (microspheres), oxygen consumption (MV˙o2), HEP levels [31P magnetic resonance spectroscopy (MRS)], and CK kinetics (31P MRS) were measured in myocardium remote from the infarct under basal conditions and during dobutamine infusion (20 μg ⋅ kg−1⋅ min−1iv). Six of the pigs with LVR had overt congestive heart failure (CHF) at the time of study. Under basal conditions, creatine phosphate (CrP)-to-ATP ratios were lower in all transmural layers of hearts with CHF and in the subendocardium of LVR hearts than in normal hearts ( P < 0.05). Myocardial ATP (biopsy) was significantly decreased in hearts with CHF. The CK forward rate constant was lower ( P < 0.05) in the CHF group (0.21 ± 0.03 s−1) than in LVR (0.38 ± 0.04 s−1) or normal groups (0.41 ± 0.03 s−1); CK forward flux rates in CHF, LVR, and normal groups were 6.4 ± 2.3, 14.3 ± 2.1, and 20.3 ± 2.4 μmol ⋅ g−1⋅ s−1, respectively ( P < 0.05, CHF vs. LVR and LVR vs. normal). Dobutamine caused doubling of the rate-pressure product in the LVR and normal groups, whereas CHF hearts failed to respond to dobutamine. CK flux rates did not change during dobutamine in any group. The ratios of CK flux to ATP synthesis (from MV˙o2) under baseline conditions were 10.9 ± 1.2, 8.03 ± 0.9, and 3.86 ± 0.5 for normal, LVR, and CHF hearts, respectively (each P < 0.05); during dobutamine, this ratio decreased to 3.73 ± 0.5, 2.58 ± 0.4, and 2.78 ± 0.5, respectively ( P = not significant among groups). These data demonstrate that CK flux rates are decreased in hearts with postinfarction LVR, but this change does not limit the response to dobutamine. In hearts with end-stage CHF, the changes in HEP and CK flux are more marked. These changes could contribute to the decreased responsiveness of these hearts to dobutamine.

scholarly journals Cardiac Energetics Before, During and After Anthracycline-based Chemotherapy in Breast Cancer Patients Using 31P Magnetic Resonance Spectroscopy: A Pilot Study

2020 ◽  
Author(s):  
Gillian Macnaught ◽  
Olga Oikonomidou ◽  
Christopher T. Rodgers ◽  
William Clarke ◽  
Annette Cooper ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pilot Study ◽  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Resonance Spectroscopy ◽  
Ventricular Ejection Fraction ◽  
Time Points ◽  
Change In Mean

Abstract PURPOSETo explore the utility of phosphorus magnetic resonance spectroscopy (31P MRS) in identifying anthracycline-induced cardiac toxicity in patients with breast cancer.METHODS20 patients with newly diagnosed breast cancer receiving anthracycline-based chemotherapy had cardiac magnetic resonance assessment of left ventricular ejection fraction (LVEF) and 31P MRS to determine myocardial Phosphocreatine/Adenosine Triphosphate ratio (PCr/ATP) at three time points: pre, mid and end-chemotherapy. Plasma high sensitivity cardiac troponin-I (cTn-I) tests and electrocardiograms were also performed at these same time points. RESULTS PCr/ATP ratio did not change significantly between pre- and mid-chemo (2.16±0.46 v 2.00±0.56, p=0.80) and pre- and end-chemo (2.16±0.46 v 2.17±0.86, p=0.99). Mean LVEF reduced significantly by 5.1% between pre- and end-chemo (61.4±4.4 vs 56.3±8.1 %, p=0.02). Change in PCr/ATP ratios from pre- to end-chemo correlated inversely with changes in LVEF over the same period (r=-0.65, p=0.006). Plasma cTn-I increased progressively during chemotherapy from pre- to mid-chemo (1.35±0.81 to 4.40±2.64 ng/L; p=0.01) and from mid to end-chemo (4.40±2.64 to 18.33±13.23 ng/L; p=0.001). CONCLUSIONSIn this small cohort pilot study, we did not observe a clear change in mean PCr/ATP values during chemotherapy despite evidence of increased plasma cardiac biomarkers and reduced LVEF. Future similar studies should be adequately powered to take account of patient drop-out and variable changes in PCr/ATP.

Nitrate induced vasoplegia depletes cardiac energy reserves: a model for acute cardiomyopathy in septic shock?

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
W Watson ◽  
P.G Green ◽  
M.K Burrage ◽  
R.R Chamley ◽  
A.J Lewis ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Heart Rate ◽  
Septic Shock ◽  
Creatine Kinase ◽  
Cardiac Output ◽  
Magnetic Resonance ◽  
Resonance Spectroscopy ◽  
Funding Source ◽  
Resonance Imaging ◽  
Cardiac Volumes

Abstract Introduction The healthy heart is at its most efficient when contractile filaments are stretched with preload. To produce the same cardiac output, oxygen requirement rises are proportionally greater with increased inotropy or heart rate than with increased preload. We hypothesized that in vasoplegia, loss of preload (owing to dilation of capacitance veins) and compensatory rises in heart rate and contractility would compromise the efficiency of the heart. We speculated that this may be one factor impairing cardiac function in conditions of distributive shock such as sepsis and looked to model the effects. We used cardiac magnetic resonance imaging to capture changes in cardiac volumes and contractility and magnetic resonance spectroscopy to investigate changes in ATP metabolism within the myocardium in healthy volunteers given GTN as a vasodilator. Methods We recruited 7 healthy volunteers (mean age 40 years, range 28–62 years; mean BMI 21.9, range 18.5–24.5) and measured their baseline cardiac volumes and function, PCr/ATP ratio and Creatine Kinase first order rate constant (CKkf), using cardiac magnetic resonance imaging and magnetic resonance spectroscopy and saturation transfer at 3 Tesla. At the same visit, they received a glyceryl trinitrate (GTN) infusion to induce vasoplegia and the measurements were repeated. We targeted GTN infusion rate to a fall in mean arterial pressure of 15mmHg. Results The GTN infusion brought about a fall in mean arterial pressure (from a baseline of 79±7mmHg to 64±7 mmHg, p&lt;0.0001) and a fall in LV end diastolic volume (169±57 ml vs 148±58 ml, p=0.003) indicating a reduction in preload. As expected, there was a compensatory rise in heart rate (61±7 bpm vs 69±10bpm, p=0.0005) and ejection fraction (62±3% vs 67±3%, p=0.001), however cardiac output remained unchanged (6.72±1.49 L/min vs 6.68±1.48 L/min, p=0.87). Cardiac work (calculated as stroke volume x MAP x heart rate) fell (477±123 vs 424±119 L.mmHg/min, p=0.03). There was a fall in PCr/ATP ratio on GTN (2.18±0.25 vs 1.91±0.2, p 0.03) while CKkf more than doubled (0.14±0.06 s-1 vs 0.23±0.08 s-1, p=0.02) and creatine kinase flux also showed a significant increase (1.65±0.78 μmol/g/s vs 2.28±0.71 μmol/g/s, p=0.05). Conclusions What is novel here is that we show a fall in PCr/ATP ratio: as ATP concentrations in the cell are strictly maintained, this suggests phosphocreatine pool depletion occurs when preload is lost and cardiac output is maintained by an increase in inotropy and chronotropy. The rise in CKkf and CK flux confirm the increased energy demand. Progressive energetic depletion during high demand may give rise to contractile dysfunction over time as the heart is unable to keep up with increased requirements for ATP, and progressively becomes more starved of energy. This could be a mechanism of cardiac dysfunction in septic shock and other vasoplegic states. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation

scholarly journals Quantification of left ventricular contribution to stroke work by longitudinal and radial force-length loops

2020 ◽  
Vol 129 (4) ◽  
pp. 880-890
Author(s):  
Felicia Seemann ◽  
Jonathan Berg ◽  
Kristian Solem ◽  
Robert Jablonowski ◽  
Håkan Arheden ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Magnetic Resonance ◽  
Magnetic Resonance ◽  
Energy Efficient ◽  
Cuff Pressure ◽  
Radial Force ◽  
Left Ventricular ◽  
Stroke Work ◽  
Heart Failure Patients ◽  
Novel Method

A novel method for quantifying the contributions of longitudinal and radial pumping to stroke work using global left ventricular force-length loops was proposed and validated, which can be quantified noninvasively using cardiovascular magnetic resonance and brachial cuff pressure. We found that longitudinal and radial pumping contributes equally to stroke work in controls and 44/56% in heart failure patients, and that the longitudinal pumping is more energy efficient in delivering stroke volume than radial pumping.

Altered high-energy phosphate metabolism predicts contractile dysfunction and subsequent ventricular remodeling in pressure-overload hypertrophy mice

2007 ◽  
Vol 292 (1) ◽  
pp. H387-H391 ◽  
Author(s):  
M. Y. Maslov ◽  
V. P. Chacko ◽  
M. Stuber ◽  
A. L. Moens ◽  
D. A. Kass ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Ventricular Remodeling ◽  
Pressure Overload ◽  
Subsequent Development ◽  
High Energy ◽  
Left Ventricular ◽  
Resonance Spectroscopy ◽  
Contractile Dysfunction ◽  
Lv Mass

To study the role of early energetic abnormalities in the subsequent development of heart failure, we performed serial in vivo combined magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) studies in mice that underwent pressure-overload following transverse aorta constriction (TAC). After 3 wk of TAC, a significant increase in left ventricular (LV) mass (74 ± 4 vs. 140 ± 26 mg, control vs. TAC, respectively; P < 0.000005), size [end-diastolic volume (EDV): 48 ± 3 vs. 61 ± 8 μl; P < 0.005], and contractile dysfunction [ejection fraction (EF): 62 ± 4 vs. 38 ± 10%; P < 0.000005] was observed, as well as depressed cardiac energetics (PCr/ATP: 2.0 ± 0.1 vs. 1.3 ± 0.4, P < 0.0005) measured by combined MRI/MRS. After an additional 3 wk, LV mass (140 ± 26 vs. 167 ± 36 mg; P < 0.01) and cavity size (EDV: 61 ± 8 vs. 76 ± 8 μl; P < 0.001) increased further, but there was no additional decline in PCr/ATP or EF. Cardiac PCr/ATP correlated inversely with end-systolic volume and directly with EF at 6 wk but not at 3 wk, suggesting a role of sustained energetic abnormalities in evolving chamber dysfunction and remodeling. Indeed, reduced cardiac PCr/ATP observed at 3 wk strongly correlated with changes in EDV that developed over the ensuing 3 wk. These data suggest that abnormal energetics due to pressure overload predict subsequent LV remodeling and dysfunction.

Effects of arteriovenous fistula on systemic and pulmonary circulations

1964 ◽  
Vol 207 (6) ◽  
pp. 1319-1324 ◽  
Author(s):  
Jiro Nakano ◽  
Christian De Schryver
Keyword(s):  
Cardiac Output ◽  
Blood Transfusion ◽  
Arterial Pressure ◽  
Left Atrial ◽  
Pulmonary Arterial Pressure ◽  
Peripheral Resistance ◽  
Systemic Arterial Pressure ◽  
Left Ventricular ◽  
Stroke Work ◽  
Pulmonary Arterial

The effects of arteriovenous fistulas of different magnitudes on cardiovascular dynamics were studied in anesthetized dogs. It was found that A-V fistula decreases mean systemic arterial pressure, effective systemic blood flow, total and pulmonary peripheral resistances, whereas it increases heart rate, total cardiac output, stroke volume, left atrial pressure, pulmonary arterial pressure, and systemic peripheral resistance. The magnitude of the above hemodynamic changes was essentially proportional to the size of the fistula. At equivalent increments in total cardiac output produced by A-V fistula and blood transfusion, the former condition causes a greater increase in pulmonary arterial pressure than the latter, although both conditions decrease the pulmonary peripheral resistance by the same degree. It was also found that, at equivalent left atrial pressures, left ventricular stroke work with A-V fistula was greater than that with blood transfusion.

Abstract 19078: Early Predictors of Survival to Heart Transplantation in Patients With Amyloid Light-chain Cardiomyopathy

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Johannes Steiner ◽  
Van Selby ◽  
Karla Verkouw ◽  
Jana Svetlichnaya ◽  
Doreen Defaria Yeh ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Heart Transplantation ◽  
Right Ventricular ◽  
Light Chain ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cell Transplant ◽  
Stroke Work ◽  
Cardiac Amyloid ◽  
Amyloid Cardiomyopathy

Background: Amyloid cardiomyopathy progresses more rapidly and has different manifestations than more common cardiomyopathies. Nevertheless, survival of selected cardiac amyloid patients after orthotopic heart transplantation (OHT) followed by autologous stem cell transplant is similar to other restrictive cardiomyopathies. The importance of clinical presentation and pre-transplantation characteristics on outcome in patients with AL amyloid cardiomyopathy evaluated for heart transplantation is still not well defined. Methods: The impact of echocardiographic, hemodynamic, and clinical parameters on outcome in 46 patients evaluated for OHT and enrolled in the International Consortium for Cardiac Amyloid Transplant (iCCAT) database was studied. Cox proportional hazards models of time to death were used. End point was death after transplant evaluation censored at transplant. Results: The median age at the time of transplant evaluated was 57.6 (+/- 9.6) years, and the mean time from presentation to listing was 27 (+/- 26) days. 19 (41%) patients underwent OHT after an average wait time of 72 days. Univariate risk factors associated with death after initial evaluation were cardiac output (p=0.012), right ventricular stroke work index (p=0.033), left ventricular end diastolic dimension (p=0.024), left ventricular outflow tract velocity time integral (p=0.019), mean arterial pressures (p=0.005), NT pro-BNP (p=0.007), presence of pleural effusion (p=0.005), as well as elevated kappa and lambda serum free light chain concentrations (p=0.004). Whereas left ventricular ejection fraction did not correlate with death after evaluation, increased right ventricular wall thickness remained a strong mortality predictor in a multivariate model with light chain difference and cardiac output (HR 1.6 for every 1 mm increase in thickness, p=0.017). Conclusions: Pleural involvement, high light chain burden, and right ventricular infiltration predicted death while awaiting a donor organ and may be markers of more systemic disease. Ultimately, this could affect transplant candidate selection and allocation strategies.

Abstract 1756: Angiotensin II Induced End Organ Damage is Attenuated in Mice Lacking the Gene for TNF: A Mitochondrial Perspective

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Nithya Mariappan ◽  
Srinivas Sriramula ◽  
Joseph Francis
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Organ Damage ◽  
Left Ventricular ◽  
Lv Function ◽  
Resonance Spectroscopy ◽  
Cardiac Damage ◽  
Atp Production ◽  
End Organ Damage

Recent findings from our lab and others suggest that the renin-angiotensin system and cytokine interaction contribute to the pathophysiology of cardiovascular disease. In this study, we determined the role played by tumor necrosis factor (TNF) in angiotensin II (ANGII) induced end organ damage at the mitochondrial level. Method : Wild type (WT) and TNF knockout (TNF (−/−)) mice were implanted with osmotic minipumps containing ANG II (1 μg/kg/min) or saline for 14 days. Blood pressure was recorded using telemetry. At the end of the study, left ventricular (LV) function was measured using echocardiography. Mice were sacrificed and the LV was removed and mitochondria isolated for oxidative stress measurement using Electron paramagnetic resonance spectroscopy. Structural integrity of mitochondria was assessed by electron microscopy (EM) and function by measuring mitochondrial redox status. Results: (see table ) ANGII infusion in WT mice resulted in a significant increase in blood pressure and was accompanied by a decrease in fractional shortening. These animals also had increased levels of superoxide and ROS in the LV tissues. The mitochondrial integrity of the cardiomyocytes was damaged both in the isolated mitochondria and tissue as evidenced by EM studies. Mitochondrial superoxide and total ROS were increased and this was accompanied by a decrease in complex activity and reduced ATP production. In contrast, ANGII infusion in TNF (−/−) attenuated cardiac damage, mitochondrial oxidative stress and restored ATP production. Conclusion: ANGII induced cardiac damage is mediated by TNF. These data also demonstrate that ANGII induced increase in TNF inhibits mitochondrial function by affecting electron transport chain activity and indirectly through an increase in oxygen free radicals thereby decreasing ATP synthesis and contributing to end organ damage in hypertension.

Effect of positive end-expiratory pressure on ventricular function in dogs

1979 ◽  
Vol 236 (4) ◽  
pp. H534-H544 ◽  
Author(s):  
R. M. Prewitt ◽  
L. D. Wood
Keyword(s):  
Cardiac Output ◽  
Left Ventricular Function ◽  
Pulmonary Edema ◽  
Ventricular Function ◽  
Diastolic Pressure ◽  
Intrathoracic Pressure ◽  
Esophageal Pressure ◽  
Left Ventricular ◽  
Stroke Work ◽  
Positive End Expiratory Pressure

Artificial ventilation with positive end-expiratory pressure (PEEP) reduces venous return by raising intrathoracic pressure. To determine whether PEEP decreases cardiac output further by depressing myocardial function, we constructed Starling curves, using rapid dextran infusion in 7 anesthetized dogs ventilated with zero (ZEEP) and 20 cm PEEP. The changes in stroke volume and in left ventricular stroke work (LVSW) when PEEP was added or removed were significantly greater than could be attributed to the corresponding change in transmural left ventricular end-diastolic pressure (LVEDPTM) on these Starling curves. To the extent that PEEP did not alter left ventricular diastolic volume-pressure characteristics, these data indicated PEEP depressed ventricular function. Identical changes with PEEP in cardiac output (-30%), esophageal pressure (+10 cmH2O), and left ventricular function were observed after pulmonary edema was induced with oleic acid. These results confirm and extend recent suggestions that high levels of PEEP depress left ventricular function in dogs, accounting for about half of the reduction in cardiac output before and during acute pulmonary edema.

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