Effects of Thyroid Hormone on Cardiac Function - The Relative Importance of Heart Rate, Loading Conditions, and Myocardial Contractility in the Regulation of Cardiac Performance in Human Hyperthyroidism

Numerous studies have examined the effect of temperature on in vivo and in situ cardiovascular function in trout. However, little information exists on cardiac function at temperatures near the trout's upper lethal limit. This study measured routine and maximum in situ cardiac performance in rainbow trout (Oncorhynchus mykiss) following acclimation to 15, 18 and 22 °C, under conditions of tonic (30 nmol l-1), intermediate (60 nmol l-1) and maximal (200 nmol l-1) adrenergic stimulation. Heart rate increased significantly with both temperature and adrenaline concentration. The Q10 values for heart rate ranged from 1.28 at 30 nmol l-1 adrenaline to 1.36 at 200 nmol l-1 adrenaline. In contrast to heart rate, maximum stroke volume declined by approximately 20 % (from 1.0 to 0.8 ml kg-1) as temperature increased from 15 to 22 °C. This decrease was not alleviated by maximally stimulating the heart with 200 nmol l-1 adrenaline. Because of the equal and opposite effects of increasing temperature on heart rate and stroke volume, maximum cardiac output did not increase between 15 and 22 °C. Maximum power output decreased (by approximately 10-15 %) at all adrenaline concentrations as temperature increased. This reduction reflected a poorer pressure-generating ability at temperatures above 15 °C. These results, in combination with earlier work, suggest (1) that peak cardiac performance occurs around the trout's preferred temperature and well below its upper lethal limit; (2) that the diminished cardiac function concomitant with acclimation to high temperatures was associated with inotropic failure; (3) that Q10 values for cardiac rate functions, other than heart rate per se, have a limited predictive value at temperatures above the trout's preferred temperature; and (4) that heart rate is a poor indicator of cardiac function at temperatures above 15 °C.

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Influence of the coronary circulation on thermal tolerance and cardiac performance during warming in rainbow trout

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00536.2016 ◽

2017 ◽

Vol 312 (4) ◽

pp. R549-R558 ◽

Cited By ~ 7

Author(s):

Andreas Ekström ◽

Michael Axelsson ◽

Albin Gräns ◽

Jeroen Brijs ◽

Erik Sandblom

Keyword(s):

Heart Rate ◽

Blood Flow ◽

Rainbow Trout ◽

Cardiac Function ◽

Thermal Tolerance ◽

Coronary Flow ◽

Coronary Circulation ◽

Cardiac Performance ◽

Juvenile Trout

Thermal tolerance in fish may be related to an oxygen limitation of cardiac function. While the hearts of some fish species receive oxygenated blood via a coronary circulation, the influence of this oxygen supply on thermal tolerance and cardiac performance during warming remain unexplored. Here, we analyzed the effect in vivo of acute warming on coronary blood flow in adult sexually mature rainbow trout ( Onchorhynchus mykiss) and the consequences of chronic coronary ligation on cardiac function and thermal tolerance in juvenile trout. Coronary blood flow at 10°C was higher in females than males (0.56 ± 0.08 vs. 0.30 ± 0.08 ml·min−1·g ventricle−1), and averaged 0.47 ± 0.07 ml·min−1·g ventricle−1 across sexes. Warming increased coronary flow in both sexes until 14°C, at which it peaked and plateaued at 0.78 ± 0.1 and 0.61 ± 0.1 ml·min−1·g ventricle−1 in females and males, respectively. Thus, the scope for increasing coronary flow was 101% in males, but only 39% in females. Coronary-ligated juvenile trout exhibited elevated heart rate across temperatures, reduced Arrhenius breakpoint temperature for heart rate (23.0 vs. 24.6°C), and reduced upper critical thermal maximum (25.3 vs. 26.3°C). To further analyze the effects of coronary flow restriction on cardiac rhythmicity, electrocardiogram characteristics were determined before and after coronary occlusion in anesthetized trout. Occlusion resulted in reduced R-wave amplitude and an elevated S-T segment, indicating myocardial ischemia, while heart rate was unaffected. This suggests that the tachycardia in ligated trout across temperatures in vivo was mainly to compensate for reduced cardiac contractility to maintain cardiac output. Moreover, our findings show that coronary flow increases with warming in a sex-specific manner. This may improve whole animal thermal tolerance, presumably by sustaining cardiac oxygenation and contractility at high temperatures.

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Adrenergic tone benefits cardiac performance and warming tolerance in two teleost fishes that lack a coronary circulation

Journal of Comparative Physiology B ◽

10.1007/s00360-021-01359-9 ◽

2021 ◽

Author(s):

Andreas Ekström ◽

Erika Sundell ◽

Daniel Morgenroth ◽

Erik Sandblom

Keyword(s):

Heart Rate ◽

Cardiac Function ◽

High Temperatures ◽

Oxygen Delivery ◽

Thermal Tolerance ◽

Heart Function ◽

Perca Fluviatilis ◽

Cardiac Performance ◽

Adrenergic Stimulation

AbstractTolerance to acute environmental warming in fish is partly governed by the functional capacity of the heart to increase systemic oxygen delivery at high temperatures. However, cardiac function typically deteriorates at high temperatures, due to declining heart rate and an impaired capacity to maintain or increase cardiac stroke volume, which in turn has been attributed to a deterioration of the electrical conductivity of cardiac tissues and/or an impaired cardiac oxygen supply. While autonomic regulation of the heart may benefit cardiac function during warming by improving myocardial oxygenation, contractility and conductivity, the role of these processes for determining whole animal thermal tolerance is not clear. This is in part because interpretations of previous pharmacological in vivo experiments in salmonids are ambiguous and were confounded by potential compensatory increases in coronary oxygen delivery to the myocardium. Here, we tested the previously advanced hypothesis that cardiac autonomic control benefits heart function and acute warming tolerance in perch (Perca fluviatilis) and roach (Rutilus rutilus); two species that lack coronary arteries and rely entirely on luminal venous oxygen supplies for cardiac oxygenation. Pharmacological blockade of β-adrenergic tone lowered the upper temperature where heart rate started to decline in both species, marking the onset of cardiac failure, and reduced the critical thermal maximum (CTmax) in perch. Cholinergic (muscarinic) blockade had no effect on these thermal tolerance indices. Our findings are consistent with the hypothesis that adrenergic stimulation improves cardiac performance during acute warming, which, at least in perch, increases acute thermal tolerance.

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Functional and metabolic adaptation of the heart to prolonged thyroid hormone treatment

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00282.2002 ◽

2003 ◽

Vol 284 (1) ◽

pp. H108-H115 ◽

Cited By ~ 32

Author(s):

H. Degens ◽

A. J. Gilde ◽

M. Lindhout ◽

P. H. M. Willemsen ◽

G. J. van der Vusse ◽

...

Keyword(s):

Thyroid Hormone ◽

Cardiac Function ◽

Atrial Natriuretic Factor ◽

Cardiac Performance ◽

Metabolic Adaptation ◽

Initial Increase ◽

Mrna Levels ◽

Long Term Effects ◽

Natriuretic Factor ◽

Atrial Natriuretic

In heart failure, thyroid hormone (TH) treatment improves cardiac performance. The long-term effects of TH on cardiac function and metabolism, however, are incompletely known. To investigate the effects of up to 28 days of TH treatment, male Wistar rats received 3,3′,5-triiodo-l-thyronine (200 μg/kg sc per day) leading to a 2.5-fold rise in plasma fatty acid (FA) level and progressive cardiac hypertrophy (+47% after 28 days) ( P < 0.001). Ejection fraction (echocardiography) was increased (+12%; P < 0.05) between 7 and 14 days and declined thereafter. Neither cardiac FA oxidation, glycolytic capacity (homogenates) per unit muscle mass, nor mRNA levels of proteins involved in FA and glucose uptake and metabolism (Northern blots and microarray) were altered. After 28 days of treatment, mRNA levels of uncoupling proteins (UCP) 2 and 3 and atrial natriuretic factor were increased ( P < 0.05). This indicates that TH-induced hypertrophy is associated with an initial increase in cardiac performance, followed by a decline in cardiac function and increased expression of UCPs and atrial natriuretic factor, suggesting that detrimental effects eventually prevail.

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Heart rate as a marker of relapse during withdrawal of heart failure therapy in patients with recovered dilated cardiomyopathy: an analysis from TRED-HF

European Heart Journal ◽

10.1093/ehjci/ehaa946.1057 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

B Halliday ◽

A Vazir ◽

R Owen ◽

J Gregson ◽

R Wassall ◽

...

Keyword(s):

Heart Rate ◽

Cardiac Function ◽

Dilated Cardiomyopathy ◽

Funding Source ◽

End Point ◽

Therapy Withdrawal ◽

The Mean ◽

Withdrawal Of Therapy ◽

Continue Therapy

Abstract Introduction In TRED-HF, 40% of patients with recovered dilated cardiomyopathy (DCM) relapsed in the short-term during phased withdrawal of drug therapy. Non-invasive markers of relapse may be used to monitor patients who wish a trial of therapy withdrawal and provide insights into the pathophysiological drivers of relapse. Purpose To investigate the relationship between changes in heart rate (HR) and relapse amongst patients with recovered DCM undergoing therapy withdrawal in TRED-HF. Methods Patients with recovered DCM were randomised to phased withdrawal of therapy or to continue therapy for 6 months. After 6 months of continued therapy, those in the control arm underwent withdrawal of therapy in a single arm crossover phase. HR was measured at each study visit. Mean HR and 95% confidence intervals (CI) were calculated at baseline, 45 days after baseline, 45 days prior to the end of the study or relapse and at the end of the study or relapse. Patients were stratified by treatment arm and the occurrence of the primary relapse end-point. Heart rate at follow-up was compared amongst patients who had therapy withdrawn and relapsed versus those who had therapy withdrawn and did not. ANCOVA was used to adjust for differences in HR at baseline between the two groups. Results Of 51 patients randomised, 26 were assigned to continue therapy and 25 to withdraw therapy. In the randomised and cross-over phases, 20 patients met the primary relapse end-point; one patient withdrew from the study and one patient completed follow-up in the control arm but did not enter the cross-over phase. Mean HR (standard deviation) at baseline and follow-up for (i) patients in the control arm was 69.9 (9.8) & 65.9 (9.1) respectively; (ii) for those who had therapy withdrawn and did not relapse was 64.6 (10.7) & 74.7 (10.4) respectively; and (iii) for those who had therapy withdrawn and relapsed was 68.3 (11.3) & 86.1 (11.8) respectively [all beats per minute]. The mean change in HR between the penultimate visit and the final visit for those who had therapy withdrawn and did not relapse was −2.4 (9.7) compared to 3.1 (15.5) for those who relapsed. After adjusting for differences in HR at baseline, the mean difference in HR measured at follow-up between patients who underwent therapy withdrawal and did, and did not relapse was 10.4bpm (95% CI 4.0–16.8; p=0.002) (Figure 1 & Table 1). Conclusion(s) A larger increase in HR may be a simple and effective marker of relapse for patients with recovered DCM who have insisted on a trial of therapy withdrawal. Whether HR control is crucial to the maintenance of remission amongst patients with improved cardiac function, or is simply a marker of deteriorating cardiac function, warrants further investigation. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): British Heart Foundation

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Circulating Catecholamines and Systolic Time Intervals in Labile and Sustained Hypertension

Clinical Science ◽

10.1042/cs055065s ◽

1978 ◽

Vol 55 (s4) ◽

pp. 65s-68s ◽

Cited By ~ 7

Author(s):

D. Cousineau ◽

J. de Champlain ◽

L. Lapointe

Keyword(s):

Heart Rate ◽

Essential Hypertension ◽

Myocardial Contractility ◽

Systolic Time Intervals ◽

Normal Range ◽

Time Intervals ◽

Hypertensive Patients ◽

Sustained Hypertension ◽

Systolic Time ◽

Hypotensive Response

1. Average supine circulating total catecholamine concentrations were found to be higher than the normal range in about 50% of patients with labile hypertension and in about 30% of patients with sustained essential hypertension. 2. These higher resting concentrations were mainly due to an increase in adrenaline in labile hypertension and to an increase in noradrenaline in sustained hypertension. 3. Patients with elevated catecholamine concentrations were also characterized by a higher heart rate, by an increased myocardial contractility and by greater hypotensive response after treatment with β-adrenoreceptor blocking agents. 4. These studies suggest the existence of subgroups of hypertensive patients with increased sympathetic tone.

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Protective effects of garlic extract on cardiac function, heart rate variability, and cardiac mitochondria in obese insulin-resistant rats

European Journal of Nutrition ◽

10.1007/s00394-013-0595-6 ◽

2013 ◽

Vol 53 (3) ◽

pp. 919-928 ◽

Cited By ~ 27

Author(s):

Luerat Supakul ◽

Hiranya Pintana ◽

Nattayaporn Apaijai ◽

Siriporn Chattipakorn ◽

Krekwit Shinlapawittayatorn ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Cardiac Function ◽

Garlic Extract ◽

Protective Effects ◽

Cardiac Mitochondria ◽

Insulin Resistant

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Rescue pre-operative treatment with Lugol’s solution in uncontrolled Graves’ disease

Endocrine Connections ◽

10.1530/ec-17-0025 ◽

2017 ◽

Vol 6 (4) ◽

pp. 200-205 ◽

Cited By ~ 6

Author(s):

Jan Calissendorff ◽

Henrik Falhammar

Keyword(s):

Heart Rate ◽

Thyroid Hormone ◽

Side Effects ◽

Definitive Treatment ◽

Graves Disease ◽

Free T4 ◽

Hormone Levels ◽

Free T3 ◽

Adherence To Medication ◽

Thyroid Hormone Levels

Background Graves’ disease is a common cause of hyperthyroidism. Three therapies have been used for decades: pharmacologic therapy, surgery and radioiodine. In case of adverse events, especially agranulocytosis or hepatotoxicity, pre-treatment with Lugol’s solution containing iodine/potassium iodide to induce euthyroidism before surgery could be advocated, but this has rarely been reported. Methods All patients hospitalised due to uncontrolled hyperthyroidism at the Karolinska University Hospital 2005–2015 and treated with Lugol’s solution were included. All electronic files were carefully reviewed manually, with focus on the cause of treatment and admission, demographic data, and effects of iodine on thyroid hormone levels and pulse frequency. Results Twenty-seven patients were included. Lugol’s solution had been chosen due to agranulocytosis in 9 (33%), hepatotoxicity in 2 (7%), other side effects in 11 (41%) and poor adherence to medication in 5 (19%). Levels of free T4, free T3 and heart rate decreased significantly after 5–9 days of iodine therapy (free T4 53–20 pmol/L, P = 0.0002; free T3 20–6.5 pmol/L, P = 0.04; heart rate 87–76 beats/min P = 0.0007), whereas TSH remained unchanged. Side effects were noted in 4 (15%) (rash n = 2, rash and vomiting n = 1, swelling of fingers n = 1). Thyroidectomy was performed in 26 patients (96%) and one was treated with radioiodine; all treatments were without serious complications. Conclusion Treatment of uncontrolled hyperthyroidism with Lugol’s solution before definitive treatment is safe and it decreases thyroid hormone levels and heart rate. Side effects were limited. Lugol’s solution could be recommended pre-operatively in Graves’ disease with failed medical treatment, especially if side effects to anti-thyroid drugs have occurred.

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Abstract 47: Loss of the Cardio Protection Inferred by S-nitrosylation of GRK2 At Cysteine 340 Leads to Decreased Cardiac Performance and a Hypertensive Phenotype With Aging

Circulation Research ◽

10.1161/res.117.suppl_1.47 ◽

2015 ◽

Vol 117 (suppl_1) ◽

Author(s):

Christopher J Traynham ◽

Ancai Yuan ◽

Erhe Gao ◽

Walter Koch

Keyword(s):

Cardiac Hypertrophy ◽

Cardiac Function ◽

Ischemia Reperfusion ◽

Cardiac Performance ◽

Heart Weight ◽

Cardiac Phenotype ◽

Cardio Protection ◽

G Protein Coupled ◽

Global Population

In the next 35 years, the global population of individuals above 60 years of age will double to approximately 2 billion. In the aged population, cardiovascular diseases are known to occur at a higher prevalence ultimately leading to increased mortality. G protein-coupled receptors (GPCRs) have been identified as vital regulators of cardiac function. GPCR kinases (GRKs) are important in cardiac GPCR regulation through desensitization of these receptors. GRK2 is highly expressed in the heart, and has been widely characterized due to its upregulation in heart failure. Studies from our lab have shown that elevated GRK2 levels in ischemia-reperfusion (I/R) injury result in a pro-death phenotype. Interestingly, cardio-protection can be inferred via S-nitrosylation of GRK2 at cysteine 340. Further, we have generated a knock-in GRK2 340S mouse, in which cysteine 340 was mutated to block dynamic GRK2 S-nitrosylation. GRK2 340S mice are more susceptible to I/R injury. Given that GRK2 340S mice are more susceptible to oxidative stress, and there is a nitroso-redox imbalance in senescence, it is possible that these mice are more likely to exhibit decreased cardiac performance as they age. Therefore, we hypothesize that with age GRK2 340S knockin mice will develop an overall worsened cardiac phenotype compared to control wild-type (WT) mice. To test this hypothesis, 340S and WT mice were aged for a year, and cardiac function was evaluated via echocardiography. Aged 340S mice exhibited significantly decreased ejection fraction and fraction shortening relative to aged WT controls. Prior to tissue harvesting, in-vivo hemodynamics was conducted via Millar catheterization. At baseline, aged 340S mice exhibited increased systolic blood pressure compared to aged WT mice. At the conclusion of this protocol, mice were sacrificed and heart weight (HW), body weight (BW), and tibia length (TL) measured to evaluate cardiac hypertrophy. Aged 340S mice exhibited significantly increased HW/BW and HW/TL ratios, indicative of cardiac hypertrophy, relative to aged WT controls. Taken together, these data suggest that with age, loss of the cardio protection inferred by S-nitrosylation of GRK2 at leads to decreased cardiac performance, and an overall worsened cardiac phenotype.

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Interaction of interval-force relationship with aortic pressure and stroke volume

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1976.230.4.893 ◽

1976 ◽

Vol 230 (4) ◽

pp. 893-900 ◽

Cited By ~ 2

Author(s):

ER Powers ◽

Foster ◽

Powell WJ

Keyword(s):

Heart Rate ◽

Stroke Volume ◽

Diastolic Pressure ◽

Aortic Pressure ◽

Left Ventricular ◽

Cardiac Performance ◽

Right Heart ◽

Anesthetized Dogs ◽

Right Heart Bypass ◽

Force Relationship

The modification by aortic pressure and stroke volume of the response in cardiac performance to increases in heart rate (interval-force relationship) has not been previously studied. To investigate this interaction, 30 adrenergically blocked anesthetized dogs on right heart bypass were studied. At constant low aortic pressure and stroke volume, increasing heart rate (over the entire range 60-180) is associated with a continuously increasing stroke power, decreasing systolic ejection period, and an unchanging left ventricular end-diastolic pressure and circumference. At increased aortic pressure or stroke volume at low rates (60-120), increases in heart rate were associated with an increased performance. However, at increased aortic pressure or stroke volume at high rates (120-180), increases in heart rate were associated with a leveling or decrease in performance. Thus, an increase in aortic pressure or stroke volume results in an accentuation of the improvement in cardiac performance observed with increases in heart rate, but this response is limited to a low heart rate range. Therefore, the hemodynamic response to given increases in heart rate is critically dependent on aortic pressure and stroke volume.

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