THE ANTIACCELERATOR EFFECT OF VERATRAMINE ON THE ISOLATED PERFUSED HEART OF THE CAT

1957 ◽  
Vol 35 (1) ◽  
pp. 173-179
Author(s):  
Maurice F. Murnaghan

When isopropylarterenol was continuously infused in the isolated perfused heart of the cat, the heart rate remained at a steady elevated level for more than 2 hours. Veratramine selectively antagonized the accelerator effect of isopropylarterenol, and the dose required to cause a 50% reduction in acceleration (I50) was determined. The mean I50 value in 13 experiments (mean of the 13 individual I50 values) is 0.415 micromolar (μM) with fiducial limits of 0.182–0.648. Cardiac irregularities, arising from the sinoauricular node, occurred in seven out of 13 experiments after the administration of veratramine. The results indicate that in this preparation coronary flow is related to amplitude but is independent of heart rate.

1957 ◽  
Vol 35 (3) ◽  
pp. 173-179 ◽  
Author(s):  
Maurice F. Murnaghan

When isopropylarterenol was continuously infused in the isolated perfused heart of the cat, the heart rate remained at a steady elevated level for more than 2 hours. Veratramine selectively antagonized the accelerator effect of isopropylarterenol, and the dose required to cause a 50% reduction in acceleration (I50) was determined. The mean I50 value in 13 experiments (mean of the 13 individual I50 values) is 0.415 micromolar (μM) with fiducial limits of 0.182–0.648. Cardiac irregularities, arising from the sinoauricular node, occurred in seven out of 13 experiments after the administration of veratramine. The results indicate that in this preparation coronary flow is related to amplitude but is independent of heart rate.


1990 ◽  
Vol 18 (4a) ◽  
pp. 497-510 ◽  
Author(s):  
Peter G. Anderson ◽  
Stanley B. Digerness ◽  
Jerald L. Sklar ◽  
Paul J. Boor

The isolated perfused rat heart model can be used to evaluate cardiotoxicity, and is especially useful in distinguishing direct vs indirect cardiac injury. Various perfusion systems can be used to characterize the pathophysiologic as well as morphologic changes induced by drugs or chemicals of interest. The isolated perfused heart was used in the studies described herein to characterize the mechanism of allylamine cardiotoxicity. Rat hearts were perfused with Krebs-Henseleit buffer containing 10 mm allylamine and a latex balloon was inserted into the left ventricle to monitor pressure. Coronary flow in hearts perfused with 10 mm allylamine was similar to control hearts at 5, 10, and 30 min, but was reduced by 1 hr (11.5 ± 0.6 ml/min/g wet heart weight vs 16.0 ± 0.7, p < 0.01). Peak left ventricular systolic pressure increased in hearts perfused with allylamine for 5 min (156 ± 8 mm Hg vs 103 ± 9, p < 0.01), but by 2 hr was decreased compared to controls (89 ± 6 vs 105 ± 5, p < 0.05). End diastolic pressure was markedly increased at 2 hr (58 ± 3 vs 4 ± 0.8, p < 0.01). Morphologically, allylamine perfused hearts exhibited significant contraction band changes as well as numerous cells with marked swelling of the sarcoplasmic reticulum. The findings in this study suggest that allylamine produces direct myocardial damage that appears to be independent of coronary flow. These studies demonstrate that the isolated perfused rat heart model can be used to evaluate mechanisms of acute cardiotoxicity.


1964 ◽  
Vol 206 (4) ◽  
pp. 905-908 ◽  
Author(s):  
Joseph C. Shipp ◽  
James R. Spencer ◽  
Lamar E. Crevasse

The pattern of distribution of Rb86 in sections of the isolated perfused heart was determined as a measure of uniformity of coronary artery flow. Results suggest that coronary flow was uniform after nonrecirculated perfusion for 15 min. Similar results were obtained in hearts perfused for 30 and for 60 min. The distribution of Rb86 was comparable in hearts perfused for 30 min with perfusate circulated through either coarse porosity, sintered-glass filters or 5-µ Millipore filters. A nonuniform distribution of isotope was demonstrated with ligation of branches of coronary arteries and with the introduction of air. The results suggest that hearts perfused by recirculation of buffer through coarse porosity, sintered-glass filters have a uniform distribution of perfusate throughout the heart.


Life Sciences ◽  
1984 ◽  
Vol 34 (2) ◽  
pp. 105-112 ◽  
Author(s):  
Dong-Hee Kim ◽  
Tai Akera ◽  
Richard H. Kennedy ◽  
Paul M. Stemmer

1989 ◽  
Vol 67 (2) ◽  
pp. 274-280 ◽  
Author(s):  
A. P. Farrell ◽  
S. Small ◽  
M. S. Graham

While adrenergic stimulation and increased filling pressure of the heart are recognized to increase cardiac stroke volume in the trout heart, the effects of factors such as heart rate and oxygen supply have not been examined. The present study used isolated, saline-perfused trout hearts to determine the maximum cardiac performance during hypoxic perfusion and during changes in pacing frequency similar to the range of heart rate observed in intact trout. The threshold oxygen tension of the perfusate was between 25 and 46 Torr (3.33–6.13 kPa) for maintaining resting and maximum cardiac ouput, but was between 46 and 67 Torr (6.13 – 8.93 kPa) for maintaining maximum power output. Increasing the pacing frequency from 30 to 58 beats/min did not produce a proportionate increase in the maximum cardiac output because maximum stroke volume was reduced significantly. It is suggested that the reduction in maximum stroke volume occurs because atrial filling time is compromised at higher pacing frequencies in the isolated perfused heart.


1961 ◽  
Vol 200 (3) ◽  
pp. 633-636 ◽  
Author(s):  
Peter F. Salisbury ◽  
Cecil E. Cross ◽  
P. Andre Rieben

Measurements of the weight and of the residual blood in an isolated, perfused heart permitted investigation of factors which influence coronary blood volume. Coronary blood volume was a near linear function of coronary arterial pressure between 30 and 125 mm Hg and was also linearly related to coronary flow in fresh preparations. For each 1 mm Hg change of mean coronary perfusion pressure, a corresponding change of the coronary blood volume occurred, amounting to about 100 mg blood/100 gm perfused heart. Decreases of contractile strength or heart rate caused reversible increases of the coronary blood volume.


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
AF Lubberding ◽  
S Veedfald ◽  
SM Sattler ◽  
BM Linz ◽  
CHE Eggertsen ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation Synergy program Novo Nordisk Foundation Center for Basic Metabolic Research Background  Treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with type 2 diabetes not only reduces hyperglycaemia, but also improves cardiovascular outcomes. However, GLP-1 RA treatment also increases heart rate: an apparent paradox. Purpose  Whether the heart rate increase is a direct effect, and whether GLP-1 affects other aspects of cardiac electrophysiology, remain unclear. To answer these questions we investigated the effect of GLP-1 infusion on cardiac electrophysiology in vivo and ex vivo in pigs and pig hearts, respectively, during sinus rhythm and pacing. Methods  Anaesthetised pigs (n = 8) received infusions of GLP-1 (10 pmol/kg/min). Electrocardiogram, atrial monophasic action potentials and atrial conduction velocity data were collected and atrial and ventricular effective refractory periods (ERP) were measured. For the ex vivo studies, pig hearts (n = 7) were excised, retrogradely perfused and exposed to consecutive bolus perfusions of 2 and 4 nmol GLP-1, 100 nmol of the GLP-1 receptor antagonist exendin-9-39 and a final 4 nmol bolus of GLP-1. The same electrophysiological parameters were measured. Results  In anaesthetised pigs, GLP-1 increased heart rate, cardiac output and diastolic pressure, while systemic vascular resistance was decreased. Infusion of GLP-1 decreased PQ interval in sinus rhythm (P = 0.019, n = 8) and during atrial pacing (P = 0.027, n = 6) with 8 ± 3 % and 12 ± 3 %, respectively. Additionally, GLP-1 decreased atrial ERP at all pacing cycle lengths (P = 0.04, n = 7), while ventricular ERP was unaffected (P = 0.29, n = 7). In the isolated perfused heart, GLP-1 increased heart rate with 13 ± 2 bpm (P = 0.001, n = 7). This increase in heart rate was completely abolished by pre-administration of exendin-9-39. Atrial ERP shortened after GLP-1 perfusion (P = 0.01, n = 7) comparable to the in vivo studies, with an average decrease of 11 ± 2 %. This effect was also abolished by exendin-9-39. Conclusion  GLP-1 increases heart rate through activation of the GLP-1 receptor in the isolated perfused heart, suggesting a direct effect of GLP-1 rather than activation through the central nervous system. Additionally, GLP-1 affects atrial electrophysiology, but not ventricular electrophysiology, in vivo and ex vivo independent of the increase in heart rate.


2020 ◽  
Vol 91 (10) ◽  
pp. 785-789
Author(s):  
Dongqing Wen ◽  
Lei Tu ◽  
Guiyou Wang ◽  
Zhao Gu ◽  
Weiru Shi ◽  
...  

INTRODUCTION: We compared the physiological responses, psychomotor performances, and hypoxia symptoms between 7000 m and 7500 m (23,000 and 24,600 ft) exposure to develop a safer hypoxia training protocol.METHODS: In altitude chamber, 66 male pilots were exposed to 7000 and 7500 m. Heart rate and arterial oxygen saturation were continuously monitored. Psychomotor performance was assessed using the computational task. The hypoxic symptoms were investigated by a questionnaire.RESULTS: The mean duration time of hypoxia was 323.0 56.5 s at 7000 m and 218.2 63.3 s at 7500 m. The 6-min hypoxia training was completed by 57.6% of the pilots and 6.1% of the pilots at 7000 m and at 7500 m, respectively. There were no significant differences in pilots heart rates and psychomotor performance between the two exposures. The Spo2 response at 7500 m was slightly severer than that at 7000 m. During the 7000 m exposure, pilots experienced almost the same symptoms and similar frequency order as those during the 7500 m exposure.CONCLUSIONS: There were concordant symptoms, psychomotor performance, and very similar physiological responses between 7000 m and 7500 m during hypoxia training. The results indicated that 7000-m hypoxia awareness training might be an alternative to 7500-m hypoxia training with lower DCS risk and longer experience time.Wen D, Tu L, Wang G, Gu Z, Shi W, Liu X. Psychophysiological responses of pilots in hypoxia training at 7000 and 7500 m. Aerosp Med Hum Perform. 2020; 91(10):785789.


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