Acute effects of amiodarone in the isolated dog heart

1983 ◽  
Vol 61 (4) ◽  
pp. 308-314 ◽  
Author(s):  
Miyoharu Kobayashi ◽  
Diane Godin ◽  
Réginald Nadeau
Keyword(s):  
Sinus Node ◽  
Direct Injection ◽  
Left Ventricular ◽  
Ventricular Muscle ◽  
Inotropic Effects ◽  
Percent Change ◽  
Sinus Node Artery ◽  
Arterial Blood ◽  
Chronotropic Effects ◽  
Dose Dependent

Direct injection of amiodarone (10–1000 μg) into the sinus node artery of the isolated blood-perfused dog atrium produced dose-dependent negative inotropic and chronotropic responses that were unaffected by atropine. Intraarterial amiodarone also had a negative inotropic action on isolated left ventricular muscle preparations electrically paced at 1.5 to 2.0 Hz. A continuous infusion of 100 μg/min of amiodarone significantly suppressed the positive chronotropic effect of norepinephrine whether expressed in percent change or in absolute values; its positive inotropic effect expressed in percent change was not suppressed but rather enhanced by amiodarone. Calcium chloride induced positive chronotropic and inotropic effects expressed in percent change were, respectively, slightly suppressed and enhanced by amiodarone. Intravenous injection of amiodarone (5 mg/kg) decreased the heart rate and blood pressure of the support dog and produced a negative inotropic response in the isolated left ventricular muscle preparation perfused with arterial blood from the support dog. These results suggest first, that amiodarone has direct negative inotropic and chronotropic effects that are not mediated by cholinergic mechanisms and second, that it has a depressive action on norepinephrine and calcium-induced positive chronotropic effects and an enhancing action on their positive inotropic effects.

THE BEHAVIOR OF ATRIO–VENTRICULAR NODAL RHYTHM FOLLOWING DIRECT PERFUSION OF THE SINUS NODE

1966 ◽  
Vol 44 (2) ◽  
pp. 317-324 ◽  
Author(s):  
R. A. Nadeau ◽  
T. N. James
Keyword(s):  
Sinus Node ◽  
Gradual Transition ◽  
Sinus Arrest ◽  
P Waves ◽  
Pharmacological Agents ◽  
Node Activity ◽  
Relaxation Oscillators ◽  
Sinus Node Artery ◽  
Chronotropic Effects ◽  
Sinus Node Activity

Direct perfusion of the canine sinus node with various pharmacological agents having negative chronotropic effects commonly leads either to abrupt sinus arrest or to a gradual transition from sinus to atrio–ventricular (A–V) nodal rhythm with progressive shortening of the P–R interval. The reappearance of sinus rhythm is usually preceded by a change in A–V nodal rate and a progressive lengthening of the P–R interval to a stable value. During A–V nodal rhythm, changes in heart rate are observed following injections into the sinus node artery. As perfusion of the sinus node is selective, these cannot be attributed to a direct pharmacological effect of the perfusates on the A–V node. Deliberate suppression of A–V nodal pacemaking dominance reveals the persistence of slow sinus node activity which is unapparent electrocardiographically during A–V nodal rhythm. It would seem that even in the absence of P waves, the sinus node may still influence the rate of the A–V node. These observations are consistent with the hypothesis that the sinus and A–V nodes behave as a system of coupled relaxation oscillators.

scholarly journals Mesenteric lymph duct ligation prevents trauma/hemorrhage shock-induced cardiac contractile dysfunction

2009 ◽  
Vol 106 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Justin T. Sambol ◽  
Marlon A. Lee ◽  
Francis J. Caputo ◽  
Kentaro Kawai ◽  
Chirag Badami ◽  
...  
Keyword(s):  
Cardiac Dysfunction ◽  
Experimental Studies ◽  
Left Ventricular ◽  
Lv Function ◽  
Contractile Dysfunction ◽  
Inotropic Effects ◽  
Arterial Blood ◽  
Mesenteric Lymph ◽  
Duct Ligation ◽  
Lymph Duct

Clinical and experimental studies have shown that trauma combined with hemorrhage shock (T/HS) is associated with myocardial contractile dysfunction. However, the initial events triggering the cardiac dysfunction are not fully elucidated. Thus we tested the hypothesis that factors carried in intestinal (mesenteric) lymph contribute to negative inotropic effects in rats subjected to a laparotomy (T) plus hemorrhagic shock (HS; mean arterial blood pressure of 30–40 Torr for 90 min) using a Langendorff isolated heart preparation. Left ventricular (LV) function was assessed 24 h after trauma plus sham shock (T/SS) or T/HS by recording the LV developed pressure (LVDP) and the maximal rate of LVDP rise and fall ( ± dP/d tmax) in five groups of rats: 1) naive noninstrumented rats, 2) rats subjected to T/SS, 3) rats subjected to T/HS, 4) rats subjected to T/SS with mesenteric lymph duct ligation (T/SS+LDL), or 5) rats subjected to T/HS+LDL. Cardiac function was comparable in hearts from naive, T/SS, and T/SS+LDL rats. Both LVDP and ± dP/d tmax were significantly depressed after T/HS. The T/HS hearts also manifested a blunted responsiveness to increases in coronary flow rates and Ca2+, and this was prevented by LDL preceding T/HS. Although electrocardiograms were normal under physiological conditions, when the T/HS hearts were perfused with low Ca2+ levels (∼0.5 mM), prolonged P-R intervals and second-degree plus Wenckebach-type atrioventricular blocks were observed. No such changes occurred in the control or T/HS+LDL hearts. The effects of T/HS were similar to those of the Ca2+ channel antagonist diltiazem, indicating that an impairment of cellular Ca2+ handling contributes to T/HS-induced cardiac dysfunction. In conclusion, gut-derived factors carried in mesenteric lymph are responsible for acute T/HS-induced cardiac dysfunction.

Effect of platelet-activating factor on coronary circulation of the domestic pig

1984 ◽  
Vol 246 (3) ◽  
pp. H466-H471 ◽  
Author(s):  
G. Feuerstein ◽  
L. M. Boyd ◽  
D. Ezra ◽  
R. E. Goldstein
Keyword(s):  
Coronary Circulation ◽  
White Blood Cells ◽  
Platelet Activating Factor ◽  
Left Ventricular Pressure ◽  
Systemic Effect ◽  
Left Ventricular ◽  
Domestic Pig ◽  
Arterial Blood ◽  
Dose Dependent Increase ◽  
Dose Dependent

The platelet-activating factor released by white blood cells and platelets has been shown to be 1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine (AGEPC). To fully understand the cardiovascular actions of this substance, we examined the effects of AGEPC on coronary blood flow (CBF) and other hemodynamic parameters in anesthetized open-chest domestic pigs. Mean arterial blood pressure (MBP), electrocardiogram, heart rate (HR), left ventricular pressure, and CBF were continuously recorded. AGEPC was injected (bolus, 0.1 ml) into the left anterior descending coronary artery at increasing doses of 0.03-10 nmol. Intracoronary AGEPC produced biphasic changes in CBF: a dose-dependent increase in CBF (up to 50%) followed by a decrease (up to 92%) in CBF. The changes in CBF were not directly related to any systemic effect, although MBP was reduced consistently after a dose higher than 1 nmol of AGEPC. The increase in CBF produced by AGEPC was not affected by pretreatment with indomethacin (6 mg/kg) or FPL 55712 (1 or 3 mg), an inhibitor of slow-reacting substance of anaphylaxis (SRS-A). The decrease in CBF produced by AGEPC was attenuated by FPL 55712 and blocked by indomethacin. These data suggest that AGEPC release from aggregating platelets might play a major role in modulating CBF and cardiac function in states involving platelet-coronary interaction.

Differential sensitivity to neurotransmitters in denervated canine sinus node

1977 ◽  
Vol 233 (2) ◽  
pp. H211-H216 ◽  
Author(s):  
G. R. Hageman ◽  
F. Urthaler ◽  
T. N. James
Keyword(s):  
Blood Pressure ◽  
Sinus Node ◽  
Differential Sensitivity ◽  
Electrical Stability ◽  
Extrinsic Denervation ◽  
Cardiac Denervation ◽  
Sinus Node Artery ◽  
Before And After ◽  
Selective Perfusion ◽  
Chronotropic Effects

This investigation determined the chronotropic effects of norepinephrine and acetylcholine (ACh) administered selectively into the canine sinus node artery after cardiac denervation. In 42 dogs the cervical vagi were isolated, the heart was exposed, and vagal stimulations were performed before and after sham procedure or extrinsic cardiac parasympathectomy. Four additional dogs underwent bilateral stellectomy. The dogs were reanesthetized 4-23 days later, and blood pressure, heart rate, ECG, and local cardiac electrograms were recorded. The vagi were again stimulated and the effectiveness of the parasympathectomy was verified in 11 of the dogs. On selective perfusion of the sinus node with 0.001- to 1-microgram doses of ACh, the sinus bradycardias of the parasympathectomized and the sham-operated dogs were not significantly different. The responses to norepinephrine (0.01 and 0.1 microgram/ml) administered via the same route in the stellectomized dogs were significantly greater than those in the sham-operated dogs, thus verifying this technique for the assessment of sinus node sensitivity to neurotrasmitters. We conclude that extrinsic denervation of the canine sinus node leads to development of a differential response between adrenergic and cholinergic neurotransmitters. These differential sensitivities may be important when considering the pharmacological responses and electrical stability of the denervated and/or transplanted heart.

Negative chronotropic and parasympatholytic effects of alinidine on canine sinus node and AV junction

1985 ◽  
Vol 248 (3) ◽  
pp. H324-H330
Author(s):  
G. R. Hageman ◽  
B. H. Neely ◽  
F. Urthaler ◽  
T. N. James
Keyword(s):  
Sinus Node ◽  
Stellate Ganglion ◽  
Stimulus Frequency ◽  
Response Curves ◽  
Sinus Node Artery ◽  
Sinus Rate ◽  
Before And After ◽  
Anesthetized Dogs ◽  
Selective Perfusion ◽  
Chronotropic Effects

The direct effects of alinidine (N-allyl-clonidine) on the sinus node and atrioventricular (AV) junction were studied in 18 anesthetized dogs. Stimulus frequency-response curves to right stellate ganglion and right cervical vagus stimulations as well as responses to norepinephrine or acetylcholine were determined before and after selective perfusion of alinidine into the sinus node artery. Alinidine (1 microgram/ml) had no effect on spontaneous sinus rate [148 +/- 5 (SE) beats/min]. However, alinidine concentrations of 5, 10, and 25 micrograms/ml produced significant (P less than 0.05) sinus slowing to 138, 127, and 121 beats/min, respectively. Recovery to control rate was dose dependent and took from 4 to 33 min. Sinus rate increases with right stellate stimulations were not affected by alinidine. However, sinus rate decreases with right vagal stimulations were significantly (P less than 0.01) attenuated by alinidine. The negative chronotropic effects of acetylcholine were not influenced by alinidine. Alinidine (1-100 micrograms/ml into AV node artery) had no effect on the A-H interval of the His bundle electrogram. However, alinidine (10 and 25 micrograms/ml) diminished the AV block produced by stimulation of the left vagus in electrically paced hearts but not the negative dromotropic actions of directly administered acetylcholine. Thus alinidine has direct negative chronotropic effects, no effect on sinus node responses to sympathetic stimulation, ability to diminish sinus node and AV junctional responses to vagal stimulations without interference at the cholinergic muscarinic receptor, and 4) no effect on AV nodal conduction.

Vasorelaxant and Antihypertensive Effects of Mentha pulegium L. in Rats: An in vitro and in vivo Approach

2020 ◽  
Vol 20 ◽  
Author(s):  
Mohammed Ajebli ◽  
Mohamed Eddouks
Keyword(s):  
Blood Pressure ◽  
Acute Experiment ◽  
Antihypertensive Activity ◽  
Mentha Pulegium ◽  
In Vitro Experiment ◽  
Arterial Blood ◽  
Dose Dependent ◽  
Ca2 Channels

Aims and objective: The aim of the study was to investigate the effect of aqueous aerial part extract of Mentha pulegium L. (Pennyrile) (MPAE) on arterial pressure parameters in rats. Background: Mentha pulegium is a medicinal plant used to treat hypertension in Morocco. Material and methods: In the current study, MPAE was prepared and its antihypertensive activity was pharmacologically investigated. L-NAME-hypertensive and normotensive rats have received orally MPAE (180 and 300 mg/kg) during six hours for the acute experiment and during seven days for the sub-chronic treatment. Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were evaluated. While, in the in vitro experiment, isolated denuded and intact thoracic aortic rings were suspended in a tissue bath system and the tension changes were recorded. Results: A fall in blood pressure was observed in L-NAME-induced hypertensive treated with MPAE. The extract also produced a dose-dependent relaxation of aorta pre-contracted with NE and KCl. The study showed that the vasorelaxant ability of MPAE seems to be exerted through the blockage of extracellular Ca2+ entry. Conclusion: The results demonstrate that the extract of pennyrile exhibits antihypertensive activity. In addition, the effect may be, at least in part, due to dilation of blood vessels via blockage of Ca2+ channels.

scholarly journals Effects of candesartan on left ventricular hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Maqsood ◽  
H.A Shakeel ◽  
H.F Shoukat ◽  
M.D Khan ◽  
S.A.Y Shah ◽  
...  
Keyword(s):  
Late Gadolinium Enhancement ◽  
Hypertrophic Cardiomyopathy ◽  
Interstitial Fibrosis ◽  
Angiotensin Receptor Blockers ◽  
Left Ventricular ◽  
Funding Source ◽  
Gadolinium Enhancement ◽  
Percent Change ◽  
Lv Mass ◽  
Significant Difference

Abstract Introduction Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular (LV) hypertrophy in the absence of pressure overload. Manifestations of the disease include heart failure associated with diastolic dysfunction and atrial and ventricular tachyarrhythmias. Pathological features of HCM include myocyte hypertrophy, interstitial fibrosis, and myocyte disarray and are mediated by angiotensin II. Purpose This study aimed to evaluate the effects of candesartan on left ventricular (LV) hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy (HCM). Methods In double-blind fashion, 30 patients (6 women, 24 men; age: 55±11 years) with HCM were randomly assigned to receive placebo (n=13) or candesartan 50 mg twice a day (n=17) for 1 year. To measure LV mass and extent of fibrosis, cardiac magnetic resonance imaging was performed at baseline and 1 year as assessed by late gadolinium enhancement. Results There was a trend toward a significant difference in the percent change in LV mass (median: +5% with placebo vs. −5% with candesartan; p=0.06). There was a significant difference in the percent change in the extent of late gadolinium enhancement, with the placebo group experiencing a larger increase (+30±27% with placebo vs. −22±44% with candesartan; p=0.03). Conclusion Our study concludes reduction of the progression of myocardial hypertrophy and fibrosis with candesartan in patients with hypertrophic cardiomyopathy. Our study population was limited so we warrant larger trials to confirm a place for angiotensin receptor blockers in the management of patients with hypertrophic cardiomyopathy. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): Self funding

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