Factors involved in delaying the rise in peripheral resistance in developing heart failure

1994 ◽  
Vol 267 (1) ◽  
pp. H211-H216 ◽  
Author(s):  
K. Kiuchi ◽  
R. P. Shannon ◽  
N. Sato ◽  
M. Bigaud ◽  
C. Lajoie ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Peripheral Resistance ◽  
Left Ventricular ◽  
Right Atrial ◽  
Plasma Norepinephrine ◽  
Peripheral Vascular ◽  
Vascular Control ◽  
Developing Heart

The development of heart failure (HF) on peripheral vascular control was studied in 10 conscious dogs with measurements of cardiac output (CO) and left ventricular (LV), arterial, and right atrial pressures. At 3 wk after pacing-induced HF, CO was not decreased from 2.5 +/- 0.2 l/min, whereas LV dP/dt fell (from 2,858 +/- 71 to 1,409 +/- 69 mmHg/s) and LV end-diastolic pressure increased (from 4.8 +/- 0.4 to 27.3 +/- 1.1 mmHg) (P < 0.05). At 4–7 wk after pacing, CO was significantly decreased (to 1.6 +/- 0.1 l/min; P < 0.05), but total peripheral resistance (TPR) did not rise, despite increases in plasma norepinephrine and renin activity (P < 0.05). In the presence of ganglionic blockade, TPR was still not increased in HF. In vitro studies in isolated femoral artery segments demonstrated reduced intrinsic tone (0.028 +/- 0.007 g/mg; P < 0.05) as compared with vessels from sham-operated controls (0.124 +/- 0.023 g/mg), whereas the intracellular calcium level was not altered in HF. Thus, during the development of HF, severe contractile dysfunction precedes the fall in CO, which, in turn, precedes the rise in TPR. The delayed rise in TPR appears to involve a reduction in intrinsic peripheral vascular tone, despite neurohumoral activation.

Abstract 13438: The Role and Mechanism of Chronic Beta3-Adrenergic Receptor Blockade on the Progression of Heart Failure in a Rat Model

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Xiaoqiang Sun ◽  
Che Cheng ◽  
Jing Cao ◽  
Zhi Zhang ◽  
Tiankai Li ◽  
...  
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Left Ventricular ◽  
Plasma Norepinephrine ◽  
Functional Responses ◽  
Generating Capacity ◽  
Precise Role ◽  
Mini Pump

Background: The negative inotrope and up-regulation of β 3 -adrenergic receptors (AR) in human and animal failing hearts suggest a direct and contributing role of cardiac β 3 -AR activation on the progression of congestive heart failure (CHF). However, its precise role is still being debated. We hypothesize that up-regulation of cardiac β 3 -AR is detrimental and chronic β 3 -AR blockade may prevent CHF-caused intrinsic defects of left ventricular (LV) myocyte force-generating capacity and relaxation and improve β-AR regulation, thereby limiting the progression of CHF. Methods: We compared the alterations of LV and myocyte functional responses and [Ca 2+ ] i transient ([Ca 2+ ] iT ) in SD rats divided into 3 groups (8/group): 1) CHF 3 months after isoproterenol (ISO) (170 mg/kg, sq, for 2 days); 2) ISO/β 3 -ANT , 2 months after receiving ISO, a selective β 3 -AR antagonist (ANT), L-748,337, was initiated (10 -7 M/kg/day, sq. by mini-pump) and was given for 1 month; and 3) Sham controls . Results: Compared with controls, the animals that received ISO treatment had CHF onset at 1 month and progressed to severe HF at 3 months after ISO. Plasma norepinephrine (NE) (1295 vs 259 pg/ml) increased 5-fold; whereas, stroke volume (SV) (39 vs 91 μl) and ejection fraction (EF) (39 vs 62%) significantly decreased, and LV end-diastolic pressure (P ED ) (13.9 vs 6.0 mmHg) was doubled. These changes were paralleled with about 50% reductions in cell contraction (dL/dt max , 93 vs 186 μm/s) and relaxation (dR/dt max , 96 vs 159 μm/s) associated with a significant decrease in the peak systolic [Ca 2+ ] iT , (0.17 vs 0.26). In addition, superfusion of ISO (10 -8 M) caused much less increases in dL/dt max (39 vs 68%), dR/dt max (23 vs 54%), and [Ca 2+ ] IT (14 vs 28%). Treatment with β 3 -ANT increased SV (89 μl) and EF (60%), decreased P ED more than 90% from ISO-treated values, and corrected the elevation of plasma NE (301 pg/ml), dL/dt max (184 μm/s), dR/dt max (152 μm/s), and [Ca 2+ ] iT (0.24). ISO-induced increase in dL/dt max and [Ca 2+ ] iT also returned close to control levels. Conclusion: Chronic β 3 -ANT treatment after CHF significantly improves LV and myocyte contractile function and [Ca 2+ ] i regulation and limits the development of CHF. Thus, β 3 -AR blocker may provide a new therapeutic strategy for the treatment of CHF.

Hemodynamic and norepinephrine responses to pacing-induced heart failure in conscious sinoaortic-denervated dogs

1996 ◽  
Vol 81 (4) ◽  
pp. 1855-1855 ◽  
Author(s):  
Marian Brändle ◽  
Kaushik P. Patel ◽  
Wei Wang ◽  
Irving H. Zucker
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Control Level ◽  
Left Ventricular ◽  
Plasma Norepinephrine ◽  
Hemodynamic Parameters ◽  
Ventricular Pacing ◽  
Arterial Baroreflex ◽  
Failure State ◽  
Observation Period

Brändle, Marian, Kaushik P. Patel, Wei Wang, and Irving H. Zucker. Hemodynamic and norepinephrine responses to pacing-induced heart failure in conscious sinoaortic-denervated dogs. J. Appl. Physiol. 81(4): 1855–1862, 1996.—The present study was undertaken to determine the effects of chronic sinoaortic (baroreceptor) denervation (SAD) on the hemodynamic and sympathetic alterations that occur in the pacing-induced model of congestive heart failure. Two groups of dogs were examined: intact ( n = 9) and SAD ( n = 9). Both groups of dogs were studied in the control (prepace) state and each week after the initiation of ventricular pacing at 250 beats/min. After the pacemaker was turned off, hemodynamic and plasma norepinephrine levels returned toward control levels in the prepaced state and after 1 and 2 wk of pacing. However, by 3 wk all hemodynamic and norepinephrine levels remained relatively constant over the 10-min observation period with the pacemaker off. With the pacemaker off, left ventricular end-diastolic pressure went from 2.7 ± 1.4 (SE) mmHg during the prepace state to 23.2 ± 2.9 mmHg in the heart failure state in intact dogs ( P < 0.01). Left ventricular end-diastolic pressure increased to 27.1 ± 2.2 mmHg from a control level of 4.2 ± 1.9 mmHg in SAD dogs ( P < 0.0003). Mean arterial pressure significantly decreased in intact and SAD dogs. Resting heart rate was significantly higher in SAD dogs and increased to 135.8 ± 8.9 beats/min in intact dogs and 136.1 ± 6.5 beats/min in SAD dogs. There were no significant differences in the hemodynamic parameters between intact and SAD dogs after pacing. Plasma norepinephrine was significantly lower in intact than in SAD dogs before pacing (197.7 ± 21.6 vs. 320.6 ± 26.6 pg/ml; P < 0.005). In the heart failure state, plasma norepinephrine increased significantly in both intact (598.3 ± 44.2 pg/ml) and SAD (644.0 ± 64.6 pg/ml) groups. There were no differences in the severity or the magnitude of the developed heart failure state in SAD vs. intact dogs. We conclude from these data that the arterial baroreflex is not the sole mechanism for the increase in sympathetic drive in heart failure.

Increased ANF secretion after volume expansion is preserved in rats with heart failure

1988 ◽  
Vol 254 (2) ◽  
pp. R185-R191 ◽  
Author(s):  
Y. W. Chien ◽  
R. W. Barbee ◽  
A. A. MacPhee ◽  
E. D. Frohlich ◽  
N. C. Trippodo
Keyword(s):  
Heart Failure ◽  
Left Ventricle ◽  
Blood Volume ◽  
Volume Expansion ◽  
Diastolic Pressure ◽  
Venous Pressure ◽  
Peripheral Resistance ◽  
Left Ventricular ◽  
Coronary Artery Ligation ◽  
Blood Volume Expansion

To examine whether the failing heart has reached a maximal capacity to increase plasma atrial natriuretic factor (ANF) concentration, the change in plasma immunoreactive ANF level due to acute blood volume expansion was determined in conscious rats with chronic heart failure. Varying degrees of myocardial infarction and thus heart failure were induced by coronary artery ligation 3 wk before study. Compared with controls, infarcted rats had decreases in mean arterial pressure (-10 mmHg, P less than 0.01), cardiac index (-27%, P less than 0.001), renal blood flow (-35%, P less than 0.01), and peak left ventricle-developed pressure after aortic occlusion (an index of pressure generating ability; -15%, P less than 0.01), and increases in central venous pressure (+1.7 mmHg, P less than 0.01), left ventricular end-diastolic pressure (+10 mmHg, P less than 0.001), total peripheral resistance (+28%, P less than 0.01), and plasma ANF level (752 +/- 109 vs. 244 +/- 33 pg/ml, P less than 0.001). Plasma ANF was correlated with infarct size, cardiac filling pressures, and left ventricle pressure-generating ability. At 5 min after 25% blood volume expansion, plasma ANF in rats with heart failure increased by 2,281 +/- 345 pg/ml; the magnitude of the changes in circulating ANF and hemodynamic measurements was similar in controls. The results suggest that plasma ANF level can be used as a reliable index of the severity of heart failure, and that the capacity to increase plasma ANF concentration after acute volume expansion is preserved in rats with heart failure. There was no evidence of a relative deficiency of circulating ANF in this model of heart failure.

Alterations in brain hexokinase activity associated with heart failure in rats

1993 ◽  
Vol 265 (4) ◽  
pp. R923-R928 ◽  
Author(s):  
K. P. Patel ◽  
P. L. Zhang ◽  
T. L. Krukoff
Keyword(s):  
Heart Failure ◽  
Coronary Occlusion ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Right Atrial ◽  
Metabolic Enzyme ◽  
Control Group ◽  
Hexokinase Activity ◽  
The Brain

This study examined the activity of discrete regions of the brain as assessed with histological localization and photodensitometric quantification of the metabolic enzyme hexokinase in a group of rats with coronary occlusion (HF) and in sham-operated control rats. Three weeks after surgery, the mean left ventricular end diastolic pressure and right atrial pressure were elevated, and left ventricular peak systolic pressure was decreased in the HF group compared with the sham group; these findings are also observed during heart failure. In addition, histological data indicated that there was a 37.6 +/- 2.8% outer and 40.8 +/- 3.1% inner infarct of the myocardium in the group of rats with HF (n = 6). Rats in the control group had no observable damage to the myocardium (n = 6). Accompanying these symptoms of heart failure were significant increases in hexokinase activity in the parvocellular (pPVN, 16.3%) and magnocellular (mPVN, 17.6%) divisions of the paraventricular nucleus of the hypothalamus, and in the locus ceruleus (LC, 17.1%). No changes in hexokinase activity were observed in the median preoptic area, supraoptic nucleus (SON), subfornical organ, or posterior hypothalamus. These results reinforce the idea that heart failure (with coronary occlusion) is associated with changes in specific areas in the brain and that metabolic alterations in the pPVN, mPVN, and LC are likely related to alterations in vasopressin production, blood volume regulation, and sympathoexcitation observed in the heart failure state.

Myocardial adrenergic changes at two stages of heart failure due to adriamycin treatment in rats

1991 ◽  
Vol 260 (3) ◽  
pp. H909-H916 ◽  
Author(s):  
J. Tong ◽  
P. K. Ganguly ◽  
P. K. Singal
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Structural Changes ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Ventricular Systolic Pressure ◽  
Two Stages

Changes in myocardial norepinephrine (NE) levels, turnover, uptake, and release in rats were examined at two stages of cardiac dysfunction induced by adriamycin (ADR) given intraperitoneally in six equal doses over a period of 2 wk for a cumulative dose of 15 mg/kg. At 3 wk posttreatment, ADR-treated animals showed no changes in left ventricular systolic pressure (LVSP), aortic systolic pressure (ASP), and aortic diastolic pressure (ADP) but left ventricular end-diastolic pressure (LVEDP) was significantly higher. At 6 wk posttreatment, LVSP, ASP, and ADP were significantly lower and LVEDP remained elevated. Animals in both ADR-treated groups showed signs of congestive heart failure as indicated by ascites, congestive liver, and elevated LVEDP. Structural changes typical of ADR cardiomyopathy were more pronounced in the 6-wk group. In vivo hemodynamic as well as in vitro muscle function response to different concentrations of epinephrine was depressed in its duration as well as extent in both 3- and 6-wk ADR-treated groups. Myocardial NE levels were increased in the 3-wk group but were depressed in the 6-wk group. NE turnover was faster in both 3- and 6-wk ADR groups, uptake was increased only in the 6-wk group, and release was unchanged. These data show increased cardiac sympathetic tone at both stages of ADR-induced congestive heart failure.

scholarly journals Estrogen restores role of basal nitric oxide in control of vascular tone in rats with chronic heart failure

1998 ◽  
Vol 274 (6) ◽  
pp. H2094-H2099 ◽  
Author(s):  
Ali Akbar Nekooeian ◽  
Catherine C. Y. Pang
Keyword(s):  
Nitric Oxide ◽  
Heart Failure ◽  
Chronic Heart Failure ◽  
Diastolic Pressure ◽  
Peripheral Resistance ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Ovariectomized Rats ◽  
17Β Estradiol

This study examined the cardiovascular effects of 17β-estradiol in ovariectomized rats with heart failure. Two groups (50–60 days old) were implanted with 60-day-release pellets containing 17β-estradiol (25 μg/day) or vehicle at 7 days before ligation of the left coronary artery. Another group was sham operated and given vehicle pellets. After 7 wk, they were studied under pentobarbital anesthesia. Relative to sham-operated rats, ligated rats had reduced mean arterial pressure (MAP, −24 ± 6 mmHg), cardiac output (−27 ± 4 ml/min), left ventricular (LV) end-systolic pressure (−29 ± 8 mmHg), depressor responses to ACh (−6 ± 4 mmHg at 7.2 μg/kg) and sodium nitroprusside (SNP, −22 ± 6 mmHg at 9 μg/kg), and pressor responses to N G-nitro-l-arginine methyl ester (l-NAME, −14 ± 6 mmHg at 8 mg/kg) and increased LV end-diastolic pressure (LVEDP, 10.3 ± 0.8 mmHg) but no change in total peripheral resistance (TPR). Treatment of ligated rats with 17β-estradiol reduced TPR (−0.19 ± 0.06 mmHg ⋅ min ⋅ ml−1), LVEDP (−3.6 ± 1 mmHg), and responses to ACh (−16 ± 4 mmHg) and augmented responses tol-NAME (14 ± 3 mmHg) but did not alter other variables. Therefore, 17β-estradiol reduces preload and afterload and restores the vasodilator role of basal nitric oxide in ovariectomized rats with chronic heart failure.

Cardiovascular effects of MnDPDP and mncl2 in Dogs with Acute Ischaemic Heart Failured

1997 ◽  
Vol 38 (5) ◽  
pp. 750-758 ◽  
Author(s):  
J. O.G. Karlsson ◽  
E. Mortensen ◽  
H. K. Pedersen ◽  
G. Sager ◽  
H. Refsum
Keyword(s):  
Heart Failure ◽  
Diastolic Pressure ◽  
Plasma Catecholamines ◽  
Cardiovascular Effects ◽  
Aortic Pressure ◽  
Left Ventricular ◽  
Right Atrial ◽  
Clinical Dose ◽  
Human Dose ◽  
Slow Infusion

Purpose: To examine the cardiovascular effects of MnDPDP in a model of acute heart failure in the dog, and to compare these effects with those of MnCl2. Material and Methods: The study involved slow i.v. infusion of either 10,60 and 300 μmol/kg of MnDPDP, or 1, 6 and 30 μmol/kg MnCl2, in increasing doses to groups of 5 dogs. Acute ischaemic heart failure was first induced by injection of polystyrene microspheres (50 ± 10 μm) into the left coronary artery until a stable left ventricular end-diastolic pressure of approximately 20 mm Hg was achieved. The following test parameters were measured: left ventricular end-diastolic pressure; the first derivatives of maximum rate of left ventricular contraction and relaxation; mean aortic pressure; pulmonary artery pressure; right atrial pressure; cardiac ouput; heart rate; QT-time; PQ-time; QRS-width; and plasma catecholamines. Results: Slow infusion of MnDPDP at doses up to and including 12 times the clinical dose was well tolerated in dogs without further depression of cardiovascular function during acute ischaemic heart failure. At 300 μmol/kg, i.e. 60 times the human dose, only minor haemodynamic and electrophysiological effects were seen, and these were similar to those seen after administration of 30 μmol/kg MnCl2. Conclusion: The present study suggests that slow infusion of MnDPDP should not cause further deteroriation of cardiac function in patients with heart failure.

Effect of a specific and a nonspecific vasodilator on regional blood flows in experimental heart faiiure

1982 ◽  
Vol 60 (2) ◽  
pp. 174-183 ◽  
Author(s):  
K. L. MacCannell ◽  
G. D. Giraud ◽  
K. Lederis ◽  
P. L. Hamilton ◽  
G. Groves
Keyword(s):  
Heart Failure ◽  
Cardiac Output ◽  
Sodium Nitroprusside ◽  
Mechanism Of Action ◽  
Diastolic Pressure ◽  
Peripheral Resistance ◽  
Cardiovascular Effects ◽  
Left Ventricular ◽  
Blood Flows ◽  
Regional Blood Flows

Urotensin I, a vasoactive peptide isolated from fish urophyses, has previously been demonstrated to cause specific mesenteric dilation in the dog. This mechanism of action should limit its maximal cardiovascular actions: no additional cardiovascular effects should ensue once maximal mesenteric vasodilatation is achieved. Provided that the mesenteric vasodilatation does not result in decreased flow to other organs, the agent may, therefore, offer a theoretical advantage as an afterload reducing agent. In pentobarbital anesthetized dogs which were in heart failure as a result of chronic aortico – left atrial shunt, the effects of urotensin I on cardiovascular hemodynamics were compared with the effects of a nonspecific vasodilator, sodium nitroprusside. At equidepressor doses (approximately 15% decrease in mean arterial pressure; sodium nitroprusside, 2 μg∙kg−1∙min−1 i.v.; urotensin I, 10 mU∙kg−1∙min−1 i.v.), both agents produced comparable falls in total peripheral resistance, left ventricular end diastolic pressure, and pulmonary capillary wedge pressure. Forward cardiac output was increased by both substances, although the increases were not statistically significant. Shunt flow, estimated by echocardiography, was reduced by both. In spite of the marked similarity in hemodynamic effects in this model, the two agents affected regional blood flows differently. Sodium nitroprusside did not significantly alter regional flows measured by radioactive microspheres, although calculated splanchnic, skin, and myocardial vascular resistances were reduced. In contrast, urotensin I, as in the normal dog, greatly increased mesenteric blood flow; this redistribution of cardiac output did not, however, result in underperfusion of other vital organs. These data suggest that urotensin I may be a useful agent in the reduction of afterload in heart failure, particularly since the unique mechanism of action appears to minimize the potential for adverse effects due to excessive dosage.

scholarly journals Tricuspid Regurgitation in Left Ventricular Systolic Dysfunction: Marker or Target?

2021 ◽  
Vol 8 ◽  
Author(s):  
Davide Margonato ◽  
Francesco Ancona ◽  
Giacomo Ingallina ◽  
Francesco Melillo ◽  
Stefano Stella ◽  
...  
Keyword(s):  
Heart Failure ◽  
Tricuspid Regurgitation ◽  
Diastolic Pressure ◽  
Left Ventricular Systolic Dysfunction ◽  
Systolic Dysfunction ◽  
The United States ◽  
Left Ventricular ◽  
Right Atrial ◽  
Common Finding ◽  
Ventricular Systolic Dysfunction

Far from being historically considered a primary healthcare problem, tricuspid regurgitation (TR) has recently gained much attention from the scientific community. In fact, in the last years, robust evidence has emerged regarding the epidemiological impact of TR, whose prevalence seems to be similar to that of other valvulopathies, such as aortic stenosis, with an estimated up to 4% of people &gt;75 years affected by at least moderate TR in the United States, and up to 23% among patients suffering from heart failure with reduced ejection fraction. This recurrent coexistence of left ventricular systolic dysfunction (LVSD) and TR is not surprising, considered the multiple etiologies of tricuspid valve disease. TR can complicate heart failure mostly as a functional disease, because of pulmonary hypertension (PH), subsequent to elevated left ventricular end-diastolic pressure, leading to right ventricular dilatation, and valve tethering. Moreover, the so-called “functional isolated” TR can occur, in the absence of PH, as a result of right atrial dilatation associated with atrial fibrillation, a common finding in patients with LVSD. Finally, TR can result as a iatrogenic consequence of transvalvular lead insertion, another frequent scenario in this cohort of patients. Nonetheless, despite the significant coincidence of these two conditions, their mutual relation, and the independent prognostic role of TR is still a matter of debate. Whether significant TR is just a marker for advanced left-heart disease, or a crucial potential therapeutical target, remains unclear. Aim of the authors in this review is to present an update concerning the epidemiological features and the clinical burden of TR in the context of LVSD, its prognostic value, and the potential benefit for early tricuspid intervention in patients affected by contemporary TR and LVSD.

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