Adrenomedullin-epinephrine cotreatment enhances cardiac output and left ventricular function by energetically neutral mechanisms

2012 ◽  
Vol 302 (8) ◽  
pp. H1584-H1590
Author(s):  
Thor Allan Stenberg ◽  
Anders Benjamin Kildal ◽  
Ole-Jakob How ◽  
Truls Myrmel
Keyword(s):  
Heart Failure ◽  
Blood Flow ◽  
Cardiac Output ◽  
Acute Heart Failure ◽  
Coronary Blood Flow ◽  
Drug Effects ◽  
Left Ventricular ◽  
Experimental Myocardial Infarction ◽  
Energetic Cost ◽  
Lv Function

Adrenomedullin (AM) used therapeutically reduces mortality in the acute phase of experimental myocardial infarction. However, AM is potentially deleterious in acute heart failure as it is vasodilative and inotropically neutral. AM and epinephrine (EPI) are cosecreted from chromaffin cells, indicating a physiological interaction. We assessed the hemodynamic and energetic profile of AM-EPI cotreatment, exploring whether drug interaction improves cardiac function. Left ventricular (LV) mechanoenergetics were evaluated in 14 open-chest pigs using pressure-volume analysis and the pressure-volume area-myocardial O2 consumption (PVA-MV˙o2) framework. AM (15 ng·kg−1·min−1, n = 8) or saline (controls, n = 6) was infused for 120 min. Subsequently, a concurrent infusion of EPI (50 ng·kg−1·min−1) was added in both groups (AM-EPI vs. EPI). AM increased cardiac output (CO) and coronary blood flow by 20 ± 10% and 39 ± 14% (means ± SD, P < 0.05 vs. baseline), whereas controls were unaffected. AM-EPI increased CO and coronary blood flow by 55 ± 17% and 75 ± 16% ( P < 0.05, AM-EPI interaction) compared with 13 ± 12% ( P < 0.05 vs. baseline) and 18 ± 31% ( P = not significant) with EPI. LV systolic capacitance decreased by −37 ± 22% and peak positive derivative of LV pressure (dP/d tmax) increased by 32 ± 7% with AM-EPI ( P < 0.05, AM-EPI interaction), whereas no significant effects were observed with EPI. Mean arterial pressure was maintained by AM-EPI and tended to decrease with EPI (+2 ± 13% vs. −11 ± 10%, P = not significant). PVA-MV˙o2 relationships were unaffected by all treatments. In conclusion, AM-EPI cotreatment has an inodilator profile with CO and LV function augmented beyond individual drug effects and is not associated with relative increases in energetic cost. This can possibly take the inodilator treatment strategy beyond hemodynamic goals and exploit the cardioprotective effects of AM in acute heart failure.

Volume expansion potentiates cardiac sympathetic afferent reflex in dogs

2001 ◽  
Vol 280 (2) ◽  
pp. H576-H581 ◽  
Author(s):  
Wei Wang ◽  
Harold D. Schultz ◽  
Rong Ma
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Blood Flow ◽  
Arterial Pressure ◽  
Coronary Blood Flow ◽  
Volume Expansion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Blood Volume Expansion ◽  
Cardiac Sympathetic Afferent Reflex

Our previous study (27) showed that the cardiac sympathetic afferent reflex (CSAR) was enhanced in dogs with congestive heart failure. The aim of this study was to test whether blood volume expansion, which is one characteristic of congestive heart failure, potentiates the CSAR in normal dogs. Ten dogs were studied with sino-aortic denervation and bilateral cervical vagotomy. Arterial pressure, left ventricular pressure, left ventricular epicardial diameter, heart rate, and renal sympathetic nerve activity were measured. Coronary blood flow was also measured and, depending on the experimental procedure, controlled. Blood volume expansion was carried out by infusion of isosmotic dextran into a femoral vein at 40 ml/kg at a rate of 50 ml/min. CSAR was elicited by application of bradykinin (5 and 50 μg) and capsaicin (10 and 100 μg) to the epicardial surface of the left ventricle. Volume expansion increased arterial pressure, left ventricular pressure, left ventricular diameter, and coronary blood flow. Volume expansion without controlled coronary blood flow only enhanced the RSNA response to the high dose (50 μg) of epicardial bradykinin (17. 3 ± 1.9 vs. 10.6 ± 4.8%, P < 0.05). However, volume expansion significantly enhanced the RSNA responses to all doses of bradykinin and capsaicin when coronary blood flow was held at the prevolume expansion level. The RSNA responses to bradykinin (16. 9 ± 4.1 vs. 5.0 ± 1.3% for 5 μg, P < 0.05, and 28.9 ± 3.7 vs. 10.6 ± 4.8% for 50 μg, P < 0.05) and capsaicin (29.8 ± 6.0 vs. 9.3 ± 3.1% for 10 μg, P < 0.05, and 34.2 ± 2.7 vs. 15.1 ± 2.7% for 100 μg, P < 0.05) were significantly augmented. These results indicate that acute volume expansion potentiated the CSAR. These data suggest that enhancement of the CSAR in congestive heart failure may be mediated by the concomitant cardiac dilation, which accompanies this disease state.

Treatment of subclinical hypothyroidism reverses ischemia and prevents myocyte loss and progressive LV dysfunction in hamsters with dilated cardiomyopathy

2005 ◽  
Vol 289 (6) ◽  
pp. H2409-H2415 ◽  
Author(s):  
Wissam I. Khalife ◽  
Yi-Da Tang ◽  
James A. Kuzman ◽  
Tracy A. Thomas ◽  
Brent E. Anderson ◽  
...  
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Cardiac Disease ◽  
Subclinical Hypothyroidism ◽  
Thyroid Dysfunction ◽  
Left Ventricular ◽  
Lv Function ◽  
Lv Dysfunction ◽  
Lv Ejection Fraction ◽  
Isolated Myocyte

Growing evidence suggests that thyroid dysfunction may contribute to progression of cardiac disease to heart failure. We investigated the effects of a therapeutic dose of thyroid hormones (TH) on cardiomyopathic (CM) hamsters from 4 to 6 mo of age. CM hamsters had subclinical hypothyroidism (normal thyroxine, elevated TSH). Left ventricular (LV) function was determined by echocardiography and hemodynamics. Whole tissue pathology and isolated myocyte size and number were assessed. TH treatment prevented the decline in heart rate and rate of LV pressure increase and improved LV ejection fraction. The percentage of fibrosis/necrosis in untreated 4-mo-old CM (4CM; 15.5 ± 2.2%) and 6-mo-old CM (6CM; 21.5 ± 2.4%) hamsters was pronounced and was reversed in treated CM (TCM; 11.9 ± 0.9%) hamsters. Total ventricular myocyte number was the same between 4- and 6-mo-old controls but was reduced by 30% in 4CM and 43% in 6CM hamsters. TH treatment completely prevented further loss of myocytes in TCM hamsters. Compared with age-matched controls, resting and maximum coronary blood flow was impaired in 4CM and 6CM hamsters. Blood flow was completely normalized by TH treatment. We conclude that TH treatment of CM hamsters with subclinical hypothyroidism normalized impaired coronary blood flow, which prevented the decline in LV function and loss of myocytes.

Myocardial, skeletal muscle, and renal blood flow during exercise in conscious dogs with heart failure

1997 ◽  
Vol 273 (5) ◽  
pp. H2452-H2457 ◽  
Author(s):  
Till Neumann ◽  
Gerd Heusch
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Cardiac Output ◽  
Renal Blood Flow ◽  
Plasma Catecholamines ◽  
Left Ventricular ◽  
Conscious Dogs ◽  
Ventricular Pacing ◽  
Control State

The present study characterizes the hemodynamic and neurohumoral responses to moderate treadmill exercise in conscious dogs with pacing-induced heart failure. Seven dogs were instrumented with a left ventricular micromanometer, ultrasonic crystals for the measurement of systolic wall thickening, left atrial and aortic catheters for the injection of colored microspheres and reference withdrawal, respectively, and ventricular pacing leads with a subcutaneous pacemaker. Dogs were run on a treadmill at a speed of 5 km/h. After control studies, heart failure was induced by rapid left ventricular pacing at 250 beats/min for (mean ± SD) 23 ± 6 days. In the control state, cardiac output was increased from 4.5 ± 1.5 to 7.9 ± 1.4 l/min ( P < 0.05 vs. rest). With heart failure, cardiac output was decreased to 2.5 ± 0.5 l/min at rest ( P < 0.05 vs. control state) and was only 3.0 ± 0.3 l/min during exercise ( P < 0.05 vs. control state; not significant vs. rest). Myocardial and, more so, skeletal muscle blood flows at rest were reduced in heart failure; their increases with exercise were attenuated. An increase in renal blood flow during exercise in the control state was no longer seen in heart failure. Increases in plasma catecholamines and lactate during exercise were more pronounced in heart failure. In conclusion, in heart failure, the increase in cardiac output during exercise was largely attenuated. Increased catecholamine levels may have contributed to splanchnic vasoconstriction and preferential distribution of cardiac output into the working skeletal muscle.

Effects of metabolic acidosis and alkalosis on coronary blood flow and myocardial metabolism in the intact dog

1961 ◽  
Vol 200 (3) ◽  
pp. 628-632 ◽  
Author(s):  
A. V. N. Goodyer ◽  
W. F. Eckhardt ◽  
R. H. Ostberg ◽  
M. J. Goodkind
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Metabolic Acidosis ◽  
Coronary Blood Flow ◽  
Venous Blood ◽  
Left Ventricular ◽  
Myocardial Uptake ◽  
Severe Metabolic Acidosis ◽  
Glucose Levels ◽  
Arterial Blood

Severe metabolic acidosis and alkalosis were induced in anesthetized dogs by the infusion of solutions of hydrochloric acid and sodium bicarbonate. Infusions of sodium chloride were administered to other dogs under the same experimental circumstances. Measurements were made of arterial blood pressure, heart rate, cardiac output and coronary blood flow, arterial blood pH, and the content of oxygen, total CO2, lactate, pyruvate and glucose in both arterial and coronary venous blood. The cardiac output and coronary blood flow were decreased by acidosis and increased by alkalosis, the changes induced by alkalosis. There were no significant changes of left ventricular efficiency. Acidosis increased blood glucose concentrations and interfered with the increased myocardial uptake of glucose expected at higher arterial glucose levels. Alkalosis increased blood lactate and pyruvate levels and, correspondingly, the myocardial uptake of these carbohydrate substrates. It is concluded that cardiac dynamic function (as indicated by measurements of cardiac efficiency and output and arterial pressure) is much less affected by severe metabolic acidosis in the intact animal than in the isolated perfused organ.

Dynamic regulation of leg vasomotor tone in patients with chronic heart failure

1991 ◽  
Vol 71 (3) ◽  
pp. 1070-1075 ◽  
Author(s):  
M. J. Sullivan ◽  
F. R. Cobb
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Cardiac Output ◽  
Chronic Heart Failure ◽  
Left Ventricular ◽  
Work Rate ◽  
Vasomotor Tone ◽  
Leg Blood Flow ◽  
Leg Exercise

We examined the central hemodynamic (n = 5) and leg blood flow (n = 9) responses to one- and two-leg bicycle exercise in nine ambulatory patients with chronic heart failure due to left ventricular systolic dysfunction (ejection fraction 17 +/- 9%). During peak one- vs. two-leg exercise, leg blood flow (thermodilution) tended to be higher (1.99 +/- 0.91 vs. 1.67 +/- 0.91 l/min, P = 0.07), whereas femoral arteriovenous oxygen difference was lower (13.6 +/- 3.1 vs. 15.0 +/- 2.9 ml/dl, P less than 0.01). Comparison of data from exercise stages matched for single-leg work rate during one- vs. two-leg exercise demonstrated that cardiac output was similar while both oxygen consumption and central arteriovenous oxygen differences were lower, indicating relative improvement in the cardiac output response at a given single-leg work rate during one-leg exercise. This was accompanied by higher leg blood flow (1.56 +/- 0.76 vs. 1.83 +/- 0.72 l/min, P = 0.02) and a tendency for leg vascular resistance to be lower (92 +/- 54 vs. 80 +/- 48 Torr.l-1.min, P = 0.08) without any change in blood lactate. These data indicate that, in patients with chronic heart failure, leg vasomotor tone is dynamically regulated, independent of skeletal muscle metabolism, and is not determined solely by intrinsic abnormalities in skeletal muscle vasodilator capacity. Our results suggest that relative improvements in central cardiac function may lead to a reflex release of skeletal muscle vasoconstrictor tone in this disorder.

scholarly journals To Balloon or Not to Balloon? The Effects of an Intra-Aortic Balloon-Pump on Coronary Artery Flow during Extracorporeal Circulation Simulating Normal and Low Cardiac Output Syndromes

2021 ◽  
Vol 10 (22) ◽  
pp. 5333
Author(s):  
Philippe Reymond ◽  
Karim Bendjelid ◽  
Raphaël Giraud ◽  
Gérald Richard ◽  
Nicolas Murith ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Coronary Artery ◽  
Coronary Blood Flow ◽  
Low Cardiac Output ◽  
Coronary Artery Flow ◽  
Artery Flow

ECMO is the most frequently used mechanical support for patients suffering from low cardiac output syndrome. Combining IABP with ECMO is believed to increase coronary artery blood flow, decrease high afterload, and restore systemic pulsatile flow conditions. This study evaluates that combined effect on coronary artery flow during various load conditions using an in vitro circuit. In doing so, different clinical scenarios were simulated, such as normal cardiac output and moderate-to-severe heart failure. In the heart failure scenarios, we used peripheral ECMO support to compensate for the lowered cardiac output value and reach a default normal value. The increase in coronary blood flow using the combined IABP-ECMO setup was more noticeable in low heart rate conditions. At baseline, intermediate and severe LV failure levels, adding IABP increased coronary mean flow by 16%, 7.5%, and 3.4% (HR 60 bpm) and by 6%, 4.5%, and 2.5% (HR 100 bpm) respectively. Based on our in vitro study results, combining ECMO and IABP in a heart failure setup further improves coronary blood flow. This effect was more pronounced at a lower heart rate and decreased with heart failure, which might positively impact recovery from cardiac failure.

Importance of injection site for coronary blood flow determinations by microspheres in rats

1982 ◽  
Vol 242 (1) ◽  
pp. H94-H97 ◽  
Author(s):  
P. Wicker ◽  
R. C. Tarazi
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Injection Site ◽  
Coronary Blood Flow ◽  
Left Atrial ◽  
Left Ventricular ◽  
Significant Difference ◽  
Standard Deviations

Because coronary blood flow (CBF) determinations require that blood and microspheres be uniformly mixed in the root of the aorta, we developed a technique of left-atrial (LA) catheterization in rats and compared the variability of results obtained by LA injection and left-ventricular (LV) injection as regards systemic [cardiac output (CO)], proximal (coronary), and distal (renal, cerebral) flows in anesthetized animals. CBF values averaged 410 +/- 224 and 358 +/- 99 (SD) ml.min-1.100 g-1 from LV and LA injection, respectively, or 5.7 +/- 2.9 and 4.9 +/- 1.3 (SD) %CO. The variability with LA injection was significantly lower than with LV injection as shown by the marked differences in standard deviations obtained with the two methods (224 vs. 99 ml.min-1.100 g-1 or 2.9 vs. 1.3 %CO, P greater than 0.01). In contrast, no significant difference in variability was found for either CO or more distal regional flows. These results indicate that LV injections might be adequate for systemic flow and regional flows to relatively distal beds but that accurate measurements of CBF require LA injection of microspheres.

Assessment of Minimally Invasive Device That Provides Simultaneous Adjustable Cardiac Support and Active Synchronous Assist in an Acute Heart Failure Model

2011 ◽  
Vol 5 (4) ◽  
Author(s):  
Michael R. Moreno ◽  
Saurabh Biswas ◽  
Lewis D. Harrison ◽  
Guilluame Pernelle ◽  
Matthew W. Miller ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Output ◽  
Minimally Invasive ◽  
Acute Heart Failure ◽  
Left Ventricular ◽  
Reverse Remodeling ◽  
Stroke Work ◽  
Mechanical Parameters ◽  
Failure Model ◽  
Mechanical Environment

One of the major maladaptive changes after a major heart attack or cardiac event is an initial decline in pumping capacity of the heart leading to activation of a variety of compensatory mechanisms, and subsequently a phenomenon known as cardiac or left ventricular remodeling, i.e., a geometrical change in the architecture of the left ventricle. Evidence suggests that the local mechanical environment governs remodeling processes. Thus, in order to control two important mechanical parameters, cardiac size and cardiac output, we have developed a minimally invasive direct cardiac contact device capable of providing two actions simultaneously: (1) adjustable cardiac support to modulate cardiac size and (2) synchronous active assist to modulate cardiac output. As a means of enabling experiments to determine the role of these mechanical parameters in reverse remodeling or ventricular recovery, the device was further designed to (1) be deployed via minimally invasive surgical procedures, (2) allow uninhibited motion of the heart, (3) remain in place about the heart via an intrinsic pneumatic attachment, and (4) provide direct cardiac compression without aberrantly inverting the curvature of the heart. These actions and features are mapped to particular design solutions and assessed in an acute implantation in an ovine model of acute heart failure (esmolol overdose). The passive support component was used to effectively shift the EDPVR leftward, i.e., counter to the effects of disease. The active assist component was used to effectively decompress the constrained heart and restore lost cardiac output and stroke work in the esmolol failure model. It is expected that such a device will provide better control of the mechanical environment and thereby provide cardiac surgeons a broader range of therapeutic options and unique intervention possibilities.

Effects of calcium entry blockade on left ventricular dynamics in exercising dogs

1986 ◽  
Vol 251 (3) ◽  
pp. H656-H663
Author(s):  
R. A. Walsh ◽  
F. X. Cleary ◽  
R. A. O'Rourke
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Coronary Blood Flow ◽  
Left Ventricular ◽  
Calcium Entry ◽  
Peak Exercise ◽  
Beta Blockade ◽  
Lv Function

To study the previously undefined effects of calcium entry blockade on left ventricular (LV) function and coronary blood flow during dynamic exercise we gave intravenous equihypotensive infusions of nifedipine (10 +/- 4 SE micrograms X kg-1 X min-1), diltiazem (60 +/- 8 micrograms X kg-1 X min-1), and verapamil (52 +/- 7 micrograms X kg-1 X min-1) before and after intravenous propranolol (2 mg/kg) to chronically instrumented dogs at rest and while running on a treadmill at 4 and 10 km/h. Prior to beta-blockade, each agent significantly and equivalently (P = NS among drugs) reduced mean arterial pressure during exercise (-13% nifedipine, -8% diltiazem, -15% verapamil at 4 km/h, each P less than or equal to 0.01 vs. exercise alone) but did not significantly alter LV end-diastolic dimension (EDD), heart rate, or cardiac output compared with exercise alone. Only verapamil blunted the positive inotropic response to exercise (LV dP/dtmax decreased 20% at 4 km/h, P less than 0.01 vs. exercise alone). Coronary blood flow was significantly and equivalently increased at rest and during submaximal exercise with each calcium blocker, but this effect was largely offset by propranolol. During exercise after beta-blockade each agent produced significant additional reductions in mean arterial pressure and dP/dtmax at peak exercise but did not alter LVEDD or heart rate compared with results obtained with propranolol alone. Combined beta-blockade and verapamil uniquely diminished myocardial contractility to a greater extent at peak exercise than at rest (dP/dtmax 1,260 +/- 410 peak exercise vs. 1,775 +/- 431 mmHg/s rest, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Altered muscle metaboreflex control of coronary blood flow and ventricular function in heart failure

2005 ◽  
Vol 288 (3) ◽  
pp. H1381-H1388 ◽  
Author(s):  
Eric J. Ansorge ◽  
Robert A. Augustyniak ◽  
Mariana L. Perinot ◽  
Robert L. Hammond ◽  
Jong-Kyung Kim ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Coronary Blood Flow ◽  
Moderate Exercise ◽  
Muscle Metaboreflex ◽  
Significant Change

We investigated the effect of muscle metaboreflex activation on left circumflex coronary blood flow (CBF), coronary vascular conductance (CVC), and regional left ventricular performance in conscious, chronically instrumented dogs during treadmill exercise before and after the induction of heart failure (HF). In control experiments, muscle metaboreflex activation during mild exercise elicited significant reflex increases in mean arterial pressure, heart rate, and cardiac output. CBF increased significantly, whereas no significant change in CVC occurred. There was no significant change in the minimal rate of myocardial shortening (−d l/d tmin) with muscle metaboreflex activation during mild exercise (15.5 ± 1.3 to 16.8 ± 2.4 mm/s, P > 0.05); however, the maximal rate of myocardial relaxation (+d l/d tmax) increased (from 26.3 ± 4.0 to 33.7 ± 5.7 mm/s, P < 0.05). Similar hemodynamic responses were observed with metaboreflex activation during moderate exercise, except there were significant changes in both −d l/d tmin and d l/d tmax. In contrast, during mild exercise with metaboreflex activation during HF, no significant increase in cardiac output occurred, despite a significant increase in heart rate, inasmuch as a significant decrease in stroke volume occurred as well. The increases in mean arterial pressure and CBF were attenuated, and a significant reduction in CVC was observed (0.74 ± 0.14 vs. 0.62 ± 0.12 ml·min−1·mmHg−1; P < 0.05). Similar results were observed during moderate exercise in HF. Muscle metaboreflex activation did not elicit significant changes in either −d l/d tmin or +d l/d tmax during mild exercise in HF. We conclude that during HF the elevated muscle metaboreflex-induced increases in sympathetic tone to the heart functionally vasoconstrict the coronary vasculature, which may limit increases in myocardial performance.

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