The inotropic effect of digoxin on an isolated rat heart in hypercapnia and (or) hypoxia

1990 ◽  
Vol 68 (3) ◽  
pp. 455-461
Author(s):  
M. Allam ◽  
C. Saunier ◽  
A. Sautegeau ◽  
D. Hartemann
Keyword(s):  
Rat Heart ◽  
Myocardial Contractility ◽  
Diastolic Pressure ◽  
Isolated Heart ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Gas Mixture ◽  
Constant Frequency

The explanation for the increased frequency of troubles with digoxin therapy in patients with chronic pulmonary diseases is debated. The reported effects of hypoxia in vivo on myocardial levels of digoxin are contradictory, and there have been few studies on the effects of hypercapnia. In the past, it has been shown in rat myocardial tissue at rest in vitro that hypoxia decreased and hypercapnia acidosis increased the digoxin uptake. We performed a new study in vitro in an isolated beating rat heart perfused at constant flow (37 °C) and stimulated at a constant frequency (6 Hz). The performances were recorded with an intraventricular balloon equipped with a tip-manometer catheter. The action of digoxin was studied by recording systolic pressure (PS) and diastolic pressure (PD), the left ventricular developed pressure (LVDP = PS − PD), the (dP/dt)max, and the ratio (dP/dt)max/PS. First, the heart was perfused for 30 min with a modified Tyrode's solution perfusate aerated with carbogen (pH = 7.40; [Formula: see text]; [Formula: see text]) (1 mmHg = 133.32 Pa). Various parameters of contractions were recorded (initial control values). Then the heart was perfused for 15 min with Tyrode's solution aerated either with a hypoxic gas mixture (pH = 7.41; [Formula: see text]; [Formula: see text]), a hypercapnic gas mixture (pH = 7.08; [Formula: see text]; [Formula: see text]), or a hypoxic–hypercapnic gas mixture (pH = 7.09; [Formula: see text]; [Formula: see text]). Control hearts were continuously perfused with Tyrode's solution aerated with carbogen. During heart perfusion with hypercapnic, hypoxic, or hypoxic–hypercapnic Tyrode's solution, a decrease in LVDP and (dP/dt)max was observed. Finally, the heart was perfused with the same Tyrode's solution plus 1.75 × 10−5 M digoxin. The increase in myocardial contractility produced by digoxin was enhanced by hypercapnia and abolished by hypoxia. The addition of hypercapnia to hypoxia in Tyrode's solution seems to enhance the depressor action of the hypoxia.Key words: isolated heart, digoxin, hypoxia, hypercapnia, myocardial contractility.

Developmental changes in cardiac contractility in fetal and postnatal sheep: in vitro and in vivo

1984 ◽  
Vol 247 (3) ◽  
pp. H371-H379 ◽  
Author(s):  
P. A. Anderson ◽  
K. L. Glick ◽  
A. Manring ◽  
C. Crenshaw
Keyword(s):  
Maximum Rate ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Developmental Changes ◽  
Common Mechanism ◽  
Postextrasystolic Potentiation ◽  
Maximum Rate Of Rise

Developmental changes in contractility were sought in the fetal and postnatal sheep heart by using postextrasystolic potentiation and force, pressure, and wall-motion measures. Two different preparations were used, isolated myocardium and the chronically instrumented lamb. In the isolated muscle, the following increased significantly with age: force of contraction, the maximum rate of rise of force, and postextrasystolic potentiation. In the intact heart prior to birth [period of study, 20 +/- 4 (SD) days] heart rate (HR) fell significantly, and the following increased significantly: postextrasystolic potentiation [measured with the maximum rate of rise of left ventricular (LV) pressure (Pmax)], LV peak systolic pressure (LVP), end-diastolic dimension (EDD), end-systolic dimension (ESD), and aortic diastolic pressure. After birth, LVP, Pmax, HR, LVEDP, EDD, and ESD increased and postextrasystolic potentiation fell. The latter fall was not found in vitro and probably demonstrates a transient change in contractility, related to hormonal or neural stimulation. Over the subsequent postnatal days (6-122 days), HR fell while potentiation, EDD, and ESD increased significantly. Both in vitro and in vivo, the overall increase in postextrasystolic potentiation demonstrates a similar long-term change in contractility. The similarity of this change to that induced by mild hypertrophy suggests that development and mild hypertrophy alter myocardial contractility through a common mechanism.

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.

Left ventricular dysfunction in early E. coli endotoxemia: effects of naloxone

1990 ◽  
Vol 259 (2) ◽  
pp. H504-H511 ◽  
Author(s):  
J. L. Parker ◽  
R. S. Keller ◽  
L. L. Behm ◽  
H. R. Adams
Keyword(s):  
Diastolic Pressure ◽  
Contractile Function ◽  
Isolated Heart ◽  
Systolic Pressure ◽  
Opiate Receptor ◽  
Left Ventricular ◽  
Cardiac Complications ◽  
Endogenous Opioid ◽  
Diastolic Compliance

Although the opiate receptor antagonist naloxone (NAL) has been reported to improve in vivo systolic performance of the heart in different circulatory shock syndromes, the influence of this drug on intrinsic cardiac mechanical function during hypodynamic circulatory states is unknown. The present study was designed to determine the effects of in vivo NAL on contraction-relaxation properties of isovolumic left ventricular (LV) preparations isolated from guinea pigs 4 h after induction of gram-negative endotoxemia. Animals were given a 1 mg/kg ip injection of Escherichia coli endotoxin and immediately treated intravenously with either NAL (4 mg/kg iv bolus plus 4 mg.kg-1.h-1 infusion) or an equivalent volume of saline. Endotoxin produced significant reduction of LV contractile function in coronary-perfused hearts, a response unaffected by NAL therapy. For example, LV systolic pressure at approximately 10 mmHg end-diastolic pressure averaged 78 +/- 3 and 82 +/- 6 mmHg in hearts from saline and NAL control animals, respectively, but only 41 +/- 2 and 40 +/- 2 mmHg in endotoxin and endotoxin plus NAL groups, respectively. LV end-diastolic pressure-volume relationships in endotoxin hearts were shifted upward and to the left of controls in the direction of decreased diastolic compliance (P less than 0.05). Importantly, in vivo NAL prevented the endotoxin-induced decrease in LV compliance of the isolated heart preparations (P less than 0.05). Thus intrinsic cardiac complications of early (4 h) nonhypotensive endotoxemia included decreased diastolic compliance as well as diminished contractility of the left ventricle. Only the diastolic compliance changes were NAL responsive and therefore may involve endogenous opioid systems in their pathophysiological expression.

Effect of human urotensin-II infusion on hemodynamics and cardiac function

2003 ◽  
Vol 81 (2) ◽  
pp. 125-128 ◽  
Author(s):  
Ghada S Hassan ◽  
Fazila Chouiali ◽  
Takayuki Saito ◽  
Fu Hu ◽  
Stephen A Douglas ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Diastolic Pressure ◽  
Cardiac Contractility ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Urotensin Ii ◽  
Ventricular Systolic Pressure ◽  
Wide Range ◽  
Dose Dependent Decrease

Recent studies have shown that the vasoactive peptide urotensin-II (U-II) exerts a wide range of action on the cardiovascular system of various species. In the present study, we determined the in vivo effects of U-II on basal hemodynamics and cardiac function in the anesthetized intact rat. Intravenous bolus injection of human U-II resulted in a dose-dependent decrease in mean arterial pressure and left ventricular systolic pressure. Cardiac contractility represented by ±dP/dt was decreased after injection of U-II. However, there was no significant change in heart rate or diastolic pressure. The present study suggests that upregulation of myocardial U-II may contribute to impaired myocardial function in disease conditions such as congestive heart failure.Key words: urotensin-II, rat, infusion, heart.

Protective effects of ceruloplasmin against electrolysis-induced oxygen free radicals in rat heart

1991 ◽  
Vol 69 (10) ◽  
pp. 1459-1464 ◽  
Author(s):  
Ramez Chamine ◽  
Mircea Alexandru Mateescu ◽  
Stéphane Roger ◽  
Nobuharu Yamaguchi ◽  
Jacques de Champlain ◽  
...  
Keyword(s):  
Free Radicals ◽  
Rat Heart ◽  
Oxygen Free Radicals ◽  
Diastolic Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Fast Method ◽  
Protective Effects

The potentially injurious effects of oxygen-derived free radicals (OFR) on the myocardium can be prevented in part by pretreatment with OFR scavengers or antioxidants. Since ceruloplasmin (CP) has been shown to possess potent antioxidant activity and scavenge a variety of OFR in vitro, we have undertaken to study its protective effects against myocardial injury induced by OFR. CP was freshly purified by a fast method that minimized proteolytic enzyme degradation. Free radicals were generated by the electrolysis (10 mA DC current for 1 min) of a Krebs–Henseleit solution perfusing an isolated rat heart preparation under constant pressure conditions. CP (0.25 μM) afforded 80 and 63% protection (n = 8, p < 0.05), respectively, against the deleterious effects of electrolysis-induced OFR on left ventricular pressure and coronary flow. The increase in left ventricular end diastolic pressure used here as an index of heart failure did not occur in the presence of 0.25 μM CP. Moreover, CP significantly reduced the increase of norepinephrine washout in the effluent perfusate after electrolysis suggesting a protection against free radical-induced injury to sympathetic nerve endings.Key words: oxygen free radicals, heart, ceruloplasmin, superoxide dismutase, norepinephrine.

Effects of Endotoxin on Neutrophil-Mediated Ischemia/Reperfusion Injury in the Rat Heart In Vivo

2001 ◽  
Vol 226 (4) ◽  
pp. 320-327 ◽  
Author(s):  
Brian P. Lipton ◽  
Joseph B. Delcarpio ◽  
Kathleen H. McDonough
Keyword(s):  
At Risk ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Isolated Heart ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Necrotic Area ◽  
Area At Risk

We have previously shown that a nonlethal dose of lipopolysaccharide (LPS) decreases L-selectin expression of neutrophils (PMNs), thereby preventing PMN-mediated reperfusion injury in the isolated heart. In the present study we determined whether or not that dose of LPS would protect hearts during in vivo ischemia and reperfusion by preventing PMN-induced reperfusion injury. Rats receiving saline vehicle showed marked myocardial injury (necrotic area/area at risk = 82% ± 2%) and significant depression in left ventricular function as assessed in the isolated isovolumic heart preparation at constant flow rates of 5, 10, 15, and 20 ml/min. The administration of LPS (100 μg/kg body wt) 7 hr prior to ischemia resulted in a reduction in myocardial damage (necrotic area/area at risk = 42% ± 3%) and preservation of function. Myocardial function was similar to that of sham ischemic saline- and LPS-treated rats. Moreover, PMN infiltration as determined by histology was quantitatively more severe in hearts of saline-treated rats than in hearts of LPS-treated rats. Isolated hearts from vehicle- and LPS-treated animals undergoing sham ischemia in vivo recovered to the same extent after in vitro ischemia/reperfusion, suggesting that LPS did not induce protection by altering intrinsic properties of the heart. Our results indicate that LPS-induced protection of the heart from in vivo PMN-mediated ischemia/reperfusion injury may be due to decreased L-selectin expression of PMNs in LPS-treated animals.

Ventricular performance, pressure-volume relationships, and O2 consumption during hypothermia

1964 ◽  
Vol 206 (1) ◽  
pp. 67-73 ◽  
Author(s):  
R. G. Monroe ◽  
R. H. Strang ◽  
C. G. LaFarge ◽  
J. Levy
Keyword(s):  
Peak Pressure ◽  
Diastolic Pressure ◽  
Isolated Heart ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Ventricular Performance ◽  
Heart Rates ◽  
Performance Pressure ◽  
Air Chamber ◽  
Lower Temperature

Left ventricular performance in the isolated heart of a dog was observed at normal temperatures (37.7 C) and under hypothermia (32.2 C) at comparable heart rates. The peak pressure of isovolumic contractions at the same ventricular end-diastolic pressures averaged 40% higher at the lower temperature. Diastolic pressure-volume relationships were similar at both temperatures. In studies in which the ventricle ejected fluid and performed work the hypothermic ventricle was capable of performing greater work at comparable heart rates, left ventricular end-diastolic pressures, and loading. When the ventricle was allowed to perform work by compressing air into a chamber of constant volume left ventricular oxygen consumption (Vo2) increased with the peak systolic pressure as the temperature was lowered. If the peak systolic pressure was maintained constant by increasing the volume of the air chamber as the temperature was lowered no consistent relationship could be shown between left ventricular Vo2 and the integral of systolic pressure in time which invariably increased with hypothermia.

Impact of exercise training on ventricular properties in a canine model of congestive heart failure

1997 ◽  
Vol 272 (3) ◽  
pp. H1382-H1390 ◽  
Author(s):  
K. Todaka ◽  
J. Wang ◽  
G. H. Yi ◽  
M. Knecht ◽  
R. Stennett ◽  
...  
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Heart Function ◽  
Systolic Pressure ◽  
Cardiac Pacing ◽  
Left Ventricular ◽  
Lv Function ◽  
Myocardial Stiffness

Exercise training improves functional class in patients with chronic heart failure (CHF) via effects on the periphery with no previously documented effect on intrinsic left ventricular (LV) properties. However, because methods used to evaluate in vivo LV function are limited, it is possible that some effects of exercise training on the failing heart have thus far eluded detection. Twelve dogs were instrumented for cardiac pacing and hemodynamic recordings. Hearts were paced rapidly for 4 wk. Six of the dogs received daily treadmill exercise (CHF(EX), 4.4 km/h, 2 h/day) concurrent with rapid pacing, while the other dogs remained sedentary (CHFs). Hemodynamic measurements taken in vivo at the end of 4 wk revealed relative preservation of maximum rate of pressure rise (2,540 +/- 440 vs. 1,720 +/- 300 mmHg/s, P < 0.05) and LV end-diastolic pressure (9 +/- 5 vs. 19 +/- 4 mmHg, P < 0.05) in CHF(EX) compared with CHFs. The hearts were then isolated and cross perfused for in vitro measurement of isovolumic pressure-volume relations; these results were compared with those of six normal dogs (N). Systolic function was similarly depressed in both groups of pacing animals [end-systolic elastance (Ees) values of 1.66 +/- 0.47 in CHFs, 1.77 +/- 0.38 in CHF(EX), and 3.05 +/- 0.81 mmHg/ml in N, with no changes in volume axis interceptors of the end-systolic pressure-volume relationship]. The diastolic myocardial stiffness constant, k, was elevated in CHFs and was normalized by exercise training (32 +/- 3 in CHFs, 21 +/- 3 in CHF(EX), 20 +/- 4 in N). Thus daily exercise training preserved in vivo hemodynamics during 4 wk of rapid cardiac pacing and was accompanied by a significant change in diastolic myocardial stiffness in vitro. These findings suggest that changes in heart function may contribute to the overall beneficial hemodynamic effects of exercise training in CHF by a significant effect on diastolic properties.

Regulatory effects of phospholamban on cardiac function in intact mice

1997 ◽  
Vol 273 (6) ◽  
pp. H2826-H2831 ◽  
Author(s):  
John N. Lorenz ◽  
Evangelia G. Kranias
Keyword(s):  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Physiological Role ◽  
Cardiovascular Effects ◽  
Left Ventricular ◽  
In Vivo Evaluation ◽  
Intact Mouse ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Inotropic Effects

Phospholamban (PLB) regulates Ca2+- adenosinetriphosphatase activity in cardiac sarcoplasmic reticulum and participates in the regulation of myocardial performance. Animal models with altered levels of PLB permit in vivo evaluation of the physiological role of PLB. This study examined left ventricular (LV) performance in intact PLB heterozygous and homozygous mice under basal and stimulated conditions. A Millar Mikro-Tip transducer was inserted into the right carotid artery and advanced into the LV for direct measurement of ventricular pressure and the first derivative of intraventricular pressure (dP/d t). Baseline blood pressures were increased in PLB heterozygotes and even more so in PLB homozygotes compared with wild types (WT), and there were no differences in heart rate or LV end-diastolic pressure. The increase in pressure was primarily caused by an increase in systolic pressure. Baseline values for positive and negative dP/d t were linearly correlated with PLB levels. In PLB heterozygotes, contractile response to isoproterenol (Iso) was blunted compared with WT, but maximum rates of contraction were similar between the two groups. Contractile performance in PLB homozygous mice, which under baseline conditions was similar to maximum levels seen in WT, showed a blunted response to Iso, and maximum rates of contraction were significantly greater than in either of the other groups, indicating an essential but perhaps not exclusive role for PLB in mediating the inotropic effects of β-adrenergic agonists. The effects of Iso on negative dP/d t were also blunted in both PLB heterozygous and PLB homozygous animals. Our results demonstrate that myocardial function is highly dependent on PLB level and suggest that the cardiovascular effects of PLB perturbations are largely uncompensated for in the intact mouse.

Simulated microgravity produces attenuated baroreflex-mediated pressor, chronotropic, and inotropic responses in mice

2005 ◽  
Vol 289 (2) ◽  
pp. H600-H607 ◽  
Author(s):  
Albert S. Jung ◽  
Robert Harrison ◽  
Kwang H. Lee ◽  
Jordan Genut ◽  
Daniel Nyhan ◽  
...  
Keyword(s):  
Orthostatic Intolerance ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Contractile Responses ◽  
Carotid Baroreceptor ◽  
Bilateral Carotid ◽  
Myocardial Contractile ◽  
Inotropic Responses

Whether myocardial contractile impairment contributes to orthostatic intolerance (OI) is controversial. Accordingly, we used transient bilateral carotid occlusion (TBCO) to compare the in vivo pressor, chronotropic, and inotropic responses ( parts 1 and 2) to open-loop selective carotid baroreceptor unloading in anesthetized mice. In part 3, in vitro myocyte responses to isoproterenol in mice exposed to hindlimb unweighting (HLU) for ∼2 wk were determined. Heart rate (HR) and mean arterial pressure (MAP) responses to TBCO were measured. In control mice, TBCO increased HR (15 ± 2 beats/min, P < 0.05) and MAP (17 ± 2 mmHg, P < 0.05). These responses were markedly potentiated in denervated control (DC) mice, in which the aortic depressor nerve and sympathetic trunk were sectioned before measurement. Baroreflex responses to TBCO were eliminated by blockade with hexamethonium bromide (10 μg/kg). In HLU (denervated) mice, HR and MAP responses were reduced ∼70% compared with DC mice. In part 2, myocardial contractile responses to TBCO were measured with a left ventricular micromanometer-conductance catheter. TBCO in DC mice increased the slope of the end-systolic pressure-volume relation (end-systolic elastance) by 86 ± 13%. This inotropic response was attenuated (14 ± 10%, P < 0.005) after HLU. In part 3, contractile responses to isoproterenol were impaired in myocytes isolated from HLU mice. In conclusion, selective carotid baroreceptor unloading stimulates HR, blood pressure, and myocardial contractility, and HLU attenuates each response. These findings have important implications for the management of OI in astronauts, the elderly, and individuals subjected to prolonged bed rest.

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