The cardiac contractile function and hemodynamic control in rats after chronic adriamycin treatment

1990 ◽  
Vol 68 (2) ◽  
pp. 211-215 ◽  
Author(s):  
E. A. Gorodetskaya ◽  
S. F. Dugin ◽  
M. A. Golikov ◽  
V. I. Kapelko ◽  
O. S. Medvedev
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Total Peripheral Resistance ◽  
Contractile Function ◽  
Peripheral Resistance ◽  
Conscious State ◽  
Left Ventricular ◽  
Cardiac Contractile Function ◽  
Baroreflex Control ◽  
Cardiac Contractile

Cardiac contractile function and hemodynamic parameters of control and adriamycin-treated (2 mg/kg once a week for 10 weeks) rats were studied both in the anesthetized (hexenal, 20 mg/kg) and conscious state. Radiolabelled microspheres (diameter, 15 μm) were used to measure systemic and regional hemodynamics. No significant differences between the control and adriamycin-treated groups in cardiac contractile function, total peripheral resistance, and regional blood flow (except muscles) was found in anesthetized animals. In the conscious state, a significantly higher (+70%) total peripheral resistance combined with lower blood flow in the skin and spleen was observed in adriamycin-treated rats. The response of the heart rate to changes in the arterial pressure induced by nitroglycerin and phenylephrine injection was greatly diminished after adriamycin treatment. Isoprenaline (0.64 μg∙kg−1∙min−1) increased left ventricular contractile indices approximately twofold and heart rate by 30% in the control group, while in adriamycin-treated rats only minor changes in these parameters were observed. However, cardiac output rose by 36% and total peripheral resistance fell by 36% in these animals. Results show that prolonged adriamycin treatment leads to decreased inotropic response to β-adrenoceptor stimulation and reduced baroreflex control. These changes occur in the stage preceding congestive heart failure.Key words: adriamycin, baroreflex control, microspheres, contractility.

Diastolic pressure and peripheral resistance during stellate ganglion stimulation

1963 ◽  
Vol 204 (1) ◽  
pp. 71-72 ◽  
Author(s):  
Edward D. Freis ◽  
Jay N. Cohn ◽  
Thomas E. Liptak ◽  
Aristide G. B. Kovach
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Total Peripheral Resistance ◽  
Diastolic Pressure ◽  
Stellate Ganglion ◽  
Peripheral Resistance ◽  
Resistance Vessels ◽  
Left Stellate Ganglion ◽  
Increased Blood Flow

The mechanism of the diastolic pressure elevation occurring during left stellate ganglion stimulation was investigated. The cardiac output rose considerably, the heart rate remained essentially unchanged, and the total peripheral resistance fell moderately. The diastolic rise appeared to be due to increased blood flow rather than to any active changes in resistance vessels.

scholarly journals Neuronostatin inhibits cardiac contractile function via a protein kinase A- and JNK-dependent mechanism in murine hearts

2009 ◽  
Vol 297 (3) ◽  
pp. R682-R689 ◽  
Author(s):  
Yinan Hua ◽  
Heng Ma ◽  
Willis K. Samson ◽  
Jun Ren
Keyword(s):  
Contractile Function ◽  
Peptide Hormone ◽  
Left Ventricular ◽  
Maximal Velocity ◽  
Cardiac Contractile Function ◽  
Mechanical Responses ◽  
Cardiac Contractile ◽  
Short Term Exposure ◽  
The Impact ◽  
Dependent Mechanism

Neuronostatin, a newly identified peptide hormone sharing the same precursor with somatostatin, exerts multiple pharmacological effects in gastrointestinal tract, hypothalamus, and cerebellum. However, the cardiovascular effect of neuronostatin is unknown. The aim of this study was to elucidate the impact of neuronostatin on cardiac contractile function in murine hearts and isolated cardiomyocytes. Short-term exposure of neuronostatin depressed left ventricular developed pressure (LVDP), maximal velocity of pressure development (±dP/d t), and heart rate in Langendorff heart preparation. Consistently, neuronostatin inhibited peak shortening (PS) and maximal velocity of shortening/relengthening (±dL/d t) without affecting time-to-PS (TPS) and time-to-90% relengthening (TR90) in cardiomyocytes. The neuronostatin-elicited cardiomyocyte mechanical responses were mimicked by somatostatin, the other posttranslational product of preprosomatostatin. Furthermore, the neuronostatin-induced cardiomyocyte mechanical effects were ablated by the PKA inhibitor H89 (1 μM) and the Jun N-terminal kinase (JNK) inhibitor SP600125 (20 μM). The PKC inhibitor chelerythrine (1 μM) failed to alter neuronostatin-induced cardiomyocyte mechanical responses. To the contrary, chelerythrine, but not H89, abrogated somatostatin-induced cardiomyocyte contractile responses. Our results also showed enhanced c-fos and c-jun expression in response to neuronostatin exposure (0.5 to 2 h). Taken together, our data suggest that neuronostatin is a peptide hormone with overt cardiac depressant action. The neuronostatin-elicited cardiac contractile response appears to be mediated, at least in part, through a PKA- and/or JNK-dependent mechanism.

Lipid peroxidation contributes to cardiac deficits after ischemia and reperfusion of the small bowel

1993 ◽  
Vol 264 (5) ◽  
pp. H1686-H1692 ◽  
Author(s):  
J. W. Horton ◽  
D. J. White
Keyword(s):  
Lipid Peroxidation ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Cardiac Contractile Function ◽  
Langendorff Preparation ◽  
Cardiac Contractile ◽  
Intestinal Ischemia Reperfusion

Our previous studies showed that intestinal ischemia-reperfusion (IR) impairs cardiac contractile function. The present study examined the contribution of oxygen free radicals and lipid peroxidation of cardiac cell membrane to cardiac dysfunction after intestinal IR in a rat model of superior mesenteric artery (SMA) occlusion (atraumatic clip for 20 min) and collateral arcade ligation. Controls were sham operated (group 1, n = 25). In group 2, 30 rats with SMA occlusion were killed 3-4 h after reperfusion without treatment. Aminosteroid (U-74389F), a pharmacological agent known to inhibit lipid peroxidation of membranes, was given 1 min before occlusion of the SMA (group 3, n = 19). All rats were killed 3-4 h after reperfusion of the ischemic intestine, and the hearts were harvested for in vitro assessment of cardiac function (Langendorff preparation). Cardiac contractile depression occurred in the untreated group as indicated by a fall in left ventricular pressure (from 76 +/- 3 to 64 +/- 3 mmHg, P = 0.01), maximum +dP/dt (from 1,830 +/- 60 to 1,577 +/- 64 mmHg/s, P = 0.05), and maximum -dP/dt (from 1,260 +/- 50 to 950 +/- 60 mmHg/s, P = 0.005). Lipid peroxidation of cardiac membranes occurred after untreated IR as indicated by the rise in cardiac malondialdehyde levels (MDA) (from 0.203 +/- 0.046 to 0.501 +/- 0.044 nM/mg protein, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Feeding the fibrillating heart: Dichloroacetate improves cardiac contractile dysfunction following VF

2015 ◽  
Vol 309 (9) ◽  
pp. H1543-H1553 ◽  
Author(s):  
Mohammed Ali Azam ◽  
Cory S. Wagg ◽  
Stéphane Massé ◽  
Talha Farid ◽  
Patrick F. H. Lai ◽  
...  
Keyword(s):  
Glucose Oxidation ◽  
Contractile Function ◽  
Lactate Production ◽  
Left Ventricular ◽  
Global Ischemia ◽  
Contractile Dysfunction ◽  
Anaerobic Glycolysis ◽  
Cardiac Contractile Function ◽  
Cardiac Contractile ◽  
Cardiac Contractile Dysfunction

Ventricular fibrillation (VF) is an important cause of sudden cardiac arrest following myocardial infarction. Following resuscitation from VF, decreased cardiac contractile function is a common problem. During and following myocardial ischemia, decreased glucose oxidation, increased anaerobic glycolysis for cardiac energy production are harmful and energetically expensive. The objective of the present study is to determine the effects of dichloroacetate (DCA), a glucose oxidation stimulator, on cardiac contractile dysfunction following ischemia-induced VF. Male Sprague-Dawley rat hearts were Langendorff perfused in Tyrode's buffer. Once stabilized, hearts were subjected to 15 min of global ischemia and 5 min of aerobic reperfusion in the presence or absence of DCA. At the 6th min of reperfusion, VF was induced electrically, and terminated. Left ventricular (LV) pressure was measured using a balloon. Pretreatment with DCA significantly improved post-VF left ventricular developed pressure (LVDP) and dp/d tmax. In DCA-pretreated hearts, post-VF lactate production and pyruvate dehydrogenase (PDH) phosphorylation were significantly reduced, indicative of stimulated glucose oxidation, and inhibited anaerobic glycolysis by activation of PDH. Epicardial NADH fluorescence was increased during global ischemia above preischemic levels, but decreased below preischemia levels following VF, with no differences between nontreated controls and DCA-pretreated hearts, whereas DCA pretreatment increased NADH production in nonischemic hearts. With exogenous fatty acids (FA) added to the perfusion solution, DCA pretreatment also resulted in improvements in post-VF LVDP and dp/d tmax, indicating that the presence of exogenous FA did not affect the beneficial actions of DCA. In conclusion, enhancement of PDH activation by DCA mitigates cardiac contractile dysfunction following ischemia-induced VF.

scholarly journals Mechanisms underlying hypothermia-induced cardiac contractile dysfunction

2010 ◽  
Vol 298 (3) ◽  
pp. H890-H897 ◽  
Author(s):  
Young-Soo Han ◽  
Torkjel Tveita ◽  
Y. S. Prakash ◽  
Gary C. Sieck
Keyword(s):  
Papillary Muscle ◽  
Myocardial Contractility ◽  
Troponin I ◽  
Contractile Function ◽  
Left Ventricular ◽  
Cardiac Contractile Function ◽  
Profound Hypothermia ◽  
Twitch Force ◽  
Cardiac Contractile ◽  
Cardiac Contractile Dysfunction

Rewarming patients after profound hypothermia may result in acute heart failure and high mortality (50–80%). However, the underlying pathophysiological mechanisms are largely unknown. We characterized cardiac contractile function in the temperature range of 15–30°C by measuring the intracellular Ca2+ concentration ([Ca2+]i) and twitch force in intact left ventricular rat papillary muscles. Muscle preparations were loaded with fura-2 AM and electrically stimulated during cooling at 15°C for 1.5 h before being rewarmed to the baseline temperature of 30°C. After hypothermia/rewarming, peak twitch force decreased by 30–40%, but [Ca2+]i was not significantly altered. In addition, we assessed the maximal Ca2+-activated force (Fmax) and Ca2+ sensitivity of force in skinned papillary muscle fibers. Fmax was decreased by ∼30%, whereas the pCa required for 50% of Fmax was reduced by ∼0.14. In rewarmed papillary muscle, both total cardiac troponin I (cTnI) phosphorylation and PKA-mediated cTnI phosphorylation at Ser23/24 were significantly increased compared with controls. We conclude that after hypothermia/rewarming, myocardial contractility is significantly reduced, as evidenced by reduced twitch force and Fmax. The reduced myocardial contractility is attributed to decreased Ca2+ sensitivity of force rather than [Ca2+]i itself, resulting from increased cTnI phosphorylation.

Peripheral vasodilatation induced by a vasopressin analogue with selective V2-agonism in dogs

1989 ◽  
Vol 256 (6) ◽  
pp. H1621-H1626 ◽  
Author(s):  
J. F. Liard
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Conscious Dogs ◽  
Hemodynamic Effects ◽  
Femoral Blood Flow ◽  
Peripheral Vasodilatation ◽  
Femoral Blood

The selective V2-agonist 4-valine-8-D-arginine vasopressin (VDAVP) increases cardiac output and heart rate and decreases total peripheral resistance in dogs. The mechanism of these hemodynamic effects was examined in the present studies. When infused into the left coronary artery of six conscious dogs for 1 h, VDAVP (10 ng.kg-1.min-1) increased cardiac output and decreased total peripheral resistance more than when given intravenously in the same animals. Administration of VDAVP into the carotid circulation elicited effects that did not differ significantly from those after intravenous infusion at the same rate in six conscious dogs. After destruction of the central nervous system in five dogs anesthetized with pentobarbital, VDAVP failed to increase cardiac output and heart rate but lowered mean arterial pressure and total peripheral resistance. Finally, infusion of VDAVP into the femoral artery of six anesthetized dogs increased femoral blood flow at rates of 1, 5, and 10 ng.kg-1.min-1, whereas none of these rates increased femoral blood flow when given intravenously. Thus the hemodynamic effects of VDAVP appear to result primarily from a peripheral vasodilatory action, with possible contribution from a positive inotropic effect. We found no evidence that central effects of VDAVP were importantly involved in its cardiovascular action.

Urotensin II causes fatal circulatory collapse in anesthesized monkeys in vivo: a “vasoconstrictor” with a unique hemodynamic profile

2004 ◽  
Vol 286 (3) ◽  
pp. H830-H836 ◽  
Author(s):  
Yi Zhun Zhu ◽  
Zhong Jing Wang ◽  
Yi Chun Zhu ◽  
Li Zhang ◽  
Reida M. E. Oakley ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Coronary Blood Flow ◽  
Nonhuman Primates ◽  
Peripheral Resistance ◽  
Left Ventricular ◽  
Circulatory Collapse ◽  
Urotensin Ii

Urotensin II (UII) is a vasoactive peptide that has recently emerged as a likely contributor to cardiovascular physiology and pathology. Acute infusion of UII into nonhuman primates results in circulatory collapse and death; however, the exact cause of death is not well understood. This study was undertaken to elucidate the mechanism underlying the fatal cardiovascular event on UII application in vivo in nonhuman primates. To this end, cynomolgus monkeys ( n = 4) were anesthetized and tracheal intubation was performed. One internal jugular vein was cannulated for administration of drugs, and one femoral artery for recording of blood pressure and heart rate using a transonic pressure transducer. Cardiac parameters were not significantly changed after administration of 0.003 nmol/kg human UII. A bolus of human UII (0.03 nmol/kg) caused a decrease of heart rate (HR) (13%), mean blood pressure (MBP) (18%), and first-order derivative of left ventricular pressure (dP/d t) (11%). Carotid and coronary blood flow were reduced by 9% and 7%, respectively; 0.3 nmol/kg of human UII resulted in a further reduction of HR (50.3%), MBP (65%), dP/d t (45%), carotid (38%), and coronary blood flow (30%), ultimately leading to cardiovascular breakdown and death. Pulmonary pressure, however, was increased by 30%. Plasma histamine levels were found to be unaffected by administration of UII. Our results indicate that systemic administration of human UII has negative inotropic and chronotropic effects and reduces total peripheral resistance ultimately leading to severe myocardial depression, pulmonary hypertension, and fatal circulation collapse in nonhuman primates. We suggest that successful design of UII antagonists might offer a new therapeutic principle in treating cardiovascular diseases.

Cardiovascular effects produced by L-glutamate stimulation of the lateral hypothalamic area

1989 ◽  
Vol 257 (2) ◽  
pp. H540-H552 ◽  
Author(s):  
S. E. Spencer ◽  
W. B. Sawyer ◽  
A. D. Loewy
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Lateral Hypothalamic Area ◽  
Hypothalamic Area ◽  
Pharmacological Blockade ◽  
Stimulation Of

L-Glutamate microinjections into the tuberal region of the lateral hypothalamic area (LHAt) caused a fall in blood pressure and heart rate in pentobarbital-anesthetized rats. The bradycardia was mediated by both beta-adrenergic and muscarinic mechanisms as demonstrated with pharmacological blockade. The hypotension was due to a decrease in cardiac output, not a decrease in total peripheral resistance. In addition, there was a reduction in coronary blood flow. If heart rate was held constant by pharmacological blockade or by electrical cardiac pacing, L-glutamate stimulation of the LHAt still caused a fall in blood pressure. When the electrically paced model was used, this hypotension was due to a fall in cardiac output. In contrast, with the pharmacological blockade of the heart, the hypotension was due to a decrease in the total peripheral resistance. The cardiac output reduction in the paced condition was not mediated solely by either beta-sympathetic or parasympathetic mechanisms as determined by pharmacological blockade. With heart rate held constant by either drugs or pacing, LHAt stimulation did not alter regional blood flow or resistance in any vascular bed, including the coronary circulation. We conclude that L-glutamate stimulation of the LHAt lowers the cardiac output and heart rate by both parasympathetic and beta-adrenergic mechanisms and elicits hypotension by lowering cardiac output in the naive and electrically paced model.

Effects of endothelin-1 and sarafotoxin S6b on regional hemodynamics in the conscious dog

1991 ◽  
Vol 260 (6) ◽  
pp. R1210-R1217 ◽  
Author(s):  
R. J. Leadley ◽  
J. L. Zhu ◽  
K. L. Goetz
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Renal Blood Flow ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Receptor Subtypes ◽  
Regional Variability ◽  
Endothelin 1 ◽  
Regional Hemodynamics

Endothelin, a potent vasoconstrictor, also is capable of producing transient vasodilation in some situations. We examined the changes in regional hemodynamics in response to constant infusions of endothelin-1 (ET-1) at 5, 10, or 20 ng.kg-1.min-1 for 1 h into conscious dogs. The dogs were instrumented with ultrasonic flow probes for measurement of blood flow in the ascending aorta (cardiac output) and in the coronary, mesenteric, renal, and iliac arteries. A compound structurally similar to ET-1, sarafotoxin S6b (S6b), was also infused in identical experiments to determine whether the responses to these two peptides might differ. Basal plasma levels of immunoreactive ET-1 averaged approximately 6 pg/ml. After 55 min of infusion of ET-1 at 5, 10, and 20 ng.kg-1.min-1, plasma immunoreactive ET-1 increased to approximately 55, 130, and 520 pg/ml, respectively. When given at 20 ng.kg-1.min-1, ET-1 increased total peripheral resistance and arterial pressure and decreased cardiac output and heart rate. ET-1 decreased coronary, mesenteric, and renal blood flow but did not change iliac flow. In comparison with ET-1, S6b produced relatively smaller changes in total peripheral resistance, cardiac output, heart rate, and coronary, mesenteric, and renal blood flow. Iliac resistance did not change in response to ET-1, but it increased during infusions of S6b. Similar but less pronounced responses were observed when these peptides were infused at 5 and 10 ng.kg-1.min-1. The regional variability in the hemodynamic response to ET-1 and the difference in regional responses to ET-1 and S6b are consistent with the existence of heterogenous receptor subtypes for these peptides.

Effects of dihydroergotamine on hemodynamic molsidomine actions in anesthetized dogs

1984 ◽  
Vol 62 (6) ◽  
pp. 634-639 ◽  
Author(s):  
Volker B. Fiedler ◽  
Helmut Göbel ◽  
Rolf-Eberhard Nitz
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Stroke Volume ◽  
Total Peripheral Resistance ◽  
Peripheral Resistance ◽  
Left Ventricular ◽  
Venous Capacitance ◽  
Heart Performance ◽  
Dose Dependent Fashion ◽  
Anesthetized Dogs

In pentobarbital-anesthetized mongrel dogs the intravenous actions of 0.50 mg/kg molsidomine on pulmonary artery and left ventricular (LV) end-diastolic pressures and internal heart dimensions (preload), left ventricular systolic and peripheral blood pressures, and total peripheral resistance (afterload), as well as on heart rate, dP/dt, stroke volume, and cardiac output (heart performance) were studied for 2 h. Hemodynamic molsidomine effects were influenced by increasing amounts of intravenously infused dihydroergotamine solution (DHE, 1–64 μg∙kg−1∙min−1). Molsidomine decreased preload, stroke volume, and cardiac output for over 2 h but decreased ventricular and peripheral pressures for 45 min. Systemic vascular resistance showed a tendency to decrease while heart rate and LV dP/dtmax were not altered. DHE infusion reversed molsidomine effects on the preload and afterload of the heart. The diminished stroke volume was elevated so that cardiac output also increased. Total peripheral resistance increased while heart rate fell in a dose-dependent fashion. The LV dP/dtmax remained unchanged until the highest dose of 64 μg∙kg−1∙min−1 DHE elevated the isovolumic myocardial contractility. These experiments indicate that DHE can reverse the intravenous molsidomine effects on hemodynamics. Most likely, this is mediated through peripheral vasoconstriction of venous capacitance vessels, thereby affecting moldisomine's action on postcapillary beds of the circulation.

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