Left ventricular function during lethal and sublethal endotoxemia in swine

1986 ◽  
Vol 251 (2) ◽  
pp. H364-H373 ◽  
Author(s):  
R. D. Goldfarb ◽  
L. M. Nightingale ◽  
P. Kish ◽  
P. B. Weber ◽  
D. J. Loegering
Keyword(s):  
Low Dose ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Lethal Dose ◽  
Cardiac Contractility ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
High Dose ◽  
Adrenergic Stimulation ◽  
And Function

Our previous studies suggested that after a median lethal dose (LD50) of endotoxin, cardiac contractility was depressed in nonsurviving dogs. The canine cardiovascular system is unlike humans in that dogs have a hepatic vein sphincter that is susceptible to adrenergic stimulation capable of raising hepatic and splanchnic venous pressures. We retested the hypothesis that lethality after endotoxin administration is associated with cardiac contractile depression in pigs, because the hepatic circulation in this species is similar to that of humans. We compared cardiac mechanical function of pigs administered a high dose (250 micrograms/kg) or a low dose (100 micrograms/kg) endotoxin by use of the slope of the end-systolic pressure-diameter relationship (ESPDR) as well as other measurements of cardiac performance. In all the pigs administered a high dose, ESPDR demonstrated a marked, time-dependent depression, whereas we observed no significant ESPDR changes after low endotoxin doses. The other cardiodynamic variables were uninterpretable, due to the significant changes in heart rate, end-diastolic diameter (preload), and aortic diastolic pressure (afterload). Plasma myocardial depressant factor activity accumulated in all endotoxin-administered animals, tending to be greater in the high-dose group. In this group, both subendocardial blood flow and global function were depressed, whereas pigs administered the low dose of endotoxin demonstrated slight, but nonsignificant, increases in flow and function. These observations indicate that myocardial contractile depression is associated with a lethal outcome to high doses of endotoxin. One possible mechanism for this loss of contractile function may be a relative hypoperfusion of the subendocardium.

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.

Effect of regional myocardial ischemia on cardiac pump performance during exercise

1978 ◽  
Vol 234 (2) ◽  
pp. H157-H162
Author(s):  
L. D. Horwitz ◽  
D. F. Peterson ◽  
V. S. Bishop
Keyword(s):  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Adrenergic Stimulation ◽  
Circumflex Coronary Artery ◽  
Pump Performance ◽  
Regional Myocardial Ischemia ◽  
Exercise Hemodynamics ◽  
Stimulation Of

The effect of brief periods of regional ischemia upon left ventricular pump performance was studied in nine dogs standing quietly at rest and during running exercise on a treadmill. Transient occlusions of the left circumflex coronary artery resulted in increase in heart rate at rest (+30 beats/min) but not during exercise. Other changes due to occlusion were similar at rest and during exercise and included decreases in stroke volume (-25% standing, -23% running); in dP/dt max, the maximum first derivative of the left ventricular pressure (-20% standing or running); and in left ventricular peak systolic pressure (-13% standing, -21% running); and rises in left ventricular end-diastolic pressure (+4.5 mmHg standing, +6.3 mmHg running). Cardiac output was unchanged by occlusions at rest but fell (-18%) during occlusions while the dogs were running. Propranolol reduced absolute levels of cardiac performance during exercise occlusions but had no effect at rest. Inotropic agents with ischemia had some effects at rest but did not alter exercise hemodynamics. It is concluded that integrated left ventricular function during ischemia is not impaired by exercise, probably because of beta-adrenergic stimulation of nonischemic myocardium.

Direct cardiac effects of vasopressin and their reversal by a vascular antagonist

1986 ◽  
Vol 251 (4) ◽  
pp. H734-H741 ◽  
Author(s):  
W. A. Boyle ◽  
L. D. Segel
Keyword(s):  
Coronary Flow ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Total Output ◽  
Stroke Work ◽  
Cardiac Effects ◽  
Myocardial O2 Consumption ◽  
Dose Dependent

We studied the direct cardiac effects of arginine vasopressin (AVP) by use of an isolated working rat heart model perfused with Krebs-Henseleit medium. At a concentration of 878 +/- 15 pg/ml, AVP produced significant (P less than 0.05) decreases in coronary flow (-31 +/- 2%); myocardial O2 consumption (-12 +/- 2%); left ventricular peak systolic pressure (-5 +/- 1%); dP/dtmax (-7 +/- 1%); -dP/dtmax (-6 +/- 3%); peak aortic flow rate (-5 +/- 1%); stroke work (-3 +/- 1%); peak power (-8 +/- 1%); and total output (-3 +/- 1%). Aortic output increased significantly (+7 +/- 1%) as did arteriovenous O2 difference (+108 +/- 14 mmHg); left ventricular end-diastolic pressure (+0.4 +/- 0.1 mmHg); efficiency (+1.5 +/- 0.4%); and rate of lactate release (+1.27 +/- 0.21 nmol/ml perfusate/min). Dose-response relationships were studied at 9 +/- 1, 25 +/- 1, 75 +/- 3, 303 +/- 15, and 817 +/- 42 pg AVP/ml. Significant dose-dependent depression of coronary flow occurred at the three highest AVP concentrations; cardiac function was significantly depressed at the highest dose. The AVP analogue d(CH2)5[Tyr(Me)]AVP (20 ng/ml) completely reversed the cardiac effects attributed to AVP. The data indicate that AVP is a potent direct coronary constrictor that produces myocardial ischemia and decreased contractile function at AVP concentrations that are observed in some pathophysiologic states.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased cardiac contractility in acute uremia: interrelationships with hypertension

1975 ◽  
Vol 229 (2) ◽  
pp. 501-505 ◽  
Author(s):  
T Nivatpumin ◽  
T Yipintsoi ◽  
S Penpargkul ◽  
J Scheuer
Keyword(s):  
Blood Pressure ◽  
Systolic Hypertension ◽  
Diastolic Pressure ◽  
Cardiac Contractility ◽  
Systolic Pressure ◽  
Pressure Rise ◽  
Left Ventricular ◽  
Ventricular Systolic Pressure ◽  
Inotropic State ◽  
Left Ventricular Systolic Pressure

To study the effects of acute uremia on the inotropic state of the rat heart, we subjected rats to bilateral nephrectomy and studied their hearts in the open chest 24 h later. Uremic rats had significantly higher systolic blood pressure than sham-operated animals. Left ventricular systolic pressure and maximum dP/dt, both during ejection and isovolumic contrations, were higher for any given end-diastolic pressure in hearts of uremic rats than in sham-operated animals. This difference in performance charcteristics was not abolished by doses of propranolol that blocked the heart rate response to isoproterenol. The administration of phenoxybenzamine during the 24 h of uremia abolished the blood pressure rise in uremic rats, but the increased contractile state persisted. Treatment of sham-operated animals with methoxamine to produce the same course of blood pressure as observed in uremic rats was also associated with an increased inotropic state. These results indicate that in the rat, acute uremia is associated with an increased inotropic state that is not mediated by beta-adrenergic mechanisms. The systolic hypertension of acute uremia is not the major cause of the increased contractility, although systolic hypertension without uremia can mimic the performance characteristics found in hearts of uremic rats.

scholarly journals Decreased cardiac SERCA2 expression, SR Ca uptake, and contractile function in hypothyroidism are attenuated in SERCA2 overexpressing transgenic rats

2011 ◽  
Vol 300 (3) ◽  
pp. H943-H950 ◽  
Author(s):  
Roland Vetter ◽  
Uwe Rehfeld ◽  
Christoph Reissfelder ◽  
Henry Fechner ◽  
Enn Seppet ◽  
...  
Keyword(s):  
Contractile Function ◽  
Heart Function ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Cardiac Contraction ◽  
Loss Of Function ◽  
Transgenic Rats ◽  
Mrna Ratio ◽  
And Function

The sarco/endoplasmic reticulum (SR) Ca2+-ATPase SERCA2a has a key role in controlling cardiac contraction and relaxation. In hypothyroidism, decreased expression of the thyroid hormone (TH)-responsive SERCA2 gene contributes to slowed SR Ca2+ reuptake and relaxation. We investigated whether cardiac expression of a TH-insensitive SERCA2a cDNA minigene can rescue SR Ca2+ handling and contractile function in female SERCA2a-transgenic rats (TG) with experimental hypothyroidism. Wild-type rats (WT) and TG were rendered hypothyroid by 6- N-propyl-2-thiouracil treatment for 6 wk; control rats received no treatment. In vivo measured left ventricular (LV) hemodynamic parameters were compared with SERCA2a expression and function in LV tissue. Hypothyroidism decreased LV peak systolic pressure, dP/d tmax, and dP/d tmin in both WT and TG. However, loss of function was less in TG. Thus slowed relaxation in hypothyroidism was found to be 1.5-fold faster in TG compared with WT ( P < 0.05). In parallel, a 1.4-fold higher Vmax value of homogenate SR Ca2+ uptake was observed in hypothyroid TG ( P < 0.05 vs. hypothyroid WT), and the hypothyroidism-caused decline of LV SERCA2a mRNA expression in TG by −24% was markedly less than the decrease of −49% in WT ( P < 0.05). A linear relationship was observed between the SERCA2a/PLB mRNA ratio values and the Vmax values of SR Ca2+ uptake when the respective data of all experimental groups were plotted together ( r = 0.90). The data show that expression of the TH-insensitive SERCA2a minigene compensates for loss of expressional activity of the TH-responsive native SERCA2a gene in the female hypothyroid rat heart. However, SR Ca2+ uptake and in vivo heart function were only partially rescued.

Abstract 042: Radiation-Associated Cardiovascular Risks for Future Deep-Space Missions

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Xinhua Yan ◽  
Sharath P Sasi ◽  
Hannah Gee ◽  
Juyong Lee ◽  
Yongyao Yang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Dose ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Heart Function ◽  
Left Ventricular ◽  
Calcium Handling ◽  
Cardiovascular Risks ◽  
Compensatory Mechanisms ◽  
Negative Effect

During the future Moon and Mars missions astronauts will be exposed to space radiation (IR) for extended time. The effect of cosmic IR during and after space flights on cardiovascular (CV) system is unknown. Nine-month old C57BL/6N male mice were IR once with proton 50 cGy or 56Fe 15 cGy, both at 1 GeV/nucleon. We evaluated IR-induced biological responses - underlying molecular mechanisms, calcium handling, signal transduction and gene expression. Cardiac function was assessed by echocardiography and hemodynamic measurements. Left ventricular end diastolic pressure (LVEDP) was increased in 56Fe mice 1 and 3 months post-IR (p<0.001). One month post-IR, compared to control, proton- and 56Fe-IR sarcolemmal Na+-Ca2+ exchanger (NCX) (p<0.007) and sarco(endo)plasmic reticulum calcium-ATPase (SERCA2a, p<0.02) were both increased more than 200% and p-p38 was decreased 400% (p<0.05), suggesting activation of compensatory mechanisms in [Ca2+]i handling in these hearts. By 3 months, compared to control, proton- and 56Fe-IR hearts SERCA2a and p-Creb1 was decreased 200-500% (p<0.02), suggesting reduced capacity in intracellular [Ca2+]i handling, suggesting that [Ca2+]i handling dysfunction combined with LVEDP increase in 56Fe-IR may be due to prolonged activation of compensatory mechanisms that lead to changes in SERCA2a and p-Creb1 levels. By 10 months, compared to control, LVESP was decreased in proton- and 56Fe-IR (p<0.03), suggesting IR-associated decrease in contractile function. However, compared to age-matched controls (18 months), the LVEDP was increased (p<0.05) and dP/dt Min was decreased (p<0.02) in proton-IR but not 56Fe-IR mice. This data suggests that after 10 months proton- but not 56Fe-IR affects considerably contractile and relaxation functions during aging. Our longitudinal 1, 3 and 10 months studies reveal that a single full body low dose proton- and 56Fe-IR have long-lasting negative effect on heart homeostasis during aging. The divergent effects of low dose proton vs. 56Fe-IR on heart function during aging suggest significantly different biological mechanisms responsible for this ion-dependent dichotomy over 10 months post-IR and necessitate further studies into underlying molecular mechanisms.

Chronic central versus systemic blockade of AT1 receptors and cardiac dysfunction in rats post-myocardial infarction

2009 ◽  
Vol 297 (3) ◽  
pp. H968-H975 ◽  
Author(s):  
Bing S. Huang ◽  
Monir Ahmad ◽  
Junhui Tan ◽  
Frans H. H. Leenen
Keyword(s):  
Myocardial Infarction ◽  
Diastolic Pressure ◽  
Systolic Pressure ◽  
Subcutaneous Administration ◽  
Pharmacokinetic Profile ◽  
Left Ventricular ◽  
Post Myocardial Infarction ◽  
Receptor Blockade ◽  
Cardiac Effects ◽  
And Function

In rats, both central and systemic ANG II type 1 (AT1) receptor blockade attenuate sympathetic hyperactivity, but central blockade more effectively attenuates left ventricular (LV) dysfunction post-myocardial infarction (MI). In protocol I, we examined whether functional effects on cardiac load may play a role and different cardiac effects disappear after withdrawal of the blockade. Wistar rats were infused for 4 wk post-MI intracerebroventricularly (1 mg·kg−1·day−1) or injected subcutaneously daily (100 mg·kg−1·day−1) with losartan. LV dimensions and function were assessed at 4 wk and at 6 wk post-MI, i.e., 2 wk after discontinuing treatments. At 4 and 6 wk post-MI, LV dimensions were increased and ejection fraction was decreased. Intracerebroventricular but not subcutaneous losartan significantly improved these parameters. At 6 wk, LV peak systolic pressure (LVPSP) and maximal or minimal first derivative of change in pressure over time (dP/d tmax/min) were decreased and LV end-diastolic pressure (LVEDP) was increased. All four indexes were improved by previous intracerebroventricular losartan, whereas subcutaneous losartan improved LVEDP only. In protocol II, we evaluated effects of oral instead of subcutaneous administration of losartan for 4 wk post-MI. Losartan (∼200 mg·kg−1·day−1) either via drinking water or by gavage similarly decreased AT1 receptor binding densities in brain nuclei and improved LVEDP but further decreased LVPSP and dP/d tmax. These results indicate that effects on cardiac load by peripheral AT1 receptor blockade or the pharmacokinetic profile of subcutaneous versus oral dosing do not contribute to the different cardiac effects of central versus systemic AT1 receptor blockade post-MI.

Effects of graded insulin therapy on cardiac function in diabetic rats

1984 ◽  
Vol 246 (3) ◽  
pp. H453-H458 ◽  
Author(s):  
M. Rubinstein ◽  
T. F. Schaible ◽  
A. Malhotra ◽  
J. Scheuer
Keyword(s):  
Cardiac Function ◽  
Atpase Activity ◽  
Insulin Therapy ◽  
Diastolic Pressure ◽  
Contractile Function ◽  
Systolic Pressure ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Heart Weight ◽  
Control Group

To determine the effects of graded insulin therapy on cardiac function and biochemistry, rats were made diabetic by streptozotocin (50 mg/kg) and subsequently treated with either 3 U of insulin per day (D3) or 5 U/day (D5) and compared with untreated diabetic rats (D phi) and a nondiabetic control group (C). Blood glucose, water consumption, and heart and body weights in D3 and D5 showed dose-dependent responses between those of D phi and C. Cardiac function was studied at similar heart rates and similar left atrial and aortic pressures in an isolated working heart apparatus. Hearts from D phi showed significant decreases in end-diastolic pressure, peak left ventricular systolic pressure, and positive dP/dt, whereas these values in D3 and D5 were similar to those in C. The isovolumic relaxation period was significantly longer in the D phi group, intermediate between D phi and C in D3, and the same in D5 and C. Ca2+-ATPase activity of myosin and actin-activated Mg2+-ATPase activity was depressed in D phi, partially corrected in D3, and completely corrected in D5. Myosin isoenzyme distribution displayed a shift from the predominant V1 pattern observed in C to a predominant V3 pattern in D phi. Treatment with 3 U of insulin per day partially corrected the isoenzyme abnormality, and treatment with 5 U/day restored the isoenzyme distribution to normal. These results indicate that gross cardiac contractile function can be normalized with insulin dosages that are not sufficient to correct hyperglycemia, polydipsia, or body and heart weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dobutamine of ventriculoarterial coupling in acute regional myocardial ischemia in dogs

1996 ◽  
Vol 270 (4) ◽  
pp. H1279-H1286
Author(s):  
H. Seki ◽  
K. Katayama ◽  
H. Sakai ◽  
T. Yonezawa ◽  
H. Kunichika ◽  
...  
Keyword(s):  
Low Dose ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
High Dose ◽  
Base Line ◽  
Work Efficiency ◽  
External Work ◽  
Regional Ischemia ◽  
Volume Relation ◽  
Acute Regional Ischemia

We assessed the effect of dobutamine on left ventricoarterial coupling during acute regional ischemia. Using a conductance catheter, we analyzed the end-systolic pressure-volume relation (ESPVR) in anesthetized dogs. We calculated the slope of ESPVR (Ees), the slope of the end-systolic pressure-stroke volume relation (Ea), (Ea/Ees) and the ratio (work efficiency) of external work to pressure-volume area at base-line during ischemia induced by occlusion of the left anterior descending coronary artery and during low-dose (1-3 micrograms.min-1.kg-1) and high-dose (4-10 micrograms.min-1.kg-1)dobutamine infusions with ischemia. ESPVR shifted to the right without a change in Ees during ischemia. Dobutamine caused dose-dependent increases in Ees but did not affect the intercept of ESPVR. During ischemia, Ea/Ees increased and work efficiency decreased. Low-dose dobutamine was associated with a return in control for Ea/Ees and work efficiency. High-dose dobutamine increased Ees and Ea but produced no further increase in Ea/Ees or work efficiency. Low-dose dobutamine would appear to be the preferable regimen to achieve the optimal ventriculoarterial coupling in acute regional ischemia associated with mismatched ventriculoarterial coupling and depressed left ventricular work efficiency.

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.

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