Testosterone receptor blockade after trauma-hemorrhage improves cardiac and hepatic functions in males

1997 ◽  
Vol 273 (6) ◽  
pp. H2919-H2925 ◽  
Author(s):  
Dierk E. Remmers ◽  
Ping Wang ◽  
William G. Cioffi ◽  
Kirby I. Bland ◽  
Irshad H. Chaudry
Keyword(s):  
Cardiac Output ◽  
Blood Volume ◽  
Maximum Velocity ◽  
Left Ventricular ◽  
Male Rats ◽  
Microvascular Blood Flow ◽  
Receptor Blockade ◽  
Ringer Lactate ◽  
Ventricular Performance ◽  
Shed Blood

Although studies have shown that testosterone receptor blockade with flutamide after hemorrhage restores the depressed immune function, it remains unknown whether administration of flutamide following trauma and hemorrhage and resuscitation has any salutary effects on the depressed cardiovascular and hepatocellular functions. To study this, male rats underwent a laparotomy (representing trauma) and were then bled and maintained at a mean arterial pressure (MAP) of 40 mmHg until the animals could not maintain this pressure. Ringer lactate was given to maintain a MAP of 40 mmHg until 40% of the maximal shed blood volume was returned in the form of Ringer lactate. The rats were then resuscitated with four times the shed blood volume in the form of Ringer lactate over 60 min. Flutamide (25 mg/kg) or an equal volume of the vehicle propanediol was injected subcutaneously 15 min before the end of resuscitation. Various in vivo heart performance parameters (e.g., maximal rate of the pressure increase or decrease), cardiac output, and hepatocellular function (i.e., the maximum velocity and the overall efficiency of indocyanine green clearance) were determined at 20 h after resuscitation. Additionally, hepatic microvascular blood flow (HMBF) was determined using a laser Doppler flowmeter. The results indicate that left ventricular performance, cardiac output, HMBF, and hepatocellular function decreased significantly at 20 h after the completion of trauma, hemorrhage, and resuscitation. Administration of the testosterone receptor blocker flutamide, however, significantly improved cardiac performance, HMBF, and hepatocellular function. Thus flutamide appears to be a novel and useful adjunct for improving cardiovascular and hepatocellular functions in males following trauma and hemorrhagic shock.

Preheparinization improves organ function after hemorrhage and resuscitation

1990 ◽  
Vol 259 (3) ◽  
pp. R645-R650 ◽  
Author(s):  
P. Wang ◽  
G. Singh ◽  
M. W. Rana ◽  
Z. F. Ba ◽  
I. H. Chaudry
Keyword(s):  
Renal Function ◽  
Cardiac Output ◽  
Microvascular Blood Flow ◽  
Maximal Velocity ◽  
Protective Effects ◽  
Organ Function ◽  
Ringer Lactate ◽  
Indocyanine Green Clearance ◽  
Shed Blood ◽  
Liver And Kidney

Recent studies indicate that heparinization before hemorrhage maintains microvascular patency in the liver and kidney during and after severe hemorrhagic shock. However, it is not known whether preheparinization has any protective effects on organ function after hemorrhage and resuscitation. To study this, unanesthetized rats (with or without preheparinization) were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of the maximum shed blood volume was returned in the form of Ringer lactate (RL). They were then resuscitated with four times the volume of the shed blood with RL. Cardiac output (CO), [3H]inulin clearance (CIn; renal function), hepatic microvascular blood flow (HMBF), and hepatocellular function (HF), i.e., maximal velocity of indocyanine green clearance (Vmax), were determined 1.5 h after resuscitation. Although CO decreased in both groups, the values in preheparinized rats were significantly higher than in the nonheparinized rats. The improvement in CIn as well as HMBF followed the same trends. HF (Vmax) was significantly depressed in the nonheparinized rats but was maintained in preheparinized rats. Thus administration of heparin before the onset of hemorrhage improves CO and renal function and restores HF to control after hemorrhage and resuscitation. These protective effects of preheparinization could be due to the maintenance of microvascular patency and prevention of blood sludging during and after hemorrhage.

Effects of nonanticoagulant heparin on cardiovascular and hepatocellular function after hemorrhagic shock

1996 ◽  
Vol 270 (4) ◽  
pp. H1294-H1302 ◽  
Author(s):  
P. Wang ◽  
Z. F. Ba ◽  
S. S. Reich ◽  
M. Zhou ◽  
K. R. Holme ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Anticoagulant Activity ◽  
Cecal Ligation ◽  
Cardiovascular Responses ◽  
Microvascular Blood Flow ◽  
Organ Function ◽  
Ringer Lactate ◽  
Shed Blood ◽  
Beneficial Effects

Although heparinization of animals before hemorrhage improves cell and organ function, the potent anticoagulant activity of conventional heparin sodium precludes its potential clinical use. To determine whether a novel nonanticoagulant heparin, GM1892, would have any beneficial effects on cardiovascular and hapatocellular functions and would decrease susceptibility to sepsis after hemorrhage, laparotomy was performed on rats (i.e., trauma induced), after which they were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximal bleedout volume was returned in the form of Ringer lactate solution (RL). The rats were then resuscitated with three times the volume of shed blood with RL over 45 min, followed by infusion of two times RL plus GM1892 (7 mg/kg body wt; approximately 2% the anticoagulant activity of regular heparin) of saline over 60 min. At 2 and 4 h after the completion of resuscitation, cardiac output, hepatocellular function, and microvascular blood flow were determined. The results indicated that cardiac output, hepatocellular function, and microvascular blood flow in the liver, spleen, and small intestine decreased significantly after hemorrhage and resuscitation. Administration of GM1892, however, restored these parameters. The morphological abnormality observed after hemorrhage in the liver, kidney, and small gut was also attenuated with GM1892 treatment. Moreover, GM1892 normalized the elevated plasma prostaglandin E2 levels. Sepsis was induced in additional rats by cecal ligation and puncture (CLP) 20 h after hemorrhage, and the necrotic cecum was excised 10 h thereafter. GM1892 treatment significantly decreased mortality after CLP and cecal excision. Thus GM1892 appears to be a useful adjunct to fluid resuscitation, since it restores the depressed cardiovascular responses and decreases susceptibility to sepsis after trauma and hemorrhage.

Preinduction of heat shock proteins protects cardiac and hepatic functions following trauma and hemorrhage

2000 ◽  
Vol 278 (2) ◽  
pp. R352-R359 ◽  
Author(s):  
Yasuaki Mizushima ◽  
Ping Wang ◽  
Doraid Jarrar ◽  
William G. Cioffi ◽  
Kirby I. Bland ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Heat Stress ◽  
Heat Shock ◽  
Plasma Levels ◽  
Left Ventricular ◽  
Hsp 70 ◽  
Ringer Lactate ◽  
Shed Blood ◽  
Tnf Α ◽  
Shock Proteins

Although studies have shown that induction of the heat shock proteins (HSPs), such as HSP-70, has various beneficial effects after ischemia-reperfusion, it remains unknown whether prior induction of HSP-70 has any salutary effects on cardiovascular and hepatocellular functions after trauma-hemorrhage and resuscitation. Male rats were exposed to heat stress (41°C, 15 min) and then allowed to recover for 24 h at room temperature (21°C). The rats then underwent laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of the maximal shed blood volume was returned in the form of Ringer lactate. Animals were then resuscitated with four times the volume of shed blood with Ringer lactate over 60 min. The maximal rate of the left ventricular pressure increase or decrease was measured up to 4 h after resuscitation. Cardiac output, hepatocellular function, plasma levels of tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were determined at 4 h after resuscitation. Cardiac and hepatic tissue were examined for HSP-70 by Western blot analysis. Left ventricular performance, cardiac output, and hepatocellular function decreased significantly following trauma-hemorrhage. Plasma levels of TNF-α and IL-6 were also significantly increased. However, prior heat stress attenuated cardiovascular and hepatocellular dysfunction, decreased circulating levels of proinflammatory cytokines following trauma-hemorrhage, and was associated with an increased abundance of HSP-70 in the heart and liver. Our data, therefore, suggest that preinduction of HSP-70 protects cardiovascular and hepatocellular functions following trauma-hemorrhage and resuscitation.

Time course of hemodynamic changes in rats with healed severe myocardial infarction

1989 ◽  
Vol 257 (1) ◽  
pp. H289-H296 ◽  
Author(s):  
A. DeFelice ◽  
R. Frering ◽  
P. Horan
Keyword(s):  
Myocardial Infarction ◽  
Blood Flow ◽  
Cardiac Output ◽  
Diastolic Pressure ◽  
Weight Ratio ◽  
Left Ventricular ◽  
Male Rats ◽  
Coronary Artery Ligation ◽  
Sham Operation ◽  
Functional Changes

Male rats were monitored for 8 mo after severe myocardial infarction (MI) to chronicle hemodynamic and left ventricular (LV) functional changes. Blood pressure (BP), heart rate (HR), cardiac output index (CO), regional blood flow, and systemic vascular resistance (SVR) were measured with catheters and radiolabeled microspheres at 4, 7, 10, 20, and 35 wk after coronary artery ligation (n = 10–16/group) or sham operation (control; n = 9–14/group). At 4 wk, 43 +/- 1% of the LV circumference was scarred, peak LV BP, LV dP/dtmax, mean BP, SVR, and HR were 11–38% less than control (P less than 0.05), and LV end-diastolic pressure (LVEDP) was increased by 313% (P less than 0.05). Mean BP, LVEDP, LVBP, and LV dP/dtmax did not further deviate after 4 wk. However, CO and SVR changed progressively and were 67 and 33%, respectively, of control by 35 wk (P less than 0.05) when blood flow to stomach, small intestine, and kidney was 55, 38, and 27% of control. Lung and heart weights were significantly increased by 148 and 22% at 4 wk, and remained elevated, and lung dry weight-to-wet weight ratio was reduced at 7 and 10 wk. Thus the trajectory of rats with healed severe MI reflects progressive cardiac decompensation, cardiac output redistribution, and terminal heart failure.

Atrial natriuretic peptide reverses angiotensin-induced venoconstriction in dogs

1989 ◽  
Vol 257 (4) ◽  
pp. H1062-H1067 ◽  
Author(s):  
R. W. Lee ◽  
R. G. Gay ◽  
S. Goldman
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Blood Volume ◽  
Left Ventricular ◽  
Ang Ii ◽  
Central Blood Volume ◽  
Venous Compliance ◽  
Induced Hypertension

To determine whether atrial natriuretic peptide (ANP) can reverse angiotensin (ANG II)-induced venoconstriction, ANP was infused (0.3 micrograms.kg-1.min-1) in the presence of ANG II-induced hypertension in six ganglion-blocked dogs. ANG II was initially administered to increase mean arterial blood pressure (MAP) 50% above control. ANG II did not change heart rate or left ventricular rate of pressure development (LV dP/dt) but increased total peripheral vascular resistance (TPVR) and left ventricular end-diastolic pressure (LVEDP). Mean circulatory filling pressure (MCFP) increased, whereas cardiac output and venous compliance decreased. Unstressed vascular volume did not change, but central blood volume increased. ANP infusion during ANG II-induced hypertension resulted in a decrease in MAP, but TPVR did not change. There were no changes in heart rate or LV dP/dt. ANP decreased cardiac output further. LVEDP returned to base line with ANP. ANP also decreased MCFP and normalized venous compliance. There was no significant change in total blood volume, but central blood volume decreased. In summary, ANP can reverse the venoconstriction but not the arterial vasoconstriction produced by ANG II. The decrease in MAP was due to a decrease in cardiac output that resulted from venodilatation and aggravation of the preload-afterload mismatch produced by ANG II alone. Because TPVR did not change when MAP fell, we conclude that the interaction between ANG II and ANP occurs primarily in the venous circulation.

Mechanism for decrease in cardiac output with atrial natriuretic peptide in dogs

1989 ◽  
Vol 256 (3) ◽  
pp. H760-H765 ◽  
Author(s):  
R. W. Lee ◽  
S. Goldman
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Atrial Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Blood Volume ◽  
Left Ventricular ◽  
Right Atrial ◽  
Total Blood Volume ◽  
Total Blood ◽  
Atrial Natriuretic

To examine the mechanism by which atrial natriuretic peptide (ANP) decreases cardiac output, we studied changes in the heart, peripheral circulation, and blood flow distribution in eight dogs. ANP was given as a bolus (3.0 micrograms/kg) followed by an infusion of 0.3 microgram.kg-1.min-1. ANP did not change heart rate, total peripheral vascular resistance, and the first derivative of left ventricular pressure but decreased mean aortic pressure from 91 +/- 4 to 76 +/- 3 mmHg (P less than 0.001) and cardiac output from 153 +/- 15 to 130 +/- 9 ml.kg-1.min-1 (P less than 0.02). Right atrial pressure and left ventricular end-diastolic pressure also decreased. Mean circulatory filling pressure decreased from 7.1 +/- 0.3 to 6.0 +/- 0.3 mmHg (P less than 0.001), but venous compliance and unstressed vascular volume did not change. Resistance to venous return increased from 0.056 +/- 0.008 to 0.063 +/- 0.010 mmHg.ml-1.kg.min (P less than 0.05). Arterial compliance increased from 0.060 +/- 0.003 to 0.072 +/- 0.004 ml.mmHg-1.kg-1 (P less than 0.02). Total blood volume and central blood volume decreased from 82.2 +/- 3.1 to 76.2 +/- 4.6 and from 19.8 +/- 0.8 to 17.6 +/- 0.6 ml/kg (P less than 0.02), respectively. Blood flow increased to the kidneys. We conclude that ANP decreases cardiac output by decreasing total blood volume. This results in a lower operating pressure and volume in the venous capacitance system with no significant venodilating effects. Cardiac factors and a redistribution of flow to the splanchnic organs are not important mechanisms to explain the decrease in cardiac output with ANP.

Doppler Cardiac Output and Left Ventricular Performance after Cardiac Surgery

CHEST Journal ◽  
1992 ◽  
Vol 102 (2) ◽  
pp. 380-386 ◽  
Author(s):  
Marie-Dominique Fratacci ◽  
Didier Payen ◽  
Sadek Beloucif ◽  
François Laborde
Keyword(s):  
Cardiac Output ◽  
Cardiac Surgery ◽  
Left Ventricular ◽  
Left Ventricular Performance ◽  
Ventricular Performance

Effects of heat stress on vascular capacitance

1994 ◽  
Vol 266 (5) ◽  
pp. H2122-H2129 ◽  
Author(s):  
A. Deschamps ◽  
S. Magder
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Heat Stress ◽  
Blood Volume ◽  
Adrenergic Receptor ◽  
Venous Return ◽  
Receptor Blockade ◽  
Ganglionic Blockade ◽  
Unstressed Volume ◽  
Adrenergic Receptor Blockade

In dogs and humans, heat stress is associated with an increase in cardiac output that sustains blood flow to heat-dissipating organs. Because cardiac output and venous return are equal in the steady state, the circulation must also adjust in heat stress to allow the venous return to increase. To analyze these adjustments, we measured blood volumes, unstressed volumes, blood flow distribution, venous compliance, venous resistance, and the time constant of venous drainage of the splanchnic and extrasplanchnic vascular beds in dogs anesthetized with alpha-chloralose at normal and at high core temperatures. We repeated the measurements at high core temperatures with ganglionic blockade, alpha-adrenergic receptor blockade, or beta-adrenergic receptor blockade to determine the efferent neurohumoral pathway. When core temperature was increased from 37.8 +/- 0.2 to 41.9 +/- 0.1 degrees C, total splanchnic blood volume decreased 23% (4.6 +/- 1.4 ml/kg) and splanchnic unstressed volume decreased 38.5%. None of the other determinants of venous return changed. Ganglionic blockade shifted the total and unstressed splanchnic blood volume during heat stress back to normothermic values. However, beta- and alpha-blockade did not affect splanchnic volumes. We conclude that a decrease in splanchnic unstressed volume is an important factor for the increased venous return during heat stress. Although mediated through sympathetic ganglions, this decrease is not abolished by alpha- or beta-receptor blockade.

Chronic opiate-receptor inhibition in experimental congestive heart failure in dogs

1997 ◽  
Vol 272 (1) ◽  
pp. H478-H484
Author(s):  
A. Yatani ◽  
N. Imai ◽  
Y. Himura ◽  
M. Suematsu ◽  
C. S. Liang
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Cardiac Output ◽  
Opiate Receptor ◽  
Left Ventricular ◽  
Right Atrial ◽  
Acute Administration ◽  
Ventricular Performance ◽  
Inotropic Effects ◽  
Receptor Inhibition

Acute administration of opiate-receptor antagonists has previously been shown to improve cardiac output aortic blood pressure, systolic ventricular performance, and the baroreflex function in conscious dogs with right-sided congestive heart failure (RHF). However, whether similar changes occur after chronic opiate-receptor inhibition in congestive heart failure is not known. To determine the chronic effects of opiate-receptor antagonism on RHF, we administered naltrexone (200 mg/day), a long-acting, orally active opiate-receptor blocking agent, to RHF and sham-operated animals for 6 wk. Naltrexone had no effects on resting heart rate, right atrial pressure, aortic pressure, or cardiac output in RHF dogs but increased the first derivative of right and left ventricular pressure with respect to time (dP/dt) at rest and improved the dP/dt response to isoproterenol. The inotropic responses to isoproterenol and forskolin in isolated right ventricular trabeculate muscle also were improved by chronic naltrexone in RHF. Myocardial beta-receptor density was reduced in the failing right ventricle compared with the control (58 +/- 3 vs. 108 +/- 6 fmol/mg protein, P < 0.01) but was unaffected by addition of naltrexone. Finally, naltrexone prevented the decline in baroreflex sensitivity that occurred in RHF (-0.2 +/- 0.5 vs. -6.0 +/- 0.5 ms/mmHg, P < 0.01). These effects of naltrexone did not occur in the shamoperated animals. Chronic opiate-receptor blockade with naltrexone attenuates the development of reduced adrenergic inotropic responsiveness and baroreflex subsensitivity that occur in RHF. Because there was a similar improvement in the forskolin response in the absence of significant alterations in myocardial beta-adrenoceptor density after naltrexone treatment, the improvement in adrenergically mediated inotropic effects probably is mediated via a postreceptor mechanism.

Testosterone receptor blockade after trauma and hemorrhage attenuates depressed adrenal function

2000 ◽  
Vol 279 (5) ◽  
pp. R1841-R1848 ◽  
Author(s):  
Zheng F. Ba ◽  
Ping Wang ◽  
Douglas J. Koo ◽  
Mian Zhou ◽  
William G. Cioffi ◽  
...  
Keyword(s):  
Adrenal Function ◽  
Male Rats ◽  
Ringer Lactate ◽  
Acth Stimulation ◽  
Camp Content ◽  
Morphological Alterations ◽  
Shed Blood ◽  
Corticosterone Response ◽  
Corticosterone Release ◽  
Adrenal Corticosterone

Although the testosterone receptor antagonist flutamide restores the depressed immune function in males after trauma and hemorrhage, it remains unknown whether this agent has any salutary effects on adrenal function. To study this, male rats underwent laparotomy and were bled to and maintained at a blood pressure of 40 mmHg until 40% of the shed blood volume was returned in the form of Ringer lactate. Animals were then resuscitated and flutamide (25 mg/kg body wt) was administered subcutaneously. Plasma adrenocorticotropic hormone (ACTH) and corticosterone, as well as adrenal corticosterone and cAMP were measured 20 h after resuscitation. In additional animals, ACTH was administered and ACTH-induced corticosterone release and adrenal cAMP were determined. The results indicate that adrenal contents of corticosterone and cAMP were significantly decreased and morphology was altered after hemorrhage. Administration of flutamide improved corticosterone content, restored cAMP content, and attenuated adrenal morphological alterations. Flutamide also improved the diminished ACTH-induced corticosterone release and adrenal cAMP response at 20 h after hemorrhage and resuscitation. Furthermore, the diminished corticosterone response to ACTH stimulation in the isolated adrenal preparation was improved with flutamide. These results suggest that flutamide is a useful adjunct for improving adrenal function in males following trauma and hemorrhage.

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