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.

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.

scholarly journals Pentoxifylline prevents the transition from the hyperdynamic to hypodynamic response during sepsis

1999 ◽  
Vol 277 (3) ◽  
pp. H1036-H1044 ◽  
Author(s):  
Shaolong Yang ◽  
Mian Zhou ◽  
Douglas J. Koo ◽  
Irshad H. Chaudry ◽  
Ping Wang
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Cardiovascular Response ◽  
Cecal Ligation ◽  
Organ Blood Flow ◽  
Adult Rats ◽  
Male Adult ◽  
Morphological Alterations ◽  
Beneficial Effects ◽  
Renal Oxygen

The cardiovascular response to sepsis includes an early, hyperdynamic phase followed by a late, hypodynamic phase. Although administration of pentoxifylline (PTX) produces beneficial effects in sepsis, it remains unknown whether this agent prevents the transition from the hyperdynamic to the hypodynamic response during the progression of sepsis. To study this, male adult rats were subjected to polymicrobial sepsis by cecal ligation and puncture (CLP). At 1 h after CLP, PTX (50 mg/kg body wt) or vehicle was infused intravenously over 30 min. At 20 h after CLP (i.e., the late stage of sepsis), cardiac output and organ blood flow were measured by radioactive microspheres. Systemic and regional (i.e., hepatic, intestinal, and renal) oxygen delivery (Do 2) and oxygen consumption (V˙o 2) were determined. Moreover, plasma levels of lactate and alanine aminotransferase (ALT) were measured, and histological examinations were performed. In additional animals, the necrotic cecum was excised at 20 h after CLP, and mortality was monitored for 10 days thereafter. The results indicate that cardiac output, organ blood flow, and systemic and regional Do 2decreased by 36–65% ( P < 0.05) at 20 h after CLP. Administration of PTX early after the onset of sepsis, however, prevented reduction in measured hemodynamic parameters and increased systemic and regional Do 2 andV˙o 2 by 50–264% ( P < 0.05). The elevated levels of lactate (by 173%, P < 0.05) and ALT (by 718%, P < 0.05), as well as the morphological alterations in the liver, small intestine, and kidneys during sepsis were attenuated by PTX treatment. In addition, PTX treatment decreased the mortality rate from 50 to 0% ( P < 0.05) after CLP and cecal excision. Because PTX prevents the occurrence of hypodynamic sepsis, this agent appears to be a useful adjunct for maintaining hemodynamic stability and preventing lethality from sepsis.

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.

A model of anemic tissue perfusion after blood transfusion shows critical role of endothelial response to shear stress stimuli

2021 ◽  
Author(s):  
Weiyu Li ◽  
Amy G. Tsai ◽  
Marcos Intaglietta ◽  
Daniel M. Tartakovsky
Keyword(s):  
Blood Flow ◽  
Shear Stress ◽  
Blood Transfusion ◽  
Critical Role ◽  
Cardiovascular Responses ◽  
Arterial Blood Flow ◽  
Microvascular Blood Flow ◽  
No Production ◽  
Arterial Blood ◽  
Transfusion Requirements

­­ ­Although some of the cardiovascular responses to changes in hematocrit (Hct) are not fully quantified experimentally, available information is sufficient to build a mathematical model of the consequences of treating anemia by introducing RBCs into the circulation via blood transfusion. We present such a model, which describes how the treatment of normovolemic anemia with blood transfusion impacts oxygen (O2) delivery (DO2, the product of blood O2 content and arterial blood flow) by the microcirculation. Our analysis accounts for the differential response of the endothelium to the wall shear stress (WSS) stimulus, changes in nitric oxide (NO) production due to modification of blood viscosity caused by alterations of both hematocrit (Hct) and cell free layer thickness, as well as for their combined effects on microvascular blood flow and DO2. Our model shows that transfusions of 1- and 2-unit of blood have a minimal effect on DO2 if the microcirculation is unresponsive to the WSS stimulus for NO production that causes vasodilatation increasing blood flow and DO2. Conversely, in a fully WSS responsive organism, blood transfusion significantly enhances blood flow and DO2, because increased viscosity stimulates endothelial NO production causing vasodilatation. This finding suggests that evaluation of a patients' pre-transfusion endothelial WSS responsiveness should be beneficial in determining the optimal transfusion requirements for treating anemic patients.

Measurement of hepatic blood flow after severe hemorrhage: lack of restoration despite adequate resuscitation

1992 ◽  
Vol 262 (1) ◽  
pp. G92-G98 ◽  
Author(s):  
P. Wang ◽  
Z. F. Ba ◽  
J. Burkhardt ◽  
I. H. Chaudry
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Hemorrhagic Shock ◽  
Hepatic Blood Flow ◽  
Microvascular Blood Flow ◽  
Midline Laparotomy ◽  
Doppler Flowmetry ◽  
Severe Hemorrhage ◽  
Icg Clearance

Although Ringer lactate (RL) is routinely used for resuscitation, it is not known whether the volume of RL that restores cardiac output after severe hemorrhagic shock also restores the depressed effective hepatic blood flow (EHBF). To study this, a 5-cm midline laparotomy was performed in rats (i.e., trauma induced), and the animals were then bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of maximum bleedout volume was returned in the form of RL. Animals were then resuscitated with four or five times the volume of maximum bleedout with RL. EHBF was determined during hemorrhage and at various intervals thereafter by an in vivo indocyanine green (ICG) clearance technique and corrected by the appropriate hepatic extraction ratio for ICG. Cardiac output was determined by ICG dilution, and hepatic microvascular blood flow (HMBF) was measured with laser Doppler flowmetry. In addition, hepatic blood flow was assessed by using radioactive microspheres. Results indicate that resuscitation markedly improved but did not restore the depressed EHBF after trauma and hemorrhagic shock despite the fact that cardiac output was restored. Similar changes in EHBF, HMBF, and hepatic blood flow as determined by microspheres were observed, suggesting that the in vivo ICG clearance is a reliable method to assess effective hepatic perfusion. Thus the lack of restoration of EHBF may be responsible for the subsequent hepatocellular dysfunction after trauma and severe hemorrhage.

A simple module for on-line computation of stroke volume and cardiac output

1975 ◽  
Vol 38 (5) ◽  
pp. 927-929 ◽  
Author(s):  
G. Pinardi ◽  
A. Sainz ◽  
E. Santiago
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Data Analysis ◽  
Stroke Volume ◽  
Simple Module ◽  
Cardiovascular Responses ◽  
Aortic Blood Flow ◽  
Aortic Blood ◽  
On Line ◽  
Aortic Blood Flow Velocity

An easily constructed, low-priced, simple, and reliable module to obtain stroke volume and cardiac output by analog integration of aortic blood flow velocity signals is described. Rapid data analysis of physiologic and pharmacologic cardiovascular responses in dogs is greatly facilitated by on line computation of these parameters.

Whole body and hindlimb cardiovascular responses of the anesthetized dog during CO hypoxia

1984 ◽  
Vol 62 (7) ◽  
pp. 769-774 ◽  
Author(s):  
C. E. King ◽  
S. M. Cain ◽  
C. K. Chapler
Keyword(s):  
Carbon Monoxide ◽  
Blood Flow ◽  
Cardiac Output ◽  
Sympathetic Innervation ◽  
Cardiovascular Responses ◽  
The Body ◽  
Whole Body ◽  
Total Resistance ◽  
Intact Group ◽  
Anesthetized Dogs

To compare with earlier studies of anemic hypoxia obtained by hemodilution, O2 carring capacity was decreased by carbon monoxide (CO) hypoxia. Arterial O2 content was reduced either 50% (moderate CO) or 65% (severe CO). In two groups of anesthetized dogs (moderate and severe CO) hindlimb innervation remained intact while in a third group (moderate CO) the hindlimb was denervated. Measurements were obtained prior to and at 30 and 60 min of CO hypoxia. Cardiac output was elevated at 30 min of CO hypoxia in all groups (p < 0.01) and in the severe CO group at 60 min (p < 0.01). Hindlimb blood flow remained unchanged during CO hypoxia in the intact groups. In the denervated group, hindlimb blood flow was greater (p < 0.05) than that in the intact groups throughout the experiment. A decrease in mean arterial pressure (p < 0.01) in all groups was associated with a fall in total resistance (p < 0.01). Hindlimb resistance remained unchanged during moderate CO hypoxia in the intact group but increased (p < 0.05) in the denervated group. In the severe CO group hindlimb resistance was decreased (p < 0.05) at 60 min. The results indicate that the increase in cardiac output during CO hypoxia was directed to nonmuscle areas of the body and that intact sympathetic innervation was required to achieve this redistribution.

scholarly journals Cardiovascular effects of the respiratory muscle metaboreflexes in dogs: rest and exercise

2003 ◽  
Vol 95 (3) ◽  
pp. 1159-1169 ◽  
Author(s):  
Joshua R. Rodman ◽  
Kathleen S. Henderson ◽  
Curtis A. Smith ◽  
Jerome A. Dempsey
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Lactic Acid ◽  
Respiratory Muscle ◽  
Cardiovascular Effects ◽  
Cardiovascular Responses ◽  
Vascular Conductance ◽  
Iliac Arteries ◽  
Muscle Metaboreflex ◽  
Arterial Blood

In awake dogs, lactic acid was injected into the phrenic and deep circumflex iliac arteries to elicit the diaphragm and abdominal muscle metaboreflexes, respectively. At rest, injections into the phrenic or deep circumflex iliac arteries significantly increased mean arterial blood pressure 21 ± 7% and reduced cardiac output 6 ± 2% and blood flow to the hindlimbs 20 ± 9%. Simultaneously, total systemic, hindlimb, and abdominal expiratory muscle vascular conductances were reduced. These cardiovascular responses were not accompanied by significant changes in the amplitude or timing of the diaphragm electromyogram. During treadmill exercise that increased cardiac output, hindlimb blood flow, and vascular conductance 159 ± 106, 276 ± 309, and 299 ± 90% above resting values, lactic acid injected into the phrenic or deep circumflex iliac arteries also elicited pressor responses and reduced hindlimb blood flow and vascular conductance. Adrenergic receptor blockade at rest eliminated the cardiovascular effects of the respiratory muscle metaboreflex. We conclude that the cardiovascular effects of respiratory muscle metaboreflex activation are similar to those previously reported for limb muscles. When activated via metabolite production, the respiratory muscle metaboreflex may contribute to the increased sympathetic tone and redistribution of blood flow during exercise.

Ambulation in simulated fractional gravity using lower body positive pressure: cardiovascular safety and gait analyses

2006 ◽  
Vol 101 (3) ◽  
pp. 771-777 ◽  
Author(s):  
Adnan Cutuk ◽  
Eli R. Groppo ◽  
Edward J. Quigley ◽  
Klane W. White ◽  
Robert A. Pedowitz ◽  
...  
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Ambient Pressure ◽  
Cardiovascular Responses ◽  
Microvascular Blood Flow ◽  
Positive Pressure ◽  
Lower Body ◽  
Lower Body Positive Pressure ◽  
Body Positive ◽  
Gait Mechanics

The purpose of this study is to assess cardiovascular responses to lower body positive pressure (LBPP) and to examine the effects of LBPP unloading on gait mechanics during treadmill ambulation. We hypothesized that LBPP allows comfortable unloading of the body with minimal impact on the cardiovascular system and gait parameters. Fifteen healthy male and female subjects (22–55 yr) volunteered for the study. Nine underwent noninvasive cardiovascular studies while standing and ambulating upright in LBPP, and six completed a gait analysis protocol. During stance, heart rate decreased significantly from 83 ± 3 beats/min in ambient pressure to 73 ± 3 beats/min at 50 mmHg LBPP ( P < 0.05). During ambulation in LBPP at 3 mph (1.34 m/s), heart rate decreased significantly from 99 ± 4 beats/min in ambient pressure to 84 ± 2 beats/min at 50 mmHg LBPP ( P < 0.009). Blood pressure, brain oxygenation, blood flow velocity through the middle cerebral artery, and head skin microvascular blood flow did not change significantly with LBPP. As allowed by LBPP, ambulating at 60 and 20% body weight decreased ground reaction force ( P < 0.05), whereas knee and ankle sagittal ranges of motion remained unaffected. In conclusion, ambulating in LBPP has no adverse impact on the systemic and head cardiovascular parameters while producing significant unweighting and minimal alterations in gait kinematics. Therefore, ambulating within LBPP is potentially a new and safe rehabilitation tool for patients to reduce loads on lower body musculoskeletal structures while preserving gait mechanics.

Increased cardiac output and microvascular blood flow during mild hemoconcentration in hamster window model

2006 ◽  
Vol 291 (1) ◽  
pp. H310-H317 ◽  
Author(s):  
Judith Martini ◽  
Amy G. Tsai ◽  
Pedro Cabrales ◽  
Paul C. Johnson ◽  
Marcos Intaglietta
Keyword(s):  
Blood Pressure ◽  
Blood Flow ◽  
Shear Stress ◽  
Cardiac Output ◽  
Cardiac Index ◽  
Systemic Blood Pressure ◽  
Second Order ◽  
Microvascular Blood Flow ◽  
Packed Red Blood Cells ◽  
Order Polynomial

The effect of small hematocrit (Hct) increases on cardiac index (cardiac output/body wt) and oxygen release to the microcirculation was investigated in the awake hamster window chamber model by means of exchange transfusions of homologous packed red blood cells. Increasing Hct between 8 and 13% from baseline increased cardiac index by 5–31% from baseline ( P < 0.05) and significantly lowered systemic blood pressure ( P < 0.05). The relationship between Hct and cardiac index is described by a second-order polynomial ( R2 = 0.84; P < 0.05) showing that Hct increases up to 20% from baseline increase cardiac index, whereas increases over 20% from baseline decrease cardiac index. Combining this data with measurements of blood pressure allowed to determine total peripheral vascular resistance, which was a minimum at 8–13% Hct increase and was described by a second-order polynomial ( R2 = 0.83; P < 0.05). Oxygen measurements in arterioles, venules, and the tissue at 8–13% Hct increase were identical to control; thus, as a consequence of increased flow and oxygen-carrying capacity, oxygen delivery and extraction increased, but the change was not statistically significant. Previous results with the same model showed that the observed effects are related to shear stress-mediated release of nitric oxide, an effect that should be also present in the heart microcirculation, leading to increased blood flow, myocardial oxygen consumption, and contractility. We conclude that a minimum viscosity level is necessary for generating the shear stress required for maintaining normal cardiovascular function.

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