Radioactive Microsphere Technique Research Articles

Influence of levosimendan, pimobendan, and milrinone on the regional distribution of cardiac output in anaesthetized dogs.

1. The distribution of cardiac output during administration of levosimendan, a new myofilament calcium sensitizer, is unknown. We examined and compared the effects of levosimendan, pimobendan, and milrinone on regional tissue perfusion by use of the radioactive microsphere technique in barbiturate-anaesthetized dogs. 2. Haemodynamics and regional blood flow were determined before and during infusions of levosimendan (0.75, 1.5, and 3.0 micrograms kg-1 min-1), pimobendan (10, 20, and 40 micrograms kg-1 min-1), or milrinone (1.0, 2.0, and 4.0 micrograms kg-1 min-1). 3. All three drugs caused similar increases in heart rate, cardiac output, and left ventricular +dP/dt and decreases in end-diastolic pressure and systemic vascular resistance. No changes in subendocardial, midmyocardial, and subepicardial blood flow occurred during administration of levosimendan. However, a redistribution of blood flow from subendocardium to subepicardium was observed. Pimobendan increased midmyocardial and subepicardial blood flow and reduced the endo/epi ratio to a greater degree than levosimendan. Milrinone did not affect myocardial perfusion. 4. Levosimendan increased blood flow to the renal medulla and decreased renal medullary and cortical vascular resistance. Levosimendan increased blood flow to the small intestine and liver and reduced vascular resistance in these organs. Pimobendan increased hepatic blood flow to a greater degree than levosimendan but did not alter small intestinal perfusion. All three drugs decreased splenic blood flow to similar degrees. Levosimendan and pimobendan reduced cerebral vascular resistance. Levosimendan and milrinone reduced skeletal muscle vascular resistance. 5. The results indicate that levosimendan, pimobendan, and milrinone cause subtlety different alterations in regional tissue perfusion while producing similar haemodynamic effects.

The effect of acute normovolemic hemodilution (ANH) on myocardial contractility in anesthetized dogs.

The influence of severe acute normovolemic hemodilution (ANH) on myocardial contractility (MC) was investigated in 14 splenectomized, anesthetized dogs. MC was assessed by the maximum rate of left ventricular pressure increase (LVdp/dt(max)), end-systolic elastance (Ees), and preload recruitable stroke work (PRSW) (conductance catheter, left ventricular pressure-volume relationship). Measurements of myocardial perfusion and oxygenation (radioactive microsphere technique) assured comparability of the model to previously performed studies. Global and regional myocardial blood flow increased significantly upon hemodilution with preference to midmyocardium and subendocardium. This resulted in preservation of both myocardial oxygen delivery and consumption after ANH. Myocardial oxygen extraction as well as coronary venous Po2 were unaffected by ANH, while coronary venous lactate concentration decreased, indicating that myocardial oxygen need was met. LVdp/dt(max) decreased significantly after hemodilution (2278 +/- 577 vs 1884 +/- 381 mm Hg/s, P < 0.01), whereas Ees and PRSW increased significantly (1.76 +/- 0.54 vs 2.15 +/- 0.75 mm Hg/mL, P < 0.05, for Ees and 33 +/- 14 vs 45 +/- 14 mm Hg.mL, P < 0.05, for PRSW). While the decrease of LVdp/dt(max) most likely reflects ANH-induced changes of ventricular pre- and afterload, the increase of Ees and PRSW indicates a true increase of myocardial contractility during ANH in anesthetized dogs.

The Effect of Acute Normovolemic Hemodilution (ANH) on Myocardial Contractility in Anesthetized Dogs

The influence of severe acute normovolemic hemodilution (ANH) on myocardial contractility (MC) was investigated in 14 splenectomized, anesthetized dogs.MC was assessed by the maximum rate of left ventricular pressure increase (LVdp/dtmax), end-systolic elastance (Ees), and preload recruitable stroke work (PRSW) (conductance catheter, left ventricular pressure-volume relationship). Measurements of myocardial perfusion and oxygenation (radioactive microsphere technique) assured comparability of the model to previously performed studies. Global and regional myocardial blood flow increased significantly upon hemodilution with preference to midmyocardium and subendocardium. This resulted in preservation of both myocardial oxygen delivery and consumption after ANH. Myocardial oxygen extraction as well as coronary venous PO2 were unaffected by ANH, while coronary venous lactate concentration decreased, indicating that myocardial oxygen need was met. LVdp/dtmax decreased significantly after hemodilution (2278 +/- 577 vs 1884 +/- 381 mm Hg/s, P < 0.01), whereas Ees and PRSW increased significantly (1.76 +/- 0.54 vs 2.15 +/- 0.75 mm Hg/mL, P < 0.05, for Ees and 33 +/- 14 vs 45 +/- 14 mm Hg centered dot mL, P < 0.05, for PRSW). While the decrease of LVdp/dtmax most likely reflects ANH-induced changes of ventricular pre- and afterload, the increase of Ees and PRSW indicates a true increase of myocardial contractility during ANH in anesthetized dogs. (Anesth Analg 1996;83:451-8)

Modification of systemic and regional circulatory effects of intracerebroventricular administration of endothelin-1 by propranolol in anesthetized rats

1. 1. Cardiovascular effects of centrally administered endothelin-1 (ET-1) were studied in control and propranolol-treated anesthetized rats using a radioactive microsphere technique. 2. 2. In the control group, blood pressure, cardiac output, and stroke volume were decreased, and heart rate was not altered after the administration of ET-1. ET-1 produced a reduction in blood flow to the brain, heart, kidneys, gastrointestinal tract, portal system, musculoskeletal system, and skin. 3. 3. Propranolol significantly attenuated the decrease in blood pressure, cardiac output and stroke volume induced by centrally administered ET-1. The reduction in blood flow to the brain, heart, kidneys, gastrointestinal tract, portal system, musculoskeletal system and skin induced by centrally administered ET-1 was blocked by propranolol. 4. 4. It is concluded that centrally administered ET-1 produces significant cardiovascular effects which are mediated through the sympathetic nervous system and could be antagonized by propranolol. These findings can also be helpful in explaining some of the beneficial effects of propranolol in various cardiovascular disorders involving central ET mechanisms.

Effects of adenosine a 2 a receptor agonist, cgs 21680, on blood pressure, cardiac index and arterial conductance in anaesthetized rats

The effects of 2- p-(2-carboxyethyl)phenethylamino-5′- N-ethylcarboxamidoadenosine (CGS 21680) on blood pressure, total peripheral resistance, cardiac index, heart rate and arterial conductance in different vascular beds in the presence and absence of hexamethonium (ganglionic blocker) and phenylephrine ( α 1-adrenoceptor agonist) were investigated in pentobarbitone-anaesthetized rats using a radioactive microsphere technique. CGS 21680 (0.1, 0.3 and 1.0 μg/kg/min) significantly decreased blood pressure and total peripheral resistance, and increased heart rate and cardiac index. In addition, after infusion with CGS 21680 (0.1, 0.3 and 1.0 μg/kg/min) arterial conductance in coronary bed significantly increased. However, while CGS 21680 (0.3 and 1.0 μg/kg/min) significantly increased conductance in skeletal muscle, it significantly decreased splenic arterial conductance. Moreover, CGS 21680 (1.0 μg/kg/min) significantly increased conductance in cerebral arterial bed. Infusion with hexamethonium (200 μg/kg/min) resulted in significant reduction in blood pressure, heart rate and cardiac index whereas stroke volume and total peripheral resistance remained unchanged. In animals that were pretreated with hexamethonium (200 μg/kg/min), further administration of CGS 21680 (0.3 μg/kg/min), compared to CGS 21680 alone, significantly reduced blood pressure, heart rate and cardiac index but did not affect total peripheral resistance or conductance in any vascular bed. Administration of phenylephrine (7 μg/kg/min) resulted in a significant increase in blood pressure and total peripheral resistance, and a significant reduction in cardiac index and heart rate. In animals infused with phenylephrine and CGS 21680 combined, in comparison to those animals that received CGS 21680 alone, no significant differences in blood pressure, heart rate, total peripheral resistance, cardiac index or conductance in any vascular beds were found. Our present findings suggest that CGS 21680 decreased blood pressure by decreasing total peripheral resistance, and increased cardiac index possibly through a reflex-mediated increase in heart rate. Moreover the coronary arterial bed is the most sensitive and cerebral arterial bed is the least sensitive to the effects of CGS 21680. In addition, the autonomic nervous system did not appear to play a major role in the actions of CGS 21680 on arterial conductance, and there was no difference in the action of this compound in the states of normal and raised vascular tone.

Effect of tacrolimus on hemodynamics and absorption of experimental small intestinal transplants.

We have previously reported the adverse effects of cyclosporine on small intestine transplant physiology. In this study, we report for the first time the effect of tacrolimus (FK) on graft intestinal blood flow and intramural distribution, vascular resistance, and absorptive function. Isogeneic small intestine transplantation was performed in Lewis rats. Animals were grouped based upon the following treatment schedules: no treatment for 1 week in group 1; 0.6 ml/kg/day i.m. polyethylene glycol (PEG) for 1 week in group 2; 2 mg/kg/day i.m. FK for 1 week in group 3; 0.6 ml/kg/day PEG for 1 week and then 0.3 ml/kg/day for 5 weeks in group 4; 2 mg/kg/day FK for 1 week and then 1 mg/kg/day for 5 weeks in group 5. Group 6 was the same as in group 5 but FK was withdrawn for 1 week prior to assessment. Maltose absorption was measured to evaluate graft absorptive function. Blood flow and its intramural distribution to mucosal and serosal/muscularis layers were determined using the radioactive microsphere technique. Perfusion pressure was measured to calculate vascular resistance. One week of FK administration in group 3 did not change graft hemodynamics and absorption significantly. Prolonged FK treatment up to 6 weeks in group 5 resulted in a significant increase in mucosal vascular resistance (71.0 +/- 9.6 versus 47.7 +/- 6.7 U/g, P<0.01) and significant decreases in mucosal blood flow (1.14 +/- O.15 versus 1.69 +/- 0.24 ml/g/min, P<0.01) and maltose absorption (30 min after loading. 155.4 +/- 26.9 versus 216.4 +/- 29.6, P<0.01; 60 min after loading: 172.9 +/- 24.5 versus 229.1 +/- 32.6 glucose mg/dl P<0.01). The serosal/muscularis layer remained relatively unaffected. Withdrawal of FK for 1 week after prolonged treatment in group 6 resulted in restorations of all parameters measured to normal ranges. We conclude that a short course of FK is safe, but prolonged FK administration has harmful effects on the hemodynamics and function of small intestinal transplants. Complete recovery is achieved when FK is discontinued.

CEREBROVASCULAR PROSTANOID PRODUCTION IN NEONATAL GROUP B STREPTOCOCCAL MENINGITIS. † 1777

Group B Streptococcal (GBS) meningitis impairs cerebral blood flow (CBF) autoregulation in newborn piglets. We determined whether the early impairment could be related to increased prostaglandin (PG) production and if dexamethasone and ibuprofen alter PG production in the early phase (1st 6 hrs) of GBS meningitis. Net cerebrovascular PG production (calculated as total CBF× (sagittal-arterial plasma PG concentration) of 6-keto-PGF1α (stable metabolite of prostacyclin), TXB2(thromboxane B2) and PGE2 were measured in 4 groups of piglets given either 1) saline 0.5 ml intracerebroventrically (icv, control grp, n=9), 2) GBS alone (109 cfu/0.5 ml GBS icv, n=7), or 3) GBS icv plus dexamethasone (DEX) 1 mg/kg intraarterial, ia, n=8) or 4) GBS icv plus ibuprofen (IBU) 30 mg/kg ia,n=7) during periods of normotension (MABP= 50-90 mmHg), hypotension (MABP 90mmHg). MABP was randomly adjusted by balloon tipped catheters in the aortic root and descending aorta. CBF was measured by radioactive microsphere technique and PG's were measured by radioimmunoassay. Results show that within each treatment group there was a decrease in cerebrovascular production of 6 keto-PGF1α, TXB2 and PGE2 (p < 0.05) during hypotension possibly due to relative depletion in tissue oxygen for cyclo-oxygenation of arachidonate. However, between treatment groups (Control, GBS alone, GBS+DEX, and GBS+IBU) PG production did not change with BP adjustments except for increased PGE2 during cerebral hypertension(mean±SD, PGE2=250±25 ng/min/100 g brain tissue) compared to hypotension in GBS alone (PGE2=325±30 ng/min/100 g brain, p< 0.05). Irrespective of MABP, cerebral PG production is highest for PGE2, followed by 6-keto PGF1α with no production of TXB2. Since cerebral PG production is minimally influenced by GBS with or without DEX or IBU over a wide range of cerebral perfusion pressures, we suggest that vasoactive mediators other than PG's may mediate CBF impairment in early meningitis. Thus, treatment directed to PG's may not prevent CBF impairment in neonatal GBS meningitis.

Hyperdynamic sepsis depresses circulatory compensation to normovolemic anemia in conscious rats.

This study was designed to determine whether sepsis modifies the ability to preserve vital organ O2 delivery (QO2) across a clinically relevant range of hematocrits. Ninety rats were randomly allocated to cecal ligation and perforation (CLP) or a sham (Sham) procedure. With the use of rat plasma, rat whole blood, or packed rat red blood cells, respectively, randomization into three different hematocrit subgroups followed: low (21-28%), middle (33-40%), and high (45-52%). Organ blood flow values (Q) were measured by the radioactive microsphere technique, and organ QO2 values were calculated. Twenty-four hours after laparotomy, the hematocrit grouping had not modified the interorgan distribution of Q or QO2 in either the CLP or Sham rats. To characterize overall metabolic O2 reserve, rats were then exposed to hypoxia (inspired O2 fraction, 0.08) for 20 min. Whereas cardiac output increased significantly during hypoxia in all experimental groups, myocardial QO2 failed to increase in the low hematocrit Sham subgroup and fell significantly in both the middle- and low-hematocrit CLP subgroups. There was also a lesser redistribution of QO2 away from the small intestine in the low-hematocrit compared with the high-hematocrit CLP subgroup. We conclude that myocardial QO2 is more effectively maintained in septic hypoxic rats if the hematocrit is maintained at levels >45%.

Noninvasive assessment of no-reflow phenomenon in a canine model of reperfused infarction by contrast-enhanced magnetic resonance imaging

The aim of this study was to test whether contrast-enhanced magnetic resonance (MR) imaging may assess in vivo the severity of the no-reflow phenomenon in a dog model of infarction with 2-hour coronary occlusion followed by reperfusion (6 hours). Subsecond MR imaging combined with intravenous bolus administration of superparamagnetic iron oxide particles (SPIO) was performed at the fifth hour of reperfusion. An MR index was calculated using the difference of signal-intensity enhancement between ischemic and nonischemic zones during the SPIO first pass. Dogs were separated into two groups according to the severity of ischemia: collateral blood flow in the central ischemic zone at 120 minutes of occlusion (radioactive microsphere technique) <22.5% of the flow in the nonischemic zone (group I) or >22.5% (group II). Mean collateral blood flow during occlusion was lower in group I (11.3% ± 2.9%, n = 7) than in group II (66.8% ± 19.8%, n = 6, p < 0.05). Mean infarct size was significantly larger in group I (58.6% ± 4.9% of the area-at-risk, n = 7) than in group II (16.5% ± 6.5%, n = 6, p < 0.05). For the entire population ( n = 13), the infarct size was inversely correlated to the collateral blood flow ( r = −0.64, p = 0.02, standard error of estimate = 0.24). The relative rate of enhancement in ischemic myocardium (MR index) was significantly lower in group I (38.1% ± 10.9%) than in group II (142.8% ± 32%; p < 0.05). In addition, there was an inverse relation between the MR index and the infarct size ( n = 13, r = −0.69, standard error of estimate = 0.07, p = 0.009). In conclusion, these data suggest that ultrafast MR images with intravenous bolus administration of SPIO during reperfusion is a valuable new method to assess the no-reflow phenomenon in a dog model of myocardial infarction.

Temporal fascial periosteal and musculoperiosteal flaps in the pig: design and blood flow assessment.

The availability of a vascularized periosteal flap with bone-forming potential could greatly enhance the reconstructive capabilities of the craniofacial surgeon. Previous observations seem to indicate that the bone-forming potential of periosteal flaps depends on the vascularity of the flap. The purpose of the present experiment was to design temporal fascial periosteal and musculoperiosteal flaps in the pig and to compare the periosteal blood flow with unoperated periosteum in the same location. The radioactive microsphere (15-micron diameter) technique was used to measure periosteal capillary blood flow in periosteal flaps and unoperated control, randomized to each side of the head in nine pigs (Yorkshire; weight, 12-14 kg). The periosteum was (1) raised based on the temporalis muscle with vascular supply from the deep temporal vessels (n = 6), (2) raised based on temporoparietal fascia-deep temporal fascia with blood supply from the superficial temporal vessels (n = 6), or (3) left intact (n = 6). The mean periosteal capillary blood flow rates in the intact periosteum (0.107 +/- 0.001 ml/min/g), the temporal musculoperiosteal flaps (0.081 +/- 0.01 ml/min/g), and temporal fascial periosteal flaps (0.087 +/- 0.012 ml/min/g) were not significantly different. These observations indicate that the blood flows for both musculoperiosteal and fascial periosteal flaps were comparable to control intact temporal periosteum.

Role of NO mechanism in cardiovascular effects of diaspirin cross-linked hemoglobin in anesthetized rats.

The role of nitric oxide (NO) in the cardiovascular actions of diaspirin cross-linked hemoglobin (DCLHb) was studied in anesthetized rats. The regional circulatory and systemic hemodynamic effects of DCLHb (400 mg/kg iv) were studied using a radioactive microsphere technique in control (untreated) and L-arginine (a NO precursor) pretreated rats. DCLHb produced a significant increase in blood pressure (75%), cardiac output (42%), stroke volume (36%), and total peripheral resistance (45%), without affecting heart rate, when administered to control rats. L-Arginine pretreatment significantly attenuated DCLHb-induced systemic hemodynamic effects. DCLHb-induced increase in blood flow to the skin and spleen was completely blocked, and that to the heart was partially blocked, by L-arginine pretreatment, suggesting that cardiovascular actions induced by DCLHb could be antagonized by the NO precursor L-arginine. The NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) produced significant increases in regional vascular resistance, leading to a decrease in blood flow to all the organs except the heart, where an increase in blood flow and a decrease in vascular resistance was observed. DCLHb, when administered in L-NAME-pretreated rats, accentuated the decrease in blood flow to the gastrointestinal system, spleen, mesentery and pancreas, skin, and musculoskeletal system. These studies provide evidence that the NO precursor L-arginine can attenuate the effects of DCLHb and that DCLHb can potentiate the effect of the NOS inhibitor L-NAME. The role of NO in the mechanism of action of DCLHb was further studied by estimating plasma guanosine 3',5'-cyclic monophosphate (cGMP) in control, DCLHb-treated, L-NAME-treated, and L-NAME followed by DCLHb-treated rats. DCLHb and L-NAME significantly decreased the concentration of circulating cGMP in blood plasma. L-NAME pretreatment potentiated DCLHb-induced decrease in cGMP levels. Because the formation of cGMP is stimulated by NO, these studies provide additional evidence for the involvement of NO in the mechanism of action of DCLHb. It is concluded that NO plays an important role in the cardiovascular effects of DCLHb.

Ureteral obstruction in the neonatal rat: Renal nerves modulate hemodynamic effects

In the neonate, chronic unilateral ureteral obstruction (UUO) reduces renal blood flow (RBF) of the ipsilateral kidney and increases RBF of the opposite kidney. To determine whether renal nerves mediate or modulate these responses, complete left UUO in the neonatal rat was used as a model of severe obstructive uropathy, and was compared with sham-operated controls. At 24-28 days of age, animals underwent left or right mechanical renal denervation or left sham renal denervation. One week after denervation, animals were anesthetized and blood pressure and heart rate were measured. Cardiac output and RBF were determined by the radioactive microsphere technique. UUO increased blood pressure and heart rate, and decreased RBF in the obstructed kidney, regardless of denervation. While left UUO increased RBF to the intact opposite kidney in rats with left renal denervation, this was attenuated by right renal denervation. Thus, in the neonatal rat, UUO modulates systemic renal hemodynamics, possibly through activation of the renin-angiotensin system. While renal nerves do not mediate the vasoconstriction of the obstructed kidney, renal nerves modulate vascular tone of the kidney contralateral to UUO.

Effect of orthotopic transplantation of liver on systemic and splanchnic hemodynamics in conscious rat.

The long-term cardiovascular effects of orthotopic liver transplantation (OLT) were studied in conscious Lewis rats with a radioactive microsphere technique. Three months after OLT with an all-suture technique for graft revascularization (s-OLT), all hemodynamic parameters were similar to control. OLT with "cuffs" fitted to the portal vein and infrahepatic inferior vena cava (c-OLT) led to prominent hemodynamic disturbances including 1) hyperkinetic circulation with increased cardiac index (CI; 22%; P < 0.05) and decreased mean arterial pressure (15%; P < 0.05) and total peripheral resistance (TPR; 28%; P < 0.05); 2) a slight increase in portal pressure (11.8 +/- 0.9 vs. 9.3 +/- 1.7 mmHg in control) and marked portal-systemic shunting (51 +/- 11 vs. 0.05 +/- 0.04% in control; P < 0.05); 3) increased hepatic arterial blood flow (0.49 +/- 0.06 vs. 0.27 +/- 0.04 ml.min-1.g liver wt-1; P < 0.05); 4) splanchnic vasodilation with vascular resistance significantly (P < 0.05) lower in the liver, stomach, and large intestine; and 5) increased blood flow and decreased vascular resistance in the kidneys and heart. Ganglionic blockade with chlorisondamine (5 mg/kg body wt iv) indicated that the increase in CI seen in the c-OLT rats was probably sympathetically mediated, whereas the increase in renal blood flow was a reflection of the increase in CI. After ganglionic blocker administration, TPR and regional vascular resistances decreased to approximately the same extent in the control and c-OLT groups, indicating that vascular sympathetic tone was unchanged in the c-OLT rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Early and late haemodynamic and morphological effects of angiotensin II subtype 1 receptor blockade during genetic hypertension development.

To investigate the haemodynamic and morphological effects resulting from the chronic administration to young spontaneously hypertensive rats (SHR) of a new selective angiotensin II subtype 1 (AT1) receptor antagonist, SR 47436/BMS-186295 (SR/BMS) both during and after the treatment period. SR/BMS (60 mg/kg per day, orally) or distilled water was chronically (from 4 to 20 weeks of age) administered to SHR. At age 8, 14, 20 and 28 weeks the effects of SR/BMS on the systemic and regional haemodynamic (radioactive microsphere technique) and the cardiac and vascular morphological parameters (automatic image analysis) were investigated. SR/BMS limited genetic hypertension development and opposed the age-related rises in total peripheral and regional vascular resistances. Simultaneously, it limited the age-related increases in heart weight, left ventricular cross-sectional area and collagen content. Age-related increases in aortic media thickness and amount of collagen were also significantly reduced, whereas aortic compliance was increased. Eight weeks after withdrawal of treatment the antihypertensive effect of SR/BMS, although attenuated, and the limitation of cardiac and vascular remodelling, persisted. Early AT1 receptor blockade in SHR opposes genetic hypertension development during the treatment period and persistently after its interruption. Prevention of genetic hypertension development during the treatment period can be accounted for by the limitation of the age-related development of the haemodynamic and morphological abnormalities, whereas the persistence of the antihypertensive effect observed after drug withdrawal is due mainly to a maintained prevention of the development of the cardiovascular morphological alterations.

Acute ischaemic preconditioning protects against skeletal muscle infarction in the pig

The aims were to investigate the efficacy of acute ischaemic preconditioning for protection of skeletal muscles against infarction and its effect on muscle blood flow and ischaemic muscle metabolism. The efficacy of preconditioning was tested by subjecting pig latissimus dorsi and gracilis muscles to different numbers and durations of ischaemia/reperfusion cycles before 4 h of global ischaemia. Infarction was assessed at 48 h of reperfusion, using nitroblue tetrazolium dye. Blood flow in the latissimus dorsi was measured at the end of preconditioning and 1.5 and 3.0 h of reperfusion, using the radioactive microsphere (15 microns) technique. Muscle biopsies were taken from the latissimus dorsi before ischaemia, at the end of 2 and 4 h of ischaemia, and 1.5 h of reperfusion. At least three cycles of 10 min ischaemia and 10 min reperfusion were required for preconditioning of latissimus dorsi and gracilis muscles for protection against infarction. Preconditioning reduced the total infarct size by 44% and 62% in latissimus dorsi and gracilis muscles, respectively. Preconditioning did not affect preischaemia muscle blood flow but it reduced the muscle content (preischaemia reserve) of phosphocreatine and ATP and the muscle energy charge potential (ECP) by 13.5%*, 27.5%*, and 8%* (*P < 0.05), respectively. In spite of a lower preischaemia reserve of phosphocreatine and ATP, the muscle contents of phosphocreatine and ATP and muscle ECP were maintained higher and the lactate lower (*P < or = 0.05) in the preconditioned than in the non-preconditioned (control) muscles at the end of 4 h of ischaemia [phosphocreatine 8.0(SEM 0.4) v 3.2(0.3)*; ATP 9.8(0.7) v 7.8(0.3); ECP 0.72(0.02) v 0.66(0.01)*; lactate 115.4(8.6) v 160.5(11.8)* mumol.g-1 dry muscle]. The level of ATP and ECP also remained significantly higher and the level of lactate significantly lower in the preconditioned than in the non-preconditioned latissimus dorsi muscles at 1.5 h of reperfusion. Hyperaemia was seen in the preconditioned latissimus dorsi muscles at 1.5 h of reperfusion and it subsided by the end of 3h of reperfusion. The protective effect of preconditioning can be induced in pig skeletal muscle but at a higher threshold than reported previously in pig cardiac muscle (one cycle). Preconditioning of pig skeletal muscle is associated with a lower energy metabolism during sustained ischaemia. At the present time, it is not known if this energy sparing effect is a major mechanism of ischaemic preconditioning against infarction in skeletal muscles.

Fetal response to carbon dioxide pneumoperitoneum in the pregnant ewe

To determine the effects of maternal abdominal carbon dioxide (CO2) insufflation on placental blood flow and fetal blood gas measurements in the pregnant ewe. Five time-bred ewes at 110 days' gestation were surgically prepared with maternal and fetal catheters placed for subsequent measurement of vascular pressures, blood gas tensions, and placental blood flows. On surgical recovery day 3, the ewe was anesthetized, placed on her right side, intubated, and manually ventilated to maintain a constant maternal carbon dioxide pressure (PCO2) range (37.1 +/- 3.3 mmHg) for the duration of the experiment. The maternal abdomen was inflated with CO2 to maintain an intraabdominal pressure of 20.7 +/- 0.6 mmHg. Maternal and fetal blood flows and blood gases were determined at 30 minutes of ventilation, 60 minutes of insufflation, and 40 minutes of desufflation. Simultaneous maternal and fetal organ blood flows were determined using the radioactive microsphere technique. Maternal perfusion pressure fell 22% (P = .01) in response to insufflation, whereas pressure in the inferior vena cava rose 53% (P = .003). Maternal placental blood flow fell to 61% (P = .002) of control. Seventy-seven percent of this blood-flow change was in response to the decreased perfusion pressure, with 23% resulting from an increased placental vascular resistance of 32% (P = .02). Maternal blood gas values did not change with insufflation or desufflation. Despite the marked decrease in maternal placental blood flow, the fetal placental perfusion pressure and blood flow, pH, and blood gas tensions were unaffected by insufflation or desufflation. The sheep fetus has sufficient placental flow reserves or compensatory responses to maintain adequate gas exchange during a 1-hour, 20 mmHg maternal pneumoperitoneum. Laparoscopic surgical procedures may prove to be a safe alternative to laparotomy during pregnancy.

Regression of bile duct damage and bile duct proliferation in the non-rearterialized transplanted rat liver is associated with spontaneous graft rearterialization

The aim of this study was to investigate the long-term consequences of non-rearterialization of the graft in rat liver transplantation. Liver transplantation with (AOLT) and without graft rearterialization (NOLT) was performed in anesthetized male Lewis rats. Quantitative morphometry and semiquantitative histopathology of the liver were performed at various times after operation. Volume fractions of tissue components were determined. The number of arteries and bile ducts per portal tract were measured in histological sections from both groups. Hepatic blood flow was measured using the radioactive microsphere technique in rats after NOLT (6 months). AOLT livers had a preserved lobular architecture at all time points and unaltered volume fractions. In addition, AOLT livers maintained approximately one artery and one bile duct per portal tract after transplantation. NOLT livers showed bile duct damage at 3 days, cellular infiltration and ductular proliferation at 1 week, increased ductular proliferation at 4 weeks, and fibrosis at 6 months. The volume fractions for nonhepatocyte parenchyma (3 days, 19.14 +/- 1.29; 1 week, 20.44 +/- 1.76; 4 weeks, 15.46 +/- 3.14), bile ducts/ductules (1 week, 4.88 +/- 1.07; 4 weeks, 7.20 +/- 2.42), and connective tissue (4 weeks, 4.02 +/- 1.66; 6 months, 14.94 +/- 0.63) were significantly increased. Hepatocyte volume fraction was significantly decreased at all time points. A total of 1.58 +/- 0.08 arteries/portal tract were found in NOLT livers after 4 weeks, rising to 2.44 +/- 0.10 arteries/portal tract after 6 months. At 6 months, hepatic arterial blood flow (0.69 mL/min/g) was significantly higher (P < .02) than control (0.25 mL/min/g).(ABSTRACT TRUNCATED AT 250 WORDS)

Regression of bile duct damage and bile duct proliferation in the non-rearterialized transplanted rat liver is associated with spontaneous graft rearterialization

The aim of this study was to investigate the long-term consequences of non-rearterialization of the graft in rat liver transplantation. Liver transplantation with (AOLT) and without graft rearterialization (NOLT) was performed in anesthetized male Lewis rats. Quantitative morphometry and semiquantitative histopathology of the liver were performed at various times after operation. Volume fractions of tissue components were determined. The number of arteries and bile ducts per portal tract were measured in histological sections from both groups. Hepatic blood flow was measured using the radioactive microsphere technique in rats after NOLT (6 months). AOLT livers had a preserved lobular architecture at all time points and unaltered volume fractions. In addition, AOLT livers maintained approximately one artery and one bile duct per portal tract after transplantation. NOLT livers showed bile duct damage at 3 days, cellular infiltration and ductular proliferation at 1 week, increased ductular proliferation at 4 weeks, and fibrosis at 6 months. The volume fractions for nonhepatocyte parenchyma (3 days, 19.14 ± 1.29; 1 week, 20.44 ± 1.76; 4 weeks, 15.46 ± 3.14), bile ducts/ductules (1 week, 4.88 ± 1.07; 4 weeks, 7.20 ± 2.42), and connective tissue (4 weeks, 4.02 ± 1.66; 6 months, 14.94 ± 0.63) were significantly increased. Hepatocyte volume fraction was significantly decreased at all time points. A total of 1.58 ± 0.08 arteries/portal tract were found in NOLT livers after 4 weeks, rising to 2.44 ± 0.10 arteries/portal tract after 6 months. At 6 months, hepatic arterial blood flow (0.69 mL/min/g) was significantly higher ( P < .02) than control (0.25 mL/min/g). The findings indicate that NOLT leads to a time-dependent overall derangement of liver structure, possibly due to bile duct damage induced by lack of an arterial blood supply. Spontaneous graft rearterialization may be responsible for the regression of bile duct damage and proliferation noted at the later stages. Nevertheless, biliary fibrosis may be a long-term consequence of NOLT.

Systemic hemodynamic and regional circulatory effects of centrally administered endothelin-1 are mediated through ET A receptors

Central endothelin (ET) has been implicated in the regulation of the cardiovascular system. The effect of intracerebroventricular (i.c.v.) administration of ET-1 or IRL 1620 (5, 15 and 45 ng) on the systemic hemodynamics and regional circulation was studied in anesthetized rats using a radioactive microsphere technique. Systemic hemodynamics and regional blood circulation were determined before (baseline) and at 30 min after the injection of each dose of ET-1 or IRL 1620. Administration of saline (5 μl, i.c.v.) did not produce any significant cardiovascular effects. The lower doses of ET-1 (5 and 15 ng) did not produce any significant effect on blood pressure (BP), heart rate (HR), cardiac output (CO), stroke volume (SV), total peripheral resistance (TPR) and regional blood circulation. However, the higher dose (45 ng) produced a transient rise (26%) followed by a sustained fall (48%) in BP. The decrease in BP was accompanied by significant decreases in CO (44%) and SV (39%), while HR and TPR were not affected. ET-1 (45 ng, i.c.v.) also produced a significant reduction in blood flow to the brain (75%), heart (49%), kidneys (66%), GIT (40%), portal system (52%) and musculo-skeletal system (38%), while blood flow to the skin was not affected. To determine pharmacological specificity of the central effects of ET-1, studies were performed in rats pretreated with BQ-123, a specific ET A receptor antagonist. Pretreatment with BQ-123 (10 μg, i.c.v.), 15 min prior to the administration of ET-1, completely antagonized the systemic hemodynamic as well as the regional circulatory effects of ET-1 (45 ng, i.c.v.). In order to determine whether stimulation of central ET B receptors produces any cardiovascular effects, studies were performed using IRL 1620, a specific ET B receptor agonist. Administration of IRL 1620 (5, 15 and 45 ng, i.c.v.) did not produce any effect on systemic hemodynamics and regional blood circulation in rats. It is concluded that ET A but not ET B receptors are involved in the central cardiovascular actions of ET.

Augmentation of coronary blood flow by ACE inhibition: role of angiotensin and bradykinin.

Inhibition of the angiotensin converting enzyme (ACE) is known to enhance coronary blood flow via partial suppression of angiotensin II and potentiation of bradykinin. The purpose of these experiments was to evaluate the contribution of each of these mechanisms to the ACE inhibition induced changes in blood flow in myocardial regions perfused by intact or stenotic coronary arteries. Seven domestic swine were submitted to an 82% stenosis of the left anterior descending artery with the circumflex artery left intact to serve as control area. Regional coronary blood flows were measured by the radioactive microsphere technique in the total area perfused by each coronary artery and in the subepicardial and subendocardial regions of each area separately, at rest and after treatments with captopril, losartan and a bradykinin antagonist given consecutively. We found a significant increase of total flow in both the stenotic and intact areas after captopril. Losartan caused a significant fall in systemic blood pressure with no further changes in overall coronary blood flow and the bradykinin antagonist produced a small but nonsignificant decline in total coronary flow. However, further separate analysis of subregions showed that subendocardial regions had a sharper increase in flow after captopril, and a significantly greater decline after bradykinin inhibition than subepicardial regions, whereas losartan tended to shunt blood from the subendocardial to the subepicardial regions. The results indicate that augmentation of coronary blood flow after ACE inhibition is not further enhanced by angiotensin II blockade and is in part mediated via potentiation of endogenous bradykinin, which exerts a preferential vasodilatory effect on the subendocardial regions of the myocardium.