The effect of aortic clamping and declamping on renal blood flow distribution

The radioactive Xenon-133 washout technique was employed to study the renal circulation during and after distal aortic occlusion in dogs. Deleterious changes in renal blood flow distribution were detected in association with the occlusion which were progressive with time and arrested with termination of the occlusion. These were manifested as a renal cortical ischemia in the presence of only slight variation in total renal blood flow. Although the changes were arrested at the end of the occlusion period, significant cortical ischemia persisted for at least 60 min thereafter. This previously undetected renal cortical ischemia associated with aortic occlusion may be important in the genesis of clinical renal failure after aortic reconstructive surgery.     

Angiotensin and adrenoceptors in the hemodynamic response to aortic cross-clamping.

This study was designed to test the hypothesis that activation of adrenoceptors and/or the renin-angiotensin system plays an important role in the overall hemodynamic response to aortic cross-clamping. The experiments were performed on anesthetized rats pretreated with either saline (control group), an angiotensin-converting enzyme inhibitor (enalapril maleate, 2 mg/kg), an alpha 1-adrenergic antagonist (prazosin hydrochloride, 0.5 mg/kg), a beta-adrenergic antagonist (propranolol hydrochloride, 5 mg/kg), or an alpha 2-adrenergic antagonist (atipamezole, 5 mg/kg). Cross-clamping of the thoracic aorta was associated with an expected increase in mean arterial pressure and systemic vascular resistance in all animals. During the period of cross-clamping, cardiac output gradually decreased in all groups. Animals pretreated with the alpha 1-adrenergic antagonist or the angiotensin-converting enzyme inhibitor developed hypertension of a lesser degree than the control animals, while rats pretreated with the beta-adrenergic or alpha 2-adrenergic antagonist demonstrated a greater arterial hypertension than the control animals. The possible mechanisms underlying the observed differences are discussed. In conclusion, the present study confirms the posed hypothesis that the reninangiotensin and sympathetic nervous systems play an important role in hemodynamic response to cross-clamping of the thoracic aorta.     

Early hemodynamic response to tibial osteotomy in rabbits: influence of indomethacin and prostaglandin E2

The hemodynamic role of prostaglandins in the inflammatory phase of bone healing was studied on day 4 after creation of a nailed midtibial osteotomy in 40 rabbits, divided into groups of 10, treated with either indomethacin (oral dosage 10 mg/kg), subcutaneous (s.c.) prostaglandin E2 (PGE2) (dosage 1 mg/kg), or PGE2 infusion into the abdominal aorta (rate 20 ng/kg/min) for a 20-min period immediately before the animals were killed. The last group served as controls. Regional blood flow was measured by means of radioactive microspheres, and plasma volume was assessed by distribution of circulating [125I]fibrinogen. Neither indomethacin nor s.c. PGE2 treatment had any hemodynamic effects in the osteotomy area. PGE2 infusion caused increased blood flow in bone, bone marrow, and muscle of the lower limbs except in the osteotomy area. Thus, the influence of prostaglandins and indomethacin on bone healing of a rabbit midtibial osteotomy does not appear to be a direct vascular effect in the early healing phase.     

Protective effect of prostaglandin E1 against ischemia of spinal cord during aortic cross clamping

PURPOSE: The purpose of this study was to investigate whether or not 5-minute segmental intraaortic perfusion of prostaglandin E1 (PGE1) in the preischemic period has a protective effect against spinal cord ischemia during aortic cross clamping. METHODS: The rabbits were divided into two groups. In group A (n = 6), the infrarenal aorta was segmentally cross clamped and the segment was perfused for 5 minutes with blood and saline solution at first. The aorta was kept cross clamped without perfusion for a subsequent 20 minutes. In group B (n = 6), the infrarenal aorta was segmentally cross clamped and the segment was perfused for 5 minutes with blood and saline solution containing PGE1 of 100 ng/kg/min at first. The aorta was kept cross clamped without perfusion for a subsequent 20 minutes. After the aorta was declamped, the experimental animals recovered from the anesthesia. Twenty-four and 48 hours after the operation, the hind limb function was estimated with Tarlov's grade. Then, the animals were killed for pathologic study. RESULTS: The systolic arterial pressures measured at the left common carotid artery through the experiment were not significantly different between the two groups. The perfusion of the aortic segment between the proximal and distal clamp was nonpulsatile. The perfusion pressures of the aortic segments at 5 minutes after aortic cross clamping were 29 +/- 6 mm Hg and 33 +/- 6 mm Hg in groups A and B, respectively. No significant differences were seen between the two groups. In group A, the hind limb functions evaluated with Tarlov's grade after 24 hours and 48 hours were 0 to 3 (1.5 +/- 1.4) and 0 to 3 (1.3 +/- 1.4), respectively. In group B, these were 3 to 4 (3.5 +/- 0.5) and 3 to 4 (3.7 +/- 0.5), respectively. A significant difference was seen between the two groups (P <.05). In the ventral horn of the L5, L6, and L7 segments, large motor neurons that seemed viable were more preserved in group B than in group A. CONCLUSION: Segmental intraaortic perfusion of PGE1 in the preischemic period reduced neurologic damage of spinal cord ischemia.     

Characterization of renal parenchymal perfusion during experimental infrarenal aortic clamping and declamping with enhanced thermodiffusion electrodes

Despite multiple previous experimental and clinical investigations, it has not been fully clarified until now whether infrarenal aortic cross-clamping (IRAC) induces a significant disturbance of renal parenchymal perfusion. Most renal cortical flow data collected thus far have been heterogenous because of inherent limitations of available measurement technology. The enhanced thermal diffusion (TD) electrode is a newly developed and previously validated prototype device that allows continuous quantification of parenchymal kidney perfusion after local probe implantation. We monitored renal perfusion during experimental IRAC with TD for the first time, thereby also evaluating the potential applicability of the method in clinical aortic surgery. IRAC (20 min) followed by sudden declamping was performed in pigs under general anesthesia (n = 14). Renal cortical blood flow (RCBF) was continuously quantified by TD, total aortic flow (TABF) and renal artery flow (RABF) were measured by ultrasonic flow probes, and parameters of systemic circulation were determined by Swan-Ganz catheter. Our results showed that kidney perfusion can be continuously quantified using TD electrodes during experimental aortic surgery in a porcine model. IRAC does not lead to a significant impairment of RCBF in young pigs as measured by TD. Renal perfusion appears to be predominantly pressure driven. Consequently, abrubt aortic declamping can bring about prolonged renal ischemia. Transfer of the TD method to RCBF monitoring during clinical aortic surgery appears to be feasible and should be investigated in selected cases.     

The effects of thoracic aortic cross-clamping and declamping on visceral organ blood flow.

Blood flow was measured using radioactive microspheres in 11 macaque monkeys 1) before hemorrhage shock, 2) after onset of shock, 3) after aortic cross-clamping and resuscitation, and 4) after release of the cross-clamp and stabilization. Hemodynamic parameters (cardiac output, arterial, right atrial and left atrial pressure) and blood gases were also monitored. Total abdominal organ flow fell with hemorrhage and fell further with aortic clamping. Reinfusion of shed volume did not restore abdominal organ flow (4.7% baselines) but increased LAP and cardiac output to the upper body. Release of the cross-clamp produced profound acidosis that was treated effectively with NcHCO3. After stabilization of blood, flow to kidney remained low (49% baseline) although intestinal flow was increased threefold (320% of baseline). It is clear that thoracic aortic cross-clamping in shock further compromises already reduced visceral blood flow and may contribute to the problem of ischemic multiple organ failure after resuscitation from hemorrhagic shock.     

The hemodynamic and metabolic changes in prostaglandin E1-induced hypotension in dogs

The hemodynamic and metabolic changes in hypotensive state induced with prostaglandin E₁ (PGE₁) or trimetaphan (TMT) infusion were investigated in dogs. Mean arterial pressure was decreased by about 50% with 1.58µg/kg/min of PGE₁ or 45µg/kg/min of TMT. Heart rate, pulmonary capillary wedge pressure and central venous pressure remained virtually unchanged in the two groups. Cardiac output was well maintained in PGE₁ group, whereas cardiac output showed the tendency to decline in TMT group.Greater reduction in systemic vascular resistance was seen in PGE₁ group than in TMT group. Pulmonary vascular resistance showed no significant change in PGE₁ group, whereas it increased significantly in TMT group. Gradual decreases in arterial pH, Pa_{O 2} and base excess and slight but significant increase in Pa_{CO 2} was observed in PGE₁ group, and these abnormalities recovered 30min after hypotension. Abnormalities in blood gases and acid-base balance were considerably more severe and prolonged in TMT group compared with those in PGE₁ group. Blood lactate and pyruvate concentrations showed no significant changes in PGE₁ group, whereas substantial elevation was seen in L/P ratio especially 30min after induction of hypotension in TMT group. Oxygen consumption showed minimal changes in PGE₁ group, whereas a significant decrease was observed in TMT group. The conclusions derived from these results are as follows;1) PGE₁ maintained cardiac output better than TMT, probably because of its direct inotropic action on the heart, and of its greater reduction of systemic vascular resistance than TMT.2) PGE₁ seemed to provide the better blood perfusion throughout the body than TMT.3) PGE₁ showed less possibility to produce the metabolic derangement compared with TMT.(Nam YT, Takahashi S, Tominaga M et al.: The hemodynamic and metabolic changes in prostaglandin E₁-induced hypotension. J Anesth 3: 210–217, 1989)     

The role of prostaglandin E2 in immune suppression following injury.

It has been thought for some time that prostaglandin E2 (PGE2) released from activated monocytes/macrophages may contribute to the suppression of immunity seen after burns and major injury because PGE2 inhibits the activation of T lymphocytes. To clarify this issue, we studied 15 patients with total body surface area burns of 20% to 90% (mean, 48%). Peripheral blood mononuclear cells (PBMC) were obtained from these patients one to two times each week for 1 month after burn and were stimulated with the T-cell mitogen phytohemagglutinin (PHA). On 14 occasions the PBMCs from eight patients were significantly suppressed (30% or more) in their response to PHA (suppressed [sup] burn) as compared with PBMCs from normal controls. In 38 instances PBMCs from 12 patients were not significantly suppressed in PHA (nonsuppressed [nonsup] burn). Sup burn PBMCs and control PBMCs were cultured with or without the addition of the cyclooxygenase (CO) inhibitor indomethacin (Indo, 1 microgram/mL) and studied for PHA response and the production of the stimulatory cytokine interleukin-2 (IL-2). Indo partially restored the PHA response of sup burn PBMCs to normal. Sup burn PBMCs also were deficient in production of IL-2. Indo increased IL-2 production by sup burn PBMCs significantly more (160% +/- 20%, p less than 0.005) than control (57% +/- 5%) and nonsup PBMCs (67% +/- 8%). Next inhibition of the PHA response of PBMCs from 12 burn patients and 17 controls was studied by exogenous PGE2. At all time periods after burn injury, patients' PBMCs were significantly more sensitive to inhibition by PGE2 (50% inhibition at 10(-8) mol/L [molar] PGE2) than PBMCs from normal controls (50% inhibition at 10(-6) mol/L PGE2) with maximum sensitivity occurring 8 to 14 days after injury. Peripheral blood mononuclear cells from patients with more than 40% burns were significantly (p less than 0.05) more sensitive to PGE2 than those from patients with lesser burns. Interleukin-2 was added to cultures of sup burn PBMC, nonsup burn PBMC, and controls containing 10(-7) mol/L PGE2. Interleukin-2 totally reversed PGE2 inhibition of the PHA response in PBMC from both controls and burn patients. Because endotoxin leak from the gut has been implicated as a trigger for a number of the metabolic and immunologic abnormalities following injury, the authors looked for the effect of a bolus infusion of Escherichia coli endotoxin (Endo, 4 ng/kg) in seven normal healthy volunteers on the response of PBMC to PHA and on the production of PGE2 and IL-2.(ABSTRACT TRUNCATED AT 400 WORDS)     

Temporary incomplete ischemia of the legs induced by aortic clamping in man. Metabolic and hemodynamic effects of temporary extracorporeal by-pass

The effects on central hemodynamics and skeletal muscle metabolism during surgery for abdominal aortic aneurysm were compared in 6 patients given a preoperative adrenergic block (group B) and in 6 patients who additionally had a temporary brachio-femoro-femoral by-pass during the aortic clamping (group B + S). The cardiac output, heart rate, arterial and pulmonary artery pressures and the cardiac filling pressure were studied. Biopsy specimens from the lateral vastus muscle and blood samples from the radial artery and the iliac vein were taken before aortic clamping and also before and 30 minutes, 4 and 16 hours after the aortic declamping. Intramuscular temperature and pH were measured. The glycogen, glucose, lactate, pyruvate, ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr) contents of the muscle and the lactate and pyruvate concentration in iliac venous and radial arterial blood were determined, using enzymatic fluorometric techniques. In group B, aortic clamping induced severe temporary incomplete ischemia with a 300% increase in lactate/pyruvate (L/P) ratio and a fall in intramuscular pH (pHm). The adenylate energy charge (EC) decreased, but the creatine (PCr + CR) and the adenylate (ATP + ADP + AMP) pool remained unchanged. After aortic declamping, the L/P ratio, EC and pHm regained their preclamping values, but the pools of energy phosphate compounds were reduced, indicating dysfunction or damage of the muscle cells. In group B + S there were no major muscle metabolic changes during clamping or after declamping of the aorta. In group B the systemic vascular resistance (SVR), mean arterial blood pressure (MAP) and left ventricular stroke work (LVSW) increased during the occlusion. On release of the clamp, cardiac output rose, possibly due to the sudden reduction of SVR. A temporary marked fall of MAP occurred. In group B + S, no increase of SVR, MAP or LVSW was observed during aortic clamping. After the declamping, only a minor MAP drop was observed. In both groups, a brief rise in pulmonary vascular resistance after the aortic declamping suggested transient pulmonary microembolism. If a high-risk patient is to undergo reconstructive surgery of the abdominal aorta and/or technical difficulties can be expected to necessitate prolonged cross-clamping during the operation, a temporary extracorporeal by-pass may be a favorable adjuvant, improving cardiac performance and preventing derangement of muscle metabolism.     

Analysis of diastolic function in patients undergoing aortic aneurysm repair and impact on hemodynamic response to aortic cross-clamping

OBJECTIVES: The purpose of this study was to analyze left ventricular diastolic function in patients undergoing aortic aneurysm repair and to investigate the effects of laparotomy and aortic cross-clamping on diastolic function. DESIGN: Prospective clinical study. SETTING: University hospital. PARTICIPANTS: Forty-five consecutive patients undergoing open aortic aneurysm repair. INTERVENTIONS: Left ventricular diastolic function and hemodynamic variables were evaluated using transesophageal Doppler echocardiography and a pulmonary artery catheter at baseline, after laparotomy, and at 1 and 10 minutes after cross-clamping. Diastolic function was determined by Doppler derivatives of mitral inflow (E/A ratio, deceleration time of early inflow) and pulmonary venous flow (S/D ratio). MEASUREMENTS AND MAIN RESULTS: Twenty of 39 patients revealed signs of diastolic dysfunction at baseline. Of these 20 patients, 14 displayed delayed relaxation and 6 displayed a pseudonormal filling pattern. Patients with pseudonormal filling exhibited a lower stroke volume (p = 0.02) and cardiac index (p < 0.01) in comparison to patients with normal diastolic function. Laparotomy was associated with an improvement of diastolic function in 9 of 20 patients with preexisting diastolic dysfunction. Only 3 patients suffered impairment of diastolic function after cross-clamping. The hemodynamic response to cross-clamping did not differ between patients with normal and abnormal diastolic function. CONCLUSIONS: About 50% of patients undergoing aortic aneurysm repair exhibit signs of diastolic dysfunction. The majority of these patients showed delayed relaxation. Patients with pseudonormal filling displayed a significantly lower cardiac index. Laparotomy resulted in an improvement in diastolic function in about half of patients with preexisting diastolic dysfunction. The effects of cross-clamping on diastolic function are minimal.     

Interactions between response to inhaled prostaglandin E2 and chronic beta-adrenergic agonist treatment.

Cumulative inhalation dose-response curves for the response to prostaglandin E2 (PGE2) have been constructed in normal subjects and patients with mild, stable asthma. In normal subjects cumulative inhalation dose-response curves were also constructed for salbutamol. In normal subjects dose-related bronchodilatation occurred in response to both PGE2 and salbutamol, although both the within-subject and the between-subject variation was significantly greater with salbutamol. Most asthmatic subjects gave a biphasic response to PGE2 on at least one occasion, PGE2 being a bronchoconstrictor above a certain level of specific airways conductance (sGaw) and a bronchodilator below. Chronic treatment with inhaled salbutamol (400 micrograms four times a day) had no effect on the normal subjects' response to salbutamol but there was a significant shift of the PGE2 dose-response curve to the left, indicating increased bronchodilatation (p less than 0.02). Stabilisation of the asthmatics' dose-response curve in the direction of bronchodilatation also occurred and was more pronounced (p less than 0.005). In the normal subjects PGE2 may be concerned in the control of airway smooth-muscle tone and in limiting bronchoconstriction induced by mediators such as histamine, and chronic salbutamol treatment may be important in enhancing these effects of PGE2. 80 mg oral propranolol given one and a half hours before had no effect on PGE2-induced bronchodilatation; but the question whether chronic treatment with beta-blockers has any effect needs investigation.