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The hemodynamic effects of ATP in retrograde perfusion of the bivascularly perfused rat liver.

AIMS/BACKGROUND: In the sinusoidal bed the distribution of water is flow-limited, but it becomes partly barrier-limited when adenosine triphosphate (ATP) is introduced. This effect could be exerted either directly by ATP or by substances released from presinusoidal regions. Furthermore, portally infused ATP seems to be able to diffuse in the direction of the arterial bed. It is not known if this diffusion route is specific. Answers to these questions can be obtained from indicator-dilution experiments in retrograde perfusion. METHODS: Indicator-dilution experiments, using [14C]sucrose and [3H]water, were conducted. Rat livers were perfused in the retrograde mode (hepatic vein+hepatic artery --> portal vein). RESULTS: When ATP was infused into the hepatic vein, the distribution of [3H]water remained essentially flow-limited. The infusion of ATP into the hepatic artery increased the sucrose and extra-sucrose spaces of the arterial bed, but infusion into the hepatic vein was without effect. CONCLUSIONS: The results indicate that the induction of barrier-limited distribution of [3H]water is not a direct effect of ATP. Furthermore, if the transhepatic diffusion of ATP can occur from presinusoidal regions to the arterial bed, as shown by previous work, a similar diffusion does not occur from postsinusoidal regions.

Adenosine Triphosphate↗

Spinal cord protection during aortic cross clamping: retrograde venous spinal cord perfusion, distal aortic perfusion, and cerebrospinal fluid drainage.

OBJECTIVE: We investigated retrograde venous spinal cord perfusion (RVP), with the established adjuncts cerebrospinal fluid drainage (CSFD), and distal aortic perfusion (DAP) in the canine model. We then examined the clinical feasibility of RVP, DAP, and CSFD. DESIGN: Canine study: Twenty dogs were randomized to four treatment groups. All animals underwent 60 min of complete aortic cross-clamp. Group 1 was the control and received only aortic cross-clamp; group 2 DAP and CSFD; group 3 DAP, CSFD, and RVP; and group 4 CSFD plus RVP. Human study: Five patients underwent aortic graft replacement of the descending or thoracoabdominal aorta, while receiving CSFD, DAP, and RVP. RESULTS: Canine study: All animals in groups 1 and 4 awoke paralyzed. One animal each in groups 2 and 3 were paraparetic, with the remaining dogs neurologically intact. Groups 2 and 3 differed from groups 1 and 4 at p < 0.0001. Human study: No mortality or permanent complications were observed in this group. CONCLUSION: While RVP did not reduce neurologic injury, neither did it increase morbidity. In humans the method is technically feasible and free from major problems. Further animal studies and randomized trials are underway at our center.

Aged↗

Doppler US with perfusion software and contrast medium injection in the early evaluation of isolated limb perfusion of limb sarcomas: prospective study of 49 cases.

BACKGROUND: The aim of this study was to prospectively evaluate the use of Doppler ultrasonography with perfusion software and contrast agent injection (DUPC) during isolated limb perfusion (ILP) with high-dose chemotherapy and TNF-alpha(biochemotherapy) in patients with locally advanced extremity soft tissue sarcoma (STS). PATIENTS AND METHODS: Fifty-two patients were prospectively included in this monocentric imaging trial. Three were excluded because the study was incomplete in two patients and one tumour did not exhibit any contrast uptake. DUPC was performed before ILP and on days 1, 7, 15, 30 and 60 after ILP. A total of 292 DUPC were performed on 55 target lesions in 49 evaluable patients. The percentage of contrast uptake was evaluated at each tumour site by two radiologists. The criterion tested was a decrease of more than 50% in intra-tumour contrast uptake compared to the pre-ILP examination. Results were compared with both MRI and histological analysis after resection of residual disease. RESULTS: According to MRI and the histological analysis, 25 (51%) patients were good responders (no difference between the four treatment arms) with tumour necrosis exceeding 90% and 24 (49%) were poor responders. As of day +1, the accuracy of DUPC in predicting tumour response was 82% (18/25 good responders and 22/24 poor responders) increasing to 91% at day +7, 95% at day +15 and 96% at day +30. At day +15, DUPC was predictive of a good response in 100% of the cases. CONCLUSION: DUPC is a simple technique, allowing early prediction of tumour response after ILP. A new treatment planning scheme can be proposed based on the results of this study.

Adolescent↗

Assessment of the selectivity of OPC-2009, a new beta2-adrenoceptor stimulatn, by the use of the blood-perfused trachea in situ and of the isolated blood-perfused papillary muscle of the dog.

1 The potency and selectivity of 5-(1-hydroxy-2-isopropylamino)butyl-8-hydroxy carbostyril hydrochloride hemihydrate (OPC-2009), a new beta(2)-adrenoceptor stimulant, was compared with those of isoprenaline, trimetoquinol and salbutamol by the use of blood-perfused tracheal preparations in situ and of blood-perfused papillary muscle preparations of the dog. All drugs were injected intra-arterially.2 All the four drugs decreased tracheal intraluminal pressure (tracheal relaxation) and increased tracheal blood flow in a dose-dependent manner. The four drugs produced a dose-dependent increase in developed tension of papillary muscles. In both preparations the duration of action of isoprenaline and salbutamol was short, whereas that of OPC-2009 and trimetoquinol was long. These effects were antagonized by propranolol.3 Dose-response curves to the four drugs for tracheal relaxation were almost parallel. OPC-2009 was 2.4 times more potent, and trimetoquinol and salbutamol were 2.2 and 6.2 times less potent than isoprenaline in causing tracheal relaxation.4 Dose-response curves to the four drugs for tracheal vasodilatation were also parallel. OPC-2009, trimetoquinol and salbutamol were 3.9, 6.7 and 23 times less potent than isoprenaline.5 Slopes of the dose-response curves to the four drugs for increased developed tension were not parallel; that of OPC-2009 was the least steep, whereas that of isoprenaline was the steepest. Trimetoquinol, salbutamol and OPC-2009 were about 18, 570 and 2400 times less potent than isoprenaline.6 Selectivity calculated from relative potencies indicate that OPC-2009 was about 6000 times, salbutamol about 92 times and trimetoquinol about 8.2 times more selective than isoprenaline for tracheal smooth muscle as compared to ventricular muscle.7 The high potency and selectivity of OPC-2009 for tracheal smooth muscle and its long duration of action suggest its potential usefulness for treatment of bronchial asthma.8 The present results are also compatible with the concept that beta(1)-adrenoceptors in cardiac muscle and beta(2)-adrenoceptors in tracheal and vascular smooth muscle can be distinguished. Furthermore, the results revealed that the beta-adrenoceptors mediating tracheal relaxation and vasodilatation may also be different.

Adrenergic beta-Agonists↗

Comparison of retrograde cerebral perfusion to antegrade cerebral perfusion and hypothermic circulatory arrest in a chronic porcine model.

Retrograde cerebral perfusion (RCP) is a new method of cerebral protection that has been touted as an improvement over hypothermic circulatory arrest (HCA). However, RCP has been used clinically for durations and at temperatures that are "safe" for HCA alone. This study was designed to compare RCP to HCA and antegrade cerebral perfusion (ACP) deliberately exceeding "safe" limits, in order to determine unequivocally whether RCP provides better cerebral protection than HCA. Four groups of six Yorkshire pigs (20 to 30 kg) were randomly assigned to undergo 90 minutes of RCP, ACP, HCA, or HCA with heads packed in ice (HCA-HP) at an esophageal temperature of 20 degrees C. Arterial, mixed venous and cerebral venous oxygen, glucose and lactate contents; quantitative EEG; were monitored at baseline (37 degrees C); at the end of cooling cardiopulmonary bypass (20 degrees C); during rewarming (30 degrees C); and at two and four hours post intervention. Animals were recovered and were evaluated daily using a quantitative behavioral score (0 to 9). Mean behavioral score was lower in the HCA group than in the other three groups at seven days (HCA 5.8 +/- 1.1; RCP 8.5 +/- 0.2; ACP 9.0 +/- 0.0; HCA-HP 8.5 +/- 0.2, p < 0.05). Recovery of QEEG was better in the ACP group than in all others, but the RCP group had faster EEG recovery than HCA alone, although not better than HCA-HP (HCA 15 +/- 4; RCP 27 +/- 3; ACP 78 +/- 5; HCA-HP 19 +/- 3, p < 0.001). However, histopathological evidence of ischemic injury was present in 5 of 6 HCA animals and also in 4 of 6 of the HCP-HP group, but only in 1 of 6 RCP animals and in none of the ACP group. This study demonstrates that ACP affords the best cerebral protection by all outcome measures, but RCP provides clear improvement compared to HCA.

Animals↗

Patterns of disturbed myocardial perfusion in patients with coronary artery disease. Regional myocardial perfusion in angina pectoris.

Fifty patients who presented with angina pectoris were studied to examine the disturbances of regional myocardial perfusion during stress. Each patient underwent 16-point precordial mapping of the ECG during an exercise test, and coronary and left ventricular angiography. Regional myocardial perfusion was assessed using an atrial pacing test and a short-lived radionuclide, krypton-81m. Eleven patients had negative exercise tests and uniform increases in myocardial activity of krypton-81m of 98 +/- 18.0% during pacing. Ten patients performed 30,000-43,000 J in positive exercise tests. These patients showed abnormal coronary anatomy and increases in myocardial activity of krypton-81m to remote and jeopardized myocardium at the onset of pacing. However, further pacing produced a decrease in activity in the affected segment of 68.0 +/- 9.0% accompanied by ST-segment depression and angina. Twelve patients achieved 26,000-32,000 J in positive exercise tests and had significant coronary artery disease. Atrial pacing produced increased activity of krypton-81m to remote myocardium. The jeopardized segment at first showed no change and then a decrease in regional activity of krypton-81m (89.0 +/- 17%) accompanied by ST-segment depression and chest pain. Seventeen patients achieved only 7000-22,000 J in positive exercise tests. These patients showed abnormal coronary anatomy and developed decreases in regional activity of krypton-81m to the affected segment of myocardium starting at the onset of atrial pacing and decreasing by 88 +/- 0 7.0% below control. We conclude that different patterns of disturbed myocardial distribution of krypton-81m are present during stress-induced ischemia in patients with coronary artery disease. There was a close temporal relationship between these disturbances and ST-segment depression.

Adult↗

The order of islet microvascular cellular perfusion is B----A----D in the perfused rat pancreas.

In order to determine whether microvascular blood flow is important in the regulation of intra-islet cellular interactions, rat pancreata were isolated and perfused in vitro, both anterogradely or retrogradely, with and without anti-insulin or anti-somatostatin gamma-globulin. Expressed as percent change, anterograde infusion of insulin antibody increased efflux concentrations of glucagon (110 +/- 20%, P less than 0.0005) and somatostatin (2,112 +/- 73%, P less than 0.0005) above their respective control. Retrograde infusion of insulin antibody did not affect efflux concentrations of glucagon (P less than 0.50) or somatostatin (P less than 0.50). The anterograde infusion of anti-somatostatin antibody had no effect upon insulin (P less than 0.50) or glucagon (P less than 0.50) efflux concentrations, whereas retrograde anti-somatostatin antibody infusion produced immediate increases in efflux concentrations of both insulin (115 +/- 33%, P less than 0.0005) and glucagon (77 +/- 8%, P less than 0.0005). These results strongly suggest that (a) the vascular compartment is important in the regulation of intra-islet cellular interactions and further suggest that (b) the order of islet cellular perfusion and interaction is from the B cell core outward to the mantle, and (c) the mantle is further subordered with the majority of D cells downstream or distal to the majority of A cells. Thus, in the vascular compartment, B cells inhibit A-cell secretion and A cells stimulate D-cell secretion.

Animals↗

Effect of spontaneous diabetes on hormone release in BB/Phi rats: comparison between the isolated perfused pancreas/stomach/duodenum/spleen and the isolated perfused pancreas.

We have studied the effects of spontaneous diabetes in BB/Phi rats on hormone release in response to amino acids (15 mM) and to amino acids (15 mM) plus glucose (10 mM) from isolated perfused pancreas/stomach/duodenum/spleen (PSDS) and from isolated perfused pancreas (P) preparations. In the PSDS preparation, diabetes reduced total integrated insulin output by 97% (from 1146 +/- 198 to 40 +/- 24 ng/65 min, P less than 0.001), and glucagon output by about 50% (from 51.6 +/- 13.1 to 24.0 +/- 3.7 ng/65 min, P less than 0.05), whereas somatostatin output did not change (105.5 +/- 48.1 to 110.1 +/- 36.9 ng/65 min). In the P preparation, integrated glucagon output fell by 91% (from 97.9 +/- 26.8 to 8.6 +/- 4.8 ng/65 min, P less than 0.01) whereas integrated somatostatin output more than doubled (from 28.1 +/- 7.5 to 69.6 +/- 14.2 ng/65 min, P less than 0.05). Intestinal glucagon and somatostatin contributions were estimated by comparing hormone release from the PSDS with that from the P preparations. We conclude that in our nondiabetic BB/Phi rats, the pancreas was the only source for the release of glucagon and that the intestinal tract secreted more somatostatin than the pancreas. In the diabetic BB/Phi rats, pancreatic glucagon and insulin release was virtually abolished while glucagon secretion from the intestinal tract increased and somatostatin secretion decreased.

Animals↗

Perfusion-time-dependent appearance of blocking effect of diltiazem on norepinephrine-induced vasoconstriction in isolated, perfused dog pulmonary veins.

Time-dependent changes in the blocking effect of diltiazem on norepinephrine (NE)-induced vasoconstrictions were investigated in isolated canine pulmonary veins. Within 2-3 hr of the perfusion period, pretreatment with diltiazem did not affect the vasoconstrictor responses to NE. However, in the 8-11 hr perfused preparations, diltiazem suppressed the NE-induced vasoconstriction significantly. It may participate in the mechanisms for the appearance of the blocking effect in the following manner: 1) a proportion of alpha adrenoceptors which are sensitive to calcium entry are increased and/or 2) spare alpha adrenoceptors are decreased time-dependently.

Animals↗

Primary pulmonary hypertension: 3D dynamic perfusion MRI for quantitative analysis of regional pulmonary perfusion.

OBJECTIVE: The purpose of this study was to determine whether quantitative pulmonary perfusion parameters obtained from 3D dynamic contrast-enhanced MR perfusion data can be used to assess the severity of primary pulmonary hypertension (PPH) as indicated by pulmonary vascular resistance (PVR) and mean pulmonary artery pressure (MPAP). CONCLUSION: Three-dimensional dynamic contrast-enhanced MRI has potential for assessment of disease severity as indicated by PVR and MPAP in patients with PPH.

Adult↗

Perfusion technique for perfusion-assisted direct coronary artery bypass (PADCAB).

The role for the perfusionist has changed at many institutions that perform Off-Pump Coronary Artery Bypass (OPCAB). Surgeons at our hospitals have adapted a technique called Perfusion-Assisted Direct Coronary Bypass (PADCAB) (1). A simple circuit and pump have been devised for the perfusionist to deliver arterial blood to the myocardium immediately after the completion of the distal coronary anastomosis. Flow is controlled by a pressure-sensing servomechanism, and grafts are perfused at systemic or suprasystemic pressure. The pump is capable of delivering optional agents for myocardial vasodilatation, myocardial resuscitation, and for increasing myocardial performance.

Coronary Artery Bypass↗

A simple and non-invasive method to determine the ventilation-perfusion ratio of the lung and the effective lung perfusion.

A method is presented to obtain the ventilation-perfusion ratio non-invasively. To describe the properties of gasexchange over the lung we used the law of mass conservation. The use of sinusoidal changes in the concentration of a tracergas in the inspired mixture results in a simple formulation of the variation in the concentration in the expired mixture over the variation in the inspired mixture. A careful selection of tracergas and cycleperiod of the sinus enables us to neglect the influence of venous return leaving the ventilation-perfusion ratio as sole physiological variable in the formulation. The lungperfusion can be obtained by measuring the total ventilation and correcting this value for deadspace ventilation. The method can be used to evaluate the influences of techniques like positive end-expired pressure and increased carbon dioxyde levels on shunting. It is also suited for monitoring purposes.

Anesthesia, General↗

[Perfusion of isolated rat liver. Utilization of a perfusion without heparin. Validity of the preparation].

The blood and liver giver animals are given "Tromexan" for a period of three days. The blood defibrination is finished off by shaking. The perfusion is made of defibrinated blood to which is added a compounding of mineral salts, albumin and glucose in adequate proportions. The fluid is used during 150 minutes with a biliary flow of 4 ul/minute (instead of 8 in perfusions with heparine). The validity of the preparation is tested by biliary acids, cholesterol and Brom Sulfon Phtalein biliary elimination research. This fluid can be used when heparin is avoided: for example in a case of investigation of fat emulsion scrubbing.

Animals↗

Subarachnoid anesthesia for loco-regional antiblastic perfusion with circulatory block (stop-flow perfusion).

AIM: Loco-regional antiblastic perfusion with circulatory block (stop-flow perfusion, SFP) is a procedure designed to treat solid tumors of the limb and pelvis in an advanced stage, like melanoma, sarcoma of the soft tissues and colon-rectal cancer. The aim of this study was to evaluate if subarachnoid anesthesia could represent a safe and suitable anesthetic technique for this procedure. METHODS: Thirty SFP procedures were performed in the angiographic room, 15 for the treatment of lower-limb neoplasias and 15 for pelvic neoplasias. The patients (ASA I-III) had a mean age of 59.1 years (range: 19-81 years). The patients were given different dosages of bupivacaine (range: 10-20 mg) in hyperbaric solution at the concentration of 0.5% and 1% by lumbar subarachnoid injection at different levels (from T12-L1 to L3-L4). Standard monitoring was set up (ECG, pulse-oximetry, and non-invasive artery pressure). The use of any anesthetic and analgesic drug, eventually used in the intra- or postoperative period, was recorded. RESULTS: The lumbar puncture was approached at L1-L2 and L2-L3 levels in 80% of the cases. Doses of bupivacaine between 12 mg and 14 mg were administered in 2/3 of the cases. Bupivacaine was formulated in hyperbaric solution and administered at a concentration of 0.5% (8 patients) or 1% (22 patients). Complica-tions related to the anesthetic technique were absent. Intraoperative pain control was almost complete with one exception, when the procedure lasted unusually long. Pain control was satisfying immediately after the procedure as well: only in 3 cases were non-opiod analgesics administered within the first 6 h. CONCLUSIONS: Spinal subarachnoid anesthesia has proven to be an effective, safe, and easy-to-manage technique for carrying out SFP procedure in a non-conventional environment such as an angiographic room. It was free of serious side effects and well tolerated even in patients in poor general conditions.

Adult↗

[The reversal of the protective effects of intermittent perfusion on ischemic myocardium by hypoxic, no-substrates, zero-K+ perfusate].

Intermittent perfusion during ischemia protected ischemic myocardium and improved recovery of function. These protective effects were reversed when hearts were perfused intermittently with hypoxic, no-substrates, zero-K+ buffer instead of oxygenated standard buffer containing substrates. We investigated the mechanisms of this reversal in isolated rat hearts. After 40 mins of sustained global ischemia, intracellular Na (Nai) increased by 6 times along with decrease in ATP and accumulation of lactate. During 30 mins of reperfusion, 45Ca2+ uptake reached 10.0 mumol/g dry with reduced recovery of ventricular function (LVEDP from 1 to 48 mmHg). When the 40 min period of ischemia was interrupted at 10 min intervals by 3 mins of IP, Nai didn't increase and reperfusion resulted in no increase in 45Ca2+ uptake (0.5 mumol/g dry). Recovery of function was 100% of the preischemic value without elevation of LVEDP. When hypoxic buffer without substrate and K+ was used for IP, Nai increased more rapidly with less recovery of function and more increased 45Ca2+ uptake (8 times) than sustained ischemia. These results indicate that disappearance of prevention of an increase in Nai with increased Ca2+ overload in hypoxic, no-substrates, zero-K+ IP, which resulted from accelerated ATP depletion and inhibition of Na/K pump is probably the main cause of the reversal of the protective effects.

Adenosine Triphosphate↗

[Cerebral blood flow rate during cardiopulmonary bypass and optimal cerebral perfusion flow rate during separated brain perfusion--a clinical study].

There is no established theory to determine the cerebral blood flow rate (CBF) during not only the standard cardiopulmonary bypass but during the cardiopulmonary bypass with separated brain perfusion. This study was carried out to answer the following questions. (1) what is the relationship during the cardiopulmonary bypass between CBF and systemic flow rate or blood pressure?. (2) what is the optimal flow rate to the innominate artery during the separated brain perfusion? Twenty-one patients were selected for this study, who were operated under the cardiopulmonary bypass with a standard roller pump and a membrane oxygenator under moderate hypothermia (nasopharyngeal temperature of 26-28 degrees C). Systemic flow rate was maintained between 40 and 70 ml/kg/min. CBF before the cardiopulmonary bypass was 30.6 +/- 5.5 ml/100 g brain/min, and increased to 33.8 +/- 8.9 ml/100 g brain/min during the cardiopulmonary bypass. CBF was proportional to systemic flow rate (r = 0.62, p less than 0.01) and showed poor association with blood pressure ranged from 35 to 94 mmHg. As for the relationship between innominate arterial and cerebral blood flow rate, CBF linearly followed the decrease of innominate arterial flow rate to below about 9 ml/kg/min, but showed almost no changes when innominate arterial flow rate was over 9 ml/kg/min. It was observed that cerebral oxygen consumption did not decrease significantly under moderate hypothermia (26-28 degrees C), as far as CBF of 25 ml/100 g brain/min was maintained. Based on the relationship between innominate arterial and cerebral blood flow rate, it was shown that the innominate arterial flow rate to provide CBF of 25 ml/100 g brain/min was 5.5 ml/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗