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To achieve adequate tissue perfusion during regional isolated perfusion, hind limbs of dogs were perfused for 60 min, regulating the extracorporeal circuit on pressure. The dogs were divided into three groups. In groups I and II perfusions were performed at a delta pressure (systemic mean arterial pressure minus hind limb mean arterial pressure) of respectively 50 and 15 mm Hg; in group III delta pressure was also 15 mm Hg but the cytostatic drug Melphalan was added. Tissue perfusion was determined by means of a multiwire polarographic oxygen electrode. Adequate tissue perfusion was obtained only at subnormal perfusion pressures (groups II and III), although in all groups perfusion flow was higher than preoperative flow. At low perfusion pressures (group I), tissue perfusion was severely impaired. In all groups leakage remained less than 10%. During regional isolated perfusion the extracorporeal circuit must be regulated at a delta pressure of 15 mm Hg to achieve adequate tissue perfusion.
BACKGROUND: Cytostatic isolated lung perfusion has been advocated for treating pulmonary metastasis of soft tissue sarcoma. Different techniques of isolated lung perfusion have been developed. METHODS: Isolated lung perfusion with and without doxorubicin was performed on white pigs during 15 minutes either by a single-pass system (n = 7) or by a recirculating-blood perfusion system (n = 7). Three animals with endovenous drug application served as controls. Leakage was assessed using isotopic tracers. Perfusion-induced lung tissue injury was determined by postperfusion chest radiographs, by angiotensin-converting enzyme-to-protein ratio in the plasma and in the bronchioalveolar lavage fluid, and by wet-to-dry weight ratio and histologic examination of lung biopsy specimens at 20 and 50 minutes. Doxorubicin concentration in lung tissue and plasma was compared between the three study groups. RESULTS: All isolated lung perfusion studies were successfully performed without significant systemic leakage (< 0.6%). Wet-to-dry weight ratio was significantly lower after single-pass as compared with recirculating-blood perfusion and endovenous drug application at both time points (5.0 +/- 1.1 and 5.3 +/- 0.8 for single-pass versus 6.6 +/- 1.1 and 6.9 +/- 0.5 for recirculating-blood versus 6.6 +/- 0.2 and 5.9 +/- 0.7 for the control group, respectively; p < 0.05). Angiotensin-converting enzyme-to-protein plasma ratio in the single-pass group was significantly lower only at 20 minutes (6.3 +/- 2.4 versus 9.3 +/- 1.0 versus 9.7 +/- 1.9, respectively; p < 0.05) but not at 50 minutes. Angiotensin-converting enzyme-to-protein ratio in bronchoalveolar lavage fluid, histology of lung biopsy specimens, and chest radiographs did not differ significantly between the three groups. Doxorubicin lung tissue concentration was not significantly different after single-pass (17.5 micrograms/g) and recirculating-blood perfusion (21.9 micrograms/g), but was significantly higher than after endovenous drug application (3.0 micrograms/g; p < 0.01). CONCLUSIONS: Both isolated lung perfusion techniques resulted in a sixfold to sevenfold higher doxorubicin lung tissue concentration than after endovenous application. Isolated lung perfusion-induced lung injury was similar for both techniques, but recirculating-blood perfusion appeared to result in more acute lung injury and was technically more demanding than single-pass perfusion.
OBJECTIVE: The aim was to compare the effects of ischaemic preconditioning in the buffer perfused and parabiotic blood perfused Langendorff rabbit heart models. METHODS: Isolated hearts were perfused with either Krebs-Henseleit buffer solution or blood from a support rabbit. Hearts were subjected to an initial 30 min stabilisation period followed by 30 min of global ischaemia and 60 min of reperfusion. Ischaemic preconditioned (IP) hearts were also subjected to one cycle of 5 min global ischaemia and 10 min of reperfusion before the 30 min ischaemia. For each experiment, left ventricular function and necrosis were measured. RESULTS: Necrosis, as measured by tetrazolium staining and expressed as a percentage of the left ventricular area, was significantly different between the buffer perfused control [42.5% (SEM 6.9), n = 7] and buffer perfused IP group [22.2% (5.4), n = 7, p < 0.01]. In the blood perfused experiments, the IP group also had less necrosis [9.3% (3.1), n = 9] as compared to controls [22.9%(4.2), n = 9, p < 0.01]. The percentage reduction in necrosis produced by ischaemic preconditioning was not significantly different between the buffer perfused and blood perfused models. Peak left ventricular systolic pressure was not different between the control and IP hearts in either model at any time during the 60 min reperfusion period. In buffer perfused hearts, left ventricular end diastolic pressure at 60 min reperfusion was not significantly different between the IP and the control groups, at 34.3(5.5) mm Hg v 37.8(4.9) mm Hg, respectively. Similarly, there was no statistically significant difference in left ventricular end diastolic pressure in the blood perfused groups at this time: 13.3(2.8) in the IP group v 24.0(6.5) in controls. CONCLUSIONS: In isolated heart models of global ischaemia and reperfusion, in which both recovery of function and necrosis were assessed together, ischaemic preconditioning was highly effective in reducing necrosis in both blood perfused and buffer perfused models. However, ischaemic preconditioning did not significantly improve postischaemic recovery of function in either of the two preparations.
Regional perfusion therapy of melanoma is followed by an apparent decrease in lymph node metastases. When regional isolated perfusion is performed by cannulating the blood vessels at the iliac level, at least the middle and distal parts of the inguinal nodal zone are included. This is not the case with femoral perfusion. These two types of perfusion were therefore compared to determine whether iliac perfusion eradicates micrometastases present in the inguinal nodes. The regional node recurrence rate and time to regional node relapse of 97 patients treated with iliac perfusion were compared with those of 20 patients who received femoral perfusion. Prognostic factors such as sex, MD Anderson stage of disease, Breslow thickness and Clark level of the primary melanoma, and number of nodules of those with recurrent melanoma were equivalent in both groups. All patients were perfused with melphalan under normothermic conditions during the period 1978-1990. Five of 20 patients (25%) receiving femoral perfusion and 31 of 97 patients (32%) receiving iliac perfusion (P = 0.7, chi 2 test) developed inguinal node metastases after a median period of 25 (8-40) and 19 (2-71) months, respectively (Mann-Whitney U test, P = 0.9). There was no statistically significant difference in the 5-year survival rate (55% versus 62%, respectively; log rank test P = 0.5). Since no advantage could be seen in terms of reduction of inguinal node relapse for iliac perfusion, it is concluded that perfusion of the distal nodes is not the major cause of reduction of regional node metastases.(ABSTRACT TRUNCATED AT 250 WORDS)
The perfusion-induced increase in cardiac contractility (Gregg phenomenon) is especially found in heart preparations that lack adequate coronary autoregulation and thus protection of changes in capillary pressure. We determined in the isolated perfused papillary muscle of the rat whether cardiac muscle contractility is related to capillary perfusion. Oxygen availability of this muscle is independent of internal perfusion, and perfusion may be varied or even stopped without loss of function. Muscles contracted isometrically at 27 degrees C (n = 7). During the control state stepwise increases in perfusion pressure resulted in all muscles in a significant increase in active tension. Muscle diameter always increased with increased perfusion pressure, but muscle segment length was unaffected. Capillary perfusion was then obstructed by plastic microspheres (15 microns). Flow, at a perfusion pressure of 66.6 +/- 26.2 cmH2O, reduced from 17.6 +/- 5.4 microliters/min in the control state to 3.2 +/- 1.3 microliters/min after microspheres. Active tension developed by the muscle in the unperfused condition before microspheres and after microspheres did not differ significantly (-12.8 +/- 29.4% change). After microspheres similar perfusion pressure steps as in control never resulted in an increase in active tension. Even at the two highest perfusion pressures (89.1 +/- 28.4 and 106.5 +/- 31.7 cmH2O) that were applied a significant decrease in active tension was found. We conclude that the Gregg phenomenon is related to capillary perfusion.
Angiographically normal coronary arteries are found in a substantial number of patients evaluated for angina pectoris. One third to one half of such patients demonstrate abnormalities of myocardial perfusion or metabolism when evaluated with invasive techniques. This study was designed to determine whether angina in such patients is attributable to abnormalities of perfusion at rest, maximal perfusion or vasodilator reserve and whether any identified abnormalities were global or regional in nature. Positron emission tomography was performed with oxygen-15-labeled water (H2(15)O) and oxygen-15-labeled carbon monoxide (C15O) before and after intravenous dipyridamole to assess regional myocardial perfusion and perfusion reserve in absolute terms in 16 normal subjects and 17 patients with chest pain and angiographically normal coronary arteries. Eight of the 17 patients had a myocardial perfusion reserve less than 2.5 (the lower limit of normal in studies with positron emission tomography, as well as with other techniques) and 9 of 17 patients had a normal response. In the patients with an impaired perfusion reserve, perfusion at rest was significantly higher than that measured in normal subjects (1.61 +/- 0.38 versus 1.25 +/- 0.28 ml/g per min, p less than 0.02) and maximal flow and perfusion reserve were significantly reduced (2.26 +/- 0.92 versus 4.62 +/- 1.58 ml/g per min and 1.4 +/- 0.5 versus 3.8 +/- 1.1, respectively; p less than 0.001 for both comparisons). Abnormalities of perfusion and perfusion reserve were spatially homogeneous without detectable regional disparities. Thus, nearly half of patients with chest pain and normal coronary arteries have abnormalities of myocardial perfusion that are detectable noninvasively with positron emission tomography and H2(15)O.
BACKGROUND: Although it is well documented that the use of a pH-stat strategy during hypothermic cardiopulmonary bypass improves cerebral blood flow, an alpha-stat strategy has been almost exclusively used during retrograde cerebral perfusion. We investigated the effects of pH-stat and alpha-stat management on brain tissue blood flow and oxygenation during retrograde cerebral perfusion in a porcine model to determine if the use of a pH-stat strategy during retrograde cerebral perfusion improves brain tissue perfusion. METHODS: Fourteen pigs were managed by an alpha-stat strategy (alpha-stat group, n = 7) or by a pH-stat strategy (pH-stat group, n = 7) during 120 minutes of hypothermic retrograde cerebral perfusion. Retrograde cerebral perfusion was established through the superior vena cava. Brain tissue blood flow and oxygenation were measured continuously with a laser flowmeter and near infrared spectroscopy, respectively. Brain tissue water content was determined at the end of the experiments. RESULTS: During cooling, brain tissue blood flow was significantly higher with use of the pH-stat strategy than with the alpha-stat strategy (86% +/- 10% versus 40% +/- 3% of baseline). During retrograde cerebral perfusion, brain tissue blood flow was also significantly higher (about three times higher) in the pH-stat group than in the alpha-stat group (15% +/- 4% versus 5% +/- 1% of baseline at 60 minutes of retrograde cerebral perfusion). Tissue oxygen saturation appeared to be higher during retrograde cerebral perfusion in the pH-stat group than in the alpha-stat group. Brain tissue blood flow during rewarming remained significantly higher with the use of pH-stat than with the use of alpha-stat. Brain tissue water contents were similar in both groups. CONCLUSIONS: In our pig model, the use of a pH-stat strategy during retrograde cerebral perfusion significantly improves brain tissue perfusion. Therefore, to improve retrograde cerebral blood flow during retrograde cerebral perfusion, it may be preferable to use a pH-stat strategy, rather than an alpha-stat strategy.
OBJECTIVE: The purpose of this study was to determine whether retrograde continuous normothermic blood cardioplegic perfusion provides better protection to ischemic areas of the left and right ventricles than does antegrade continuous normothermic blood cardioplegic perfusion. Localized phosphorus 31 magnetic resonance spectroscopy was used to monitor the changes in energy metabolism and intracellular pH in the ventricles of pig hearts. METHODS: Ten isolated pig hearts received 20 minutes of antegrade continuous normothermic blood cardioplegic perfusion for collection of control (baseline) data, followed by 60 minutes of either antegrade continuous normothermic blood cardioplegic perfusion (n = 5) or retrograde continuous normothermic blood cardioplegic perfusion (n = 5) with occlusion of the left anterior descending and the right coronary arteries. The hearts were then subjected to antegrade continuous normothermic blood cardioplegic perfusion for 20 minutes. The perfusion pressures were maintained between 80 and 100 mm Hg and between 38 and 43 mm Hg during antegrade and retrograde continuous normothermic blood cardioplegic perfusions, respectively. Intracellular pH and creatine phosphate, inorganic phosphate, and adenosine triphosphate levels were measured continuously in each ventricle by means of localized phosphorus 31 magnetic resonance spectroscopy with 2 surface coils. RESULTS: Both antegrade and retrograde continuous normothermic blood cardioplegic perfusion resulted in a significant increase in inorganic phosphate level and decreases in creatine phosphate level, adenosine triphosphate level, and intracellular pH. No significant differences in these changes were observed between the two groups. The creatine phosphate and adenosine triphosphate levels were significantly lower in the right ventricle than in the left ventricle during retrograde continuous normothermic blood cardioplegic perfusion. On reperfusion, the inorganic phosphate level, creatine phosphate level, and intracellular pH recovered completely; however, no recovery in the adenosine triphosphate level was seen in the ventricles of either group. CONCLUSIONS: Retrograde continuous normothermic blood cardioplegic perfusion does not provide better protection to ischemic areas of the ventricles than does antegrade continuous normothermic blood cardioplegic perfusion under our experimental conditions.
RATIONALE AND OBJECTIVE: The aim of this study was to demonstrate and measure perfusion deficits caused by central bronchogenic carcinoma and to compare magnetic resonance angiography (MRA) perfusion data with data of perfusion scintigraphy. The diagnostic value of 2D MRA in detection of malignant pulmonary artery stenosis in comparison with conventional DSA was investigated. MATERIALS AND METHODS: Eighteen patients were included in the study. MRA, conventional pulmonary angiograms, and pulmonary perfusion scintigrams were performed. MRA and DSA were compared and MR pulmonary perfusion data were assessed and compared with scintigraphical data. RESULTS: Perfusion defect could be demonstrated and localized in all patients. A quantitative perfusion deficit and a side dependent perfusion ratio could be evaluated. There was statistically significant correlation between MR perfusion and scintigraphically acquired data. 2D MRA showed a high correlation for detection and grading of stenosis compared with angiograms. CONCLUSIONS: Pulmonary perfusion could be demonstrated by using an ultrafast 2D projection MR DSA sequence. This technique allows measurement and quantification of pulmonary perfusion abnormalities in patients with malignant stenosis with statistically significant correlation to perfusion scintigraphy. The diagnostic potency in the evaluation of malignant pulmonary artery stenosis compared with conventional DSA could be shown.
The effects of changes in viscosity on pressure flow relations in the in situ perfused left circumflex coronary artery were studied in open chest dogs. Vascular reactivity was abolished by maximal pharmacological coronary dilatation. Blood and suspensions of red cells (hematocrit 8-14%) in dextran solutions were used as perfusates. Total perfusion energy dissipation, represented by perfusion pressure drop across the perfused vascular bed, can be separated into a viscous and an inertial fraction: P = Pvisc + Pinert. Perfusing the heart with approximately Newtonian fluids of different viscosities enabled us to compute the amount of the inertial fraction of total perfusion pressure dissipation. At constant viscosity, the inertial fraction increased with flow rate. However, the rise of the inertial fraction due to reduced viscosity at a constant perfusion pressure was much more pronounced. Variations of perfusion pressure and viscosity of the perfusates between 70 to 130 mm Hg and 1.2-3.2 cP, respectively, resulted in inertial perfusion pressure dissipation between 16 and 54%. This inertial pressure drop may become a noteworthy factor under conditions of low whole blood viscosity (e.g. anemia or therapeutical hemodilution.
Rabbit livers were preserved by continuous hypothermic (5 degrees C) perfusion at a flow rate of 1 ml/min-1 g-1 for as long as 72 hr. Cell swelling (total tissue water, TTW) and the rate at which intracellular enzymes were released into the perfusate were measured. Livers perfused with a simple NaCl-based solution containing hydroxyethyl starch as a colloid released relatively large amounts of aspartate aminotransferase (AST, 442 +/- 224 u/liter-1 100 g-1) and lactic dehydrogenase (LDH, 1580 +/- 688 u/liter-1 100 g-1) into the perfusate during 72 hr of perfusion. The addition of Ca (0.5 mmol/liter) to the perfusate reduced the leakage of enzymes into the perfusate (AST, 70 +/- 30 u; LDH, 450 +/- 50 u) and reduced cell swelling (TTW, 3.1 kg/kg dry mass vs 4.4 kg/kg dry mass without added Ca). But the use of a higher concentration of Ca (1.5 mmol/liter) caused membrane damage (AST, 4000 +/- 1500 u; LDH, 10,000 +/- 2222 u) and increased cell swelling (TTW, 3.7 kg/kg dry mass). The release of intracellular enzymes caused by continuous perfusion with a chloride-based perfusate also could be reduced by replacing the chloride with lactobionate (AST, 100 +/- 30 u; LDH, 400 +/- 100 u, at 72 hr). In the lactobionate-containing perfusate, the addition of Ca (0.5 or 1.5 mmol/liter) did not alter the rate at which intracellular enzymes were released. There was no tissue swelling after 72 hr of preservation with the lactobionate-containing perfusate, and the TTW (2.1 kg/kg dry mass) was similar to the TTW of freshly harvested rabbit livers.(ABSTRACT TRUNCATED AT 250 WORDS)
The optimal dosing schedule for melphalan therapy of recurrent malignant melanoma in isolated limb perfusions has been examined using a physiological pharmacokinetic model with data from isolated rat hindlimb perfusions (IRHP). The study included a comparison of melphalan distribution in IRHP under hyperthermia and normothermia conditions. Rat hindlimbs were perfused with Krebs-Hen-seleit buffer containing 4.7% bovine serum albumin at 37 or 41.5 degrees C at a flow rate of 4 ml/min. Concentrations of melphalan in perfusate and tissues were determined by high performance liquid chromatography with fluorescence detection. The concentration of melphalan in perfusate and tissues was linearly related to the input concentration. The rate and amount of melphalan uptake into the different tissues was higher at 41.5 degrees C than at 37 degrees C. A physiological pharmacokinetic model was validated from the tissue and perfusate time course of melphalan after melphalan perfusion. Application of the model involved the amount of melphalan exposure in the muscle, skin and fat in a recirculation system was related to the method of melphalan administration: single bolus > divided bolus > infusion. The peak concentration of melphalan in the perfusate was also related to the method of administration in the same order. Infusing the total dose of melphalan over 20 min during a 60 min perfusion optimized the exposure of tissues to melphalan whilst minimizing the peak perfusate concentration of melphalan. It is suggested that this method of melphalan administration may be preferable to other methods in terms of optimizing the efficacy of melphalan whilst minimizing the limb toxicity associated with its use in isolated limb perfusion.
OBJECTIVE: To compare brain perfusion-computed tomography (CT) results with invasive cerebral perfusion pressure (CPP) monitoring in severe head trauma patients. DESIGN: Prospective cohort study. SETTING: Emergency room and surgical intensive care unit of our hospital. PATIENTS: Sixty-one severe head trauma patients. INTERVENTIONS: We prospectively collected 103 perfusion-CT examinations with simultaneous measurement of mean arterial pressure and intracranial pressure, affording calculation of CPP. The statistical relationship between perfusion-CT results and the corresponding CPP values was evaluated using Wilcoxon (Mann-Whitney) and generalized F-tests. The functional outcome of the 61 patients was evaluated 3 months after trauma on the basis of the Glasgow Outcome Scale score and compared between groups using Fisher's exact tests. MEASUREMENTS AND MAIN RESULTS: Perfusion-CT enabled us to distinguish between two groups of patients. Within each group, a significant correlation (p <.001) between the CPP values and the corresponding perfusion-CT results was demonstrated. There was also a significant correlation (p <.001) between the CPP values and the extent of the abnormal perfusion-CT areas (R up to.817). The first group was characterized by a weak dependence of perfusion-CT results on the corresponding CPP values (low slope) and the second group by a strong dependence (steep slope). These groups were interpreted as having preserved (or pseudo) and impaired cerebral vascular autoregulation, respectively. The functional outcome was better in the second group of patients. CONCLUSIONS: Intermittent perfusion-CT measurements plus continuous CPP measurement provide more information than continuous CPP alone. Perfusion-CT gives unique information regarding regional heterogeneity of brain perfusion. It might allow clinicians to distinguish between patients with preserved auto-regulation (or pseudoautoregulation) and those with impaired autoregulation and could therefore guide interpretation of CPP measurements and therapy.
The relative effects of perfusate alkaline phosphatase activity and net water absorption on 2 microM pyridoxal 5'-phosphate (PLP) luminal disappearance from rat jejunum were studied in a single-pass, in vivo perfused intestinal segment model. Perfusate consisted of unlabeled PLP in buffer (pH = 7.4). Net water flux was monitored by inclusion of [3H]polyethylene glycol. PLP was measured by the [14C]tyrosine apodecarboxylase assay. Single and multiple regression analysis of results during perfusion of 2 microM PLP in Krebs bicarbonate buffer demonstrated no correlation between perfusate alkaline phosphatase activity and net water absorption and significant correlations between PLP luminal disappearance and both perfusate alkaline phosphatase activity and net water absorption. Correlation for the latter was improved when disappearance results were corrected for variations in perfusate alkaline phosphatase activity. When perfusate buffers were selected to yield divergent rates of net water absorption, the one associated with greater net water absorption was also associated with greater PLP disappearance. That this could not be explained by changes in perfusate alkaline phosphatase activity was demonstrated both by assessment of the rate of decay of PLP added in vitro to exited perfusate incubated at 37 degrees C and by measurement of alkaline phosphatase activity under conditions defined by the buffers using a modified spectrophotometric assay. Conclusions were: (1) In vivo PLP luminal disappearance correlates significantly with both perfusate alkaline phosphatase activity and net water absorption; (2) these two factors appear to act as independent variables; and (3) future studies on PLP intestinal absorption will need to take both of these variables into account in the interpretation of results.
The present study assesses the detectability of perfusion defect and the influence of breathhold on pulmonary magnetic resonance (MR) perfusion imaging using contrast-enhanced thick-slice two-dimensional (2D) fast gradient-echo sequence compared with three-dimensional (3D) fast spoiled gradient-recalled sequence. Dynamic studies were performed in 16 patients. MR perfusion images were interpreted by two independent observers using perfusion scintigraphy as the reference standard. The patients were divided into two groups according to the duration of holding the breath measured during MR imaging. The sensitivity and specificity of 2D MR perfusion imaging in detecting perfusion defects were 93% and 94%, respectively, while those of 3D MR perfusion imaging were 89% and 85%, respectively. The diagnostic accuracy of 2D MR perfusion imaging was significantly higher than that of 3D MR perfusion imaging (P < 0.05) among those who could not hold their breath. Therefore, 2D MR perfusion imaging offers promise for evaluating pulmonary perfusion even among patients who cannot hold their breath.
Equilibrated rat hearts were perfused for 60 min with a standard crystalloid buffer containing either 0.9, 1.8, 3.5, or 5.0 mM Ca with or without added lead (0.3 and 30 microM). Contractile tension (T), rate of tension development (dT/dt), electrocardiographic (EKG), His bundle electrographic (HBE) indices, heart rate (HR), preejection period (PEP), and coronary flow rate (CFR) were recorded as a function of perfusion time. Endpoint analyses of myocardial phosphatic metabolites were performed on heart perchloric acid extracts by standard phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopic techniques. The contractile activity and glycerol 3-phosphorylcholine content of the myocardium were found to vary directly as a function of the perfusate calcium concentration; however, except for a prolonged atrioventricular-His bundle conduction time detected in hearts treated with 0.9 mM Ca, the variable perfusate calcium concentrations were devoid of any other significant physiologic and metabolic effects. In contrast, perfusion of control equilibrated hearts with 30 microM lead significantly attenuated the positive, and exacerbated the negative, inotropic responses to elevated, and low perfusate calcium concentrations, respectively. Moreover, a secondary, time-dependent decline in myocardial contractile strength was also observed in response to this lead concentration, which was progressively more pronounced with each increment in the perfusate calcium concentration. The preejection period of ventricular systole was also prolonged in response to 30 microM lead; however, this effect was less pronounced at higher perfusate calcium concentrations. Hearts perfused with 30 microM lead were also characterized by significant prolongation in atrioventricular node and His bundle conduction time, reduced coronary flow rate, and decreased heart rate, irrespective of the perfusate calcium concentration. Hearts treated with 0.3 microM lead exhibited functional properties that were diminished, but still comparable to control hearts. Analysis of myocardial phosphatic metabolite amounts following 60 min of perfusion revealed a significant lead-induced reduction in the energy status of the heart. The combination of 5.0 mM calcium with either 0.3 or 30 microM lead resulted in significant disturbances in phosphoglyceride, glycolytic, and high-energy phosphate pathways. These findings suggest that the cardiotoxic actions of lead are linked to complex mechanisms that are partially related to an interference with calcium-dependent cellular processes.(ABSTRACT TRUNCATED AT 400 WORDS)
BACKGROUND: Both epicardial and myocardial perfusion have been associated with clinical outcomes in the setting of ST elevation myocardial infarction (STEMI), and the performance of adjunctive/rescue percutaneous coronary intervention (PCI) may further improve clinical outcomes after fibrinolytic administration. METHODS: The goal was to develop a simple, broadly applicable angiographic metric that takes into account indices of epicardial and myocardial perfusion both before and after PCI to arrive at a single perfusion grade in patients undergoing cardiac catheterization after fibrinolysis. The angiographic perfusion score (APS) is the sum of the Thrombolysis in Myocardial Infarction (TIMI) flow grade (TFG; 0-3) added to the TIMI myocardial perfusion grade (TMPG; 0-3) before and after PCI (total possible grade, 0-12). Failed perfusion was defined as an APS of 0 to 3, partial perfusion was defined as an APS of 4 to 9, and full perfusion was defined as an APS of 10 to 12. The APS was evaluated in patients from the Double-blind, Placebo-contolled, Multicenter Angiographic Trial of Rhumab CD18 in Acute Myocardial Infarction (LIMIT-AMI; n = 394) and Enoxaparin as Adjunctive Antithrombin Therapy for ST-Elevation Myocardial Infarction-Thrombolysis In Myocardial Infarction (ENTIRE-TIMI) 23 trials (n = 483), and infarct size (120-216 hours after AMI SPECT Technetium-99m Sestamibi data) was assessed in the LIMIT-AMI trial. RESULTS: The APS was associated with the incidence of death or myocardial infarction (failed, 16.7% [n = 18]; partial, 2.5% [n = 155]; full, 2.4% [n = 82]; P =.039 for trend) and larger SPECT infarct sizes (failed, median 39% [n = 10]; partial, 12% [n = 79]; and full, 8% [n = 35]; P =.002). No patient with full APS died, whereas the mortality rate was 11.1% in patients with a failed APS (P =.03). CONCLUSIONS: The APS combines grades of epicardial and tissue level perfusion before and after PCI or at the end of diagnostic cardiac catheterization to arrive at a single angiographic variable that is associated with infarct size and the rates of 30-day death or MI. Partial or full angiographic perfusion scores are associated with a halving of infarct size, and no patients with full angiographic perfusion died.