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Evaluation of extrahepatic perfusion of anticancer drugs in the right gastric arterial region on fused images using combined CT/SPECT: is extrahepatic perfusion predictive of gastric toxicity?

BACKGROUND: Hepatic arterial infusion (HAI) chemotherapy is effective for treating primary and metastatic carcinomas of the liver. Since hepatic arteries also supply the stomach and duodenum, HAI may result in unwanted infusion into the upper gastrointestinal tract and consequent gastric toxicity. Using fused images obtained with a combined SPECT/CT system, we assessed extrahepatic perfusion (EHP) and its correlation with gastrointestinal toxicity in patients receiving HAI. METHODS: We studied 41 patients with primary or metastatic carcinoma of the liver who received HAI chemotherapy consisting of 5-fluorouracil and cisplatin. All underwent abdominal SPECT using a (99m)Tc-MAA (185 MBq) instrument and an injection rate of 0.1 ml/min, identical to the chemotherapy infusion rate. Delivery was through an implantable port. We analyzed the distribution of the anticancer agent on fused images and the relationship between EHP of the right gastric arterial region and gastric toxicity. All patients underwent esophagogastroduodenoscopy (EGDS). RESULTS: Of the 41 patients, 11 (27%) manifested enhancement of the duodenal and gastric pyloric region on fused images. EGDS at the time of reservoir placement detected gastric ulcers in 10 of these patients. CONCLUSION: Fusion imaging with combined SPECT/CT reflects the actual distribution of the infused anticancer agents. The detection of EHP on fused images is predictive of the direct gastric toxicity from anticancer agents in patients undergoing HAI.

Adult↗

Increase of beta-actin mRNA upon hypotonic perfusion of perfused rat liver.

beta-Actin mRNA levels in livers exposed to hypotonic perfusion (from 305 to 225 mosmol/l) for one hour are increased 2-fold relative to albumin mRNA. Like albumin, glyceraldehyde-3-phosphate dehydrogenase and tyrosine aminotransferase mRNAs remain at the levels observed under normotonic conditions. The increase in beta-actin mRNA is interpreted as a cytoskeletal response due to cell swelling.

Actins↗

Electrocardiographic prediction of the severity of posterior wall perfusion defects on rest technetium-99m Sestamibi myocardial perfusion imaging.

To identify electrocardiogram (ECG) variables predicting the severity of previous posterior wall myocardial infarction as measured by technetium-99m-Sestamibi rest single-photon emission computed tomography, we assessed agreement between ECG criteria and posterior wall perfusion defects (PWPDs) in 236 patients. Established ECG criteria for posterior and posterolateral infarctions were present in 22% and 19% of patients, respectively, and did not predict severity of PWPD ( P = NS). Univariate predictors of severity were the Selvester QRS score (SQS) ( P = .001) and an upright T wave in V 1 (UTV 1 ) greater than 0.2 mV ( P = .001). Regression analysis demonstrated that SQS ( P = .0001) and UTV 1 greater than 0.2 mV ( P = .006) were highly predictive of severity ( c statistic = 0.793). All severe PWPDs had an SQS of 2 or higher. Established ECG patterns for diagnosis of posterior infarction are insensitive and poor predictors of severity. The SQS and UTV 1 are effective for the diagnosis of posterior infarction and useful for the estimation of infarct severity.

Coronary Circulation↗

Gated SPECT perfusion imaging for the simultaneous assessment of myocardial perfusion and ventricular function in the BARI 2D trial: an initial report from the Nuclear Core Laboratory.

BACKGROUND: The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial, a National Heart, Lung, and Blood Institute-sponsored study in type 2 diabetic patients with coronary artery disease, completed patient recruitment in March 2005. This trial had a nuclear substudy in addition to many other substudies. METHODS AND RESULTS: After patient enrollment, adenosine gated single photon emission computed tomography perfusion imaging is performed at years 1 and 3. The images are interpreted at the core laboratory. Among the objectives of the nuclear substudy are (1) to determine the impact of the mode of therapy on left ventricular function, extent of ischemia, and scar; (2) to determine the impact of therapy on the progression/regression of ischemia/scar and changes in left ventricular function between years 1 and 3; and (3) to determine the independent and incremental prognostic value of ischemia, scar, and left ventricular function on the primary and secondary endpoints of the trial in the entire patient population and specified subgroups such as women, elderly patients, and minorities. CONCLUSIONS: This article describes the methodology and the initial experience of the nuclear core laboratory in this large multicenter trial and provides a summary of variables that are available for future analysis by the working group.

Adenosine↗

The influence of downstream arterial perfusion parameters on doppler pulsatility index and resistance index in an in-vitro perfusion model.

BACKGROUND: To investigate in vitro how downstream perfusion parameters influence pulsatility index (PI), resistance index (RI) and their constituting Doppler velocities. MATERIALS AND METHODS: We analyzed the influence of resistance, compliance, reflection coefficient and input impedance on PI and RI in an in-vitro model of arterial flow. RESULTS: The nominators of PI and RI were determined by resistance. The numerators were determined by compliance and by the reflection coefficient. There were close relationships of PI and RI with resistance under the condition of constant compliance, but not when compliance was variable. CONCLUSION: PI and RI consist of velocity terms which are independently influenced by different parameters of impedance: compliance, reflection coefficient and resistance. These findings explain the contradictory results reported for the relationship between the indices and peripheral resistance in studies where compliance and reflection effects were not considered.

Animals↗

Splanchnic perfusion during hemodialysis: evidence for marginal tissue perfusion.

OBJECTIVE: Splanchnic perfusion may be compromised during hemodialysis because of hypovolemia, inflammatory response, and blood flow redistribution. The aim of this study was to assess the response of splanchnic blood flow and oxygen transport to hemodialysis. DESIGN: A prospective clinical study. SETTING: A mixed medical-surgical intensive care unit in a university hospital. PATIENTS: Nine patients with acute renal failure. INTERVENTIONS: A 4-hr period of hemodialysis. MEASUREMENTS AND MAIN RESULTS: Systemic (via a pulmonary artery catheter), hepatosplanchnic, and femoral (via dye dilution) blood flow and gastric mucosal Pco2 were measured before, during, and 2 hrs after hemodialysis. During hemodialysis, despite unchanged arterial blood pressure, cardiac output and stroke volume decreased from 3.0 +/- 1.0 L/m2/min (mean +/- sd) to 2.3 +/- 0.7 L/m2/min (p =.02), and from 38 +/- 16 mL/m2/min to 28 +/- 12 mL/m2/min (p =.01), respectively. Splanchnic but not femoral blood flow decreased from 0.9 +/- 0.3 L/m2/min to 0.7 +/- 0.2 L/m2/min (p =.02). The blood flows returned to baseline values after dialysis without need for therapeutic interventions. Gastric mucosal-arterial Pco2 gradients were high before dialysis (35 +/- 23 torr [4.6 +/- 3.1 kPa]) and did not change. Renin but not atrial natriuretic peptide concentration increased during hemodialysis from 13 +/- 13 microg/L to 35 +/- 40 microg/L and decreased afterward to baseline values (13 +/- 13 microg/L; p =.01). Whereas interleukin 6 tended to decrease, tumor necrosis factor alpha increased during hemodialysis from 74 +/- 24 pg/mL to 86 +/- 31 pg/mL and continued to increase after hemodialysis to 108 +/- 66 pg/mL (p =.022). CONCLUSION: Hemodialysis and fluid removal in normotensive patients with acute renal failure may result in a reduction of systemic and splanchnic blood flow that is undetectable using traditional clinical signs. In contrast to what is observed in hypovolemia, the changes in regional blood flow are rapidly reversible after hemodialysis.

Acute Kidney Injury↗

Sensitivity, specificity and accuracy of stress SPECT myocardial perfusion imaging for detection of coronary artery disease in the distribution of first-order branch vessels, using an anatomical matching of angiographic and perfusion data.

We sought to investigate the utility of stress single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) for the identification of coronary artery disease (CAD) in the distribution of first-order branch vessels. We evaluated 135 consecutive patients with coronary angiography and stress SPECT MPI. We anatomically matched angiography and SPECT to assess the sensitivity, specificity and accuracy of SPECT MPI for the detection of CAD in the distribution of first-order branches. Subgroup analysis for stress test performance and previous coronary artery bypass grafting (CABG) was also performed. The sensitivity, specificity and accuracy of stress SPECT MPI for the detection of CAD in the distribution of first-order branch vessels were all 67%. For isolated branch vessel CAD, stress SPECT MPI had a sensitivity of 44%. In patients without CABG, the sensitivity, specificity and accuracy for the detection of CAD in the distribution of first-order branch vessels were 71%, 67% and 68%, compared with 60%, 67% and 64% for patients with CABG. The sensitivity for isolated branch vessel CAD was 50% for patients without CABG, but only 29% for patients with CABG. The sensitivity and specificity for CAD in the distribution of branch vessels were similar for all patients for all stress test modalities and heart rate response (sensitivity, 64-69%; specificity, 61-69%). Stress SPECT MPI offers intermediate sensitivity, specificity and accuracy for the detection of CAD in the distribution of first-order coronary artery branch vessels. However, for isolated branch vessel CAD, stress SPECT has a lower sensitivity, particularly in patients with previous CABG.

Coronary Angiography↗

Is hypertension a tissue perfusion disorder? Implications for renal and myocardial perfusion.

Structural alterations in the microcirculation form a major link between hypertension and target organ damage. More than 60% of the overall peripheral resistance of the circulatory system arises at the level of the microcirculation. The primary function of the microcirculation is to supply oxygen and nutrients to tissues. In hypertension, remodelling of the microvascular vessels occurs, leading to an early, functional then anatomical reduction in the number of arterioles or capillaries in a given vascular bed. Such changes have been seen in the structure and density of the microvasculature of different target organs such as the myocardium and the kidneys. In hypertension, capillary rarefaction induces an increase in blood pressure, a relative decrease in tissue perfusion and an increased cardiovascular risk. Recent in-vivo non-invasive techniques for exploring the human microcirculation have allowed the detection of myocardial and renal microvascular impairment in hypertensive patients. In comparative therapeutic studies, antihypertensive drugs have been shown to have different capacities for preventing or reversing changes to the microvasculature of affected organs.

Adrenergic beta-Antagonists↗

Prognostic value of myocardial perfusion imaging in patients with known or suspected stable angina pectoris: evaluation in a setting in which myocardial perfusion imaging did not influence the choice of treatment.

OBJECTIVE: Previous investigations on the prognostic value of myocardial perfusion imaging (MPI) were performed under circumstances in which the test result was known to the patient's physician. We wanted to examine the prognostic value of MPI in patients with known or suspected stable angina in a setting in which MPI could not influence the diagnostic and therapeutic strategy. DESIGN: A prospective series of 507 patients referred to coronary angiography for this condition were examined by MPI before angiography. Management was based on symptoms and angiographic findings, as the results of MPI were not communicated. Patients were followed for a mean of 45.3 +/- 7.7 months. RESULTS: During follow-up, 20 patients (3.9%) suffered from myocardial infarction, 19 (3.8%) died and eight (1.6%) were revascularized >1 year after MPI resulting in a combined annual event rate of 2.5%. Patients with normal MPI had a low annual event rate of 1.6% (or 1.1% with regard to myocardial infarction or death only). In contrast, event rates in patients with reversible or mixed ischaemia were 4.0% per year. MPI added independent prognostic value to standard clinical data in a multivariate Cox model. CONCLUSION: We could confirm that in patients with known or suspected stable angina, MPI is a valuable risk stratifying tool.

Adult↗

An update on perfusion safety: does the type of perfusion practice affect the rate of incidents related to cardiopulmonary bypass?

Cardiopulmonary bypass (CPB) techniques vary among adult and pediatric patients undergoing cardiac surgery. This may result in a differential conduct of CPB between various aged patients. The present study reports on perfusion incidents occurring in hospitals using extracorporeal circulation. An 80 question survey was mailed to chief perfusionists at all 1030 US cardiac surgical centers. Respondents were asked to report on device use and incidents occurring during a 2-year period from July 1996 to June 1998. Five hundred and twenty-four completed surveys were returned with the age of surgical patients operated on at each hospital defined as either an adult (n=407), pediatric (n=17), or combined-adult and pediatric (n=100). Centrifugal pumps were used as the primary systemic pumps in 54% of adult, 12% of pediatric, and 36% of combined centers. In-line blood gas monitoring was used in 76% of all pediatric hospitals, but in only 30% of adult facilities. Incident rates occurred once per every 120.9, 83.9, and 220.2 cases in adult, pediatric, and combined centers, respectively. Mortality rates related to CPB occurred 2.7 times higher in adult and pediatric centers as compared to combined hospitals. Arterial dissection was the number one cause of death in both pediatric and combined hospitals, while coagulation disturbances resulted in the highest mortality for adult procedures. Results of this study show that the lowest incident rates occur at hospitals performing combined adult and pediatric CPB.

Adult↗

Veno-venous perfusion-induced systemic hyperthermia: case report with perfusion considerations.

Cancer cells are more susceptible to destruction by heat than are their normal counterparts. However, optimization of this hyperthermic susceptibility for selective cancer cell kill has been difficult to define and technically difficult to achieve. A whole-body hyperthermic technique veno-venous perfusion-induced systemic hyperthermia (VV-PISH) was designed in in vitro and in swine experiments to achieve selective hyperthermic cancer cell destruction. In this case report, VV-PISH is studied for its safety and therapeutic efficiency in a Food and Drug Administration (FDA) approved phase-I study, where hyperthermia is used to treat advanced (Stage III B or IV) lung cancer. VV-PISH, utilizing the ThermoChem HT system in an extracorporeal circuit, was used to induce hyperthermia to 42.5 degrees C sustained for 120 min. Cooling returned the body temperature to 37 degrees C. After completion of the treatment, the patient was transferred to the intensive care unit on a ventilator, norepinephrine and diuretics. The patient remained somnolent for 36 h, developed pulmonary congestion requiring an additional 48 h before extubation, was transferred to the intermediate unit on day 4 and discharged in good condition on day 8. He did experience hyperthermia-related shrinkage of his lung cancer; however, he succumbed 270 days after this treatment from further progression of this disease. Hyperthermia is not a benign therapy; management techniques have been developed that have ameliorated many of the problems associated with extremely high temperatures, but pathophysiology still exists. Using these techniques, VV-PISH can be safety implemented, albeit not without temporary sequelae and further hospitalization.

Body Temperature↗

Effects of preload alteration on the degree of ischemia and function of ischemic myocardium under constant mean aortic pressure, coronary perfusion pressure and heart rate in isolated perfused canine heart.

We examined the effects of preload alteration on global and regional (i.e., non-ischemic and ischemic areas) function in the presence of regional myocardial ischemia and on the degree of ischemia using 18 isolated, metabolically supported canine left ventricles. For this purpose, cardiac output (CO), systolic segment length change (SL), myocardial CO2 tension (PmCO2) and ST level of epicardial ECG were measured at 3 levels of left ventricular end-diastolic pressure (LVEDP), i.e., approximately 7 (low LVEDP), 11 (middle LVEDP), and 16 mmHg (high LVEDP) without and with left circumflex artery (LCx) stenosis under a constant mean aortic pressure (90 mmHg), mean coronary perfusion pressure (90 mmHg) and heart rate. In the Pre-ischemic stage, CO and SL increased significantly when LVEDP was elevated in a stepwise fashion by changing the height of the reservoir connected to the left atrium. There were no significant changes in PmCO2 or ST level. On the other hand, with LCx stenosis, CO did not show a subsequent increase at higher LVEDPs (i.e., from 796 +/- 103 ml/min at middle LVEDP to 931 +/- 153 ml/min at high LVEDP). Furthermore, there was no significant SL response in the LCx area following alterations of LVEDP, although there was considerable lengthening of end-diastolic length. Both increased PmCO2 and ST level of the LCx area, following LCx stenosis, further increased significantly with elevation of LVEDP. These results suggest the possibility that considerable elevation of LVEDP worsens the degree of ischemia and does not significantly augment ischemic regional myocardial function or global function, while mild elevation of preload improves or tends to improve simultaneously regional ischemic and global functions without aggravating the ischemic injury significantly. Therefore, we conclude that the preload level is quite important in managing ischemia induced myocardial dysfunction.

Animals↗

Cerebral perfusion MR imaging using FAIR-HASTE in chronic carotid occlusive disease: comparison with dynamic susceptibility contrast-perfusion MR imaging.

To determine the efficacy of flow-sensitive alternating inversion recovery using half-Fourier single-shot turbo spin-echo (FAIR-HASTE) in detecting cerebral hypoperfusion in chronic carotid occlusive disease, we subjected 12 patients with various degrees of cervical internal carotid artery stenoses and/or occlusion (Stenosis group) and 24 volunteers (Normal group) to FAIR-HASTE. In addition, 10 out of 12 patients in the Stenosis group underwent dynamic susceptibility contrast-perfusion magnetic resonance imaging (DSC-pMRI) before and after revascularization in the dominantly affected side. The absolute asymmetry indexes (AIs) of both cerebral hemispheres in the Normal and Stenosis groups were compared in FAIR-HASTE. In addition, the AIs were compared with those in the Stenosis group before and after revascularization in both FAIR-HASTE and regional cerebral blood flow (rCBF), calculated with DSC-pMRI. A statistically significant difference was recognized between the AIs in the Normal and Stenosis groups (AI = 2.25 +- 1.92, 8.09 +- 4.60, respectively ; p < 0.0001). Furthermore, in the Stenosis group the AIs on both FAIR-HASTE (8.88 +- 4.93, 2.22 +- 1.79, respectively ; p = 0.0003) and rCBF (7.13 +- 3.57, 1.25 +- 1.33, respectively ; p = 0.0003) significantly decreased after revascularization. In the Stenosis group, before revascularization, signal intensity on both FAIR-HASTE and rCBF had a tendency to be lower in the dominantly affected side. FAIR-HASTE imaging was useful in the detection and evaluation of cerebral hypoperfusion in chronic occlusive carotid disease.

Adult↗

Pressure-volume index as a function of cerebral perfusion pressure. Part 1: The effects of cerebral perfusion pressure changes and anesthesia.

The pressure-volume index (PVI) was measured as a function of cerebral perfusion pressure (CPP) in 12 adult cats. Anesthesia was induced with methohexital in six animals and with pentobarbital in six animals; all were maintained on an N2O:O2 (70%:30%) mixture. The CPP was either increased in 10-torr increments using norepinephrine or decreased by a combination of adenosine triphosphate and hemorrhage in subgroups. Three estimations of PVI were made at each level of CPP. The PaCO2, body temperature, and hematocrit were controlled at normal levels throughout. In both groups there was a linear relationship between PVI and CPP with increasing CPP being reflected by a rise in PVI. This relationship was more marked in the methohexital group: PVI = 0.37 ml + 0.0005 mm Hg CPP in the pentobarbital group, and PVI = 0.14 ml + 0.0019 mm Hg CPP in the methohexital group. These results indicate that the PVI is not independent of CPP but is a function of CPP and is profoundly influenced by anesthesia.

Animals↗

Pressure-volume index as a function of cerebral perfusion pressure. Part 2: The effects of low cerebral perfusion pressure and autoregulation.

The pressure-volume index (PVI) was measured in six adult cats while cerebral perfusion pressure (CPP) was reduced from normal levels to below the autoregulatory range by a continuous infusion of adenosine triphosphate. Anesthesia was induced with methohexital and maintained with an N2O:O2 (70%:30%) mixture. Body temperature, hematocrit, and PaCO2 were held constant throughout each experiment. Cerebral blood flow (CBF) was measured by the hydrogen clearance method. At CPP levels over 50 mm Hg, CBF remained relatively constant despite changes in CPP. Within this range, the PVI varied directly with CPP (PVI = 0.24 ml + 0.0013 mm Hg CPP). Below the autoregulatory range, CBF fell progressively with further decreases in CPP; in this range, PVI was found to increase as CPP fell (PVI = 0.84 ml - 0.0071 mm Hg CPP). These results indicate that the PVI is a complex function of CPP, varying directly with CPP within the autoregulatory range and indirectly with CPP below the autoregulatory range.

Animals↗

Dynamic perfusion CT: optimizing the temporal resolution and contrast volume for calculation of perfusion CT parameters in stroke patients.

BACKGROUND AND PURPOSE: Numerous parameters are involved in dynamic perfusion CT (PCT). We assessed the influence of the temporal sampling rate and the volume of contrast material. METHODS: Sixty patients with ischemic hemispheric stroke lasting > or = 12 hours underwent PCT. Groups of 15 patients each received 30, 40, 50, or 60 mL of contrast agent. Regional cerebral blood volume (rCBV), regional cerebral blood flow (rCBF), mean transit time (MTT), and time-to-peak (TTP) maps were calculated for temporal sampling intervals of 0.5, 1, 2, 3, 4, 5, and 6 seconds. Results were statistically compared. Signal-to-noise ratios (SNRs), duration of arterial entrance to venous exit, and radiation dose were also assessed. RESULTS: Increasing temporal sampling intervals lead to significant overestimation of rCBV, rCBF, and TTP and significant underestimation of MTT compared with values for an interval of 1 second. Maximal allowable intervals to avoid these effects were 2, 3, 3, and 4 seconds for 30, 40, 50, and 60-mL boluses, respectively. Venous exit of contrast material occurred in 97.5% of patients after 36, 42, 42, and 48 seconds, respectively, for the four volumes. SNRs did not differ with volume. The effective radiation dose varied between 0.852 and 1.867 mSv, depending on the protocol. The cine mode with two 40-mL boluses and the toggling-table technique with one 60-mL bolus had the lowest doses. CONCLUSION: Temporal sampling intervals greater than 1 second can be used without altering the quantitative accuracy of PCT. Increased sampling intervals reduce the radiation dose and may allow for increased spatial coverage.

Aged↗