Comparative myocardial extraction of two technetium-labeled BATO derivatives (SQ30217, SQ32014) and thallium

The transcapillary exchange of a new class of 99mTc-labeled compounds (BATO) were compared to 201Tl in isolated, blood perfused rabbit hearts. During variable blood flow (0.15-2.44 ml/min/g), peak and net extraction (Emax and Enet, respectively), and capillary permeability-surface area product (PScap) were determined with paired indicator-dilution techniques. Serial bolus injections of 201Tl, [111In]albumin, and [99mTc]BATO; chloro[tris(cyclohexanedionedioxime)methyl boronic acid]Tc (SQ30217, n = 8) and a hydroxy-substituted derivative (SQ32014, n = 5) were given to a total of 13 hearts. Mean (+/- s.d.) SQ30217 Emax and Enet were 0.72 +/- 0.09 and 0.55 +/- 0.18, respectively, which were higher than thallium values of 0.57 +/- 0.10 and 0.46 +/- 0.17 (p less than 0.03). Mean SQ30217 PScap was 1.1 +/- 0.4 ml/min/g and was also higher than corresponding thallium determinations (0.7 +/- 0.3; p less than 0.001). SQ32014 Emax, Enet, and PScap were all significantly less than thallium values (p less than 0.001). Thallium and SQ30217 values for Emax and PScap were closely correlated with blood flow (r greater than or equal to 0.73), whereas those for SQ32014 were weakly correlated (r = 0.09). A small clinical pilot study (n = 3) was performed, which showed that SQ32014 was a poor myocardial perfusion agent in man. In summary, transcapillary exchange of SQ30217 is greater than thallium, which in turn, is greater than SQ32014. Therefore, SQ30217 appears to have good clinical potential, but SQ32014 does not

Comparison of hypoxia and ouabain effects on the myocardial uptake kinetics of technetium-99m hexakis 2-methoxyisobutyl isonitrile and thallium-201

Effects of hypoxia and ouabain on transcapillary exchange of [99mTc]hexakis (2-methoxyisobutylisonitrile) [SESTAMIBI, also known as MIBI or HEXAMIBI] and 201TI were investigated with indicator-dilution studies using isolated rabbit hearts. Peak myocardial extraction (Emax), permeability-surface area products (PScap), and net myocardial extraction (Enet) were compared among serial injections during constant coronary flows. Overall, measures of transcapillary transport (Emax and PScap) for SESTAMIBI were significantly lower (p less than 0.001) than those simultaneously determined for thallium, but estimates of tissue retention (Enet) for SESTAMIBI and thallium were not statistically distinguishable. Hypoxia had no significant effect on mean (+/- s.d.) Emax for SESTAMIBI (0.31 +/- 0.13) or thallium (0.59 +/- 0.11), nor on mean PScap or Enet values. Ouabain (1.5 X 10(-7) M and 1.5 X 10(-6) M) had no effect on SESTAMIBI or thallium Emax (respectively, 0.29 +/- 0.08 and 0.60 +/- 0.05) or on PScap for SESTAMIBI. Thallium PScap was depressed with higher ouabain dose (control, 1.22 +/- 0.40; high ouabain, 1.06 +/- 0.41 ml/min/g; p less than 0.01). Ouabain also caused a significant and progressive increase in average SESTAMIBI Enet (control, 0.23 +/- 0.10 to high ouabain, 0.33 +/- 0.12; p less than 0.05), but depressed thallium Enet (control, 0.38 +/- 0.14 to high ouabain, 0.32 +/- 0.18; p less than 0.01). These results suggest myocardial metabolic and/or functional status have minor influence on transcapillary transport of SESTAMIBI and thallium, but significantly affects cellular retention

The effect of dipyridamole on transmural blood flow gradients

The effect of dipyridamole (DP) on subendocardial (ENDO) and subepicardial (EPI) blood flow in stenosed and normal regions was determined with radioactive microspheres before and after intravenous infusion of 0.08 mg/kg.min-1 of DP in two groups of dog hearts in situ. Group 1 (n = 6) had coronary stenoses that did not reduce distal perfusion at rest, but did attenuate hyperemic response, and group 2 (n = 6) had stenoses which reduced resting blood flow. In nonstenosed zones, a doubling in perfusion during DP infusion induced proportionate changes in ENDO and EPI flows (unchanged ENDO/EPI ratio) in group 1 hearts, but increased EPI more than ENDO flows in group 2 hearts (decreased ENDO/EPI ratio). In mildly stenosed regions, a 47 percent increase in perfusion during DP was associated with an increase in only EPI flow, which thereby reduced the ENDO/EPI ratio. In severely stenosed zones, the ENDO/EPI ratio was already significantly reduced at rest and a further reduction in ENDO flow during DP caused a significant decline in the ENDO/EPI ratio. Therefore, during pharmacologic vasodilation, a redistribution of coronary transmural flow occurs (relative ENDO to EPI steal) in non- and mildly stenosed regions while an absolute decrease or steal in ENDO flow was noted only in regions distal to more severe stenoses. These studies suggest that an interaction between the stenosis severity and vasodilation is a determining factor in ENDO/EPI ratios with dipyridamole

Myocardial extraction of technetium-99m-[2-(1-methoxybutyl) isonitrile] in the isolated rabbit heart: a myocardial perfusion agent with high extraction and stable retention

Technetium-99m-[2-(1-methoxybutyl) isonitrile] (MBI) is a potential new compound for the scintigraphic imaging of coronary flow. Evaluation in the blood-perfused isolated rabbit heart model showed this compound to have a myocardial uptake comparable to 201Tl and higher than sestamibi. Although the mean +/- s.d. maximum extraction (Emax) and capillary permeability-surface area product (PScap) of 99mTc-MBI (Emax = 0.45 +/- 0.10, PScap = 1.07 +/- 0.47 ml/min.g) were much less than 201Tl (Emax = 0.71 +/- 0.07, PScap = 2.21 +/- 0.76 ml/min.g, p \u3c 0.0001), the net extraction of 99mTc-MBI (Enet = 0.52 +/- 0.10) was only slightly less than the value for 201Tl (Enet = 0.56 +/- 0.10, p \u3c 0.05). There was no significant difference in the myocardial uptake versus flow between 99mTc-MBI and 201Tl. These data indicate that assessment of relative coronary flow based on the myocardial uptake of 99mTc-MBI should give results comparable to 201Tl. Therefore, 99Tc-MBI may have clinical potential as a radiolabeled myocardial perfusion agent

Reduction in myocardial infarct size at 48 hours after brief intravenous infusion of ATL-146e, a highly selective adenosine A2A receptor agonist

This study was undertaken to determine whether the myocardial infarct-sparing effect of ATL-146e, a selective adenosine A2A receptor agonist, persists without a rebound effect for at least 48 h and to determine the optimal duration of ATL-146e treatment in anesthetized dogs. Reperfusion injury after myocardial infarction (MI) is associated with inflammation lasting 24–48 h that contributes to ongoing myocyte injury. We previously showed that an ATL-146e infusion, starting just before reperfusion, decreased inflammation and infarct size in dogs examined 2 h after MI without increasing coronary blood flow. In the present study, adult dogs underwent 90 min of left anterior descending coronary artery occlusion. Thirty minutes before reperfusion, ATL-146e (0.01 μg·kg−1·min−1; n = 21) or vehicle (n = 12) was intravenously infused and continued for 2.5 h (protocol 1) or 24 h (protocol 2). At 48 h after reperfusion hearts were excised and assessed for histological risk area and infarct size. Infarct size based on triphenyltetrazolium chloride (TTC) staining as a percentage of risk area was significantly smaller in ATL-146e-treated vs. control dogs (16.7 ± 3.7% vs. 33.3 ± 6.2%, P < 0.05; protocol 1). ATL-146e reduced neutrophil accumulation into infarcted myocardium of ATL-146e-treated vs. control dogs (30 ± 7 vs. 88 ± 16 cells/high-power field, P < 0.002). ATL-146e infusion for 24 h (protocol 2) conferred no significant additional infarct size reduction compared with 2.5 h of infusion. A 2.5-h ATL-146e infusion initiated 30 min before reperfusion results in marked, persistent (48 h) reduction in infarct size as a percentage of risk area in dogs with a reduction in infarct zone neutrophil infiltration. No significant further benefit was seen with a 24-h infusion

Pancreatic surgery outcomes: multicentre prospective snapshot study in 67 countries

Background: Pancreatic surgery remains associated with high morbidity rates. Although postoperative mortality appears to have improved with specialization, the outcomes reported in the literature reflect the activity of highly specialized centres. The aim of this study was to evaluate the outcomes following pancreatic surgery worldwide.Methods: This was an international, prospective, multicentre, cross-sectional snapshot study of consecutive patients undergoing pancreatic operations worldwide in a 3-month interval in 2021. The primary outcome was postoperative mortality within 90 days of surgery. Multivariable logistic regression was used to explore relationships with Human Development Index (HDI) and other parameters.Results: A total of 4223 patients from 67 countries were analysed. A complication of any severity was detected in 68.7 percent of patients (2901 of 4223). Major complication rates (Clavien-Dindo grade at least IIIa) were 24, 18, and 27 percent, and mortality rates were 10, 5, and 5 per cent in low-to-middle-, high-, and very high-HDI countries respectively. The 90-day postoperative mortality rate was 5.4 per cent (229 of 4223) overall, but was significantly higher in the low-to-middle-HDI group (adjusted OR 2.88, 95 per cent c.i. 1.80 to 4.48). The overall failure-to-rescue rate was 21 percent; however, it was 41 per cent in low-to-middle-compared with 19 per cent in very high-HDI countries.Conclusion: Excess mortality in low-to-middle-HDI countries could be attributable to failure to rescue of patients from severe complications. The authors call for a collaborative response from international and regional associations of pancreatic surgeons to address management related to death from postoperative complications to tackle the global disparities in the outcomes of pancreatic surgery (NCT04652271; ISRCTN95140761)