Noninvasive evaluation of microcirculatory hemodynamic changes during hemorrhage followed by saline or blood transfusion.

The purpose of the study was to examine the ability of a system combining laser Doppler flowmetry (LDF), photoplethysmograph (PPG), and transcutaneous oxygen tension (tc-PO2) to follow changes in the microcirculation during hemorrhage and following blood or saline return, and to test the hypothesis that such changes precede and might predict changes in the systemic blood pressure. Measurements were performed on the skin of anesthetized rabbits (n = 10) during mild (0-8%), moderate (9-24%), and severe (25-30% of blood volume) hemorrhage, and following complete volume restitution by blood or saline. We found the following: 1) hemorrhage caused typical changes in the LDF, PPG, and tc-PO2 signals that could be formulated by mathematical models, 2) these signals identified blood as being more efficient than saline for volume restitution following hemorrhage, and 3) microcirculatory changes precede and might predict systemic hemodynamic events.

Beneficial effect of nitroglycerin on arterial rethrombosis after thrombolysis. Results from a rabbit thrombosis model.

BACKGROUND: Although nitroglycerin (NTG) is commonly administered to patients with acute myocardial infarction, its effect on concomitant thrombolytic therapy has not been fully elucidated. We examined whether NTG administration further optimizes thrombolysis with rt-PA, combined with aspirin and heparin. METHODS AND RESULTS: Blood clots were produced in a rabbit femoral artery with endothelial damage and distal stenosis. rt-PA was administered in repeated bolus i.v. injections of 0.3 mg.kg-1 every 10 min for 50 min. Femoral artery flow was measured continuously for 2 h. Fourteen rabbits were randomized into two groups (group A and B), both receiving aspirin (i.v. 17 mg.kg-1) and heparin (i.v. 200 units.kg-1) prior to the first rt-PA bolus injection. NTG was administered in group B only, 10 min prior to the first rt-PA bolus, at 10 micrograms.kg-1.min-1 for 130 min. Reperfusion at the end of the 120 min observation period occurred in 5/7 group A and 6/7 group B rabbits (P = ns). In 3/7 group A rabbits, re-flow was achieved but persistent re-occlusion subsequently developed in 1/3 and oscillatory re-flow and re-occlusion cycles (cyclic re-flow) with subsequent patency developed in the remaining two rabbits. These flow patterns were not observed in any of group B rabbits. Overall patency duration was significantly prolonged with NTG (group B; 578/840 min) compared to controls (group A; 258/840 min) (P < 0.001). The mean recanalization time (group A; 30.8 +/- 9.3 vs group B; 22.5 +/- 4.7 min, P = 0.16) as well as mean rt-PA boluses needed to achieve complete recanalization (group A; 4.3 +/- 0.7 vs group B; 3.3 +/- 0.6 boluses/rabbit, P = 0.3) did not differ between groups. However, NTG infusion was associated with increased restored femoral flow following recanalization (expressed as % of stenotic flow value over observation time) compared to control group (P = 0.025 by repeated measures ANOVA). CONCLUSION: Adding NTG to a thrombolytic regimen with rt-PA, aspirin and heparin increases the magnitude of restored flow and total patency duration following recanalization in a rabbit model of arterial thrombosis.

Failure of captopril to attenuate myocardial damage, neutrophil accumulation, and mortality following coronary artery occlusion and reperfusion in rat.

Captopril, a sulfhydryl-containing angiotensin-converting enzyme inhibitor, has been suggested as possessing antiischemic and antiinflammatory properties. To test the hypothesis that captopril may prevent neutrophil-induced myocardial injury during acute myocardial infarction (AMI), the authors subjected rats to coronary occlusion for thirty minutes and reperfusion for twenty-four hours (MI) or to sham operation (sham MI). Oral captopril (100 mg/kg) or vehicle was administered thirty minutes before coronary occlusion. The effect of captopril on mean arterial blood pressure was assessed in separate group of animals (n = 8). Infarct size and neutrophil accumulation in myocardium were determined by measuring creatine phosphokinase depletion and myeloperoxidase (MPO) activity, respectively, in the left ventricular free wall (LVFW). Animals treated with 100 mg/kg of captopril exhibited significant reduction in mean arterial blood pressure compared with vehicle-treated animals (P < 0.01). Compared with vehicle-treated animals, administration of 100 mg/kg of captopril to MI animals attenuated neither twenty-four-hour mortality (56% vs 52%, respectively), nor infarct size (36 +/- 7% vs 34% +/- 7% respectively), nor MPO activity (1.0 +/- 0.17 vs 1.26 +/- 0.19). Thus, in the present experiment captopril did not reduce neutrophil-induced myocardial damage following coronary occlusion and reperfusion. These findings may be partly explained by the negative effect of captopril on arterial blood pressure during AMI.