Effect of PAR3 versus PAR4 deficiency on thromboplastin-induced pulmonary embolism and death.

Female offspring of PAR3 (A) or PAR4 (B) heterozygote crosses were studied blind to genotype. (A,B) Time from thromboplastin injection to death during a 30-minute observation period. Data are expressed as the fraction of mice alive as a function of time. The number of mice studied for each genotype is indicated at right. The effect of genotype on survival was significant by log-rank test ([A]P < .04; [B] P < .005), and the fraction of Par3^−/−mice andPar4^−/− mice that survived for 30 minutes was significantly greater than the fraction of wild-type mice (+/+) that survived ([A] P < .05; [B] P < .005, χ² test). (C,D) Mice in panel A were perfused with Evans blue 2 minutes after onset of respiratory arrest or at 30 minutes for those mice that survived the study; lungs were then excised, photographed, and scored for perfusion defects. (C) Key for perfusion defect scores. Zero indicates no perfusion defect (entirely blue) and 4 a complete lack of perfusion (entirely pink). (D) Perfusion defect scores by Par3 genotype (mean ± SE). The effect of genotype was significant by one-way analysis of variance (ANOVA), and Par3^+/+ andPar3^−/− groups were different by t test with Bonferroni correction (P < .01). (E,F) Representative histologic sections of lungs ranked with perfusion defect scores of 4 (E) and 0 (F) (genotypes happen to be wild-type in panel E and Par3^−/−in panel F). Note frequent occurrence of occlusive intravascular thrombi in panel E (arrowheads) compared with partially occluded and unobstructed vessels in panel F (arrowheads). Scale bars = 100 μm.