We scrutinized the recently reported correlation between the canine left ventricular systolic pressure-volume area (PVA) and cardiac oxygen consumption rate per beat (Vo2) by use of an improved method of Vo2 assessment. PVA is the specific area in the pressure-volume (PV) plane bounded by the end-systolic and end-diastolic PV lines and the systolic segment of the PV loop. Different from the previous study in which Vo2-PVA data from isovolumic and ejecting contractions were pooled for analyses, we analyzed Vo2-PVA data from the two different modes separately to examine whether there was any difference of Vo2-PVA relationship between them. The results indicated that the linear regressions of Vo2 on PVA were virtually the same for isovolumic and ejecting contractions. The regression line was Vo2 (ml O2/beat) = a[PVA (mmHg x ml x beat-1)] + b, where a = 1.64 (+/- 0.12 SE) X 10(-5) (ml O2/beat)/(mmHg x ml x beat-1) and b = 0.015 +/- 0.002 ml O2/beat in 10 hearts. We conclude that PVA serves as a reliable predictor of Vo2 regardless of the mode of contraction in a given left ventricle with a stable inotropic background.

We report a case of haemophilia A with a high responding inhibitor of factor VIII (FVIII) who had a serious retroperitoneal haematoma caused by penetration of a duodenal ulcer. Inhibitor-bypassing therapy was commenced immediately on admission. On the 17th day of treatment with activated prothrombin complex concentrate (APCC; FEIBA, re-bleeding occurred and thrombelastography (TEG) demonstrated resistance to therapy. Treatment was changed to recombinant activated factor VII (rFVIIa; NovoSeven and resulted in clinical improvement together with an improvement in TEG parameters. On the 10th day of continuous infusion with NovoSeven, however, TEG again showed resistance to therapy. FEIBA infusions were re-introduced and TEG results remained satisfactory for 7 days. On day 34, however, further retroperitoneal bleeding was evident and a decline in the haemostatic efficiency of FEIBA was recorded by TEG. NovoSeven was again successfully administered for 7 days. There were no laboratory findings to indicate disseminated intravascular coagulation (DIC), hypercoagulability or abnormal fibrinolysis. The plasma-based clotting tests did not show any additional prolongation on the occasions when the TEG demonstrated unresponsiveness to FEIBA or NovoSeven. These findings suggested that some component of whole blood, other than plasma might have governed the TEG data. The long-term use of APCC such as FEIBA or rFVIIa, requires careful monitoring in terms of FVIII inhibitor bypassing activity as well as the tendency to DIC.

Left ventricular systolic pressure-volume area (PVA) has been reported to be a reliable predictor of cardiac oxygen consumption rate per beat (VO2) in a given heart with a stable inotropic background. PVA is the specific area in the pressure-volume (PV) diagram, consisting of the area (EW) within the PV loop and the area (PE) bound by the end-systolic and end-diastolic PV lines and the relaxation segment of the PV loop. EW and PE correspond to the external mechanical work and the end-systolic elastic potential energy in the ventricular wall, respectively. We determined the optimal combination of EW and PE for the best prediction of VO2, using the linear multiple regression analysis. From EW, PE, and VO2, data of many isovolumic and ejecting contractions, the optimal coefficients of EW and PE were 1.67 +/- 0.43 (SD; 7 hearts) and 1.74 +/- 0.49 (10(-5) ml O2/mmHg . ml), virtually identical to each other, corroborating that PVA, i.e., a simple sum of EW and PE, can reliably predict VO2 of a given heart in a stable contractile state.

SUMMARY Left ventricular systolic pressure-volume area (PVA) has been found to be highly linearly correlated with cardiac oxygen consumption rate per beat (Voi) in a given canine heart with a stable inotropic background. PVA is a specific area in the pressure-volume (P-V) diagram that is bounded by the end-systolic and end-diastolic P-V relationship lines and the systolic segment of the P-V loop, consisting of the sum of external mechanical work and what Is considered the end-systolic elastic potential energy in the ventricular wall. In this study, we compared VOi's of steady state entirely isovolumic and variously ejecting contractions that were made to have equal PVA's in the canine left ventricle. We found that Voj's of these Isovolumic and ejecting contractions with equal PVA's (isovolumic vs. ejecting -1008 ± 64 (SB) vs. 1022 ± 62 mm Hg ml/beat, n = 32 pairs in 10 hearts) were equal to each other (0.0376 ± 0.0021 vs. 0.0368 ± 0.0021 ml Oi/beat) regardless of the marked differences in stroke volume (0 vs. 9.8 ± 0.6 ml), end-diastolic volume (20.3 ± 0.8 vs. 23.7 ± 0.9 ml), end-systolic volume (20.3 ± 0.8 vs. 13.9 ± 0.7 ml), peak pressure (123 ± 5 vs. 88 ± 5 mm Hg), stroke work (0 vs. 636 ± 36 mm Hg ml/beat), and calculated peak total wall force (1688 ± 77 vs. 1077 ± 72 g). Therefore, we conclude that PVA can serve as a reliable predictor of Vo» in a given canine left ventricle with a stable inotropic background whether the contraction mode is isovolumic or ejecting. Circ Res 49:1082-1091, 1981 MANY cardiodynamic variables and indices have been proposed as primary determinants of cardiac oxygen consumption (Braunwald et aL, 1976;Gibbs, 1978; Gibbs and Chapman, 1979). However, none of them alone or appropriately combined so far can consistently serve as a reliable predictor of cardiac oxygen consumption rate per beat (V02) under a variety of cardiac loading conditions. Even peak wall force of the ventricle, which has been widely accepted as the most important determinant of Vo 2 in a constant inotropic state, cannot uniquely predict V02 of a given contraction because its Vo 2 varies with ventricular ejection at a constant peak wall force (Coleman et al., 1969;Burns and Covell, 1972;Weber and Janicki, 1977).In search of a more reliable predictor of V02, our recent experiments on canine excised cross-circulated hearts have shown that Vo 2 is highly linearly correlated with the left ventricular systolic pressure volume area (PVA) (Suga, 1979;Khalafbeigui et al., 1979;Suga et al., 1981). PVA is a specific area in the pressure-volume (P-V) diagram that is bounded by the end-systolic and end-diastolic P-V relationship lines and the systolic segment of the P-V loop trajectory, as shown in Figure 1. PVA is therefore the sum of two areas; one for the external mechanical work and the other for what is considered the end-systolic elastic potential energy in the ventricular wall (Suga, 1979(Suga, ,1980. PVA can be considered total mechanical energy required for one contraction of the ventricle (Suga, 1979). However, the...

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The process of angiogenesis from aortic segments turned inside out and embedded in collagen gel was studied. Two to three days after inoculation, fibroblastic cells migrated from both ends of the segments. Later, capillary sprouts also appeared from both ends of the segments but not from the outer surface, even though there was a covering of endothelial cells. If the outer surface was injured, capillaries sometimes appeared at the damaged site. This may suggest that endothelial cells have more affinity for basement membrane than collagen gel and that they migrate only from an injured site. Immunohistochemical staining demonstrated factor VIII-related antigen in the capillary structures but not in the fibroblastic cells. Electron microscopically, capillary lumina were lined with several endothelial cells, and fibroblastic cells had the characteristics of smooth muscle cells. Since these fibroblastic cells have been known to appear under angiogenetic conditions in uiuo, they may play an important role in angiogenesis, and the present culture technique may be a useful model for studying this process. ACTA PATHOL JPN 38: 1503 -1512, 1988

To assess oxidative stress (OS) induced by endurance exercise, concentrations of serum reactive oxygen species (ROS) were determined in 70 Japanese male amateur runners completing a two-day ultra-marathon race. Serum ROS levels were analyzed at three time points: before the race (baseline), after the 1st day race (mid-race), and after the 2nd day race (goal) (post-race). The means (SE) of ROS were 151.4(3.7) (U. CARR.), 168.7(4.4), and 156.8(4.4), respectively. Significant positive trends were noted between age and serum ROS concentrations at the three race points (p<0.05 for all). After adjusting for age, BMI and average monthly running distance, the baseline serum ROS concentrations were positively associated with completion times of the first-day race, in particular (p<0.05), suggesting that the concentrations may predict physical performance. The ROS production increased at mid-race (p<0.05), but the levels returned to baseline levels at post-race, indicating that an antioxidant defense system may develop post-race to reduce OS.

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