We assessed limit to cardiac compensation during isovolemic hemodilution (HD) in 14 anesthetized dogs. Radioactive microspheres were used to evaluate myocardial blood flow (MBF) and its transmural distribution (endo/epi). Myocardial O2 consumption (MVO2) and percent lactate extraction were determined. Coronary vasodilator reserve was assessed from reactive hyperemic responses. Dogs were divided into group 1, with intact left anterior descending coronary artery (LAD), and group 2, with critical stenosis of LAD. Measurements were obtained at baseline and during graded HD (Hespan) until cardiac failure (CF). CF occurred at lower hematocrit in group 1 compared with group 2 (9 +/- 1 vs. 17 +/- 1%). In group 1, MBF increased during HD to maintain MVO2 constant; increases in MBF were transmurally uniform until CF, when decreased endo/epi and lactate production suggested subendocardial ischemia. Coronary vasodilator reserve decreased progressively during HD and was absent at CF. In group 2, stenotic LAD demonstrated constant MBF (resulting in decreased MVO2) during HD. At CF, these responses along with reduced endo/epi and lactate production indicated local myocardial ischemia. We conclude that 1) with normal coronary circulation, cardiac function was well maintained over a wide range of hematocrits because increases in MBF were transmurally uniform and sufficient to maintain myocardial oxygenation: CF occurred during extreme HD when MBF became maldistributed, resulting in subendocardial ischemia; 2) critical coronary stenosis impaired coronary vascular adjustment to HD and reduced significantly tolerance of left ventricle to HD; and 3) present findings underscore the importance of recruitment of coronary vasodilator reserve in preserving total and regional myocardial oxygenation during HD.
The efficacy and safety of losartan and valsartan were evaluated in a multicenter, double-blind, randomized trial in patients with mild to moderate essential hypertension. Blood pressure responses to once-daily treatment with either losartan 50 mg (n = 93) or valsartan 80 mg (n = 94) for 6 weeks were assessed through measurements taken in the clinic and by 24-hour ambulatory blood pressure monitoring (ABPM). Both drugs significantly reduced clinic sitting systolic (SiSBP) and diastolic blood pressure (SiDBP) at 2, 4, and 6 weeks. Maximum reductions from baseline in SiSBP and SiDBP on 24-hour ABPM were also significant with the two treatments. The reduction in blood pressure was more consistent across patients in the losartan group, as indicated by a numerically smaller variability in change from baseline on all ABPM measures, which achieved significance at peak (P = .017) and during the day (P = .002). In addition, the numerically larger smoothness index with losartan suggested a more homogeneous antihypertensive effect throughout the 24-hour dosing interval. The antihypertensive response rate was 54% with losartan and 46% with valsartan. Three days after discontinuation of therapy, SiDBP remained below baseline in 73% of losartan and 63% of valsartan patients. Both agents were generally well tolerated. Losartan, but not valsartan, significantly decreased serum uric acid an average 0.4 mg/dL at week 6. In conclusion, once-daily losartan 50 mg and valsartan 80 mg had similar antihypertensive effects in patients with mild to moderate essential hypertension. Losartan produced a more consistent blood pressure-lowering response and significantly lowered uric acid, suggesting potentially meaningful differences between these two A II receptor antagonists.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.