Alan M. Fujii

Noninvasive determination of systolic, diastolic and end-systolic blood pressure in neonates, infants and young children: Comparison with central aortic pressure measurements

Noninvasive determinations of systolic and diastolic blood pressure using the oscillometric method for pressure measurement were combined with externally recorded axillary pulse tracings to estimate end-systolic pressure in 32 neonates, infants and young children. Results were compared with central aortic pressure measurements made at the time of central aortic catheter placement. Studies were performed in patients aged 1 day to 48 months who weighed 0.9 to 18.1 kg. A wide range of systolic (41 to 141 mm Hg), diastolic (22 to 73 mm Hg) and end-systolic (30 to 111 mm Hg) pressure values were found. The mean absolute pressure differences and percent errors (pressure difference divided by central aortic pressure) were 1.8 mm Hg and 2.5% for systolic, 0.8 mm Hg and 0.8% for diastolic and 1.4 mm Hg and 2.1% for end-systolic pressure. No correlation was noted between percent error and age, weight, heart rate, cardiac index or systemic vascular resistance. The ability to perform reliable noninvasive pressure measurements should prove invaluable for clinical and research purposes. In addition, this method of end-systolic blood pressure determination enables sensitive indexes of left ventricular contractility to be measured noninvasively in small children.

Effect of young age on coronary adaptations to left ventricular pressure overload hypertrophy in sheep

OBJECTIVES This study attempted to determine the effect of young age on changes in coronary conductance and capillary density with left ventricular pressure overload hypertrophy. Mechanisms responsible for age differences in perfusion capacity were examined. BACKGROUND Hypertension in adults causes alterations in the coronary vasculature, resulting in diminished coronary perfusion capacity and myocardial ischemia. These processes are worsened in adults by advanced age. Young age may provide advantages in coronary adaptation to hypertension. METHODS Coronary conductance was examined in conscious chronically instrumented 10-week old lambs and adult sheep with progressive ascending aortic stenosis of 6-weeks duration and age-matched control sheep by means of the microsphere technique and vasodilators. Capillary density was measured post-mortem. RESULTS Adult sheep with aortic stenosis had a decrease in left ventricular subendomyocardial capillary density by 17% and maximal coronary conductance with adenosine by 67%. In the nonhypertrophied right ventricle, maximal coronary conductance was depressed by 47%, whereas capillary density was normal, implying an effect of coronary hypertension on resistance vessels. In contrast, lambs with aortic stenosis maintained normal left ventricular capillary density, maximal coronary conductance and coronary reserve and had relatively little impairment of conductance in the right ventricular coronary bed (-15%, p = NS). Similar responses were found with other vasodilators, isoproterenol and chromonar. CONCLUSIONS Young age confers advantages to coronary adaptation to left ventricular pressure overload, including angiogenesis proportionate to hypertrophy, resulting in normal capillary density and coronary conductance. There is also less hypertension-induced impairment of coronary conductance distinct from the effects of hypertrophy.

Effects of Chronic Heparin Administration on Coronary Vascular Adaptation to Hypertension and Ventricular Hypertrophy in Sheep

BACKGROUND Hypertension decreases myocardial perfusion capacity in adults for several reasons, including insufficient coronary angiogenesis with left ventricular (LV) hypertrophy, arteriolar hypertrophy, and altered vasomotion. Heparin influences growth factors that promote angiogenesis and vasodilation and inhibit arteriolar wall thickening. METHODS AND RESULTS Adult sheep were given heparin 200 U/kg body wt SC twice daily throughout 6 weeks of LV and coronary hypertension from a progressively constricted ascending aortic band (n=14). They were compared with untreated sheep with (n=13) and without (n=13) aortic stenosis. After 6 weeks, maximum myocardial perfusion was measured during adenosine infusion in the conscious state by the microsphere method. Sheep with aortic stenosis had less maximum coronary flow per gram, less conductance reserve, and thicker arteriolar walls in the LV and nonhypertrophied right ventricle. Capillary density decreased in the LV endomyocardium and remained unchanged in the right ventricle. Heparin-treated sheep had significant partial normalization of coronary conductance reserve and maximum perfusion in both ventricles and capillary density in the LV endomyocardium. Arteriolar wall thickness was unchanged. Compared with untreated sheep with aortic stenosis, in heparin-treated sheep LV FGF-2 protein increased 2-fold, whereas FGF-2 mRNA remained unchanged. VEGF mRNA and protein increased 3-fold and 1.4-fold, respectively, whereas TGF-beta(1) mRNA declined 3-fold. CONCLUSIONS Heparin administration during LV hypertension increases heparin-binding angiogenic factors FGF-2 and VEGF in the LV and ameliorates decreases in LV perfusion capacity and capillary density.

Low radiation iridium 191m radionuclide angiography: Detection and quantitation of left-to-right shunts in infants

Radionuclide angiography using iridium 191m was carried out in 34 premature infants and young children for detection and quantitation of left-to-right shunts. Ir-191m has a physical half-life of 4.96 seconds and can be imaged with conventional gamma scintillation cameras. The whole body radiation absorbed dose from Ir-191m is 3.5 mrad/mCi, which is about 40 times less radiation than with technetium 99m. Other advantages of Ir-191m include high photon flux for improved imaging and the possibility of multiple studies within a short period of time without background. Nine patients had simultaneous measurement of pulmonary-to-systemic flow ratio by Ir-191m angiography and oxymetry during cardiac catheterization; the correlation coefficient was 0.90. Radionuclide angiography with Ir-191m is a method with virtually no risk, rapid, accurate, and reproducible, and is ideally suited for the evaluation of left-to-right shunts in small children.

Maturation-dependent differences in regulation of sarcoplasmic reticulum Ca(2+) ATPase in sheep myocardium in response to pressure overload: a possible mechanism for maturation-dependent systolic and diastolic dysfunction.

We have previously demonstrated that pressure-overload hypertrophy in adult sheep is associated with myocardial dysfunction whereas that in young lambs is associated with normal contractility. To probe for possible mechanisms of these age-dependent differences, we assessed mRNA expression of genes encoding critical components of myocardial Ca2+ handling in the same animal model. We studied left ventricular myocardium of young and adult sheep with short-term (48 h) and long-term (6 wk) pressure overload induced by ascending aortic constriction. Six weeks of pressure overload induced the significant left ventricular hypertrophy (36 and 39% increase in left ventricular/body weight ratio in lambs and sheep, respectively). The Ca2+ ATPase and Na+/Ca2+ exchanger mRNA decreased with pressure overload only in the adult (p < 0.05). Ca2+ channel mRNA was slightly increased by pressure overload regardless of age (p < 0.05). Calsequestrin, sarcoplasmic reticulum Ca2+ release channel, or myosin heavy-chain mRNA levels did not significantly differ. In adult sheep after 6 wk of pressure overload, decreases in load-adjusted midwall shortening (systolic dysfunction) and prolongation of relaxation time constant (diastolic dysfunction) correlated with decreases in Ca2+-ATPase mRNA. The sarcoplasmic reticulum Ca2+-ATPase protein level and Ca2+ uptake activity of isolated sarcoplasmic reticulum vesicles were depressed only in the adult with pressure-overload hypertrophy but not in the young. We demonstrated age-dependent differences in mRNA expression of Ca2+-handling protein genes in response to pressure overload, which preceded the occurrence of hypertrophy and myocardial dysfunction. Thus, altered expression of Ca2+-handling protein genes may be one of the primary responses to pressure overload rather than a phenomenon secondary to myocardial hypertrophy.

Radionuclide angiocardiographic assessment of pulmonary vascular reactivity in patients with left to right shunt and pulmonary hypertension

Radionuclide angiocardiography was used to assess pulmonary vascular reactivity in eight patients (nine studies) with a large, relatively unrestrictive intracardiac defect and pulmonary arterial hypertension. Radionuclide angiocardiograms, using technetium-99m pertechnetate, were performed first with the patient breathing room air and then after 10 minutes of breathing a mixture containing 90 percent or more of oxygen. The pulmonary to systemic flow ratios obtained by gamma variate analysis of the radionuclide time-activity curves were compared with those calculated with the Fick principle at the time of cardiac catheterization. There was a good correlation between the two methods both in room air studies (r = 0.88) and in those obtained with 90 percent or more of oxygen (r = 0.94). All six studies (in five patients) with a reactive pulmonary vasculature (judged by a pulmonary vascular resistance at cardiac catheterization of less than 6 units/m2 with oxygen or after tolazoline) had a radionuclide pulmonary to systemic flow ratio of 3.0 or greater with oxygen. The three patients with a nonreactive pulmonary vasculature had a radionuclide pulmonary to systemic flow ratio of 2.3 or less with oxygen, a value that was unchanged from the room air value. These data suggest that radionuclide angiocardiography may be a useful, relatively noninvasive method of assessing pulmonary vascular reactivity in patients with a large, relatively unrestrictive intracardiac defect.

An automated algorithm for radionuclide angiocardiographic quantitation of circulatory shunting

Circulatory shunting may be quantitated by analysis of time-activity curves obtained from radionuclide angiocardiography. A new automated algorithm for performing this analysis is proposed. The algorithm uses mathematical deconvolution techniques to increase the temporal separation of the components of this curve and thereby improves the accuracy of the analysis. The stability of the algorithm to random data errors was assessed by experiments on simulated time-activity curves degraded with pseudorandom noise. Excellent performance was obtained on a set of test problems previously used in the literature. The algorithm was used to quantitate left-to-right shunting in patients undergoing radionuclide angiocardiography during cardiac catheterization. A strong correlation (r = 0.96) was found between pulmonary to systemic flow ratios (Qp:Qs) obtained using the algorithm on radionuclide angiocardiographic data and Qp:Qs values obtained by oximetry at cardiac catheterization.