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Biomedical subjects

H Kuida

Publications and source records attributed to H Kuida.

At least 37 records · Page 2Linked to original sources

Familial correlations from genes and shared environment for urine, plasma, and intraerythrocytic sodium.

Spouse-spouse, sib-sib, and parent-offspring correlations were calculated for urinary, plasma, and intracellular sodium levels on over 1,900 persons aged 3-86 years in 98 Utah kindreds. For 36 hours prior to their clinic visit, 31% of the sample was salt-loaded with salt tablets, while the rest followed their normal diet. For those on their normal diet, urine creatine-, age-, and sex-adjusted urinary sodium excretion from a timed 12-hour overnight sample showed similar and significant correlations between spouses (r = .29), sibs less than 20 years old (r = .38), and parent-offspring pairs for offspring less than 20 years old (r = .29). This contrasted with the lower correlations between sibs 20 years of age and older (r = .10) and parent-offspring pairs for offspring 20 years of age and older (r = .13), presumed to live in different households. Adult plasma sodium sib-sib (r = .13) and parent-offspring (r = .15) correlations were similar to the urinary sodium correlations, while the spouse-spouse (r = .48), the sib-sib (r = .64), and the parent-offspring (r = .63) correlations for those presumed to live in the same household nearly doubled. Intracellular sodium correlations for the adult sibs (r = .32) and offspring (r = .36) were over twice as large as for urinary or plasma sodium, although the spouse-spouse correlation (r = .37) remained large also.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Evidence that men with familial hypercholesterolemia can avoid early coronary death. An analysis of 77 gene carriers in four Utah pedigrees.

To study the genetic influence on serum cholesterol levels and early coronary heart disease, 1,134 individuals were screened from 18 Utah pedigrees. In most pedigrees, serum cholesterol appeared to be a purely polygenic trait, with 54% heritability. In four pedigrees with dominant familial hypercholesterolemia, male heterozygotes had a mean serum cholesterol level of 352 mg/dL, myocardial infarction at an average age of 42 years, and coronary death at an average age of 45 years. An informative pedigree structure allowed the identification of four ancestral males born before 1880 who carried this lethal gene and survived to ages 62, 68, 72, and 81 years. This suggests that some healthy life-style factors protected these men against the expression of a gene that has led to coronary disease by age 45 years in all of their heterozygous great-grandsons. One heterozygote showed a drop in serum cholesterol level from 426 to 248 mg/dL, with strict adherence to a low-fat diet without drugs. These observations should help encourage physicians to try harder to identify and help such individuals.

Adult↗

Factor analysis suggesting contrasting determinants for different blood pressure measurements.

A multiple regression analysis was performed on statistically independent factors derived from blood pressure measurements and possible predictive variables in 618 Utah adults. Nine blood pressure factors obtained in a previous study composed the dependent variables; 35 anthropometric, questionnaire, and biochemical variables were reduced by factor analysis to 10 factors and used as independent variables. Body size and obesity had significant independent effects on different types of blood pressure: body size correlated most highly with systolic blood pressure, while obesity correlated most highly with sitting diastolic blood pressure measurements. Smoking did not correlate with sitting blood pressure but did show a significant positive correlation (after controlling for obesity) with tilt and supine diastolic pressure. Alcohol consumption correlated positively with sitting diastolic pressure when the effects of body size and obesity were controlled. No correlations were found between urinary potassium or sodium excretion and any blood pressure factors, but a significant positive correlation was seen between plasma sodium concentration and several different types of diastolic blood pressure measurements. Psychological stress showed a significant independent positive correlation with systolic blood pressure measurements that was strongest in adults over 35 years of age. The multiple correlation values for the multiple regression equations ranged from 0.19 to 0.52.

Adolescent↗

Effects of household sharing on high density lipoprotein and its subfractions.

Household effects accounted for significant proportions of the observed variance of high density lipoprotein cholesterol (HDL-C) and subfractions HDL2 and HDL3. It was found that 19.3% of HDL-C variance could be attributed to a juvenile sib effect (under age 18); 17.4% of HDL2 variance could be attributed to a sib effect (of any age); and 22.1% and 32.6% of the HDL3 variance could be attributed to a parent-offspring effect and a sib effect (of any age), respectively. In addition, additive genetic effects accounted for 56.5%, 37.3%, and 28.3% of the variances of HDL-C, HDL2, and HDL3, respectively. These are maximum likelihood estimates obtained using a variance components model on 2,149 HDL-C levels measured on members of 54 Utah pedigrees, and 337 HDL2 and HDL3 levels measured on a subset of 14 pedigrees.

Adult↗

The relationship of lithium-potassium cotransport and the passive lithium leak to hypertension in Utah subjects.

Rate constants for lithium-potassium cotransport (kLPC) and the lithium efflux into MgCl2 with furosemide (passive lithium leak) along with sodium-lithium countertransport (SLC) were measured in erythrocytes from 351 normotensive adults age 18 and over, 220 youth under age 18 and in 27 hypertensives. The kLPC was significantly higher in the hypertensives than the adult normotensives with means and standard deviations of 13.9 +/- 9.2 vs. 8.7 +/- 5.9 10(-3)/hr (p less than 0.01). Adjusting for the significant weight (p = 0.014) and sex (p = 0.066, normotensive males higher than females) associations with kLPC in an analysis of covariance, increased the significant difference between the hypertensives and normotensives (p = 0.0004). The passive lithium leak rate constant was also higher in hypertensives than normotensives (20.2 +/- 7.6 vs. 15.5 +/- 5.3 10(-3)/hr, p less than 0.01). Weight (p=0.0003), but not sex, was related to the leak but did not account for the difference between hypertensives and normotensives (p = 0.0009). Mean blood pressure was positively associated with the lithium leak but not the kLPC or SLC values in a multivariate regression.

Adolescent↗

Effect of coronary vasodilation on ventricular fibrillation threshold: role of exogenous vasodilators and perfusion conditions.

Even without myocardial ischemia, coronary blood flow (CBF) constitutes a major determinant of ventricular fibrillation threshold (VFT). To clarify whether abnormal distribution of normal or increased CBF plays any additional role, 14 open-chest chloralose-anesthetized dogs with fixed-normalized heart rate, cardiac output, and systemic arterial pressure and separate servocontrolled left main coronary artery perfusion were studied as follows: VFT was determined first with coronary perfusion pressure (CPP) set at systemic level (80 mm Hg). Then CBF index was fixed at control levels (134.0 +/- 9.5 ml/min X 100 gm-1 LV) and coronary vasodilation was induced by intracoronary infusion of adenosine until CPP decreased to 49.0 +/- 2.0 mm Hg. Myocardial O2 consumption, LV pressure, LV dp/dt, and surface ECG remained unchanged. However, VFT decreased in all trials by about 45% (p less than 0.001). When CPP was reset to 80 mm Hg while maintaining vasodilation, CBF index increased by 90% to 255.4 +/- 15.4 ml/min X 100 gm-1 LV and VFT by 26% (p less than 0.005) from control. Yet these VFT increases in response to intraluminal pharmacologic vasodilation were about 19% (p less than 0.002) lower than expected for similar CBF index increases occurring physiologically. We conclude that intraluminal coronary vasodilation not matched by appropriate CBF increase results in substantial decrease of VFT. Moreover, at comparable increase of CBF, spontaneous physiologic vasodilation is more effective than intraluminal pharmacologic coronary vasodilation in increasing VFT.

Adenosine↗

Sodium-lithium countertransport in erythrocytes of hypertension prone families in Utah.

Sodium-lithium countertransport was measured in July 1980-December 1982 in 841 persons from 48 Utah families prone to hypertension. Mean countertransport in 54 hypertensive adults (0.32 +/- 0.01 standard error of the mean) was significantly higher than in 511 normotensive adults (0.26 +/- 0.005, p less than 0.001) but with much overlap between the two groups. This difference was observed in both men and women. Only 26% of the subjects with essential hypertension had values above 0.40 (considered "high" by most other published reports). High values were seen in only 2% of 276 youths under age 18 years in contrast to 11% of the normotensive adults (p less than 0.001). Among normotensive adults, countertransport was higher in men than women, and correlated with weight, diastolic blood pressure, and age (all significant at p less than 0.01). None of these findings were seen in youths. In multivariate analyses, only weight continued to be significantly correlated with countertransport. The difference between countertransport levels in hypertensive vs. normotensive adults remained significant even after adjusting for weight. While confirming other reports of higher mean sodium-lithium countertransport in persons with essential hypertension, this study shows much overlap of values between groups and potential confounding effects of weight. When the authors compared their results with studies that show little overlap between hypertensive and normotensive adults, they found that the data for the normotensive adults in this study are similar to those reported in the other studies, but that the hypertensive adults include a larger percentage of individuals with low countertransport values.

Adolescent↗

Dependence of ventricular fibrillation propensity on coronary blood flow without myocardial ischemia.

Ventricular fibrillation threshold (VFT) changes have been linked to coronary blood flow (CBF) in the context of CBF reduction and subsequent myocardial hypoxia. To clarify the effect of CBF on VFT in the absence of myocardial hypoxia, 18 open-chest pentobarbital-anesthetized dogs with uniformly controlled heart rate, cardiac output, and mean systemic arterial pressure (SAP) were studied as follows: CBF, coronary sinus O2 content (CcsO2), and thereby myocardial O2 consumption were continuously monitored. Baseline VFT determined by the single stimulus scanning technique was 33.0 +/- 3.9 mA. Initial values of CBF index (I) and VFT (n = 18) were positively correlated (VFTmA = 0.8 +/- 0.245 . CBFI ml/min . 100g-1LV; r = 0.60, p less than 0.01). Stepwise CBFI increments up to five times in excess of initial 131.5 +/- 9.7 ml/min . 100g-1LV were then induced by changing in random order. SAP (n = 10), left coronary perfusion pressure (n = 7), and arterial O2 content (n = 10) with VFT determined at each step; CcsO2 remained above 5.5 vol% while CBFI and VFT changes were positively correlated, and mean weighted slope of VFTmA = 16.6 +/- 0.103 . CBFI ml/min . 100 g-1Lv (r = 0.82, p less than 0.05). Systemic or coronary perfusion pressure and arterial or coronary sinus O2 content did not appear to affect VFT independently. It is concluded that even in the absence of myocardial hypoxia, CBF itself is a major determinant of VFT and thereby of innate arrhythmogenic propensity.

Animals↗

Absence of clinical pulmonary edema despite elevated wedge pressures.

Pulmonary hemodynamic data were collected for 116 patients with a resting mean pulmonary artery wedge pressure of 25 mm Hg or greater who underwent exercise during cardiac catheterization without showing acute pulmonary edema. While the mechanism for the absence of evidence of pulmonary edema with pulmonary artery wedge pressure in excess of plasma oncotic pressure is unclear, presumably, it relates to compensatory changes in the structure and function of the pulmonary capillaries, alveolar wall, and lymphatic drainage capacity.

Adult↗

Effect of arterial pressure on left ventricular O2 consumption, coronary blood flow, and reserve capacity following coronary occlusion.

The effect of mean systemic arterial pressure (SAP) on myocardial O2 consumption (MVO2) coronary blood flow (CBF) and the reduction of left ventricular (LV) reserve capacity resulting from coronary artery occlusion was studied in 25 open-chest pentobarbital anesthetized dogs with fixed cardiac output and controlled heart rate (HR) and SAP. In all animals, baseline MVO2 and CBF were obtained and LV reserve capacity was determined by identifying the HR and SAP level which raised mean left atrial pressure to 12 mm. Hg. After uniform placement of a pericoronary snare, the dogs were randomized to five equal groups, and SAP was set at 40, 70 (two groups), 100, and 130 mm. Hg. MVO2 and CBF were redetermined and the coronary artery was ligated in all except one group (70 mm. Hg) which served as sham control. thirty minutes after coronary occlusion, MVO2, CBF, and LV reserve capacity were determined again. Percent of nonperfused myocardium did not differ among groups (27.6 +/- 1%). MVO2 bore a linear relationship to SAP setting wheras CBF bore a curvilinear relationship. Coronary occlusion did not modify these relationships. Significant, but similar decreases in tolerated HR (23.1 +/- 4.7 min.-1) and SAP (41.9 +/- 6.2 mm. Hg) from control values were observed in all four groups regardless of SAP setting. We concluded that the impact of coronary ligation on MVO2, CBF, the loss of functional reserve capacity, and possibly the extent of ischemic injury of the left ventricle, is not modified by afterload changes. However, optimal O2 supply-to-demand ratio appears at SAP of about 100 mm. Hg.

Analysis of Variance↗

Comparative effect of counterpulsation and bypass on left ventricular myocardial oxygen consumption and dynamics before and after coronary occlusion.

In this preparation counterpulsation effect was found equivalent to 42 +/- 7% of complete left ventricular bypass before, and 46 +/- 9% post-coronary occlusion. We conclude that counterpulsation is effective mainly by reducing a major determinant of myocardial oxygen consumption, i.e., afterload, whereas left ventricular bypass by reducing primarily preload results in secondary afterload reduction when peripheral resistance is unchanged. At the higher left ventricular bypass levels, reduction of myocardial oxygen consumption is far greater than during balloon counterpulsation. Acute functional loss of myocardium does not alter the effect of these assist methods regarding the reduction of myocardial oxygen consumption. Whether selection of either method for clinical application should be made only on the basis of its capability for reduction of myocardial oxygen consumption remains to be justified by conclusive demonstration of beneficial effect of reduction of myocardial oxygen consumption in the specific circulatory disorders.

Animals↗

Endotoxin-induced prostaglandin E and F release in dogs.

Prostaglandin E and F (PGE and PGF) levels in sequential blood samples obtained simultaneously from the renal and portal veins and aorta during endotoxin shock in dogs were determined by radioimmunoassay. Four groups of dogs were studied. In five control dogs in which no endotoxin was given, PGE and PGF levels did not change significantly at 0, 15, 30, 60, and 90 min. In eight dogs given endotoxin alone, PGE and PGF levels did not change in the aorta. In samples taken from the portal vein there was a significant rise in PGE and PGF 15 min after endotoxin, whereas renal vein PGE and PGF did not become significantly elevated until 60 and 90 min after endotoxin. In six dogs pretreated with acetylsalicylic acid and six dogs pretreated with indomethacin, PGE and PGF levels did not change after endotoxin. Indomethacin modified the delayed hemodynamic effects of endotoxin whereas acetylsalicylic acid did not. Neither drug blocked the immediate hemodynamic effects of endotoxin. Endotoxin-induced PGE and PGF release is probably due to increased synthesis. The mechanism whereby synthesis is stimulated and the extent to which vasomotor tone is influenced by PGE and PGF during endotoxin shock cannot be determined from our data.

Animals↗

Prostaglandin F and E levels during endotoxin-induced pulmonary hypertension in calves.

Prostaglandin F and E (PGF and PGE) concentrations in sequential blood samples obtained simultaneously from the pulmonary artery (PA) and pulmonary vein (PV) during endotoxin-induced pulmonary hypertension in calves were determined by radioimmunoassay. Three groups of calves were studied. In nine control calves in which no endotoxin was given PA pressure and PGF and PGE concentrations in four pairs of samples taken at 0, 5, 15, and 45 min did not change. In 17 calves given 1 mg E. coli endotoxin, PGF concentrations were increased significantly in the PV and to a lesser degree in the PA in the 15-and 45-min samples. The increased PGF concentration in the 15-min sample corresponded to an increased PA pressure of 74 plus or minus 4 mmHg (mean plus or minus SE). In three of the endotoxin-treated calves studied a second time and three separate calves indomethacin pretreatment completely blocked the hemodynamic effect of endotoxin as well as PGF release. PGE concentrations did not change in either group. These data suggest that endotoxin-induced pulmonary hypertension may be mediated by PGF, a known pulmonary pressor agent in the bovine, and that blockade of this effect by indomethacin may be due to inhibition of prostaglandin synthesis and/or release.

Animals↗