Biomedical subjects

R A Walsh

Publications and source records attributed to R A Walsh.

At least 145 records · Page 8Linked to original sources

PubMed1988

A comparative trial of digoxin and digitoxin in the treatment of congestive heart failure.

A randomized, crossover, single-blind study compared the efficacy and dosing accuracy of digoxin and digitoxin in 15 ambulatory patients wth congestive heart failure. Loading doses and maintenance doses were calculated according to published equations that adjust for sex, height, and lean body weight (for digitoxin), plus estimated creatinine clearance (for digoxin). At each 2-week visit, serum drug concentrations were measured and compliance with the prescribed regimen was assessed by tablet count. At the end of each study period, a congestive heart failure (CHF) score was determined in a blinded fashion by the same physician. Patient compliance was unusually high (greater than or equal to 80%) at every visit. Therapeutic concentrations were achieved with digoxin and digitoxin in 5 and 14 patients, respectively (p less than 0.05). During digitoxin therapy, CHF scores were lower than pretreatment values (p less than 0.05). The difference between CHF scores during the digoxin and digitoxin periods did not achieve significance (0.05 less than p less than 0.06). Therapeutic serum concentrations can be achieved more easily and frequently with digitoxin than digoxin without compromising the patient's CHF status.

Adult↗

PubMed1988

Radionuclide determination of the relationship between left ventricular contractile state and ejection fraction.

To determine whether the relationship between various measures of left ventricular (LV) contractile state and ejection fraction (EF) is linear in man, we studied 30 patients during right atrial pacing over a range of loading conditions. With the use of micromanometer LV pressures and radionuclide LV volumes, pressure-volume (P-V) loops were generated for each loading condition. Then isochronal, instantaneous P-V data points were obtained by linear regression analysis to attain the maximum slope (Emax) of these time-varying isochrones. Other measures of LV end systole were also used to calculate end-systolic P-V relations in a similar fashion, and indirect P-V relations were obtained from the linear regression analysis of brachial artery peak pressure vs minimum LV volume data points. When the slopes of these LV contractile measures were compared to the radionuclide LV EFs, the linear correlation coefficients ranged from 0.53 to 0.67. After natural log transformation of the LV contractile state and EF data, the correlation coefficients for the polynomial curve fits ranged from 0.80 to 0.88. When the correlation coefficients for the polynomial curve fits of the natural log transformed data were compared to those for the linear regression analyses of the raw data, significant improvements were evident (p less than 0.05). Thus the relationship between various measures of LV contractile state and EF obtained with radionuclide angiography is best approximated by a complex, curvilinear relationship that is due, in part, to the wide range of LV contractile states within the relatively narrow normal range of LV ejection fractions.

Adult↗

PubMed1988

Acute determinants of the hangout interval in the pulmonary circulation.

Previous investigations have suggested that the duration of the hangout interval is determined by long-term alterations in right ventricular systolic loading rather than the length of right ventricular systole. The factor(s) that effect short-term changes in this interval are unknown. Accordingly, we altered pulmonary artery pressure with phenylephrine and nitroprusside to achieve three peak pressures at low, medium, and high levels in each of 10 normal patients. Simultaneous biplane right ventricular volumes, high-fidelity pulmonary artery and right ventricular pressures, and pulmonary artery flow/velocity were obtained at each condition. After pharmacologic autonomic blockade (atropine and propranolol) at a constant heart rate achieved with atrial pacing (93 beats/min), peak pulmonary artery pressures differed significantly at low, medium, and high loading conditions (23 +/- 3 vs 31 +/- 7 vs 42 +/- 6 mm Hg, p less than 0.01). No associated significant change occurred in the preejection period (109 +/- 24 vs 98 +/- 14 vs 106 +/- 21 msec) and right ventricular ejection time (298 +/- 24 vs 318 +/- 23 vs 316 +/- 24 msec). The hangout interval differed significantly at each loading condition (43 +/- 16 vs 34 +/- 13 vs 23 +/- 6 msec, p less than 0.01) and correlated inversely with both the peak pulmonary artery pressure (r = -0.53, p less than 0.01) and the right ventricular end-systolic pressure (r = -0.56, p less than 0.01). In contrast, the hangout interval and right ventricular ejection time were not linearly related.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗

PubMed1988

A microassay for ATPase.

A newly developed microtechnique for quantitating activity of myosin ATPase (EC 3.6.1.32) is more sensitive and less time-consuming than existing spectrophotometric methods. Measurement of ATPase activity using the new method can be accomplished in a final volume of 0.25 ml, allowing the assay to be conducted in individual wells of 96-well microplates commonly used for the enzyme-linked immunosorbent assay (ELISA). The microassay is performed by adding purified myosin to microplate wells followed by addition of ATP to initiate the enzymatic reaction. The reaction is subsequently terminated by addition of an acidic solution containing malachite green and ammonium molybdate. The level of inorganic phosphate produced by enzymatic hydrolysis of ATP is measured by scanning the microplates using a microELISA plate reader. An entire 96-well microplate can be scanned in less than 2 min, and data from the microassay can be transferred directly to a microprocessor for statistical analysis. The microassay is capable of detecting between 0.2 and 3 nmol of inorganic phosphate in a reaction volume of 50 microliter, and the ATPase activity of as little as 10 ng of rat cardiac myosin can be measured. The increased sensitivity compared with that of other spectrophotometric assays and ease of performing the microassay enable a detailed analysis of the enzymatic properties of cardiac myosin to be conducted on large numbers of small tissue specimens. Several kinetic properties of rat cardiac myosin were determined using this technique.

Adenosine Triphosphatases↗

PubMed1988

Application of a time varying elastance model to right ventricular performance in man.

To evaluate instantaneous right ventricular pressure-volume relations we studied nine patients with normal coronary anatomy and ventricular function with simultaneous high fidelity pressure, flow-velocity, and biplane cineventriculographic volumes (60 frames.s-1) during atrial pacing at 93(SD5) beats-min-1, partial autonomic blockade, and pharmacologically altered ventricular loading. The maximum time varying elastance, Emax, was defined as the maximum slope of isochronal, simultaneous pressure-volume data points derived by linear regression analysis from three loading conditions. The slope of the non-isochronal maximum pressure/volume ratio, pressure at minimum volume, end ejection pressure/volume, and peak right ventricular pressure/minimum volume were also derived from the three loading conditions. The mean slope for Emax was 1.30(0.84) mm Hg.ml-1 (range 0.62-2.87) and the volume axis intercept at zero pressure (Vo) was 46(21) ml (range 24-89 ml). Time dependent Emax was characterised by a series of parallel shifting lines of best fit with large changes in Vo in addition to changes in the slope of the pressure volume relations. Only maximum pressure/volume ratio and peak pressure/minimum volume were linearly related to Emax (r = 0.82 and 0.84 respectively, p = 0.05) while pressure at minimum volume and end ejection pressure/volume did not correlate with Emax. We conclude that in normal human subjects (1) right ventricular systolic function may be approximated using a time varying elastance model characterised by a time dependent Vo; (2) end systolic pressure-volume relations using maximum pressure/volume ratio and peak pressure/minimum volume systematically estimate Emax; and (3) other right ventricular end systolic pressure-volume relations near end ejection bear no obvious relation to Emax because of the wide temporal separation between peak systolic elastance and end ejection in this chamber.

Adult↗

PubMed1988

Right ventricular diastolic pressure-volume relations and regional dimensions during acute alterations in loading conditions.

Acute pharmacologically mediated parallel shifts in the left ventricular diastolic pressure-volume relation may be due to the restraining effect of the pericardium and/or leftward displacement of the interventricular septum. The existence and cause of this phenomenon in the right ventricle has not been studied in animals or in man. Accordingly, we altered right ventricular pressure with intravenous phenylephrine (0.2 to 0.3 mg) and nitroprusside (0.5 to 1.5 micrograms/kg/min) to achieve three disparate peak right ventricular pressures in nine normal subjects after partial autonomic blockade with atropine (1 mg) and propranolol (0.15 mg/kg). Simultaneous high-fidelity right ventricular pressures and biplane cineventriculographic volumes were acquired during the three resultant loading conditions. Right atrial pacing maintained heart rate constant at each pressure level. Peak right ventricular systolic pressure (23 +/- 3 vs 31 +/- 9 vs 45 +/- 6 mm Hg, all p less than .01) and right ventricular end-diastolic pressure (4 +/- 2 vs 8 +/- 4 vs 11 +/- 3 mm Hg, all p less than .01) were significantly different at low, medium, and high loading conditions, respectively. Right ventricular diastolic pressure-volume relations were, in parallel, shifted upward with altered loading in each patient. This was manifest by an unchanged dynamic chamber stiffness constant and a significant increase in the diastolic pressure volume y intercept at each load (1.98 +/- 2.21 vs 5.33 +/- 5.39 vs 8.51 +/- 3.99 mm Hg, p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Ventricular/vascular coupling and regional arterial dynamics in the chronically hypertensive baboon: correlation with cardiovascular structural adaptation.

Ventricular/vascular coupling dynamics and regional hemodynamics of five hypertensive baboons with concentric left ventricular (LV) hypertrophy (mean arterial pressure +/- SD, 148 +/- 16 mm Hg; LV mass/body weight ratio 3.42 +/- 0.8) were compared with five normotensive controls (mean arterial pressure 89 +/- 3 mm Hg; LV mass/body wt ratio 2.73 +/- 0.5) at different mean arterial pressures. Ventricular/vascular dynamics were assessed by aortic input impedance, pulsatile/total power ratio, effective arterial elastance and compliance from a three-element Windkessel "lumped" model of the circulation. Regional arterial dynamics were assessed by pulse-wave velocities and local reflection coefficients. Systemic arterial compliance was similarly decreased with elevated pressure in both groups but was significantly more reduced for the hypertensive group compared with control animals at control (0.49 +/- 0.16 vs. 0.96 +/- 0.09 ml/mm Hg; p less than 0.05) and acutely lowered arterial pressure (0.62 +/- 0.26 vs. 1.41 +/- 0.24 ml/mm Hg, respectively). Changes in compliance were paralleled by differences in effective arterial elastance derived from cineventriculographic pressure-volume ratios. Regional foot-foot and apparent phase pulse-wave velocities were significantly increased for distal aortic segments of the hypertensive animals during elevated pressures compared with controls (cff, 17.5 +/- 7.5 vs. 8.7 +/- 3.0 m/sec; p less than 0.05). Histology of the aorta revealed significant increases in collagen content (microgram/mg dry wt) from proximal to distal aortic segments (27 +/- 2 vs. 38 +/- 6; p less than 0.005) in hypertensive animals but not in controls (27 +/- 2 vs. 32 +/- 6; NS). With pharmacological normalization of systemic arterial pressures, hypertensive baboons developed aortic wave speeds similar to controls but manifested significantly reduced compliance compared with controls. In contrast, with acute elevations of pressure, systemic arterial aortic compliances were similar for both groups, but distal pulse-wave velocities were significantly increased for hypertensive animals compared with controls. We conclude that measures of ventricular/vascular coupling and arterial dynamics are determined by both the level of arterial pressure and the physical characteristics of the cardiovascular system in chronic systemic hypertension and pressure overload ventricular hypertrophy.

Adaptation, Physiological↗

PubMed1988

Assessment of the radionuclide angiographic left ventricular maximum time-varying elastance calculation in man.

This investigation was designed to determine whether left ventricular (LV) maximum time-varying elastance (Emax) calculations obtained using equilibrium radionuclide angiography (RNA) were comparable to those obtained using biplane contrast cineangiography (CINE), and whether simple, indirect P-V relations might provide reasonable, alternative estimates of Emax. Accordingly, we studied 19 patients with simultaneous high-fidelity micromanometer LV and fluid brachial artery (Ba) pressure recordings, CINE, and RNA under control conditions and during methoxamine and nitroprusside infusions. Emax was defined for CINE and RNA as the maximum slope of the linear relation of isochronal, instantaneous P-V data points obtained from each of the three loading conditions. The indirect P-V relations were similarly obtained from Ba peak (P) pressure versus minimum RNA LV volume (BaP/minV) and Ba dicrotic notch (di) pressure versus minimum RNA LV volume (Badi/minV) data points. The mean heart rates and LV (+)dP/dtmax values were minimally altered during the three loading conditions. The isochronal Emax values ranged from 1.40 to 6.73 mmHg/ml (mean 4.13 +/- 1.99 s.d. mmHg/ml) for CINE and from 1.48 to 7.25 (mean 4.35 +/- 1.81 mmHg/ml) for RNA (p = N.S.). Similarly, the unstressed volumes ranged from -10 to 80 ml (mean 30 +/- 23 ml) for CINE and from -8 to 77 ml (29 +/- 21 ml) for RNA (p = N.S.). The individual, isochronal Emax values by RNA correlated with those by CINE (r = 0.86). In 14 of the 19 patients, the BaP/minV and Badi/minV relations correlated with the isochronal Emax values calculated by RNA (r = 0.83 and 0.82, respectively), and these relations also correlated with the Emax values calculated by CINE (r = 0.82 and 0.78, respectively). The slope and V0 values for the BaP/minV and Badi/minV relations underestimated those for Emax by RNA and CINE (p less than 0.01 and p less than 0.05, respectively, for both). Thus, the isochronal Emax values calculated using RNA are comparable to those obtained using CINE in man. Moreover, indirect P-V relations underestimate these Emax values, but they are linearly related with the isochronal Emax values calculated by RNA and CINE. Consequently, these indirect P-V relations may provide a more simple, alternative estimate of LV contractile function in man.

Adult↗

PubMed1987

Experience with calcium antagonist drugs in congestive heart failure.

Several clinical studies have demonstrated beneficial hemodynamic effects of calcium antagonist drugs when used as arterial vasodilators in the treatment of certain patients with moderate to severe congestive heart failure. These drugs usually decrease systemic vascular resistance and improve ejection phase indexes of left ventricular function in such patients. However, calcium antagonists have intrinsic negative inotropic effects and other vasodilators such as nitroprusside, hydralazine and captopril appear to be more beneficial when used in the treatment of severe congestive heart failure.

Calcium Channel Blockers↗

PubMed1987

Cardiovascular effects of the aging process.

An understanding of the effects of aging upon the cardiovascular system assumes greater clinical importance as the population ages. Animal studies demonstrate prolonged tension development, impaired relaxation, and diminished response to receptor-mediated inotropic interventions in the cardiac muscle of senescent animals. Ventricular afterload is augmented at rest and increases during exercise through age-related alterations in peripheral arteries. Increased impedance to ejection may result in the modest concentric left ventricular hypertrophy seen in the elderly. Despite changes in cardiovascular function, resting and exercising cardiac outputs are well maintained in healthy elderly individuals who are free of occult coronary artery disease. The reduction in maximal oxygen consumption appears secondary to altered peripheral oxygen utilization rather than to cardiac causes.

Aged↗

PubMed1987

Value of tomographic thallium-201 imagining in patients with chest pain following coronary artery bypass grafting.

To determine whether thallium-201 washout profile analysis can detect regional myocardial ischemia caused by coronary artery bypass graft occlusion or progression of disease in nonbypassed coronary arteries, 19 consecutive patients with chest pain following bypass grafting were evaluated with coronary arteriography and thallium-201 scintigraphy. Twenty of the 55 coronary artery regions were perfused by an occluded bypass graft or a significantly stenosed (greater than or equal to 70% diameter narrowing) nonbypassed coronary artery, while 35 coronary regions were perfused by patent bypass grafts or insignificantly diseased coronary arteries. The tomographic thallium-201 washout profile results correlated with the bypass graft and coronary arteriographic findings (k = 0.67, P less than 0.001). The sensitivity of tomographic thallium-201 washout profile abnormalities for arteriographic abnormalities was 75%, while the specificity was 86%. The authors conclude that tomographic thallium-201 washout profile analysis may be very useful in the evaluation of patients with chest pain following coronary artery bypass grafting by detecting regional myocardial ischemia caused by occlusion of specific bypass grafts or progression of disease in nonbypassed coronary arteries.

Adult↗

PubMed1987

Nonhuman primate model for regional wave travel and reflections along aortas.

Arterial pulse transmission and wave reflections were studied in five mature anesthetized baboons (Papio anubis) using multisensor micromanometry. Simultaneous pressures were recorded from the left ventricle and every 10 cm along the aorta and its terminal branches, and flow velocity was measured in the aortic root. Aortic input impedance and regional foot-to-foot and apparent phase velocities were calculated. Aortography provided dimensional data for local reflection coefficients. Regional foot-to-foot wave speeds were somewhat lower than corresponding segments in humans. Proximal aortic pressure waveforms and characteristic impedance (110 +/- 29 dyn X s X cm-5) were not characteristic of middle-aged humans. Reflection coefficients at the terminal aortic bifurcation (0.06) at the level of the renal artery branches (0.09) were less than those found in humans. We conclude that the junction of the renal artery branches and the aorta in the baboon is closely matched and represents much less of a discrete reflection site than in humans. Although the baboon may be used to study pulse transmission characteristics in the baboon, this species is not a good model for the proximal systemic reflective characteristics of normal middle-aged humans.

Animals↗

PubMed1987

Frequency-dependent myocardial depression induced by verapamil in conscious dogs.

To determine the effects of calcium entry-blocking drugs on the frequency-dependent rate of peak positive left ventricular pressure development [(+)dP/dtmax] we evaluated the effects of incremental left atrial pacing during verapamil, diltiazem, and nifedipine under equivalent loading conditions in seven conscious preinstrumented mongrel dogs. To eliminate the effects of reflex sympathetic stimulation the animals were pretreated with propranolol (2 mg/kg). Prior to atrial pacing (+)dP/dtmax was similar for verapamil [2,392 +/- 416 (SD) mmHg/s], diltiazem (2,661 +/- 606 mmHg/s), and nifedipine (2,731 +/- 636 mmHg/s), P = NS among drugs. At a common peak paced heart rate (150 beats/min) under equivalent loading conditions, (+)dP/dtmax was significantly reduced from the corresponding preatrial pacing value only after verapamil (2,131 +/- 415 mmHg/s, P less than 0.03) and was significantly lower than after either diltiazem (2,547 +/- 550 mmHg/s) or nifedipine (2,633 +/- 705 mmHg/s, P less than 0.04). No significant linear relation was observed between stimulation frequency and (+)dP/dtmax during atrial pacing alone (slope = -2.2 +/- 1.3, r = -0.30 +/- 0.23, P = 0.12), during atrial pacing with beta-blockade alone (slope = 1.7 +/- 1.5, r = 0.24 +/- 0.25, P = 0.25), or beta-blockade combined with diltiazem (slope = -0.91 +/- 1.3, r = 0.02 +/- 0.23, P = 0.38) or nifedipine (slope = -1.2 +/- 1.3, r = 0.01 +/- 0.23, P = 0.48). By contrast, a significant negative force-frequency relation was seen during incremental atrial pacing after verapamil (slope = -4.1 +/- 1.3, r = -0.80 +/- 0.23, P = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

The relationship of various measures of end-systole to left ventricular maximum time-varying elastance in man.

This investigation was designed to calculate left ventricular maximum time-varying elastance (Emax), to define the relationship between Emax and pressure-volume (P-V) relations at other, more easily defined measured of end-systole, and to determine whether these measures of left ventricular contractile function can be normalized in man. Accordingly, we studied 10 subjects with simultaneous high-fidelity micromanometer left ventricular and ascending aortic pressure recordings and biplane contrast cineangiograms at control conditions and during infusion of methoxamine and nitroprusside. Emax was defined as the maximum slope of the linear relation of isochronal, instantaneous P-V data points obtained from each of the three loading conditions. Left ventricular end-systole was also defined for each loading condition as: the time of the maximum P-V ratio (maxPV), minimum ventricular volume (minPV), (-)dP/dtmin [(-)dP/dtPV], and zero systolic flow approximated by the central aortic dicrotic notch (AodiPV). The mean heart rates and LV (+)dP/dtmax were insignificantly altered during the three loading conditions. Isochronal Emax ranged from 3.38 to 6.73 mm Hg/ml (mean 5.48 +/- 1.23 [SD] mm Hg/ml) and the volume-axis intercepts at zero pressure ranged from -2 to 51 ml (mean 18 +/- 16 ml). The isochronal slope calculations were reproducible (r = .97 to .99). The end-systolic P-V slope values for the maxPV, minPV, (-)dP/dtPV, and AodiPV relations correlated with isochronal Emax (r = .90, .88, .69, and .74, respectively). The average slope values for these end-systolic P-V relations, however, underestimated the mean Emax (p less than .01 to p less than .001). The mean extrapolated volume-axis intercepts for these end-systolic P-V relations also underestimated that for Emax. Finally, the isochronal Emax and other end-systolic P-V relation slope values demonstrated inverse linear relationships with left ventricular mass (r = -.68 to -.91, p less than .05 to p less than .001). Only the Emax volume-axis intercepts showed a linear relationship with left ventricular end-diastolic volume (r = .75). Thus we conclude that the time-varying elastic properties of the left ventricle can be calculated in man, that commonly used end-systolic P-V relations significantly underestimate isochronal Emax, and that normalization of isochronal Emax and other end-systolic P-V relation slope values might be performed in man with left ventricular mass; no obvious relationship between volume-axis intercepts and measures of left ventricular or body size was apparent.

Adult↗

PubMed1987

Load independence of the rate of isovolumic relaxation in man.

This investigation was designed to determine whether the rate of isovolumic left ventricular pressure decline is affected by load in man. Fourteen patients were instrumented with micromanometer left ventricular and right atrial pacing catheters to maintain a constant heart rate during control conditions and infusion of methoxamine or nitroprusside. The isovolumic relaxation period was defined as the time from peak (-)dP/dt to 5 mm Hg above left ventricular end-diastolic pressure of the following beat. The rate of isovolumic relaxation was calculated as time constants (Tau) from the linear regression of natural log pressure vs time (Tln) and instantaneous (-)dP/dt vs pressure (TD), which includes a variable asymptote (PB). The mean heart rates and average (+)dP/dt values normalized at 40 mm Hg development pressure (DP40) did not differ significantly, despite 33% and 43% increases in left ventricular peak and end-diastolic pressures during the infusion of methoxamine (p less than .001 and p less than .01, respectively) and 24% and 29% decreases during the infusion of nitroprusside (p less than .001 and p less than .01, respectively). The average Tln and TD values were not significantly affected by these alterations in load. In two patients, an inverse linear relationship was demonstrated between decreases in Tau and increases in contractile state produced by an infusion of dobutamine, as shown by correlation of Tln and TD with (+)dP/dt/DP40 (r = -.88 and -.83, respectively). We conclude that the time constants of left ventricular isovolumic relaxation are unaffected by modest alterations in loading conditions in man when heart rate is maintained constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1987

Effects of nifedipine on diastolic function during brief periods of flow-limiting ischemia in the conscious dog.

To determine the contribution of transsarcolemmal calcium flux to abnormal diastolic function produced by brief periods of flow-limiting ischemia and reperfusion, we evaluated early and late diastolic function during transient coronary occlusion and reperfusion before and during administration of intravenous nifedipine (NIF) (10 +/- 1 microgram/kg/min) in nine preinstrumented conscious dogs. We also assessed the effects of nitroprusside (NTP) (2 +/- 0.2 micrograms/kg/min) during an identical period of ischemia and reperfusion to independently assess the consequences of altered loading alone on diastolic function. To minimize the effects of temporal dysynchrony and altered ventricular loading conditions on isovolumetric relaxation, we developed a conscious dog preparation of reversible transient (30 to 60 sec) bilateral coronary occlusion (BCO). BCO was characterized by significant systolic depression: maximum (+)dP/dt decreased (from 2617 +/- 600 to 1981 +/- 565 mm Hg/sec, p less than .05), left ventricular transverse dimension shortening diminished (from 20 +/- 5 to 9 +/- 5%, p less than .05), and the left ventricle dilated (42.4 +/- 6.4 to 43.8 +/- 6.3 mm, p less than .05). Concomitantly the time constants of isovolumetric relaxation prolonged (from 22 +/- 3 to 28 +/- 4 msec, p less than .05) and minimal diastolic left ventricular pressure increased (from -3 +/- 6 to 6 +/-6 mm Hg, p less than .05). The passive diastolic pressure-dimension relationship shifted upward and to the right and was associated with increased chamber stiffness (from 0.50 +/- 0.26 to 1.03 +/- 0.53 mm Hg/mm, p less than .05) and increased left ventricular end-diastolic pressure (from 7 +/- 7 to 19 +/- 7 mm Hg, p less than .05). Reperfusion immediately after BCO was characterized by prompt restoration of systolic contractile performance [maximum (+)dP/dt 3220 +/- 530 mm Hg/sec] but persistently abnormal early and late diastolic function (time constant of isovolumetric relaxation 30 +/- 6 msec, left ventricular end-diastolic pressure 20 +/- 7 mm Hg). The effects of drug administration on ventricular function during BCO were then evaluated under matched loading conditions. NTP improved time constant of isovolumetric relaxation (20 +/- 8 vs 28 +/- 4 msec, p less than .05) and minimal diastolic left ventricular pressure (2 +/- 5 vs 6 +/- mm Hg, p less than .05) during BCO, but NIF did not (time constant of isovolumetric relaxation 27 +/- 6 msec, minimal diastolic left ventricular pressure 7 +/- 5 mm Hg).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1987

Echocardiographic left ventricular mass and function in the hypertensive baboon.

Nonhuman primates with chronic systemic hypertension provide an ideal model for studying structural and functional alterations associated with compensatory cardiac hypertrophy. Since noninvasive techniques are useful for the longitudinal evaluation of these animals, we sought to critically asses the M-mode echocardiographic estimation of left ventricular mass in the baboon and to characterize estimates of left ventricular size and function in baboons with chronic renal hypertension. In 23 baboons (12 normotensive, 11 chronic hypertensive), M-mode echocardiography-determined left ventricular mass was 73 +/- 13 (SE) g as compared with the necropsy weight of 69 +/- 11 g (p = NS), and the correlation was excellent (r = 0.94). When 30 chronically hypertensive baboons being observed longitudinally were compared with 10 normotensive control animals studied under identical conditions, several differences were noted in measures derived from echocardiography and high fidelity pressure measurements. Left ventricular systolic pressure was considerably higher in the hypertensive baboons (113 +/- 23 vs 90 +/- 11 mm Hg; p less than 0.001), as was left ventricular mass (148 +/- 60 vs 103 +/- 38 g; p less than 0.03). However, since the ratio of posterior wall thickness to cavity dimension was larger in the hypertensive baboons (0.52 +/- 0.17 vs 0.43 +/- 0.07; p less than 0.05), this concentric hypertrophy maintained values for left ventricular meridional stress at the same level as in the control animals. Despite matched heart rate and left ventricular stress, the rates of change in left ventricular dimensions and wall thickness in systole and diastole were all approximately 25% less in the hypertrophied baboons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Role of the isocitrate dehydrogenases and other Krebs cycle enzymes in lactating bovine mammary gland.

The role of the isocitrate dehydrogenases and other Krebs cycle enzymes in bovine mammary metabolism was studied by investigation of their distribution between cytosol and mitochondria. Citrate synthase was used as a marker for mitochondrial disruption, and distributions were normalized to this enzyme. Aconitase, fumarase, and NAD+:malate dehydrogenase were distributed between the mitochondria and the cytosol; evidence for the possible involvement of an aspartate:malate shuttle was also found. The NADP+:isocitrate dehydrogenase is predominantly cytosolic with a small but significant amount of mitochondrial component. Using the dye dichlorophenol-indophenol, a low level of NAD+:isocitrate dehydrogenase activity was observed in bovine mammary tissues. This assay also allows for detection of the enzyme in fresh mitochondria from a variety of other bovine tissues (heart, liver, kidney, and brain). Activities of the isocitrate dehydrogenases were also examined as a function of gestation and lactation. The NAD+:isocitrate dehydrogenase is apparently depressed during gestation with the NADP+ form of the enzyme (cytosolic) elevated postpartum. These results indicate that a substantial portion of Krebs cycle activity may become extramitochondrial in bovine mammary gland at the onset of lactation.

Animals↗