Biomedical subjects

C P Cheng

Publications and source records attributed to C P Cheng.

At least 37 records · Page 2Linked to original sources

PubMed1997

Left ventricular spherical dilation and regional contractile dysfunction in dogs with heart failure.

Left ventricular (LV) short- and long-axis contractile function and LV structural changes were serially measured in eight instrumented dogs during the development of congestive heart failure (CHF) induced by rapid right ventricular (RV) pacing. After 10 days of pacing, LV end-diastolic volume (VED) had not increased; however, the slope of LV end-systolic pressure-volume relation had decreased from 7.4 +/- 2.6 to 4.9 +/- 1.1 mmHg/ml (P < 0.05), and the slope of LV stroke work-VED relation had fallen from 78.4 +/- 9.1 to 64.2 +/- 7.2 mmHg (P < 0.05). The slopes of end-systolic pressure-dimension relation and the stroke work area-end-diastolic dimension relation in the short axes (i.e., anteroposterior and septal-lateral) had decreased by 30% (P < 0.05), whereas the slopes of the long-axis (i.e., apical-basal) relations were unchanged (not significant). After 20 days of pacing, VED had significantly increased by 14% due to selective dilation of the short axes by 7%, and LV global contractility had further declined with a 40% contractile depression in the short axes and a 25% contractile depression in the long axis. After 30 days, the long-axis dimension at end diastole was also significantly increased with a further increase in the short-axis dimensions. In contrast to the spherical dilation occurring during CHF, acute volume loading of normal animals produced symmetrical LV dilation. These observations suggest that heterogeneous contractile depression initiates the spherical end-diastolic chamber dilation in pacing-induced CHF.

Animals↗

PubMed1997

The cardiac effects of pimobendan (but not amrinone) are preserved at rest and during exercise in conscious dogs with pacing-induced heart failure.

We compared the effects of pimobendan (0.25 mg/kg i.v.), a Ca++ sensitizer, with some phosphodiesterase-III inhibition effects, and amrinone (1 mg/kg plus 10 microg/kg/min i.v.), a PDE-III inhibitor, on left ventricular (LV) systolic and diastolic performance, both at rest and during exercise, in seven conscious dogs before and after pacing-induced congestive heart failure (CHF). Before CHF, under resting conditions, both pimobendan and amrinone caused a similar significant decrease in left ventricle size and end-systolic pressure, arterial elastance, and the time constant of LV relaxation. Similar results were obtained during exercise. Both agents also produced a similar increase in E(ES), the slope of the LV end-systolic pressure-volume relation (3.4 +/- 1.5 vs. 4.2 +/- 1.1 mm Hg/ml; amrinone vs. pimobendan). After CHF, the vasodilatory effects of amrinone and pimobendan were preserved both at rest and during exercise; however, the inotropic actions were different. After CHF, pimobendan increased E(ES) (3.9 +/- 0.5 vs. 5.7 +/- 0.4 mm Hg/ml, P < .05), decreased the time constant of LV relaxation, increased the maximum rate of LV filling (37 +/- 19 ml/sec) (P < .05) and produced a downward shift of the early diastolic portion of LV pressure-volume loop. Pimobendan also augmented LV contractile performance during CHF exercise. In contrast, after CHF, amrinone no longer produced a positive inotropic effect. Amrinone improved LV relaxation and filling, both at rest and during exercise after CHF, but significantly less than pimobendan. We conclude that after CHF, the cardiac response to a PDE-III inhibitor is attenuated, but the response to Ca++ sensitizer is preserved. Thus, after CHF, pimobendan is more effective than amrinone in enhancing LV contractile state, LV relaxation and LV filling both at rest and during exercise.

Amrinone↗

PubMed1996

The ORF I and II proteins of Commelina yellow mottle virus are virion-associated.

Antibodies were prepared against bacterially expressed Commelina yellow mottle badnavirus (CoYMV) proteins. Antiserum against purified virions and antiserum against the C-terminus of the putative coat protein-encoding region of ORF III detected the same virus-specific proteins, indicating that the CoYMV coat protein is encoded in ORF III. In addition to the two major forms of the coat protein (37 and 39 kDa), several high molecular weight virus-specific proteins were detected when virions were isolated without chloroform treatment. These proteins are possible ORF III polyprotein processing intermediates and might be associated with "immature" virions which are eliminated by chloroform treatment. As predicted by the genomic sequence, a 20-kDa virus-specific protein was detected by an antiserum raised against the C-terminus of the putative ORF I protein. Results of filtration experiments suggest that the ORF I protein is equally associated with virions and with plant component(s). The association between the ORF I protein and the virions was further confirmed using immunosorbent electron microscopy and immunogold labeling. The ORF I protein was not detected in virus preparations treated with chloroform, and colocalized with virions containing immature coat protein on sucrose-cesium sulfate density gradients, suggesting that it is associated with immature virions. An antiserum raised against the putative ORF II gene product detected a 15-kDa virus-specific protein whose association with the virions was unaffected by chloroform treatment. The ORF II protein was found to be sensitive to some protease(s) that copurified with the virions, and protease inhibitors preventing this degradation have been identified.

Bacterial Proteins↗

PubMed1996

Altered ventricular and myocyte response to angiotensin II in pacing-induced heart failure.

Alterations in the cardiac response to angiotensin II (Ang II) may contribute to the functional impairment in tachycardia-induced heart failure (congestive heart failure [CHF]). Accordingly, we studied the response to Ang II in eight conscious instrumented dogs before and after inducing CHF. Left ventricular (LV) performance was assessed by measuring LV pressure and LV volume. Isolated myocyte function was evaluated using computer-assessed videomicroscopy. In conscious animals before CHF, Ang II produced a load-dependent slowing of the time constant of LV relaxation (tau) and did not depress intact LV contractile function. After CHF, although Ang II produced a similar increase in LV systolic pressure, the increases in LV diastolic pressure and time constant tau were much greater, and contractile performance was depressed. These changes persisted when the elevation of end-systolic pressure was prevented by nitroprusside. Similar changes were also present after autonomic blockade. In isolated myocytes, before CHF, Ang II (10(-6) mol/L) produced a slight positive inotropic effect. In contrast, after CHF, Ang II produced a negative inotropic effect and slowed the rate of relengthening. The effects in the intact LV and myocytes were reversed by an Ang II AT1 receptor blocker (losartan). We conclude that pacing-induced CHF alters the LV and myocyte response to Ang II, so that Ang II produces direct depressions in intact LV contraction, relaxation, and filling and exacerbates myocyte contractile dysfunction. These effects are mediated through the activation of AT1 receptors.

Angiotensin II↗

PubMed1996

[Effect of L-TYR on the uterine cytosol estradiol and progesterone receptors in rat].

The effect of L-TYR on rat uterine cytosol estradiol and progesterone receptor contents was studied. The rats were divided into 4 groups: proestrus, estrus, metestrus and diestrus. One horn of each uterus was injected with L-TYR (2 mmol/L, 0.1 ml), while the other with 0.1 ml 0.9% NaCl serving as control. The mole concentration of receptor was calculated with RRA and cytosol receptor content was expressed as fmol/mg protein. It was shown that L-TYR decreased significantly the uterine estradiol and progesterone receptors in proestrus, estrus and diestrus phases of the estrus cycle, but without effect on metestrus. This was most probably due to competitive combination of TYR with some functional groups of the estradiol receptor because of similar chemical conformation of TYR to estradiol. Threonine could also decrease, to some extent, the uterine cytosol progesterone receptor content at estrus and dioestrus phases. Serine had no effect on the contents of uterine cytosol either estradiol or progesterone receptor in normal and ovariectomized rats. The present observation indicates that L-TYR appears to affect the synthesis of the cytosol estradiol and progesterone receptor in the rat uterus independent, however, of endogenous ovarian sex hormones, since the effect is still present in the ovariectomized animals.

Animals↗

PubMed1996

[Effect of human inhibin alpha-fragments and monoaminergic neurotransmitters on progesterone(P4) production by corpus luteum(CL) of rat in vitro].

The effects of exogenenous monoaminergic neurotransmitters (norepinephrine, NE; epinephrine, E; dopamine, DA and 5-HT) and inhibin alpha N-terminal fragments P32 (1-32), P32-Tyr on P4 production by incubated rat CL cells were studied. The results demonstrated that: (1) alpha fragments caused significant inhibition on P4 production. (2) 0.1 mmol/L NE (or E) and 10 mumol/L DA produced a marked increase in both basal and hCG induced P4 production by CL cells (P < 0.001). The rank orders of potency of the catecholamines in stimulating P4 production were different, for basal P4 production, NE > E > DA; but for hCG induced P4 production, DA > E > NE, i.e. the order just reversed. Addition of P32-Tyr significantly neutrolized the stimulatory action of E, but only slightly increased the action of NE. (3) alpha receptor blocker phentolamine and beta receptor blocker propranolol were effective in decreasing basal and hCG-induced P4 production, the latter being more effective than the former. It was further shown that both blockers augmented the inhibitory effect of alpha-fragments on P4 production. (4) Unlike NE, E, and DA, 5-HT at 0.5 mumol/L exerted inhibitory effect on the basal and hCG-induced P4 production, but profoundly supressed the inhibitory effect of alpha-fragments on P4 production. The above results suggested: (1) Adrenergic, DA and 5-HT receptors are present in rat CL, where catecholamine might exert a stimulating effect on basal and hCG-induced P4 production via different pathways. (2) The inhibitory effect of P32, P32-Tyr on P4 production might be related to their inhibition by partial blocking alpha/beta receptors, which were antagnized by 5-HT. (3) The action of P32, P32-TYr on P4 production is brought on the participation of neurotransmitters NE, E, DA and 5-HT.

Adrenergic alpha-Agonists↗

PubMed1995

Determination of left ventricular chamber stiffness from the time for deceleration of early left ventricular filling.

BACKGROUND: A noninvasive measure of left ventricular (LV) chamber stiffness (KLV) would be clinically useful. Our theoretical analysis predicts that KLV can be calculated from the time for deceleration of LV early filling (tdec) by [formula: see text] where p = density of blood, L = effective mitral length, and A = mitral area. METHODS AND RESULTS: We tested this hypothesis in eight conscious dogs instrumented for measurement of LV pressure (P) with use of a micromanometer and volume (V) with use of sonomicrometers. KLV was determined as the slope of the late diastolic portion of the LV P-V loop. KLV was varied from 0.99 +/- 0.35 to 2.58 +/- 0.92 mm Hg/mL with use of three graded doses of phenylephrine. We assumed that p = 1.0 and that L/A = 3.4. Thus, we predicted that KLV = (0.08/tdec)2. The LV filling pattern was determined from the derivative of LV volume (dV/dt). tdec was measured from peak early filling to the end of early filling. Predicted KLV and actual KLV were closely correlated (r = .94, SEE = 0.06 mm Hg/mL, P < .05). The regression line was close to the line of identity (slope = 0.95, intercept = 0.13 mm Hg/mL). Dobutamine did not alter the relation between tdec and KLV.tdec determined from the mitral valve flow velocity measured with Doppler echocardiography correlated well with that measured by dV/dt (r = .89, P < .01) but was 0.02 seconds longer. KLV-calculated tdec from the corrected Doppler tdec provided a good estimate of measured KLV (r = .75, SEE = 0.5 mm Hg/mL, P < .01). CONCLUSIONS: LV chamber stiffness can be determined from the time for deceleration of LV early filling, which can be measured noninvasively.

Animals↗

PubMed1995

Vascular selective calcium entry blockers in the treatment of cardiovascular disorders: focus on felodipine.

Calcium entry through L-type calcium channels is essential for contraction of both arterial smooth muscle and the myocardium, and is important in cardiac conduction. First-generation calcium entry blockers lack or have a modest degree of vascular selectivity and inhibit cardiac function at doses producing therapeutic arterial dilatation. Such agents may cause deterioration in patients with left ventricular dysfunction, and their combination with a beta-adrenergic blocker may adversely affect cardiac contractility and conduction. Development of newer agents has focused on obtaining a higher degree of vascular selectivity. Felodipine is a highly vascular selective calcium entry blocker, with a vascular selectivity ratio greater than 100, as shown experimentally. Isradipine and nicardipine are also vascularly selective calcium entry blockers. Hemodynamic studies in patients with hypertension, coronary artery disease, congestive heart failure, or in patients receiving beta-adrenergic blockade, show that felodipine can produce profound arteriolar dilatation without the negative effects of left ventricular systolic performance. Furthermore, felodipine alone or when added to a beta-adrenergic blocker does not interfere with cardiac conduction. The primary mechanism that accounts for the efficacy of dihydropyridine calcium entry blockers in hypertension and angina pectoris is arterial dilation, whereas nondihydropyridines may also derive part of their effect from inhibition of cardiac performance. As some of these patients, most commonly the elderly, have concomitant left ventricular dysfunction, it should be advantageous to avoid myocardial depression in the treatment of their primary disease. Preliminary studies in patients with heart failure indicate that felodipine and amlopidine may improve hemodynamics, reduce neurohormonal activation, and increase exercise tolerance, but final conclusions must await the randomized clinical trials now underway.

Amlodipine↗

PubMed1994

Coupling of the left ventricular and arterial system.

We investigated the coupling of the left ventricle (LV) and the arterial system in eight conscious dogs, instrumented to measure LV pressure and determine LV volume from three ultrasonically determined dimensions. The LV end-systolic pressure (PES)-volume (VES) relation was determined by caval occlusion. Its slope (EES) was compared to the arterial elastance (EA), determined as PES/stroke volume. At rest, with intact reflexes, EES/EA was 0.9 +/- 0.20. EES/EA was varied over a wide range (0.18-2.59) by the infusion of graded doses of phenylephrine and nitroprusside and dobutamine. Maximum LV SW, at constant inotropic state and end-diastolic volume, occurred when EES/EA = 0.99 +/- 0.15. However, SW was within 20% of its maximum value when EES/EA was between 0.56 and 2.29. As EES/EA decreased below 0.59, SW fell precipitously. The shape of the observed relation of SW to EES/EA was similar to that predicted by the theoretical consideration of linear LV PES-VES and arterial PES-stroke volume relations. We conclude that the LV and arterial system produce maximum SW at constant VED when EES and EA are equal; however, the relation of SW to EES/EA has a broad plateau.

Animals↗

PubMed1994

Relation between left ventricular oxygen consumption and pressure-volume area in conscious dogs.

BACKGROUND: The relation between left ventricular (LV) oxygen consumption (MVO2) and pressure-volume area (PVA) developed in isolated hearts provides a powerful method to understand cardiac energetics. We investigated application of this relation to the intact circulation, determining its response to steady-state and transient load alterations and enhanced contractility in conscious animals. METHODS AND RESULTS: Eight dogs were instrumented to measure LV pressure (micromanometer), LV volume (three sonomicrometers), and left circumflex and anterior descending coronary artery flows (ultrasonic flowmeter). Data were acquired after recovery from the surgery with the animals awake and unsedated. After administration of hexamethonium and atropine, steady-state loading conditions were changed with phenylephrine or nitroprusside in four to five steps before and during the infusion of dobutamine (6 to 10 micrograms.-1kg.-1min). MVO2 and PVA obtained under steady-state conditions were linearly correlated both before and during dobutamine. The MVO2-PVA relation obtained on a beat-to-beat basis during transient caval occlusion was less linear and not coincident with the steady-state relation. Dobutamine shifted the steady-state MVO2-PVA relation upward in all hearts, increasing the MVO2 axis intercept of the MVO2-PVA relation (P < .01). This intercept correlated with ventricular contractility assessed by the slope (Ees) of the LV end-systolic pressure-volume relation determined by caval occlusion (r = .76, P < .05). The slope of the MVO2-PVA relation increased with dobutamine in seven of eight animals, with the inverse of the slope (representing contractile efficiency) being 31 +/- 6% during control and 24 +/- 6% after dobutamine (P = .06). CONCLUSIONS: MVO2 and PVA are linearly related during steady-state alterations in loading conditions in conscious dogs but not on a beat-by-beat basis during transient caval occlusion. Increase in contractility by dobutamine produces an upward shift of the MVO2-PVA relation.

Animals↗

PubMed1994

Mechanism of altered patterns of left ventricular filling during the development of congestive heart failure.

BACKGROUND: The mechanism of the alterations in the pattern of left ventricular (LV) filling during the development of congestive heart failure (CHF) is not fully understood. METHODS AND RESULTS: We studied six conscious dogs instrumented to measure LV and left atrial (LA) pressures and LV volume as CHF was induced by rapid pacing. Diastolic filling dynamics were serially measured over 4 weeks during normal sinus rhythm. Four days after we initiated pacing, the peak early diastolic filing rate decreased from 108 +/- 24 to 88 +/- 27 mL/s (P < .05) as the maximal early diastolic LA-LV pressure gradient decreased associated with a slowing of the rate of LV relaxation. Subsequently, the peak early filling rate progressively increased, returning to control at 1 week, and by the fourth week, it had increased to 168 +/- 39 mL/s (P < .05). These changes in early filling rates occurred as the maximal early diastolic LA-LV pressure gradient increased in association with a progressive increase in LV pressure despite further progressive slowing of the rate of LV relaxation. Throughout the development of CHF, peak early filling rate and the maximal LA-LV pressure gradient correlated (r = .99, P < .001). The early filling deceleration rate increased and deceleration time progressively decreased over the 4 weeks as LV stiffness and net LA plus LV stiffness increased (P < .05). As predicted by a theoretical analysis, the deceleration time was linearly related to the reciprocal of the square root of LV stiffness (r = .94, P < .01). CONCLUSIONS: Early in CHF, slowing of LV relaxation reduces the maximal early diastolic LA-LV pressure gradient, decreasing the peak early filling rate. As CHF progresses, this is overcome by an increase in LA pressure that augments the early diastolic LA-LV pressure gradient, increasing peak early filling rate. Increasing LV stiffness during the development of CHF progressively shortens the early filling deceleration time and augments the early filling deceleration rate. These observations suggest that the early filling deceleration time reflects LV stiffness.

Animals↗

PubMed1994

Effect of exercise on left ventricular mechanical efficiency in conscious dogs.

BACKGROUND: We studied the effect of exercise (7.2 to 8.0 km/h) on the efficiency of the conversion of metabolic energy to external work or stroke work (SW) by the left ventricle (LV). METHODS AND RESULTS: Energy use was calculated from LV myocardial oxygen consumption per beat (MVO2). LV volume was calculated from orthogonal dimensions and coronary flow measured with ultrasonic flow probes. The total mechanical energy of the LV was calculated as the pressure-volume area (PVA). At rest, the MVO2-PVA point fell on the MVO2-PVA relation determined by steady-state changes in arterial pressure produced by graded infusions of phenylephrine. Exercise increased the slope (Ees) of LV end-systolic pressure-volume (PV) relation by 29%. During exercise, the MVO2-PVA point shifted to the right only slightly above the control MVO2-PVA relation by 0.007 +/- 0.005 mL O2.beat-1.100 g LV-1. Despite the increase in ventricular contractility with exercise, the PVA/MVO2 ratio was unchanged because of the marked increase in PVA. During exercise, the transmission of total mechanical energy to external work (SW/PVA) increased from 65 +/- 5% to 72 +/- 4% (P < .01) as the ratio of the arterial end-systolic elastance to Ees decreased from 1.1 +/- 0.2 to 0.8 +/- 0.1 (P < .05). Thus, LV mechanical efficiency (SW/MVO2 = SW/PVA.PVA/MVO2) improved from 12.9 +/- 1.5% to 14.3 +/- 1.1% (P < .05) during exercise. CONCLUSIONS: Exercise increases the efficiency of conversion of metabolic energy to external work by the LV due to alteration in LV arterial coupling resulting in increased production of mechanical energy and enhanced transmission of mechanical energy to external work, which more than offsets any increased metabolic cost of the enhanced contractility.

Animals↗

PubMed1994

Vascular versus myocardial effects of calcium antagonists.

As vascular smooth muscle tone and myocardial contractility both depend on calcium entry, the calcium antagonists are not only potent arterial vasodilators, but may also have important negative inotropic effects. For example, verapamil is nearly equipotent in reducing vascular smooth muscle tone and myocardial contraction in isolated tissue preparations. In contrast, felodipine has high vascular selectivity in such preparations, and drug concentrations required to depress myocardial contraction are more than 100 times greater than those required to relax vascular smooth muscle. In the isolated, isovolumetrically contracting canine left ventricle, clinically relevant concentrations of felodipine (14 nmol/L) produce coronary vasodilation and a mild positive inotropic response. Using left ventricular (LV) pressure-volume analysis, we evaluated a similar dose of felodipine (plasma drug concentration 16 nmol/L) in conscious dogs. Felodipine produced a 25mm Hg fall in arterial pressure and a 10% reduction in peripheral vascular resistance. There was no negative inotropic effect. Instead, myocardial contractile performance was slightly but significantly enhanced. These results were not altered by adrenergic blockade. Further studies in our laboratory showed that doses of amlodipine and nifedipine producing arterial vasodilation of a magnitude similar to that produced by felodipine had negative inotropic effects in the conscious dog. Only felodipine enhanced the rate of LV relaxation and the rate of early diastolic filling. Thus, felodipine was significantly more vasoselective than amlodipine and nifedipine. The direct inotropic effects of calcium antagonists are difficult to evaluate in clinical studies because of the load-dependence of most conventional measures of LV performance. However, no negative inotropic effects are clinically relevant doses of felodipine have been identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Amlodipine↗

PubMed1994

[Effect of tyrosine on progesterone production by perifused rat large and small corpus luteal cells].

The effect of tyrosine on progesterone production by rat large and small luteal cells was studied by perifusion method. The large and small luteal cells were separated by sucrose density gradient centrifugation. After pre-perifusion for 1 h the effluent from the perifused large or small cells was separately collected at 10 min intervals by a fraction collector. Progesterone content of each sample was measured by RIA. Results showed that the basal progesterone production by large luteal cells was 2-fold more than that of the small ones. However, the suppressive effect of tyrosine on hCG- induced progesterone production was more pronounced in small luteal cells. These differences may be due to the fact that small luteal cells uptake more 3H- tyrosine.

Animals↗

PubMed1994

Effects of felodipine on left ventricular systolic and diastolic performance in congestive heart failure.

We studied the effects of a dihydropyridine calcium blocker, felodipine, on left ventricular (LV) contractile performance and diastolic filling dynamics in conscious dogs with pacing-induced congestive heart failure (CHF) before and after autonomic blockade. Eleven conscious dogs were instrumented to measure micromanometer LV and left atrial (LA) pressure (P) and to determine LV volume (V) from three dimensions. CHF was induced by 4 to 5 weeks of right ventricular pacing. After CHF, the mean LV end-diastolic (ED) P increased (9.7 +/- 2.9 vs. 27.9 +/- 6.8 mm Hg, P < .05), LVEDV and end-systolic (ES) V increased and stroke volume (SV) decreased (15.3 +/- 2.4 vs. 9.6 +/- 3.0 ml, P < .05). The time constant of LV relaxation (T) (25.9 +/- 2.9 vs. 37.9 +/- 5.1 msec, P < .05) and LVES wall stress (WS) (63.4 +/- 21.0 vs. 74.6 +/- 23.7 g/cm2, P < .05) also increased. After CHF, felodipine (25 nmol/kg i.v., plasma concentrations 17.4 +/- 3.2 nmol/L) produced significant decreases in LVESP (119 +/- 12 vs. 96 +/- 11 mm Hg, P < .05), arterial elastance, total systolic resistance (TSR) (0.11 +/- 0.04 vs. 0.07 +/- 0.03 mm Hg/ml/min, P < .05) and LVESWS (74.6 +/- 23.7 vs. 60.2 +/- 17.3 g/cm2, P < .05). Felodipine increased the slopes of the ESP-V relation (5.6 +/- 1.5 vs. 7.8 +/- 0.7 mm Hg/ml, P < .05), the dP/dtmax-EDV relation (51.4 +/- 6.1 vs. 85.3 +/- 10.1 mm Hg/ml sec, P < .05) and the stroke work-EDV relation (69.8 +/- 7.1 vs. 78.9 +/- 7.1 mm Hg, P < .05) and shifted all three relations to the left, indicating enhanced contractile performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Comparison of effects of dihydropyridine calcium antagonists on left ventricular systolic and diastolic performance.

We compared the effects of three dihydropyridine calcium antagonists (felodipine, nifedipine and amlodipine) on left ventricular (LV) contractile performance and diastolic filling dynamics in eight conscious animals. After administering metoprolol and atropine, felodipine (25 nmol/kg i.v.) produced significant decreases in LV end-systolic pressure (PES) (109 +/- 15 vs. 88 +/- 12 mmHg, P < .05) and arterial elastance (Ea) (12.6 +/- 4.5 vs. 8.5 +/- 3.4 mmHg/ml, P < .05), whereas the heart rate was unchanged. Felodipine increased the slopes of the end-systolic P-V relation (7.4 +/- 0.9 vs. 9.9 +/- 1.0 mmHg/ml, P < .05), the dP/dtmax-end diastolic volume (VED) relation (68.1 +/- 11.2 vs. 94.9 +/- 14.3 mmHg/sec/ml, P < .05), and the stroke work (SW)-VED relation (72.1 +/- 3.1 vs. 82.8 +/- 5.2 mmHg, P < .05), and shifted all three relations to the left, indicating enhanced contractile performance. In contrast, at doses that produced equivalent reductions of PES, nifedipine (375 nmol/kg i.v.) and amlodipine (780 nmol/kg i.v.), significantly decreased the slopes of the end-systolic P-V relation, the dP/dtmax-VED relation and the SW-VED relation and shifted all three relations to the right, indicating depressed LV contractile performance. Felodipine decreased the time constant (T) of LV relaxation (32.2 +/- 5.2 to 28.8 +/- 5.2 msec, P < .05) and increased the maximum rate of early diastolic LV filling (dV/dtmax) (167 +/- 22 to 207 +/- 26 ml/sec, P < .05). Amlodipine had the opposite effect, slowing T (31.0 +/- 4.9 to 33.9 +/- 5.4 msec, P < .05) and decreasing dV/dtmax (173 +/- 39 to 154 +/- 30 ml/sec, P < .05), whereas nifedipine had no significant effects on T, PGmax or dV/dtmax. Thus, we conclude that in conscious dogs after autonomic blockade, at dosages that produced equivalent arterial vasodilation, felodipine augmented, whereas amlodipine depressed, LV contractile performance, LV relaxation and early LV filling. Nifedipine decreased LV contractile performance but had no significant effect on LV relaxation and early LV filling.

Amlodipine↗

PubMed1993

Estimation of left ventricular elastance without altering preload or afterload in the conscious dog.

OBJECTIVE: The aim was to determine the slope (EES) of the left ventricular end systolic pressure-volume line (ESPVL) without altering preload or afterload in conscious dogs. METHODS: Dogs (n = 10) were instrumented to determine left ventricular volume from ultrasonic left ventricular internal dimensions, and to measure left ventricular pressure using a micromanometer. Studies were performed one to two weeks after instrumentation while the animals were conscious. ESPVL was determined from variably loaded left ventricular pressure-volume (P-V) loops generated by the vena caval occlusion. Contractile state was increased by intravenous dobutamine (8 micrograms.kg-1 x min-1) and decreased by intravenous verapamil (10 mg) given after autonomic blockade. From a single normally ejecting beat, we calculated EES-single beat (mm Hg.ml-1) as peak isovolumetric pressure (Pmax) minus end systolic pressure divided by stroke volume. Sunagawa's technique was used to estimate Pmax by fitting the pressure during the isovolumetric contraction and relaxation as: P(t) = 1/2 X Piso[1-cos(omega t+c)]+LVEDP, where Piso = peak isovolumetric developed pressure, LVEDP = left ventricular end diastolic pressure, c = constant accounting for variations in phase angle, and omega = 2 pi/T in which T is duration of contraction. RESULTS: After dobutamine, EES increased, from 8.9(SEM 0.8) to 12.5(1.0) mm Hg.ml-1 (p < 0.05), and EES-single beat increased from 9.1(0.9) to 12.0(1.4) mm Hg.ml-1 (p < 0.05). Conversely, after verapamil, EES decreased, from 11.1(1.2) to 6.3(1.1) mm Hg.ml-1, (p < 0.05), and EES-single beat also decreased, from 9.6(1.0) to 7.3(1.2) mm Hg.ml-1, (p < 0.05). CONCLUSIONS: EES calculated from one beat is similar to EES determined from variably loaded left ventricular loops and responds appropriately to inotropic stimulation. This technique provides a reasonable method to calculate EES from left ventricular pressure and stroke volume without altering preload or afterload.

Animals↗

PubMed1993

Effect of vasopressin on left ventricular performance.

We assessed the effect of arginine vasopressin (AVP) on left ventricular (LV) performance in eight conscious dogs. Five minutes after AVP infusion (6 microns.kg-1 x min-1 for 2 min) the plasma AVP was elevated from 3.9 +/- 0.9 to 14.7 +/- 4.6 pg/ml (P < 0.05). With all reflexes intact, AVP caused significant increases in LV end-systolic pressure (P) (112 +/- 8 vs. 122 +/- 7 mmHg, P < 0.05) end-systolic volume (V) (30 +/- 5.8 vs. 38 +/- 7.7 ml, P < 0.05), total systemic resistance (6.2 +/- 1.8 vs. 10.6 +/- 4.0 mmHg.dl-1 x min, P < 0.01) and arterial elastance (Ea) (6.8 +/- 3.0 vs. 8.6 +/- 3.9 mmHg/ml, P < 0.05), while the heart rate (110 +/- 6 vs. 82 +/- 10 beats/min, P < 0.05) and stroke volume (16.5 +/- 4.3 vs. 14.2 +/- 3.9 ml, P < 0.05) were decreased. There was no significant change in the coronary sinus blood flow (82 +/- 19 vs. 78 +/- 22 ml/min, P = not significant). AVP decreased the slopes of LV end-systolic P-V relation (10.7 +/- 1.1 vs. 8.1 +/- 1.9 mmHg/ml, P < 0.05), the maximal first derivative of LV pressure (dP/dtmax)-end-diastolic volume (VED) relation (135.2 +/- 18.7 vs. 63.1 +/- 7.7 mmHg.s-1 x ml-1, P < 0.05), and the stroke work-VED relation (81.1 +/- 4.1 vs. 66.7 +/- 2.8 mmHg, P < 0.05) and shifted the relations to the right, indicating a depression of LV performance. A similar increase in Ea produced by methoxamine did not depress LV performance.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗