Biomedical subjects

H Ikenouchi

Publications and source records attributed to H Ikenouchi.

18 recordsLinked to original sources

PubMed1996

Survival of metabolically inhibited ventricular myocytes is enhanced by inhibition of rigor and SR Ca2+ cycling.

During severe ATP depletion, sarcolemmal rupture resulting from rigor- and/or Ca(2+)-induced myofilament force development is considered to be an important cause of irreversible cell injury. Recent experiments in our laboratory demonstrated that during prolonged metabolic inhibition (MI) in adult rabbit ventricular myocytes, in which rigor was prevented by exposure to 30 mM 2,3-butanedione monoxime (BDM), cyclic uptake and release of cystolic Ca2+ occurred and was associated with strong phasic contractions. To investigate the relative contribution of this sarcoplasmic reticulum Ca2+ cycling and associated force development to energy depletion injury, the effects of BDM together with 7 mM caffeine were examined in isolated rabbit ventricular myocytes subjected to MI with 2 mM NaCN and 20 mM 2-deoxyglucose (2-DG). During 90 min of MI with CN and 2-DG, no cells retained a rod shape in the absence of BDM or caffeine. In the presence of both 30 mM BDM and 7 mM caffeine during MI, preservation of rod morphology was enhanced, and 52 +/- 6.2% of cells retained a rod shape 48 h after metabolic inhibition and had normal ATP content and resting membrane potential. Both systolic and diastolic functions of cells that survived MI, however, were impaired. We conclude that exposure to caffeine together with BDM markedly enhances survival of myocytes during severe prolonged ATP depletion. After recovery, these isolated myocytes show some characteristics of stunning.

Adenosine Triphosphate↗

PubMed1995

Mechanisms of adrenomedullin-induced vasodilation in the rat kidney.

To explore the mechanisms of adrenomedullin-induced vasorelaxation, we tested the effects of adrenomedullin on renal function in rats in vivo and measured the release of endothelium-derived nitric oxide from isolated perfused rat kidney (using a chemiluminescence assay) and the diameters of the glomerular arterioles in the hydronephrotic kidney. Adrenomedullin decreased blood pressure in a dose-dependent manner (3 nmol/kg: -29 +/- 2% [SEM]; P < .01) and slightly increased the glomerular filtration rate and urinary sodium excretion (+108%; P < .05). These changes were associated with significant increases in urinary excretion of cyclic AMP (+54%; P < .05). Adrenomedullin decreased renal vascular resistance (10(-7) mol/L adrenomedullin: -41 +/- 2%; P < .001) and increased release of nitric oxide (+5.1 +/- 0.7 fmol/min per gram kidney weight; P < .001) in the isolated kidney. This increase in nitric oxide release was abolished by the inhibitor NG-monomethyl-L-arginine, and it also reversed the decrease in renal vascular resistance seen with adrenomedullin. Renal responses of deoxycorticosterone acetate-salt hypertensive rats to adrenomedullin were significantly smaller than those of control rats for both release of nitric oxide (10(-7) mol/L adrenomedullin: +0.8 +/- 0.2 fmol/min per gram kidney weight; P < .01 versus control) and renal vasodilation (-28 +/- 6%; P < .05). Videomicroscopic analysis revealed that adrenomedullin increased the diameters of both afferent and efferent arterioles (3 nmol/kg: +11%; P < .05). Thus, adrenomedullin-induced renal vasodilation is partially endothelium dependent and is attenuated in deoxycorticosterone acetate-salt hypertension, probably due to endothelial damage.

Adrenomedullin↗

PubMed1995

Ca(2+)-growth coupling in angiotensin II-induced hypertrophy in cultured rat cardiac cells.

OBJECTIVES: There remain some controversies about the effect of angiotensin II on intracellular Ca2+ concentration ([Ca2+]i) in cardiac myocytes. The aim of this study was to investigate different roles of intracellular Ca2+ in the responses to angiotensin II between cardiac myocytes and nonmyocytes. METHODS: Primary cultures of neonatal rat cardiac myocytes and nonmyocytes were prepared. [Ca2+]i was measured with indo-1. Cellular growth was assayed by [3H]thymidine uptake, RNA content, [3H]phenylalanine incorporation and protein content. Induction of immediate-early gene was examined by Northern blot analysis. RESULTS: In myocytes, angiotensin II decreased [Ca2+]i transients, induced c-fos mRNA, and accelerated hypertrophy. These effects were completely suppressed by AT1 receptor blockade or protein kinase C inhibition. After chelation of extracellular Ca2+, angiotensin II caused no change in [Ca2+]i or no induction of c-fos in myocytes. Phorbol 12-myristate 13-acetate also decreased [Ca2+]i transients, caused c-fos induction, and provoked hypertrophy in myocytes. In nonmyocytes, angiotensin II increased [Ca2+]i transiently, induced c-fos mRNA and hypertrophy. These effects of angiotensin II were not fully abolished by protein kinase C inhibition. Extracellular Ca2+ chelation did not completely inhibit the effects of angiotensin II on [Ca2+]i or c-fos induction in nonmyocytes. Phorbol 12-myristate 13-acetate did not affect [Ca2+]i or cellular growth in nonmyocytes but did cause c-fos induction. CONCLUSIONS: These results suggest that angiotensin II induces cellular hypertrophy and immediate-early genes through the activation of protein kinase C in myocytes, although angiotensin II decreases [Ca2+]i transients via this signaling pathway. Induction by angiotensin II of hypertrophy and immediate-early genes in nonmyocytes may be in part mediated by a transient increase in [Ca2+]i which acts synergistically with protein kinase C activation.

Angiotensin II↗

PubMed1994

Effects of angiotensin II on intracellular Ca2+ and pH in isolated beating rabbit hearts and myocytes loaded with the indicator indo-1.

1. Angiotensin II increases myocardial contractility in several species, including the rabbit and man. However, it is controversial whether the predominant mechanism is an increase in free cytosolic [Ca2+]i or a change in myofilament Ca2+ sensitivity. To address this question, we infused angiotensin II in isolated perfused rabbit hearts loaded with the Ca2+ indicator indo-1 AM and measured changes in beat-to-beat surface transients of the Ca2+i-sensitive 400:500 nm ratio and left ventricular contractility. The effects of angiotensin II were compared with the response to a Ca(2+)-dependent increase in the inotropic state produced by a change in the perfusate [Ca2+] from 0.9 to 3.6 nM. 2. In the isolated beating heart, an increase in perfusate [Ca2+] caused an increase in left ventricular pressure +dP/dt in association with an increase in peak systolic [Ca2+]i. Angiotensin II perfusion caused a similar increase in left ventricular +dP/dt in the absence of any increase in peak systolic [Ca2+]i. 3. To exclude any contribution of non-myocyte sources of Ca(2+)-sensitive fluorescence which may be present in the intact heart, we also compared the effects of angiotensin II and a change in superfusate [Ca2+] in collagenase-dissociated paced adult rabbit ventricular myocytes loaded with indo-1 AM. In the isolated rabbit myocytes a change in perfusate [Ca2+] from 0.9 to 3.6 mM caused an increase in peak systolic cell shortening coincident with an increase in peak systolic [Ca2+]i. In contrast, angiotensin II caused a similar increase in peak systolic cell shortening whereas there was no increase in peak systolic [Ca2+]i. There was also no change in inward Ca2+ current (ICa) in response to angiotensin II. 4. To investigate further the mechanism of the positive inotropic action of angiotensin II, its effects on intracellular pH were studied in isolated rabbit myocytes loaded with the fluorescent H+ probe SNARF 1. These experiments demonstrated that angiotensin II induced a 0.2 pH unit increase coincident with the development of a positive inotropic effect in isolated rabbit myocytes. 5. In summary, angiotensin II has a direct positive inotropic effect in beating rabbit hearts and in isolated paced rabbit myocytes. These experiments provide support for the hypothesis that the predominant mechanism is not an increase in free cytosolic Ca2+ but is due in part to an increase in myofilament Ca2+ sensitivity due to intracellular alkalosis.

Angiotensin II↗

PubMed1994

Effect of 2,3-butanedione monoxime on myocyte resting force during prolonged metabolic inhibition.

The chemical phosphatase 2,3-butanedione monoxime (BDM) has been reported to inhibit both Ca(2+)-induced myofilament force development and rigor due to ATP depletion. However, during prolonged hypoxia in cultured ventricular myocytes BDM delays but does not prevent a marked increase in resting force. To investigate the mechanisms involved we measured the effects of BDM on intracellular Ca2+ concentration ([Ca2+]i; indo 1), force development (video motion detector), and ATP contents (luciferase assay) in cultured embryonic chick ventricular myocytes and adult rabbit ventricular myocytes subjected to prolonged metabolic inhibition with 1 mM NaCN and 20 mM 2-deoxyglucose. In the absence of metabolic inhibition, 20 mM BDM depressed force development even when [Ca2+]i was markedly elevated by exposure to zero-Na solution or 10 mM caffeine in chick cells, and 30 mM BDM completely inhibited Ca(2+)-induced force development in rabbit myocytes. During metabolic inhibition, 20 mM BDM delayed the onset of an increase in resting force (from 5.44 +/- 0.87 to 13.67 +/- 1.34 min in chick myocytes; from 19.13 +/- 2.23 to 32.43 +/- 3.30 min in rabbit myocytes, means +/- SE, n = 8-9). However, the rates of ATP depletion and rise in [Ca2+]i after metabolic inhibition were not altered by BDM. In the presence of BDM, during prolonged metabolic inhibition in both chick and rabbit myocytes, abrupt spontaneous or evoked alterations in [Ca2+]i were associated with corresponding changes in force. During the initial increase in resting force induced by metabolic inhibition, exposure to BDM caused a partial transient relaxation. We conclude that the delayed increase in resting force during metabolic inhibition in the presence of BDM is due to redevelopment of Ca2+ sensitivity of the myofilaments in the presence of an increased [Ca2+]i as a consequence of severe ATP depletion, whereas in the absence of BDM the more rapidly developing increase in resting force during metabolic inhibition is initially due to a rise in [Ca2+]i followed by development of rigor.

Adenosine Triphosphate↗

PubMed1993

ATP depletion causes a reversible decrease in Na+ pump density in cultured ventricular myocytes.

To examine factors contributing to impaired K+ homeostasis induced by prolonged but sublethal ATP depletion, we subjected cultured chick ventricular myocytes to metabolic inhibition with 20 mM 2-deoxy-D-glucose plus 1 mM NaCN for 2 h and then allowed myocytes to recover for 5 days in medium containing 6% fetal calf serum (FCS) or in hormone-supplemented serum-free medium. We measured spontaneous contractions (with a video motion detector), K+ content, K+ uptake, membrane potential, and Na+ pump density ([3H]ouabain binding). Exposure to metabolic inhibition for 2 h caused an acute decrease in Na+ pump site density [8.2 +/- 1.1 to 3.8 +/- 0.8 (SE) pmol/mg protein; n = 9, P < 0.02]. Compared with control cells (no metabolic inhibition, cultured for 5 days in serum-free medium), Na+ pump density remained depressed in cells recovered from metabolic inhibition in serum-free medium (3.0 +/- 0.7 pmol/mg), and this was associated with persistently depressed K+ uptake (54% of control), K+ content (67% of control), and membrane depolarization (-19 +/- 2 mV), a significant decrease in cell number (79% of control), and failure to resume spontaneous contractions. Exposure of cells inhibited for 2 h to culture medium containing 6% FCS resulted in a return of Na+ pump site density toward normal levels by 5 days, associated with recovery of K+ uptake and K+ content, preservation of cell number, and resumption of contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1993

Variable effects of endothelin-1 on [Ca2+]i transients, pHi, and contraction in ventricular myocytes.

We examined the effects of endothelin-1 (ET-1) on intracellular free calcium concentration ([Ca2+]i) transients, intracellular pH (pHi), and cell contraction in both embryonic and neonatal as well as in adult ventricular myocytes. Exposure of chick ventricular myocytes to ET-1 (10 nM) significantly decreased both peak systolic and end-diastolic [Ca2+]i (from 949 +/- 43 to 628 +/- 59 nM and from 230 +/- 13 to 162 +/- 8 nM, respectively; P < 0.05, n = 12). The amplitude of cell contraction was also decreased during exposure to 10 nM ET-1 (81.7 +/- 1.2% of control, P < 0.01, n = 12). Exposure to 10 nM ET-1 slightly decreased pHi (-0.055 +/- 0.020 U; P < 0.05). Exposure of cultured neonatal rat ventricular myocytes to ET-1 (10 nM) produced similar effects. Responses of adult rabbit ventricular myocytes to ET-1 were dramatically different from those of embryonic or neonatal ventricular myocytes. Exposure to 10 nM ET-1 increased the amplitude of cell contraction to 159 +/- 32% of control (P < 0.01) without an increase in [Ca2+]i transients. ET-1 also increased pHi (+0.081 +/- 0.047 U; P < 0.01). These results indicate that ET-1 produces a negative inotropic effect by decreasing [Ca2+]i transients and induces a slight intracellular acidosis in immature ventricular myocytes. However, ET-1 causes a positive inotropic effect in adult ventricular myocytes via an intracellular alkalinization, rather than by an increase in the [Ca2+]i transient. Thus the response of myocytes to vasoactive peptides may vary with development and/or species.

Aging↗

PubMed1991

Lysophosphatidylcholine increases cytosolic calcium in ventricular myocytes by direct action on the sarcolemma.

Lysophosphatidylcholine (LPC) accumulates in myocardial tissues during ischemia, and has toxic effects which may contribute to the arrhythmias and relaxation abnormalities that occur during acute ischemia. These effects of LPC may be mediated in part by calcium overload. To test this hypothesis, spontaneously contracting cultured embryonic chick ventricular myocytes were superfused with various concentrations of LPC (10, 50 and 100 microM) while effects on contractile motion (video motion detector) and changes in free intracellular calcium ion concentration ([Ca2+]i indo-1 fluorescence) were determined. At concentrations greater than or equal to 10 microM, a dose-related, time-dependent effect occurred after exposure to LPC, consisting of the development of contracture and marked elevation of [Ca2+]i. LPC also produced a dose-related, time-dependent inhibition of K+ uptake, indicating there was inhibition of the Na(+)-K+ ATPase Na+ pump. However, the LPC-induced increase in [Ca2+]i was not due to Na+ overload caused by inhibition of the Na(+)-K+ ATPase Na+ pump because superfusion with a zero-Na+ solution did not prevent an increase in [Ca2+]i after LPC exposure; and the increase in [Ca2+]i after exposure to LPC occurred too rapidly to be accounted for by Na+ pump inhibition. Removal of extracellular Ca2+ prevented the rise in [Ca2+]i, after exposure to LPC but treatment with verapamil failed to inhibit the increase in [Ca2+]i induced by LPC. We conclude that LPC produces contracture due to an increase [Ca2+]i. These effects are seen at concentrations of 10 microM and greater, are not due to altered Na(+)-K+ ATPase Na+ pump or calcium channel function, and are probably related to the detergent properties of this amphiphile. There effects may account in part for myocardial dysfunction during ischemia in intact tissue.

Animals↗

PubMed1991

Evidence that binding of Indo-1 to cardiac myocyte protein does not markedly change Kd for Ca2+.

Quantitative measurement of [Ca2+]i with the fluorescent Ca(2+)-indicators Indo-1 and Fura-2 is complicated by the possibility that the value of the dissociation constant (Kd) may be influenced by binding to intracellular proteins. We investigated this question in cultured chick ventricular myocytes by use of two different Indo-1 calibration methods. First, the Indo-1 fluorescence ratio (R) (400/500 nm) was measured in beating myocytes loaded by exposure to Indo-1/AM. Then, cells were exposed to the Ca2+ ionophore Br A-23187 and fluorescence ratio was measured in the presence of 500 nM Ca2+ (EGTA-Ca2+ buffer). Subsequently cells were permeabilized to Ca2+ by a 1 min exposure to 25 microM digitonin in the presence of 'zero' Ca2+ (10 mM EGTA) and saturating 1 mM Ca2+ to obtain Rmin, Rmax and beta. We then calculated [Ca2+]i from the formula ([Ca2+]i = Kd [( R - Rmin)/(Rmax - R)]beta). With Kd = 250 nM, calculated systolic [Ca2+]i was 750 +/- 44 nM and diastolic 269 +/- 19 nM (means +/- SEM, n = 16). The R value calculated for an assumed [Ca2+]i = 500 nM using the above formula and digitonin derived constants was very similar to the value measured using Br A-23187 (digitonin, 0.67 +/- 0.03: Br A-23187, 0.66 +/- 0.03, ns). As the Br A-23187 method is independent of the value chosen for Kd, we conclude that the Kd of 250 nM for Indo-1 measured in free solutions closely approximates the Kd for intracellular Indo-1 in these cells, and that therefore the Kd of Indo-1 for Ca2+ does not appear to be markedly affected by binding to proteins or other intracellular molecules.

Animals↗

PubMed1991

Contributions of [Ca2+]i, [Pi]i, and pHi to altered diastolic myocyte tone during partial metabolic inhibition.

Ischemia may cause increased or decreased distensibility of the left ventricle, but the cellular mechanisms involved have not been clarified. We examined the possible contributions of changes in intracellular inorganic phosphate, pH, and Ca2+ concentrations to altered diastolic function in cultured myocytes subjected to partial metabolic inhibition. Paced cultured embryonic chick and adult rabbit ventricular myocytes superfused with 20 mM 2-deoxyglucose (2DG) exhibited an increase in end-diastolic intracellular free calcium concentration ([Ca2+]i) and an upward shift in end-diastolic cell position. These results indicate that glycolytic blockade increases diastolic and systolic calcium in paced ventricular myocytes, and that this elevated diastolic calcium influences the extent of diastolic relaxation. In contrast, paced ventricular myocytes superfused with 1 mM cyanide (CN) exhibited a similar increase in end-diastolic [Ca2+]i but a decrease in end-diastolic cell position and amplitude of motion. Although changes in ATP contents were similar in both groups (2DG, -29.9%; CN, -40.1%), alterations of intracellular pH and inorganic phosphate concentrations were different. In 2DG-treated cells, pHi did not decrease significantly (7.18 +/- 0.04 to 7.12 +/- 0.11, n = 14) but in the CN group it decreased markedly within 6 min (7.18 +/- 0.04 to 6.76 +/- 0.11, n = 11, P less than 0.01). Intracellular inorganic phosphate decreased slightly in the 2DG group (-14.8%, NS) but increased in cells exposed to CN (45.7%, P less than 0.02). We conclude that while a prominent increase in diastolic [Ca2+]i occurs in rapidly paced ventricular myocytes exposed to either inhibitors of glycolysis or oxidative phosphorylation, the effects of this increase in [Ca2+]i on diastolic distensibility may be influenced by intracellular accumulation of metabolites that decrease the sensitivity of myofilament to [Ca2+]i.

Animals↗

PubMed1991

Effects of nifedipine on diastolic abnormalities in low-flow and pacing-induced ischemia in isolated rat hearts.

An animal experimental model which stimulates human effort angina, especially in terms of diastolic abnormalities, was developed using isovolumically beating perfused rat hearts. Using this model, we studied the effects of nifedipine, a Ca2+ channel blocker, on diastolic properties during pacing-induced ischemia. When the preload of the left ventricle was set at a low level, low-flow ischemia (coronary perfusion pressure of 40 mmHg) plus tachycardia (480 beats/min for 4 min) did not induce an increase in left ventricular end-diastolic pressure (LVEDP). However, with a high preload, low-flow ischemia plus pacing tachycardia induced an increase in LVEDP of 8.4 +/- 5.4 mmHg (p less than 0.01) and a prolongation of the time constant of ventricular pressure decline (6.8 +/- 4.6 msec, p less than 0.05) immediately after pacing tachycardia. Pretreatment with nifedipine (3 x 10(-8) M) prevented the rise in LVEDP induced by pacing tachycardia. Thus, in isolated perfused hearts, diastolic abnormalities similar to those seen in angina pectoris were obtained by low-flow ischemia plus pacing tachycardia. The response to nifedipine suggested that an alteration of Ca2+ movement may play an important role in the increase in left ventricular stiffness under these conditions.

Angina Pectoris↗

PubMed1991

Forearm venous distensibility in relation to severity of symptoms and hemodynamic data in patients with congestive heart failure.

The distensibility of the forearm veins in 24 patients with congestive heart failure was studied by occlusion plethysmography. Relationships between forearm venous distensibility and symptoms, hemodynamic data obtained by right heart catheterization and plasma levels of vasoactive hormones were evaluated. Forearm venous pressure (VP) and volume change (delta V) were measured simultaneously by the venous occlusion technique with strain gauge plethysmography. The relationship between venous pressure and volume change was fitted by the equation VP = c* exp (k* delta V) (r = 0.98 +/- 0.01) and the venous stiffness constant (k) was calculated. Venous volume change at a venous pressure of 20 mmHg (V20) was also measured as another index of venous compliance. The pressure-volume curve of the peripheral veins shifted leftward on the volume axis and the stiffness constant (k) increased as the New York Heart Association functional class grade increased. Mean pulmonary arterial pressure and pulmonary vascular resistance were closely related to k (r = 0.74, p less than 0.001; r = 0.73, p less than 0.001, respectively), and less closely to V20 (r = -0.56, p less than 0.004; r = -0.59, p less than 0.002, respectively). K and V20 were also related to stroke index (r = -0.57, p less than 0.004; r = 0.44, p less than 0.03, respectively) and stroke work index (r = -0.47, p less than 0.02; r = 0.45, p less than 0.03, respectively). K was also related to heart rate (r = 0.55, p less than 0.007), pulmonary capillary wedge pressure (r = 0.54, p less than 0.02), right atrial pressure (r = 0.51, p less than 0.02), cardiac index (r = -0.45, p less than 0.03), and systemic vascular resistance (r = 0.45, p less than 0.03). Both indexes were related to the plasma level of norepinephrine (r = 0.64, p less than 0.008; r = -0.52, p less than 0.04, respectively). We concluded that the venous tone was related to the severity of heart failure, especially to the symptoms, pulmonary arterial pressure and plasma concentration of norepinephrine, and that the venous stiffness constant, k, was a better parameter with which to assess peripheral venous tone.

Aged↗

PubMed1990

Doppler echocardiographic-determined changes in left ventricular diastolic filling flow velocity during the lower body positive and negative pressure method.

Changes in parameters of left ventricular (LV) diastolic filling flow obtained with Doppler echocardiography during the lower body positive and negative pressure method were analyzed in 15 patients (12 with coronary artery disease and 3 with dilated cardiomyopathy). Lower body pressure was altered at 5 steps (+20, +10, 0, -20 and -40 mm Hg vs atmospheric pressure). Pulmonary capillary wedge pressure measured with a balloon-tipped catheter was changed proportionally with lower body pressure during the procedures (p less than 0.01). Mean systemic arterial pressure was changed slightly during lower body positive pressure and negative pressure of -40 mm Hg. Heart rate was almost unchanged except at lower body pressure of -40 mm Hg. The peak velocity of LV early diastolic filling flow was changed with pulmonary capillary wedge pressure in an almost parallel fashion during the procedures (p less than 0.01). The peak velocity of LV late diastolic filling flow showed smaller changes than that of early diastolic filling flow. Changes in pulmonary capillary wedge pressure correlated positively with changes in the peak velocity of LV early diastolic filling flow (r = 0.759, p less than 0.01), but not with changes in the peak velocity of LV late diastolic filling flow (r = 0.039, not significant) during lower body negative pressure of -20 mm Hg. These data suggest that left atrial pressure is one of the important determinants of LV early diastolic filling flow in this acute clinical setting and that LV late diastolic filling flow is less sensitive to changes in left atrial pressure than LV early diastolic filling flow.

Adult↗

PubMed1990

Acute hemodynamic effects of nilvadipine, a new calcium channel blocker, in patients with congestive heart failure.

The acute hemodynamic effects of nilvadipine, a newly synthesized calcium channel blocker, were studied in 12 patients with congestive heart failure. Hemodynamic measurements were made before and 15, 30, and 60 min after oral administration of 6 mg nilvadipine. Substantial reductions in systemic vascular resistance (-28.8 +/- 6.3%, p less than 0.01) and forearm vascular resistance (-52.0 +/- 6.2%, p less than 0.01) after nilvadipine administration were associated with increases in cardiac index (31.1 +/- 8.3%, p less than 0.01) and forearm blood flow (105.2 +/- 27.4%, p less than 0.01). Mean arterial and pulmonary arterial pressures were decreased by 12.2 +/- 3.0% (p less than 0.01) and 14.7 +/- 5.0% (p less than 0.05), respectively, after nilvadipine administration; however, heart rate remained unchanged. Decreases in mean arterial pressure correlated with the baseline arterial pressure (y = 0.58x - 41.6, r = 0.75, p less than 0.01). Pulmonary capillary wedge pressure decreased by 33.1 +/- 9.1% (p less than 0.01) after nilvadipine administration. However, right atrial pressure and the venous stiffness constant remained unchanged, and the venous pressure-volume curve was not shifted significantly. Therefore, the decrease in pulmonary capillary wedge pressure was attributed primarily to afterload reduction. Nilvadipine holds promise as a vasodilator for the therapy of congestive heart failure.

Aged↗

PubMed1989

Wall motion asynchrony prolongs time constant of left ventricular relaxation.

To evaluate the effects of wall motion asynchrony on left ventricular (LV) relaxation, we performed atrioventricular sequential pacing with the second stimulation at six epicardial sites in open-chest anesthetized dogs. Myocardial segment lengths in the basal, mid, and apical LV free wall were measured by ultrasonic crystals. The standard deviation of interval from the onset of the QRS complex to that of elongation in each segment length was used as a quantitative index for asynchrony (asynchrony index, AI). The AI increased significantly in all sequential pacing modes compared with the control right atrial pacing. The time constant (T) of LV relaxation derived from exponential fit with zero-asymptote was prolonged significantly in all sequential pacing modes except for pacing at the LV base. In each dog there was a good correlation between changes in AI and T [r = 0.61 - 0.98 (mean = 0.84)]. Since the regional inactivation process of the myocardium is considered to be unchanged during these interventions, we concluded that asynchronous wall motion plays an important role in the impairment of LV relaxation.

Animals↗

PubMed1989

Pathophysiology and evaluation of severity of congestive heart failure on the basis of venous characteristics.

To elucidate the possibility of grading the severity of congestive heart failure by using venous characteristics, we constructed venous pressure-volume curves (PVR) and calculated venous stiffness constants (K). In addition, effects of vasoactive drugs on venous distensibility were studied. A venous pressure-volume curve could be fit well by an exponential curve (r = 0.98 +/- 0.01). The PVR was shifted to the left with an increase in the clinical severity of congestive heart failure. The exponent of these curves, K, increased as the PVR was shifted to the left. K correlated with heart rate (r = 0.52, p less than 0.01), right atrial pressure (r = 0.54, p less than 0.02) and mean pulmonary arterial pressure (r = 0.47, p less than 0.04). Nitroglycerin and amrinone dilated veins and decreased K by 19.6 +/- 6.9% (p less than 0.03) and 14.0 +/- 4.3% (p less than 0.02), respectively. Changes in K (delta K) during the nitroglycerin and amrinone infusions correlated closely with the baseline K (delta K = -0.41 K + 0.22, r = 0.92, p less than 0.01). Therefore, the venodilating effects of these drugs were greater in patients with more severe congestive heart failure. The venous stiffness constant could be useful to grade the severity of congestive heart failure.

Adult↗

PubMed1989

Lack of venodilative activity of alpha human atrial natriuretic polypeptide in patients with congestive heart failure.

We studied the effect of alpha human atrial natriuretic polypeptide (hANP) on venous vessels by occlusion plethysmography in 7 patients with congestive heart failure. In another 8 patients the effect of nitroglycerin was studied to validate the methodology. Forearm venous pressure (VP) and volume change (delta V) were measured simultaneously. The relationship between venous pressure and volume change was described by the equation VP = C x e(K x delta V) (r = 0.98 +/- 0.01) and the venous stiffness constant (K) was calculated. Alpha human atrial natriuretic polypeptide (0.1 microM/kg/min) was infused intravenously at a dose sufficient to cause arteriodilation. The pressure-volume curve of the peripheral veins was shifted rightward on the volume axis and the stiffness constant (K) was decreased (-28.1%, p less than 0.03) significantly by nitroglycerin. Alpha human atrial natriuretic polypeptide significantly decreased systemic vascular resistance but did not shift the pressure-volume curve of the vein nor did it decrease the stiffness constant (K). We conclude that hANP has far less venodilating effect than arteriodilating effect in congestive heart failure patients.

Atrial Natriuretic Factor↗

PubMed1988

Combined factor VII and protein C deficiency found in a patient with peripheral pulmonary artery stenosis accompanied by progressive pulmonary hypertension and hemoptysis.

A congenital deficiency of factor VII and protein C was found in a 21-year-old female suffering from recurrent and progressive attacks of dyspnea and hemoptysis over the last four years. She has been followed in our Department since the age of 17 under a diagnosis of peripheral pulmonary artery stenosis and pulmonary hypertension as confirmed by cardiac catheterization and angiography. Prolonged prothrombin time repeatedly examined during this time period prompted us to perform detailed coagulation studies. We found that factor VII and protein C were both half normal in activity as well as in antigen. Three other members of her immediate family were also found to be affected with this combined deficiency. Since the genes encoding factor VII and protein C are located in different chromosomes, the 13th and the second chromosomes, respectively, expression of the combined hereditary deficiency is a random and very rare association on the basis of frequencies of 1:50,000 for factor VII and 1:16,000 for protein C deficiencies.

Adult↗