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Biomedical subjects

K Sagawa

Publications and source records attributed to K Sagawa.

At least 109 records · Page 6Linked to original sources
PubMed1989

Mechanically induced action potential changes and arrhythmia in isolated and in situ canine hearts.

Stretch of excised myocardial tissue causes electrophysiological and potentially arrhythmogenic changes in transmembrane action potentials but corresponding data of the intact mammalian heart are lacking. The effects of increases in ventricular volume and pressure on epicardial monophasic action potentials were therefore investigated in isolated, cross circulated and in situ canine hearts. In seven isolated hearts, increases in ventricular volume and pressure resulted in (1) a linearly related decrease in action potential amplitude (r = 0.988; slope = 0.41% amplitude.ml-1; volume intercept = 17.6 ml), mainly due to a decrease in maximum diastolic potential; (2) a decrease in action potential plateau duration (at 20% repolarisation) by 19 (SD 8)%; and (3) appearance of early afterdepolarizations, reaching up to 18% of total action potential amplitude. Afterdepolarizations occurred only when ventricular outflow was obstructed at end diastole but not at end systole. In eight in situ hearts, increase in left intraventricular pressure produced by transient occlusions of the ascending aorta was also accompanied by decrease in maximum diastolic potential and action potential plateau duration, and by appearance of early afterdepolarizations. In both isolated and in situ intact ventricles, the loading induced electrophysiological changes were associated with occurrence of ectopic ventricular beats. These data show that mechanical overload produces significant electrophysiological changes in the intact canine ventricle which may lead to arrhythmia.

Action Potentials↗
PubMed1989

The effect of halothane, enflurane, and isoflurane on the dynamic stiffness of rabbit papillary muscle.

The authors examined the effect of halothane, enflurane, and isoflurane on the dynamic stiffness of rabbit papillary muscles in Ba2+ contracture. Ca2+ was replaced by Ba2+ in order to constantly activate myofibrils. The dynamic stiffness of the contractured muscle was examined by exposing the muscle to sinusoidal length perturbations at frequencies of 0.05-30 Hz under two concentrations of anesthetic, approximately 0.5, and 1.5-2 mM, and at two Ba2+ concentrations, 0.5 and 1.5-2 mM. The anesthetics had no effect on the frequency (fmin) at which minimum stiffness occurred, but markedly decreased the stiffness modulus at high frequencies (Khi). The decrease in Khi was significant for all anesthetics at the P less than 0.05 level. Increasing the Ba2+ concentration from 0.5 to 1.5-2 mM in the presence of 0.5 mM of anesthetic resulted in a return of Khi to control levels. The authors conclude that halothane, enflurane, and isoflurane did not alter actin-myosin ATPase kinetics, because fmin was unchanged, but decreased the number of crossbridge interactions, because Khi was significantly decreased by all three anesthetics.

Animals↗
PubMed1989

Relative importance of four pressoregulatory mechanisms after 10% bleeding in rabbits.

Four physiological mechanisms are known to be important for recovery of arterial pressure (AP) after acute hemorrhage. These are the sino-aortic baroreflex (SA), the vagally mediated cardiopulmonary baroreflex (CP), the renin-angiotensin system (RA), and the vasopressin system (VP). We evaluated in anesthetized rabbits the relative importance of these mechanisms by repeating rapid, 10% arterial hemorrhage (6.5 ml/kg) once before and once after eliminating one of them and comparing the posthemorrhage hypotension. The study was conducted in two series. In the first series, we randomly grouped 24 rabbits into four groups, i.e., a sinoaortic baroreceptor-denervated group (SA) a vagotomized group (CP), a renin-angiotensin-blocked group (RA), and a vasopressin-blocked group (VP). In control conditions, AP fell to 88% at 2 min and 92% at 6 min after completing the hemorrhage. Significantly greater hypotension (e.g., 74% at 6 min) occurred only in the SA group. In the second series, we randomly classified 18 rabbits into three groups, i.e., an autonomic ganglion-blocked group (AB) plus a RA group and a VP group as before. Hypotension significantly greater than control (68% opposed to 91% at 6 min) occurred only in the AB group. We submit that as far as restoration of arterial pressure after rapid, mild hemorrhage in the rabbit is concerned, the arterial baroreceptor reflex system plays a far more important role than the vagally mediated cardiopulmonary baroreflex, the vasopressin system, or the renin-angiotensin system triggered directly by a fall in renal arterial pressure.

Animals↗
PubMed1989

Electrophysiological effect of volume load in isolated canine hearts.

In isolated isovolumic ventricles and in in situ ventricles under nonsteady-state conditions, alterations in load have been shown to affect electrophysiological properties via contraction-excitation feedback. However, the effect of alterations in loading conditions on electrophysiological properties in normal ventricles under physiological loading conditions remains unknown. Furthermore, the arrhythmogenic significance of these load-induced electrophysiological changes is uncertain. We increased end-diastolic volume (27 +/- 4 ml vs. 51 +/- 6 ml) and assessed conduction, refractoriness, ventricular fibrillation thresholds (VFTs), and inducibility of ventricular arrhythmias in 14 isolated blood-perfused ejecting canine ventricles under steady-state conditions. We also examined the effect of increased end-diastolic volume on refractoriness and monophasic action potential (MAP) duration and contour under isovolumic versus ejecting conditions. Under ejecting conditions, increased end-diastolic volume resulted in very small (less than 1.5%) changes in the absolute refractory period (10 mA) and in local activation time but no change in local electrogram duration, overall dispersion of refractoriness, MAP duration or contour, VFT, or inducibility of ventricular arrhythmias. Increased volume loading under isovolumic conditions resulted in a very slight (less than 1%) shortening of MAP duration and refractoriness but had no effect on the MAP contour. These findings provide strong evidence that alterations in volume load are of little electrophysiological or arrhythmogenic importance in normal canine ventricles under physiologically loaded conditions (contraction-excitation feedback, load and arrhythmias, volume load).

Action Potentials↗
PubMed1989

Summation of sinoaortic baroreflexes depends on size of input signals.

We studied sinoaortic baroreflex summation in seven anesthetized rabbits by paying special attention to the sigmoidal nature of the open-loop characteristic curve of the two reflexes. Carotid sinuses were isolated to control carotid sinus pressure (CSP). Aortic nerves were cut, and the left aortic nerve was electrically stimulated. Initially, CSP was set between 75 and 95 mmHg, and the parameters for aortic nerve stimulation (ANS) were chosen so that mean arterial pressure (MAP) was between 80 and 100 mmHg. We then increased CSP and ANS mildly so that MAP would fall by 10-20 mmHg in each case. Comparison of the sum of these decreases with the decrease caused by simultaneous increases in CSP and ANS showed no statistical difference, indicating a simply additive summation. With mild decreases in CSP and ANS, a similar additive summation was observed in the reflex increases in MAP. When we input slightly larger changes in CSP and ANS so that MAP fell by 20-30 mmHg for each stimulus, comparison of the sum of the separate effects with the combined effect on MAP indicated a mildly inhibitory summation. By analyzing the total peripheral resistance calculated from aortic flow data, we found this inhibitory summation occurred in the reflex controls of the total peripheral resistance. We conclude that the summation of the sinoaortic reflex controls of arterial pressure can be regarded as simply additive when small input signals are given in the physiological range of both reflexes, but the summation is mildly to moderately inhibitory when moderately larger input signals are given.

Animals↗
PubMed1989

Influence of mean pressure on aortic impedance and reflections in the systemic arterial system.

The present investigation sought to determine the extent to which primary changes in mean arterial pressure (MAP) might influence the calculated aortic impedance. In seven open-chest, anesthetized, autonomically blocked dogs, we measured aortic impedance using white-noise analysis at various levels of MAP achieved by adjusting the height of a left atrial reservoir rather than by pharmacological intervention. Impedance spectra so obtained were parameterized according to best-fit wind-kessel models (Ra, Rc, Ca) and three parameters to characterize wave reflections: the frequency at which the phase of the impedance approached or crossed through 0 degree (phi 0), the frequency of the first minimum of the impedance modulus (fmin), and the amplitude of the first oscillation of the impedance modulus (a 1). The dependency of each of these parameters on MAP was investigated. In addition, we calculated the reflection coefficient spectrum (RCS). Results show that windkessel parameters were not significantly influenced by MAP and that the reflection parameters and the RCS depended on increased levels of MAP in a manner consistent with an increase in pulsewave velocity.

Animals↗
PubMed1989

Influence of contractile state on curvilinearity of in situ end-systolic pressure-volume relations.

Although in situ end-systolic pressure-volume relations (ESPVRs) are approximately linear throughout a limited load range, they often yield seemingly "negative" volume axis intercepts (V0) and V0 shifts with inotropic interventions. We tested whether or not these findings could stem from in situ ESPVR nonlinearity, and we examined the physiologic meaning and limitations of linearized ESPVR variables frequently used for assessing contractile state. Continuous left ventricular pressures and volumes were obtained by micromanometer and conductance (volume) catheters in six open-chest dogs. Left ventricular loading was varied throughout a wide range by rapid left atrial hemorrhage into a reservoir. Propranolol and verapamil were administered to reduce inotropic state, with heart rate maintained by atrioventricular sequential pacing. ESPVRs were fit to nonlinear [Pes = a(Ves-V'0)2 + b(Ves-V'0)] and linear (Pes = Ees (Ves-V0)] models. Contractile state was assessed by the slope of the ESPVR at V'0 (b, of nonlinear model) and by two other ESPVR model-independent measures: the slope of the dP/dtmax and end-diastolic volume relation, and the slope of the stroke work and end-diastolic volume relation. ESPVR was frequently curvilinear, and a significant correlation existed between the extent of nonlinearity (a) and contractile state. Volume intercepts derived from linear fits to the high load ESPVR range were mostly negative and were dependent on changes in Ees. V0 estimates derived from the low load portion were positive and relatively insensitive to Ees. Thus, in situ ESPVR displays contractility-dependent curvilinearity. The contractility range throughout which ESPVRs are essentially linear is typical for isolated hearts, but the range represents low values for in situ ventricles. Despite curvilinearity, Ees determined in situ throughout limited load ranges can accurately assess inotropic state; however, comparisons between ESPVRs should consider potential nonlinearity, and if possible, they should be made within similar end-systolic pressure ranges.

Animals↗
PubMed1989

Effect of acute volume load on refractoriness and arrhythmia development in isolated, chronically infarcted canine hearts.

In normal isolated, perfused canine ventricles, increased ventricular volume leads to shortening of refractoriness. To test the hypothesis that myocardium within an infarction zone is more susceptible to volume-induced changes in refractoriness than is normal myocardium, we measured strength-interval curves at low and high end-diastolic volumes at control and infarcted sites in 14 isolated, blood perfused, canine hearts with chronic (greater than 25 days) infarctions. In addition, the effect of volume load on inducing ventricular arrhythmias was studied at one to six sites in 11 hearts. Differences in refractoriness and inducibility at low (22 +/- 5 ml) and high (48 +/- 6 ml) end-diastolic volumes were compared. At control sites, volume load reduced the absolute refractory period from 178 +/- 16.5 to 175 +/- 16.7 msec (p less than 0.05), but no significant change in the relative refractory period occurred. At infarcted sites, the change in refractoriness with volume load was greater, and the absolute refractory period decreased from 171.5 +/- 21 to 160.6 +/- 26.3 msec (p less than 0.01), and the relative refractory period decreased from 180.1 +/- 22.1 to 169.9 +/- 26 msec (p = 0.05). This differential effect of volume load on refractoriness led to an increased dispersion of overall refractoriness at high volume. Infarcted sites showing the largest changes in refractoriness were characterized by patchy scars extending at least to the midmyocardium, whereas sites located within areas of transmural scar, endocardial scar, or rare microfoci of fibrosis showed no increased sensitivity to volume load. Of eight hearts in which no tachyarrhythmias were inducible during programmed electrical stimulation at low volume, four had tachyarrhythmias induced at high volume. Sites of stimulation associated with a conversion from noninducible to inducible tachyarrhythmias showed a larger degree of shortening of refractoriness (change in absolute refractory period: 24.7 +/- 16.5 vs. 3.9 +/- 6.5 msec, p less than 0.05). These data indicate that volume loading may have electrophysiologic significance and that it may be of greater functional importance under pathologic conditions.

Animals↗
PubMed1989

Determinants of end-systolic pressure-volume relations during acute regional ischemia in situ.

The influence of extent and location of regional ischemia, baseline left ventricular systolic function, and autonomic reflexes on in situ left ventricular end-systolic pressure-volume relations (ESPVRs) during coronary occlusion were studied in 13 open-chest dogs. Circumflex or left anterior descending arteries were randomly occluded (at proximal or distal sites) for 3 minutes in reflex-blocked (n = 6, hexamethonium/vagotomy) and unblocked (n = 7) animals. Pressure-volume data were obtained by the conductance-catheter technique, with ESPVRs determined by transient inferior vena caval occlusion. Ischemic zone size was estimated for each occlusion by radiolabeled microspheres. The relative influence of each variable on ESPVR change with ischemia was determined by multiple regression analysis. As in previous studies, regional ischemia displaced ESPVRs to the right by an amount that varied directly with ischemic bed size (y = +0.48x, r = 0.76, p less than 0.001). However, in contrast to previous data, coronary occlusion also reduced the ESPVR slope (end-systolic elastance, Ees) in the majority of cases. The extent of slope change was primarily dependent on the baseline elastance (Eesbase), such that the higher the initial elastance, the larger its subsequent reduction for any amount of ischemia (delta Ees = -0.78Eesbase, r = 0.94, p less than 0.001). Active reflexes added an offset constant to this relation (+3.15 mm Hg/ml, p less than 0.001). In addition, Ees fell slightly more with larger ischemic regions. Thus, although previous studies have reported primarily rightward parallel shifts in ESPVR with regional ischemia, the present data also demonstrate that the slope of the relation is often reduced. Greater baseline elastances typical of in situ, as opposed to isolated, ventricles probably explain the differences in apparent responses.

Animals↗
PubMed1989

Long-term versus intrabeat history of ejection as determinants of canine ventricular end-systolic pressure.

We studied the effect of ejection on end-systolic pressure in isolated heart preparations. Ejecting beats were compared with isovolumic beats having the same volume as at end systole. While holding end-systolic volume constant, various stroke volumes, including negative stroke volumes (volume injected during systole), were imposed using a predetermined volume command. After switching contraction mode between ejecting and isovolumic, we measured the immediate and steady changes in end-systolic pressure. In the first isovolumic beat after switching from steady-state ejecting beats, the change in end-systolic pressure was variable, depending on the stroke volume. The end-systolic pressure of the ejecting beat exceeded that of the isovolumic beat on average by up to 18 mm Hg with small stroke volume, but the ejecting end-systolic pressure became lower than isovolumic with either large stroke volume (stroke volume/end-systolic volume less than 0.96) or with negative stroke volume. During the transient phase following a switch from ejecting to isovolumic, the end-systolic pressure gradually decreased to a steady state. Consequently, even in steady state, ejecting end-systolic pressure exceeded isovolumic pressure over a significant range of stroke volume (stroke volume/end-systolic volume less than 1.18). After returning contraction mode from isovolumic back to ejecting, we observed responses that were a mirror image. These results indicated that in addition to negative uncoupling effect, ejection exerts positive effects on ventricular end-systolic pressure that are manifest both quickly and gradually. We hypothesized that the mechanism responsible for the positive effect is length-dependent activation via the larger volume (both at the initiation of contraction and averaged over a cardiac cycle) of a beat that ejects compared to one held isovolumic at end-systolic volume. The results with volume injection were consonant with this concept.

Animals↗
PubMed1989

Establishment and characterization of a clonal human T-cell line, MKB-1 derived from a patient with acute myeloblastic leukemia.

A human T-cell line, designated as MKB-1, was established by cloning procedures in a suspension culture from a peripheral blood of a 17-year-old female patient with acute myeloblastic leukemia. The immunological marker profile of MKB-1 indicated that unlike a myeloid phenotype of the original leukemic cells, the cells were positive for CD3 (both cell surface and cytoplasm), T cell receptor (TcR) alpha/beta heterodimer, CD4, CD5, CD7, CD10, CD57 (Leu7), SN-1 and the cytoplasmic TcR beta chain. These findings indicate the T cell nature of the established cells. Terminal deoxynucleotidyl transferase (TdT) was also detected in 60%. We did not detect markers of human myeloid and B cell associated antigens, HLA-class II or immunoglobulin chains. Cytogenetic study revealed that the MKB-1 cells had a female hypo-tetraploid karyotype with chromosomal abnormalities including a translocation between chromosomes 10 and 14. The breakpoint of chromosome 14 of this translocation, 14q11.2, is known to be the location of TcR alpha and delta genes; t(10; 14) (q26; q11.2) is a variant type of a T cell neoplasm-associated translocation, t (10; 14) (q24; q11.2). The MKB-1 cell line is unusual in that its T cell characteristics are phenotypically and cytogenetically distinct from the original myeloid leukemia cells.

Adolescent↗
PubMed1988

A highly specific and sensitive radioimmunoassay of caerulein, an analogue of cholecystokinin-8.

A highly specific and sensitive competitive radioimmunoassay was developed for caerulein (CLN), an analogue of cholecystokinin-8 (CCK-8), in plasma and brain. Antiserum was produced in rabbit by immunization with N delta-[CLN-(1-6)]-ornithine amide conjugated with bovine serum albumin by the glutaraldehyde method. N alpha-[CLN-(1-6)]-lysine amide was labelled with 125I-Bolton & Hunter reagent and used as a labelled antigen after purification by high-performance liquid chromatography. This assay was highly specific for CLN, and cross reactivities for other related peptides, CCK-4, CCK-8, gastrin-I, and gastrin-(14-17), were not observed (less than 0.01%). The limits of determination in biological specimens after CLN administration were 11 pg/ml in human plasma and rat plasma and 80 pg/g in rat brain. This study showed that the slight structure difference between hapten and 125I-labelled antigen is important to the assay performance.

Animals↗
PubMed1988

Conserved immunogenic region of a major core protein (p24) of human and simian immunodeficiency viruses.

A murine monoclonal antibody (MoAb), VAK 4, has been known to specifically react with a major core protein (p24) as well as with its precursor (p55-57) and intermediate precursor (p40) of human immunodeficiency virus strain IIIB (HTLV-IIIB). Radioimmunoprecipitation assays revealed that VAK 4 MoAb precipitated a major core protein and its precursors from a variety of strains of HIV and also from simian immunodeficiency virus (SIV), although the molecular weights of the precursor proteins in each viral strain were slightly different. A protein synthesized by transfected Escherichia coli containing amino acid sequences corresponding to residues 121-436 of the HTLV-IIIB gag gene was reactive with VAK 4 MoAb, but the protein carrying only residues 121-309 was not reactive, suggesting that the epitope recognized by VAK 4 MoAb resides at the carboxyl terminus of p24 protein. A competitive enzyme-linked immunosorbent assay showed that patient sera containing anticore protein antibody inhibited the binding of VAK 4 to HTLV-IIIB. These findings suggested that VAK 4 MoAb recognized an immunogenic and conserved epitope belonging to a major core protein of HIV-related viruses.

Antigens, Viral↗
PubMed1988

Deterioration of B cell proliferation correlates with dendritic reticulum cell destruction in germinal centers of an AIDS patient. Case study.

A lymph node from a bisexual Caucasian male infected with human immunodeficiency virus (HIV) and in the persistent generalized lymphadenopathy (PGL) stage was studied. Dendritic reticulum cells (DRCs) were well preserved in over half of the germinal centers (GCs), while in the rest, they showed marked destruction, producing patchy or rather wide DRC-depleted areas. Proliferation-associated antigens, i.e., PC antigen and DNA-polymerase alpha, were demonstrated in nuclei of germinal center B cells in areas where the DRC network was intact, while they were prominently depleted in areas where the DRC network was lost. The p-24 viral core antigen was shown to be localized in DRCs, especially those in the process of degeneration. These results suggest that the DRC in this patient, when infected with HIV, were destroyed, and that the resulting DRC depletion led to the suppression of B cell proliferation in GCs.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Pulsatile vs. mean component of baroreflex compensation for posthemorrhage hypotension.

We studied the influence of pulsatile pressure and mean arterial pressure signals on the restoration of arterial pressure after 10% hemorrhage in seven anesthetized dogs. After transection of the aortic nerve, a quick 10% hemorrhage was repeated under four different sinus conditions: condition 1, carotid sinus pressure depulsated and fixed at a level equal to the prehemorrhage level (no feedback); condition 2, pulsatile component of aortic pressure fed back to the carotid sinus with a fixed mean pressure (pulsatile feedback); condition 3, depulsated mean aortic pressure fed back (mean pressure feedback); condition 4, both pulsatile and mean pressure fed back (pulsatile plus mean component feedback). The restoration of arterial pressure in condition 2 was not significantly different from that in condition 1, but there was greater restoration in conditions 3 and 4. At 1.5 min posthemorrhage, the open-loop gains calculated from the restoration values were nearly zero for the pulsatile feedback only, 2.8 +/- 0.8 for mean arterial pressure feedback, and 1.5 +/- 0.3 for pulsatile and mean pressure feedback. These results indicate that the pulsatile component of the carotid baroreflex contributes minimally to the restoration of arterial pressure after 10% hemorrhage in the anesthetized dog.

Animals↗
PubMed1988

Effect of nitroglycerin on aortic impedance, diameter, and pulse-wave velocity.

The effects of an intravenous infusion of 1 microgram/kg/min nitroglycerin were studied on systemic arterial properties in nine acutely instrumented dogs. Aortic impedance and pulse-wave velocity were calculated from measured pressure and flow signals collected during random ventricular pacing. Central aortic diameter was simultaneously determined with ultrasonic dimension crystals. Mean blood pressure was maintained constant to avoid the confounding effects of passive, pressure-induced changes in vascular properties. Nitroglycerin both reduced the amplitude of peripheral vascular reflections and delayed the return of these reflections to the aortic root. This reflection delay was manifested as a consistent leftward shift in both impedance modulus and phase. The magnitude of this reflection delay could not be entirely accounted for on the basis of the measured changes in average pulse-wave velocity along the aorta.

Animals↗
PubMed1988

Effect of nisoldipine on coronary resistance, contractility and oxygen consumption of the isolated blood-perfused canine left ventricle.

Nisoldipine reportedly has little direct myocardial effect. However, because of interactions between the heart and vascular load, the effects on myocardial contractility and left ventricular oxygen consumption (LVO2) have not been established. The authors performed experiments on six isolated, blood-perfused canine left ventricles that were isovolumically contracting and paced at constant rate. Coronary arterial pressure (CAP) and coronary blood flow were measured for evaluation of coronary vascular resistance, and coronary arteriovenous oxygen difference was measured for determination of LVO2. Intracoronary injection of 1 and 10 micrograms of nisoldipine decreased coronary vascular resistance by 16.9 and 36.8% (CAP approximately 40 mm Hg), respectively, and by 21.5 and 47.7% (CAP approximately 80 mm Hg). At both doses, nisoldipine caused no decrease in peak systolic pressure as long as CAP was kept constant at 80 mm Hg. However, when CAP was decreased to 40 mm Hg, peak systolic pressure was significantly decreased even without nisoldipine. This impaired contractile state was associated with a decreased coronary blood flow and a slight decrease in LVO2, whereas 10 micrograms of nisoldipine at CAP approximately 80 mm Hg increased LVO2 significantly. Using the end-systolic pressure-volume relationship as an index of contractility, the authors found nisoldipine not to change the contractile state at CAP approximately 80 mm Hg. They conclude that nisoldipine decreases coronary vascular resistance over a wide range of CAP. It neither depresses the contractile state nor decreases LVO2 in the canine left ventricle. Nisoldipine might effectively counteract anginal attacks by dilating the coronary vessels without depressing myocardial contractility as found in this study on normal ventricle.

Animals↗