摘要:

Several studies have related 12-lead ECG waveform during ventricular tachycardia to ECG waveform during ventricular pacing to identify ablation sites for therapy of ventricular tachycardia. QRS isopotential maps and QRS isointegral maps derived from body surface isopotential maps have also been correlated with left ventricular pacing sites with the same objective. The comparison process used is subjective and only semiquantitative. Improved accuracy of catheter placement may improve success rates of ablation therapy.Methods and ResultsThis animal study was performed to determine the spatial resolution with which left ventricular pacing sites could be distinguished by body surface isopotential mapping. Potentials were recorded from 64 evenly spaced thoracic leads. Hexapolar or octapolar pacing catheters with 2-mm interelectrode spacing were placed percutaneously in the left ventricle in each of six dogs, and bipolar endocardial pacing was performed using each pair of adjacent electrodes. QRS isopotential maps of each pacing site for each catheter placement were cross-correlated by computer. Difference maps for each pair of pacing sites were calculated lead by lead and time instant by time instant, and root-mean-square voltage differences were calculated. Results indicated that correlation coefficients and root-mean-square error of voltage differences monotonically decrease and increase, respectively, with stimulus site separation. Both measures were significantly different (P< .05) for separations of 4 mm or more.ConclusionsA method of quantitative comparison of body surface potential maps can be used in normal hearts to localize ventricular pacing sites within a 4-mm range. The method may have utility in determining potential ablation sites for therapy of ventricular tachycardia or preexcitation syndromes.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We have previously shown major differences in β-adrenergic and muscarinic modulation of L-type calcium currents (Ica) in newborn and adult rabbit heart. However, little is known about developmental changes in modulation of Icaby phosphodiesterases (PDEs), which also regulate intracellular cAMP concentration by its hydrolysis.Methods and ResultsEnzymatically isolated adult and newborn (1- to 3-day-old) rabbit ventricular myocytes were used to study the effects of PDE inhibitors on Icameasured by the whole-ell patch-clamp method. 3-Isobutyl-1-methyl-xanthine (IBMX), a nonselective PDE inhibitor, increased Icain a dose-dependent manner for both groups. The maximal effect of IBMX, expressed as percentage increase in Icaover control levels, was greater for newborn myocytes than for adult myocytes, but the effects of IBMX applied alone were observed only at concentrations >10 μmol/L. The concomitant use of 0.1 μmol/L isoproterenol produced a significant potentiation of the IBMX effect on Ica, with a significant additive effect of IBMX in newborn myocytes even at 0.05 μmol/L IBMX. The concomitant use of a subthreshold concentration of IBMX (0.1 μmol/L) did not potentiate the dose dependence of adult Icaon isoproterenol but did markedly potentiate the dose dependence of newborn Icaon isoproterenol. The E⊂max and EC50of isoproterenol in the presence of 0.1 μmol/L IBMX on newborn Icawere 235% and 8 nmol/L, respectively, whereas the E⊂max and EC50of isoproterenol in the absence of IBMX on newborn Icawere 111% and 81 nmol/L, respectively. The addition of 50 μmol/L IBMX to 10 μmol/L isoproterenol markedly increased the newborn Ic, density up to a level equivalent to that reached with 200 μmol/L cAMP in the pipette (14.9±1.2 versus 13.4±0.7 pA/pF). Our data suggest that the inhibition constant (Ki) of IBMX for inhibiting PDEs that participate in the regulation of Icais much lower in newborn than in adult myocytes. Milrinone 1 μmol/L, a selective PDE III inhibitor, increased the 0.1 μmol/L isoproterenol-stimulated Icaof adult myocytes but had no significant additive effect for the 0.1 1tmol/L isoproterenol- stimulated Icaof newborn myocytes. Rolipram 1 μmol/L, a selective PDE IV inhibitor, increased the 0.1 μmol/L isoproterenol-stimulated Icafor newborn myocytes but had no significant additive effect for the 0.1 1A/L isoproterenol-stimulated Icafor adult myocytes.ConclusionsThese results suggest that the most important PDE isozyme for regulation of Icaof rabbit myocytes changes from PDE IV to PDE III during the postnatal period.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Diabetic cardiomyopathy presents with significant collagen accumulation; decreased solubility, increased glucose-mediated abnormal cross-linking, free radical crosslinking, or glucose-induced increased transcription of collagen is incriminated. In a previous study, we reduced collagen accumulation in the kidneys of diabetic mice by treatment with oral arginine. This observation led us to examine the effect of arginine on cardial fibrosis.Methods and ResultsTwenty-nine db/db spontaneously diabetic mice were used in the experiments. Sixteen were given L-arginine (free base, in tap water, 50 mg/kg body wt per day) for 4 months. At the end of the experiment, we determined total collagen content of total ventricular tissue, acid solubility, carboxymethyllysine, O-tyrosine, glutathione, blood glucose, and fructosamine as parameters for glycemic control. Heart collagen level was significantly (P= .0001) reduced in the experimental group (mean, 0.24±0.05) compared with the control group (mean, 0.49±0.10 μmol hydroxyproline per 100 mg heart tissue). Significantly more collagen could be eluted from heart samples of the experimental group (P= .02). Carboxymethyllysine and O-tyrosine did not differ when related to heart weight. Glutathione level was significantly higher in the untreated group (P= .003). Parameters of glycemic control did not differ between the groups.ConclusionsOur findings clearly indicate that L-arginine reduced total heart collagen and increased acid solubility of heart collagen. Both findings are compatible with the cross-linking hypothesis. The data for carboxymethyllysine, O-tyrosine, and glutathione would rule out the glycoxidation hypothesis and, therefore, free radical cross-linking. The postulated mechanism of action is most likely the blocking of reactive carbonyl functions by L-arguiine in analogy to aminoguanidine activity. Correlations of collagen with glycemic control, however, point to an association of glucose with collagen metabolism, a phenomenon documented in cell cultures at the transcriptional level.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The role of nonhemodynamic cardiac trophic mechanisms differs not only between different models of cardiac hypertrophy but also within the same model for development versus maintenance of cardiac hypertrophy. Our previous studies pointed to a major role for the renin-angiotensin system (RAS) as a cardiac trophic stimulus in the remodeling of the heart in response to volume overload by aortocaval shunt or minoxidil treatment.Methds and ResultsIn the present study, we evaluated the effects of blockade of the RAS by the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II receptor blocker losartan on left ventricular (LV) and right ventricular mass and LV dilation in relation to changes in central hemodynamics during the maintenance of minoxidil and aortocaval shunt-induced cardiac hypertrophy. Both blockers similarly decreased LV end-diastolic pressure (LVEDP) and LV peak systolic pressure, whereas cardiac output remained unchanged in both models of volume overload. This suggests a major contribution of improved LV performance and decreased afterload to the decrease in cardiac preload by the two blockers rather than decreased venous return. Both blockers reversed LV hypertrophy in parallel to their effects on LVEDP in both models of volume overload. In minoxidil-treated rats, the extent of reversal in LV mass and dilation by the two blockers was similar to “spontaneous regression” after discontinuation of minoxidil treatment.ConclusionsThese results indicate that in contrast to the development phase of cardiac hypertrophy, the RAS does not contribute to the maintenance of volume overload-induced cardiac hypertrophy in these two models via direct cardiac trophic effects. The RAS, however, maintains cardiac hypertrophy indirectly by contributing to the persistence of high filling pressures.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Despite the current clinical use of radiofrequency (RF) catheter ablation in infants, the acute and late effects of RF lesion production in immature myocardium remain unknown. This study was specifically designed to investigate the pathology of RF lesions in developing sheep myocardium.Methods and ResultsIn study 1, RF lesions were made on the epicardial left ventricular surface of the beating heart in 15 sheep, 5 approximately 4 weeks of age (11.0±1.0 kg) and 10 approximately 8 weeks of age (23.8±3.4 kg), to assess the effects of RF application duration (10 to 90 seconds) and electrode tip temperature (45° to 90°C) on lesion size in immature myocardium. Lesion width and depth increased asymptotically with RF duration, to 7.0±0.7 and 4.8±1.0 mm at 90 seconds, respectively. The time to reach one-half lesion size was 6.5 seconds for width and 12.0 seconds for depth. Lesion width increased nearly linearly with tip temperature above 50°C, but depth followed a sigmoid relation, with no increase above 80°C. In study 2, RF lesions were made in all four cardiac chambers under fluoroscopic guidance in 19 infant sheep (10.9±1.4 kg). Lesion sizes and histological characteristics were assessed acutely (acute, n=5), at 1.07±0.02 months (1 month, n=5), and at 8.5±0.5 months (late, n=9). Atrial and ventricular lesions but not atrioventricular groove lesions apparently increased in size during the follow-up period. Atrial lesions width increased from 5.3±0.5 to 8.7±0.7 mm at 1 month (164%) but did not increase further at late follow-up, while ventricular lesion width increased from 5.9±0.8 to 10.1±0.7 mm (171%) at late follow-up but was not significantly changed at 1 month. Histological evaluation revealed replacement of normal myocytes with fibrous and elastic tissue at 1 month and late follow-up in all locations but also demonstrated a poorly delineated border with multiple extensions of fibrous and elastic tissue into surrounding normal myocardium in late ventricular lesions.ConclusionsRF lesion formation in immature sheep myocardium is similar to that in adult myocardium acutely but is associated with late lesion enlargement and fibrous tissue invasion of normal myocardium. These findings may have implications for clinical RF ablation procedures in infants.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Skeletal muscle metabolic abnormalities have been described in patients with heart failure that are independent of total limb perfusion, histochemical changes, and muscle mass. However, these skeletal muscle metabolic abnormalities may result from tissue hypoxia caused by maldistribution of flow. Myoglobin is an 02binding protein that can indirectly assess tissue hypoxia.Methods and ResultsIn vivo measurement of deoxymyoglobin was performed by use of proton (1H) magnetic resonance spectroscopy in 16 heart failure (HF) (left ventricular ejection fraction=20±6%; &OV0622;o2=14.5±5.1 mL/kg per minute) and 7 healthy (Nl) subjects. Simultaneous phosphorus (31P) magnetic resonance spectroscopy and near-infrared spectroscopy also were obtained to examine muscle metabolism and oxygenation. Supine calf plantarflexion was performed every 4 seconds. Incremental steady-state work was performed. A second exercise protocol studied rapid incremental (RAMP) exercise with plantarflexion every 2 seconds. Arterial occlusion at end exercise provided physiological calibration for myoglobin and hemoglobin signals.With steady-state exercise, the work slope, ie, inorganic phosphorus to phosphocreatine ratios versus work, was significantly greater in patients with heart failure (Nl: 0.18±0.08; HF: 0.40±0.32 W−1;P< .05). Intracellular pH was reduced significantly at end exercise in patients but not healthy subjects. Despite these metabolic abnormalities, muscle oxygenation derived from 760- to 850-nm absorption was comparable in both groups throughout exercise. The relation of inorganic phosphorus/phosphocreatine (P1/PCr) ratio and muscle oxygenation was shifted upward in patients with heart failure such that at the same muscle oxygenation, Pi/PCr ratio in these patients was increased. No deoxymyoglobin signals were observed at rest. At maximal exercise, 4 of the healthy subjects and 3 of the patients exhibited deoxymyoglobin (P=NS). With RAMP exercise, the work slope was again significantly greater in patients with heart failure (N1: 0.21±0.10; HF: 0.57±0.32 W−1;P< .05). Intracellular pH again was significantly decreased at end exercise in patients but not healthy subjects. Five of the healthy subjects and 3 of the heart failure patients had deoxymyoglobin signal (P=NS). With arterial occlusion, deoxymyoglobin was seen in all subjects.ConclusionsAbnormal skeletal muscle metabolism in patients with heart failure usually occurs in the absence of myoglobin deoxygenation, suggesting that the abnormalities are not a result of cellular hypoxia during exercise with minimal cardiovascular stress.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Vasoactive drugs could alter the fluid restitution from the tissue and redistribute blood volume between the macrocirculation and microcirculation.Methods and ResultsWith bolus injections of vasoactive drugs in anesthetized rabbits, we measured the changes in blood and plasma density for the determination of the volume of restitution and redistribution. Epinephrine 3.5, μg/kg caused a fluid loss to the tissue, leading to a transient decrease in total blood volume by 2.30 mL/kg. Because of blood volume redistribution, the peak volume reduction was accompanied by a volume reduction of 0.81 mL/kg from the macrocirculation and 1.49 mL/kg from the microcirculation. Phenylephrine 70 μg/kg caused a peak reduction in total blood volume of 1.40 mbVkg (with 0.41 mL/kg from macrocirculation and 0.99 mb/kg from microcirculation). Nitroprusside 7 μg/kg increased the blood volume by 1.44 mL/kg (0.83 mb/kg macro and 0.61 mb/kg micro), nitroglycerin 7 μg/kg by 1.48 mL/kg (0.97 mL/kg macro and 0.51 mL/kg micro), and isoproterenol 7 μg/kg by 2.07 mL/kg (0.68 mL/kg macro and 1.39 mL/kg micro). All plasma (or blood) density changes measured for the five drugs (with epinephrine, phenylephrine, and nitroprusside done over a wide dosage range) correlated linearly with the drug-induced changes in arterial pressures.ConclusionsThese results indicate that vasoactive drugs alter total blood volume and the volume of microcirculation and macrocirculation.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Platelet aggregation with the release of their vasoactive mediators is an important factor contributing to the patency of coronary bypass grafts. However, the role of leukocyte-derived mediators on graft performance is unclear. Leukotrienes (LTs) are proinflammatory mediators released from a variety of leukocytes that possess both vasoactive and mitogenic properties. We have therefore compared the effects of the cysteinyl LTs (C4, D4, and E4) on the human saphenous vein (SV) and human internal mammary artery (IMA).Methods and ResultsHuman SVs from 43 patients (mean age, 58 years) and IMAs from 33 patients (mean age, 57 years) were obtained from individuals undergoing coronary artery bypass surgery for coronary artery disease. The samples were set up in organ baths to record changes in vessel wall tension. In undistended SVs the cysteinyl LTs elicited concentration-dependent contractions. The Emaxfor LTE4(4.231.0 mN; n=6) was significantly less than that observed with either LTC4(25.7±4.01 mN; n=7;P.001) or LTD4(26.193.16mN; n=7;P.001). In addition, the LTD4receptor antagonist ICI 198615 (30 nmol/L) significantly inhibited the LTD4concentration-response curve but not the LTC4responses. Furthermore, treatment of the SV with acivicin (0.05 mmol/L), a γ-glutamyl transpeptidase inhibitor, caused a significant rightward displacement of the LTC4concentration-response curve. In contrast, LTC4and LTD4produced a response in IMAs from only 3 of 29 patients. LTC4and LTD4produced small contractions, of which the maximum responses were 3.28±1.92 mN (n=5) and 3.12±1.38 mN (n=5). LTE4produced no responses in the IMA. Experiments in which the SV was pretreated with L-NG-monomethyl-L-arginine (LNMMA; 10−4mol/L) or indomethacin (10−5mol/L) or was denuded of endothelium had no significant effect on the Emaxvalues for LTE4. Also, the IMA remained unresponsive to cysteinyl leukotrienes after treatment with L-NMMA or indomethacin or endothelium removal. In vitro autoradiography localized specific [3H]-LTC4and [3HI-LTD4binding sites (putative receptors) to the smooth muscle cells of both SV and IMA, with greater binding to the SV.ConclusionsOur data show that there is a preferential contraction to LTs in SV compared with IMA. This difference in smooth muscle cell reactivity to the cysteinyl LTs suggests that endogenous LT production from circulating or infiltrating leukocytes may be an important factor contributing to graft function.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

There have been many anecdotal reports that regular, moderate exercise confers some protective immunity against infection. There has been little scientific evidence to support this. It is also unclear whether training alters lymphocyte trafficking from the spleen to the periphery after a bout of exhaustive exercise.Methods and ResultsTo determine the effect of moderate training on in vivo antibody production, using rats as an animal model, we gradually trained 18 rats using a swimming protocol for a 4-week period after injection and booster with Keyhole limpet hemocyanin antigen. There were 9 age-matched controls. At the conclusion of training, both groups underwent a short-term exhaustive swim. The trained group showed marked enhancement of IgM and IgG production. After short-term exercise, both groups had acute lymphocytosis, mainly Tsuppressor/cytolyticand natural killer cells with decreases in Thelper(trained), B cells, and the Th-to-Ts, ratio. The changes in the splenocyte subsets were the opposite of the changes in the peripheral blood. With respect to function, after exhaustive exercise, there was a slight increase in mitogenesis and interleukin- 2 receptor expression to concanavalin A (untrained more than trained) compared with controls.ConclusionsRegular, moderate training enhances antibody production to specific de novo antigen both early and late. In addition, short-term exercise leads to selective release of immune cells from the spleen and results in slightly enhanced function of splenocytes. Direct stimulation by the sympathetic nervous system and catecholamines is the proposed mechanism for the changes seen after short-term exercise and possibly antibody production during training.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Cardiac hypertrophy in response to systolic pressure overloading frequently results in contractile dysfunction, the cause for which has been unknown. Since, in contrast, the same degree and duration of hypertrophy in response to systolic volume overloading does not result in contractile dysfunction, we postulated that the contractile dysfunction of pressure hypertrophied myocardium might result from a direct effect of stress as opposed to strain loading on an intracellular structure of the hypertrophied cardiocyte. The specific hypothesis tested here is that the microtubule component of the cytoskeleton is such an intracellular structure, which, forming in excess, impedes sarcomere motion. The feline right ventricle was either pressure overloaded by pulmonary artery banding or volume overloaded by atrial septotomy. The quantity of microtubules was estimated from immunoblots and immunofluorescent micrographs, and their mechanical effects were assessed by measuring sarcomere motion during microtubule depolymerization. We show here that stress loading increases the microtubule component of the cardiac muscle cell cytoskeleton; this apparently is responsible for the entirety of the cellular contractile dysfunction seen in our model of pressurehypertrophied myocardium. No such effects were seen in right ventricular cardiocytes from normal or volume-overloaded cats or in left ventricular cardiocytes from any group of cats. Importantly, the linked microtubule and contractile abnormalities are persistent and thus may be found to have significance for the deterioration of initially compensatory cardiac hypertrophy into the congestive heart failure state.

ISSN:0009-7322    

出版商:OVID    

年代:1994

数据来源: OVID